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Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement

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Abstract

This review describes in detail the phytochemistry and neurological effects of the medicinal herb Centella asiatica (L.) Urban. C. asiatica is a small perennial plant that grows in moist, tropical and sub-tropical regions throughout the world. Phytochemicals identified from C. asiatica to date include isoprenoids (sesquiterpenes, plant sterols, pentacyclic triterpenoids and saponins) and phenylpropanoid derivatives (eugenol derivatives, caffeoylquinic acids, and flavonoids). Contemporary methods for fingerprinting and characterization of compounds in C. asiatica extracts include liquid chromatography and/or ion mobility spectrometry in conjunction with high-resolution mass spectrometry. Multiple studies in rodent models, and a limited number of human studies, support C. asiatica’s traditional reputation as a cognitive enhancer, as well as its anxiolytic and anticonvulsant effects. Neuroprotective effects of C. asiatica are seen in several in vitro models, for example against beta amyloid toxicity, and appear to be associated with increased mitochondrial activity, improved antioxidant status, and/or inhibition of the pro-inflammatory enzyme, phospholipase A2. Neurotropic effects of C. asiatica include increased dendritic arborization and synaptogenesis, and may be due to modulations of signal transduction pathways such as ERK1/2 and Akt. Many of these neurotropic and neuroprotective properties of C. asiatica have been associated with the triterpene compounds asiatic acid, asiaticoside and madecassoside. More recently, caffeoylquinic acids are emerging as a second important group of active compounds in C. asiatica, with the potential of enhancing the Nrf2-antioxidant response pathway. The absorption, distribution, metabolism and excretion of the triterpenes, caffeoylquinic acids and flavonoids found in C. asiatica have been studied in humans and animal models, and the compounds or their metabolites found in the brain. This review highlights the remarkable potential for C. asiatica extracts and derivatives to be used in the treatment of neurological conditions, and considers the further research needed to actualize this possibility.

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Adapted from Azerad (2016)

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Adapted from Gray et al. J. Ethnopharmacology (2016)

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Adapted from Soumyanath et al. (2012)

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References

  • Actis-Goretta L, Lévèques A, Giuffrida F, Romanov-Michailidis F, Viton F, Barron D, Duenas-Paton M, Gonzalez-Manzano S, Santos-Buelga C, Williamson G, Dionisi F (2012) Elucidation of (-)-epicatechin metabolites after ingestion of chocolate by healthy humans. Free Radic Biol Med 53:787–795

    Article  CAS  PubMed  Google Scholar 

  • Alqahtani A, Tongkao-On W, Li KM, Razmovski-Naumovski V, Chan K, Li GQ (2015) Seasonal variation of triterpenes and phenolic compounds in Australian Centella asiatica (L.) Urb. Phytochem Anal 26:436–443

    Article  CAS  PubMed  Google Scholar 

  • Antognoni F, Perellino NC, Crippa S, Dal Toso R, Danieli B, Minghetti A, Poli F, Pressi G (2011) Irbic acid, a dicaffeoylquinic acid derivative from Centella asiatica cell cultures. Fitoterapia 82:950–954

    Article  CAS  PubMed  Google Scholar 

  • Apichartsrangkoon A, Wongfhun P, Gordon M (2009) Flavor characterization of sugar-added pennywort (Centella asiaticaL.) juices treated with ultra-high pressure and thermal processes. J Food Sci 74:C643–C646

    Article  CAS  PubMed  Google Scholar 

  • Appa Rao M, Srinivasan K, Rao K (1973) The effect of Mandookaparni (Centella asiatica) on the general mental ability (Medhya) of mentally retarded children. J Res Ind Med 8(4):9–16

    Google Scholar 

  • Arun S, Liu L, Donmez G (2016) Mitochondrial biology and neurological diseases. Curr Neuropharmacol 14:143–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Awad R, Levac D, Cybulska P, Merali Z, Trudeau V, Arnason J (2007) Effects of traditionally used anxiolytic botanicals on enzymes of the gamma-aminobutyric acid (GABA) system. Can J Physiol Pharmacol 85:933–942

