Neuroprotective potential of Moringa oleifera mediated by NF-kB/Nrf2/HO-1 signaling pathway: A review
Maroti Mundkar
Department of Pharmacology, Central University of Punjab, Bathinda, India
Search for more papers by this authorAnjali Bijalwan
Department of Pharmacology, Central University of Punjab, Bathinda, India
Search for more papers by this authorDivya Soni
Department of Pharmacology, Central University of Punjab, Bathinda, India
Search for more papers by this authorCorresponding Author
Puneet Kumar
Department of Pharmacology, Central University of Punjab, Bathinda, India
Correspondence
Puneet Kumar, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India.
Email: [email protected]
Search for more papers by this authorMaroti Mundkar
Department of Pharmacology, Central University of Punjab, Bathinda, India
Search for more papers by this authorAnjali Bijalwan
Department of Pharmacology, Central University of Punjab, Bathinda, India
Search for more papers by this authorDivya Soni
Department of Pharmacology, Central University of Punjab, Bathinda, India
Search for more papers by this authorCorresponding Author
Puneet Kumar
Department of Pharmacology, Central University of Punjab, Bathinda, India
Correspondence
Puneet Kumar, Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India.
Email: [email protected]
Search for more papers by this authorAbstract
Moringa oleifera is a traditional Indian herb belonging to the Moringaceae family, it is commonly known as the horse-radish tree, drumstick, or sahajna. In developing countries, Moringa is used as feed for both humans and animals due to its well-known antioxidant, anti-inflammatory, and anti-apoptotic properties owing to its several phytoconstituents including β-carotene, quercetin, kaempferol, ascorbic acid, flavonoids, phenolic acid, rhamnose, glycosylates, glucomoringin, and isothiocyanates. These constituents help to maintain the brain antioxidant enzyme levels, mitochondrial functions, and neurogenesis, showing neuroprotective effects in several neurodegenerative disorders including Parkinson's Disease, Alzheimer's Disease, Huntington's Disease, and Amyotrophic lateral sclerosis. This review discusses various phytoconstituent of moringa and their therapeutic potential in various neurological disorders. Additionally, we also concise the safety and toxicity profile, of different molecular pathways involved in the neuroprotective effect of M. oleifera including M. oleifera nanoparticles for better therapeutic value.
Practical applications
Several clinical and preclinical studies on Moringa oleifera have been conducted, and the outcomes indicate moringa could be used in the treatment of brain disorders. As a result, we conclude that moringa and its nanoformulations could be employed to treat neurological problems. In the future, M. oleifera phytoconstituents could be evaluated against specific signaling pathways, which could aid researchers in discovering their mechanism of action. Furthermore, the use of moringa as a nutraceutical owing to its myriad pharmacological potential will go a long way in boosting the economy of countries that grow moringa on a large scale.
CONFLICT OF INTEREST
The authors declared that they have no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- Abd Rani, N. Z., Husain, K., & Kumolosasi, E. (2018). Moringa genus: A review of phytochemistry and pharmacology. Frontiers in Pharmacology, 9, 108.
- Abdallah, N. H., Baulies, A., Bouhlel, A., Bejaoui, M., Zaouali, M. A., Ben Mimouna, S., Messaoudi, I., Fernandez-Checa, J. C., García Ruiz, C., & Ben Abdennebi, H. (2018). The effect of zinc acexamate on oxidative stress, inflammation and mitochondria induced apoptosis in rat model of renal warm ischemia. Biomedicine & Pharmacotherapy, 105, 573–581. https://doi.org/10.1016/j.biopha.2018.06.017
- Abdelsayed, E. M., Medhat, D., Mandour, Y. M., Hanafi, R. S., & Motaal, A. A. (2021). Niazimicin: A thiocarbamate glycoside from Moringa oleifera lam. Seeds with a novel neuroprotective activity. Journal of Food Biochemistry, 45 ( 12 ), e13992.
- Ademosun, A. O., Oboh, G., & Ajeigbe, O. F. (2022). Influence of moringa (Moringa oleifera) enriched ice creams on rats' brain: Exploring the redox and cholinergic systems. Current Research in Food Science, 5, 366–373. https://doi.org/10.1016/j.crfs.2022.01.021
- Adugba, A., Eke, B., Onahinon, C., Ibu, J., Eru, E., Akwaras, N., Saalu, L., & Ibu, J. (2018). Moringa oleifera causes gastro protection on acid-alcohol induced ulcer. IOSR Journal of Dental and Medical Sciences, 17(7), 44–49. https://doi.org/10.9790/0853-1707064449
10.9790/0853?1707064449 Google Scholar
- Ajibade, T. O., Arowolo, R., & Olayemi, F. O. (2013). Phytochemical screening and toxicity studies on the methanol extract of the seeds of Moringa oleifera. Journal of Complementary and Integrative Medicine, 10(1), 11–16. https://doi.org/10.1515/jcim-2012-0015
- Akintunde, J., Farai, T., Arogundade, M. R., & Adeleke, J. T. (2021). Biogenic zinc-oxide nanoparticles of Moringa oleifera leaves abrogates rotenone induced neuroendocrine toxicity by regulation of oxidative stress and acetylcholinesterase activity. Biochemistry and Biophysics Reports, 26, 100999. https://doi.org/10.1016/j.bbrep.2021.100999
- Amara, I., Ontario, M. L., Scuto, M., Lo Dico, G. M., Sciuto, S., Greco, V., Abid-Essefi, S., Signorile, A., Salinaro, A. T., & Calabrese, V. (2021). Moringa oleifera protects SH-SY5YCells from DEHP-induced endoplasmic reticulum stress and apoptosis. Antioxidants, 10(4), 532. https://doi.org/10.3390/antiox10040532
- Ansari, K. A. (2017). Sahjana (Moringa oleifera), pharmacognosy and pharmacology: A review. Journal of Pharmacognosy and Phytochemistry, 6(1), 442–445.
