Neem - Evidence-Based Health Benefits

By Hugo Francisco de SouzaReviewed by Benedette Cuffari, M.Sc.

Introduction
What is neem?
Botanical profile
Antimicrobial activity
Antiviral effects
Oral health applications
Anti-inflammatory and immunomodulatory effects
Dermatological applications
Metabolic and chronic disease management
Cancer and chemoprevention
Safety, toxicity, and limitations
Conclusion
References
Further reading

Explore how centuries-old neem remedies are being validated by modern science, as researchers unlock its antimicrobial, antiviral, and metabolic benefits for a new era of evidence-based healthcare.

Azadirachta indica. Image Credit: nipaporn kamkasem / Shutterstock.com

Introduction

From ancient Ayurvedic remedies to modern clinical laboratories, Azadirachta indica, commonly referred to as ‘neem,’ is widely recognized for its potent antimicrobial, anti-inflammatory, and metabolic properties. Neem has been increasingly studied for its role in managing infections, chronic diseases, and even cancer.

This article explores recent research highlighting the in vitro and in vivo antibacterial efficacy of neem, as well as its antiviral potential, immunomodulatory effects, and dermatological applications.

What is neem?

For over two millennia, the neem tree has been a staple of traditional medicine in South Asia. The various components of neem, including its leaves, seeds, bark, and oil, have been valued in Ayurveda, Unani, and folk remedies for their broad-spectrum therapeutic properties. Historically, neem has been used to treat skin disorders, infections, and metabolic ailments.

With rising global interest in evidence-based natural products, neem has gained attention in modern healthcare. To this end, biomedical researchers are actively validating many of the plant’s traditional uses while highlighting its potential as a bioactive agent in integrative and evidence-based medicine.

Botanical profile

Neem is a fast-growing tree belonging to the mahogany family, Meliaceae, and thrives in tropical and semi-tropical climates. The evergreen tree is native to the Indian subcontinent and widely cultivated in Africa, the Americas, and Southeast Asia. This tree can reach up to 20 meters in height and is known for its drought resistance and longevity.¹

Neem leaves, bark, seeds, fruit, and oil are used in traditional remedies and commercial formulations, as these preparations are rich in secondary metabolites including azadirachtin, nimbin, nimbidin, and quercetin. Azadirachtin is primarily known for its insecticidal properties, whereas nimbin and nimbidin exhibit anti-inflammatory and antimicrobial activity.¹

Neem oil, which is extracted from crushed seeds, contains high concentrations of triglycerides and is widely used in topical dermatological preparations and personal care products.²

This vast chemical profile has increased interest in isolating specific compounds for subsequent pharmaceutical development. However, variability in phytochemical content based on plant part, age, and geographic location remains a challenge for standardization and clinical applications.¹

Antimicrobial activity

Among neem’s most extensively studied properties is its antimicrobial efficacy. Recent in vitro research using methanolic neem leaf extract has identified β-d-mannofuranoside, O‑geranyl as a key antibacterial agent. This compound has been characterized by minimum inhibitory concentrations (MICs) of 32 and 64 µg/mL against Staphylococcus aureus and Escherichia coli, respectively, with extract concentrations as low as 3.125%.³

Neem-synthesized silver nanoparticles have also demonstrated effectiveness against multiple drug-resistant pathogens, highlighting the potential of this plant in combating antibiotic-resistant bacteria.²

Antiviral effects

Neem extracts have demonstrated antiviral effects against Herpes simplex virus (HSV) types 1 and 2 (HSV-1 and HSV-2), with this activity mediated by glycolipid compounds that block viral entry into host cells.⁴ Similar antiviral efficacy has been reported in vitro against influenza and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Oral health applications

Neem chewing sticks and mouthwashes have been used as dental hygiene tools for centuries. Clinical studies have confirmed that neem mouthwash provides similar protection against plaque and gingivitis when compared to chlorhexidine, a broad-spectrum antiseptic and disinfectant commonly used in mouthwashes and toothpastes.

