Efficacy and Mechanism of Traditional Medicinal Plants and Bioactive Compounds against Clinically Important Pathogens

Suresh  Mickymaray

Traditional medicinal plants have been cultivated to treat various human illnesses and avert numerous infectious diseases. They display an extensive range of beneﬁcial pharmacological and health effects for humans. These plants generally synthesize a diverse range of bioactive compounds which have been established to be potent antimicrobial agents against a wide range of pathogenic organisms. Various research studies have demonstrated the antimicrobial activity of traditional plants scientifically or experimentally measured with reports on pathogenic microorganisms resistant to antimicrobials. The antimicrobial activity of medicinal plants or their bioactive compounds arising from several functional activities may be capable of inhibiting virulence factors as well as targeting microbial cells. Some bioactive compounds derived from traditional plants manifest the ability to reverse antibiotic resistance and improve synergetic action with current antibiotic agents. Therefore, the adva...

antibiotics Review Efficacy and Mechanism of Traditional Medicinal Plants and Bioactive Compounds against Clinically Important Pathogens Suresh Mickymaray Department of Biology, College of Science, Al-Zulfi-, Majmaah University, Majmaah 11952, Saudi Arabia; s.maray@mu.edu.sa Received: 4 November 2019; Accepted: 28 November 2019; Published: 9 December 2019 Abstract: Traditional medicinal plants have been cultivated to treat various human illnesses and avert numerous infectious diseases. They display an extensive range of beneficial pharmacological and health effects for humans. These plants generally synthesize a diverse range of bioactive compounds which have been established to be potent antimicrobial agents against a wide range of pathogenic organisms. Various research studies have demonstrated the antimicrobial activity of traditional plants scientifically or experimentally measured with reports on pathogenic microorganisms resistant to antimicrobials. The antimicrobial activity of medicinal plants or their bioactive compounds arising from several functional activities may be capable of inhibiting virulence factors as well as targeting microbial cells. Some bioactive compounds derived from traditional plants manifest the ability to reverse antibiotic resistance and improve synergetic action with current antibiotic agents. Therefore, the advancement of bioactive-based pharmacological agents can be an auspicious method for treating antibiotic-resistant infections. This review considers the functional and molecular roles of medicinal plants and their bioactive compounds, focusing typically on their antimicrobial activities against clinically important pathogens. Keywords: traditional medicinal plants; bioactive compounds; antimicrobial activities; mechanisms 1. Introduction The incidence of microbial infectious diseases and their hitches consistently elevates, mostly due to microbial drug resistance to presently offered antimicrobial agents [1]. These multidrug-resistant microbes cause various infections globally and are connected with greater levels of morbidity and mortality [2]. These augmentations of antibiotic resistance and higher recurrence rates of such common infections have a great impact on our society [3–5]. Several investigations associated with antimicrobial resistance predict that the mortality toll owing to antimicrobial resistance may exceed 10 million by 2050, theoretically leading to greater mortality in the context of other infectious diseases and malignancies [6]. It is well known that infections are generally difficult to treat due to the development of biofilm in the host, which aids the proliferation of microbes as well as the aggressiveness of the infections [7]. Studies have also well-established that the physical structures of biofilm establishing organisms confer natural resistance to hostile environments, including antimicrobial agents [8]. Therefore, it is an urgent requirement to generate novel antimicrobial drugs which can inhibit the development of, or abolish the complete biofilms, and hence increase the vulnerability of microbes to antimicrobials. The requisite for new antimicrobials which could meritoriously fight against antimicrobial resistant clinical pathogens is extremely augmented. Plant-derived antimicrobials have been established to be one of the most auspicious sources considered as safe due to their natural origin when compared with synthetic compounds [9,10]. There Antibiotics 2019, 8, 257; doi:10.3390/antibiotics8040257 www.mdpi.com/journal/antibiotics Antibiotics 2019, 8, 257 2 of 57 is an accumulating interest in the practice of either crude extract of medicinal plants, as well as the screening plant-derived compounds as an alternative therapy for microbial infections [11]. Plants generally produce a diverse range of bioactive compounds which have been widely used in clinical practice [12]. Remarkably, a significant number of marketed drugs are obtained from nature or result in natural products through either chemical transformations or de novo synthesis [13]. Plant-derived compounds are a group of secondary metabolites that are used to treat chronic as well as infectious diseases. These traditional medicinal plants or active compounds remain included as part of the habitual treatment of various maladies [9]. These compounds could have other target sites than conventional antimicrobials as well as diverse mechanisms of action against pathogenic microbes. An electronic search was performed using PubMed, Science Direct, and Google Scholar using the keywords “medicinal plants” AND “bioactive compounds” AND “antimicrobial activities” AND “antibiotic resistance” in “Title/Abstract/Keywords” without date restriction in order to identify all published studies (in vitro, in vivo, clinical and case-control) that have investigated the connection between medicinal plants and their antimicrobial effects. Antimicrobial mechanisms were gathered and for review. 2. Traditional Medicinal Plants The species of the plant kingdom are estimated to number about 500,000 and only a minor portion of them have been investigated for antimicrobial activity [9,14]. Traditional medicinal plants can be cultivated by humans over centuries without existing systematic standards and analysis due to their safety and efficacy. Hence, bioactive compounds derived from these medicinal plants apparently have more potential to succeed in toxicology screening when compared with the de novo synthesis of chemicals. The cumulative attention on traditional ethnomedicine may lead to the revealing of innovative therapeutic agents since traditional medicinal plant contains potential antimicrobial components that are beneficial for the development of pharmaceutical agents for the therapy of ailments. Nowadays, studies are progressively turning their consideration to traditional medicine and advancing better drugs to treat diabetes, cancer, and microbial infections [15,16]. A large number of studies have been piloted using medicinal plant extracts and their active principles on bacteria, fungi, algae, and viruses in different localities of the world [9,10]. Various families of traditional medicinal plants have been scientifically tested for their antimicrobial activities and are presented in Table 1. The extracts of plant organs, namely the root, stem, rhizome, bulb, leaf, bark, flower, fruit, and seed, may encompass distinctive phytochemicals with antimicrobial activities [17]. It is well-known that sole plant species of traditional medicine are habitually used to heal a great number of infections or diseases [18]. The plant extracts with an antiquity of folk use should be confirmed using contemporary methods for activities against human pathogens with the intention of identifying potential novel therapeutic drugs. Antibiotics 2019, 8, 257 3 of 57 Table 1. Antimicrobial screening performed on various medicinal plants. Botanical Name Family Plant Used Leaves Barleria prionitis L. Acanthaceae Extracts MIC * Gram Positive Gram Negative Fungi Pet. Ether 3.33–33.3 mg/mL B. subtilis, M. luteus, B. cereus, S. mutans, S. aureus, L. sporogenes - Chloroform 5–50 mg/mL B. subtilis, L. sporogenes Methanol Ethanol 10–100 mg/mL 50–600 µg/mL 25, 50, 100 mg/mL 25, 50, 100 mg/mL 25, 50, 100 mg/mL B. subtilis, L. sporogenes - S. typhi, V. Cholera, M. luteus, Citrobacter S. typhi, V. cholerae, Citrobacter, Providencia V. cholerae, S. typhi, S. typhi Bacillus spp., S. mutans, S. aureus, Pseudomonas spp., S. cerevisiae, C. albicans 4% v/v 625 µg/mL M. tuberculosis, S. aureus E. coli, S. typhi E. coli, S. typhi - 250 µg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes 50 µg/mL S. aureus, S. agalactiae E. coli, S. typhimurium and K. pneumoniae C. albicans [22] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrataC. krusei [23] Acetone Bark References Ethanol Methanol Aqueous Methanol - [19] [20] Adhatoda vasica L. Acanthaceae Leaves Pellaea calomelanos L. Adiantaceae Leaves, Rhizomes Sambucus australis Cham. & Schltdl. Adoxaceae Leaves and Bark Carpobrotus edulis L N.E.Br. Aizoaceae Leaves Achyranthes aspera L. Amaranthaceae Root, Leaves, Stem Ethanol 1 mg/mL S. aureus, B. subtilis, E. coli, P. vulgaris, K. pneumoniae - [16] Alternanthera Sessile L. Amaranthaceae Leaves Ethanol 75 µg/mL S. pyogenes S. typhi - [24,25] Aqueous, Dichloromethane/ Methanol Hexane Ethanol Aqueous Dichloromethane/ Methanol 100 µg/mL 750–12,000 µg/mL P. aeruginosa T. mentagrophytes, M. canis [21] Antibiotics 2019, 8, 257 4 of 57 Table 1. Cont. Botanical Name Family Plant Used Amaranthus caudatus L. Amaranthaceae Leaves Amaranthus hybridus L. Amaranthaceae Amaranthus spinosus L. Boophane disticha L.f. Extracts MIC * Gram Positive Gram Negative Fungi References Chloroform Methanol 162.2–665 mg/mL 1.25 mg/mL 3–5 mg/mL S. aureus, Bacillus spp. E. coli, S. typhi, P. mirabilis - [26] Leaves Ethyl Acetate Chloroform Methanol 200–755 mg/mL 1.25 mg/mL 3–5 mg/mL - E. coli, S. typhi, k. pneumoniae, P. aeruginosa - [26] Amaranthaceae Leaves Ethyl Acetate Chloroform Methanol 129 mg/mL 1.25 mg/mL 3–5 mg/mL - S. typhi - [26] Amaryllidaceae Leaves Aqueous, 20–100 mg/mL T. mentagrophytes, M. canis [21] T. mentagrophytes, M. canis [21] T. mentagrophytes, M. canis [21] T. mentagrophytes, M. canis [21] Ethyl Acetate Rhizomes, Roots Scadoxus puniceus (L.) Friis &Nordal. Amaryllidaceae Harpephyllum caffrum Bernh. exKrauss Anacardiaceae Bark, Leaves Lannea discolor Engl. Anacardiaceae Leaves Polyalthia cerascides L. Annonaceae Berula erecta Huds., Coville Apiaceae Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol Aqueous 750–12,000 µg/mL 50 µg/mL 750–12,000 µg/mL 125–500 µg/mL 750–12,000 µg/mL 50–200 µg/mL Dichloromethane/ Methanol 750–12,000 µg/mL Stem Bark Dichloromethane 100 µg/mL