Author(s):
Renuka Ekka, Shashikala Bhagat, Shubham Kumar Sahu, Bharti Ahirwar
Email(s):
ekkarenu66@gmail.com
DOI:
10.52711/0975-4385.2026.00014
Address:
Renuka Ekka*, Shashikala Bhagat, Shubham Kumar Sahu, Bharti Ahirwar
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Koni, Bilaspur, Chhattisgarh, 495009 - India.
*Corresponding Author
Published In:
Volume - 18,
Issue - 1,
Year - 2026
ABSTRACT:
Alzheimer’s disease is a progressive neurodegenerative disorder marked by cognitive decline, amyloid-beta accumulation, tau hyperphosphorylation, and chronic oxidative stress. Emerging evidence highlights mitochondrial dysfunction and impaired bioenergetics as central contributors to Alzheimer's disease pathogenesis. Centella asiatica a medicinal herb widely used in traditional systems of medicine, has demonstrated promising neuroprotective properties through its rich phytochemical profile, particularly triterpenoids such as asiaticoside and madecassoside. This review systematically explores the role of Centella asiatica in modulating mitochondrial bioenergetics and antioxidant pathways in the context of Alzheimer’s disease. Centella asiatica enhances mitochondrial function by upregulating ATP synthesis, preserving mitochondrial membrane potential, and promoting biogenesis via PGC-1a activation. Concurrently, it activates the Nrf2 signalling pathway, leading to increased expression of endogenous antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. These mechanisms collectively reduce reactive oxygen species (ROS), mitigate lipid peroxidation, and prevent neuronal apoptosis. Preclinical studies support Centella asiatica's efficacy in improving cognitive performance, reducing neuroinflammation, and protecting against neurotoxicity. Although clinical data remain limited, the safety profile and multi-targeted action of Centella asiatica position it as a promising candidate for adjunctive therapy in Alzheimer’s disease. Further translational research and clinical trials are warranted to validate its therapeutic potential and optimise its pharmacological application.
Cite this article:
Renuka Ekka, Shashikala Bhagat, Shubham Kumar Sahu, Bharti Ahirwar. Centella asiatica (L.) as a Neuroprotective agent in Alzheimer’s Disease: A Focus on Mitochondrial Bioenergetics and Antioxidant Pathways. Research Journal of Pharmacognosy and Phytochemistry. 2026; 18(1):96-5. doi: 10.52711/0975-4385.2026.00014
Cite(Electronic):
Renuka Ekka, Shashikala Bhagat, Shubham Kumar Sahu, Bharti Ahirwar. Centella asiatica (L.) as a Neuroprotective agent in Alzheimer’s Disease: A Focus on Mitochondrial Bioenergetics and Antioxidant Pathways. Research Journal of Pharmacognosy and Phytochemistry. 2026; 18(1):96-5. doi: 10.52711/0975-4385.2026.00014 Available on: https://rjpponline.org/AbstractView.aspx?PID=2026-18-1-14
REFERENCE:
1. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer's disease. The Lancet. 2021; 397(10284): 1577-90.
2. Association As. 2019 Alzheimer's disease facts and figures. Alzheimer's and Dementia. 2019;15(3):321-87.
3. Sehar U, Rawat P, Reddy AP, Kopel J, Reddy PH. Amyloid beta in aging and Alzheimer’s disease. International Journal of Molecular Sciences. 2022; 23(21): 12924.
4. Swerdlow RH. Pathogenesis of Alzheimer’s disease. Clinical Interventions in Aging. 2007;2(3):347-59.
5. Cheong SL, Tiew JK, Fong YH, Leong HW, Chan YM, Chan ZL, et al. Current pharmacotherapy and multi-target approaches for Alzheimer’s disease. Pharmaceuticals. 2022; 15(12): 1560.
6. Chandrika UG, Kumara PAP. Gotu Kola (Centella asiatica): nutritional properties and plausible health benefits. Advances in Food and Nutrition Research. 2015;76:125-57.
7. Orhan IE. Centella asiatica (L.) Urban: From traditional medicine to modern medicine with neuroprotective potential. Evidence‐Based Complementary and Alternative Medicine. 2012; 2012(1): 946259.
