Bridging Ethnobotany and Clinical Microbiology Through the Discovery of Novel Antimicrobials from Medicinal Plants

1. Introduction

Antimicrobial resistance (AMR) has emerged as one of the most critical public health challenges of the 21st century. The overuse and misuse of antibiotics in human medicine, agriculture, and animal husbandry have contributed significantly to the rapid evolution of resistant microbial strains. Today, once-easily treatable infections caused by pathogens such as Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis, and Candida albicans are becoming increasingly difficult, and sometimes impossible, to treat with standard antimicrobial therapies. This growing resistance threatens the efficacy of surgical procedures, cancer chemotherapy, and the management of chronic illnesses, thereby undermining decades of medical progress [1], the global scientific community is intensifying efforts to identify new antimicrobial agents with novel mechanisms of action. However, the conventional antibiotic development pipeline is lengthy, expensive, and fraught with high failure rates. Moreover, the majority of synthetic compounds discovered through combinatorial chemistry and high-throughput screening have not yielded the expected therapeutic breakthroughs [2]. In this context, natural products—especially those derived from plants—are re-emerging as valuable sources of new antimicrobial candidates.

Medicinal plants have been used for millennia across diverse cultures to treat infectious diseases. Traditional healing systems such as Ayurveda, Traditional Chinese Medicine (TCM), and Indigenous ethnomedicine rely heavily on the antimicrobial potential of botanicals [3]. Ethnobotany, the interdisciplinary field that explores the cultural and biological relationships between people and plants, plays a pivotal role in cataloging these traditional practices [4]. It serves as a bridge between ancient knowledge and modern drug discovery, providing a focused, knowledge-guided approach to selecting plant species for antimicrobial screening.

The phytochemical diversity found in medicinal plants is vast. Plants produce a range of secondary metabolites—such as alkaloids, terpenoids, flavonoids, saponins, and tannins—that serve as chemical defense mechanisms against microbial pathogens, herbivores, and environmental stressors [5]. Many of these compounds exhibit potent antimicrobial, anti-inflammatory, and immunomodulatory properties, making them attractive candidates for pharmaceutical development [6]. Unlike synthetic drugs, which often target a single microbial mechanism, plant-derived compounds frequently exert multifaceted effects, reducing the likelihood of resistance development.

Recent advances in analytical chemistry, molecular biology, and bioinformatics have significantly enhanced our ability to identify and characterize the active constituents of plant extracts. High-throughput screening technologies, mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, and next-generation sequencing (NGS) have facilitated detailed phytochemical profiling and functional analysis [7]. These tools also enable the study of microbial responses to phytochemicals at the molecular level, helping to elucidate mechanisms of action such as membrane disruption, enzyme inhibition, interference with nucleic acid synthesis, and inhibition of quorum sensing and biofilm formation, there is growing interest in the synergistic potential of combining plant extracts or isolated compounds with conventional antibiotics. Such combinations can enhance antimicrobial efficacy, lower required drug dosages, minimize toxicity, and potentially reverse resistance in multidrug-resistant (MDR) pathogens [8]. For example, polyphenols from Camellia sinensis (green tea) and essential oils from Thymus vulgaris (thyme) have demonstrated significant synergism with antibiotics like ciprofloxacin and ampicillin, respectively [9], the integration of ethnobotanical knowledge with clinical microbiology still faces numerous challenges. Variability in plant composition due to environmental factors, lack of standardization in extract preparation, limited toxicological data, and the absence of regulatory frameworks for herbal-derived antimicrobials hinder clinical application, these issues requires a multidisciplinary approach that encompasses pharmacognosy, microbiology, ethnopharmacology, and medicinal chemistry, [10]. the phytochemical landscape of medicinal plants with antimicrobial potential, highlighting both their traditional uses and scientific validation. We examine key bioactive compounds, their mechanisms of microbial inhibition, and the potential for synergistic applications with conventional antibiotics. By bridging ethnobotany with clinical microbiology, the importance of preserving traditional plant knowledge and leveraging modern science to develop effective and sustainable antimicrobial therapies in the fight against AMR.

