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Planta Med 2019; 85(16): 1203-1215
DOI: 10.1055/a-1008-6138
Biological and Pharmacological Activity
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Cardiovascular Protective Effects of Centella asiatica and Its Triterpenes: A Review

Nur Nadia Mohd Razali
1   Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia
,
Chin Theng Ng
2   Physiology Unit, Faculty of Medicine, AIMST University, Bedong, Kedah, Malaysia
,
Lai Yen Fong
1   Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang, Selangor, Malaysia
› Author Affiliations
Further Information

Publication History

received 01 April 2019
revised 09 August 2019

accepted 30 August 2019

Publication Date:
20 September 2019 (online)

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Abstract

Centella asiatica, a triterpene-rich medicinal herb, is traditionally used to treat various types of diseases including neurological, dermatological, and metabolic diseases. A few articles have previously reviewed a broad range of pharmacological activities of C. asiatica, but none of these reviews focuses on the use of C. asiatica in cardiovascular diseases. This review aims to summarize recent findings on protective effects of C. asiatica and its active constituents (asiatic acid, asiaticoside, madecassic acid, and madecassoside) in cardiovascular diseases. In addition, their beneficial effects on conditions associated with cardiovascular diseases were also reviewed. Articles were retrieved from electronic databases such as PubMed and Google Scholar using keywords “Centella asiatica,” “asiatic acid,” “asiaticoside,” “madecassic acid,” and “madecassoside.” The articles published between 2004 and 2018 that are related to the aforementioned topics were selected. A few clinical studies published beyond this period were also included. The results showed that C. asiatica and its active compounds possess potential therapeutic effects in cardiovascular diseases and cardiovascular disease-related conditions, as evidenced by numerous in silico, in vitro, in vivo, and clinical studies. C. asiatica and its triterpenes have been reported to exhibit cardioprotective, anti-atherosclerotic, antihypertensive, antihyperlipidemic, antidiabetic, antioxidant, and anti-inflammatory activities. In conclusion, more clinical and pharmacokinetic studies are needed to support the use of C. asiatica and its triterpenes as therapeutic agents for cardiovascular diseases. Besides, elucidation of the molecular pathways modulated by C. asiatica and its active constituents will help to understand the mechanisms underlying the cardioprotective action of C. asiatica.

Key words

Centella asiatica - Apiaceae - asiatic acid - asiaticoside - madecassic acid - madecassoside - cardiovascular protective effect
 

  • References

  • 1 Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79: 629-661
    CrossrefPubMedGoogle Scholar
  • 2 CABI. Centella asiatica [original text by Chris Parker]. In: Invasive Species Compendium. 2019. .Available at https://www.cabi.org/isc/datasheet/12048 Accessed September 13
    Google Scholar
  • 3 Chandrika UG, Prasad Kumarab PA. Gotu Kola (Centella asiatica): nutritional properties and plausible health benefits. Adv Food Nutr Res 2015; 76: 125-157
    PubMedGoogle Scholar
  • 4 Gohil KJ, Patel JA, Gajjar AK. Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian J Pharm Sci 2010; 72: 546-556
    CrossrefPubMedGoogle Scholar
  • 5 Joshi K, Chaturvedi P. Therapeutic efficiency of Centella asiatica (L.) Urb. An underutilized green leafy vegetable: an overview. Int J Pharma Bio Sci 2013; 4: 135-149
    PubMedGoogle Scholar