    Article  CAS  PubMed  Google Scholar 

  • Azerad R (2016) Chemical structures, production and enzymatic transformations of sapogenins and saponins from Centella asiatica (L.) Urban. Fitoterapia 114:168–187

    Article  CAS  PubMed  Google Scholar 

  • Barbosa NR, Pittella F, Gattaz WF (2008) Centella asiatica water extract inhibits iPLA2 and cPLA2 activities in rat cerebellum. Phytomedicine 15:896–900

    Article  CAS  PubMed  Google Scholar 

  • Basavarajappa BS, Nagre NN, Xie S, Subbanna S (2014) Elevation of endogenous anandamide impairs LTP, learning, and memory through CB1 receptor signaling in mice. Hippocampus 24:808–818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belcaro G, Maquart FX, Scoccianti M, Dugall M, Hosoi M, Cesarone MR, Luzzi R, Cornelli U, Ledda A, Feragalli B (2011) TECA (Titrated Extract of Centella Asiatica): new microcirculatory, biomolecular, and vascular application in preventive and clinical medicine. A status paper. Panminerva Med 53:105–118

    CAS  PubMed  Google Scholar 

  • Boettler U, Sommerfeld K, Volz N, Pahlke G, Teller N, Somoza V, Lang R, Hofmann T, Marko D (2010) Coffee constituents as modulators of Nrf2 nuclear translocation and ARE (EpRE)-dependent gene expression. J Nutr Biochem 22:426–440

    Article  PubMed  CAS  Google Scholar 

  • Bonfill M, Mangas S, Cusido RM, Osuna L, Pinol MT, Palazon J (2006) Identification of triterpenoid compounds of Centella asiatica by thin-layer chromatography and mass spectrometry. Biomed Chromatogr 20:151–153

    Article  CAS  PubMed  Google Scholar 

  • Botanica (2017) Gotu-Kola. http://www.bangkokbotanica.com/gotukola.html. Accessed  17 Jan 2017

  • Bradwejn J, Zhou Y, Koszycki D, Shlik J (2000) A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 20:680–684

    Article  CAS  PubMed  Google Scholar 

  • Bravo L (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 56:317–333

    Article  CAS  PubMed  Google Scholar 

  • Brinkhaus B, Lindner M, Schuppan D, Hahn EG (2000) Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine 7:427–448

    Article  CAS  PubMed  Google Scholar 

  • Cao X, Xiao H, Zhang Y, Zou L, Chu Y, Chu X (2010) 1, 5-Dicaffeoylquinic acid-mediated glutathione synthesis through activation of Nrf2 protects against OGD/reperfusion-induced oxidative stress in astrocytes. Brain Res 1347:142–148

    Article  CAS  PubMed  Google Scholar 

  • Ceremuga T, Valdivieso D, Kenner C, Lucia A, Lathrop K, Stailey O, Bailey H, Criss J, Linton J, Fried J, Taylor A, Padron G, Johnson A (2015) 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 83:91–98

    PubMed  Google Scholar 

  • Cesarone MR, Incandela L, De Sanctis MT, Belcaro G, Bavera P, Bucci M, Ippolito E (2001) Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model. Angiology 52(Suppl 2):S49–S54

    Google Scholar 

  • Chanana P, Kumar A (2016) Possible involvement of nitric oxide modulatory mechanisms in the neuroprotective effect of Centella asiatica against sleep deprivation induced anxiety like behaviour, oxidative damage and neuroinflammation. Phytother Res 30:671–680

    Article  CAS  PubMed  Google Scholar 

  • Chandrika UG, Prasad Kumarab PA (2015) Gotu kola (Centella asiatica): nutritional properties and plausible health benefits. Adv Food Nutr Res 76:125–157

    Article  PubMed  Google Scholar 

  • Chassaud LF, Fry BJ, Hawkins DR, Lewis JD, Sword IP, Taylor T, Hathway DE (1971) The metabolism of asiatic acid,-madecassic acid and asiaticoside in the rat. Arzneimittelforschung 21:1379–1384

    CAS  PubMed  Google Scholar 

  • Chen S, Yin Z, Jiang C, Ma Z, Fu Q, Qu R, Ma S (2014) Asiaticoside attenuates memory impairment induced by transient cerebral ischemia-reperfusion in mice through anti-inflammatory mechanism. Pharmacol Biochem Behav 122:7–15