Rhizome, Leaves, Stem Aqueous Dichloromethane/ Methanol 2–16 µg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa P. aeruginosa P. aeruginosa P. aeruginosa C. Dipthieriae - - [27] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] Antibiotics 2019, 8, 257 5 of 57 Table 1. Cont. Botanical Name Family Plant Used Acokanthera oppositifolia L. Codd. Apocynaceae Leaves, Stem Plumeria ruba L. Apocynaceae Leaves Acokanthera oppositifolia (Laim.) Codd., Rauvolfia caffra Sond. Apocynaceae Apocynaceae Leaves Leaves Extracts MIC * Aqueous Dichloromethane/ Methanol 25–200 µg/mL 750–12,000 µg/mL Aqueous Dichloromethane/ Methanol 50–200 µg/mL Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol 10–50 µg/mL 750–12,000 µg/mL 25, 50 µg/mL 750–12,000 µg/mL Apocynaceae Latex Ethanol 1–8 mg/mL Plumeria alba L. Apocynaceae Root Methanol Aqueous Aquifoliaceae Anchomanes difformis Engl. Araceae Roots Zantedeschia aethiopica Spreng Araceae Leaves Bark, Leaves Dichloromethane/ Methanol Gram Negative Fungi References S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] S. epidermidis E. coli - [16] T. mentagrophytes, M. canis [21] T. mentagrophytes, M. canis [21] 100 µg/mL Calotropis gigantea L. Ilex mitis Radlk. Gram Positive S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa - - 10–40 µg/mL - E. coli 1–8 mg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes 750–12,000 µg/mL Methanol 20–100 mg/mL methicillin-resistant S. aureus Aqueous 50 µg/mL 15–150 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Dichloromethane/ Methanol P. aeruginosa P. aeruginosa P. aeruginosa C. albicans, T. mentagrophytes, T. rubrum [16] [16] T. mentagrophytes, M. canis [21] - [28] T. mentagrophytes, M. canis [21] Arum dioscoridis L. Araceae Leaves Aqueous 125–500 µg/mL S. aureus, S. pneumoniae E. coli, S. typhi, P. aeruginosa - [29] Aristolochia Indica L. Aristolochiaceae Leaves Ethanol 1–8 mg/mL - - A. niger A. flavus A. fumigatus [3,4,30,31] Antibiotics 2019, 8, 257 6 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Vernonia blumeoides Hook. f. Asteraceae Aerial Part Ethanol 100 µg/mL methicillin-resistant S. aureus - - [28] Artemisia afra Jacq. ex Willd. Asteraceae Leaves, Stem S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] Tarchonanthus camphoratus L. Asteraceae Leaves S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] Helichrysum paronychioides L. Asteraceae Whole Plant B. cereus S. flexneri Senecio longiflorus L. Asteraceae Stem and Leaves B. cereus S. flexneri Dahlia pinnata L. Asteraceae Leaves Chloroform 2–16 µg/mL – E. aerogenes, P. aeruginosa Athrixia phylicoides DC. Asteraceae Leaves Aqueous 25–200 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Dicoma anomala Sond. Asteraceae Vernonia natalensis Sch. Bip. exWalp. Asteraceae Achillea millefolium L. Asteraceae Leaves Ethanol 100 µg/mL S. aureus P. aeruginosa S. typhi, E. coli C. albicans [29] Blumea balsamifer (Linn.) D.C. Asteraceae Whole Plant Ethanol 250 µg/mL methicillin-resistant S. aureus - - [32] Impatiens balsamina L. Balsaminaceae Leaf Ethanol 50–200 µg/ml methicillin-resistant S. aureus - - [28] Berberis chitria L. Berberidaceae Roots Ethanol, Methanol 5.5–6.5 mg/mL 2.5–3.5 mg/mL S. aureus E. coli - [33] Aqueous Dichloromethane/ Methanol 2–16 µg/mL 750–12,000 µg/mL Aqueous Dichloromethane/ Methanol 25–200 µg/mL 750–12,000 µg/mL Pet ether Methanol 50–200 µg/mL 50–200 µg/mL Pet ether 125–625 µg/mL Methanol 50–200 µg/mL Dichloromethane/ Methanol Tuber Aqueous Dichloromethane/ Methanol Leaves, Roots Aqueous Dichloromethane/ Methanol 750–12,000 µg/ml 50–200 µg/mL 750–12,000 µg/mL 10–50 µg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa P. aeruginosa P. aeruginosa C. glabrata, C. krusei, T. rubrum and T. tonsurans C. glabrata, C. krusei, T. rubrum and T. tonsurans – T. mentagrophytes, M. canis T. mentagrophytes, M. canis T. mentagrophytes, M. canis [2] [2] [16] [21] [21] [21] Antibiotics 2019, 8, 257 7 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Alnus nepalensis D. Don. Betulaceae TBL Ethanol 50–200 µg/mL Methicillin-resistant S. aureus - - [32] Tecoma capensis Lindl. Bignoniaceae Leaves, Stem S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] Spathodea campanulata L. Bignoniaceae Kigelia africana (Lam.) Benth. Bignoniaceae Opuntia ficus-indica Mill. Cactaceae Leaves Senna italic L. Caesalpiniaceae Leaves Cassia fistula L. Caesalpiniaceae Seeds Warburgia salutaris (G. Bertol.) Chiov. Cadaba fruticosa L. Leaves Aqueous, Dichloromethane/ Methanol Ethanol Flowers Fruit Capparaceae Bark, Twigs Leaves 2.5 mg/mL 221–254 µg/mL B. subtilis, S. aureus, 156–173 µg/mL Aqueous Dichloromethane/ Methanol Canellaceae 10–50 µg/mL 2–16 µg/mL 750–12,000 µg/mL Aqueous 25–200 µg/mL Dichloromethane Methanol 750–12,000 µg/mL Acetone Aqueous Ethanol Aqueous S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes E. coli, K. pneumonia, P. vulgaris, S. typhi, Pseudomonas spp., V. cholerae P. aeruginosa - [6,34,35] T. mentagrophytes, M. canis [21] S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa T. mentagrophytes, M. canis [21] 2.5 mg/mL B. cereus, B. pumilus, B. subtilis, S. aureus, E. faecalis, - - [36] 780–6250 µg /mL 2–16 µg/mL S. aureus - - [6] 5.0–10 mg/mL S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] 50–200 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa Dichloromethane, Methanol 750–12,000 µg/mL Acetone Aqueous Benzene Butanol Chloroform Ethanol 100–200 µg/mL 4–16 µg/mL 4–16 µg/mL 4–16 µg/mL 4–16 µg/mL 4–16 µg/mL S. pyogens, S. aureus, B. subtilis S. typhi, P. vulgaris, K. pneumoniae, P. aeruginosa, E. coli T. mentagrophytes, M. canis - [21] [37] Antibiotics 2019, 8, 257 8 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Boscia senegalensis Del. Capparidaceae Roots Methanol 10–20 µg/mL methicillin-resistant S. aureus - - [28] Celastrus orbiculatus Thunb. Celastraceae Vane Ethanol 1–2 mg/mL methicillin-resistant S. aureus - - [32] Euonymus fortunei (Turcz.); Hand. Mazz. Celastraceae Leaves Ethanol 10–40 µg/mL methicillin-resistant S. aureus - - [32] Chenopodiaceae Leaves Aqueous 2–16 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes T. mentagrophytes, M. canis [21] Chenopodium ambrosioides Bert. ex Steud. Dichloromethane/ Methanol 750–12,000 µg/mL P. aeruginosa Garcinia mangostana L. Clusiaceae Fruit Shell Ethanol 25–200 µg/mL methicillin-resistant S. aureus - - [28] Garcinia morella Desr. Clusiaceae Whole Plant Ethanol 100–400 µg/mL methicillin-resistant S. aureus - - [32] Terminalia paniculata L. Combretaceae Stem Bark Ethyl Acetate Methanol 3.25, 3.5 mg/mL 5–20 µg/mL S. aureus, B. subtilis - - [38] Terminalia sericea Burch. ex DC. Combretaceae Roots Aqueous 100–300 µg/mL T. mentagrophytes, M. canis [21] Eupatorium odoratum L. Compositae Leaves Benzene Aqueous Acetone 300–600 µg/mL 300–600 µg/mL 300–600 µg/mL B. cereus, S. aureus E. coli, K. pneumoniae, V. cholerae C. albicans [39] Acmella paniculata L. Compositae Whole Plant Chloroform Pet. ether Methanol 15 µg/mL 5–15 µg/mL 5–15 µg/mL - E. aerogenes - [40] Dichloromethane/ Methanol 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa Antibiotics 2019, 8, 257 9 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Cotyledon orbiculata L. Crassulaceae Leaves Aqueous Dichloromethane Methanol 5–30 µg/mL 750–12,000 µg/mL S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] Cotyledono rbiculata Forssk. Crassulaceae Leaves Aqueous 25–200 µg/mL Mormodica basalmina L. Cucurbitaceae Whole Plant Coccinia grandis L. Cucurbitaceae Leaves Luffa acyntangula L. Cucurbitaceae Leaves Mukia maderspatana L. Cucurbitaceae Leaves Trichosanthes cucumerina L. Cucurbitaceae Leaves Momordica balsamina L. Cucurbitaceae Leaves, Roots Acetone Carex prainii C.B. Clarke Cyperaceae Whole Plant Ethanol Dichloromethane/ Methanol Methanol 750–12,000 µg/mL 500 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa T. mentagrophytes, M. canis [21] methicillin-resistant S. aureus - - [28] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] 500 µg/mL B. cereus, B. pumilus, B. subtilis, S. aureus, E. faecalis E. coli, E. cloaceae, K. pneumoniae, P. aeruginosa, S. marcescens - [42] 15–45 µg/mL methicillin-resistant S. aureus - - [32] Aqueous Dichloromethane/ Methanol 500 µg/mL Aqueous Dichloromethane Methanol 5 mg/mL Aqueous Dichloromethane/ Methanol 5 mg/mL Aqueous Dichloromethane/ Methanol 5 mg/mL 2 mg/mL 2 mg/mL 1 mg/mL 1 mg/mL Antibiotics 2019, 8, 257 10 of 57 Table 1. Cont. Botanical Name Family Plant Used Dioscorea dregeana T. Durand & Schinz. Dioscoreaceae Tuber Sansevieria hyacinthoides L. Dracaenaceae Leaves, rhizome Diospyros mespiliformis Hochst. exA. DC. Ebenaceae Leaves Phyllanthus amarus Schum. Thonn. Euphorbiaceae Whole Plant Croton gratissimus Burch. Euphorbiaceae Leaves, Stem, Spirostachys africana Sond. Euphorbiaceae Leaves, Bark Acalypha indica L. Euphorbiaceae Leaves Bridelia micrantha Baill. Euphorbiaceae Bark, Leaves Emblica officinalis L. Euphorbiaceae Extracts MIC * Gram Positive Aqueous 5–30 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Dichloromethane/ Methanol 750–12,000 µg/mL Aqueous, Dichloromethane/ Methanol 1–4 mg/mL 750–12,000 µg/mL Aqueous Dichloromethane/ Methanol Methanol Aqueous 750–12,000 µg/mL 650–600 µg/mL 5 mg/mL Dichloromethane/ Methanol 750–12,000 µg/mL Aqueous Dichloromethane/ Methanol 490 µg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes [21] C. albicans C. glabrataC. krusei [23] T. mentagrophytes, M. canis [21] [28] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrataC. krusei [23] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrataC. krusei [23] - - [43] T. mentagrophytes, M. canis [21] C. albicans [39] Aqueous 5 mg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes 350–600 µg/mL 300–600 µg/mL 300–600 µg/mL P. aeruginosa T. mentagrophytes, M. canis - M. tuberculosis Benzene Aqueous Acetone P. gingivalis F. nucleatum References - 4% v/v 750–12,000 µg/mL P. aeruginosa Fungi methicillin-resistant S. aureus Aqueous Dichloromethane/ Methanol Leaves 15–45 µg/mL S. mutans, S. sanguis, L. acidophilus L. casei Gram Negative B. cereus, S. aureus P. aeruginosa E. coli, K. pneumoniae, V. cholerae Antibiotics 2019, 8, 257 11 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Hevea brasiliensis L. Euphorbiaceae Leaves Benzene Aqueous Acetone 350–600 µg/mL 300–600 µg/mL 300–600 µg/mL B. cereus, S. aureus E. coli, K. pneumoniae, V. cholerae C. albicans [39] Mallotus yunnanensis Pax et. Hoffm. Euphorbiaceae Tender Branches & Leaves Ethanol 8–256 µg/mL methicillin-resistant S. aureus - - [32] Acacia albida Del. Acacia catechu (L. f.) Willd Fabaceae Stem Bark Methanol 50 µg/mL methicillin-resistant S. aureus - - [28] Fabaceae Wood Ethanol 100 µg/mL methicillin-resistant S. aureus - - [28] Peltophorum ptercarpum (DC.) Fabaceae Bark Ethanol 4% v/v methicillin-resistant S. aureus - - [28] Acacia erioloba Edgew. Fabaceae Bark and Leaves Dichloromethane/ Methanol 1.56–3.12 