2. Ethnobotanical Significance in Antimicrobial Discovery

For centuries, medicinal plants have served as the primary source of healthcare for countless communities worldwide, particularly in resource-limited settings. Long before the advent of modern antibiotics, traditional healers relied on plant-based remedies to treat infections, wounds, fevers, and inflammation—many of which were likely caused by bacterial or fungal pathogens [11]. The accumulated empirical knowledge preserved within indigenous and traditional medical systems, such as Ayurveda, Traditional Chinese Medicine (TCM), Unani, and numerous tribal pharmacopeias, offers an invaluable reservoir of leads for modern drug discovery efforts.

Ethnobotany, the scientific study of the relationships between people and plants, plays a pivotal role in guiding antimicrobial research. Ethnobotanical surveys systematically document traditional uses of plants, capturing local knowledge regarding species used for treating infections, methods of preparation (e.g., decoctions, poultices, tinctures), dosage, and observed efficacy [12]. These surveys help identify promising plant candidates for antimicrobial screening, significantly improving the hit rate compared to random bio-prospecting.

Numerous medicinal plants, identified through ethnobotanical investigation, have demonstrated notable antimicrobial activity in laboratory studies. For example:

• Azadirachta indica (neem), widely used in Indian traditional medicine, exhibits strong antibacterial and antifungal properties attributed to compounds like nimbin, azadirachtin, and quercetin. Neem extracts have shown effectiveness against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa.
• Allium sativum (garlic), a culinary and medicinal staple, contains allicin—a sulfur-containing compound known for its potent broad-spectrum antimicrobial activity. Allicin acts rapidly on microbial membranes and enzymes, making it effective even against multidrug-resistant strains.
• Curcuma longa (turmeric), a cornerstone of South Asian herbal medicine, contains curcumin, which has demonstrated antimicrobial, anti-inflammatory, and antioxidant properties. Curcumin has shown inhibitory effects on a range of bacterial and fungal species, often through disruption of membrane integrity and interference with microbial signaling pathways.

Other notable plants include Ocimum sanctum (holy basil), Eucalyptus globulus, Zingiber officinale (ginger), and Tinospora cordifolia, each recognized in multiple traditional systems and validated for antimicrobial properties in modern pharmacological studies.

Importantly, ethnopharmacological documentation not only identifies plants of interest but also provides insight into optimal parts used (e.g., leaves, roots, bark), traditional combination therapies, and modes of delivery [13]. This knowledge can inform extract preparation and experimental design in preclinical studies, increasing reproducibility and relevance, ethnobotanical knowledge as a foundation, researchers can reduce the time, cost, and uncertainty involved in the early stages of drug discovery. This targeted approach also enhances cultural sensitivity and encourages collaboration with indigenous communities—who are often the custodians of this knowledge [14]. Ethical considerations and benefit-sharing agreements are therefore essential to ensure responsible and equitable use of ethnobotanical data, ethnobotany offers a practical and culturally rooted strategy for identifying novel plant-based antimicrobials [15]. When integrated with modern microbiological, phytochemical, and molecular tools, ethnobotanical insights can accelerate the discovery of new drugs to combat infectious diseases, especially in the era of increasing antimicrobial resistance.

3. Phytochemicals as Antimicrobial Agents

Medicinal plants produce a wide spectrum of secondary metabolites known as phytochemicals, which serve as chemical defenses against microbial invasion, herbivory, and environmental stress [16]. These bioactive compounds are increasingly recognized for their potential as novel antimicrobial agents, especially in the face of rising antimicrobial resistance. Key classes of phytochemicals include alkaloids, flavonoids, tannins, saponins, terpenoids, and phenolic compounds—each exhibiting distinct structures and mechanisms of action against a broad range of pathogens.

