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Botanical Briefs: Neem Oil (Azadirachta indica)
Commonly known as neem or nimba, Azadirachta indica traditionally has been used as an oil or poultice to lighten skin pigment and reduce joint inflammation. Neem is a drought-resistant evergreen tree with thin serrated leaves, white fragrant flowers, and olivelike fruit (Figure 1). This plant is indigenous to India but also is readily found within tropical and semitropical environments throughout the Middle East, Southeast Asia, North Africa, and Australia.
Traditional Uses
For more than 4000 years, neem leaves, bark, fruit, and seeds have been used in food, insecticide, and herbal medicine cross-culturally in Indian Ayurvedic medicine and across Southeast Asia, particularly in Cambodia, Laos, Thailand, Myanmar, and Vietnam.1-3 Because of its many essential nutrients—oleic acid, palmitic acid, stearic acid, linoleic acid, behenic acid, arachidic acid, and palmitoleic acid—and readily available nature, some ethnic groups include neem in their diet.4 Neem commonly is used as a seasoning in soups and rice, eaten as a cooked vegetable, infused into teas and tonics, and pickled with other spices.5
All parts of the neem tree—both externally and internally—have been utilized in traditional medicine for the treatment of various diseases and ailments. The flowers have been used to treat eye diseases and dyspepsia, the fruit has been employed as an anthelmintic, the seeds and leaves have been used for malaria treatment and insecticide, the stem bark has been used for the treatment of diarrhea, and the root bark has been used for skin diseases and inflammation.6 Neem oil is a yellow-brown bitter substance that often is utilized to treat skin diseases such as psoriasis, eczema, fungal infections, and abscesses.
Case Report—A 77-year-old man presented with a diffuse rash across the lower back. He reported that he had been using topical neem oil to alleviate lower back pain and arthritis for the last 6 months with noted relief and improvement of back pain. After roughly 3 to 4 months of using neem oil, he noted a rash on the lower back, bilateral flanks, and buttocks (Figure 2). The rash was asymptomatic, and he denied any pruritus, scaling, pain, or burning. The patient was referred to dermatology and received a diagnosis of chemical leukoderma secondary to contact with A indica. The patient was advised to stop using the topical neem oil, and the rash was simply monitored, as it was asymptomatic.
Bioactivity
Research has elucidated multiple bioactivity mechanisms of neem, including melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity.1,7-9 Literature on the diverse phytochemical components of A indica indicate high levels of limonoids, flavonoids, and triterpenoids that are responsible for much of its antioxidant, anti-inflammatory, and insecticide properties.1,10
Melanogenesis-Inhibitory Activity—To date, neem has been added to a number of cosmetic products used in Ayurvedic medicine. One study of isolated compounds in A indica showed superior inhibitory activities against melanogenesis with minimal toxicity to cells (86.5%–105.1% cell viability). Western blot analysis of samples extracted and isolated from neem root and bark showed melanogenesis-inhibitory activities in B16 melanoma cells through the inhibition of microphthalmia-associated transcription factor expression and decreased expression of tyrosinase, as well as tyrosinase-related proteins 1 and 2, which are largely responsible for melanin synthesis.11 In another study, A indica flowers and their extracted constituents—6-deacetylnimbin and kaempferide—suggest melanogenesis-inhibitory activities in B16 melanoma cells with little to no toxicity to the cells (81.0%–111.7% cell viability).1 In an evaluationof A indica seed extracts, some of the isolated limonoids and diterpenoids exhibited a marked melanogenesis-inhibitory effect (74%–91% reduction of melanin content) with no toxicity to the cell.5 All of these studies indicate that active compounds in neem root, bark, flowers, and seeds may be potential skin-lightening agents.