  • 6 Tee ES, Mohd Idris N, Mohd Nasir A, Khatijah I. Nutrient Composition of Malaysian Food. In: Tee ES, Mohd Idris N, Mohd Nasir A, Khatijah I. Malaysian Food Composition Database Programme. 4th ed. Kuala Lumpur: Institute of Medical Research; 1997: 16
    Google Scholar
  • 7 Cox DN, Rajasuriya SV, Soysa PE, Gladwin J, Ashworth A. Problems encountered in the community-based production of leaf concentrate as a supplement for pre-school children in Sri Lanka. Int J Food Sci Nutr 1993; 44: 123-132
    CrossrefPubMedGoogle Scholar
  • 8 Shinomol GK, Muralidhara. Bharath MM. Exploring the role of “Brahmi” (Bacopa monnieri and Centella asiatica) in brain function and therapy. Recent Pat Endocr Metab Immune Drug Discov 2011; 5: 33-49
    CrossrefPubMedGoogle Scholar
  • 9 Hamidpour R, Hamidpour S, Hamidpour M, Zarabi M, Sohraby M, Hamidpour R. Medicinal property of Gotu kola (Centella asiatica) from the selection of traditional applications to the novel phytotherapy. Arch Cancer Res 2015; 3: 1-7
    CrossrefPubMedGoogle Scholar
  • 10 Saini S, Dhiman A, Nanda S. Traditional indian medicinal plants with potential wound healing activity: a review. Int J Pharm Sci Res 2016; 7: 1809-1819
    PubMedGoogle Scholar
  • 11 Singh B, Rastogi R. A reinvestigation of the triterpenes of Centella asiatica . Phytochem 1969; 8: 917-921
    CrossrefPubMedGoogle Scholar
  • 12 Bylka W, Znajdek-Awizen P, Studzinska-Sroka E, Danczak-Pazdrowska A, Brzezinska M. Centella asiatica in dermatology: an overview. Phytother Res 2014; 28: 1117-1124
    CrossrefPubMedGoogle Scholar
  • 13 James JT, Dubery IA. Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules 2009; 14: 3922-3941
    CrossrefPubMedGoogle Scholar
  • 14 Anukunwithaya T, Tantisira MH, Tantisira B, Khemawoot P. Pharmacokinetics of a standardized extract of Centella asiatica ECa 233 in rats. Planta Med 2017; 83: 710-717
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Cotellese R, Hu S, Belcaro G, Ledda A, Feragalli B, Dugall M, Hosoi M, Ippolito E. Centella asiatica (Centellicum®) facilitates the regular healing of surgical scars in subjects at high risk of keloids. Minerva Chir 2018; 73: 151-156
    PubMedGoogle Scholar
  • 16 Srivastava R, Shukla YN, Kumar S. Chemistry and pharmacology of Centella asiatica: a review. J Med Arom Plant Sci 1997; 19: 1049-1056
    PubMedGoogle Scholar
  • 17 Hashim P, Sidek H, Helan MH, Sabery A, Palanisamy UD, Ilham M. Triterpene composition and bioactivities of Centella asiatica . Molecules 2011; 16: 1310-1322
    CrossrefPubMedGoogle Scholar
  • 18 Sawatdee S, Choochuay K, Chanthorn W, Srichana T. Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats. Acta Pharm 2016; 66: 233-244
    CrossrefPubMedGoogle Scholar
  • 19 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. Oxid Med Cell Longev 2017; 2017: 7023091
    PubMedGoogle Scholar
  • 20 Ariffin F, Heong Chew S, Bhupinder K, Karim AA, Huda N. Antioxidant capacity and phenolic composition of fermented Centella asiatica herbal teas. J Sci Food Agric 2011; 91: 2731-2739
    CrossrefPubMedGoogle Scholar
  • 21 Cao SY, Wang W, Nan FF, Liu YN, Wei SY, Li FF, Chen L. Asiatic acid inhibits LPS-induced inflammatory response in endometrial epithelial cells. Microb Pathog 2018; 116: 195-199
    CrossrefPubMedGoogle Scholar
  • 22 World Health Organization. Cardiovascular diseases (CVDs) fact sheet. Available at: https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) Accessed January 3, 2019
    PubMedGoogle Scholar
  • 23 Department of Statistics Malaysia. Statistics on Causes of Death, Malaysia, 2018. Available at: https://www.dosm.gov.my/v1/index.php?r=column/pdfPrev&id=aWg2VjJkZHhYcDdEM3JQSGloeTVlZz09 Accessed December 3, 2018
