Asiatic acid: a review on its polypharmacological properties and therapeutic potential against various Maladies

Figures & data

Figure 1. Major source, chemical structure and health benefits of asiatic acid.

Table 1. Clinical studies published on asiatic acid with findings against different diseases.

Study	Compound	Disease	Findings
Kavitha et al.^[Citation27]; Thakor et al.^[Citation26] Siddique et al.^[Citation107]; Siddique et al.^[Citation108]; Hao et al.^[Citation109] Ren et al.^[Citation110] Wu et al.^[Citation111] Wu et al.^[Citation111]	Asiatic acid	Cancer	Retard the growth of cancer cell lines of glioblastoma Reduce Lower down the inflamation and pave way to natural death of cancer colon cancer cells. Lower down the expressions of PI3K/AKT/mTOR signaling Limit the growth of lung cancer cells Induce the natural death of human cancer cells
Ramchandran & Saravanan,^[Citation48] Sun et al.^[Citation46] Xue et al.^[Citation112] Chen et al.^[Citation113]	Asiatic acid	Diabetes	Increased the uptake of sugars in skeletal muscles Reduces the blood sugar levels Lower down the formation of islet fibrosis Provides the protection against diabetes induced kidney issues
Liu et al.^[Citation114] Gao et al.^[Citation115] Wu et al.^[Citation45] Si et al.^[Citation116] Huo et al.^[Citation66] Ma et al.^[Citation58] Xu et al.^[Citation69] Bunbupha et al.^[Citation117] Maneesai et al.^[Citation118] Hung et al.^[Citation53] Fong et al.^[Citation119]; Fong et al.^[Citation120]	Asiatic acid	CVD	Lower down the isoproterenol-induced cardiotoxicity. Mitigate the lactate-induced cardiomyocyte cell death. Provides the protection against hypoxia-induced cell death Protects the heart functionality, Lower down the remodeling of left ventricular and lessen the death of cardiomyocytes Lower down the expression of p38 MAPK and ERK 1/2 phosphorylation signaling pathways Provides protection against cardiac fibrosis and hypertrophy Stop the signaling of IL-1 activated NF-B Cause a reduction in oxidative stress and inflammation Improves the functionality of ventricular Decrease down the coagulatory disorders and glycative injury Provides protection to human aortic endothelial cells
Rather et al.^[Citation121] Rather et al.^[Citation121] Rather et al.^[Citation122] Cheng et al.^[Citation123] Ternchoocheep et al.^[Citation11] Umka et al.^[Citation74] Nataraj et al.^[Citation124] Ding et al.^[Citation125] Nataraj et al.^[Citation126] Gopi & Janardham^[Citation127] Park et al.^[Citation128] Loganathan and Thayumanavan^[Citation22] Ceremuga et al.^[Citation129] Wang et al.^[Citation130]	Asiatic acid	Neurological Dysfunctioning	Lower down the dysfunctioning of mitochondria and stress induced oxidation Control the amount of Alluminium, behavior performanes, AChE activity, neuroinflammation Provides protection against oxidative stress normal cell death, tau pathology and cholinergic deficits Provides protection against A 25–35 induced tau protein hyperphosphorylation Provides the protection against cholesterol cytotoxicity Prevent from the memory impairment and neurogenesis Lower down the Malondialdehyde (MDA), enhanced GSH content Provides the protection against mitochondria injury Reduction in the oxidative stress and protect mitochondrial membrane potential Enhance the signals of proteins expression involved in phosphoinotiside Provides protection against neurotoxicity and neuroinflammation Lower down the oxidative stress and provides protection from spatial memory loss Act as antidepressant and anxiety Lower down the oxidative stress and hippocampal inflammatory actions
Wei et al.^[Citation131] Fan et al.^[Citation132] Lu et al.^[Citation133]; Xu et al.^[Citation134] Kamble et al.^[Citation135]		Liver Disease	Upregulate PI3K/AKT/mTOR and Bcl-2/Bax signaling pathways Lower down the NF-B/IB and JAK1/STAT3 signaling Provides the protection to the mitochondrial functioning Acts as an organ protective agent
Dong et al.^[Citation5] Li et al.^[Citation106] Jiang et al.^[Citation105] Lee et al.^[Citation7]	Asiatic acid	Respiratory Disease	Lower down the inflammation and lung fibrosis Decreased the signaling of toll like receptor-4 pathway Takes part in the activation of Nrf2 and deter the NLRP3 inflammasome pathway Lower down inflammation mediators and induction of HO-1

Kavitha, C. V.; Jain, A. K.; Agarwal, C.; Pierce, A.; Keating, A.; Huber, K. M.; Wempe, M. F.; Agarwal, R.; Deep, G. Asiatic Acid Induces Endoplasmic Reticulum Stress and Apoptotic Death in Glioblastoma Multiforme Cells Both in vitro and in vivo. Mol. Carcinog. 2015, 54(11), 1417–1429. DOI: 10.1002/mc.22220.

