Phytochemical Compounds as Antibacterial Agents: A Mini Review
Alaa MM Sadeek and Emad M Abdallah*
College of Sciences and Arts at Al-Rass
Submission:September 18, 2019; Published:September 26, 2019
*Corresponding author:Emad Mohamed Abdallah, associate professor, Department of Laboratory Sciences, College of Sciences and Arts at Al-Rass, Post-code 51921 P.O. Box 53, Qassim University, Saudi Arabia
How to cite this article:Alaa MM Sadeek, Emad M Abdallah. Phytochemical Compounds as Antibacterial Agents: A Mini Review. Glob J Pharmaceu Sci. 2019; 7(3): 555720. DOI: 10.19080/GJPPS.2019.06.555720.
Abstract
Phytochemicals are secondary metabolites mostly produced by higher plants to enable them to survive under various biotic and abiotic stresses. Scientific reports exhibited that these natural compounds have direct and indirect effects on human, animal, fungal and bacterial physiology. Among them, the ability of some phytochemical compounds to suppress or eradicate the pathogenic bacteria with various mode of actions such as phenolic compounds,alkoloids, terpenoids, carotenoids, and some sulfur-containing phytochemicals. Such phytochemical molecules are suggested to meet the urgent need for new antibacterial drugs to overcome the growing phenomenon of the emergence of multi-drug resistant bacterial pathogens. This mini review aimed to demonstrate the recent reports on some phytochemical molecules which showed potent antibacterial activity and may help future researchers working on innovation of new antibacterial drugs with a different mode of action to control the crisis of antibiotics resistant pathogens.
Keywords: Phytochemical; Secondary metabolites; Antibacterial; Antibiotics; Medicinal plants
Introduction
Ancient humans have used plants as a medicine since antiquity, this assumption was built upon interesting fossil records discovered dates to 60000 years ago in Iraq (Mesopotamia) [1,2]. Therefore, plants considered as the main source for medications against various diseases including bacterial infections since the appearance of man on Earth. Accordingly, herbal products were the cornerstone for both of ancient and modern medicine. Recently, in some developed countries such as the United States, pharmaceutical drugs derived from herbs represent about 25%, whereas, in some fast-developing countries of large populations and great cultural heritage such as China and India, it comprises about 80% of the total pharmaceuticals [3].
The secret lies behind the continued use of medicinal plants as a remedy to its amazing ability of producing various and renewable bioactive secondary metabolites known as phytochemical compounds. In recent years, despite huge advances in antibiotic therapies and sophisticated infection strategies, the overuse and improper consumption and wrong implementation of antibiotics to treat pathogenic infections, have led to emergence of multi-drug resistant bacteria which recorded resistance against almost all known antibiotics, this crisis could lead to a disaster threaten the Human existence on Earth in the near future unless new alternatives to the regular antibiotics innovated [4-6]. In scientific literature, Massive researches suggest that some phytochemical compounds extracted from medicinal plants showed effective antibacterial potential against multi-drug-resistant pathogens and these compounds could be exploited as antibacterial drugs [7]. In view of the potential of some phytochemicals as promising antibacterial drugs soon, the current mini review is aimed at briefly reviewing the scientific reports that exhibited the in vitro antibacterial activity of some major classes of phytochemical agents.
Production of Plant Bioactive Compounds
Recent advances in analytical chemistry revealed that plants produce a vast array of metabolites, it is estimated that each single plant species produce between five thousand to tens of thousands of these bioactive metabolites which enables the plant to adapt and survive under various biotic and abiotic stresses in the environment [8].
Two main types of metabolites are produced by plants, primary and secondary metabolites. Primary metabolites are a kind of metabolites that are directly involved in the plant growth, increasing and proliferation. They usually pull off some basic physiological functions in the plant cells. Some common examples of primary metabolites include Carbohydrates, lipids, proteins, nucleic acids, and vitamins. Whereas, secondary metabolites are a kind of metabolites that are produced for special functions required for the plant to survive in its environment and these compounds have no role in the growth or the development of the plant (Figure 1).