mg/mL 750–12,000 µg/mL S. aureus, methicillin– resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Dichrostachys cinerea L. Fabaceae Stem Aqueous Dichloromethane/ Methanol 129 mg/mL 750–12,000 µg/mL Albizia odoratissima (L.f.) Benth Fabaceae Leaves Hexane Chloroform Ethyl Acetate Methanol Prosopis juliflora L. Fabaceae Pod Chloroform Bauhinia macranthera Benth. Ex Hemsl. Fabaceae Leaves Aqueous Aqueous, Dichloromethane/ Methanol P. aeruginosa T. mentagrophytes, M. canis C. albicans C. glabrata C. krusei [21] [23] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum 7.5–15 mg/mL 859–6875 µg/mL 136–546 µg/mL 136–546 µg/mL S. aureus K. pneumoniae, E. coli, P. aeruginosa, P. vulgaris - [44] 250 µg/mL M. luteus, S. aureus, S. mutans - - [36] 1.56–3.12 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa T. mentagrophytes, M. canis [21] Antibiotics 2019, 8, 257 12 of 57 Table 1. Cont. Botanical Name Family Plant Used Erythrina lysistemon Hutch. Fabaceae Elephantorrhiza elephantina (Burch.) Skeels Fabaceae Albizia lebbeck L. Fabaceae Leaves Adenanthera pavonina L. Fabaceae Leaves Alysicarpus vaginalis L. Fabaceae Leaves Bauhinia acuminate L. Fabaceae Leaves Bauhinia purpurea L. Fabaceae Leaves Bauhinia racemose L. Fabaceae Leaves, Stem Bark Cassia alata L. Fabaceae Leaves Cassia auriculata L. Fabaceae Leaves Cassia fistula L. Fabaceae Root Bark, Stem Bark Leaves Extracts Aqueous Dichloromethane/ Methanol Leaves, roots and rhizomes Aqueous Dichloromethane/ Methanol Benzene, Aqueous and Acetone Aqueous Dichloromethane/ Methanol MIC * Gram Negative Fungi S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes, S. mutans, S. sanguis, L. acidophilus L. casei P. aeruginosa, P. gingivalis F. nucleatum T. mentagrophytes, M. canis, C. albicans C. glabrata C. krusei 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes, B. cereus P. aeruginosa, S. flexneri T. mentagrophytes, M. canis, C. glabrata, C. krusei, T. rubrum and T. tonsurans 350–600 µg/mL B. cereus, S. aureus E. coli, K. pneumoniae, V. cholera C. albicans [39] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] 4 mg/mL 750–12,000 µg/mL 1–4 mg/mL 5 mg/mL Gram Positive References [21] [21] 60 µg mg/mL Aqueous Dichloromethane/ Methanol 5 mg/mL Aqueous Dichloromethane/ Methanol 5 mg/mL 2 mg/mL 50 µg mg/mL Aqueous Dichloromethane/ Methanol 5 mg/mL Aqueous Dichloromethane/ Methanol 500 µg/mL 1 mg/mL 500 µg/mL Aqueous Dichloromethane/ Methanol 250 µg/mL Aqueous Dichloromethane/ Methanol 1 mg/mL 500 µg/mL 4 mg/mL Aqueous 1–5 mg/mL Dichloromethane/ 500–1000 µg/mL Methanol Antibiotics 2019, 8, 257 13 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Cassia tora L. Fabaceae Leaves, Root Bark, Stem Bark Aqueous 250–4000 µg/mL Crotalaria retusa L. Fabaceae Leaves Crotalaria verrucosa L. Fabaceae Leaves Derris Scandens L. Fabaceae Leaves Desmodium triflorum (L.) DC. var. majus Wight & Arn. Fabaceae Stem Bark Erythuria variegate L. Fabaceae Leaves, Stem Bark Indigofera tinctoria L. Fabaceae Leaves Mimosa pudica L. Fabaceae Stem Bark Myroxylon balsamum L. Fabaceae Leaves Pterocarpus marsupium Roxb. Fabaceae Leaves Pterocarpus santalinus L. Fabaceae Leaves Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol 4 mg/mL Aqueous Dichloromethane/ Methanol 100 µg/mL Aqueous Dichloromethane/ Methanol 1 mg/mL B. cereus, S. aureus - - B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] [41] 4 mg/mL 25 µg/mL 500 µg/mL 4 mg/mL Aqueous 1–2 mg/mL Dichloromethane/ 250–5000 µg/mL Methanol Aqueous Dichloromethane/ Methanol References 1 mg/mL Aqueous 1–5 mg/mL Dichloromethane/ 250–1000 µg/mL Methanol Aqueous Dichloromethane/ Methanol Fungi 60 µg/mL 1 mg/mL Aqueous Dichloromethane/ Methanol Gram Negative 1000–4000 µg/mL Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol Gram Positive 1 mg/mL 500 µg/mL 4 mg/mL 250 µg/mL 2 mg/mL 4 mg/mL Antibiotics 2019, 8, 257 14 of 57 Table 1. Cont. Botanical Name Family Plant Used Saraca asoca (Roxb.) Willd Fabaceae Leaves Sesbania grandiflora (L.) Poiret Fabaceae Stem Bark, Root Bark, Leaves Tamarindus indica L. Fabaceae Leaves Tephrosia purpurea L. Pers. Fabaceae Leaves Butea monosperma L. Fabaceae Leaves Extracts MIC * Aqueous Dichloromethane/ Methanol 120 µg/mL Aqueous, Dichloromethane/ Methanol 2 mg/mL Gram Negative Fungi References B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus, methicillin-resistant S. aureus - - [41,45] 5 mg/mL 100 µg/mL Aqueous 250–500 µg/mL Dichloromethane/ 60–100 µg/mL Methanol Aqueous Dichloromethane/ Methanol Gram Positive 5 mg/mL 5 mg/mL Aqueous 4 mg/mL Dichloromethane/ 2 mg/mL Methanol Ethanol 100–200 µg/mL Senna alata Fabaceae Leaf Ethanol 100 µg/mL methicillin-resistant S. aureus - - [46] Quercus infectoria Olivier Fagaceae Nutgalls Ethanol 100–200 µg/mL methicillin-resistant S. aureus - - [16] Cyclobalanopsis austroglauca Y.T. Chang Fagaceae TBL Ethanol 8–256 µg/mL methicillin-resistant S. aureus - - [32] Scaevola spinescens L. Goodeniaceae Aerial parts Ethyl Acetate, Methanol 500 µg/mL S. pyogenes, S. aureus - - [38] Gunnera perpensa L. Gunneraceae Leaves, Rhizome Aqueous, 4 mg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. mutans, S. sanguis, L. acidophilus L. casei T. mentagrophytes, M. canis [21] Eucomis punctate L’Her. Hyacinthaceae Leaves Dichloromethane/ Methanol 750–12,000 µg/mL Aqueous, Dichloromethane/ Methanol 500 µg/mL 750–12,000 µg/mL P. aeruginosa P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] Antibiotics 2019, 8, 257 15 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Drimia sanguinea L. Hyacinthaceae Bulb Pet ether 18.75, 37.5, 300, 600, 1200 µg/mL B. cereus S. flexneri C. glabrata, C. krusei, T. rubrum and T. tonsurans [2] Hypoxis hemerocallidea L. Hypoxidaceae Leaves Pet ether 195–12,500 µg/mL B. cereus S. flexneri Methanol 390–3125 µg/mL Curculigo orchioides Gaertn. Hypoxidaceae Whole Plant Ethanol 8–256 µg/mL methicillin-resistant S. aureus - - [32] Illicium simonsii Maxim. Illiciaceae TBL Ethanol 8–256 µg/mL methicillin-resistant S. aureus - - [32] Aristea ecklonii Baker. Iridaceae Leaves and Roots Aqueous 129 mg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. mutans, S. sanguis, L. acidophilus L. casei T. mentagrophytes, M. canis [21] Tetradenia riparia Hochst. Lamiaceae Leaves, Stem Thymus vulgaris L. Lamiaceae Leaves Lamiaceae Aerial Parts Stachys guyoniana Noë ex. Batt. Lamiaceae Leaves Ocimum basilicum L. Lamiaceae Stem, leaves Lamiaceae Leaves 750–12,000 µg/mL Aqueous 200–755 mg/mL 750–12,000 Dichloromethane/ Methanol µg/mL Essential Oil P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [47] [23] 50 µg/mL methicillin-resistant S. aureus - - [48] Chloroform Acetone 1.56–3.12 mg/mL 128 µg/mL 32–128 µg/mL S. aureus E. coli, P. aeruginosa, S. heidelberg, K. pneumoniae, E. aerogenes, M. morganii - [49] n-Butanol 4 mg/mL E. coli, P. aeruginosa, S. heidelberg, K. pneumoniae, E. aerogenes, M. morganii - Methanol Mentha aquatica L. Ocimum gratissimum L. Dichloromethane/ Methanol P. aeruginosa T. rubrum, T.urans, C. glabrata C. krusei [49] Ethyl Acetate Chloroform 128 µg/mL 32–128 µg/mL S. aureus Ethanol 1–4 mg/mL S. aureus - - [38] S. aureus S. typhi, E. coli, S. paratyphi - [38] Methanol 780–6250 µg/mL Antibiotics 2019, 8, 257 16 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Ocimum sanctum L. Lamiaceae Whole Plant Methanol 360 µg/mL S. aureus, S. saprophyticus S. typhi, E. coli, S. paratyphi - [6] Mentha longifolia Huds. Lamiaceae Leaves Melissa officinalis L. Lamiaceae Leaves Aqueous Dichloromethane/ Methanol Ethanol 150, 300, 600 µg/mL 750–12,000 µg/mL P. aeruginosa T. mentagrophytes, M. canis [21] K. pneumoniae - [42] 2.5 mg/mL B. cereus, B. pumilus, B. subtilis, S. aureus, E. faecalis - - [16] Ethanol 500 µg/mL methicillin-resistant S. aureus - - [32] TBL Ethanol 1–4 mg/mL methicillin-resistant S. aureus - - [32] Leguminosae Aerial Parts, Seeds Ethanol 129 mg/mL B. subtilis, S. aureus, B. subtilis P. aeruginosa - [50] Acacia karroo Hayne. Leguminosae Leaves, Stem S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei Acacia polyacantha Willd. Leguminosae Leaves, Stem S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei Ocimum americanum L. Lamiaceae Leaves Acetone Machilus salicina Hance. Lauraceae Tender Branches & Leaves Meliosma squamulata Hance. Lauraceae Sophora alopecuroides Aqueous, 200–755 mg/mL 750–12,000 Dichloromethane/ Methanol µg/mL Aqueous Dichloromethane/ Methanol Dalbergia obovate E. Mey. Leguminosae Leaves, stem 49 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes - Aqueous Dichloromethane/ Methanol 50 µg/mL [23] [23] 750–12,000 µg/mL 1.56–3.12 mg/mL 750–12,000 µg/mL [23] Antibiotics 2019, 8, 257 17 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Sophora jaubertii Leguminosae Aerial Parts, Seeds Ethanol 4 mg/mL B. subtilis, P. aeruginosa, S. aureus - - [38] Glycyrrhiza glabra L. Leguminosae Leaves Methanol 1–4 mg/mL K. kristinae, M. luteus, S. auricularis, B. megaterium A. bohemicus, E. coli - [51] Allium cepa L. Liliaceae Bulb Aqueous 780–6250 µg/mL M. tuberculosis - - [43] Allium sativum L. Liliaceae Bulb Aqueous 4% v/v M. tuberculosis - - [43] Allium vera L. Liliaceae Gel Aqueous 4% v/v M. tuberculosis - - [43] Chloroform Acetone Ethanol 129 mg/mL 6 mg/mL 6 mg/mL S. aureus P. aeruginosa - [39] S. aureus, B. cereus S. typhi, E. coli, S. dysenteriae. V. cholerae - [37] 50 µg/mL methicillin-resistant S. aureus - - [32] 500 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes T. mentagrophytes, M. canis [21] - [38] Lobelia nicotianaefolia L. Lobeliaceae Root Woodfordia fruticose L. Lythraceae Flower Manglietia hongheensis Y.m Shui et. W.H. Chen. Magnoliaceae TBL Malva parviflora L. Malvaceae Leaves Aqueous 200–755 mg/mL Dichloromethane/ 100 mg/mL Methanol Ethanol Aqueous Dichloromethane/ Methanol Sida rhombifolia L. Malvaceae Stem 750–12,000 µg/mL Chloroform 162.2–665 mg/mL S. lutea, B. subtilis, P. aeruginosa E. coli, Shigella shiga Walsura robusta L. Meliaceae Wood Ethanol 250 µg/mL methicillin-resistant S. aureus - - [28] Swietenia mahagoni Meliaceae Seed Ethanol 500 µg/mL methicillin-resistant S. aureus - - [52] Azadirachta indica Meliaceae LeavesStem 1.56–3.12 mg/mL M. luteusS. aureus, S. pyogenes P. vulgarisE. coli, P. aeruginosa – [53] MethanolAqueous Antibiotics 2019, 8, 257 18 of 57 Table 1. Cont. Botanical Name Family Plant Used Ekebergia capensis Sparrm. Meliaceae Bark, Leaves Trichilia emetica Vahl Meliaceae Leaves Extracts Meliaceae Leaves Aqueous 1.59–25 mg/mL 750–12,000 Dichloromethane/ Methanol µg/mL Aqueous Dichloromethane/ Methanol S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Melianthaceae Melianthus major L. Melianthaceae Leaves Aqueous Aqueous 50 mg/mL Ethanol Dichloromethane/ Methanol Leaves Melianthus major L. Melianthaceae Leaves Cissampelos torulosa E. Mey. Ex Harv. Menispermaceae Leaves, Stem Tinospora crispa L. Menispermaceae Stem Cissampelos capensis Thunb. Menispermaceae Leaves 50–600 µg/mL 750–12,000 