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Thakor, F. K.; Wan, K.; Welsby, P. J.; Welsby, G. Pharmacological Effects of Asiatic Acid in Glioblastoma Cells Under Hypoxia. Mol. Cell. Biochem. 2017, 430(1–2), 179–190. DOI: 10.1007/s11010-017-2965-5.

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Siddique, A. I.; Mani, V.; Arivalagan, S.; Thomas, N. S.; Namasivayam, N. Asiatic Acid Attenuates Pre-Neoplastic Lesions, Oxidative Stress, Biotransforming Enzymes and Histopathological Alterations in 1,2-Dimethylhydrazine-Induced Experimental Rat Colon Carcinogenesis. Toxicol. Mech. Methods. 2017, 27(2), 136–150. DOI: 10.1080/15376516.2016.1273422.

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Siddique, A. I.; Mani, V.; Renganathan, S.; Ayyanar, R.; Nagappan, A.; Namasivayam, N. Asiatic Acid Abridges Pre-Neoplastic Lesions, Inflammation, Cell Proliferation and Induces Apoptosis in a Rat Model of Colon Carcinogenesis. Chem. Biol. Interact. 2017, 278, 197–211. DOI: 10.1016/j.cbi.2017.10.024.

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Hao, Y.; Huang, J.; Ma, Y.; Chen, W.; Fan, Q.; Sun, X.; Shao, M.; Cai, H. Asiatic Acid Inhibits Proliferation, Migration and Induces Apoptosis by Regulating Pdcd4 via the PI3K/Akt/mTOR/p70S6K Signaling Pathway in Human Colon Carcinoma Cells. Oncol. Lett. 2018, 15, 8223–8230. DOI: 10.3892/ol.2018.8417.

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Ren, L.; Cao, Q.; Zhai, F.; Yang, S.; Zhang, H. Asiatic Acid Exerts Anticancer Potential in Human Ovarian Cancer Cells via Suppression of PI3K/Akt/mTOR Signalling. Pharm. Biol. 2016, 54(11), 2377–2382. DOI: 10.3109/13880209.2016.1156709.

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Wu, T.; Geng, J.; Guo, W.; Gao, J.; Zhu, X. Asiatic Acid Inhibits Lung Cancer Cell Growth in vitro and in vivo by Destroying Mitochondria. Acta. Pharmaceutica Sinica B. 2017, 7(1), 65–72. DOI: 10.1016/j.apsb.2016.04.003.

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Ramachandran, V.; Saravanan, R. Efficacy of Asiatic Acid, a Pentacyclic Triterpene on Attenuating the Key Enzymes Activities of Carbohydrate Metabolism in Streptozotocin-Induced Diabetic Rats. Phytomed. 2013, 20(3–4), 230–236. DOI: 10.1016/j.phymed.2012.09.023.

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Sun, W.; Xu, G.; Guo, X.; Luo, G.; Wu, L.; Hou, Y.; Guo, X.; Zhou, J.; Xu, T.; Qin, L. Protective Effects of Asiatic Acid in a Spontaneous Type 2 Diabetic Mouse Model. Mol. Med. Rep. 2017, 16(2), 1333–1339. DOI: 10.3892/mmr.2017.6684.

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Xue, W.; Qian, L.; Dong-Sheng, Y.; Yu-Peng, C.; Shang, J.; Zhang, L.; Hong-Bin, S.; Jun, L. Asiatic Acid Mitigates Hyperglycemia and Reduces Islet Fibrosis in Goto-Kakizaki Rat, a Spontaneous Type 2 Diabetic Animal Model. Chin. J. Nat. Med. 2015, 13(7), 529–534. DOI: 10.1016/S1875-5364(15)30047-9.

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Chen, Y. N.; Wu, C. G.; Shi, B. M.; Qian, K.; Ding, Y. The Protective Effect of Asiatic Acid on Podocytes in the Kidney of Diabetic Rats. Am. J. Transl. Res. 2018, 10(11), 3733–3741.