    PubMedGoogle Scholar
  • 24 McMahan CA, Gidding SS, McGill jr. HC. Coronary heart disease risk factors and atherosclerosis in young people. J Clin Lipidol 2008; 2: 118-126
    CrossrefPubMedGoogle Scholar
  • 25 Farooqui AA, Farooqui T, Madan A, Ong JH, Ong WY. Ayurvedic medicine for the treatment of dementia: mechanistic aspects. Evid Based Complement Alternat Med 2018; 2018: 2481076
    PubMedGoogle Scholar
  • 26 Lv J, Sharma A, Zhang T, Wu Y, Ding X. Pharmacological review on asiatic acid and its derivatives: a potential compound. SLAS Technol 2018; 23: 111-127
    PubMedGoogle Scholar
  • 27 Lokanathan Y, Omar N, Ahmad Puzi NN, Saim A, Hj Idrus R. Recent updates in neuroprotective and neuroregenerative potential of Centella asiatica . Malays J Med Sci 2016; 23: 4-14
    PubMedGoogle Scholar
  • 28 Heineke J, Molkentin JD. Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 2006; 7: 589-600
    CrossrefPubMedGoogle Scholar
  • 29 Tham YK, Bernardo BC, Ooi JY, Weeks KL, McMullen JR. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets. Arch Toxicol 2015; 89: 1401-1438
    CrossrefPubMedGoogle Scholar
  • 30 Huang Y, Wu D, Zhang X, Jiang M, Hu C, Lin J, Tang J, Wu L. Cardiac-specific Traf2 overexpression enhances cardiac hypertrophy through activating AKT/GSK3β signaling. Gene 2014; 536: 225-231
    CrossrefPubMedGoogle Scholar
  • 31 Huang X, Zuo L, Lv Y, Chen C, Yang Y, Xin H, Li Y, Qian Y. Asiatic acid attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3β/HIF-1α signaling in rat H9c2 cardiomyocytes. Molecules 2016; 21: pii:E1248
    CrossrefPubMedGoogle Scholar
  • 32 Ma ZG, Dai J, Wei WY, Zhang WB, Xu SC, Liao HH, Yang Z, Tang QZ. Asiatic acid protects against cardiac hypertrophy through activating AMPKα signalling pathway. Int J Biol Sci 2016; 12: 861-871
    CrossrefPubMedGoogle Scholar
  • 33 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: 1787-1797
    PubMedGoogle Scholar
  • 34 Si L, Xu J, Yi C, Xu X, Wang F, Gu W, Zhang Y, Wang X. Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo . Int J Mol Med 2014; 34: 499-506
    CrossrefPubMedGoogle Scholar
  • 35 Gnanapragasam A, Ebenezar KK, Sathish V, Govindaraju P, Devaki T. Protective effect of Centella asiatica on antioxidant tissue defense system against adriamycin induced cardiomyopathy in rats. Life Sci 2004; 76: 585-597
    CrossrefPubMedGoogle Scholar
  • 36 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: 57-64
    CrossrefPubMedGoogle Scholar
  • 37 Bian GX, Li GG, Yang Y, Liu RT, Ren JP, Wen LQ, Guo SM, Lu QJ. Madecassoside reduces ischemia-reperfusion injury on regional ischemia induced heart infarction in rat. Biol Pharm Bull 2008; 31: 458-463
    CrossrefPubMedGoogle Scholar
  • 38 Cao W, Li XQ, Zhang XN, Hou Y, Zeng AG, Xie YH, Wang SW. Madecassoside suppresses LPS-induced TNF-α production in cardiomyocytes through inhibition of ERK, p38, and NF-κB activity. Int Immunopharmacol 2010; 10: 723-729
    CrossrefPubMedGoogle Scholar
  • 39 Shrivastava AK, Singh HV, Raizada A, Singh SK. C-reactive protein, inflammation and coronary heart disease. Egypt Heart J 2015; 67: 89-97
    PubMedGoogle Scholar
  • 40 Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, Rhee JS, Silverstein R, Hoff HF, Freeman MW. Scavenger receptors class A–I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem 2002; 277: 49982-49988
    CrossrefPubMedGoogle Scholar
  • 41 Satake T, Kamiya K, An Y, Oishi Nee Taka T, Yamamoto J. The anti-thrombotic active constituents from Centella asiatica . Biol Pharm Bull 2007; 30: 935-940
    CrossrefPubMedGoogle Scholar