µg/mL 3.33–33.3 mg/mL 500 µg/mL 1.56–3.12 mg/mL 10–30 mg/mL Pet.ether Melianthus comosus Vahl. Gram Positive S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Methanol Melia azedarach L. MIC * Ethanol Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol Ethanol Aqueous Dichloromethane/ Methanol Gram Negative P. aeruginosa P. aeruginosa B. cereus, S. aureus E. coli, P. aeruginosa S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes, methicillin-resistant S. aureus P. aeruginosa 10–100 mg/mL methicillin-resistant S. aureus - 5–50 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes 4–64 mg/mL 25, 50, 100 mg/mL 750–12,000 µg/mL P. aeruginosa Fungi T. mentagrophytes, M. canis T. mentagrophytes, M. canis A. niger, A. flavus, F. oxysporum, R. stolonifer [21] [21] [16] T. mentagrophytes, M. canis [28] - [28] T. mentagrophytes, M. canis S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei 10 mg/mL methicillin-resistant S. aureus - - 3.33–33.3 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa References T. mentagrophytes, M. canis [21] [23] [21] [21] Antibiotics 2019, 8, 257 19 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Aqueous Dichloromethane/ Methanol 250 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Gram Negative Fungi Aqueous, Dichloromethane/ Methanol 10–100 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes 5–50 mg/mL methicillin-resistant S. aureus - - S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei T. mentagrophytes, M. canis References Ficus natalensis Hochst. Moraceae Leaves Ficus sur Forssk. Moraceae Bark, Leaves Moringa oleifera Lam. Moringacceae Leaf Myrothamnus flabellifolia Welw., Myrothamnaceae Leaves Embelia ruminate (E. Mey.exA.Dc.) Mez Myrsinaceae leaves Embelia burm f. Myrsinaceae Leaves Ethanol 500 µg/mL methicillin-resistant S. aureus - - [32] Callistemon rigidus R.Br. Myrtaceae Leaf Methanol 800 mg/disc methicillin-resistant S. aureus - - [28] Psidium guajava L. Myrtaceae Leaf Ethanol 600, 1200 µg/mL methicillin-resistant S. aureus - - [28] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei Heteropyxis natalenesis Harv. Myrtaceae Leaves, Stem Eucalyptus camaldulensis Dehnh. Myrtaceae Bark Ethanol Aqueous 156–625 µg/mL 750–12,000 Dichloromethane/ Methanol µg/mL Aqueous 350–600 µg/mL 750–12,000 Dichloromethane/ Methanol µg/mL Aqueous, Dichloromethane/ Methanol 5 mg/mL 750–12,000 µg/mL 9.375, 18.75, 37.5, 75, 150, 300, 600 µg/mL 750–12,000 Dichloromethane/ Methanol µg/mL Aqueous S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa P. aeruginosa P. aeruginosa P. aeruginosa T. mentagrophytes, M. canis T. mentagrophytes, M. canis T. mentagrophytes, M. canis [21] [21] [28] [23] [21] [23] [21] Antibiotics 2019, 8, 257 20 of 57 Table 1. Cont. Botanical Name Family Plant Used Eucalyptus deglupta Myrtaceae Leaves Myrtus communis L. Myrtaceae Nelumbo nucifera L. Nymphaea lotus L. Oxalis corniculata L. MIC * Gram Positive Gram Negative Fungi References Aqueous Acetone 37.5, 75, 150, 300, 600 µg/mL 4–8 mg/mL 6 mg/mL B. cereus, S. aureus E. coli, K. pneumoniae, V. cholerae C. albicans [39] Leaves Ethanol 12.5–50 mg/mL B. cereus, L. monocytogenes E. coli C. albicans [42] Nelumbonaceae Flower Ethanol 8–32 mg/mL B. subtilis, S. aureus, E. coli, K. pneumonia, P. aeruginosa - [54] Nymphaeaceae Leaf Ethanol 500 µg/mL methicillin-resistant S. aureus - - [21] Aqueous B. cereus, S. aureus E. coli, K. pneumoniae, V. cholera C. albicans [39] Acetone 5 mg/mL 37.5, 75, 150, 300, 600 µg/mL 6 mg/mL Oxalidaceae Extracts Benzene Leaves Benzene Paeonia lactiflora Pall. Paeoniaceae Leaves Ethanol 22.4–52.3 µg/mL K. kristinae, M. luteus, S. auricularis, B. megaterium A. bohemicus, E. coli - [51] Argemone mexicana Papaveraceae Stem Chloroform 32.4–55.8 µg/mL S. aureus E. coli, P. aeruginosa, k. pneumoniae - [55] Passiflora Mexicana L. Passifloraceae Aerial Parts Ethanol 33.7–58.3 µg/mL S. aureus - - [21] Cleistanthus collinus Phyllanthaceae Leaves Benzene Aqueous Acetone 100 mg/mL 4–8 mg/mL 5 mg/mL B. cereus, S. aureus E. coli, K. pneumoniae, V. cholerae C. albicans [39] Piper nigrum L. Piperaceae Bark, Seeds S. aureus, B. cereus, S. fecalis P. aeruginosa, E. coli, S. typhi - [38] Ethanol Acetone Dichloromethane/ Methanol 500 µg/mL 6 mg/mL 12.5–50 µg/mL Antibiotics 2019, 8, 257 21 of 57 Table 1. Cont. Botanical Name Family Plant Used Pittosporum viridiflorum Sims. Pittosporaceae Leaves Extracts Aqueous Dichloromethane/ Methanol MIC * Gram Positive 600 µg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Gram Negative Fungi References P. aeruginosa T. mentagrophytes, M. canis [21] Spinifex littoreus Poaceae Grass Acetone 2.5 mg/mL - - Dermatophytes [27] Polygonum molle D. Don. Polygonaceae Whole Plant Ethanol 25–50 µg/mL Methicillin-resistant S. aureus - - [32] Eichhornia crassipes L. Pontederiaceae Leaves, Shoot Ethanol Chloroform Aqueous 500–4000 µg/mL 32.4–55.8 µg/mL 2.5–15 µg/mL M. luteus R. rubrum M. ruber, A. fumigates [56] Punica granatum L. Punicaceae Fruit Shell Ethanol 70 mg/mL Methicillin-resistant S. aureus - - [28] Clematis brachiate Thunb. Ranunculaceae Flower, Leaves, Stem, Root S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei Ziziphus mucronata Willd. Rhamnaceae Bark, Leabes S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes, S. mutans, S. sanguis, L. acidophilus L. casei P. aeruginosa, P. gingivalis F. nucleatum T. mentagrophytes, M. canis, C. albicans C. glabrata C. krusei Eriobotrya japonica (Thunb.) Lindl. Rosaceae Leaves Ethanol 2–16 µg/mL K. kristinae, M. luteus, S. auricularis, B. megaterium A. bohemicus, E. coli - [51] Rubiaceae Leaf Methanol 12.5–50 mg/mL methicillin-resistant S. aureus - - [28] Rubiaceae Leaf, Stem Ethanol 8–32 mg/mL methicillin-resistant S. aureus - - [28] Rubiaceae Leaves Ethyl Acetate 500 µg/mL S. aureus E. coli, K. pneumoniae, P. aeruginosa - [57] Pavetta crassipes K. Schum. Uncaria gambir (Hunter) Roxb. Vangueria spinose L. Aqueous, Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol 1 mg/mL 750–12,000 µg/mL 2.5 mg/mL 750–12,000 µg/mL [23] [21] Antibiotics 2019, 8, 257 22 of 57 Table 1. Cont. Botanical Name Family Plant Used Pentanisia prunelloides Walp. Rubiaceae Root Bark Rothmannia capensis Thunb. Rubiaceae Leaves Geophila repens L. Rubiaceae Leaves, Stem Bark Rubiaceae Leaves Rubiaceae Leaves Hedyotis auricularia L. Rubiaceae Leaves Knoxia zeylanica L. Rubiaceae Leaves, Stem Mitragyna parvifolia L. Rubiaceae Leaves Morinda umbellate L. Rubiaceae Leaves, Stem Bark Nauclea orientalis L. Rubiaceae Leaves Oldenlandia biflora L. Rubiaceae Leaves Rubiaceae Stem, Root Guettarda speciose L. Haldina cordifolia L. Oldenlandia herbacea L. Extracts Aqueous Dichloromethane/ Methanol MIC * Gram Positive 5 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Aqueous 22.4–52.3 µg/mL Dichloromethane/ 750–12,000 Methanol µg/mL Aqueous Dichloromethane/ methanol Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol 1 mg/mL P. aeruginosa P. aeruginosa Fungi T. mentagrophytes, M. canis T. mentagrophytes, M. canis References [21] [21] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] 250 µg/mL 2 mg/mL 2 mg/mL 1 mg/mL 500 µg/mL 300 µg/mL 250 µg/mL Aqueous Dichloromethane/ Methanol 250 µg/mL Aqueous Dichloromethane/ Methanol 300 µg/mL Aqueous Dichloromethane/ Methanol 100 µg/mL 1 mg/mL 1 mg/mL 250 µg/mL Aqueous Dichloromethane/ Methanol 500 µg/mL Aqueous Dichloromethane/ Methanol 2 mg/mL Aqueous Dichloromethane/ Methanol S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Gram Negative 500 µg/mL 5 mg/mL 5mg/mL 60 µg/mL Antibiotics 2019, 8, 257 23 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts Ophiorrhiza mungos L. Rubiaceae Leaves Gram Positive Gram Negative Fungi References B. cereus, S. aureus - - [41] Paederia foetida L. Rubiaceae Leaves, Stem B. cereus, S. aureus - - [41] Pavetta lanceolate Eckl. Rubiaceae Leaves B. cereus, S. aureus - - [41] Spermacoce hispida L. Rubiaceae Leaves, Stem B. cereus, S. aureus - - [41] Wendlandia bicuspidate Wight & Arn. Rubiaceae Leaves B. cereus, S. aureus - - [41] Chassalia kolly Rubiaceae Whole Plant Mthanol 5 mg/mL S. aureus E. coli, P. aeruginosa, S. typhi, P. aeruginosa - [16] Randia dumetorum L. Rubiaceae Fruits Methanol 9.375, 18.75, 37.5, 75, 150, 300, 600 µg/mL S. aureus, S. epidermidis, B. subtilis E. coli, S. typhi - [23] Mitragyna speciosa L. Rubiaceae Leaves Methanol 37.5, 75, 150, 300, 600 µg/mL S. typhi Clausena anisate (Willd) Hook. f. ex. Rutaceae Leaves, Stem, Twigs Zanthoxylum capense Harv. Rutaceae Stem Aegle marmelos L. Rutaceae Leaves and Fruits Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol Aqueous Dichloromethane/ Methanol MIC * 2 mg/mL 500 µg/mL 300 µg/mL 60 µg/mL 1 mg/mL 250 µg/mL Aqueous Dichloromethane/ Methanol 300 µg/mL Aqueous Dichloromethane/ Methanol 60 µg/mL 120 µg/mL 5 mg/mL [42] Aqueous 12.5–50 mg/mL 750–12,000 Dichloromethane/ Methanol µg/mL S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] Aqueous Dichloromethane/ Methanol 8–32 mg/mL 750–12,000 µg/mL S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] 500 µg/ml S.aureus, B. cereus E. coli, S. typhi, P. aeruginosa, S. boydii, K. aerogenes, P.vulgaris, Methanol [20] Antibiotics 2019, 8, 257 24 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Evodia daneillii (Benn) Hemsl. Rutaceae Tender Branches & Leaves Ethanol 3.33–33.3 mg/mL Methicillin-resistant S. aureus - - [32] Skimmia arborescens Anders. Rutaceae TBL Ethanol 250 mg/mL Methicillin-resistant S. aureus - - [32] 10–100 mg/mL B. cereus, B. pumilus, B. subtilis, S. aureus, E. faecalis - - [18] 5–50 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes 156–625 µg/mL methicillin-resistant S. aureus - - S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei 500 µg/mL 60 µg/mL 40 µg/mL S. aureus, S. agalactiae E. coli, S. typhimurium and K. pneumoniae T. rubrum, C. albicans 800 mg/disc 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Salvadora australis Salvadoraceae Leaves Viscum capense L.f. Santalaceae Leaves Dodonaea angustifolia (L.f.) Benth Sapindaceae Leaves Dodonaea viscosa Jacq. Sapindaceae Leaves, Stem Cardiospermum halicacabum L. Sapindaceae Leaves Dodonaea angustifolia L. f. Sapindaceae Leaves Sapotaceae Leaves, Stem Schisandraceae Vane Englerophytum magalismontanum Sonder. Schisandra viridis A.c. Smith. Acetone Aqueous Dichloromethane/ Methanol Ethanol Aqueous 350–600 µg/mL 750–12,000 Dichloromethane/ Methanol µg/mL n-Butanol Ethyl acetate Chloroform Aqueous Dichloromethane/ Methanol Aqueous 600, 1200 µg/mL 750–12,000 Dichloromethane/ Methanol µg/mL Ethanol 5 mg/mL P. aeruginosa P. aeruginosa T. mentagrophytes, M. canis T. mentagrophytes, M. canis [21] [28] [23] [58] [21] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrataC. krusei [23] Methicillin-resistant S. aureus - - [32] Antibiotics 2019, 8, 257 25 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts Aqueous Dichloromethane/ Methanol MIC * Gram Positive 1–8 