• Alkaloids, nitrogen-containing compounds found in plants like Berberis spp. and Papaver somniferum, often interfere with microbial DNA and RNA synthesis. Their intercalation into nucleic acid structures or inhibition of topoisomerases can block replication and transcription.
• Flavonoids, such as quercetin and catechins, possess antimicrobial activity through mechanisms like disruption of microbial membranes, inhibition of energy metabolism, and interference with quorum sensing pathways—crucial for microbial virulence and biofilm formation.
• Tannins, polyphenolic compounds found in plants like Terminalia chebula, can precipitate microbial proteins, disrupt enzyme activity, and affect cell wall integrity.
• Saponins exhibit surfactant properties that lead to pore formation and lysis of microbial membranes, particularly against fungi and Gram-positive bacteria.
• Terpenoids and essential oils from plants such as Thymus vulgaris (thyme) and Mentha piperita (peppermint) integrate into microbial lipid membranes, causing membrane destabilization and ion leakage.
• Phenolic acids, including caffeic acid and gallic acid, interfere with microbial enzymes and oxidative balance, reducing pathogen viability. These compounds often exhibit synergistic effects when combined within whole plant extracts, offering multifaceted attacks on microbial targets and minimizing the likelihood of resistance development.

---

4. Screening and Validation Methods

The translation of ethnobotanical leads into viable antimicrobial agents requires robust screening and validation strategies. Modern microbiology and analytical chemistry offer a toolkit for identifying, isolating, and characterizing bioactive compounds with precision and efficiency.

• Agar diffusion methods (e.g., disk diffusion and well diffusion assays) provide a qualitative assessment of antimicrobial activity by measuring zones of inhibition. These are useful for preliminary screening of crude extracts or fractions.
• Broth microdilution assays are the gold standard for quantifying antimicrobial potency. They determine the Minimum Inhibitory Concentration (MIC)—the lowest concentration of a compound that inhibits visible microbial growth—and Minimum Bactericidal/Fungicidal Concentration (MBC/MFC).
• Bioautography combines chromatography and microbial overlay techniques to localize antimicrobial constituents in complex mixtures. It enables rapid screening of active spots on thin-layer chromatography (TLC) plates, guiding compound isolation.
• Molecular docking and in silico analysis offer predictive insights into how phytochemicals interact with microbial enzymes, receptors, or structural components. These computational tools accelerate the discovery pipeline by highlighting promising compound-target interactions before labor-intensive wet-lab studies.
• Omics technologies—including metabolomics, proteomics, and transcriptomics—allow for comprehensive profiling of phytochemical action on microbial cells. They can elucidate global changes in gene expression or metabolic pathways in response to treatment, providing deeper mechanistic understanding. Together, these methods create a robust framework for evaluating the antimicrobial potential of phytochemicals [17]. When applied systematically, they bridge the gap between traditional knowledge and modern scientific validation, facilitating the development of plant-derived antimicrobials into clinically viable therapeutics.

5. Synergistic Effects and Resistance Modulation

Beyond their intrinsic antimicrobial activity, plant-derived compounds can synergize with conventional antibiotics, offering a powerful approach to counteract antimicrobial resistance (AMR). Phytochemicals can disrupt microbial defense mechanisms—such as efflux pumps, biofilm formation, or enzymatic degradation—thereby restoring the efficacy of otherwise ineffective antibiotics [18]. For instance, catechins from Camellia sinensis (green tea) have demonstrated the ability to potentiate beta-lactam antibiotics against resistant Staphylococcus aureus strains. Such synergistic interactions can not only lower the required therapeutic doses of antibiotics but also reduce the risk of adverse effects and delay the emergence of resistance. This dual strategy—targeting both pathogens and resistance pathways—underscores the value of integrating phytochemicals into antimicrobial regimens.

---

6. Clinical Translation and Challenges

Despite robust in vitro and preclinical evidence supporting the antimicrobial potential of medicinal plants, the pathway to clinical application remains fraught with challenges. Chief among these is the standardization of plant extracts. The complex and variable composition of botanical preparations makes it difficult to ensure consistency, reproducibility, and quality control, especially across different batches and sources.

Toxicological evaluation is another critical bottleneck. Many phytochemicals have not been comprehensively assessed for safety in humans, and potential interactions with pharmaceuticals must be carefully considered [19]. Moreover, regulatory approval processes are often ill-equipped to handle multi-component plant extracts, which fall outside the typical single-compound pharmaceutical paradigm, the challenges include variability in phytochemical content due to environmental, seasonal, and genetic factors; lack of harmonized intellectual property frameworks for protecting indigenous knowledge; and concerns over equitable benefit-sharing with local communities who are the custodians of ethnobotanical wisdom [20].