Toxicity Against Pests—Neem seeds have phytochemicals that convey some insecticidal properties. The seeds often are ground into a powder, combined with water, and sprayed onto crops to act as an insecticide. As a natural method of nonpesticidal management, A indica acts as an antifeedant, insect repellent, and egg-laying deterrent that protects crops from damage. Studies of A indica have noted effective nonpesticidal management against arthropod pests such as armyworm, termites, and the oriental fruit fly.7,12,13
Antimalarial Activity—One study indicated that nimbolide, a limonoid from the neem plant, demonstrated antimalarial activity against Plasmodium falciparum. In separate cultures of asexual parasites and mature gametocytes, parasite numbers were less than 50% of the number in control cultures (8.0% vs 8.5% parasitemia, respectively).14 Thus, the lower parasite numbers indicated by this study highlight the antimalarial utility of nimbolide and neem oil.
Antioxidant and Anti-inflammatory Activity—Neem bark has been reported to have considerable antioxidant activity due to its high phenolic content.1,15 One study showed that azadirachtin and nimbolide in neem exhibited concentration-dependent antiradical scavenging activity and antioxidant properties.16
The anti-inflammatory potential for neem may occur via the inhibition of the nuclear factor-κB signaling pathway, which is linked to cancer, inflammation, and apoptosis.17 It also has been observed that nimbidin within neem extracts—such as leaves, bark, and seed extract—suppresses the function of macrophages and neutrophils relevant to inflammation.16 Another study indicated neem’s anti-inflammatory activity due to the regulation of proinflammatory enzymes such as cyclooxygenase and lipoxygenase.18
Safety, Toxicity, and Risks
Ingestion—Although neem is safe to use in the general population, neem oil poisoning has been reported, particularly in young children. Ingesting large quantities of neem has resulted in vomiting, hepatic toxicity, metabolic acidosis, late neurologic sequelae, and encephalopathy in young children.19 The diagnosis of neem oil poisoning is based on patient history, clinical examination, and imaging findings. Poisoning can manifest as drowsiness, tachypnea, and generalized seizures.20
Topical Application—Topical use of neem appears to be safe if the substance is diluted with other ingredients. However, direct application to the skin is not advised, as it may cause leukoderma and could induce allergic contact dermatitis and other allergic reactions.4
Final Thoughts
The use of neem extract for disease prevention and treatment has been prevalent around the world since ancient times. Neem has been documented to possess melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity by means of tyrosinase inhibition, phytochemical production, limonoid expression, and nuclear factor-κB regulation, respectively. However, topical use of neem may trigger a cutaneous response, highlighting the importance of considering a diagnosis of neem oil–induced chemical leukoderma when patients present with a hypopigmented rash and relevant history.
- Kitdamrongtham W, Ishii K, Ebina K, et al. Limonoids and flavonoids from the flowers of Azadirachta indica var. siamensis, and their melanogenesis-inhibitory and cytotoxic activities. Chem Biodivers. 2014;11:73-84. doi:10.1002/cbdv.201300266
- Singh A, Srivastava PS, Lakshmikumaran M. Comparison of AFLP and SAMPL markers for assessment of intra-population genetic variation in Azadirachta indica A. Juss. Plant Sci. 2002;162:17-25. doi:10.1016/S0168-9452(01)00503-9
- Pandey G, Verma K, Singh M. Evaluation of phytochemical, antibacterial and free radical scavenging properties of Azadirachta Indica (neem) leaves. Int J Pharm Pharmaceut Sci. 2014;6:444-447.
- Romita P, Calogiuri G, Bellino M, et al. Allergic contact dermatitis caused by neem oil: an underrated allergen. Contact Dermatitis. 2019;81:133-134. doi:10.1111/cod. 13256
- Akihisa T, Noto T, Takahashi A, et al. Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of limonoids from the seeds of Azadirachta indica A. Juss. (neem). J Oleo Sci. 2009;58:581-594.
- Subapriya R, Nagini S. Medicinal properties of neem leaves: a review. Curr Med Chem Anticancer Agents. 2005;5:149-156. doi:10.2174/1568011053174828
- Areekul S, Sinchaisri P, Tigvatananon S. Effect of Thai plant extracts on the Oriental fruit fly. I: toxicity test. Agriculture and Natural Resources. 1987;21:395-407.
- Rochanakij S, Thebtaranonth Y, Yenjai C, et al. Nimbolide, a constituent of Azadirachta indica, inhibits Plasmodium falciparum in culture. Southeast Asian J Trop Med Public Health. 1985;16:66-72.