- Anwar, F., Ashraf, M., & Bhanger, M. I. (2005). Interprovenance variation in the composition of Moringa oleifera oilseeds from Pakistan. Journal of the American Oil Chemists' Society, 82(1), 45–51.
- Anwar, F., Latif, S., Ashraf, M., & Gilani, A. H. (2007). Moringa oleifera: A food plant with multiple medicinal uses. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 21(1), 17–25. https://doi.org/10.1002/ptr.2023
- Barhoi, D., Upadhaya, P., Barbhuiya, S. N., Giri, A., & Giri, S. (2021). Aqueous extract of Moringa oleifera exhibit potential anticancer activity and can be used as a possible cancer therapeutic agent: A study involving in vitro and in vivo approach. Journal of the American College of Nutrition, 40(1), 70–85. https://doi.org/10.1080/07315724.2020.1735572
- Bezerra, K., Silva, N. G., de Souza, A., Sá, G., & de Araújo, F. (2016). Moringa oleifera: A new perspective for the synthesis of natural products. Mol2net, 2, 1–5.
- Bhalla, N., Ingle, N., Patri, S. V., & Haranath, D. (2021). Phytochemical analysis of Moringa oleifera leaves extracts by GC-MS and free radical scavenging potency for industrial applications. Saudi Journal of Biological Sciences, 28(12), 6915–6928. https://doi.org/10.1016/j.sjbs.2021.07.075
- Bhatia, V., & Sharma, S. (2021). Role of mitochondrial dysfunction, oxidative stress and autophagy in progression of Alzheimer's disease. Journal of the Neurological Sciences, 421, 117253. https://doi.org/10.1016/j.jns.2020.117253
- Bhattacharya, A., Naik, M. R., Agrawal, D., Sahu, P. K., Kumar, S., & Mishra, S. S. (2014). CNS depressant and muscle relaxant effect of ethanolic leaf extract of Moringa oleifera on albino rats. International Journal of PharmTech Research, 6, 1441–1449.
- Bhattacharya, A., Tiwari, P., Sahu, P. K., & Kumar, S. (2018). A review of the phytochemical and pharmacological characteristics of Moringa oleifera. Journal of Pharmacy & Bioallied Sciences, 10(4), 181–191. https://doi.org/10.4103/JPBS.JPBS_126_18
- Bichi, M. H. (2013). A review of the applications of Moringa oleifera seeds extract in water treatment. Civil and Environmental Research, 3(8), 1–10.
- Biswas, S. K., Chowdhury, A., Das, J., Roy, A., & Hosen, S. Z. (2012). Pharmacological potentials of Moringa oleifera lam.: A review. International Journal of Pharmaceutical Sciences and Research, 3(2), 305. https://doi.org/10.13040/IJPSR.0975-8232.3(2).305-10
10.13040/IJPSR.0975?8232.3(2).305?10 Google Scholar
- Boopathi, N. M., & Raveendran, M. (2021). Moringa and its importance . In The Moringa genome (pp. 1–9 ). Springer.