Anti-inflammatory and immunomodulatory effects

Neem exhibits pronounced anti-inflammatory actions, which are largely attributed to its ability to downregulate pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6.

Nimbin and quercetin have also been shown to downregulate cyclooxygenase (COX) and lipoxygenase (LOX) inflammatory pathways in vitro and animal models. These mechanisms indicate that neem has the potential to ameliorate symptoms associated with arthritis and other autoimmune inflammatory diseases; however, robust clinical trials are warranted.

Dermatological applications

Neem oil and extracts are widely used to treat skin conditions such as acne, eczema, and psoriasis, as well as for wound healing, both historically and in recent cosmetic and dermatological products. The antioxidant and anti-inflammatory properties of neem likely contribute to its effectiveness in improving skin health.

Randomized controlled trials have reported that neem-based gels can reduce acne lesion counts by over 50% within eight weeks. Neem formulations also promote wound closure and collagen synthesis, with these products outperforming standard antiseptic ointments in both healing efficacy and scar appearance.⁹

Metabolic and chronic disease management

Bioactive ingredients isolated from neem leaf extracts can reduce fasting blood glucose levels, improve glucose tolerance, and inhibit carbohydrate-digesting enzymes, all of which are therapeutically relevant when targeting type 2 diabetes (T2D), obesity, and cardiovascular diseases (CVDs).

These effects can be attributed to increased glucose uptake in peripheral tissues and modulation of hepatic gluconeogenesis. Animal studies confirm these benefits and further report significant reductions in total cholesterol, triglycerides, and harmful low-density lipoproteins (LDL).¹⁰

Cancer and chemoprevention

The antioxidant and cytotoxic properties of neem are being increasingly investigated for their potential as chemopreventive agents. Furthermore, emerging in vitro data suggest that neem treatment has antiproliferative effects on cancer cells.

For example, neem seed extracts exhibit selective cytotoxic activity against breast and prostate cancer lines.⁷ Nevertheless, additional studies are needed to confirm the efficacy and safety of these plant-derived bioactives.

Safety, toxicity, and limitations

Neem is generally considered safe and well-tolerated when used in supplemental or topical doses. Side effects are uncommon and mild, typically involving gastrointestinal or dermal irritation.¹¹

However, high doses, particularly of neem oil, have been associated with hepatotoxicity and neurotoxicity in animal models. In rare cases, neem oil ingestion has caused severe metabolic acidosis and encephalopathy in children.¹¹

Pregnant and lactating women are advised to avoid neem and its extracts due to abortifacient effects in animal models. Other reported side effects include allergic dermatitis, gastrointestinal upset, and impaired liver function at high doses or with long-term use. Furthermore, the potential for neem to interact with medications for diabetes, hypertension, or immunosuppression warrants medical supervision.

The lack of dosage standardizations in public health agency-prescribed recommendations leads to significant product variability. As a result, active compound levels in neem products can vary significantly between preparations, which impacts efficacy and safety.⁷

Conclusions

Contemporary research supports the traditional use of neem and confirms its utility as a valuable natural agent in modern healthcare. The antimicrobial and antiviral potency of neem, which has been confirmed through antibacterial MICs and viral inhibition studies, reinforces its traditional uses.

Despite these advances, there remains an urgent need for standardized formulations, rigorously designed clinical trials, and safety evaluations in humans. Until then, neem holds promise as a complementary therapy; however, its use should be guided by quality-controlled products and medical advice. Integrating neem into evidence-based medicine could enrich holistic strategies for managing infection, inflammation, and chronic diseases.