  • 42 Belcaro G, Cornelli U. Variations in echogenicity in carotid and femoral atherosclerotic plaques with Pycnogenol + Centella asiatica supplementation. Int J Angiol 2017; 26: 95-101
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Belcaro G, Dugall M, Hosoi M, Ippolito E, Cesarone M, Luzzi R, Cornelli U, Ledda A. Pycnogenol® and Centella asiatica for asymptomatic atherosclerosis progression. Int Angiol 2014; 33: 20-26
    PubMedGoogle Scholar
  • 44 Belcaro G, Ippolito E, Dugall M, Hosoi M, Cornelli U, Ledda A, Scoccianti M, Steigerwalt RD, Cesarone MR, Pellegrini L, Luzzi R, Corsi M. Pycnogenol® and Centella asiatica in the management of asymptomatic atherosclerosis progression. Int Angiol 2015; 34: 150-157
    PubMedGoogle Scholar
  • 45 Whelton PK, Carey RM, Aronow WS, Casey jr. DE, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith jr. SC, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams sr. KA, Williamson JD, Wright jr. JT. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Hypertension 2018; 71: 1269-1324
    CrossrefPubMedGoogle Scholar
  • 46 Kannel WB, Dawber TR, Kagan A, Revotskie N, Stokes 3rd J. Factors of risk in the development of coronary heart disease-six year follow-up experience. The Framingham Study. Ann Intern Med 1961; 55: 33-50
    PubMedGoogle Scholar
  • 47 Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387: 957-967
    CrossrefPubMedGoogle Scholar
  • 48 Saxena T, Ali AO, Saxena M. Pathophysiology of essential hypertension: an update. Expert Rev Cardiovasc Ther 2018; 16: 879-887
    CrossrefPubMedGoogle Scholar
  • 49 Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Oshima T, Chayama K. Endothelial function and oxidative stress in renovascular hypertension. N Engl J Med 2002; 346: 1954-1962
    CrossrefPubMedGoogle Scholar
  • 50 Maneesai P, Bunbupha S, Kukongviriyapan U, Senggunprai L, Kukongviriyapan V, Prachaney P, Pakdeechote P. Effect of asiatic acid on the Ang II-AT1R-NADPH oxidase-NF-κB pathway in renovascular hypertensive rats. Naunyn Schmiedebergs Arch Pharmacol 2017; 390: 1073-1083
    CrossrefPubMedGoogle Scholar
  • 51 Bunbupha S, Pakdeechote P, Kukongviriyapan U, Prachaney P, Kukongviriyapan V. Asiatic acid reduces blood pressure by enhancing nitric oxide bioavailability with modulation of eNOS and p47phox expression in L-NAME-induced hypertensive rats. Phytother Res 2014; 28: 1506-1512
    CrossrefPubMedGoogle Scholar
  • 52 Pakdeechote P, Bunbupha S, Kukongviriyapan U, Prachaney P, Khrisanapant W, Kukongviriyapan V. Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats. Nutrients 2014; 6: 355-370
    CrossrefPubMedGoogle Scholar
  • 53 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. BMC Complement Altern Med 2016; 16: 123
    CrossrefPubMedGoogle Scholar
  • 54 Wang XB, Wang W, Zhu XC, Ye WJ, Cai H, Wu PL, Huang XY, Wang LX. The potential of asiaticoside for TGF-β1/Smad signaling inhibition in prevention and progression of hypoxia-induced pulmonary hypertension. Life Sci 2015; 137: 56-64
    CrossrefPubMedGoogle Scholar
  • 55 Wang X, Cai X, Wang W, Jin Y, Chen M, Huang X, Zhu X, Wang L. Effect of asiaticoside on endothelial cells in hypoxia-induced pulmonary hypertension. Mol Med Rep 2018; 17: 2893-2900
    PubMedGoogle Scholar
  • 56 Belcaro GV, Rulo A, Grimaldi R. Capillary filtration and ankle edema in patients with venous hypertension treated with TTFCA. Angiology 1990; 41: 12-18
    CrossrefPubMedGoogle Scholar
  • 57 Belcaro GV, Grimaldi R, Guidi G. Improvement of capillary permeability in patients with venous hypertension after treatment with TTFCA. Angiology 1990; 41: 533-540
    CrossrefPubMedGoogle Scholar