10.1007/978-3-030-80956-0_1 Google Scholar
- Cheng, D., Gao, L., Su, S., Sargsyan, D., Wu, R., Raskin, I., & Kong, A. N. (2019). Moringa isothiocyanate activates Nrf2: Potential role in diabetic nephropathy. The AAPS Journal, 21(2), 1–14. https://doi.org/10.1208/s12248-019-0301-6
- Choudhary, M. K., Bodakhe, S. H., & Gupta, S. K. (2013). Assessment of the antiulcer potential of Moringa oleifera root-bark extract in rats. Journal of Acupuncture and Meridian Studies, 6(4), 214–220. https://doi.org/10.1016/j.jams.2013.07.003
- Cuellar-Nuñez, M., Luzardo-Ocampo, I., Campos-Vega, R., Gallegos-Corona, M. A., De Mejía, E. G., & Loarca-Piña, G. (2018). Physicochemical and nutraceutical properties of moringa (Moringa oleifera) leaves and their effects in an in vivo AOM/DSS-induced colorectal carcinogenesis model. Food Research International, 105, 159–168. https://doi.org/10.1016/j.foodres.2017.11.004
- Das, P. E., Abu-Yousef, I. A., Majdalawieh, A. F., Narasimhan, S., & Poltronieri, P. (2020). Green synthesis of encapsulated copper nanoparticles using a hydroalcoholic extract of Moringa oleifera leaves and assessment of their antioxidant and antimicrobial activities. Molecules, 25(3), 555. https://doi.org/10.3390/molecules25030555
- Das, P. E., Majdalawieh, A. F., Abu-Yousef, I. A., Narasimhan, S., & Poltronieri, P. (2020). Use of a hydroalcoholic extract of Moringa oleifera leaves for the green synthesis of bismuth nanoparticles and evaluation of their anti-microbial and antioxidant activities. Materials, 13(4), 876. https://doi.org/10.3390/ma13040876
- Dasgupta, S., Gunda, N. S. K., & Mitra, S. K. (2016). Evaluation of the antimicrobial activity of Moringa oleifera seed extract as a sustainable solution for potable water. RSC Advances, 6(31), 25918–25926. https://doi.org/10.1039/C6RA04011J
- Devaraj, V., Asad, M., & Prasad, S. (2007). Effect of leaves and fruits of Moringa oleifera. On gastric and duodenal ulcers. Pharmaceutical Biology, 45(4), 332–338. https://doi.org/10.1080/13880200701212924
- Dhakad, A. K., Ikram, M., Sharma, S., Khan, S., Pandey, V. V., & Singh, A. (2019). Biological, nutritional, and therapeutic significance of Moringa oleifera lam. Phytotherapy Research, 33(11), 2870–2903. https://doi.org/10.1002/ptr.6475
- Dhasmana, S., Dhasmana, A., Narula, A. S., Jaggi, M., Yallapu, M. M., & Chauhan, S. C. (2022). The panoramic view of amyotrophic lateral sclerosis: A fatal intricate neurological disorder. Life Sciences, 288, 120156. https://doi.org/10.1016/j.lfs.2021.120156
- Do, B. H., Nguyen, T. P. T., Ho, N. Q. C., Le, T. L., Hoang, N. S., & Doan, C. C. (2020). Mitochondria-mediated caspase-dependent and caspase-independent apoptosis induced by aqueous extract from Moringa oleifera leaves in human melanoma cells. Molecular Biology Reports, 47(5), 3675–3689. https://doi.org/10.1007/s11033-020-05462-y
- Ekong, M. B., Ekpo, M. M., Akpanyung, E. O., & Nwaokonko, D. U. (2017). Neuroprotective effect of Moringa oleifera leaf extract on aluminium-induced temporal cortical degeneration. Metabolic Brain Disease, 32(5), 1437–1447. https://doi.org/10.1007/s11011-017-0011-7
- Elsayed, E. A., Sharaf-Eldin, M. A., & Wadaan, M. (2015). In vitro evaluation of cytotoxic activities of essential oil from Moringa oleifera seeds on HeLa, HepG2, MCF-7, CACO-2 and L929 cell lines. Asian Pacific Journal of Cancer Prevention, 16(11), 4671–4675. https://doi.org/10.7314/APJCP.2015.16.11.4671
- Ezhilarasi, A. A., Vijaya, J. J., Kaviyarasu, K., Maaza, M., Ayeshamariam, A., & Kennedy, L. J. (2016). Green synthesis of NiO nanoparticles using Moringa oleifera extract and their biomedical applications: Cytotoxicity effect of nanoparticles against HT-29 cancer cells. Journal of Photochemistry and Photobiology B: Biology, 164, 352–360.
- Fahal, M., Rani, B., Aklakur, M. D., Chanu, T. I., & Saharan, N. (2018). Qualitative and quantitative phytochemical analysis of Moringa oleifera (lam) pods. International Journal of Current Microbiology and Applied Sciences, 7(5), 657–665. https://doi.org/10.20546/ijcmas.2018.705.080
10.20546/ijcmas.2018.705.080 Google Scholar
- Fahey, J. W. (2015). Moringa oleifera: A review of the medicinal potential . In Paper presented at the I international symposium on moringa 1158. ISHS Acta Horticulturae.
- Fernandes, F., Dias-Teixeira, M., Delerue-Matos, C., & Grosso, C. (2021). Critical review of lipid-based nanoparticles as carriers of neuroprotective drugs and extracts. Nanomaterials, 11(3), 563. https://doi.org/10.3390/nano11030563
- Ferrara, L., Joksimovic, M., & D'Angelo, S. (2021). Modulation of mitochondrial biogenesis: Action of physical activity and phytochemicals. Journal of Physical Education and Sport, 21(1), 425–433. https://doi.org/10.7752/jpes.2021.01042
10.7752/jpes.2021.01042 Google Scholar
- Forouzandeh, P., Ganguly, P., Dahiya, R., & Pillai, S. C. (2022). Supercapacitor electrode fabrication through chemical and physical routes. Journal of Power Sources, 519, 230744.
- Galts, C. P., Bettio, L. E., Jewett, D. C., Yang, C. C., Brocardo, P. S., Rodrigues, A. L. S., Thacker, J. S., & Gil-Mohapel, J. (2019). Depression in neurodegenerative diseases: Common mechanisms and current treatment options. Neuroscience & Biobehavioral Reviews, 102, 56–84. https://doi.org/10.1016/j.neubiorev.2019.04.002
- Galuppo, M., Giacoppo, S., Iori, R., de Nicola, G. R., Bramanti, P., & Mazzon, E. (2015). Administration of 4-(α-L-rhamnosyloxy)-benzyl isothiocyanate delays disease phenotype in SOD1G93A rats: A transgenic model of amyotrophic lateral sclerosis. BioMed Research International, 2015, 1–12. https://doi.org/10.1155/2015/259417
- Ganguly, R., & Guha, D. (2008). Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera. Indian Journal of Medical Research, 128(6), 744–751.