---

7. Future Directions

To fully realize the promise of ethnobotanical resources in antimicrobial drug discovery, a forward-looking and integrative approach is essential [21]. Key future directions include:

• Development of ethnobotanical databases that systematically link traditional use with pharmacological and microbiological data. These resources can serve as valuable repositories for hypothesis generation and research prioritization.
• Application of artificial intelligence (AI) and machine learning to predict antimicrobial activity based on phytochemical structures, ethnobotanical use patterns, and existing bioassay data. This can dramatically accelerate lead identification.
• Fostering participatory research models that include indigenous communities in all phases of research—from documentation and screening to commercialization. This promotes ethical practices and ensures that benefits are shared equitably.
• Investments in sustainable sourcing and cultivation of medicinal plants to safeguard biodiversity and ensure a consistent supply of quality raw materials. By bridging traditional knowledge systems with cutting-edge technologies and ethical frameworks, the field can make meaningful strides toward the discovery of novel, effective, and sustainable antimicrobial agents [22-23].

8. Conclusion

The convergence of ethnobotany and clinical microbiology offers a powerful and underutilized avenue for discovering novel antimicrobial agents. Traditional knowledge, accumulated over centuries, provides a valuable blueprint for identifying medicinal plants with therapeutic potential. When integrated with modern pharmacological and microbiological methodologies, this knowledge can be harnessed to uncover bioactive compounds that are effective against resistant pathogens. Amid the global crisis of antimicrobial resistance, plant-based therapeutics represent a sustainable and diverse reservoir of pharmacologically active molecules. By bridging empirical ethnobotanical practices with contemporary drug discovery pipelines, we can accelerate the development of next-generation antimicrobials. Moreover, this approach reinforces the importance of preserving both biological and cultural diversity, as they serve as foundational resources for future medical innovation, interdisciplinary collaboration, ethical engagement with indigenous communities, and investments in translational research will be essential to realize the full potential of this integrative paradigm. Through this holistic strategy, we not only enrich scientific discovery but also promote equitable and sustainable healthcare solutions worldwide.