8. Gray NE, Alcazar Magana A, Lak P, Wright KM, Quinn J, Stevens JF, et al. Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement. Phytochemistry Reviews. 2018; 17(1): 161-94.
9. Gray NE, Sampath H, Zweig JA, Quinn JF, Soumyanath A. Centella asiatica attenuates amyloid-β-induced oxidative stress and mitochondrial dysfunction. Journal of Alzheimer’s Disease. 2015; 45(3): 933-46.
10. Naidoo DB, Phulukdaree A, Anand K, Sewram V, Chuturgoon AA. Centella asiatica fraction-3 suppresses the nuclear factor erythroid 2-related factor 2 anti-oxidant pathway and enhances reactive oxygen species-mediated cell death in cancerous lung A549 cells. Journal of Medicinal Food. 2017; 20(10): 959-68.
11. Islam MT, Ali ES, Uddin SJ, Khan IN, Shill MC, de Castro e Sousa JM, et al. Anti-cancer effects of asiatic acid, a triterpene from Centilla asiatica L: a review. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2020; 20(5): 536-47.
12. Gray NE, Zweig JA, Matthews DG, Caruso M, Quinn JF, Soumyanath A. Centella asiatica attenuates mitochondrial dysfunction and oxidative stress in Aβ‐exposed hippocampal neurons. Oxidative medicine and cellular longevity. 2017; 2017(1): 7023091.
13. Iqubal A, Rahman SO, Ahmed M, Bansal P, Haider MR, Iqubal MK, et al. current quest in natural bioactive compounds for Alzheimer’s disease: Multi-targeted-designed-ligand based approach with preclinical and clinical based evidence. Current Drug Targets. 2021; 22(6): 685-720.
14. Dewi RL, Yuniati R. Utiliization of Natural Compound from Pegagan (Centella asiatica (L.) Urb.) and Their Potential Role in the Health Sector. Jurnal Penelitian Pendidikan IPA. 2025; 11(4): 94-103.
15. Roy DC, Barman SK, Shaik MM. Current updates on Centella asiatica: phytochemistry, pharmacology and traditional uses. Medicinal Plant Research. 2013;3.
16. Singh S, Singh D, Banu VS. Functional constituents (micronutrients and phytochemicals) and antioxidant activity of Centella asiatica (L.) Urban leaves. Industrial Crops and Products. 2014; 61: 115-9.
17. Tan SC, Bhattamisra SK, Chellappan DK, Candasamy M. Actions and therapeutic potential of madecassoside and other major constituents of Centella asiatica: a review. Applied Sciences. 2021; 11(18): 8475.
18. Bandopadhyay S, Mandal S, Ghorai M, Jha NK, Kumar M, Radha n, et al. Therapeutic properties and pharmacological activities of asiaticoside and madecassoside: A review. Journal of Cellular and Molecular Medicine. 2023; 27(5): 593-608.
19. Zainol N, Voo S, Sarmidi M, Aziz R. Profiling of Centella asiatica (L.) Urban extract. Malaysian Journal of Analytical Sciences. 2008; 12(2): 322-7.
20. Doughari JH. Phytochemicals: extraction methods, basic structures and mode of action as potential chemotherapeutic agents: Intech Open Access Publisher Rijeka, Croatia; 2012.
21. Ogunka-Nnoka C, Igwe F, Agwu J, Peter O, Wolugbom P. Nutrient and phytochemical composition of Centella asiatica leaves. Med Aromat Plants. 2020; 9(2): 2167-0412.
22. Siddiqui B, Aslam H, Ali S, Khan S, Begum S. Chemical constituents of Centella asiatica. Journal of Asian Natural Products Research. 2007; 9(4): 407-14.
23. Imbimbo BP, Lombard J, Pomara N. Pathophysiology of Alzheimer's disease. Neuroimaging Clinics. 2005;15(4):727-53.
24. Penke B, Bogár F, Fülöp L. β-Amyloid and the pathomechanisms of Alzheimer’s disease: a comprehensive view. Molecules. 2017; 22(10): 1692.