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Tsai W, Chen C, Pan TM (2015) Centella asiatica extract protects against amyloid β1-40-induced neurotoxicity in neuronal cells by activating the antioxidative defence system. J Tradit Complement Med 6:362–369

    Article  PubMed  PubMed Central  Google Scholar 

  • Choi S, Kim J, Suh S, Kim C, Kim H, Kim C, Park G, Park C, Shin D (2014) Ligularia fischeri extract protects against oxidative-stress-induced neurotoxicity in mice and PC12 cells. J Med Food 17:1222–1231

    Article  CAS  PubMed  Google Scholar 

  • Clifford MN, Knight S, Kuhnert N (2005) Discriminating between the six isomers of dicaffeoylquinic acid by LC-MSn. J Agric Food Chem 53:3821–3832

    Article  CAS  PubMed  Google Scholar 

  • Conley K, Jubrias S, Esselman P (2000) Oxidative capacity and ageing in human muscle. J Physiol 52:203–210

    Article  Google Scholar 

  • Defillipo PP, Raposo AH, Fedoce AG, Ferreira AS, Polonini HC, Gattaz WF, Raposo NR (2012) Inhibition of cPLA2 and sPLA2 activities in primary cultures of rat cortical neurons by Centella asiatica water extrac. Nat Prod Commun 7:841–843

    CAS  PubMed  Google Scholar 

  • Deshmukh R, Kaundal M, Bansal V (2016) Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats. Biomed Pharmacother 81:56–62

    Article  CAS  PubMed  Google Scholar 

  • Dev RDO, Mohamed S, Hambali Z, Samah BA (2009) Comparison on cognitive effects of Centella asiatica in healthy middle age female and male volunteers. Eur J Sci Res 31(4):553–565

    Google Scholar 

  • Devkota A, Dall’Acqua S, Comai S, Innocenti G, Jha PK (2010) Centella asiatica (L.) urban from Nepal: quali-quantitative analysis of samples from several sites, and selection of high terpene containing populations for cultivation. Biochem Syst Ecol 38:12–22

    Article  CAS  Google Scholar 

  • Dewick P (2002) The Shikimate pathway: aromatic amino acids and phenylpropanoids. Meicinal natural products. Wiley, New York, pp 121–166

    Google Scholar 

  • Dhanasekaran M, Holcomb L, Hitt A, Tharakan B, Porter J, Young K, Manyam B (2009) Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer’s disease animal model. Phytother Res 23:14–19

    Article  PubMed  Google Scholar 

  • Diallo B, Vanhaelenfastre R, Vanhaelen M (1991) Direct coupling of high-speed countercurrent chromatography to thin-layer chromatography—application to the separation of asiaticoside and madecassoside from Centella-asiatica. J Chromatogr 558:446–450

    Article  CAS  Google Scholar 

  • Doknark S, Mingmalairak S, Vattanajun A, Tantisira B, Tantisira M (2014) Study of ameliorating effects of ethanolic extract of Centella asiatica on learning and memory deficit in animal models. J Med Assoc Thai 97:S68–S76

    PubMed  Google Scholar 

  • Dong LL, Shion H, Davis RG, Terry-Penak B, Castro-Perez J, van Breemen RB (2010) Collision cross-section determination and tandem mass spectrometric analysis of isomeric carotenoids using electrospray ion mobility time-of-flight mass spectrometry. Anal Chem 82:9014–9021

    Article  CAS  PubMed  Google Scholar 

  • Drewes LR (2001) Molecular architecture of the brain microvasculature: perspective on blood-brain transport. J Mol Neurosci 16:93–98 (discussion 151–157)

    Article  CAS  PubMed  Google Scholar 

  • Du QZ, Jerz G, Chen P, Winterhalter P (2004) Preparation of ursane triterpenoids from Centella asiatica using high speed countercurrent chromatography with step-gradient elution. J Liq Chromatogr Relat Technol 27:2201–2215