- Ghimire, S., Subedi, L., Acharya, N., & Gaire, B. P. (2021). Moringa oleifera: A tree of life as a promising medicinal plant for neurodegenerative diseases. Journal of Agricultural and Food Chemistry, 69, 14358–14371. https://doi.org/10.1021/acs.jafc.1c04581
- Giacoppo, S., Iori, R., Bramanti, P., & Mazzon, E. (2017). Topical moringin cream relieves neuropathic pain by suppression of inflammatory pathway and voltage-gated ion channels in murine model of multiple sclerosis. Molecular Pain, 13, 1744806917724318. https://doi.org/10.1177/1744806917724318
- Giacoppo, S., Rajan, T. S., de Nicola, G. R., Iori, R., Rollin, P., Bramanti, P., & Mazzon, E. (2017). The isothiocyanate isolated from Moringa oleifera shows potent anti-inflammatory activity in the treatment of murine subacute Parkinson's disease. Rejuvenation Research, 20(1), 50–63. https://doi.org/10.1089/rej.2016.1828
- González-Trujano, M. E., Martínez-González, C. L., Flores-Carrillo, M., Luna-Nophal, S. I., Contreras-Murillo, G., & Magdaleno-Madrigal, V. M. (2018). Behavioral and electroencephalographic evaluation of the anticonvulsive activity of Moringa oleifera leaf non-polar extracts and one metabolite in PTZ-induced seizures. Phytomedicine, 39, 1–9. https://doi.org/10.1016/j.phymed.2017.12.009
- Gupta, R., Mathur, M., Bajaj, V. K., Katariya, P., Yadav, S., Kamal, R., & Gupta, R. S. (2012). Evaluation of antidiabetic and antioxidant activity of Moringa oleifera in experimental diabetes. Journal of Diabetes, 4(2), 164–171. https://doi.org/10.1111/j.1753-0407.2011.00173.x
- Hamza, A. A. (2010). Ameliorative effects of Moringa oleifera lam seed extract on liver fibrosis in rats. Food and Chemical Toxicology, 48(1), 345–355. https://doi.org/10.1016/j.fct.2009.10.022
- Hannan, M. A., Kang, J.-Y., Mohibbullah, M., Hong, Y. K., Lee, H. S., Choi, J. S., Choi, I. S., & Moon, I. S. (2014). Moringa oleifera with promising neuronal survival and neurite outgrowth promoting potentials. Journal of Ethnopharmacology, 152(1), 142–150. https://doi.org/10.1016/j.jep.2013.12.036
- Ingale, S. P., & Gandhi, F. P. (2016). Effect of aqueous extract of Moringa oleifera leaves on pharmacological models of epilepsy and anxiety in mice. International Journal of Epilepsy, 3(1), 12–19. https://doi.org/10.1016/j.ijep.2016.02.001
10.1016/j.ijep.2016.02.001 Google Scholar
- Jaafaru, M. S., Nordin, N., Rosli, R., Shaari, K., Bako, H.’. Y., Saad, N., Noor, N. M., & Abdull Razis, A. F. (2019). Neuroprotective effects of glucomoringin-isothiocyanate against H2O2-induced cytotoxicity in neuroblastoma (SH-SY5Y) cells. Neurotoxicology, 75, 89–104. https://doi.org/10.1016/j.neuro.2019.09.008
- Jaafaru, M. S., Nordin, N., Shaari, K., Rosli, R., & Abdull Razis, A. F. (2018). Isothiocyanate from Moringa oleifera seeds mitigates hydrogen peroxide-induced cytotoxicity and preserved morphological features of human neuronal cells. PLoS One, 13(5), e0196403. https://doi.org/10.1371/journal.pone.0196403
- Jaiswal, D., Rai, P. K., Mehta, S., Chatterji, S., Shukla, S., Rai, D. K., Sharma, G., Sharma, B., khair, S., & Watal, G. (2013). Role of Moringa oleifera in regulation of diabetes-induced oxidative stress. Asian Pacific Journal of Tropical Medicine, 6(6), 426–432. https://doi.org/10.1016/S1995-7645(13)60068-1
- Jazwa, A., Rojo, A. I., Innamorato, N. G., Hesse, M., Fernández-Ruiz, J., & Cuadrado, A. (2011). Pharmacological targeting of the transcription factor Nrf2 at the basal ganglia provides disease modifying therapy for experimental parkinsonism. Antioxidants & Redox Signaling, 14(12), 2347–2360. https://doi.org/10.1089/ars.2010.3731
- Jin, S. I., Kim, H. J., Jeong, J. H., Jin, D. E., Choi, S. G., & Heo, H. J. (2014). Nutritional composition and cytoprotective effect of Moringa oleifera lam. Korean Journal of Food Science and Technology, 46(5), 609–615. https://doi.org/10.9721/KJFST.2014.46.5.609
10.9721/KJFST.2014.46.5.609 Google Scholar
- Joy, A. E., Kunhikatta, S. B., & Manikkoth, S. (2013). Anti-convulsant activity of ethanolic extract of Moringa concanensis leaves in Swiss albino mice. Archives of Medicine and Health Sciences, 1(1), 6. https://doi.org/10.4103/2321-4848.113548
10.4103/2321?4848.113548 Google Scholar
- Kadir, A., Singh, J., Rahi, V., & Kumar, P. (2022). Berberine ameliorate haloperidol and 3-Nitropropionic acid-induced neurotoxicity in rats. Neurochemical Research, 47, 1–13. https://doi.org/10.1007/s11064-022-03677-y