Plant secondary metabolites can be classified into four main categories;
(i) Phenolic compounds such as flavonoids, tannins, chalcones, coumarins and phenolic acids.,
(ii) terpenes such as hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterpenes, triterpenes, tetraterpenes and polyterpenes,
(iii) Nitrogen-containing compounds such as non-protein amino acids, cyanogenic glucosides and alkaloids, and
(iv) Sulphur-containing compounds such as glucosinolates, alliinins, phytoalexins, thionins, defensins and lectins [9-11]. Plant secondary metabolites are known also as phytochemical compounds, these phytochemicals were reported having direct or indirect effects on the human, animal, fungal and bacterial cells; Some phytochemical compounds showed bioactive effects such as stimulation of the immune system, modulation of enzyme actions, modulation of hormone metabolism, pain-relieving properties, anti-oxidant, antiinflammatory, anti-cancer, anti-bacterial and antiviral activity [12].
Phytochemical Compounds as Antibacterial Agents

In recent years, the phenomenon of antibiotic-resistant bacteria has grown dramatically, which considered as a major global health threat. Chemically synthetic antibiotics are failed to keep pace with the bacterial mutations machine which can neutralize the effects of most known antibiotics. Regretfully, antibiotics are not consumed as a human drug only, but they are also consumed in large amounts for farm animals and fish in aquaculture Which doubled the crisis of antibiotics misuse to become a health and environmental problem [13,14]. The reason behind this amazing resistance to antibiotics is related to the fact that the pathogenic bacterial cell has a sophisticated mechanism of mutation enables them to survive inside the host effectively with various strategies. Among these strategies; The ability of bacteria to modify the target sites to avoid the action of antibiotics, decrease the antibiotic penetration and efflux, and make some chemical alternation on the antibiotic molecule to neutralize its effect [15]. Accordingly, introducing some antibacterial phytochemical molecules as drugs which act on bacterial cells with a different mode of action could help in combat this antibacterial crisis. Scientific reports cited that many phytochemical molecules have effective antibacterial activities, such as phenolic compounds, alkaloids, terpenoids, carotenoid and some sulfur-containing phytochemicals. In this mini review, we will mention only a few examples (only 2 to 4 previous studies) to explain the efficacy of these phytochemical categories as antibacterial agents (Table 1).
Phenolic Compounds
Phenolic compounds are well known bioactive phytochemical molecules, scientific reports evaluated up-to-date about 8000 phenolic compounds, halve of them are flavonoids; Phenolic compounds have versatile benefits for human health, for example, but not limited, antioxidants, anti-inflammatory, anti-cancer, antibacterial, immune system promoting, cardioprotective agents, and skin protection from UV radiation, [16]. With regard to antibacterial activity, hundreds of plants showed antibacterial phenolic compounds extracted from different plant parts, such as Pomegranate peels the methanol, ethanol and aqueous extracts showed high content of phenolic compounds and exhibited remarkable antibacterial activities against Staphylococcus aureus, Enterobacter aerogenes, Klebsiella pneumoniae and Salmonella typhi [17]. The leaves extracts using deep eutectic solvents of Rue (Ruta graveolens) revealed the highest antibacterial activity against gramnegative Pseudomonas aeruginosa, and it was also active but with lesser degrees against Bacillus subtilis, Staphylococcus aureus and Escherichia coli [18]. The crude extract and isolated phytochemical compounds of the seed kernel inside the Nutmeg fruit (Myristica fragrans) were tested against 29 tested Gramnegative bacterial strains, the best antibacterial activity recorded with Providencia stuartii ATCC299645, while the other strains recorded varying degrees of susceptibility towards these extracts [19]. The kernel of mango fruit (Mangifera indica) exhibited noticeable antibacterial activity against some acnecausing bacteria such as Propionibacterium acne, Staphylococcus aureus, and Staphylococcus epidermidis [20].
