GCMS Profile of Bioactive Secondary Metabolites with Therapeutic Potential in the Ethanolic Leaf Extracts of Azadirachta indica¬: A Sacred Traditional Medicinal Plant of INDIA
Neem (Azadirachta indica) a member of Meliaceae plays an immense role in human health and disease which is attributed to its composition of Bioactive Secondary Metabolites (BASM). It has been widely used in Indian Traditional Systems of Medicine that includes Ayurveda, Siddha, Unani, Homeopathy and other Folklore Systems of Medicine practiced in the Indian Subcontinent for the treatment and prevention of various diseases. Current global health perspectives and medical practice in the post COVID era has no other way but to seek to merge alternative systems of medicine with evidence-based therapeutic aspects for a better understanding of the metabolic process and its effects in the human body. The studies based on animal model established that neem and its chief constituents play pivotal role in anticancer management through the modulation of various molecular pathways including p53, pTEN, NF-κB, PI3K/Akt, Bcl-2, and VEGF. Besides, NEEM plays a vital role in the management of diabetics and its associated long term complication through ROS scavenging and ameliorative potentials to restore oxidative injury/ inhibit enzymes linked to. Overall NEEM is considered as GRAS medicinal plant that modulates metabolic inflammations without side effects. Though it has been confirmed that neem and its constituents play role in the scavenging of free radical and prevention of disease pathogenesis, a clear scientific basis of its pharmacoinformatics is still lacking. Gas Chromatography–Mass Spectroscopy (GC–MS) analysis of the fractions revealed the presence of 62 metabolites.
Keywords: Azadirachta indica; NEEM; GCMS; Bioactive Secondary Metabolites; GRAS; Medicinal Plants
2. Zeenat F, Ravish MS, Ahmad W, Ahmad I. Therapeutic, phytochemistry and pharmacology of Azadirachta indica: A review. Int J Unani Integr Med. 2018; 2(1):20-8.
3. Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U. Biological activities and medicinal properties of neem (Azadirachta indica). Current Science. 2002:1336-45.
4. Kumar VS, Navaratnam V. Neem (Azadirachta indica): Prehistory to contemporary medicinal uses to humankind. Asian Pacific Journal of Tropical Biomedicine. 2013; 3(7):505-14. https://doi.org/10.1016/S2221-1691(13)60105-7
5. Negi PS, Jayaprakasha GK, Jena BS. Distribution and introduction cultivation state of Azadirachta indica Food Chemistry. 2002;80:293-7.
6. Yan_ping ZH, Yong_qi LA, Xing_ming PE, Juan LI. Global Distribution and Introduction Cultivation State of Azadirachta indica [J]. Forest Inventory and Planning. 2002; 3(2)5-9.
7. Braga TM, Rocha L, Chung TY, Oliveira RF, Pinho C, Oliveira AI, Morgado J, Cruz A. Azadirachta indica A. Juss. In Vivo Toxicity - An Updated Review. Molecules.2021; 26(2):252. https://doi.org/10.3390/molecules26020252
8. Bussmann RW, Paniagua-Zambrana NY, Njoroge GN. Azadirachta indica A. Juss. M eliaceae. Ethnobotany of the Mountain Regions of Africa. 2021:185-7.
9. Ramya S, & Jayakumararaj R. Antifeedant activity of selected ethno-botanicals used by tribals of Vattal Hills on Helicoverpa armigera (Hübner). Journal of Pharmacy Research. 2009; 2(8):1414-1418.
10. Islas JF, Acosta E, Zuca G, Delgado-Gallegos JL, Moreno-Treviño MG, Escalante B, Moreno-Cuevas JE. An overview of Neem Azadirachta indica and its potential impact on health. Journal of Functional Foods. 2020; 74:104171. https://doi.org/10.1016/j.jff.2020.104171
11. Rahmani A, Almatroudi A, Alrumaihi F, Khan A. Pharmacological and therapeutic potential of neem (Azadirachta indica). Pharmacognosy Reviews. 2018; 12(24).
12. Bhowmik D, Chiranjib YJ, Tripathi KK, Kumar KS. Herbal remedies of Azadirachta indica and its medicinal application. J Chem Pharm Res. 2010; 2(1):62-72.
13. Chen J, Fan X, Zhu J, Song L, Li Z, Lin F, Yu R, Xu H, Zi J. Limonoids from seeds of Azadirachta indica A. Juss. and their cytotoxic activity. Acta pharmaceutica sinica B. 2018; 8(4):639-44. https://doi.org/10.1016/j.apsb.2017.12.009
14. Khanal P, Magadum P, Patil BM, Hullatti KK. In silico docking study of Limonoids from Azadirachta indica with pfpk5: A Novel Target for Plasmodium falciparum. Indian Journal of Pharmaceutical Sciences. 2019; 81(2):326-32. https://doi.org/10.36468/pharmaceutical-sciences.514
15. Kraus W, Cramer R, Sawitzki G. Tetranortriterpenoids from the seeds of Azadirachta indica Phytochemistry. 1981; 20(1):117-20.