- Sithisarn P, Supabphol R, Gritsanapan W. Antioxidant activity of Siamese neem tree (VP1209). J Ethnopharmacol. 2005;99:109-112. doi:10.1016/j.jep.2005.02.008
- Yin F, Lei XX, Cheng L, et al. Isolation and structure identification of the compounds from the seeds and leaves of Azadirachta indica A. Juss. J China Pharmaceut University. 2005;36:10-12.
- Su S, Cheng J, Zhang C, et al. Melanogenesis-inhibitory activities of limonoids and tricyclic diterpenoids from Azadirachta indica. Bioorganic Chemistry. 2020;100:103941. doi:j.bioorg.2020.103941
- Tulashie SK, Adjei F, Abraham J, et al. Potential of neem extracts as natural insecticide against fall armyworm (Spodoptera frugiperda (JE Smith)(Lepidoptera: Noctuidae). Case Stud Chem Environ Eng. 2021;4:100130. doi:10.1016/j.cscee.2021.100130
- Yashroy RC, Gupta PK. Neem-seed oil inhibits growth of termite surface-tunnels. Indian J Toxicol. 2000;7:49-50.
- Udeinya JI, Shu EN, Quakyi I, et al. An antimalarial neem leaf extract has both schizonticidal and gametocytocidal activities. Am J Therapeutics. 2008;15:108-110. doi:10.1097/MJT.0b013e31804c6d1d
- Bindurani R, Kumar K. Evaluation of antioxidant activity of hydro distilled extracts of leaf, heart wood and flower of Azadirachta indica. Int J Pharm Sci Rev Res. 2013;20:222.
- Alzohairy MA. Therapeutics role of Azadirachta indica (Neem) and their active constituents in diseases prevention and treatment [published online March 1, 2016]. Evid Based Complement Alternat Med. doi:10.1155/2016/7382506
- Schumacher M, Cerella C, Reuter S, et al. Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway. Genes Nutr. 2011;6:149-160. doi:10.1007/s12263-010-0194-6
- Kaur G, Sarwar Alam M, Athar M. Nimbidin suppresses functions of macrophages and neutrophils: relevance to its anti-inflammatory mechanisms. Phytotherapy Res. 2004;18:419-424. doi:10.1002/ptr.1474
- Dhongade RK, Kavade SG, Damle RS. Neem oil poisoning. Indian Pediatr. 2008;45:56-57.
- Bhaskar MV, Pramod SJ, Jeevika MU, et al. MR imaging findings of neem oil poisoning. Am J Neuroradiol. 2010;31:E60-E61. doi:10.3174/ajnr.A2146
Commonly known as neem or nimba, Azadirachta indica traditionally has been used as an oil or poultice to lighten skin pigment and reduce joint inflammation. Neem is a drought-resistant evergreen tree with thin serrated leaves, white fragrant flowers, and olivelike fruit (Figure 1). This plant is indigenous to India but also is readily found within tropical and semitropical environments throughout the Middle East, Southeast Asia, North Africa, and Australia.
Traditional Uses
For more than 4000 years, neem leaves, bark, fruit, and seeds have been used in food, insecticide, and herbal medicine cross-culturally in Indian Ayurvedic medicine and across Southeast Asia, particularly in Cambodia, Laos, Thailand, Myanmar, and Vietnam.1-3 Because of its many essential nutrients—oleic acid, palmitic acid, stearic acid, linoleic acid, behenic acid, arachidic acid, and palmitoleic acid—and readily available nature, some ethnic groups include neem in their diet.4 Neem commonly is used as a seasoning in soups and rice, eaten as a cooked vegetable, infused into teas and tonics, and pickled with other spices.5
All parts of the neem tree—both externally and internally—have been utilized in traditional medicine for the treatment of various diseases and ailments. The flowers have been used to treat eye diseases and dyspepsia, the fruit has been employed as an anthelmintic, the seeds and leaves have been used for malaria treatment and insecticide, the stem bark has been used for the treatment of diarrhea, and the root bark has been used for skin diseases and inflammation.6 Neem oil is a yellow-brown bitter substance that often is utilized to treat skin diseases such as psoriasis, eczema, fungal infections, and abscesses.