25. Ahuja M, Patel M, Majrashi M, Mulabagal V, Dhanasekaran M. Centella asiatica, an ayurvedic medicinal plant, prevents the major neurodegenerative and neurotoxic mechanisms associated with cognitive impairment. Medicinal plants and fungi: recent advances in research and development: Springer; 2017. p. 3-48.
26. Kontush A. Amyloid-β: an antioxidant that becomes a pro-oxidant and critically contributes to Alzheimer’s disease. Free Radical Biology and Medicine. 2001; 31(9): 1120-31.
27. Wang W-Y, Tan M-S, Yu J-T, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Annals of Translational Medicine. 2015; 3(10):136.
28. Hambali A, Kumar J, Hashim NFM, Maniam S, Mehat MZ, Cheema MS, et al. Hypoxia-induced neuroinflammation in Alzheimer’s disease: potential neuroprotective effects of Centella asiatica. Frontiers in Physiology. 2021; 12: 712317.
29. Yan H, Feng L, Li M. The role of Traditional Chinese Medicine Natural Products in β-amyloid deposition and tau protein hyperphosphorylation in Alzheimer’s disease. Drug Design, Development and Therapy. 2023: 3295-323.
30. Duyckaerts C, Delatour B, Potier M-C. Classification and basic pathology of Alzheimer disease. Acta Neuropathologica. 2009; 118(1): 5-36.
31. Lokanathan Y, Omar N, Puzi NNA, Saim A, Idrus RH. Recent updates in neuroprotective and neuroregenerative potential of Centella asiatica. The Malaysian Journal of Medical Sciences: MJMS. 2016; 23(1): 4.
32. Nataraj J, Manivasagam T, Justin Thenmozhi A, Essa MM. Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells. Nutritional Neuroscience. 2017; 20(6): 351-9.
33. Park D-W, Lee Y-G, Jeong Y-J, Jeon H, Kang S-C. Preventive effects against retinal degeneration by Centella asiatica extract (CA-HE50) and asiaticoside through apoptosis suppression by the Nrf2/HO-1 signaling pathway. Antioxidants. 2021; 10(4): 613.
34. Süntar I, Akkol EK, Nahar L, Sarker SD. Wound healing and antioxidant properties: do they coexist in plants? Free Radicals and Antioxidants. 2012; 2(2): 1-7.
35. Legiawati L, Fadilah F, Bramono K, Indriatmi W. In silico study of Centella asiatica active compounds as anti-inflammatory agent by decreasing Il-1 and Il-6 activity, promoting Il-4 activity. Journal of Pharmaceutical Sciences and Research. 2018; 10(9): 2142-7.
36. Xu M-f, Xiong Y-y, Liu J-k, Qian J-j, Zhu L, Gao J. Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells. Acta Pharmacologica Sinica. 2012; 33(5): 578-87.
37. Ji D, Cui M, Tian C, Chen K, Shao J. Asiatic acid alleviates dexamethasone-induced muscle atrophy through regulating the Sirt1/PGC-1α/FOXO3 pathway. Histology and histopathology.18991.
38. Haghparast Azad M, Niktab I, Dastjerdi S, Abedpoor N, Rahimi G, Safaeinejad Z, et al. The combination of endurance exercise and SGTC (Salvia–Ginseng–Trigonella–Cinnamon) ameliorate mitochondrial markers’ overexpression with sufficient ATP production in the skeletal muscle of mice fed AGEs-rich high-fat diet. Nutrition & metabolism. 2022; 19(1): 17.
39. Peng L, Bestard-Lorigados I, Song W. The synapse as a treatment avenue for Alzheimer’s Disease. Molecular Psychiatry. 2022; 27(7): 2940-9.
40. Mamtha B, Kavitha K, Srinivasan K, Shivananda P. An in vitro study of the effect of Centella asiatica [Indian pennywort] on enteric pathogens. Indian Journal of Pharmacology. 2004; 36(1): 41.
41. Shukla A, Rasik A, Jain G, Shankar R, Kulshrestha D, Dhawan B. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. Journal of Ethnopharmacology. 1999; 65(1): 1-11.
42. Oyenihi AB, George TT, Oyenihi OR, Obilana AO, Opperman M. Three decades of research on Centella asiatica: Insights and future trends from bibliometric analysis. Journal of Herbal Medicine. 2023; 39: 100662.