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Liu, J.; Chen, L.; Lu, H. Research Article Asiatic Acid Enhances Antioxidant and Anti-Inflammatory Activity to Suppress Isoproterenol Induced Cardiotoxicity. 2018, 14(7), 1038–1045. DOI: 10.3923/ijp.2018.1038.1045.

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Gao, C.; Wang, F.; Wang, Z.; Zhang, J.; Yang, X. Asiatic Acid Inhibits Lactate-Induced Cardiomyocyte Apoptosis Through the Regulation of the Lactate Signaling Cascade. Int. J. Mol. Med. 2016, 38(6), 1823–1830. DOI: 10.3892/ijmm.2016.2783.

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Wu, K.; Hu, M.; Chen, Z.; Xiang, F.; Chen, G.; Yan, W.; Peng, Q.; Chen, X. Asiatic Acid Enhances Survival of Human AC16 Cardiomyocytes Under Hypoxia by Upregulating MiR-1290. IUBMB Life. 2017, 69(9), 660–667. DOI: 10.1002/iub.1648.

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Si, L.; Xu, J.; Yi, C.; Xu, X.; Ma, C.; Yang, J.; Wang, X. Asiatic Acid Attenuates the Progression of Left Ventricular Hypertrophy and Heart Failure Induced by Pressure Overload by Inhibiting Myocardial Remodeling in Mice. J. Cardiovasc. Pharmacol. 2015, 66(6), 558–568. DOI: 10.1097/FJC.0000000000000304.

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Huo, L.; Shi, W.; Chong, L.; Wang, J.; Zhang, K.; Li, Y. Asiatic Acid Inhibits Left Ventricular Remodeling and Improves Cardiac Function in a Rat Model of Myocardial Infarction. Exp. Ther. Med. 2016, 11(1), 57–64. DOI: 10.3892/etm.2015.2871.

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Ma, Z. G.; Dai, J.; Wei, W. Y.; Zhang, W. B.; Xu, S. C.; Liao, H. H.; Tang, Q. Z. Asiatic Acid Protects Against Cardiac Hypertrophy Through Activating AMPKα Signalling Pathway. Int. J. Bio. Sci. 2016, 12(7), 861. DOI: 10.7150/ijbs.14213.

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Xu, X.; Si, L.; Xu, J.; Yi, C.; Wang, F.; Gu, W.; Zhang, Y.; Wang, X. Asiatic Acid Inhibits Cardiac Hypertrophy by Blocking Interleukin-1β-Activated Nuclear Factor-Κb Signaling in vitro and in vivo. J. Thorac. Dis. 2015, 7(10), 1787–1797. DOI: 10.3978/j.issn.2072-1439.2015.10.41.

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Bunbupha, S.; Prachaney, P.; Kukongviriyapan, U.; Kukongviriyapan, V.; Welbat, J. U.; Pakdeechote, P. Asiatic Acid Alleviates Cardiovascular Remodelling in Rats with L-NAME-Induced Hypertension. Clin. Exp. Pharmacol. Physiol. 2015, 42(11), 1189–1197. DOI: 10.1111/1440-1681.12472.

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Maneesai, P.; Bunbupha, S.; Kukongviriyapan, U.; Prachaney, P.; Tangsucharit, P.; Kukongviriyapan, V.; Pakdeechote, P. Asiatic Acid Attenuates Renin-Angiotensin System Activation and Improves Vascular Function in High-Carbohydrate, High-Fat Diet Fed Rats.

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Hung, Y. C.; Yang, H. T.; Yin, M. C. Asiatic Acid and Maslinic Acid Protected Heart via Anti-Glycative and Anti-Coagulatory Activities in Diabetic Mice. Food Funct. 2015, 6(9), 2967–2974. DOI: 10.1039/C5FO00549C.

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Fong, L. Y.; Ng, C. T.; Cheok, Z. L.; Moklas, M. A. M.; Hakim, M. N.; Ahmad, Z. Barrier Protective Effect of Asiatic Acid in TNF-α-Induced Activation of Human Aortic Endothelial Cells. Phytomed. 2016, 23(2), 191–199. DOI: 10.1016/j.phymed.2015.11.019.