Alkaloids Compounds
Alkaloids are one of the largest and diverse phytochemical group, there are about 12000 alkaloids extracted from various plants and extensively studied; Alkaloids have many benefits for human health, for example, but not limited, muscle relaxant, narcotic analgesics, anti-cancer and antimicrobial agents, also some drugs were derived from alkaloids such as morphine, apomorphine and codeine [21]. The following are few examples of plants rich in alkaloids and showed effective antibacterial properties; The alkaloids extracted from leaves of Callistemon citrinus exhibited highest antibacterial activity against Staphylococcus aureus (ATCC 9144) and good activity against Pseudomonas aeruginosa (ATCC 27853) the mode of action of the extracted alkaloids showed that these molecules inhibiting ATP-dependent transport of compounds across the bacterial cell membrane [22]. Alkaloids from leaf extract of Eclipta alba was tested against some human pathogenic bacteria, Staphylococcus aureus and Escherichia coli were among the most susceptible bacteria and it was found that the inhibitory action of the alkaloid increased with the increase in concentration against all tested pathogens [23]. A plant growing in Southeast Asia known as Twin-apple (Ochrosia oppositifolia) was investigated for its antibacterial potential, all plant parts (Leaves, stem-bark and roots) reported different degrees of antibacterial activities; However, leaves and stem bark showed the highest inhibitory effect against Staphylococcus aureus followed by Bacillus subtilis Salmonella thyphimurium and Serratia marcescens, where the highest inhibitory effect of roots was against MRSA (Methicillin Resistant Staphylococcus aureus) and Vibrio fluvialis [24]. The alkaloid rich fraction extracted from a small shrub known as Mesquite (Prosopis juliflora) recorded high antibacterial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli, Psuedomonas putida, Klebsiella sp., Salmonella sp., Acinetobacter sp. and Alcaligen sp. [25].
Terpenoids Compounds
Terpenoids are an important diverse class of phytochemical compounds. Based on scientific literature, it has been confined about 40 000 compounds belonging to terpenoids which makes it one of the largest classes of phytochemicals. Terpenoids are widely used as flavors, fragrances, insecticides, pharmaceutical and industrial compounds [26]. A lot of studies claimed that many terpenoid compounds have potent antibacterial activity. Twelve pure terpenoid compounds extracted from the wood and bark of an aromatic cypress tree (Pilgerodendron uviferum) exhibited varied degrees of remarkable antibacterial activities against twelve different microorganisms including Staphylococcus aureus, Bacillus subtilis, Streptococcus pyogenes, Escherichia coli, Pseudomonas aureginosa, Fusarium graminearum, Ophiostoma piliferum, Rhizoctonia solani, Phragmidium violaceum, Schizophyllum commune, Pythium irregulare and Botrytis cinerea [27]. Terpenoids extracted from leaves of Eremophila lucida possess good antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus ATCC 29213 and Staphylococcus aureus ATCC 25923) but did not show activity against the Gram-negative bacteria (Escherichia coli ATCC 25922) [28]. Terpenoids isolated from an Indonesian plant known as Sarang Semut (Myrmecodia pendans) revealed significant antibacterial activity against Streptococcus mutans, the main causative agent of Caries in Human [29].
Carotenoids
Carotenoids are lipid phytochemical metabolites; they are an important phytochemical class of bioactive diverse properties and till now there are up to 600 carotenoids have been identified and isolated from plants. One of its main roles in the plant is the production of pigments for coloring fruits and vegetables; Scientific studies showed that they possess many protective roles against some diseases and disorders such as cancer, aging-associated diseases, cardiovascular diseases, antioxidant properties and many more [30]. Unfortunately, investigations on the antibacterial potential of carotenoids from plants are little and many studies focusing on carotenoids of some fungal species and Streptomyces. Although, some interesting investigations stated that carotenoids exhibited a remarkable antibacterial activity; Galls of Guiera plant (Guiera senegalensis) from Burkina Faso showed good contents of carotenoids which recorded significant antibacterial activities against Staphylococus aureus ATCC 6538, Bacillus cereus 13061, Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 13311, and no effect with Proteus mirabilis ATCC 35659 [31]. Carotenoids extracted from fruits of Annato (Bixa orellana L., growing in Philippine, revealed high antibacterial activity against Staphylococus aureus [32].