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Gram Negative Fungi T. mentagrophytes, M. canis References Halleria lucida L. Scrophulariaceae Leaves Stem Brandisia hancei Hook.f. Scrophulariaceae Whole Plant Ethanol 3.33–33.3 mg/mL Methicillin-resistant S. aureus - - [32] Selaginella tamariscina (Seauv.) Spring. Selaginellaceae Whole Plant Ethanol 250 mg/mL Methicillin-resistant S. aureus - - [32] Datura stramonium L. Solanaceae Leaves, Stem, Fruit S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei Solanum incanum L Solanaceae Leaves Solanum trilobatum L. Solanaceae Leaves Datura metel L. Solanaceae Leaves Solanum macrocarpon L. Solanaceae Leaves, Stem P. aeruginosa [21] Aqueous Dichloromethane/ Methanol 10–100 mg/mL 750–12,000 µg/mL Aqueous Dichloromethane/ Methanol 5–50 mg/mL 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes 156–625 µg/mL 250 mg/mL 10–100 mg/mL 5–50 mg/mL 60 µg/mL 5 mg/mL S. pyogens, S. aureus, B. subtilis S. typhi, P. vulgaris, K. pneumoniae, P. aeruginosa, E. coli - [37] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] Acetone Aqueous Benzene Butanol Chloroform Ethanol Aqueous 350–600 µg/mL Dichloromethane/ 1 mg/mL Methanol Aqueous Dichloromethane/ Methanol 500 µg/mL 60 µg/mL P. aeruginosa T. mentagrophytes, M. canis [23] [21] Antibiotics 2019, 8, 257 26 of 57 Table 1. Cont. Botanical Name Family Plant Used Solanum melongena L. Solanaceae Leaves, Root Stem Solanum nigrum L. Solanaceae Leaves, Stem Solanum torvum Sw. Solanaceae Leaves Extracts Aqueous Dichloromethane/ Methanol MIC * 800 mg/disc Dichloromethane/ Methanol Gram Negative Fungi References B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus - - [41] B. cereus, S. aureus, methicillin-resistant S. aureus - - [41,59] 100 µg/mL Aqueous 600, 1200 µg/mL Dichloromethane/ 1 mg/mL Methanol Aqueous Gram Positive 3.33–33.3 mg/mL 60 µg/mL Aqueous Dichloromethane/ Methanol 250 mg/mL Aqueous Dichloromethane/ Methanol 10–100 mg/mL Solanum virginianum L. Solanaceae Leaves, Stem, Root Withania somnifera (L.) Dunal Solanaceae Roots & Leaves Cola acuminate L. Sterculiaceae Stem Acetone Methanol 5–50 mg/mL 100 µg/mL S. aureus - C. albicans [16] Schima sinensis (Hemsl. et. Wils) Airy-shaw. Theaceae Tbl Ethanol 156–625 µg/mL methicillin-resistant S. aureus - - [32] Coriandrum sativum Umbelliferae Seeds Aqueous 350–600 µg/mL S. aureus K. pneumoniae, P. aeruginosa, A. niger, P. lilacinum [27] Clerodendrum inerme L Verbenaceae Leaves Methanol 500 µg/mL S. aureus - A. niger [60] Lantana rugosa Thunb. Verbenaceae Leaves 800 mg/disc 750–12,000 µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes Aqueous Dichloromethane/ Methanol 4 mg/mL 1 mg/mL P. aeruginosa T. mentagrophytes, M. canis [21] Antibiotics 2019, 8, 257 27 of 57 Table 1. Cont. Botanical Name Family Plant Used Extracts MIC * Gram Positive Gram Negative Fungi References Lantana camara L. Verbenaceae Leaves, Flower Chloroform Acetone Methanol Aqueous 600, 1200 µg/mL 5 mg/mL 1–8 mg/mL 1–2 mg/mL S. aureus, B. cereus E. coli, S. typhi, P. aeruginosa, K. aerogenes, P. vulgaris, S. Boydii, K. pneumoniae, V. cholerae A. fumigatus, A. flavus, A. niger, C. albicans [39] Lantana indica L. Verbenaceae Leaves 3.33–33.3 mg/mL 4 mg/mL B. subtilis, S. aureus, S. pyogenes, E. coli, P. vulgaris, K. pneumoniae C.albicans, [61] Cyphostemma lanigerum Harv. Vitaceae Leaves, Stem S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum Cyphostemma setosum Roxb. Vitaceae Leaves, Stem, Fruit S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum Aloe arborescens Mill. Xanthorrhoeaceae Leaves Zingiberaceae Leaves, Stem, Root Curcuma xanthorrhiza Zingiberaceae Rhizome Ethanol Kaempferia pandurata Roxb. Zingiberaceae Rhizome Peganum harmala L. Zygophyllaceae Seeds Siphonochilus aethiopicus Schweinf., Methanol Aqueous Aqueous Dichloromethane/ Methanol 250 mg/mL 750–12,000 µg/mL Aqueous Dichloromethane/ Methanol 10–100 mg/mL 750–12,000 µg/mL Aqueous Dichloromethane/ Methanol 5–50 mg/mL 750–12,000 µg/mL Aqueous 156–625 µg/mL 750–12,000 Dichloromethane/ Methanol µg/mL S. aureus, methicillin- resistant S. aureus, gentamycin– methicillin-resistant S. aureus, S. epidermidis, B. agri, P. acnes P. aeruginosa C. albicans C. glabrata C. krusei C. albicans C. glabrata C. krusei T. mentagrophytes, M. canis [23] [23] [21] S. mutans, S. sanguis, L. acidophilus L. casei P. gingivalis F. nucleatum C. albicans C. glabrata C. krusei [23] 350–600 µg/mL methicillin-resistant S. aureus - - [46] Ethanol 500 µg/mL methicillin-resistant S. aureus - - [46] Ethanol 800 mg/disc S. aureus E. coli - [21] * MIC (minimum inhibitory concentration) is the lowest drug concentration at which a given antimicrobial extract inhibits the visible growth of a tested organism. MIC absolute value: the given absolute value of drug concentration inhibits the growth of all tested organisms/ MIC ranges: the given range of drug concentrations (minimum to maximum) inhibit the growth of the individual to all tested organisms. Antibiotics 2019, 8, 257 28 of 57 Phytocomponent Fractions and Antimicrobial Methods Fresh or dried plant extracts were prepared using aqueous and different organic solvents in traditional extraction techniques (maceration, percolation, Soxhlet extraction). During the extraction method, the solvents penetrate into the plant material and dissolve active compounds with a related polarity [62]. At the completion of the technique, solvents have been vaporized, resulting in the formation of a concentrated mixture that yields the active compounds [63]. A successful extraction is mainly reliant on the nature of the solvent utilized during the extraction. The most regularly established extracts are aqueous extract followed by organic solvents, which include using methanol, ethanol, hexane, isopropanol, ethyl acetate, benzene, acetone, chloroform, and dichloromethane [64]. Two popular types of antibacterial susceptibility test, namely diffusion and dilution methods, are generally performed to determine the antibacterial efficacy of the plant materials. The method of diffusion is a screening test to classify bacteria that aid susceptibility or resistance to the tested plant material based on the size or diameter of the inhibition zone [62]. On the other hand, the activity of plant materials is determined as minimum inhibitory concentration (MIC) in the dilution method. In the MIC method, the lowest concentration is capable of inhibiting bacterial growth. Redox indicators and turbidity are most often measured for the analysis of results in broth dilution methods. The turbidity can be calculated colorimetrically while changing the indicator color represents the inhibition of bacterial growth [62]. The screening of traditional plant extracts has been of great attention to researchers investigating novel bioactive compounds effective in the treatment of microbial infections. Plant extracts exhibit: (a) direct antimicrobial activity presenting effects on metabolism and development of microbes and (b) indirect activity as antibiotic resistance adapting substances which, joint with antibiotics, upsurge their efficiency. Numerous studies have considered the antimicrobial screening of traditional plant extracts. The studies of medicinal plants from diverse topographical areas include: Armenia [65], Iran [66], Mexico [67], Saudi Arabia [68], Libya [26], Ethiopia [64], India [63], Poland [69], Cameroon [70], Nigeria [71], and other Middle Eastern countries [72]. Based on the available information, the traditional plant extracts showed antimicrobial activity against a huge number of pathogenic bacteria, fungi, viruses, algae, protozoan, and Trypanosoma [26,63,64,66]. 3. Bioactive Compounds (Bioactive Phytocomponents) Traditional medicinal plants possess various chemical substances that support certain physiological and biochemical activities in the human body and they are known as phytochemicals or phytocomponents. These chemicals are non-nutritive substances used to heal various infectious diseases, as well as provide disease preventive properties [9,10]. With advances in phytochemical practices, numerous active principles have been isolated from medicinal plants and presented as a valuable drug in contemporary systems of medicine. Mostly, the pharmacological activity of medicinal plants resides in their secondary metabolites, which are relatively smaller in quantity in contrast to the primary molecules such as carbohydrates, proteins, and lipids. Plant secondary metabolites are commonly accountable for their antimicrobial properties [62]. These metabolites offer clues to manufacture new structural types of antimicrobial and antifungal chemicals that are comparatively safe to humans [62]. The classes of secondary metabolites that have greater antimicrobial properties are flavonoids (flavones, flavonols, flavanols, isoflavones, anthocyanidins), phenolic acids (hydroxybenzoic, hydroxycinnamic acids), stilbenes, lignans, quinones, tannins, coumarins (simple coumarins, furanocoumarins, pyranocoumarins), terpenoids (sesquiterpene lactones, diterpenes, triterpenes, polyterpenes), alkaloids, glycosides, saponins, lectins, steroids, and polypeptides [6,16,56,62,73–83]. These compounds have copious mechanisms that underlie antimicrobial activity, e.g., disturbing microbial membranes, weakening cellular metabolism, control biofilm formation, inhibiting bacterial capsule production, attenuating bacterial virulence by controlling quorum-sensing, and reducing microbial toxin production [3–6,73–85]. Various bioactive compounds have been scientifically tested for their antimicrobial activities and are presented in Table 2. Antibiotics 2019, 8, 257 29 of 57 Table 2. Antimicrobial activities of bioactive compounds. Botanical Name Allium sativum L. Searsia chirindensis (Baker f.) Moffett Xylopia aethiopica (Dunal) A. Rich. Family Alliaceae Extracts Bioactive Compounds MIC * Organism Inhibited Methanol Cyanidin-3-(6’-malonyl)-glucoside, vanillic acid caffeic acid, p-coumaric acid, ferulic acid, sinapic acid, L-alliin, alliin isomer and methiin - B. cereus, L. monocytogenes S. aureus, P. aeruginosa, E. coli [11] Ethanol Methyl gallate myricetin-3-O-arabinopyranoside myricetrin-3-O-rhamnoside kaempferol-3-O-rhamnoside quercetin-3-O-arabinofuranoside 30–130 µg/mL 60–250 µg/mL 60–250 µg/mL 130–250 µg/mL 250 µg/mL C. jejuni, E. coli, S. flexneri, S. aureus [86] S. aureus, B. licheniformis, E. coli, K. pneumoniae [87] Anacardiaceae Dichloromethane/ Methanol n-butanol Ethyl Acetate Crude Annonaceae Aqueous References 250–6250 µg/mL 130–3125 µg/mL 60–780 µg/mL 60–780 µg/mL 1R-a-Pinene, β-Pinene, 2-Carene, Cyclohexene,5-methyl-3-(1-methylethenyl)-trans-(-)Bicyclo [3.1.0] hexane,6-isopropylidene-1-methyl-, Eucalyptol, Ethyl 2-(5-methyl-5-vinyltetrahydrofuran-2-yl) propan-2-yl carbonate, Isogeraniol, α-Campholenal, L-trans-Pinocarveol, Pinocarvone, Myrtenal, (-)-Spathulenol 1–256 µg/mL Antibiotics 2019, 8, 257 30 