    Article  CAS  Google Scholar 

  • Du H, Guo L, Yan S, Sosunov A, McKhann G, Yan S (2010) Early deficits in synaptic mitochondria inan Alzheimer’s disease mouse model. Proc Natl Acad Sci 107:18670–18675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Erk T, Williamson G, Renouf M, Marmet C, Steiling H, Dionisi F, Barron D, Melcher R, Richling E (2012) Dose-dependent absorption of chlorogenic acids in the small intestine assessed by coffee consumption in ileostomists. Mol Nutr Food Res 56:1488–1500

    Article  CAS  PubMed  Google Scholar 

  • Farah A, Monteiro M, Donangelo CM, Lafay S (2008) Chlorogenic acids from green coffee extract are highly bioavailable in humans. J Nutr 138:2309–2315

    Article  CAS  PubMed  Google Scholar 

  • Farhana KM, Malueka RG, Wibowo S, Gofir A (2016) Effectiveness of gotu kola extract 750 mg and 1000 mg compared with folic acid 3 mg in improving vascular cognitive impairment after stroke. Evid Based Complement Altern Med 2016:2795915

    Article  Google Scholar 

  • Farooqui AA, Ong WY, Horrocks LA (2006) Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev 58:591–620

    Article  CAS  PubMed  Google Scholar 

  • Flora S, Gupta R (2007) Beneficial effects of Centella asiatica aqueous extract against arsenic-induced oxidative stress and essential metal status in rats. Phytother Res 21:980–988

    Article  CAS  PubMed  Google Scholar 

  • Floridata (2016). Floridata Plant Encyclopedia. http://floridata.com/Plants/Apiaceae/Centella%20asiatica. Accessed 30 Dec 2016

  • Flowers D (1998) On the properties of bit string-based measures of chemical similarity. J Chem Inf Comput Sci 38:379–386

    Article  Google Scholar 

  • Gadahad M, Rao M, Rao G (2008) Enhancement of hippocampal CA3 neuronal dendritic arborization by Centella asiatica (Linn) fresh leaf extract treatment in adult rats. J Chin Med Assoc 71:6–13

    Article  PubMed  Google Scholar 

  • Gallego A, Ramirez-Estrada K, Vidal-Limon HR, Hidalgo D, Lalaleo L, Kayani WK, Cusido RM, Palazon J (2014) Biotechnological production of centellosides in cell cultures of Centella asiatica (L) Urban. Eng Life Sci 14:633–642

    Article  CAS  Google Scholar 

  • Gasperotti M, Passamonti S, Tramer F, Masuero D, Guella G, Mattivi F, Vrhovsek U (2015) Fate of microbial metabolites of dietary polyphenols in rats: is the brain their target destination? ACS Chem Neurosci 6:1341–1352

    Article  CAS  PubMed  Google Scholar 

  • Gray NE, Morré J, Kelley J, Maier CS, Stevens JF, Quinn JF, Soumyanath A (2014) Caffeoylquinic acids in Centella asiatica protect against amyloid-β toxicity. J Alzheimer’s Dis 40:359–373

    CAS  Google Scholar 

  • Gray NE, Sampath H, Zweig JA, Quinn JF, Soumyanath A (2015) Centella asiatica attenuates amyloid-β-induced oxidative stress and mitochondrial dysfunction. J Alzheimer’s Dis 45:933–946

    Google Scholar 

  • Gray NE, Harris C, Quinn J, Soumyanath A (2016) Centella asiatica modulates antioxidant and mitochondrial pathways and improves cognitive function in mice. J Ethnopharmacol 180:78–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimaldi R, De Ponti F, D’Angelo L, Caravaggi M, Guidi G, Lecchini S, Frigo GM, Crema A (1990) Pharmacokinetics of the total triterpenic fraction of Centella asiatica after single and multiple administrations to healthy volunteers. A new assay for asiatic acid. J Ethnopharmacol 28:235–241

    Article  CAS  PubMed  Google Scholar 

  • Gunther B, Wagner H (1996) Quantitative determination of triterpenes in extracts and phytopreparations of Centella asiatica (L) Urban. Phytomedicine 3:59–65