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Fong, L. Y.; Ng, C. T.; Yong, Y. K.; Hakim, M. N.; Ahmad, Z. Asiatic Acid Stabilizes Cytoskeletal Proteins and Prevents TNF--induced disorganization of cell-cell junctions in human aortic endothelial cells. Vasc. Pharmacol. 2019, 117, 15–26.

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Rather, M. A.; Thenmozhi, A. J.; Manivasagam, T.; Bharathi, M. D.; Essa, M. M.; Guillemin, G. J. Neuroprotective Role of Asiatic Acid in Aluminium Chloride Induced Rat Model of Alzheimer’s Disease. Front. Biosci (Schol. Ed.). 2018, 10(1), 262–275. DOI: 10.2741/s514.

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Rather, M. A.; Justin-Thenmozhi, A.; Manivasagam, T.; Saravanababu, C.; Guillemin, G. J.; Essa, M. M. Asiatic Acid Attenuated Aluminum Chloride-Induced Tau Pathology, Oxidative Stress and Apoptosis via AKT/GSK-3β Signaling Pathway in Wistar Rats. Neurotox. Res. 2019, 35(4), 955–968. DOI: 10.1007/s12640-019-9999-2.

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Cheng, W.; Chen, W.; Wang, P.; Chu, J. Asiatic Acid Protects Differentiated PC12 Cells from a 25–35-Induced Apoptosis and Tauhyperphosphorylation via Regulating PI3K/Akt/GSK-3 Signaling. Life. sci. 2018, 208, 96–101. DOI: 10.1016/j.lfs.2018.07.016.

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Ternchoocheep, K.; Surangkul, D. The Recovery and Protective Effects of Asiatic Acid on Differentiated Human Neuroblastoma SH-SY5Y Cells Cytotoxic-Induced by Cholesterol. Asian Pac. J. 2017, 7(5), 416–420. DOI: 10.1016/j.apjtb.2017.01.012.

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Umka Welbat, J.; Sirichoat, A.; Chaijaroonkhanarak, W.; Prachaney, P.; Pannangrong, W.; Pakdeechote, P.; Sripanidkulchai, B.; Wigmore, P. Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival. Nutrients. 2016, 8(5), 303. DOI: 10.3390/nu8050303.

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Nataraj, J.; Manivasagam, T.; Justin Thenmozhi, A.; Essa, M. M. Neuroprotective Effect of Asiatic Acid on Rotenone-Induced Mitochondrial Dysfunction and Oxidative Stress-Mediated Apoptosis in Differentiated SH-SYS5Y Cells. Nutr. Neurosci. 2017, 20(6), 351–359. DOI: 10.1080/1028415X.2015.1135559.

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Ding, H.; Xiong, Y.; Sun, J.; Chen, C.; Gao, J.; Xu, H. Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of Synuclein into Mitochondria. Front. Neurosci. 2018, 12, 431. DOI: 10.3389/fnins.2018.00431.

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Nataraj, J.; Manivasagam, T.; Thenmozhi, A. J.; Essa, M. M. Neurotrophic Effect of Asiatic Acid, a Triterpene of Centella Asiatica Against Chronic 1-Methyl 4-Phenyl 1, 2, 3, 6-Tetrahydropyridine Hydrochloride/Probenecid Mouse Model of Parkinson’s Disease: The Role of MAPK, Pi3K-Akt-GSK3β and mTOR Signalling Pathways. Neurochem. Res. 2017, 42(5), 1354–1365. DOI: 10.1007/s11064-017-2183-2.

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Gopi, M.; Janardhanam, V. A. Asiaticoside: Attenuation of Rotenone Induced Oxidative Burden in a Rat Model of Hemiparkinsonism by Maintaining the Phosphoinositide-Mediated Synaptic Integrity. Pharmacol. Biochem. Behav. 2017, 155, 1–15. DOI: 10.1016/j.pbb.2017.02.005.

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Park, J. H.; Seo, Y. H.; Jang, J. H.; Jeong, C. H.; Lee, S.; Park, B. Asiatic Acid Attenuates Methamphetamine-Induced Neuroinflammation and Neurotoxicity Through Blocking of NF-Kb/STAT3/ERK/STAT3/ERK and Mitochondria-Mediated Apoptosis Pathway. J. Neuroinflammation. 2017, 14(1), 1–15. DOI: 10.1186/s12974-017-1009-0.

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Loganathan, C.; Thayumanavan, P. AA Prevents the Quinolinic Acid-Induced Oxidative Stress and Cognitive Impairment. Metab. Brain Dis. 2018, 33(1), 151–159. DOI: 10.1007/s11011-017-0143-9.