of 57 Table 2. Cont. Botanical Name Family Extracts Bioactive Compounds MIC * Organism Inhibited Polyalthia cerasoides Annonaceae Hexane Dichloromethane N-(4-hydroxy-β-phenethyl-4-hydroxy cinnamide 64–128 µg/mL 32–256 µg/mL C. diphtheria, B. subtilis, B. cereus, M. lutens References [88] Unonopsis lindmanii R. E. Fries Anonaceae Hexane Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 25–250 µg/mL C.albicans [89] Allagoptera leucocalyx (Drude) Kuntze, Arecaceae Hexane Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 162.2–665 mg/mL C.albicans [89] Bactris glaucescens Drude Arecaceae Hexane Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 200–755 mg/mL C.albicans [89] Scheelea phalerata Mart Arecaceae Hexane Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 129 mg/mL C.albicans [89] Artemisia herba-alba Asso Asteraceae Aqueous 1,8-cineole, β-thujone, α-thujone, camphor 640–2500 µg/mL T. rubrum and E. floccosum [90] Vernonia adoensis Sch. Bip. ex Walp. Asteraceae Acetone Chondrillasterol 50 µg/mL S. aureus, K. pneumonia, P. aeruginosa [1] Antibiotics 2019, 8, 257 31 of 57 Table 2. Cont. Botanical Name Matricaria chamomilla Solidago graminifolia L. Salisb. Family Asteraceae Extracts Ethanol Ethanol Asteraceae Methanol Aqueous Bioactive Compounds MIC * Organism Inhibited Phenolic acid 1.56–3.12 mg/mL S. typhimurium di-C-glycosylflavones (schaftoside, isoschaftoside), caftaric acid, gentisic acid, chlorogenic acid, p-coumaric acid, ferulic acid, hyperoside, rutin, quercitrin, quercetin, Luteolin, kaempferol, gallic acid, protocatechuic acid, vanillic acid, syringic acid, rosmarinic acid 40–3120 µg/mL 90–3120 µg/mL 190–6250 µg/mL References [19] [12] S. aureus, C. albicans, C. parapsilosis. Baccharis trimera Asteraceae Crude Polyphenols, flavonoids, alkaloids, and terpenes 7.8–500 µg/mL E. coli, S. aureus, P. aeruginosa, C. albicans, C. tropicalis, C. parapsilosis, Epicoccum sp., C. sphaerospermum, C. neoformans, P. brasiliensis, C. gatti, Pestalotiopsis sp., C. lunatus, Nigrospora sp. Tecoma stans Bignoniaceae Aqueous Phenolic compounds 50–600 µg/mL S. aureus [91] Bixa orellana L. Bixaceae Aqueous Bixin, catechin, chlorogenic acid, chrysin, butein, hypolaetin, licochalcone A, and xanthohumol. 16–32 µg/mL B. cereus, S. aureus [9] Trichodesma indicum Boraginaceae Ethanol Lanast-5-en-3β-D- glucopyranosyl-21(24)-oilde 2.4–19.2 µg/mL S. aureus [92] [88] Antibiotics 2019, 8, 257 32 of 57 Table 2. Cont. Botanical Name Family Extracts Bioactive Compounds MIC * Organism Inhibited References [93] Boswellia dalzielii Hutch. Burseraceae Crude Oleic acid, squalene and n-hexadecanoic acid - S. pyogenes, S. aureus, E. coli, E. faecalis, K. pneumonia, P. aeruginosa, P. mirabilis, S. typhi, and C. albicans Caesalpinia coriaria (Jacq) Willd Caesalpiniaceae Aqueous Ethanol Methyl gallate and gallic acid 1.56–25 mg/mL 390–6250 µg/mL S. typhi, E. coli, P. aeruginosa, L. monocytogenes, S. aureus. [94] Senna aculeate (Bth.) Irw et Barn Ceasalpinioideae Hexane Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 25, 50, 100 mg/mL C.albicans [89] [8] [89] Kochia scoparia Chenopodiaceae Crude Polyphenols, flavonoids, alkaloids, and terpenes 3.125 mg/mL C. graminicola, T. deformans, A. flavus, H. carbonum, C. zeaemaydis, C. macrocarpum, P. innundatus, S. japonicas, E. ficariae, P. herbarum, M. verticillata, Rhisoclosmatium sp., S. pseudodichotomus, S. kneipii, R. solani, P. sojae. Buchenavia tomentosa (Mart) Eichler Combretaceae Hexane Gallic acid, Kaempferol, Ellagic acid, epicatechin, Vitexin, Corilagin 10 mg/mL C.albicans Antibiotics 2019, 8, 257 33 of 57 Table 2. Cont. Botanical Name Terminalia phanerophlebia Engl. & Diels Buchenavia tomentosa L. Diadema setosum f. depressa Dollfus & Roman. Monotes kerstingii Gilg Croton doctoris S Moore Family Extracts Bioactive Compounds MIC * Organism Inhibited Combretaceae Crude Dichloromethane Hexane Ethyl Acetate n-butanol Methyl gallate (methyl-3,4,5-trihydroxybenzoate) and a phenylpropanoid glucoside, 1,6-di-O-coumaroyl glucopyranoside 125 µg/mL 16–250 µg/mL 31–250 µg/mL 8–125 µg/mL 31–250 µg/mL M. aurum, M. tuberculosis, S. aureus, K. pneumoniae [95] Crude Gallic acid, quinic acid, kaempferol, (-) epicatechin, ellagic acid, buchenavianine, eschweilenol b, eschweilenol c, vitexin, corilagin, 1α,23β-dihydroxy-12-oleanen-29-oicacid-23β-o-αl-4-acetylramnopiranoside and punicalin 200–12500 µg/mL Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei and Candida dubliniensis. [96] Combretaceae Diadematidae Acetone Dipterocarpaceae Crude Euphorbiaceae Hexane Polyunsaturated fatty acids (PUFAs) and β-carotene Stilbene-coumarin derivative, coumarin-carbinol and fatty glycoside Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 500–4000 µg/mL 1–8 mg/mL 500 µg/mL S. typhi, S. typhimurium, S. flexneri, P. aeruginosa, A. hydrophila, Acinetobacter sp, C. freundii and K. pneumonia, B. subtilis, S. epidermidis S. aureus B. subtilis, Septoria tritici Desm C.albicans References [1] [7] [89] Antibiotics 2019, 8, 257 34 of 57 Table 2. Cont. Botanical Name Jatropha weddelliana Baillon Family Euphorbiaceae Extracts Hexane Bioactive Compounds Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 4-butylamine, cannabinoid, dronabinol, methyl-6-hydroxy Cassia alata Fabaceae Ethanol Dalbergia scandens Roxb., Corom. Acacia nilotica Fabaceae Ethanol Dalpanitin, vicenin-2 and 3, rutin Fabaceae Alkaloids Salvia sessei Benth Lamiaceae Mentha piperita Lamiaceae Crude Hexane Dichloromethane Methanol Methanol Sessein, isosessein 1,1-diphenyl-2-picrylhydazyl-hydrate MIC * Organism Inhibited References 4–32 µg/mL C.albicans [89] 1.25, 1.5 mg/mL S. aureus, E. coli, P. aeruginosa, C. albicans B. cereus, S. aureus, E. coli, P. aeruginosa, C. albicans S. aureus S. haemolyticus, S. hominis, E. faecalis, S. epidermis, S. pyogenes, S.aureus S. aureus, E. coli, C. albicans [28] 780–6250 mg/mL 600–1200 µg/mL 12.5–100 µg/mL 100 µg/mL 12.5–100 µg/mL 1–4 mg/mL [41] [27] [14] [97] Antibiotics 2019, 8, 257 35 of 57 Table 2. Cont. Botanical Name Ocimum basilicum L. Family Lamiaceae Extracts Bioactive Compounds Ethanol Gallic acid, 3,4-dihydroxy benzoic acid, 4-hydroxy benzoic acid, 2,5 dihydroxybenzoic acid, chlorogenic acid, vanillic acid, Epicatechin, caffeic acid, p-coumaric acid, ferulic acid, rutin, ellagic acid, naringin, quercetin, cinnamic acid, α-pinene, camphene, sabinene, β-pinene, myrcene, 3-octanol, α-terpinene, p-cymene, limonene, 1,8-cineole, (Z)-β-ocimene, (E)-β-ocimene, γ-terpinene, cis-sabinene hydrate, terpinolene, linalool, nonanal, pentylisovalerate, 1-octen-3-yl acetate, cis-p-menth-2-en-1-ol, 3-octyl acetate, α-campholenal, camphor, trans-verbenol, δ-terpineol, 4-terpineol, α-terpineol, cis-dihydrocarvone, trans-carveol, (Z)-3-hexenyl isovalerate, pulegone, neral, carvone, linalyl acetate, bornyl acetate, dihydroedulan IA, isodihydrocarvyl acetate, α-terpinyl acetate, cis-carvyl acetate, neryl acetate, geranyl acetate, β-elemene, (Z)-jasmone, β-caryophyllene, β-copaene, aromadendrene, α-humulene, (E)-β-farnesene, cis-muurola-4(14), 5-diene germacrene D, bicyclogermacrene, germacrene A, δ-cadinene, (E)-α-bisabolene, (E)-nerolidol, Spathulenol, caryophyllene oxide, viridiflorol, 1, 10-di-epi-cubenol, T-cadinol, T-muurolol, monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, apocarotenes non-terpene derivatives MIC * Organism Inhibited 16–256 µg/mL S. epidermidis S. aureus, B. subtilis, E. coli, P. aeruginosa, K. pneumoniae, C. glabrata, C. albicans References [98] Antibiotics 2019, 8, 257 36 of 57 Table 2. Cont. Botanical Name Thymus algeriensis Boiss. & Reut Family Lamiaceae Extracts Bioactive Compounds Ethanol Gallic acid, 3,4-dihydroxy benzoic acid, 4-hydroxy benzoic acid, 2,5 dihydroxybenzoic acid, chlorogenic acid, vanillic acid, epicatechin, caffeic acid, p-coumaric acid, ferulic acid, rutin, ellagic acid, naringin, quercetin, cinnamic acid, α-pinene, camphene, sabinene, β-pinene, myrcene, 3-octanol, α-terpinene, p-cymene, limonene, 1,8-cineole, (Z)-β-ocimene, (E)-β-ocimene, γ-terpinene, cis-sabinene hydrate, terpinolene, linalool, nonanal, pentylisovalerate, 1-octen-3-yl acetate, cis-p-menth-2-en-1-ol, 3-octyl acetate, α-campholenal, camphor, trans-verbenol, δ-terpineol, 4-terpineol, α-terpineol, cis-dihydrocarvone, trans-carveol, (Z)-3-hexenyl isovalerate, pulegone, neral, carvone, linalyl acetate, bornyl acetate, dihydroedulan IA, isodihydrocarvyl acetate, α-terpinyl acetate, cis-carvyl acetate, neryl acetate, geranyl acetate, β-elemene, (Z)-jasmone, β-caryophyllene, β-copaene, aromadendrene, α-humulene, (E)-β-farnesene, cis-muurola-4(14), 5-diene germacrene D, bicyclogermacrene, germacrene A, δ-cadinene, (E)-α-bisabolene, (E)-nerolidol, spathulenol, caryophyllene oxide, viridiflorol, 1, 10-di-epi-cubenol, T-cadinol, T-muurolol, monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, oxygenated sesquiterpenes, apocarotenes non-terpene derivatives MIC * Organism Inhibited 32–512 µg/mL S. epidermidis S. aureus, B. subtilis, E. coli, P. aeruginosa, K. pneumoniae, C. glabrata, C. albicans References [98] Antibiotics 2019, 8, 257 37 of 57 Table 2. Cont. Botanical Name Family Extracts Bioactive Compounds MIC * Organism Inhibited Cinnamomun inerme Lauraceae Ethyl Acetate Hexane Acetone n-butanol 5-(1,5-dimethyl-2-4-hexenyl)- methyl phenol) 100–800 µg/mL 8000 µg/mL 8000 µg/mL 100–800 µg/mL References S. aureus, E. coli [99] Allium sativam Liliaceae Crude Allicin 49 µg/mL C. albicans [100] Strychnos nigritana Baker Loganiaceae Crude Nigritanine, Speciociliatine, Mytragine Paynantheine Rhyncophylline 128–256 µg/mL S. aureus [10] Mascagnia benthamiana (Gries) WR Anderson Malpighiaceae Hexane Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 17.84 mg/mL C.albicans [89] Mouriri elliptica Mart Memecylaceae Hexane Gallic acid, kaempferol, ellagic acid, epicatechin, vitexin, corilagin 100 µg/mL C.albicans [89] Artocarpus communis Moraceae Crude Atonin E, 2-(3,5-dihydroxy)-(Z)-4-(3 methyl but-1-etnyl 4–512 µg/mL P. aeruginosa, S.typhi, S.aureus, K.pneumoniae [101] Myrtus nivellei Batt. & Trab. Myrtaceae Crude 1,8-cineole, limonene, isoamylcyclopentane, di-nor-sesquiterpenoids 5 mg/mL C. neoformans [102] Antibiotics 2019, 8, 257 38 of 57 Table 2. Cont. Botanical Name Family Extracts Bioactive Compounds MIC * Organism Inhibited References [102] Myrtus communis L Myrtaceae Crude α-pinene, 1,8-cineole, linalool, and linalyl acetate 156–625 µg/mL E. floccosum, M. canis, T. rubrum Piper nigrum Piperaceae Aqueous Piperine 500–1000 µg/mL E. coli, M. luteus [91] Citrus aurantium L. Rutaceae Ethanol Polyphenols, flavonoids, alkaloids, and terpenes 1562–6250 µg/mL Amoxycillin resistant B. cereus [13] Salix babylonica L. Salicaceae Hydroalcoholic Luteolin, luteolin 7-O-glucoside 1.56–100 mg/mL E. coli, S. aureus and L. monocytogenes [103] Verbascum glabratum subsp. bosnense (K. Malý) Murb Scrophulariaceae Ethanol quercitrin and rosmarinic acid, 4-hydroxybenzoic acid, salicylic acid, morin, and apigenin 600, 1200 µg/mL E. coli, S. aureus, Candida albicans [17] Simaba ferruginea A. St.