    Article  CAS  PubMed  Google Scholar 

  • Gupta Y, Veerendra Kumar M, Srivastava A (2003) Effect of Centella asiatica on pentylenetetrazole-induced kindling, cognition and oxidative stress in rats. Pharmacol Biochem Behav 74:579–585

    Article  CAS  PubMed  Google Scholar 

  • Haleagrahara N, Ponnusamy K (2010) Neuroprotective effect of Centella asiatica extract (CAE) on experimentally induced parkinsonism in aged Sprague Dawley rats. J Toxicol Sci 35:41–47

    Article  CAS  PubMed  Google Scholar 

  • Han J, Miyamae Y, Shigemori H, Isoda H (2010) Neuroprotective effect of 3,5-di-O-caffeoylquinic acid on SH-SY5Y cells and senescence-accelerated-prone mice 8 through the up-regulation of phosphoglycerate kinase-1. Neuroscience 169:1039–1045

    Article  CAS  PubMed  Google Scholar 

  • Han WJ, Xia YF, Dai Y (2012) Development and validation of high-performance liquid chromatography/electrospray ionization mass spectrometry for assay of madecassoside in rat plasma and its application to pharmacokinetic study. Biomed Chromatogr 26:26–32

    Article  CAS  PubMed  Google Scholar 

  • Hensley K, Carney J, Mattson M, Aksenova M, Harris M, Wu J, Floyd R, Butterfield D (1994) A model for betaamyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci 91:3270–3274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hollman PCH (2004) Absorption, bioavailability, and metabolism of flavonoids. Pharm Biol 42:74–83

    Article  CAS  Google Scholar 

  • Hollman PC, Bijsman MN, van Gameren Y, Cnossen EP, de Vries JH, Katan MB (1999) The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 31:569–573

    Article  CAS  PubMed  Google Scholar 

  • Incandela L, Belcaro G, De Sanctis MT, Cesarone MR, Griffin M, Ippolito E, Bucci M, Cacchio M (2001) Total triterpenic fraction of Centella asiatica in the treatment of venous hypertension: a clinical, prospective, randomized trial using a combined microcirculatory model. Angiology 52(Suppl 2):S61–S67

    PubMed  Google Scholar 

  • IPNI (2016) International plant names index. Royal Botanic Gardens, Kew

    Google Scholar 

  • Itoh KTC, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236:313–322

    Article  CAS  PubMed  Google Scholar 

  • Jäger AK, Saaby L (2011) Flavonoids and the CNS. Molecules 16:1471–1485

    Article  PubMed  CAS  Google Scholar 

  • James JT, Dubery IA (2009) Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules 14:3922–3941

    Article  CAS  PubMed  Google Scholar 

  • James J, Dubery I (2011) Identification and quantification of triterpenoid centelloids in Centella asiatica (L.) urban by densitometric TLC. JPC J Plan Chromatogr Mod TLC 24:82–87

    Article  CAS  Google Scholar 

  • Jamil S, Nizami Q, Salam M (2007) Centella asiatica (Linn.) Urban: a review. Nat Product Radiance 6:158–170

    Google Scholar 

  • Jana U, Sur TK, Maity LN, Debnath PK, Bhattacharyya D (2010) A clinical study on the management of generalized anxiety disorder with Centella asiatica. Nepal Med Coll J 12:8–11

    CAS  PubMed  Google Scholar 

  • Jew SS, Yoo CH, Lim DY, Kim H, MookJung I, Jung MW, Choi H, Jung YH, Kim H, Park HG (2000) Structure activity relationship study of asiatic acid derivatives against beta amyloid (A beta)induced neurotoxicity. Bioorg Med Chem Lett 10:119–121

    Article  CAS  PubMed  Google Scholar 

  • Jiang W, Li M, He F, Bian Z, He Q, Wang X, Yao W, Zhu L (2016) Neuroprotective effect of asiatic acid against spinal cord injury in rats. Life Sci 157:45–51

    Article  CAS  PubMed  Google Scholar 

  • Kahle K, Huemmer W, Kempf M, Scheppach W, Erk T, Richling E (2007) Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption. J Agric Food Chem 55:10605–10614