- Kandeil, M. A., Mohammed, E. T., Hashem, K. S., Aleya, L., & Abdel-Daim, M. M. (2020). Moringa seed extract alleviates titanium oxide nanoparticles (TiO2-NPs)-induced cerebral oxidative damage, and increases cerebral mitochondrial viability. Environmental Science and Pollution Research, 27(16), 19169–19184. https://doi.org/10.1007/s11356-019-05514-2
- Kaur, G., Invally, M., Sanzagiri, R., & Buttar, H. S. (2015). Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine. Journal of Ayurveda and Integrative Medicine, 6(4), 273–279. https://doi.org/10.4103/0975-9476.172384
- Kavitha, C., Ramesh, M., Kumaran, S. S., & Lakshmi, S. A. (2012). Toxicity of Moringa oleifera seed extract on some hematological and biochemical profiles in a freshwater fish, Cyprinus carpio. Experimental and Toxicologic Pathology, 64(7–8), 681–687. https://doi.org/10.1016/j.etp.2011.01.001
- Kesh, S., Kannan, R. R., Sivaji, K., & Balakrishnan, A. (2021). Hesperidin downregulates kinases lrrk2 and gsk3β in a 6-OHDA induced Parkinson's disease model. Neuroscience Letters, 740, 135426. https://doi.org/10.1016/j.neulet.2020.135426
- Kirindage, K. G. I. S., Fernando, I. P. S., Jayasinghe, A. M. K., Han, E. J., Dias, M. K. H. M., Kang, K. P., Moon, S. I., Shin, T. S., Ma, A., & Ahn, G. (2022). Moringa oleifera hot water extract protects Vero cells from hydrogen peroxide-induced oxidative stress by regulating mitochondria-mediated apoptotic pathway and Nrf2/HO-1 signaling. Food, 11(3), 420. https://doi.org/10.3390/foods11030420
- Kirisattayakul, W., Wattanathorn, J., Tong-Un, T., Muchimapura, S., Wannanon, P., & Jittiwat, J. (2013). Cerebroprotective effect of Moringa oleifera against focal ischemic stroke induced by middle cerebral artery occlusion. Oxidative Medicine and Cellular Longevity, 2013, 1–10. https://doi.org/10.1155/2013/951415
- Kou, X., Li, B., Olayanju, J., Drake, J., & Chen, N. (2018). Nutraceutical or pharmacological potential of Moringa oleifera lam. Nutrients, 10(3), 343. https://doi.org/10.3390/nu10030343
- Kumar, S., & Kumar, P. (2021). The beneficial effect of Rice bran extract against rotenone-induced experimental Parkinson's disease in rats. Current Molecular Pharmacology, 14(3), 428–438. https://doi.org/10.2174/1874467214666210126113324
- Kumari, S., Kumari, C., Virk, A. K., Kumar, V., Attri, C., & Kulshrestha, S. (2022). Preliminary screening of qualitative and quantitative analysis of Moringa Moringa oleifera seeds using different solvents . In Paper presented at the AIP conference proceedings. AIP Publishing LLC.
10.1063/5.0086123 Google Scholar
- Lazarini-Lopes, W., Silva-Cardoso, G. K., Leite-Panissi, C. R. A., & Garcia-Cairasco, N. (2022). Increased TRPV1 channels and FosB protein expression are associated with chronic epileptic seizures and anxiogenic-like behaviors in a preclinical model of temporal lobe epilepsy. Biomedicine, 10(2), 416. https://doi.org/10.3390/biomedicines10020416
- Liu, R., Liu, J., Huang, Q., Liu, S., & Jiang, Y. (2022). Moringa oleifera: A systematic review of its botany, traditional uses, phytochemistry, pharmacology and toxicity. Journal of Pharmacy and Pharmacology, 74, 296–320. https://doi.org/10.1093/jpp/rgab131
- Mahajan, S. G., Mali, R. G., & Mehta, A. A. (2007). Protective effect of ethanolic extract of seeds of Moringa oleifera lam. Against inflammation associated with development of arthritis in rats. Journal of Immunotoxicology, 4(1), 39–47. https://doi.org/10.1080/15476910601115184
- Mahaman, Y. A. R., Huang, F., Wu, M., Wang, Y., Wei, Z., Bao, J., Salissou, M. T. M., Ke, D., Wang, Q., Liu, R., Wang, J. Z., Zhang, B., Chen, D., & Wang, X. (2018). Moringa oleifera alleviates homocysteine-induced Alzheimer's disease-like pathology and cognitive impairments. Journal of Alzheimer's Disease, 63(3), 1141–1159. https://doi.org/10.3233/JAD-180091
- Matinise, N., Fuku, X., Kaviyarasu, K., Mayedwa, N., & Maaza, M. J. A. S. S. (2017). ZnO nanoparticles via Moringa oleifera green synthesis: Physical properties & mechanism of formation. Applied Surface Science, 406, 339–347. https://doi.org/10.1016/j.apsusc.2017.01.219
- Meireles, D., Gomes, J., Lopes, L., Hinzmann, M., & Machado, J. (2020). A review of properties, nutritional and pharmaceutical applications of Moringa oleifera: Integrative approach on conventional and traditional Asian medicine. Advances in Traditional Medicine, 20(4), 495–515. https://doi.org/10.1007/s13596-020-00468-0
10.1007/s13596-020-00468-0 Google Scholar
- Minj, E., Upadhayay, S., & Mehan, S. (2021). Nrf2/HO-1 signaling activator acetyl-11-keto-beta Boswellic acid (AKBA)-mediated neuroprotection in methyl mercury-induced experimental model of ALS. Neurochemical Research, 46(11), 2867–2884.