16. Willy S, Nilan R, Kekare MB, Vikas V. Estimation of two bioactive compounds from Azadirachta indica A. Juss. leaves using HPLC. International Journal of Pharma and Bio Sciences. 2010; 1(2).
17. Mitra CR, Garg HS, Pandey GN. Identification of nimbidic acid and nimbidinin from Azadirachta indica Phytochemistry. 1971; 10(4):857-64.
18. Moga MA, Bălan A, Anastasiu CV, Dimienescu OG, Neculoiu CD, Gavriș C. An overview on the anticancer activity of Azadirachta indica (Neem) in gynecological cancers. International journal of molecular sciences. 2018; 19(12):3898. https://doi.org/10.3390/ijms19123898
19. Baildya N, Khan AA, Ghosh NN, Dutta T, Chattopadhyay AP. Screening of potential drug from Azadirachta indica (Neem) extracts for SARS-CoV-2: an insight from molecular docking and MD-simulation studies. Journal of Molecular Structure 2021; 1227:129390 https://doi.org/10.1016/j.molstruc.2020.129390
20. Eid A, Jaradat N, Elmarzugi N. A Review of chemical constituents and traditional usage of Neem plant (Azadirachta indica). Palestinian Medical and Pharmaceutical Journal. 2017; 2(2):75-81.
21. Hossain MA, Al-Toubi WA, Weli AM, Al-Riyami QA, Al-Sabahi JN. Identification and characterization of chemical compounds in different crude extracts from leaves of Omani neem. Journal of Taibah University for Science. 2013; 7(4):181-8. https://doi.org/10.1016/j.jtusci.2013.05.003
22. Kumar R, Sharma S, Devi L. Investigation of total phenolic, flavonoid contents and antioxidant activity from extracts of Azadirachta indica of Bundelkhand Region. Int. J. Life. Sci. Scienti. Res. eISSN. 2018; 2455(1716):1716.
23. Siddiqui BS, Afshan F, Faizi S, Naqvi SN, Tariq RM. Two insecticidal tetranortriterpenoids from Azadirachta indica Phytochemistry. 2000; 53(3):371-6.
24. Awolu OO, Obafaye RO, Ayodele BS. Optimization of solvent extraction of oil from neem Azadirachta indica and its characterizations. Journal of Scientific Research and Reports. 2013; 10:304-314 https://doi.org/10.9734/JSRR/2013/3705
25. Agrawal S, Popli DB, Sircar K, Chowdhry A. A review of the anticancer activity of Azadirachta indica (Neem) in oral cancer. Journal of Oral Biology and Craniofacial Research. 2020 Apr 1; 10(2):206-9.
26. Agrawal S, Popli DB, Sircar K, Chowdhry A. A review of the anticancer activity of Azadirachta indica (Neem) in oral cancer. Journal of Oral Biology and Craniofacial Research. 2020 Apr 1; 10(2):206-9.
27. Upadhyay SN, Dhawan S, Garg S, Talwar GP. Immunomodulatory effects of neem Azadirachta indica oil. International Journal of Immunopharmacology. 1992; 14(7):1187-93. https://doi.org/10.1016/0192-0561(92)90054-O
28. Muhammad A, Kashere MA. NEEM, Azadirachta indica L.(A. Juss): an eco-friendly botanical insecticide for managing farmers 'insects pest problems - a review. FUDMA Journal of Sciences. 2020; 4(4):484-91. https://doi.org/10.33003/fjs-2020-0404-506
29. Benelli G, Canale A, Toniolo C, Higuchi A, Murugan K, Pavela R, Nicoletti M. Neem (Azadirachta indica): towards the ideal insecticide?. Natural product research. 2017; 31(4):369-86. https://doi.org/10.1080/14786419.2016.1214834
30. Schmutterer H. Properties and potential of natural pesticides from the neem tree, Azadirachta indica Annual review of entomology. 1990; 35(1):271-97.
31. Gupta SC, Prasad S, Tyagi AK, Kunnumakkara AB, Aggarwal BB. Neem (Azadirachta indica): An Indian traditional panacea with modern molecular basis. Phytomedicine. 2017; 34:14-20. https://doi.org/10.1016/j.phymed.2017.07.001
32. Hashmat I, Azad H, Ahmed A. Neem (Azadirachta indica A. Juss) - A nature's drugstore: an overview. Int Res J Biol Sci. 2012; 1(6):76-9.