Case Report—A 77-year-old man presented with a diffuse rash across the lower back. He reported that he had been using topical neem oil to alleviate lower back pain and arthritis for the last 6 months with noted relief and improvement of back pain. After roughly 3 to 4 months of using neem oil, he noted a rash on the lower back, bilateral flanks, and buttocks (Figure 2). The rash was asymptomatic, and he denied any pruritus, scaling, pain, or burning. The patient was referred to dermatology and received a diagnosis of chemical leukoderma secondary to contact with A indica. The patient was advised to stop using the topical neem oil, and the rash was simply monitored, as it was asymptomatic.
Bioactivity
Research has elucidated multiple bioactivity mechanisms of neem, including melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity.1,7-9 Literature on the diverse phytochemical components of A indica indicate high levels of limonoids, flavonoids, and triterpenoids that are responsible for much of its antioxidant, anti-inflammatory, and insecticide properties.1,10
Melanogenesis-Inhibitory Activity—To date, neem has been added to a number of cosmetic products used in Ayurvedic medicine. One study of isolated compounds in A indica showed superior inhibitory activities against melanogenesis with minimal toxicity to cells (86.5%–105.1% cell viability). Western blot analysis of samples extracted and isolated from neem root and bark showed melanogenesis-inhibitory activities in B16 melanoma cells through the inhibition of microphthalmia-associated transcription factor expression and decreased expression of tyrosinase, as well as tyrosinase-related proteins 1 and 2, which are largely responsible for melanin synthesis.11 In another study, A indica flowers and their extracted constituents—6-deacetylnimbin and kaempferide—suggest melanogenesis-inhibitory activities in B16 melanoma cells with little to no toxicity to the cells (81.0%–111.7% cell viability).1 In an evaluationof A indica seed extracts, some of the isolated limonoids and diterpenoids exhibited a marked melanogenesis-inhibitory effect (74%–91% reduction of melanin content) with no toxicity to the cell.5 All of these studies indicate that active compounds in neem root, bark, flowers, and seeds may be potential skin-lightening agents.
Toxicity Against Pests—Neem seeds have phytochemicals that convey some insecticidal properties. The seeds often are ground into a powder, combined with water, and sprayed onto crops to act as an insecticide. As a natural method of nonpesticidal management, A indica acts as an antifeedant, insect repellent, and egg-laying deterrent that protects crops from damage. Studies of A indica have noted effective nonpesticidal management against arthropod pests such as armyworm, termites, and the oriental fruit fly.7,12,13
Antimalarial Activity—One study indicated that nimbolide, a limonoid from the neem plant, demonstrated antimalarial activity against Plasmodium falciparum. In separate cultures of asexual parasites and mature gametocytes, parasite numbers were less than 50% of the number in control cultures (8.0% vs 8.5% parasitemia, respectively).14 Thus, the lower parasite numbers indicated by this study highlight the antimalarial utility of nimbolide and neem oil.
Antioxidant and Anti-inflammatory Activity—Neem bark has been reported to have considerable antioxidant activity due to its high phenolic content.1,15 One study showed that azadirachtin and nimbolide in neem exhibited concentration-dependent antiradical scavenging activity and antioxidant properties.16
The anti-inflammatory potential for neem may occur via the inhibition of the nuclear factor-κB signaling pathway, which is linked to cancer, inflammation, and apoptosis.17 It also has been observed that nimbidin within neem extracts—such as leaves, bark, and seed extract—suppresses the function of macrophages and neutrophils relevant to inflammation.16 Another study indicated neem’s anti-inflammatory activity due to the regulation of proinflammatory enzymes such as cyclooxygenase and lipoxygenase.18
Safety, Toxicity, and Risks
Ingestion—Although neem is safe to use in the general population, neem oil poisoning has been reported, particularly in young children. Ingesting large quantities of neem has resulted in vomiting, hepatic toxicity, metabolic acidosis, late neurologic sequelae, and encephalopathy in young children.19 The diagnosis of neem oil poisoning is based on patient history, clinical examination, and imaging findings. Poisoning can manifest as drowsiness, tachypnea, and generalized seizures.20
Topical Application—Topical use of neem appears to be safe if the substance is diluted with other ingredients. However, direct application to the skin is not advised, as it may cause leukoderma and could induce allergic contact dermatitis and other allergic reactions.4
Final Thoughts
The use of neem extract for disease prevention and treatment has been prevalent around the world since ancient times. Neem has been documented to possess melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity by means of tyrosinase inhibition, phytochemical production, limonoid expression, and nuclear factor-κB regulation, respectively. However, topical use of neem may trigger a cutaneous response, highlighting the importance of considering a diagnosis of neem oil–induced chemical leukoderma when patients present with a hypopigmented rash and relevant history.