Other Phytochemical compounds
Plentiful phytochemicals not mentioned above have been found to exhibit antibacterial properties such as sulfurcontaining phytochemicals and many more. However, this mini-review has attempted to focus only on the limited number of reports on some phytochemical molecules which showed potent antibacterial activity. Surprisingly, in nature, sometimes different categories of phytochemical compounds may act synergistically all together effectively on microbes than if separated into pure compounds. To better illustrate the image, we will give an example on a virus known as Herpes simplex (HSV), it was found that some phytochemical constituents of latex and propolis are more effective as an antiviral agent than if separated to individual compounds Cowan [2]. Accordingly, it would be advantageous to Establishing scientific programs and international research groups supported by governments, Scientific Associations and pharmaceutical companies for more investigations in that worthy field.
Conclusion and Future Perspectives
No doubt that numerous studies in the past few decades have shown that plants are a good potential source for new antibacterial drugs. Accordingly, there is a promising future for the antibacterial medicinal plants as there are tremendous and diverse numbers of plants on Earth and most of them are not investigated well yet. Moreover, herbal medicine is gaining popularity day by day and subsequently launching new natural antibacterial drugs in the pharmaceutical markets will gain wide acceptance. However, more comprehensive studies related to the isolation of antibacterial phytochemical compounds from medicinal plants much work must still be carried out, to ensure the selection of bioactive and non-toxic or possible side effects of the nominated antibacterial phytochemicals. On the other side, financial support is crucial to push the scientific efforts forward which rely on the interest of pharmaceutical companies to invest in that promising field.
References
- Abdallah EM (2011) Plants: An alternative source for antimicrobials. Journal of Applied Pharmaceutical Science 1 (6): 16-20.
- Cowan MM (1999) Plant Products as Antimicrobial Agents. Clinical Microbiology Review 12(4): 564-582.
- Qazi MA, Molvi KI (2016) Herbal Medicine: A Comprehensive Review. International Journal of Pharmaceutical Research 8(2): 1-5.
- Bassetti M, Righi E (2013) Multidrug-resistant bacteria: what is the threat. Hematology Am Soc Hematol Educ Program 13: 428-432.
- Medina E, Pieper DH (2016) Tackling Threats and Future Problems of Multidrug-Resistant Bacteria. Curr Top Microbiol Immunol 398: 3-33.
- Abdallah EM (2017) Beyond antibiotics, is there any Hope for New Alternatives. American Journal of Preventive medicine and Public Health 1(1): 52-53.
- Bello F, Babandi A, Murtala Y (2016) Phytochemicals as Potential Alternatives to Counteract Bacterial Antibiotic Resistance: A Mini-Review. J Biomed Sci 1(1): 124-141.
- Fang C, Fernie AR, Luo J (2019) Exploring the Diversity of Plant Metabolism. Trends in Plant Science 24(1): 83-98.
- Clemensen AK (2018) Understanding Plant Secondary Metabolites; Above and Below Ground. All Graduate Theses and Dissertations. USA.
- Maria de Lourdes Reis Giada (2013) Food Phenolic Compounds: Main Classes, Sources and Their Antioxidant Power.
- Ahmed E, Arshad M, Khan MZ, Amjad MS, Sadaf HM, et al. (2017) Secondary metabolites and their multidimensional prospective in plant life. Journal of Pharmacognosy and Phytochemistry 26(2): 205-214.
- Njeru SN, Matasyoh J, Mwaniki CG, Mwendia CM, Kobia GK (2013) A Review of some Phytochemicals commonly found in Medicinal Plants. International Journal of Medicinal Plants. Photon 105: 135-140.
- Nikaido H (2009) Multidrug resistance in bacteria. Annual review of biochemistry 78: 119-146.
- Tanwar J, Das S, Fatima Z, Hameed S (2014) Multidrug Resistance: An Emerging Crisis. Interdisciplinary Perspectives on Infectious Diseases Article ID 541340.
- Munita JM, Arias CA (2016) Mechanisms of Antibiotic Resistance. Microbiology spectrum 4(2): PMCID: PMC4888801.
- Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A (2018) Flavonoids and Other Phenolic Compounds from Medicinal Plants for Pharmaceutical and Medical Aspects: An Overview. Medicines 5(93): 1-16.
- Malviya S, Arvind JA, Hettiarachchy N (2014) Antioxidant and antibacterial potential of pomegranate peel extracts. Journal of food science and technology 51(12): 4132-4137.
- Pavic V, Flacer D, Jakovljevic M, Molnar M, Jokic S (2019) Assessment of Total Phenolic Content, In Vitro Antioxidant and Antibacterial Activity of Ruta graveolens L. Extracts Obtained by Choline Chloride Based Natural Deep Eutectic Solvents. Plants 8(69): 1-9.
- Dzotam JK, Simo IK, Bitchagno G, Celik I, Sandjo LP, et al. (2018) In vitro antibacterial and antibiotic modifying activity of crude extract, fractions and 3',4',7-trihydroxyflavone from Myristica fragrans Houtt against MDR Gram-negative enteric bacteria. BMC Complement. Altern Med 18(1): 15.
- Poomanee W, Chaiyana W, Mueller M, Viernstein H, Khunkitti W, Leelapornpisid P (2018) In-vitro investigation of anti-acne properties of Mangifera indica L. kernel extract and its mechanism of action against Propionibacterium acnes. Anaerobe 52: 64-74.
- Bribi N (2018) Pharmacological activity of Alkaloids: A Review. Asian Journal of Botany 1:1-6.
- Mabhiza D, Chitemerere T, Mukanganyama S (2016) Antibacterial Properties of Alkaloid Extracts from Callistemon citrinus and Vernonia doensis against Staphylococcus aureus and Pseudomonas aeruginosa. International Journal of Medicinal Chemistry 2016: 1-7.
- Gurrapu S, Estari Mamidala E (2017) In vitro Antibacterial Activity of Alkaloids Isolated from Leaves of Eclipta alba Against Human Pathogenic Bacteria. Pharmacogn J 9(4): 573-577.
- Mahmud PIAM, Yacob WA, Ibrahim N (2017) Antibacterial Activity of Alkaloid Extracts from Ochrosia oppositifolia. Sains Malaysiana 46(8): 1279–1284.
- Singh S, Swapnil, Verma SK (2011) Antibacterial properties of Alkaloid rich fractions obtained from various parts of Prosopis juliflora. International Journal of Pharma Sciences and Research 2(3):114-120.
- Tholl D (2015) Biosynthesis and Biological Functions of Terpenoids in Plants. Adv. Biochem. Eng Biotechnol 148: 63-106.
- Solís C, Becerra J, Flores C, Robledo J, Silva M (2004) Antibacterial and antifungal terpenes from Pilgerodendron uviferum (D. Don) Florin. J Chil Chem Soc 49(2): 157-161.
- Biva IJ, Ndi CP, Semple SJ, Griesser HJ (2019) Antibacterial Performance of Terpenoids from the Australian Plant Eremophila lucida. Antibiotics 8(63): 8020063.
- Gartika M, Pramesti HT, Kurnia D, Satari MH (2018) A terpenoid isolated from sarang semut (Myrmecodia pendans) bulb and its potential for the inhibition and eradication of Streptococcus mutans biofilm. BMC Complement. Altern Med 18(1): 151.
- Kiokias S, Proestos C, Varzakas T (2016) A Review of the Structure, Biosynthesis, Absorption of Carotenoids-Analysis and Properties of their Common Natural Extracts. Current Research in Nutrition and Food Science 4(S1): 25-37.
- Djifaby SPAE, Yacouba CA, Adama H, Kiessoum K, Compaore Marie Hyacinthe M, et al. (2012) Carotenoids content and antibacterial activity from galls of Guiera senegalensis j.f. Gmel (Combretaceae). International Journal of Phytomedicine 4: 441-446.
- Natividad LR, Rafael RR (2014) Carotenoid Analyses and Antibacterial Assay of Annato (Bixa orellana L.), Carrot (Daucus carota L.), Corn (Zea mays L.) and Tomato (Solanum lycopersicum L.) Extracts. Res J Recent Sci 3(3): 40-45.