- Mishra, G., Singh, P., Verma, R., Kumar, S., Srivastav, S., Jha, K. K., & Khosa, R. L. (2011). Traditional uses, phytochemistry and pharmacological properties of Moringa oleifera plant: An overview. Der Pharmacia Lettre, 3(2), 141–164.
- Moodley, I. (2017). Acute toxicity of Moringa oleifera leaf powder in rats. Journal of Medicinal Plants Studies, 5, 180–185.
- More, S. V., Kumar, H., Cho, D. Y., Yun, Y. S., & Choi, D. K. (2016). Toxin-induced experimental models of learning and memory impairment. International Journal of Molecular Sciences, 17(9), 1447. https://doi.org/10.3390/ijms17091447
- Muhammed, R. E., El-Desouky, M. A., Abo-Seda, S. B., Nahas, A. A., Elhakim, H. K., & Alkhalaf, M. I. (2020). The protecting role of Moringa oleifera in cypermethrin-induced mitochondrial dysfunction and apoptotic events in rats brain. Journal of King Saud University-Science, 32(6), 2717–2722. https://doi.org/10.1016/j.jksus.2020.06.006
- Mutar, Y. S., Al-Rawi, K. F., & Mohammed, M. T. (2021). Protective effect of Moringa oleifera extract on oxidative stress through ischemia/reperfusion in rat brain. Egyptian Journal of Chemistry, 64(11), 5–6.
- Niu, Y., Zhang, J., & Dong, M. (2021). Nrf2 as a potential target for Parkinson's disease therapy. Journal of Molecular Medicine, 99(7), 917–931. https://doi.org/10.1007/s00109-021-02071-5
- Ogundipe O. (2019). Nuerobehavioural investigation of the role/S of moringa oleifera on 3-Nitropropionic acid model of Huntington's disease. International Journal of research and scientific innovation (IJRSI).
- Ogundipe O. (2020). Morphological and histochemical investigation of the role (S) of moringa oleifera (lam) on 3-Nitropropionic acid model of Huntington's disease. International Journal of research and scientific innovation (IJRSI).
- Oguntibeju, O., Aboua, G., & Omodanisi, E. I. (2020). Effects of Moringa oleifera on oxidative stress, apoptotic and inflammatory biomarkers in streptozotocin-induced diabetic animal model. South African Journal of Botany, 129, 354–365. https://doi.org/10.1016/j.sajb.2019.08.039
- Omodanisi, E. I., Aboua, Y. G., & Oguntibeju, O. O. (2017). Assessment of the anti-hyperglycaemic, anti-inflammatory and antioxidant activities of the methanol extract of Moringa oleifera in diabetes-induced nephrotoxic male wistar rats. Molecules, 22(4), 439. https://doi.org/10.3390/molecules22040439
- Omotoso, G. O., Gbadamosi, I. T., Afolabi, T. T., Abdulwahab, A. B., & Akinlolu, A. A. (2018). Ameliorative effects of moringa on cuprizone-induced memory decline in rat model of multiple sclerosis. Anatomy & Cell Biology, 51(2), 119–127. https://doi.org/10.5115/acb.2018.51.2.119
- Onasanwo, S. A., Adamaigbo, V. O., Adebayo, O. G., & Eleazer, S. E. (2021). Moringa oleifera-supplemented diet protect against cortico-hippocampal neuronal degeneration in scopolamine-induced spatial memory deficit in mice: Role of oxido-inflammatory and cholinergic neurotransmission pathway. Metabolic Brain Disease, 36(8), 2445–2460. https://doi.org/10.1007/s11011-021-00855-9
- Ouédraogo, M., Lamien-Sanou, A., Ramdé, N., Ouédraogo, A. S., Ouédraogo, M., Zongo, S. P., Goumbri, O., Duez, P., & Guissou, P. I. (2013). Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits. Experimental and Toxicologic Pathology, 65(3), 335–339. https://doi.org/10.1016/j.etp.2011.11.006
- Paikra, B. K. (2017). Phytochemistry and pharmacology of Moringa oleifera lam. Journal of Pharmacopuncture, 20(3), 194–200. https://doi.org/10.3831/KPI.2017.20.022
- Pal, S., Mondal, S., Maity, J., & Mukherjee, R. (2018). Synthesis and characterization of ZnO nanoparticles using Moringa oleifera leaf extract: Investigation of photocatalytic and antibacterial activity. International Journal of Nanoscience and Nanotechnology, 14(2), 111–119.