Commonly known as neem or nimba, Azadirachta indica traditionally has been used as an oil or poultice to lighten skin pigment and reduce joint inflammation. Neem is a drought-resistant evergreen tree with thin serrated leaves, white fragrant flowers, and olivelike fruit (Figure 1). This plant is indigenous to India but also is readily found within tropical and semitropical environments throughout the Middle East, Southeast Asia, North Africa, and Australia.
Traditional Uses
For more than 4000 years, neem leaves, bark, fruit, and seeds have been used in food, insecticide, and herbal medicine cross-culturally in Indian Ayurvedic medicine and across Southeast Asia, particularly in Cambodia, Laos, Thailand, Myanmar, and Vietnam.1-3 Because of its many essential nutrients—oleic acid, palmitic acid, stearic acid, linoleic acid, behenic acid, arachidic acid, and palmitoleic acid—and readily available nature, some ethnic groups include neem in their diet.4 Neem commonly is used as a seasoning in soups and rice, eaten as a cooked vegetable, infused into teas and tonics, and pickled with other spices.5
All parts of the neem tree—both externally and internally—have been utilized in traditional medicine for the treatment of various diseases and ailments. The flowers have been used to treat eye diseases and dyspepsia, the fruit has been employed as an anthelmintic, the seeds and leaves have been used for malaria treatment and insecticide, the stem bark has been used for the treatment of diarrhea, and the root bark has been used for skin diseases and inflammation.6 Neem oil is a yellow-brown bitter substance that often is utilized to treat skin diseases such as psoriasis, eczema, fungal infections, and abscesses.
Case Report—A 77-year-old man presented with a diffuse rash across the lower back. He reported that he had been using topical neem oil to alleviate lower back pain and arthritis for the last 6 months with noted relief and improvement of back pain. After roughly 3 to 4 months of using neem oil, he noted a rash on the lower back, bilateral flanks, and buttocks (Figure 2). The rash was asymptomatic, and he denied any pruritus, scaling, pain, or burning. The patient was referred to dermatology and received a diagnosis of chemical leukoderma secondary to contact with A indica. The patient was advised to stop using the topical neem oil, and the rash was simply monitored, as it was asymptomatic.
Bioactivity
Research has elucidated multiple bioactivity mechanisms of neem, including melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity.1,7-9 Literature on the diverse phytochemical components of A indica indicate high levels of limonoids, flavonoids, and triterpenoids that are responsible for much of its antioxidant, anti-inflammatory, and insecticide properties.1,10
Melanogenesis-Inhibitory Activity—To date, neem has been added to a number of cosmetic products used in Ayurvedic medicine. One study of isolated compounds in A indica showed superior inhibitory activities against melanogenesis with minimal toxicity to cells (86.5%–105.1% cell viability). Western blot analysis of samples extracted and isolated from neem root and bark showed melanogenesis-inhibitory activities in B16 melanoma cells through the inhibition of microphthalmia-associated transcription factor expression and decreased expression of tyrosinase, as well as tyrosinase-related proteins 1 and 2, which are largely responsible for melanin synthesis.11 In another study, A indica flowers and their extracted constituents—6-deacetylnimbin and kaempferide—suggest melanogenesis-inhibitory activities in B16 melanoma cells with little to no toxicity to the cells (81.0%–111.7% cell viability).1 In an evaluationof A indica seed extracts, some of the isolated limonoids and diterpenoids exhibited a marked melanogenesis-inhibitory effect (74%–91% reduction of melanin content) with no toxicity to the cell.5 All of these studies indicate that active compounds in neem root, bark, flowers, and seeds may be potential skin-lightening agents.