References

1. Biswas, K., Chattopadhyay, I., Banerjee, R. K., & Bandyopadhyay, U. (2002). Biological activities and medicinal properties of neem. Current Science, 82(11), 1336–1345. https://www.jstor.org/stable/24106000
2. Alqahtani, O., Mirajkar, K. K., Kumar, K. R. A., et al. (2022). In vitro antibacterial activity of green synthesized silver nanoparticles using Azadirachta indica aqueous leaf extract against MDR pathogens. Molecules, 27(21), 7244. DOI: 10.3390/molecules27217244, https://www.mdpi.com/1420-3049/27/21/7244
3. Altayb, H. N., Yassin, N. F., Hosawi, S., et al. (2022, May 25). In‑vitro and in‑silico antibacterial activity of Azadirachta indica (Neem) methanolic extract... BMC Plant Biology, 22, 262. DOI:10.1186/s12870‑022‑03650‑5, https://bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-022-03650-5
4. Bharitkar, Y. P., Bathini, S., Ojha, D., Ghosh, S., Mukherjee, H., Kuotsu, K., Hazra, A., & Mondal, N. B. (2014). Antibacterial and antiviral evaluation of sulfonoquinovosyldiacylglyceride: a glycolipid isolated from Azadirachta indica leaves. Letters in Applied Microbiology, 58(2), 184–189. frontiersin.org +6 scholar.google.com +6 onlinelibrary.wiley.com, DOI: 10.1111/lam.12174, https://academic.oup.com/lambio/article-abstract/58/2/184/6699495?redirectedFrom=fulltext&login=false
5. Bioactive Azadirachta indica and Melia azedarach leaves extracts with anti-SARS-CoV-2 and antibacterial activities Hemdan BA, Mostafa A, Elbatanony MM, El-Feky AM, Paunova-Krasteva T, et al. (2023) Bioactive Azadirachta indica and Melia azedarach leaves extracts with anti-SARS-CoV-2 and antibacterial activities. PLOS ONE 18(3): e0282729. DOI:10.1371/journal.pone.0282729, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282729
6. Pai, M. R., Acharya, L. D., & Udupa, N. (2004). Evaluation of antiplaque activity of Azadirachta indica leaf extract gel—a 6-week clinical study. Journal of Ethnopharmacology, 90(1), 99–103. DOI:10.1016/j.jep.2003.09.035 https://linkinghub.elsevier.com/retrieve/pii/S037887410300357X
7. Munir, M., Shah, S., Almas, U., Khan, F., Zaidi, A., Bukhari, S., & Murtaza, G. (2021). An assessment of the wound healing potential of a herbal gel containing an Azadirachta indica leaf extract. Veterinární Medicína, 66(3), 99–109. DOI: 10.17221/46/2020-vetmed, https://vetmed.agriculturejournals.cz/artkey/vet-202103-0003_an-assessment-of-8239-the-wound-healing-potential-of-8239-a-herbal-gel-containing-an-8239-azadirachta-indica.phpv
8. Upadhyay, S. N., Dhawan, S., & Talwar, G. P. (2010). Antifertility effects of neem (Azadirachta indica) oil by single intrauterine administration: A novel contraceptive approach. Indian Journal of Medical Research, 131(2), 189–195. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840928/
9. Banerjee, K., Chatterjee, M., Sandur V, R., Nachimuthu, R., Madhyastha, H., & Thiagarajan, P. (2021). Azadirachta indica A. Juss (Neem) oil topical formulation with liquid crystals ensconcing depot water for anti-inflammatory, wound healing and anti-methicillin resistant Staphylococcus aureus activities. Journal of Drug Delivery Science and Technology, 64, 102563. DOI: 10.1016/j.jddst.2021.102563, https://www.sciencedirect.com/science/article/abs/pii/S1773224721002434
10. Hussain, S., et al. (2023). Azadirachta indica against diabetes mellitus: a critical review. ACS Omega. https://pubmed.ncbi.nlm.nih.gov/34562010/
11. Mishra, A., & Dave, N. (2013). Neem oil poisoning: Case report of an adult with toxic encephalopathy. Indian Journal of Critical Care Medicine, 17(5), 321–322. DOI: 10.4103/0972-5229.120330, https://www.ijccm.org/doi/pdf/10.4103/0972-5229.120330

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