    Article  CAS  PubMed  Google Scholar 

  • Kapoor L (1990) Handbook of Ayurvedic medicinal plants. CRC Press, Boca Raton

    Google Scholar 

  • Kim J, Lee H, Hwang B, Kim S, Yoo J, Seong Y (2012a) Neuroprotection of Ilex latifolia and caffeoylquinic acid derivatives against excitotoxic and hypoxic damage of cultured rat cortical neurons. Arch Pharm Res 35:1115–1122

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Bolton EE, Bryant SH (2012b) Effects of multiple conformers per compound upon 3-D similarity search and bioassay data analysis. J Cheminform 4:28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krishnamurthy R, Senut M, Zemke D, Min J, Frenkel M, Greenberg E, Yu S, Ahn N, Goudreau J, Kassab M, Panickar K, Majid A (2009) Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia. J Neurosci Res 87:2541–2550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J 2013:162750

    Google Scholar 

  • Kumar A, Dogra S, Prakash A (2009) Neuroprotective effects of Centella asiatica against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress. Int J Alzheimers Dis 972178

  • Kumar A, Prakash A, Dogra S (2011) Centella asiatica attenuates D-galactose-induced cognitive impairment, oxidative and mitochondrial dysfunction in mice. Int J Alzheimers Dis 2011:347569

    PubMed  PubMed Central  Google Scholar 

  • Kumari S, Deori M, Elancheran R, Kotoky J, Devi R (2016) In vitro and in vivo antioxidant, anti-hyperlipidemic properties and chemical characterization of Centella asiatica (L.) extract. Front Pharmacol 7:400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon S, Lee H, Kim J, Hong S, Kim H, Jo T, Park Y, Lee C, Kim Y, Lee S, Jang C (2010) Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via anti-acetylcholinesterase and anti-oxidative activities in mice. Eur J Pharmacol 649:210–217

    Article  CAS  PubMed  Google Scholar 

  • Lal RK, Gupta P, Dubey BK (2017) Genetic variability and associations in the accessions of Manduk parni {Centella asiatica (L)}. Ind Crops Prod 96:173–177

    Article  Google Scholar 

  • Leng DD, Han WJ, Rui Y, Dai Y, Xia YF (2013) In vivo disposition and metabolism of madecassoside, a major bioactive constituent in Centella asiatica (L.) Urb. J Ethnopharmacol 150:601–608

    Article  CAS  PubMed  Google Scholar 

  • Liang G, Shi B, Luo W, Yang J (2015) The protective effect of caffeic acid on global cerebral ischemia-reperfusion injury in rats. Behav Brain Funct 11:18. https://doi.org/10.1186/s12993-015-0064-x

  • Lin X, Huang R, Zhang S, Wei L, Zhuo L, Wu X, Tang A, Huang Q (2013) Beneficial effects of asiaticoside on cognitive deficits in senescence-accelerated mice. Fitoterapia 87:69–77

    Article  CAS  PubMed  Google Scholar 

  • Lin X, Zhang S, Huang R, Wei L, Tan S, Liang C, Lv S, Chen Y, Liang S, Tian Y, Lu Z, Huang Q (2014) Protective effect of madecassoside against cognitive impairment induced by D-galactose in mice. Pharmacol Biochem Behav 124:434–442

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Dou G, Dong X, Yuan D, Ji X, Wu Z, Meng Z (2010) An improved LC-MS/MS method for simultaneous determination of 1,5-dicaffeoylquinic acid and its active metabolites in human plasma and its application to a pharmacokinetic study in patients. Biomed Chromatogr 24:935–940

    Article  CAS  PubMed  Google Scholar 

  • Long HS, Stander MA, Van Wyk BE (2012) Notes on the occurrence and significance of triterpenoids (asiaticoside and related compounds) and caffeoylquinic acids in Centella species. South Afr J Bot 82:53–59

    Article  CAS  Google Scholar 

  • Lu Q, Li WH, Hu SQ (2011) Studies on fingerprints of Centella asiatica by HPLC. Zhong Yao Cai 34:46–50

    CAS  PubMed  Google Scholar 

  • Lu L, Qian D, Yang J, Jiang S, Guo J, Shang EX, Duan JA (2013) Identification of isoquercitrin metabolites produced by human intestinal bacteria using UPLC-Q-TOF/MS. Biomed Chromatogr 27:509–514