Toxicity Against Pests—Neem seeds have phytochemicals that convey some insecticidal properties. The seeds often are ground into a powder, combined with water, and sprayed onto crops to act as an insecticide. As a natural method of nonpesticidal management, A indica acts as an antifeedant, insect repellent, and egg-laying deterrent that protects crops from damage. Studies of A indica have noted effective nonpesticidal management against arthropod pests such as armyworm, termites, and the oriental fruit fly.7,12,13
Antimalarial Activity—One study indicated that nimbolide, a limonoid from the neem plant, demonstrated antimalarial activity against Plasmodium falciparum. In separate cultures of asexual parasites and mature gametocytes, parasite numbers were less than 50% of the number in control cultures (8.0% vs 8.5% parasitemia, respectively).14 Thus, the lower parasite numbers indicated by this study highlight the antimalarial utility of nimbolide and neem oil.
Antioxidant and Anti-inflammatory Activity—Neem bark has been reported to have considerable antioxidant activity due to its high phenolic content.1,15 One study showed that azadirachtin and nimbolide in neem exhibited concentration-dependent antiradical scavenging activity and antioxidant properties.16
The anti-inflammatory potential for neem may occur via the inhibition of the nuclear factor-κB signaling pathway, which is linked to cancer, inflammation, and apoptosis.17 It also has been observed that nimbidin within neem extracts—such as leaves, bark, and seed extract—suppresses the function of macrophages and neutrophils relevant to inflammation.16 Another study indicated neem’s anti-inflammatory activity due to the regulation of proinflammatory enzymes such as cyclooxygenase and lipoxygenase.18
Safety, Toxicity, and Risks
Ingestion—Although neem is safe to use in the general population, neem oil poisoning has been reported, particularly in young children. Ingesting large quantities of neem has resulted in vomiting, hepatic toxicity, metabolic acidosis, late neurologic sequelae, and encephalopathy in young children.19 The diagnosis of neem oil poisoning is based on patient history, clinical examination, and imaging findings. Poisoning can manifest as drowsiness, tachypnea, and generalized seizures.20
Topical Application—Topical use of neem appears to be safe if the substance is diluted with other ingredients. However, direct application to the skin is not advised, as it may cause leukoderma and could induce allergic contact dermatitis and other allergic reactions.4
Final Thoughts
The use of neem extract for disease prevention and treatment has been prevalent around the world since ancient times. Neem has been documented to possess melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity by means of tyrosinase inhibition, phytochemical production, limonoid expression, and nuclear factor-κB regulation, respectively. However, topical use of neem may trigger a cutaneous response, highlighting the importance of considering a diagnosis of neem oil–induced chemical leukoderma when patients present with a hypopigmented rash and relevant history.
- Kitdamrongtham W, Ishii K, Ebina K, et al. Limonoids and flavonoids from the flowers of Azadirachta indica var. siamensis, and their melanogenesis-inhibitory and cytotoxic activities. Chem Biodivers. 2014;11:73-84. doi:10.1002/cbdv.201300266
- Singh A, Srivastava PS, Lakshmikumaran M. Comparison of AFLP and SAMPL markers for assessment of intra-population genetic variation in Azadirachta indica A. Juss. Plant Sci. 2002;162:17-25. doi:10.1016/S0168-9452(01)00503-9
- Pandey G, Verma K, Singh M. Evaluation of phytochemical, antibacterial and free radical scavenging properties of Azadirachta Indica (neem) leaves. Int J Pharm Pharmaceut Sci. 2014;6:444-447.
- Romita P, Calogiuri G, Bellino M, et al. Allergic contact dermatitis caused by neem oil: an underrated allergen. Contact Dermatitis. 2019;81:133-134. doi:10.1111/cod. 13256
- Akihisa T, Noto T, Takahashi A, et al. Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of limonoids from the seeds of Azadirachta indica A. Juss. (neem). J Oleo Sci. 2009;58:581-594.