-Hil Simaroubaceae Methanol Canthin-6-one, indole β-carboxylic 12.5–200 µg/mL S. flexneri, S. aureus and S. aureus [91] Camellia sinensis Theaceae Aqueous Catechin 7.81–31.25 µg/mL S. mutans [104] Talaromyces sp. Trichocomaceae Aqueous Talaropeptide A and B 5 mg/mL B. subtilis [18] Hybanthus enneasperm us Violaceae Crude Flavonoids, Tannins 37.5, 75, 150, 300, 600 µg/mL P. vulgaris, V. cholera [100] Antibiotics 2019, 8, 257 39 of 57 4. Mechanism of Actions of Antibacterial Bioactive Compounds As proven by in vitro experiments, medicinal plants produce a boundless quantity of secondary metabolites that have great antimicrobial activity [9,10,18]. These plant-produced low molecular ‐ weight antibiotics are classified according to two types, namely phytoanticipins, which are involved in microbial inhibitory actions, and phytoalexins, which are generally anti-oxidative and synthesized de ‐ novo by plants in response to microbial infection [16,74]. Plant antimicrobial secondary metabolites are generally categorized into three broad classes, namely phenolic compounds, terpenes, and alkaloids. Numerous studies have shown that the antimicrobial activity of the plant extracts and their active compounds have the following potential: to promote cell wall disruption and lysis, induce reactive oxygen species production, inhibit biofilm formation, inhibit cell wall construction, inhibit microbial DNA replication, inhibit energy synthesis, and inhibit bacterial toxins to the host [75,85,105–109]. In addition, these compounds may prevent antibacterial resistance as well as synergetics to antibiotics, which can ultimately kill pathogenic organisms (Figure 1). Figure 1. Mechanisms of antimicrobial activity of bioactive compounds. 4.1. Promote Cell Wall Disruption and Lysis Phenolic compounds are a family of aromatic rings consisting of a hydroxyl functional group (-OH) which is alleged to absolute toxicity to microorganisms, although increased reactions of hydroxylation‐ result in microbial cell lysis [110]. Quinones also have aromatic rings with two ketone molecules, which enables the production of an irreversible complex with nucleophilic amino acids, resulting in greater antimicrobial properties. These potential aromatic compounds are usually targeted to microbial cell surface adhesins, membrane-bound polypeptides, enzymes, and eventually lysis of the microbes [111]. Flavonoids are hydroxylated phenolic ‐substances which are also able to complex with bacterial cell walls and disrupt microbial membranes [75,105]. Highly active flavonoids, quercetin (1), rutin (2), naringenin (3), sophoraflavanone (4), tiliroside (5) and 2, 4, 6-trihydroxy-30-methyl chalcone (6) (Figure 2) decreased lipid bilayer thickness and fluidity levels and increased membrane permeability,‐ ‐ leaking of intracellular protein and ions in S. aureus and S. mutans [112,113]. These supporting‐ the compounds contribute to the synergistic effect with ampicillin and tetracycline [114]. The other active flavonoids, acacetin (7), apigenin (8), morin (9), and rhamnetin (10) (Figure 2) cause weakening of the Antibiotics 2019, 8, 257 40 of 57 bacterial cell wall by disarrangement and disorientation of the lipid bilayer and ultimately persuade vesicle leakage [115–117]. The synthetic flavonoid lipophilic 3-arylidene (11) was found to be very active ‐ against S. aureus, S. epidermidis, and E. faecalis due to a bacterial cell clump that influences the integrity of the cell wall as a result of biofilm disruption [118]. Tannins are classes of another polymeric phenolic substance, characterized as astringency, which is capable to deactivate microbial adhesins, enzymes, and membrane transporter systems [105,119]. Coumarins (12) are benzo-α-pyrones known to stimulate macrophages, which could have ‐α‐ an adverse effect on infections [7,120]. Terpenes are organic compounds containing isoprene subunits, which involve microbial membrane disruption [121,122]. Thymol (13), eugenol (14), Cinnamaldehyde (15), carvone (16), and carvacrol (17) (Figure 2) disintegrate the external ‐ membrane of various Gram-negative bacteria, releasing LPS and increasing the permeability [123–125]. Quercetin (1) Rutin (2) Naringenin (3) sophoraﬂavanone (4) Tiliroside (5) 2, 4, 6‐trihydroxy‐30‐ methyl chalcone (6) Acacetin (7) Apigenin (8) Morin (9) Rhamnetin (10) Lipophilic 3‐arylidene (11) Coumarins (12) Thymol (13) Eugenol (14) Cinnamaldehyde (15) Carvone (16) Carvacrol (17) Galangin (18) Figure 2. Cont. Antibiotics 2019, 8, 257 41 of 57 Isovitexin (19) EGCG (20) 3‐O‐octanoyl‐epicatechin (21) 5, 7, 40‐trihydroxyﬂavanol (22) Kaempferol (23) Chrysin (24) Phloretin (25) epicatechin gallate (26) Proanthocyanidins (27) 6‐aminoﬂavone (28) 6‐hydroxyﬂavone (29) Daidzein (30) Genistein (31) Auronol (32) Pinostrobin (33) Catechins (34) Epicatechin (35) Sakuranetin (36) Figure 2. Cont. Antibiotics 2019, 8, 257 42 of 57 Eriodictyol (37) Taxifolin (38) 5, 6, 7, 40, 50‐ pentahydroxyﬂavone (39) 5‐hydroxy‐40, 7‐ dimethoxyﬂavone (40) 4, 20, 40‐trihydroxychalcone (41) Fisetin (42) Myricetin (43) Baicalein (44) Luteolin (45) Butein (46) Isoliquirtigenin (47) Kaempferide (48) DL‐cycloserine (49) kaempferide‐3‐O‐glucoside (50) Nobiletin (51) Tangeritin (52) Robinetin (53) Iso bavachalcone (54) 6‐prenylapigenin (55) Licochalcones (56) Silibinin (57) Figure 2. Cont. Antibiotics 2019, 8, 257 43 of 57 Isoquercetin (58) quercitrin (59) Silymarin (60) 40, 50, 5‐trihydroxy‐6, 7‐ dimethoxy‐ﬂavone (61) kaempferol‐3‐O‐rutinoside (62) quercetin glycoside (63) Emodin (64) Carnosic acid (65) Rosmarinic acid (66) Figure 2. Chemical structures of antibacterial bioactive compounds. 4.2. Inhibition of Biofilm Formation The key features of bacteria developing biofilms are generally 100–1000 times more resistant to antimicrobial drugs while related to their usual planktonic forms [64]. Interestingly, numerous researchers have described how flavonoids cause the aggregation of multicellular composites of bacteria and inhibit bacterial growth after aggregation, which indicates that flavonoids are potent antibiofilm‐ compounds. The bioactive flavonoids such as ‐galangin (18), isovitexin (19), EGCG (20) ‐ ‐ and 3-O-octanoyl-epicatechin (21), as well as 5, 7, and 40-trihydroxyflavanol (22) induce pseudo multicellular aggregation of S. aureus and S. mutans [106–109]. Quorum sensing involves cell signaling molecules called autoinducers present in E. coli, Vibrio cholerae, and S. typhi, which is a notable regulatory factor for biofilm formation [126]. Interestingly, apigenin (8), kaempferol (23), quercetin (1), and naringenin (3) are effective antagonists of cell–cell signaling [126,127] that ‐ have been revealed to inhibit enteroaggregative biofilm formation in E. coli and P. aeruginosa in a concentration-dependent manner [128,129]. Moreover, chrysin (24), phloretin (25), ‐ ‐ ‐ naringenin (3), kaempferol‐ (23), epicatechin gallate (26), proanthocyanidins (27), and EGCG (20) (Figure 2) inhibited N-acyl homoserine lactones-mediated QS [130–132]. Hydrophilic flavonoids such as 6-aminoflavone (28), 6-hydroxyflavone (29), apigenin (8), chrysin (24), daidzein (30), genistein (31), auronol (32), and phloretin (25) (Figure 2) have inhibitory effects on E. coli biofilm formation [133,134]. In addition, Phloretin (25) inhibited fimbriae formation in E. coli by reducing the expression of the curli genes (csgA, csgB) and toxin genes (hemolysin E, Shiga toxin 2) [6], eventually inhibiting the formation of ‐ biofilm. Hence, phloretin (25) is well known as an antibiotic resistant compound. Pinostrobin (33), ‐ EGCG (20) and prenylated flavonoids enhanced membrane permeability in E. faecalis, S. aureus, E. coli, and P. aeruginosa, Porphyromonas gingivalis, which is consistent with its effect on efflux-pump inhibitors and anti-biofilm formation [34,135,136]. Antibiotics 2019, 8, 257 44 of 57 4.3. Inhibition of Cell Wall Construction The bacterial cell wall is accountable for osmoregulation, respiration, the transport mechanism, and biosynthesis of lipids. For the execution of these functions, membrane integrity is very important, and its disruption can directly or indirectly cause metabolic dysfunction eventually leads to bacterial death. Catechins (34) attract lipid bilayers of the membrane which involves the following mechanisms [137]. Catechins form hydrogen bonds, which attract polar head groups of lipids at the membrane edge. Epicatechin (35) and epigallocatechin gallate (26) alter phospholipids, which can alter structural changes in the cell membrane. Moreover, these catechins promote the inactivation or inhibition of intracellular and extracellular enzyme synthesis [137]. Generally, the inhibition of enzymes in fatty acid biosynthesis is an excellent target for antimicrobial agents for blocking bacterial growth, especially the key enzyme fatty acid synthase II (FAS-II) inhibitor is significant as an antimicrobial drug. Quercetin (1), apigenin (8), and sakuranetin (36) have been demonstrated to inhibit 3-hydroxyacyl-ACP dehydrase from Helicobacter pylori [138] and eriodictyol (37). Further, naringenin (3) and taxifolin (38) (Figure 2) inhibit 3-ketoacyl- ACP synthase from E. faecalis [139]. Flavonoids such as Epigallocatechin gallate (EGCG) (20), 5, 6, 7, 40, 50- pentahydroxyflavone (39), and 5-hydroxy-40, 7-dimethoxyflavone (40) inhibit the malonyl CoA-acyl carrier protein transacylase that regulates bacterial FAS-II [140,141]. EGCG (20) inhibits 3-ketoacyl-ACP reductase and enoyl-ACP reductase and prevents fatty acid biosynthesis [142]. Quercetin (1), kaempferol (23), 4, 20, 40-trihydroxychalcone (41), fisetin (42), morin (9), myricetin (43), baicalein (44), luteolin (45), EGCG (20), butein (46), and isoliquirtigenin (47) (Figure 2) inhibit various enzymes involved in fatty acid synthesis, including, FAS-II, enoyl-ACP-reductase, β-ketoacyl-ACP reductase, and β-hydroxy acyl-ACP dehydratases in Mycobacterium sp. [143]. Baicalein (44), EGCG (20), galangin (18), kaempferide (48), DL-cycloserine (49), quercetin (1), apigenin (8), and kaempferide-3-O-glucoside (50) (Figure 2) inhibit the synthesis of peptidoglycan, which is an essential component of the bacterial cell wall, resulting in cell wall damage [144–146]. 