- Pandey, A., Pandey, R., Tripathi, P., Gupta, P. P., Haider, J., Bhatt, S., & Singh, A. V. (2012). Moringa oleifera lam. Sahijan-a plant with a plethora of diverse therapeutic benefits: An updated retrospection. Medicinal and Aromatic Plants, 1(1), 1–8. https://doi.org/10.4172/map.1000101
10.4172/map.1000101 Google Scholar
- Pappas, I. S., Siomou, S., Bozinou, E., & Lalas, S. I. (2021). Moringa oleifera leaves crude aqueous extract down-regulates of BRCA1, mta-1 and oncogenes c-myc and p53 in AsPC-1, MCF-7 and HTC-116 cells. Food Bioscience, 43, 101221. https://doi.org/10.1016/j.fbio.2021.101221
- Paul, S., Basak, P., Majumder, R., Mukherjee, A., Ghosh, J., Patra, S., & Jana, N. K. (2020). Biochemical estimation of Moringa oleifera leaf extract for synthesis of silver nanoparticle mediated drug delivery system. Journal of Plant Biochemistry and Biotechnology, 29(1), 86–93. https://doi.org/10.1007/s13562-019-00517-z
- Ragasa, C. Y., Ng, V. A. S., & Shen, C. C. (2016). Chemical constituents of Moringa oleifera lam. Seeds. International Journal of Pharmacognosy and Phytochemical Research, 8(3), 495–498.
- Rahman, M. M., Sheikh, M. M. I., Sharmin, S. A., Islam, M. S., Rahman, M. A., Rahman, M. M., & Alam, M. F. (2009). Antibacterial activity of leaf juice and extracts of Moringa oleifera lam. Against some human pathogenic bacteria. Chiang Mai University Journal of Natural Sciences, 8(2), 219.
- Randriamboavonjy, J. I., Loirand, G., Vaillant, N., Lauzier, B., Derbré, S., Michalet, S., Pacaud, P., & Tesse, A. (2016). Cardiac protective effects of Moringa oleifera seeds in spontaneous hypertensive rats. American Journal of Hypertension, 29(7), 873–881. https://doi.org/10.1093/ajh/hpw001
- Ray K., Hazra R., Debnath, P. K. and Guha, D. (2004). Role of 5-hydroxytryptamine in Moringa oleifera induced potentiation of pentobarbitone hypnosis in albino rats. Indian Journal of Experimental Biology.
- Rocha-Filho, C. A., Albuquerque, L. P., Silva, L. R., Silva, P. C., Coelho, L. C., Navarro, D. M., Albuquerque, M. C., Melo, A. M. M., Napoleão, T. H., Pontual, E. V., & Paiva, P. M. (2015). Assessment of toxicity of Moringa oleifera flower extract to Biomphalaria glabrata, Schistosoma mansoni and Artemia salina. Chemosphere, 132, 188–192. https://doi.org/10.1016/j.chemosphere.2015.03.041
- Saini, R. K., Sivanesan, I., & Keum, Y. S. (2016). Phytochemicals of Moringa oleifera: A review of their nutritional, therapeutic and industrial significance. 3 Biotech, 6(2), 1–14.
- Seervi, M., Rani, A., Sharma, A. K., & Santhosh Kumar, T. R. (2018). ROS mediated ER stress induces Bax-Bak dependent and independent apoptosis in response to thioridazine. Biomedicine & Pharmacotherapy, 106, 200–209. https://doi.org/10.1016/j.biopha.2018.06.123
- Senthilkumar, A., Karuvantevida, N., Rastrelli, L., Kurup, S. S., & Cheruth, A. J. (2018). Traditional uses, pharmacological efficacy, and phytochemistry of Moringa peregrina (Forssk.) Fiori. —A review. Frontiers in Pharmacology, 9 ( 465 ), 1–17. https://doi.org/10.3389/fphar.2018.00465
- Singh, A., Kukreti, R., Saso, L., & Kukreti, S. (2019). Oxidative stress: A key modulator in neurodegenerative diseases. Molecules, 24(8), 1583. https://doi.org/10.3390/molecules24081583
- Singh, S., & Kumar, P. (2016). Piperine potentiates neuroprotective effect of curcumin in MPTP model of Parkinson's disease in rats: Impact on neurochemical modulation . In Paper presented at the movement disorders. Hoboken, NJ: Wiley-Blackwell.