- Subapriya R, Nagini S. Medicinal properties of neem leaves: a review. Curr Med Chem Anticancer Agents. 2005;5:149-156. doi:10.2174/1568011053174828
- Areekul S, Sinchaisri P, Tigvatananon S. Effect of Thai plant extracts on the Oriental fruit fly. I: toxicity test. Agriculture and Natural Resources. 1987;21:395-407.
- Rochanakij S, Thebtaranonth Y, Yenjai C, et al. Nimbolide, a constituent of Azadirachta indica, inhibits Plasmodium falciparum in culture. Southeast Asian J Trop Med Public Health. 1985;16:66-72.
- Sithisarn P, Supabphol R, Gritsanapan W. Antioxidant activity of Siamese neem tree (VP1209). J Ethnopharmacol. 2005;99:109-112. doi:10.1016/j.jep.2005.02.008
- Yin F, Lei XX, Cheng L, et al. Isolation and structure identification of the compounds from the seeds and leaves of Azadirachta indica A. Juss. J China Pharmaceut University. 2005;36:10-12.
- Su S, Cheng J, Zhang C, et al. Melanogenesis-inhibitory activities of limonoids and tricyclic diterpenoids from Azadirachta indica. Bioorganic Chemistry. 2020;100:103941. doi:j.bioorg.2020.103941
- Tulashie SK, Adjei F, Abraham J, et al. Potential of neem extracts as natural insecticide against fall armyworm (Spodoptera frugiperda (JE Smith)(Lepidoptera: Noctuidae). Case Stud Chem Environ Eng. 2021;4:100130. doi:10.1016/j.cscee.2021.100130
- Yashroy RC, Gupta PK. Neem-seed oil inhibits growth of termite surface-tunnels. Indian J Toxicol. 2000;7:49-50.
- Udeinya JI, Shu EN, Quakyi I, et al. An antimalarial neem leaf extract has both schizonticidal and gametocytocidal activities. Am J Therapeutics. 2008;15:108-110. doi:10.1097/MJT.0b013e31804c6d1d
- Bindurani R, Kumar K. Evaluation of antioxidant activity of hydro distilled extracts of leaf, heart wood and flower of Azadirachta indica. Int J Pharm Sci Rev Res. 2013;20:222.
- Alzohairy MA. Therapeutics role of Azadirachta indica (Neem) and their active constituents in diseases prevention and treatment [published online March 1, 2016]. Evid Based Complement Alternat Med. doi:10.1155/2016/7382506
- Schumacher M, Cerella C, Reuter S, et al. Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway. Genes Nutr. 2011;6:149-160. doi:10.1007/s12263-010-0194-6
- Kaur G, Sarwar Alam M, Athar M. Nimbidin suppresses functions of macrophages and neutrophils: relevance to its anti-inflammatory mechanisms. Phytotherapy Res. 2004;18:419-424. doi:10.1002/ptr.1474
- Dhongade RK, Kavade SG, Damle RS. Neem oil poisoning. Indian Pediatr. 2008;45:56-57.
- Bhaskar MV, Pramod SJ, Jeevika MU, et al. MR imaging findings of neem oil poisoning. Am J Neuroradiol. 2010;31:E60-E61. doi:10.3174/ajnr.A2146
- Kitdamrongtham W, Ishii K, Ebina K, et al. Limonoids and flavonoids from the flowers of Azadirachta indica var. siamensis, and their melanogenesis-inhibitory and cytotoxic activities. Chem Biodivers. 2014;11:73-84. doi:10.1002/cbdv.201300266
- Singh A, Srivastava PS, Lakshmikumaran M. Comparison of AFLP and SAMPL markers for assessment of intra-population genetic variation in Azadirachta indica A. Juss. Plant Sci. 2002;162:17-25. doi:10.1016/S0168-9452(01)00503-9
- Pandey G, Verma K, Singh M. Evaluation of phytochemical, antibacterial and free radical scavenging properties of Azadirachta Indica (neem) leaves. Int J Pharm Pharmaceut Sci. 2014;6:444-447.