4.4. Inhibition of Prokaryotic DNA Replication Alkaloids are nitrogenous compounds characterized by their alkaline nature, which aids the inhibition of cell respiration, intercalates with DNA, and inhibits various enzymes involved in replication, transcription, and translation [147]. Plant-based bioactive compounds such as quercetin (1), nobiletin (51), myricetin (43), tangeritin (52,) genistein (31), apigenin (8), chrysin (24), kaempferol (23), and 3, 6, 7, 30, 40-pentahydroxyflavone (39) have been recognized as noteworthy DNA gyrase inhibitors, which are essential for DNA replication in prokaryotes including V. harveyi, B. subtilis, M. smegmatis, M. tuberculosis, and E. coli [146,148–151]. These bioactive compounds binding to the β subunit of gyrase and the corresponding blockage of the ATP binding pocket eventually contribute to the antimicrobial activity. Bioactive compounds have mediated the dysfunction of DNA gyrase functions in a dose-dependent manner that leads to the impairment of cell division and/or completion of chromosome replication, resulting in the inhibition of bacterial growth [149]. Luteolin (45), morin (9), and myricetin (43) have been demonstrated to inhibit the helicases of E. coli [152]. Helicases consititute another significant replicative enzyme responsible for separating and/or rearranging DNA double-strands [153]. Furthermore, myricetin (43) and baicalein (44) have been proposed as potent inhibitors of numerous DNA and RNA polymerases, as well as viral reverse transcriptase, resulting in the inhibition of bacterial growth [154]. EGCG (20), myricetin (43), and robinetin (53) have been demonstrated as inhibitors of dihydrofolate reductase in Streptomonas maltophilia, P.vulgaris, S. aureus, M. tuberculosis, and E. coli [43,155,156]. Dihydrofolate reductase is key enzyme for the synthesis of the purine and pyrimidine rings of nucleic acid, resulting in reduced DNA, RNA, and protein synthesis [156]. Antibiotics 2019, 8, 257 45 of 57 4.5. Inhibition of Energy Production Energy production or ATP synthesis is the supreme vital requirement for the existence and development of bacteria as these chemicals are the main source of living systems. The treatment of flavonoids such as isobavachalcone (54) and 6-prenylapigenin (55) with S. aureus cause membrane depolarization, resulting in bacterial cell wall lysis [101]. Similarly, licochalcones (56) inhibited oxygen consumption in M. luteus, interruping the electron transport system eventually killing the bacteria [6]. It has been described that flavonoids such as baicalein (44), morin (9), silibinin (57), quercetin (1), isoquercetin (58), quercitrin (59), and silymarin (60) can constrain the F1FO ATPase system of E. coli and result in the obstruction of ATP synthesis [157–159]. Additionally, EGCG (20), 40, 50, 5-trihydroxy-6, 7-dimethoxy-flavone (61), and proanthocyanidins (27) have also inhibited S. mutans, P. aeruginosa and S. aureus through the enzymatic activity of F1FO ATPase respectively [100,104,141]. 4.6. Inhibition of Bacterial Toxins It is noteworthy that catechins and other flavonoids can cause bacterial cell wall destruction, resulting in an inability to discharge toxins [160,161]. Catechins (34), pinocembrin, kaempferol, EGCG (20), gallocatechin gallate (26), kaempferol-3-O-rutinoside (62), genistein (31), quercetin glycoside (63), and proanthocyanidins (27) (Figure 2) are suggested to neutralize bacterial toxic factors initiating from V. cholerae, E. coli, S. aureus, V. vulnificus, B. anthracis, N. gonorrhoeae, and C. botulinum [162–165]. Bacterial hyaluronidases are enzymes formed by both Gram-positive and Gram-negative bacteria and directly interact with host tissues, causing the permeability of connective tissues and reducing the viscosity of body fluids due to hyaluronidase-mediated degradation [166]. Flavonoids such as myricetin (43) and quercetin (1) have been identified as hyaluronic acid lyase inhibitors in Streptococcus equisimilis and Streptococcus agalactiae [167]. 4.7. Mechanism of Resistance to Antibacterial Agents Pathogenic bacteria generally receive the resistance to various antibiotics through diverse mechanisms. Such mechanisms include: (a) bacteria can share the resistance genes through transformation, transduction, and conjugation; (b) bacteria produce various enzymes to deactivate the antibiotics through the process of phosphorylation, adenylation, or acetylation; (c) damage or alteration of the drug compound; (c) prevent the interaction of the drug with the target; (d) efflux of the antibiotic from the cell [168–170]. Emodin (1, 2, 8-trihydroxy-6-methylanthraquinone) (64) is an anthraquinone derivative which prevents the transformation of resistance genes in S. aureus [171]. Baicalein is a potent inhibitor of the expression of the SOS genes, RecA, LexA, and SACOL1400 that prevent rifampin-resistant mutation in S. aureus [172]. Phenolic compounds such as Carnosic (65) and rosmarinic acids (66) inactivate cmeB, cmeF, and cmeR genes in Campylobacter jejuni [173]. 4.8. Antimicrobial Action with Generation of Reactive Oxygen Species Reactive oxygen species (ROS) can be formed by the partial reduction of molecular oxygen that targets the exertion of antimicrobial activity, which aids host defense against various disease-causing pathogens. The suggested method of antimicrobial activity of catechins (34) involves augmentation of the production of oxidative stress (ROS and RNS), which can alter membrane permeability and cause as cell wall damage [174]. In addition, catechins damage liposomes as they contain a high amount of negatively charged lipids and are susceptible to damage [175]. An earlier study indicated that catechins support the leaking of potassium and disturbs the membrane transport system in a methicillin-resistant S. aureus strain [85]. This team has further demonstrated that acylated 3-O-octanoyl-epicatechin (21) is a lipophilic compound that produces more outcomes in antibacterial activity. Antibiotics 2019, 8, 257 46 of 57 5. Conclusions Since time immemorial, traditional medicinal plants have been cultivated by diverse populations to treat a great number of infectious diseases. Various investigations on the pharmacognostics and kinetics of medicinal plants have shown that crude extracts and plant-derived bioactive compounds may enhance the effects of traditional antimicrobials, which may be cost-effective, have fewer side effects, and improve the quality of treatment. Numerous studies have shown that the antimicrobial activity of plant extracts and their active compounds have the following potential: promote cell wall disruption and lysis, induce reactive oxygen species production, inhibit biofilm formation, inhibit cell wall construction, inhibit microbial DNA replication, inhibit energy synthesis, and inhibit bacterial toxins to the host. In addition, these compounds may prevent antibacterial resistance as well as synergetics to antibiotics, which can ultimately kill pathogenic organisms. Based on these comprehensive antimicrobial mechanisms, the cultivation of traditional plant extracts and bioactive compounds offers a promising treatment for disease-causing infectious microbial pathogens. Hence, this mechanism constitutes an encouraging ally in the development of pharmacological agents required to combat the growing number of microbial strains that have become resistant to extant antibiotics in clinical practice. Author Contributions: S.M. as sole author conceived, designed, written, revised and improved the review. Funding: The author would like to thank the Deanship of Scientific Research, Majmaah University, Kingdom of Saudi Arabia for academic support under the project no: R-1441-41. Conflicts of Interest: The authors declare no conflict of interest. Abbreviations A. bohemicus A. flavus A. fumigatus A. niger A. solani B. agri B. brevis B. cereus B. megaterium B. pumilus B. subtilis C. albicans C. Dipthieriae C. dubliniensis C. glabrata C. graminicola C. jejuni C. krusei C. lunat C. lunatus C. macrocarpum C. neoformans C. parapsilosis C. sphaerospermum C. tropicalis C. maydis D. turcica Acinetobacter bohemicus Aspergillus flavus Aspergillus fumigatus Aspergillus niger Alternaria solani Brevibacillus agri Brevibacillus brevis Bacillus cereus Bacillus megaterium Bacillus pumilus Bacillus subtilis Candida albicans Corynebacterium Dipthieriae Candida dubliniensis Candida glabrata Colletotrichum graminicola Campylobacter jejuni Candida krusei Candida lunat Cochliobolus lunatus Cladosporium macrocarpum Cryptococcus neoformans Candida parapsilosis Cladosporium sphaerospermum Candida tropicalis Cercospora zeae-maydis Drechslera turcica Antibiotics 2019, 8, 257 E. aerogenes E. cloacae E. coli E. faecalis E. ficariae E. floccosum F. nucleatum F. oxysporum F. verticillioides H. carbonum H. pylori K. aerogenes K. kristinae K. pneumonia L. acidophilus L. casei L. innocua L. monocytogenes L. sporogenes M. canis M. luteus M. morganii M. ruber M. smegmatis M. tuberculosis M. verticillata P. acnes P. aeruginosa P. brasiliensis P. fluorescens P. gingivalis P. herbarum P. innundatus P. intermedia P. lilacinum P. mirabilis P. sojae P. vulgaris R. rubrum R. solanacearum R. solani R. stolonifera S. agalactiae S. anginosus S. aureus S. auricularis S. boydii S. dysenteriae S. epidermidis S. fecalis S. flexneri S. gordonii S. haemolyticus 47 of 57 Enterobacter aerogenes Enterobacter cloacae Escherichia coli Enterococcus faecalis Entyloma ficariae Epidermophyton floccosum Fusobacterium nucleatum Fusarium oxysporum Fusarium verticillioides Helminthosporium carbonum Helicobacter pylori Klebsiella aerogenes Kocuria kristinae Klebsiella pneumonia Lactobacillus acidophilus Lactobacillus casei Listeria innocua Listeria monocytogenes Lactobacillus sporogenes Microsporum canis Micrococcus luteus Morganella morganii Monascus ruber Mycobacterium smegmatis Mycobacterium tuberculosis Mortierella verticillata Propionibacterium acnes Pseudomonas aeruginosa Paracoccidioides brasiliensis Pseudomonas fluorescens Porphrymonas gingivalis Pleospora herbarum Protomyces innundatus Prevotella intermedia Purpureocillium lilacinum Proteus mirabilis Phytophthora sojae Proteus vulgaris Rhodospirillum rubrum Ralstonia solanacearum Rhizoctonia solani Rhizopus stolonifera Streptococcus agalactiae Streptococcus anginosus Staphylococcus aureus Staphylococcus auricularis Shigella boydii shigella dysenteriae Staphylococcus epidermidis Streptococcus fecalis Shigella flexneri Streptococcus gordonii Staphylococcus haemolyticus Antibiotics 2019, 8, 257 S. heidelberg S. hominis S. japonicas S. kneipii S. lutea S. marcescens S. mutans S. para typhi S. pneumoniae S. pseudodichotomus S. pyogenes S. sanguis S. saprophyticus S. shiga S. typhi T. deformans T. mentagraphytes T. rubrum T. tonsurans T. urans V. cholerae V. fischeri X. axonopodis Pv. malvacearum X. vesicatoria Y. enterocolitica 48 of 57 Salmonella heidelberg Staphylococcus hominis Schizosaccharomyces japonicas Spizellomyces kneipii Sarcina lutea Serratia marcescens Streptococcus mutans Salmonella para typhi Streptococcus pneumoniae Spizellomyces pseudodichotomus Streptococcus pyogenes Streptococcus sanguis Staphylococcus saprophyticus Shigella shiga Salmonella typhi Taphrina deformans Trichophyton mentagraphytes Trichophyton rubrum Trichophyton tonsurans Trichophytontonsurans Vibrio cholerae Vibrio fischeri Xanthomonas axonopodis pv. 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