33. Ramya S, Neethirajan K & Jayakumararaj R. Profile of bioactive compounds in Syzygium cumini-a review. J. Pharm. Res 2012; 5(8):4548-4553.
34. Soorya C, Balamurugan S, Basha AN, Kandeepan C, Ramya S, Jayakumararaj R. Profile of Bioactive Phyto-compounds in Essential Oil of Cymbopogon martinii from Palani Hills, Western Ghats, INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(4):60-5. https://doi.org/10.22270/jddt.v11i4.4887
35. Saleem S, Muhammad G, Hussain MA, Bukhari SN. A comprehensive review of phytochemical profile, bioactives for pharmaceuticals, and pharmacological attributes of Azadirachta indica Phytotherapy research. 2018; 32(7):1241-72.
36. Sarkar S, Singh RP, Bhattacharya G. Exploring the role of Azadirachta indica (neem) and its active compounds in the regulation of biological pathways: an update on molecular approach. 3 Biotech. 2021; 11(4):1-2. https://doi.org/10.1007/s13205-021-02745-4
37. Ahmad S, Maqbool A, Srivastava A, Gogol S. Biological detail and therapeutic effect of Azadirachta indica (neem tree) products-a review. J. Evidence Based Med. Healthcare. 2019; 6(22):1607-1612.
38. Alzohairy MA. Therapeutics role of Azadirachta indica (Neem) and their active constituents in diseases prevention and treatment Evidence-Based Complementary and Alternative Medicine. 2016; 2016
39. Venugopal V. Antidermatophytic activity of neem Azadirachta indica leaves in vitro. Indian Journal of Pharmacology. 1994; 26(2):141.
40. Tembe-Fokunang EA, Charles F, Kaba N, Donatien G, Michael A, Bonaventure N. The potential pharmacological and medicinal properties of neem (Azadirachta indica A. Juss) in the drug development of phytomedicine Journal of Complementary and Alternative Medical Research. 2019; 23:1-8
41. Srivastava SK, Agrawal B, Kumar A, Pandey A. Phytochemicals of Azadirachta indica source of active medicinal constituent used for cure of various diseases: A Review. Journal of Scientific Research. 2020; 64(1):385-90. https://doi.org/10.37398/JSR.2020.640153
42. Krist S. Neem Oil. InVegetable Fats and Oils 2020 (pp. 467-473). Springer, Cham.
43. Jain S, Ganeshpurkar A, Dubey N. Molecular Docking of some Neem Constituents with COX-2 and NOs: An in silico Study. Pharmacognosy Communications. 2020 Jul 1; 10(3):134-5.
44. Rajasekaran C, Meignanam E, Vijayakumar V, Kalaivani T, Ramya S, Premkumar N, Siva R, Jayakumararaj R Investigations on antibacterial activity of leaf extracts of Azadirachta indica A. Juss (Meliaceae): a traditional medicinal plant of India. Ethnobotanical Leaflets. 2008; 2008(1):161-.167
45. Roy S, Bhattacharyya P. Possible role of traditional medicinal plant Neem Azadirachta indica for the management of COVID-19 infection. Int. J. Res. Pharm. Sci. 2020:122-5.
46. Patel SM, Venkata KC, Bhattacharyya P, Sethi G, Bishayee A. Potential of neem (Azadirachta indica L.) for prevention and treatment of oncologic diseases. In Seminars in cancer biology 2016; 40:100-115. Academic Press.
47. Paul R, Prasad M, Sah NK. Anticancer biology of Azadirachta indica L (neem): a mini review. Cancer biology & therapy. 2011; 12(6):467-76. https://doi.org/10.4161/cbt.12.6.16850
48. Lloyd AC, Menon T, Umamaheshwari K. Anticandidal activity of Azadirachta indica Indian Journal of Pharmacology. 2005; 37(6):386.
49. Waheed A., Miana G.A., Ahmad S.I. Clinical investigation of hypoglycemic effect of seeds of Azadirachta indica in type 2 (NIDDM) diabetes mellitus. Pak. J. Pharm. Sci. 2006; 19:322-325.
50. Khan MR, Chonhenchob V, Huang C, Suwanamornlert P. Antifungal Activity of Propyl Disulfide from Neem (Azadirachta indica) in Vapor and Agar Diffusion Assays against Anthracnose Pathogens (Colletotrichum gloeosporioides and Colletotrichum acutatum) in Mango Fruit. Microorganisms. 2021 Apr; 9(4):839.