43. Wright KM, McFerrin J, Alcázar Magaña A, Roberts J, Caruso M, Kretzschmar D, et al. Developing a rational, optimized product of Centella asiatica for examination in clinical trials: Real world challenges. Frontiers in Nutrition. 2022; 8: 799137.
44. Jamil AS, Saputro PG. Molecular docking and ADME studies of Centella asiatica as anti hyperuricemia. Pharmacognosy Journal. 2023; 15(2).
45. Mohapatra P, Ray A, Jena S, Nayak S, Mohanty S. Influence of extraction methods and solvent system on the chemical composition and antioxidant activity of Centella asiatica L. leaves. Biocatalysis and Agricultural Biotechnology. 2021; 33: 101971.
46. Jusril NA, Muhamad Juhari ANN, Abu Bakar SI, Md Saad WM, Adenan MI. Combining in silico and in vitro studies to evaluate the acetylcholinesterase inhibitory profile of different accessions and the biomarker triterpenes of Centella asiatica. Molecules. 2020; 25(15): 3353.
47. Giribabu N, Karim K, Kilari EK, Nelli SR, Salleh N. Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammation, and apoptosis in male rats with type-2 diabetes. Inflammopharmacology. 2020; 28(6): 1599-622.
48. Mahmud N, Ramasamy S, Manickam S, Wan-Mohtar WAAQI. Synergistic-antagonistic interaction of vegetable extracts, Acalypha indica, Centella asiatica, and Sesbania grandiflora: Wound healing, antioxidant, protectivity, and antimicrobial properties. Malaysian Journal of Microbiology. 2020; 16(6).
49. Kumar V, Kumar CS, Hari G, Venugopal NK, Vijendra PD, B GB. Homology modeling and docking studies on oxidosqualene cyclases associated with primary and secondary metabolism of Centella asiatica. Springer Plus. 2013; 2(1):189.
50. Bhat BA, Almilaibary A, Mir RA, Aljarallah BM, Mir WR, Ahmad F, et al. Natural therapeutics in aid of treating alzheimer’s disease: a green gateway toward ending quest for treating neurological disorders. Frontiers in Neuroscience. 2022; 16: 884345.
51. Puttarak P, Dilokthornsakul P, Saokaew S, Dhippayom T, Kongkaew C, Sruamsiri R, et al. Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis. Scientific reports. 2017; 7(1): 1-12.
52. Aszrin FN, Adam SH, Abdul Mutalib M, Tang H, Tang S. An overview of Centella asiatica and its therapeutic applications. Life Science, Medicine and Biomedicine. 2024; 8(1).
53. Sosa AE, Hassan Z. Traditional Herbal Medicine for Dementia Therapy. Nutrition in Brain Aging and Dementia: Springer; 2024. p. 235-75.
54. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer's disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2018 Jan 1; 4: 575-90.
55. Bai R, Guo J, Ye XY, Xie Y, Xie T. Oxidative stress: The core pathogenesis and mechanism of Alzheimer’s disease. Ageing Research Reviews. 2022 May 1; 77:101619.
56. Ju Y, Tam KY. Pathological mechanisms and therapeutic strategies for Alzheimer’s disease. Neural Regeneration Research. 2022 Mar 1; 17(3): 543-9.
57. Abbas S, Latif M, Shafie N, Ghazali M, Abidin N, Mustafa M, Kormin F. A review of antioxidant and anti-acetylcholinesterase activities of Centella asiatica (L.) Urb. for the treatment of Alzheimer’s disease. Food Res. 2021 Apr; 5(2): 1-7.
58. Gray NE, Alcazar Magana A, Lak P, Wright KM, Quinn J, Stevens JF, Maier CS, Soumyanath A. Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement. Phytochemistry Reviews. 2018 Feb; 17(1): 161-94.
59. Lokanathan Y, Omar N, Puzi NN, Saim A, Idrus RH. Recent updates in neuroprotective and neuroregenerative potential of Centella asiatica. The Malaysian Journal of Medical Sciences: MJMS. 2016 Jan; 23(1): 4.