    Article  CAS  PubMed  Google Scholar 

  • Luo Y, Yang Y, Liu J, Li W, Yang J, Sui X, Yuan X, Nie Z, Liu Y, Chen D, Lin S, Wang Y (2014) Neuroprotective effects of madecassoside against focal cerebral ischemia reperfusion injury in rats. Brain Res 1565:37–47

    Article  CAS  PubMed  Google Scholar 

  • Maldini M, Natella F, Baima S, Morelli G, Scaccini C, Langridge J, Astarita G (2015) Untargeted metabolomics reveals predominant alterations in lipid metabolism following light exposure in broccoli sprouts. Int J Mol Sci 16:13678–13691

    Article  PubMed  PubMed Central  Google Scholar 

  • Mangas S, Moyano E, Osuna L, Cusido RM, Bonfill M, Palazon J (2008) Triterpenoid saponin content and the expression level of some related genes in calli of Centella asiatica. Biotechnol Lett 30:1853–1859

    Article  CAS  PubMed  Google Scholar 

  • Marmet C, Actis-Goretta L, Renouf M, Giuffrida F (2014) Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee. J Pharm Biomed Anal 88:617–625

    Article  CAS  PubMed  Google Scholar 

  • Mato L, Wattanathorn J, Muchimapura S, Tongun T, Piyawatkul N, Yimtae K, Thanawirattananit P, Sripanidkulchai B (2011) Centella asiatica improves physical performance and health-related quality of life in healthy elderly volunteer. Evid Based Complement Altern Med 2011:579467

    Article  Google Scholar 

  • Maulidiani H, Khatib A, Shaari K, Abas F, Shitan M, Kneer R, Neto V, Lajis NH (2012) Discrimination of three pegaga (Centella) varieties and determination of growth-lighting effects on metabolites content based on the chemometry of 1H nuclear magnetic resonance spectroscopy. J Agric Food Chem 60:410–417

    Article  CAS  Google Scholar 

  • Maulidiani H, Abas F, Khatib A, Shaari K, Lajis NH (2014) Chemical characterization and antioxidant activity of three medicinal Apiaceae species. Ind Crops Prod 55:238–247

    Article  CAS  Google Scholar 

  • McGuffin M, Hobbs C, Upton R, Goldberg A (1997) Botanical safety handbook. American Herbal Products Association, CRC Press, Boca Raton

    Google Scholar 

  • Meena H, Pandey H, Pandey P, Arya M, Ahmed Z (2012) Evaluation of antioxidant activity of two important memory enhancing medicinal plants Baccopa monnieri and Centella asiatica. Indian J Pharmacol 44:114–117

    Article  PubMed  PubMed Central  Google Scholar 

  • Mikami Y, Yamazawa T (2015) Chlorogenic acid, a polyphenol in coffee, protects neurons against glutamate neurotoxicity. Life Sci 139:69–74

    Article  CAS  PubMed  Google Scholar 

  • Mohandas Rao K, Muddanna Rao S, Gurumadhva Rao S (2006) Centella asiatica (L.) leaf extract treatment during the growth spurt period enhances hippocampal CA3 neuronal dendritic arborization in rats. Evid Based Complement Altern Med 3:349–357

    Article  CAS  Google Scholar 

  • Mohandas Rao K, Muddanna Rao S, Gurumadhva Rao S (2009) Enhancement of amygdaloid neuronal dendritic arborization by fresh leaf juice of Centella asiatica (Linn) during growth spurt period in rats. Evid Based Complement Altern Med 6:203–210

    Article  CAS  Google Scholar 

  • Mohandas Rao K, Rao M, Rao G (2012) Evaluation of amygdaloid neuronal dendritic arborization enhancing effect of Centella asiatica (Linn) fresh leaf extract in adult rats. Chin J Integr Med 1–6

  • Monteiro M, Farah A, Perrone D, Trugo LC, Donangelo C (2007) Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans. J Nutr 137:2196–2201