51. Afolabi OJ, Simon-Oke IA, Oladokun OI. Antiplasmodial Activity of Ethanolic Extract of Neem Leaf (Azadirachta indica) in Albino Mice Infected with Plasmodium berghei. Int Arch Clin Pharmacol. 2021; 7:024.
52. Dharshini AD, Muralidharan NP. Neem as antiviral agents. International Journal of Pharmaceutical Research. 2020 Jan 1; 12.
53. Patil SM, Shirahatti PS, Ramu R, Prasad N. Azadirachta indica A. Juss (neem) as a contraceptive: An evidence-based review on its pharmacological efficiency. Phytomedicine. 2021; 19:153596. https://doi.org/10.1016/j.phymed.2021.153596
54. Kalaivani T, Meignanam E, Premkumar N, Siva R, Vijayakumar V, Rajasekaran C, Ramya S, Jayakumararaj R. Studies on hepatoprotective properties of leaf extracts of Azadirachta indica A. Juss (Meliaceae). Ethnobotanical Leaflets 2009; 2009(1):20.
55. Isdadiyanto S, Sitasiwi AJ, Mardiati SM. The lipid profile of rats (Rattus norvegicus L.) induced by high fat ration after exposed to ethanolic neem (Azadirazchta indica) leaf extract. Journal of Physics: Conference Series 2020; 1524(1): 012126). IOP Publishing.
56. Dwivedi VD, Bharadwaj S, Afroz S, Khan N, Ansari MA, Yadava U, Tripathi RC, Tripathi IP, Mishra SK, Kang SG. Anti-dengue infectivity evaluation of bioflavonoid from Azadirachta indica by dengue virus serine protease inhibition. Journal of Biomolecular Structure and Dynamics. 2021; 39(4):1417-30. https://doi.org/10.1080/07391102.2020.1734485
57. Sundari A & Jayakumararaj R, Herbal remedies used to treat skin disorders in Arasankulam region of Thoothukudi District in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics, 2020; 10(5):33-38. https://doi.org/10.22270/jddt.v10i5.4277
58. Sundari A & Jayakumararaj R. Medicinal plants used to cure cuts and wounds in Athur region of Thoothukudi district in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics, 2020; 10(6-s):26-30.
59. Borkotoky S, Banerjee M. A computational prediction of SARS-CoV-2 structural protein inhibitors from Azadirachta indica (Neem). Journal of Biomolecular Structure and Dynamics. 2020; 8:1-1. https://doi.org/10.1080/07391102.2020.1774419
60. Muhammed D, Odey BO, Alozieuwa BU, Alawode RA, Okunlola BM, Ibrahim J, Lawal A, Berinyuy EB. Azadirachtin-A a bioactive compound from Azadirachta indica is a potential inhibitor of SARS-CoV-2 main protease. AROC in Pharmaceutical and Biotechnology. 2021; 1(1):1-8.
61. Fernandes SR, Barreiros L, Oliveira RF, Cruz A, Prudêncio C, Oliveira AI, Pinho C, Santos N, Morgado J. Chemistry, bioactivities, extraction and analysis of azadirachtin: State-of-the-art. Fitoterapia. 2019; 134:141-50. https://doi.org/10.1016/j.fitote.2019.02.006
62. Adegbola PI, Semire B, Fadahunsi OS, Adegoke AE Molecular docking and ADMET studies of Allium cepa, Azadirachta indica and Xylopia aethiopica isolates as potential anti-viral drugs for Covid-19. Virus Disease. 2021; 32(1):85-97.
63. Durán-Iturbide NA, Díaz-Eufracio BI, Medina-Franco JL. In silico ADME/Tox profiling of natural products: A focus on BIOFACQUIM. ACS omega. 2020; 5(26):16076-84. https://doi.org/10.1021/acsomega.0c01581
64. Medina-Franco JL, Saldívar-González FI. Cheminformatics to characterize pharmacologically active natural products. Biomolecules. 2020; 10(11):1566. https://doi.org/10.3390/biom10111566
65. Soorya C, Balamurugan S, Ramya S, Neethirajan K, Kandeepan C, & Jayakumararaj R. Physicochemical, ADMET and Druggable properties of Myricetin: A Key Flavonoid in Syzygium cumini that regulates metabolic inflammations. Journal of Drug Delivery and Therapeutics, 2021; 11(4):66-3. https://doi.org/10.22270/jddt.v11i4.4890
66. Govindachari TR. Chemical and biological investigations on Azadirachta indica (the neem tree). Current science. 1992;63(3):117-22.
67. Lakshmi T, Krishnan V, Rajendran R, Madhusudhanan N. Azadirachta indica: A herbal panacea in dentistry-An update. Pharmacognosy reviews. 2015; 9(17):41. https://doi.org/10.4103/0973-7847.156337
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).