  • 58 Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013; 40: 195-211
    CrossrefPubMedGoogle Scholar
  • 59 Stancu CS, Toma L, Sima AV. Dual role of lipoproteins in endothelial cell dysfunction in atherosclerosis. Cell Tissue Res 2012; 349: 433-446
    CrossrefPubMedGoogle Scholar
  • 60 Boulanger CM, Tanner FC, Bea ML, Hahn AW, Werner A, Luscher TF. Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. Circ Res 1992; 70: 1191-1197
    CrossrefPubMedGoogle Scholar
  • 61 Estrada-Luna D, Ortiz-Rodriguez MA, Medina-Briseno L, Carreon-Torres E, Izquierdo-Vega JA, Sharma A, Cancino-Diaz JC, Perez-Mendez O, Belefant-Miller H, Betanzos-Cabrera G. Current therapies focused on high-density lipoproteins associated with cardiovascular disease. Molecules 2018; 23: 2730
    CrossrefPubMedGoogle Scholar
  • 62 Anderson TJ, Gregoire J, Hegele RA, Couture P, Mancini GB, McPherson R, Francis GA, Poirier P, Lau DC, Grover S, Genest jr. J, Carpentier AC, Dufour R, Gupta M, Ward R, Leiter LA, Lonn E, Ng DS, Pearson GJ, Yates GM, Stone JA, Ur E. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013; 29: 151-167
    CrossrefPubMedGoogle Scholar
  • 63 Kumari S, Deori M, Elancheran R, Kotoky J, Devi R. In vitro and in vivo antioxidant, anti-hyperlipidemic properties and chemical characterization of Centella asiatica (L.) extract. Front Pharmacol 2016; 7: 400
    PubMedGoogle Scholar
  • 64 Zhao Y, Shu P, Zhang Y, Lin L, Zhou H, Xu Z, Suo D, Xie A, Jin X. Effect of Centella asiatica on oxidative stress and lipid metabolism in hyperlipidemic animal models. Oxid Med Cell Longev 2014; 2014: 154295
    PubMedGoogle Scholar
  • 65 Oyenihi AB, Chegou NN, Oguntibeju OO, Masola B. Centella asiatica enhances hepatic antioxidant status and regulates hepatic inflammatory cytokines in type 2 diabetic rats. Pharm Biol 2017; 55: 1671-1678
    CrossrefPubMedGoogle Scholar
  • 66 Gao L, Lin Z, Liu Y, Wang X, Wan L, Zhang L, Liu X. Hypolipidemic effect of Fragarianilgerrensis Schlecht. medicine compound on hyperlipidemic rats. Lipids Health Dis 2018; 17: 222
    CrossrefPubMedGoogle Scholar
  • 67 Ramachandran V, Saravanan R, Senthilraja P. Antidiabetic and antihyperlipidemic activity of asiatic acid in diabetic rats, role of HMG CoA: in vivo and in silico approaches. Phytomedicine 2014; 21: 225-232
    CrossrefPubMedGoogle Scholar
  • 68 Rameshreddy P, Uddandrao VVS, Brahmanaidu P, Vadivukkarasi S, Ravindarnaik R, Suresh P, Swapna K, Kalaivani A, Parvathi P, Tamilmani P, Saravanan G. Obesity-alleviating potential of asiatic acid and its effects on ACC1, UCP2, and CPT1 mRNA expression in high fat diet-induced obese Sprague-Dawley rats. Mol Cell Biochem 2018; 442: 143-154
    CrossrefPubMedGoogle Scholar
  • 69 Larsson SC, Wallin A, Hakansson N, Stackelberg O, Back M, Wolk A. Type 1 and type 2 diabetes mellitus and incidence of seven cardiovascular diseases. Int J Cardiol 2018; 262: 66-70
    CrossrefPubMedGoogle Scholar
  • 70 Nicholls SJ, Tuzcu EM, Kalidindi S, Wolski K, Moon KW, Sipahi I, Schoenhagen P, Nissen SE. Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol 2008; 52: 255-262
    CrossrefPubMedGoogle Scholar
  • 71 Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus – mechanisms, management, and clinical considerations. Circulation 2016; 133: 2459-2502
    CrossrefPubMedGoogle Scholar
  • 72 Kabir AU, Samad MB, DʼCosta NM, Akhter F, Ahmed A, Hannan JM. Anti-hyperglycemic activity of Centella asiatica is partly mediated by carbohydrase inhibition and glucose-fiber binding. BMC Complement Altern Med 2014; 14: 31
    CrossrefPubMedGoogle Scholar
  • 73 Wang X, Lu Q, Yu DS, Chen YP, Shang J, Zhang LY, Sun HB, Liu J. 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: 529-534