References

1. Porras, G., Chassagne, F., Lyles, J. T., Marquez, L., Dettweiler, M., Salam, A. M., … & Quave, C. L. (2020). Ethnobotany and the role of plant natural products in antibiotic drug discovery. Chemical reviews, 121(6), 3495-3560.
2. Quave, C. L. (2016). Antibiotics from nature: traditional medicine as a source of new solutions for combating antimicrobial resistance. AMR Control, 98, 102.
3. Ashraf, M. V., Pant, S., Khan, M. H., Shah, A. A., Siddiqui, S., Jeridi, M., … & Ahmad, S. (2023). Phytochemicals as antimicrobials: prospecting Himalayan medicinal plants as source of alternate medicine to combat antimicrobial resistance. Pharmaceuticals, 16(6), 881.
4. Rai, M., & Kosalec, I. (Eds.). (2022). Promising antimicrobials from natural products (Vol. 2022, p. 19). Dordrecht, The Netherlands:: Springer.
5. Unnisa, S. A., Chandana, M., Neeharika, M., & Revathi, E. (2023). Epidemic of Mucormycosis in India: A Covid-19 Complications. Environmental Reports; an International Journal.
6. Ngashangva, N., Mukherjee, P., Sharma, K. C., Kalita, M. C., & Indira, S. (2021). Analysis of antimicrobial peptide metabolome of bacterial endophyte isolated from traditionally used medicinal plant Millettia pachycarpa Benth. Frontiers in Microbiology, 12, 656896.
7. Coopoosamy, R., Singh, K., Naidoo, K., & Nadasan, D. S. (2023). The role of phytomedicine: Bridging the gap between the past, present, and future. Journal of Medicinal Plants for Economic Development, 7(1), 7.
8. George, U. U., Mbong, E. O., Bolarinwa, K. A., & Abiaobo, N. O. (2023). Ethno-botanical verification and phytochemical profile of ethanolic leaves extract of two medicinal plants (Phragmenthera capitata and Lantana camara) used in Nigeria using GC-MS Technique. In Acta Biology Forum (Vol. 5, No. 2, pp. 78-89).
9. Woo, S., Marquez, L., Crandall, W. J., Risener, C. J., & Quave, C. L. (2023). Recent advances in the discovery of plant-derived antimicrobial natural products to combat antimicrobial resistant pathogens: insights from 2018–2022. Natural product reports, 40(7), 1271-1290.
10. Wiyakrutta, S., Sriubolmas, N., Panphut, W., Thongon, N., Danwisetkanjana, K., Ruangrungsi, N., & Meevootisom, V. (2004). Endophytic fungi with anti-microbial, anti-cancer and anti-malarial activities isolated from Thai medicinal plants. World journal of microbiology and biotechnology, 20(3), 265-272.
11. Tagboto, S., & Townson, S. (2001). Antiparasitic properties of medicinal plants and other naturally occurring products.
12. Sharma, V., & Sarkar, I. N. (2013). Bioinformatics opportunities for identification and study of medicinal plants. Briefings in bioinformatics, 14(2), 238-250.
13. Woldeamanuel, M. M., Geda, M. K., Mohapatra, S., Bastia, T. K., Rath, P., & Panda, A. K. (2022). Ethnobotanical study of endemic and non-endemic medicinal plants used by indigenous people in environs of Gullele botanical garden Addis Ababa, central Ethiopia: a major focus on Asteraceae family. Frontiers in Pharmacology, 13, 1020097.
14. Chinyama, R. F. (2009). Biological activities of medicinal plants traditionally used to treat septicaemia in the Eastern Cape, South Africa. Masters, Biomedical Technology, Nelson Mandela Metropolitan University.
15. Alemu, T. T. (2023). Effect of storage time and room temperature on physicochemical and geometric properties of banana (Musa Spp.) Fruit. Journal of Plant Biota, 30-40.
16. Nelson, D. W., Millar, B. C., Rao, J. R., & Moore, J. E. (2021). The role of plants and macrofungi as a source of novel antimicrobial agents. Reviews and Research in Medical Microbiology, 32(4), 231-236.
17. Dutta, T., Anand, U., Saha, S. C., Mane, A. B., Prasanth, D. A., Kandimalla, R., … & Dey, A. (2021). Advancing urban ethnopharmacology: A modern concept of sustainability, conservation and cross-cultural adaptations of medicinal plant lore in the urban environment. Conservation physiology, 9(1), coab073.
18. Caruso, D. J., Palombo, E. A., Moulton, S. E., & Zaferanloo, B. (2022). Exploring the promise of endophytic fungi: a review of novel antimicrobial compounds. Microorganisms, 10(10), 1990.
19. Naik, D. B., Rao, B. B., Kumar, C. U., & Bhavani, N. L. (2022). Phytochemical analysis of different varieties of sorghum biocolor in Telangana State, India. Agriculture Archives, 1, 16-20.
20. Alshawsh, M. A., Mothana, R. A., Al-Shamahy, H. A., Alsllami, S. F., & Lindequist, U. (2009). Assessment of antimalarial activity against Plasmodium falciparum and phytochemical screening of some Yemeni medicinal plants. Evidence‐Based Complementary and Alternative Medicine, 6(4), 453-456.
21. Nazneen, S., & Nausheed, R. (2022). Exploring the Contribution of Botanical Families to Medicinal Ethnobotany. Journal of Plant Biota.
22. Bentley, R. (1997). Microbial secondary metabolites play important roles in medicine; prospects for discovery of new drugs. Perspectives in biology and medicine, 40(3), 364-394.
23. Hassan, M., Haq, S. M., Rasool, A., Fatima, S., Ashraf, A., Zulfajri, M., & Hanafiah, M. M. (2021). Ethnobotanical properties and traditional uses of medicinal plant Abutilon theophrasti Medik. In Medicinal and Aromatic Plants: Healthcare and Industrial Applications (pp. 271-285). Cham: Springer International Publishing.