- Sivaranjani, V., & Philominathan, P. (2016). Synthesize of titanium dioxide nanoparticles using Moringa oleifera leaves and evaluation of wound healing activity. Wound Medicine, 12, 1–5. https://doi.org/10.1016/j.wndm.2015.11.002
10.1016/j.wndm.2015.11.002 Google Scholar
- Soni, D., & Kumar, P. (2022). GSK-3β-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders. Pharmacological Reports, 74, 557–569. https://doi.org/10.1007/s43440-022-00390-z
- Sreelatha, S., & Padma, P. (2011). Modulatory effects of Moringa oleifera extracts against hydrogen peroxide-induced cytotoxicity and oxidative damage. Human & Experimental Toxicology, 30(9), 1359–1368. https://doi.org/10.1177/0960327110391385
- Stohs, S. J., & Hartman, M. J. (2015). Review of the safety and efficacy of Moringa oleifera. Phytotherapy Research, 29(6), 796–804. https://doi.org/10.1002/ptr.5325
- Sutalangka, C., Wattanathorn, J., Muchimapura, S., & Thukham-mee, W. (2013). Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia. Oxidative Medicine and Cellular Longevity, 2013, 1–9. https://doi.org/10.1155/2013/695936
- Tiloke, C., Anand, K., Gengan, R. M., & Chuturgoon, A. A. (2018). Moringa oleifera and their phytonanoparticles: Potential antiproliferative agents against cancer. Biomedicine & Pharmacotherapy, 108, 457–466. https://doi.org/10.1016/j.biopha.2018.09.060
- Tiloke, C., Phulukdaree, A., Anand, K., Gengan, R. M., & Chuturgoon, A. A. (2016). Moringa oleifera gold nanoparticles modulate oncogenes, tumor suppressor genes, and caspase-9 splice variants in a549 cells. Journal of Cellular Biochemistry, 117(10), 2302–2314.
- Umar, Z. A., Liaqat, U., Ahmed, R., Hedwig, R., Ramli, M., Marpaung, M. A., Kurniawan, K. H., Pardede, M., & Baig, M. A. (2022). Determination of micronutrients and toxic elements in Moringa oleifera leaves by calibration free laser-induced breakdown spectroscopy (LIBS). Analytical Letters, 55(5), 755–769. https://doi.org/10.1080/00032719.2021.1966794
- Upadhayay, S., Mehan, S., Prajapati, A., Sethi, P., Suri, M., Zawawi, A., Almashjary, M. N., & Tabrez, S. (2022). Nrf2/HO-1 signaling stimulation through Acetyl-11-keto-Beta-Boswellic acid (AKBA) provides neuroprotection in ethidium bromide-induced experimental model of multiple sclerosis. Genes, 13(8), 1324.
- Villarruel-López, A., López-de la Mora, D., Vázquez-Paulino, O. D., Puebla-Mora, A. G., Torres-Vitela, M. R., Guerrero-Quiroz, L. A., & Nuño, K. (2018). Effect of Moringa oleifera consumption on diabetic rats. BMC Complementary and Alternative Medicine, 18(1), 1–10. https://doi.org/10.1186/s12906-018-2180-2
- Wang, L., Yang, P., Yang, C., Yang, D., Wu, X., Cao, T., Zeng, C., Chen, Q., Zhang, S., Zhu, Z., Jiao, S., & Cai, H. (2022). Disturbance of neurotransmitter metabolism in drug-naïve, first-episode major depressive disorder: A comparative study on adult and adolescent cohorts. European Archives of Psychiatry and Clinical Neuroscience, 272, 1–14. https://doi.org/10.1007/s00406-022-01406-8
- Yassa, H. D., & Tohamy, A. F. (2014). Extract of Moringa oleifera leaves ameliorates streptozotocin-induced Diabetes mellitus in adult rats. Acta Histochemica, 116 ( 5 ), 844–854. https://doi.org/10.1016/j.acthis.2014.02.002
- Yu, H., Shi, J., Lin, Y., Zhang, Y., Luo, Q., Huang, S., Wang, S., Wei, J., Huang, J., Li, C., & Ji, L. (2022). Icariin ameliorates Alzheimer's disease pathology by alleviating myelin injury in 3× Tg-AD mice. Neurochemical Research, 47, 1049–1059. https://doi.org/10.1007/s11064-021-03507-7
- Yunusa, S., & Musa, A. (2018). Evaluation of antidepressant effect of ethanol extract and chloroform fraction of Moringa oleifera lam.(Moringaceae) leaf in mice. Journal of Drug Research and Development, 4 ( 1 ), 2470–1009. https://doi.org/10.16966/2470-1009.140
10.16966/2470?1009.140 Google Scholar
- Zeng, K., Li, Y., Yang, W., Ge, Y., Xu, L., Ren, T., Zhang, H., Zhuo, R., Peng, L., Chen, C., Zhou, Y., Zhao, Y., Li, W. J., Jin, X., & Yang, L. (2019). Moringa oleifera seed extract protects against brain damage in both the acute and delayed stages of ischemic stroke. Experimental Gerontology, 122, 99–108. https://doi.org/10.1016/j.exger.2019.04.014
- Zhou, J., Yang, W. S., Suo, D. Q., Li, Y., Peng, L., Xu, L. X., Zeng, K. Y., Ren, T., Wang, Y., Zhou, Y., Zhao, Y., Yang, L. C., & Jin, X. (2018). Moringa oleifera seed extract alleviates scopolamine-induced learning and memory impairment in mice. Frontiers in Pharmacology, 9, 389. https://doi.org/10.3389/fphar.2018.00389
- Zhu, W.-B., Tian, F.-J., & Liu, L. Q. (2017). Chikusetsu (CHI) triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species (ROS) production. Biomedicine & Pharmacotherapy, 90, 446–454. https://doi.org/10.1016/j.biopha.2017.03.050