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Ceremuga, T. E.; Valdivieso, D.; Kenner, C.; Lucia, A.; Lathrop, K.; Stailey, O.; Bailey, H.; Criss, J.; Linton, J.; Fried, J. Evaluation of the Anxiolytic and Antidepressant Effects of Asiatic Acid, a Compound from Gotu Kola or Centella Asiatica, in the Male Sprague Dawley Rat. Aana J. 2015, 83(2), 91–98.

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Wang, Z.; Mong, M.; Yang, Y.; Yin, M. Asiatic Acid and Maslinic Acid Attenuated Kainic Acid-Induced Seizure Through Decreasing Hippocampal Inflammatory and Oxidative Stress. Epilepsy Res. 2018, 139, 28–34. DOI: 10.1016/j.eplepsyres.2017.11.003.

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Wei, L.; Chen, Q.; Guo, A.; Fan, J.; Wang, R.; Zhang, H. Asiatic Acid Attenuates CCl4-Induced Liver Fibrosis in Rats by Regulating the PI3K/AKT/mTOR and Bcl-2/bax Signaling Pathways. Int. Immunopharmacol. 2018, 60, 1–8. DOI: 10.1016/j.intimp.2018.04.016.

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Fan, J.; Chen, Q.; Wei, L.; Zhou, X.; Wang, R.; Zhang, H. Asiatic Acid Ameliorates CCl4-Induced Liver Fibrosis in Rats: Involvement of Nrf2/ARE, NF-kappaB/ikappabalpha, and JAK1/STAT3 Signaling Pathways. Drug Des. Dev. Ther. 2018, 12, 3595–3605. DOI: 10.2147/DDDT.S179876.

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Lu, Y.; Liu, S.; Wang, Y.; Wang, D.; Gao, J.; Zhu, L. Asiatic Acid Uncouples Respiration in Isolated Mouse Liver Mitochondria and Induces HepG2 Cells Death. Eur. J. Pharmacol. 2016, 786, 212–223. DOI: 10.1016/j.ejphar.2016.06.010.

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Xu, Y.; Yao, J.; Zou, C.; Zhang, H.; Zhang, S.; Liu, J.; Ma, G.; Jiang, P.; Zhang, W. Asiatic Acid Protects Against Hepatic Ischemia/Reperfusion Injury by Inactivation of Kupffer Cells via PPARγ/NLRP3 Inflammasome Signaling Pathway. Oncotarget. 2017, 8(49), 86339–86355. DOI: 10.18632/oncotarget.21151.

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Kamble, S. M.; Patil, C. R. Asiatic Acid Ameliorates Doxorubicin-Induced Cardiac and Hepato-Renal Toxicities with Nrf2 Transcriptional Factor Activation in Rats. Cardiovasc. Toxicol. 2018, 18(2), 131–141. DOI: 10.1007/s12012-017-9424-0.

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Dong, S. H.; Liu, Y. W.; Wei, F.; Tan, H. Z.; Han, Z. D. Asiatic Acid Ameliorates Pulmonary Fibrosis Induced by Bleomycin (BLM) via Suppressing Pro-Fibrotic and Inflammatory Signaling Pathways. Biomed. Pharmacother. 2017, 89, 1297–1309. DOI: 10.1016/j.biopha.2017.03.005.

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Li, Z.; Xiao, X.; Yang, M. Asiatic Acid Inhibits Lipopolysaccharide-Induced Acute Lung Injury in Mice. Inflammation. 2016, 39(5), 1642–1648. DOI: 10.1007/s10753-016-0398-z.

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Jiang, W.; Li, M.; He, F.; Yao, W.; Bian, Z.; Wang, X.; Zhu, L. Protective Effects of Asiatic Acid Against Spinal Cord Injury-Induced Acute Lung Injury in Rats. Inflammation. 2016, 39(6), 1853–1861. DOI: 10.1007/s10753-016-0414-3.

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Lee, J.; Park, H.; Kwon, O.; Jang, Y. G.; Kim, J. Y.; Choi, B. K.; Lee, H. J.; Lee, S.; Paik, J. H.; Oh, S. R., et al. Asiatic Acid Inhibits Pulmonary Inflammation Induced by Cigarette Smoke. Int. Immunopharmacol. 2016, 39, 208–217. DOI: 10.1016/j.intimp.2016.07.010.

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