- Romita P, Calogiuri G, Bellino M, et al. Allergic contact dermatitis caused by neem oil: an underrated allergen. Contact Dermatitis. 2019;81:133-134. doi:10.1111/cod. 13256
- Akihisa T, Noto T, Takahashi A, et al. Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of limonoids from the seeds of Azadirachta indica A. Juss. (neem). J Oleo Sci. 2009;58:581-594.
- Subapriya R, Nagini S. Medicinal properties of neem leaves: a review. Curr Med Chem Anticancer Agents. 2005;5:149-156. doi:10.2174/1568011053174828
- Areekul S, Sinchaisri P, Tigvatananon S. Effect of Thai plant extracts on the Oriental fruit fly. I: toxicity test. Agriculture and Natural Resources. 1987;21:395-407.
- Rochanakij S, Thebtaranonth Y, Yenjai C, et al. Nimbolide, a constituent of Azadirachta indica, inhibits Plasmodium falciparum in culture. Southeast Asian J Trop Med Public Health. 1985;16:66-72.
- Sithisarn P, Supabphol R, Gritsanapan W. Antioxidant activity of Siamese neem tree (VP1209). J Ethnopharmacol. 2005;99:109-112. doi:10.1016/j.jep.2005.02.008
- Yin F, Lei XX, Cheng L, et al. Isolation and structure identification of the compounds from the seeds and leaves of Azadirachta indica A. Juss. J China Pharmaceut University. 2005;36:10-12.
- Su S, Cheng J, Zhang C, et al. Melanogenesis-inhibitory activities of limonoids and tricyclic diterpenoids from Azadirachta indica. Bioorganic Chemistry. 2020;100:103941. doi:j.bioorg.2020.103941
- Tulashie SK, Adjei F, Abraham J, et al. Potential of neem extracts as natural insecticide against fall armyworm (Spodoptera frugiperda (JE Smith)(Lepidoptera: Noctuidae). Case Stud Chem Environ Eng. 2021;4:100130. doi:10.1016/j.cscee.2021.100130
- Yashroy RC, Gupta PK. Neem-seed oil inhibits growth of termite surface-tunnels. Indian J Toxicol. 2000;7:49-50.
- Udeinya JI, Shu EN, Quakyi I, et al. An antimalarial neem leaf extract has both schizonticidal and gametocytocidal activities. Am J Therapeutics. 2008;15:108-110. doi:10.1097/MJT.0b013e31804c6d1d
- Bindurani R, Kumar K. Evaluation of antioxidant activity of hydro distilled extracts of leaf, heart wood and flower of Azadirachta indica. Int J Pharm Sci Rev Res. 2013;20:222.
- Alzohairy MA. Therapeutics role of Azadirachta indica (Neem) and their active constituents in diseases prevention and treatment [published online March 1, 2016]. Evid Based Complement Alternat Med. doi:10.1155/2016/7382506
- Schumacher M, Cerella C, Reuter S, et al. Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway. Genes Nutr. 2011;6:149-160. doi:10.1007/s12263-010-0194-6
- Kaur G, Sarwar Alam M, Athar M. Nimbidin suppresses functions of macrophages and neutrophils: relevance to its anti-inflammatory mechanisms. Phytotherapy Res. 2004;18:419-424. doi:10.1002/ptr.1474
- Dhongade RK, Kavade SG, Damle RS. Neem oil poisoning. Indian Pediatr. 2008;45:56-57.
- Bhaskar MV, Pramod SJ, Jeevika MU, et al. MR imaging findings of neem oil poisoning. Am J Neuroradiol. 2010;31:E60-E61. doi:10.3174/ajnr.A2146
Practice Points
- Neem is a traditional herb with various bioactivities, such as melanogenesis-inhibitory activity, toxicity against pests, antimalarial activity, and antioxidant activity.
- Neem should be used with caution as a remedy because of its skin-lightening properties, which are attributed to melanogenesis-inhibitory activity via tyrosinase inhibition.
- Chemical leukoderma should be included in the differential diagnosis when a patient presents with a hypopigmented rash after topical use of neem products.