    PubMedGoogle Scholar
  • 74 Chen YN, Wu CG, Shi BM, Qian K, Ding Y. The protective effect of asiatic acid on podocytes in the kidney of diabetic rats. Am J Transl Res 2018; 10: 3733-3741
    PubMedGoogle Scholar
  • 75 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. Phytomedicine 2013; 20: 230-236
    CrossrefPubMedGoogle Scholar
  • 76 Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J 2012; 5: 9-19
    CrossrefPubMedGoogle Scholar
  • 77 Chen X, Andresen BT, Hill M, Zhang J, Booth F, Zhang C. Role of reactive oxygen species in tumor necrosis factor-alpha induced endothelial dysfunction. Curr Hypertens Rev 2008; 4: 245-255
    CrossrefPubMedGoogle Scholar
  • 78 Dikalov S, Griendling KK, Harrison DG. Measurement of reactive oxygen species in cardiovascular studies. Hypertension 2007; 49: 717-727
    CrossrefPubMedGoogle Scholar
  • 79 Gupta S, Prakash J. Studies on Indian green leafy vegetables for their antioxidant activity. Plant Foods Hum Nutr 2009; 64: 39-45
    CrossrefPubMedGoogle Scholar
  • 80 Pittella F, Dutra RC, Junior DD, Lopes MT, Barbosa NR. Antioxidant and cytotoxic activities of Centella asiatica (L) Urb. Int J Mol Sci 2009; 10: 3713-3721
    CrossrefPubMedGoogle Scholar
  • 81 Bajpai M, Pande A, Tewari SK, Prakash D. Phenolic contents and antioxidant activity of some food and medicinal plants. Int J Food Sci Nutr 2005; 56: 287-291
    CrossrefPubMedGoogle Scholar
  • 82 Bian D, Liu M, Li Y, Xia Y, Gong Z, Dai Y. Madecassoside, a triterpenoid saponin isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress. J Biochem Mol Toxicol 2012; 26: 399-406
    CrossrefPubMedGoogle Scholar
  • 83 Arora R, Kumar R, Agarwal A, Reeta KH, Gupta YK. Comparison of three different extracts of Centella asiatica for anti-amnesic, antioxidant and anticholinergic activities: in vitro and in vivo study. Biomed Pharmacother 2018; 105: 1344-1352
    CrossrefPubMedGoogle Scholar
  • 84 Golia E, Limongelli G, Natale F, Fimiani F, Maddaloni V, Pariggiano I, Bianchi R, Crisci M, DʼAcierno L, Giordano R, Di Palma G, Conte M, Golino P, Russo MG, Calabro R, Calabro P. Inflammation and cardiovascular disease: from pathogenesis to therapeutic target. Curr Atheroscler Rep 2014; 16: 435
    CrossrefPubMedGoogle Scholar
  • 85 Molteni M, Gemma S, Rossetti C. The role of toll-like receptor 4 in infectious and noninfectious inflammation. Mediators Inflamm 2016; 2016: 6978936
    PubMedGoogle Scholar
  • 86 George M, Joseph L. Anti-allergic, anti-pruritic, and anti-inflammatory activities of Centella asiatica extracts. Afr J Tradit Complement Altern Med 2009; 6: 554-559
    PubMedGoogle Scholar
  • 87 Saha S, Guria T, Singha T, Maity TK. Evaluation of analgesic and anti-inflammatory activity of chloroform and methanol extracts of Centella asiatica Linn. ISRN Pharmacol 2013; 2013: 789613
    PubMedGoogle Scholar
  • 88 Huang SS, Chiu CS, Chen HJ, Hou WC, Sheu MJ, Lin YC, Shie PH, Huang GJ. Antinociceptive activities and the mechanisms of anti-inflammation of asiatic acid in mice. Evid Based Complement Alternat Med 2011; 2011: 895857
    PubMedGoogle Scholar
  • 89 Yang C, Guo Y, Huang TS, Zhao J, Huang XJ, Tang HX, An N, Pan Q, Xu YZ, Liu HF. Asiatic acid protects against cisplatin-induced acute kidney injury via anti-apoptosis and anti-inflammation. Biomed Pharmacother 2018; 107: 1354-1362
    CrossrefPubMedGoogle Scholar
  • 90 Branen L, Hovgaard L, Nitulescu M, Bengtsson E, Nilsson J, Jovinge S. Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 2004; 24: 2137-2142
    CrossrefPubMedGoogle Scholar
