Neem - A Wonder Tree

Neem (Azadirachta indica), also called margosa, belongs to the Meliaceae family. Neem is native to the Indian subcontinent. Nearly all parts of the neem tree are beneficial. Neem plays a vital role in disease prevention and treatment by enhancing antioxidant activity, inhibiting bacterial growth, and modulating genetic pathways. Due to its antibacterial, antifungal, insecticidal, and fungicidal properties, it is used in medicine, cosmetics, and as a pesticide. Neem is commonly used for treating dandruff, skin conditions such as acne, psoriasis, and athlete’s foot. It is a component of some toothpaste and mouthwashes, and its young twigs are used directly as crude toothbrushes in rural areas. Neem leaves and bark have long been used as a traditional treatment for diabetes.

Neem contains various active principles that exhibit antioxidant, anti-inflammatory, antiulcer, antifungal, antiviral, hepatoprotective, antimutagenic, anticancer, and immunoenhancing properties. Different studies prove antioxidant properties of leaf aqueous extract and ethanol extracts of flower & stem bark of neem. Quercetin and ß-sitosterol, the first polyphenolic flavonoids purified from fresh leaves of neem, have antifungal, antibacterial, and anti-inflammatory properties. Polysaccharides isolated from the bark of neem possess anti-inflammatory and anti-tumour activity. Peptidoglycan, Gallic acids, (–) epicatechin, and catechin isolated from the bark have an immune-modulatory effect. Phytosterols isolated from the neem fruits exhibit antiulcer activity in stress-induced gastric lesions.

Benefits of Neem

Anti-Cancerous properties of Neem

Neem has an influential role in managing cancer by regulating cell signaling pathways. Neem modulates the activity of various tumour suppressor genes such as p53, pTEN, transcription factors such as NF-κB, angiogenesis, and apoptosis such as bcl2, bax. Limonoids extracted from neem inhibit the growth & spread of various cancers such as breast, lung, stomach, colon, lymphoma, melanoma, leukaemia, prostate, and skin by inducing apoptosis and retarding tumour cell migration, invasion, and tumour angiogenesis. A finding shows that ethanolic neem leaf extract enhances the expression of pro-apoptotic genes, such as caspase-8 and caspase-3, and suppresses the expression of Bcl-2 and mutant p53 in cancer cells. Nimbolide downregulated cell survival proteins, including I-FLICE, cIAP-1, cIAP-2, Bcl-2, Bcl-xL, survivin, and X-linked inhibitor of apoptosis protein, and upregulated the pro-apoptotic proteins p53 and Bax. The ethanolic fraction of neem leaf significantly increases the expression of pTEN, which inhibits mammary tumourigenesis through its inhibitory effect on the Akt pathway. Another study on breast cancer patients shows that neem leaf extract significantly suppresses c-Myc oncogene expression. Another study concluded that water-soluble fractions of methanolic extract of neem root could inhibit angiogenesis. Results suggest that the effect of leaf extract induces apoptosis and inhibits cell proliferation by inhibiting PI3K/Akt pathway in prostate cancer. Other important study results demonstrate that nimbolide induces intrinsic apoptosis in hepatocarcinoma.

Azadirachtin and nimbolide found in limonoids have potent antioxidant and antiproliferative effects. A study shows that azadirachtin and nimbolide exert cytotoxic effects on cervical cancer by arresting the cell cycle inducing apoptosis in cancer cells, offering immense potential as an anti-cancer therapeutic drug. Another study showed that treatment with nimbolide found in leaves and flowers resulted in inhibition of the growth of choriocarcinoma cells. Aqueous extract of neem leaves effectively suppresses squamous cell carcinoma of the oral cavity. It also possesses potent immune-stimulant activity. Ethanolic extract of neem inhibits growth & spread of prostate cancer by inducing apoptosis and anti-androgenic effect. Neem also reduces the side effects of chemotherapy & radiotherapy.

Effect of Neem as an Anti-Inflammatory

The anti-inflammatory role of neem is via the regulation of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. Studies suggest that nimbidin from leaf extract suppresses the functions of macrophages and neutrophils relevant to inflammation. Findings indicate that neem seed oil shows significant anti-inflammatory and analgesic effects.

Neem as a Hepatoprotective Agent

A study performed to investigate the hepatoprotective role of azadirachtin-A confirmed that pre-treatment with azadirachtin-A reduced hepatocellular necrosis and moderately restored the liver to normal. In another study, neem leaf extract was found to have protection against liver necrosis. Research suggests that nimbolide is the active constituent to possess a hepatoprotective effect. Another study assessed the hepatoprotective activity of neem leaf extract on antitubercular drug-induced hepatotoxicity. Results confirmed that aqueous leaf extract significantly prevented changes in the serum levels of bilirubin, protein, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and prevented the histological changes as compared to the group receiving antitubercular drugs. Results establish that the plant has good potential to act as a hepatoprotective agent.

Wound Healing Effect of Neem

Extract of neem significantly promotes the wound healing activity through increased inflammatory response and neovascularization.

Anti-diabetic Activity of Neem

A study undertaken on neem root bark extract shows a statistically significant reduction in glucose levels in diabetic patients. Another critical study suggests that the neem leaf extract has important antidiabetic activity and could be a potential source for the treatment of diabetes mellitus.

Anti-bacterial activity of neem

Evaluation of the antibacterial activity of neem extract against foodborne pathogens suggests that neem extract possesses compounds containing antibacterial properties that can potentially be useful to control foodborne pathogens and spoilage organisms. Another experiment on bacteria isolated from adult mouth shows that bark, leaf, seed, and fruit extracts of the neem show antibacterial activity against all the test bacteria.

Both alcoholic and water extract of the neem leaf and the neem oil significantly inhibit and control the growth of fungi. Another finding shows the antimicrobial role of aqueous extracts of neem in inhibition of spore germination and growth against fungi such as Aspergillus flavus, Alternaria solani, and Cladosporium.

Anti-malarial effect of neem

Studies show that azadirachtin and other limonoids available in neem extracts are active on malaria vectors.

Immuno-modulatory Effect of Neem

An experiment performed to investigate immunomodulatory effects of neem showed that neem leaves infusion successfully improved antibody titre. Another study with powdered dry leaves of neem on humoral and cell-mediated immune responses significantly enhanced the antibody titres. Neem has a significant role as an antinephrotoxic and neuroprotective agent.

Antiviral Activity of Neem

Studies show that neem bark extract significantly blocks herpes simplex virus entry into cells. Similarly, the leaf extract of neem has virucidal activity against coxsackievirus by inactivation and yield reduction assay besides interfering at an early event of its replication cycle. Recent studies show a reduced risk of COVID-19 infection in people using neem, demonstrating its potential as a prophylactic treatment for preventing COVID-19 infection.