  • 91 Tay C, Liu YH, Hosseini H, Kanellakis P, Cao A, Peter K, Tipping P, Bobik A, Toh BH, Kyaw T. B-cell-specific depletion of tumour necrosis factor alpha inhibits atherosclerosis development and plaque vulnerability to rupture by reducing cell death and inflammation. Cardiovasc Res 2016; 111: 385-397
    CrossrefPubMedGoogle Scholar
  • 92 Ohta H, Wada H, Niwa T, Kirii H, Iwamoto N, Fujii H, Saito K, Sekikawa K, Seishima M. Disruption of tumor necrosis factor-α gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis 2005; 180: 11-17
    CrossrefPubMedGoogle Scholar
  • 93 Boesten LS, Zadelaar AS, van Nieuwkoop A, Gijbels MJ, de Winther MP, Havekes LM, van Vlijmen BJ. Tumor necrosis factor-α promotes atherosclerotic lesion progression in APOE*3-Leiden transgenic mice. Cardiovasc Res 2005; 66: 179-185
    CrossrefPubMedGoogle Scholar
  • 94 Jeng JR, Chang CH, Shieh SM, Chiu HC. Oxidized low-density lipoprotein enhances monocyte-endothelial cell binding against shear-stress-induced detachment. Biochim Biophys Acta 1993; 1178: 221-227
    CrossrefPubMedGoogle Scholar
  • 95 Pirillo A, Norata GD, Catapano AL. LOX-1, OxLDL, and atherosclerosis. Mediators Inflamm 2013; 2013: 152786
    PubMedGoogle Scholar
  • 96 Guo F, Zhou Z, Dou Y, Tang J, Gao C, Huan J. GEF-H1/RhoA signalling pathway mediates lipopolysaccharide-induced intercellular adhesion molecular-1 expression in endothelial cells via activation of p38 and NF-κB. Cytokine 2012; 57: 417-428
    CrossrefPubMedGoogle Scholar
  • 97 Di Tomo P, Di Silvestre S, Cordone VG, Giardinelli A, Faricelli B, Pipino C, Lanuti P, Peng T, Formoso G, Yang D, Arduini A, Chiarelli F, Pandolfi A, Di Pietro N. Centella asiatica and lipoic acid, or a combination thereof, inhibit monocyte adhesion to endothelial cells from umbilical cords of gestational diabetic women. Nutr Metab Cardiovasc Dis 2015; 25: 659-666
    CrossrefPubMedGoogle Scholar
  • 98 Fong LY, Ng CT, Zakaria ZA, Baharuldin MT, Arifah AK, Hakim MN, Zuraini A. Asiaticoside inhibits TNF-α-induced endothelial hyperpermeability of human aortic endothelial cells. Phytother Res 2015; 29: 1501-1508
    CrossrefPubMedGoogle Scholar
  • 99 Fong LY, Ng CT, Cheok ZL, Mohd Moklas MA, Hakim MN, Ahmad Z. Barrier protective effect of asiatic acid in TNF-α-induced activation of human aortic endothelial cells. Phytomedicine 2016; 23: 191-199
    CrossrefPubMedGoogle Scholar
  • 100 Fong LY, Ng CT, Yong YK, Hakim MN, Ahmad Z. Asiatic acid stabilizes cytoskeletal proteins and prevents TNF-α-induced disorganization of cell-cell junctions in human aortic endothelial cells. Vascul Pharmacol 2019; 117: 15-26
    CrossrefPubMedGoogle Scholar
  • 101 Jing L, Haitao W, Qiong W, Fu Z, Nan Z, Xuezheng Z. Anti inflammatory effect of asiaticoside on human umbilical vein endothelial cells induced by ox-LDL. Cytotechnology 2018; 70: 855-864
    CrossrefPubMedGoogle Scholar
  • 102 Nhiem NX, Tai BH, Quang TH, Kiem PV, Minh CV, Nam NH, Kim JH, Im LR, Lee YM, Kim YH. A new ursane-type triterpenoid glycoside from Centella asiatica leaves modulates the production of nitric oxide and secretion of TNF-α in activated RAW 264.7 cells. Bioorg Med Chem Lett 2011; 21: 1777-1781
    CrossrefPubMedGoogle Scholar
  • 103 Yun KJ, Kim JY, Kim JB, Lee KW, Jeong SY, Park HJ, Jung HJ, Cho YW, Yun K, Lee KT. Inhibition of LPS-induced NO and PGE2 production by asiatic acid via NF-κB inactivation in RAW 264.7 macrophages: Possible involvement of the IKK and MAPK pathways. Int Immunopharmacol 2008; 8: 431-441
    CrossrefPubMedGoogle Scholar
  • 104 Won JH, Shin JS, Park HJ, Jung HJ, Koh DJ, Jo BG, Lee JY, Yun K, Lee KT. Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Med 2010; 76: 251-257
    Article in Thieme ConnectPubMedGoogle Scholar