    Article  CAS  PubMed  Google Scholar 

  • Mook-Jung I, Shin JE, Yun SH, Huh K, Koh JY, Park HK, Jew SS, Jung MW (1999) Protective effects of asiaticoside derivatives against beta amyloid neurotoxicity. J Neurosci Res 59:417–425

    Article  Google Scholar 

  • Motohashi H, Yamamoto M (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10:549–557

    Article  CAS  PubMed  Google Scholar 

  • Muller V, Albert A, Winkler JB, Lankes C, Noga G, Hunsche M (2013) Ecologically relevant UV-B dose combined with high PAR intensity distinctly affect plant growth and accumulation of secondary metabolites in leaves of Centella asiatica L. Urban. J Photochem Photobiol B Biol 127:161–169

    Article  CAS  Google Scholar 

  • Mustafa RA, Hamid AA, Mohamed S, Bakar F, Bakar FA (2010) Total phenolic compounds, flavonoids, and radical scavenging activity of 21 selected tropical plants. J Food Sci 75(1):C28–C35

    Article  CAS  PubMed  Google Scholar 

  • Nadkarni AK (1976) Dr. K.M. Nadkarni’s Indian Materia medica. Popular Prakashan Pvt. Ltd, Mumbai

    Google Scholar 

  • Nair SN, Menon S, Shailajan S (2012) A liquid chromatography/electrospray ionization tandem mass spectrometric method for quantification of asiatic acid from plasma: application to pharmacokinetic study in rats. Rapid Commun Mass Spectrom 26:1899–1908

    Article  CAS  PubMed  Google Scholar 

  • Nasir M, Habsah M, Zamzuri I, Rammes G, Hasnan J, Abdullah J (2011) Effects of asiatic acid on passive and active avoidance task in male Spraque–Dawley rats. J Ethnopharmacol 134:203–209

    Article  CAS  PubMed  Google Scholar 

  • Nasir M, Abdullah J, Habsah M, Ghani R, Rammes G (2012) Inhibitory effect of asiatic acid on acetylcholinesterase, excitatory post synaptic potential and locomotor activity. Phytomedicine 19:311–316

    Article  CAS  PubMed  Google Scholar 

  • Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292:C670–C686

    Article  CAS  PubMed  Google Scholar 

  • Ncube EN, Steenkamp PA, Madala NE, Dubery IA (2016) Chlorogenic acids biosynthesis in Centella asiatica cells is not stimulated by salicylic acid manipulation. Appl Biochem Biotechnol 179:685–696

    Article  CAS  PubMed  Google Scholar 

  • Németh K, Plumb GW, Berrin JG, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42:29–42

    Article  PubMed  CAS  Google Scholar 

  • Newall CA, Anderson L, Phillipson JD (1996) Herbal medicines. A guide for healthcare professionals. Pharmaceutical Press, London

    Google Scholar 

  • Nicolas AN, Plunkett GM (2009) The demise of subfamily Hydrocotyloideae (Apiaceae) and the re-alignment of its genera across the entire order Apiales. Mol Phylogenet Evol 53:134–151

    Article  CAS  PubMed  Google Scholar 

  • Oyedeji OA, Afolayan AJ (2005) Chemical composition and antibacterial activity of the essential oil of Centella asiatica growing in South Africa. Pharm Biol 43:249–252

    Article  CAS  Google Scholar 

  • Pacini T, Fu W, Gudmundsson S, Chiaravalle AE, Brynjolfson S, Palsson BO, Astarita G, Paglia G (2015) Multidimensional analytical approach based on UHPLC-UV-ion mobility-MS for the screening of natural pigments. Anal Chem 87:2593–2599

    Article  CAS  PubMed  Google Scholar 

  • Pinheiro Fernandes F, Fontenele Menezes A, de Sousa Neves J, Fonteles A, da Silva A, de Araújo Rodrigues P, Santos do Carmo M, de Souza C, de Andrade G (2014) Caffeic acid protects mice from memory deficits induced by focal cerebral ischemia. Behav Pharmacol 25:637–647

    Article  PubMed  CAS  Google Scholar 

  • Pittella F, Dutra R, Junior D, Lopes M, Barbosa N (2009) Antioxidant and cytotoxic activities of Centella asiatica (L) Urb. Int J Mol Sci 10:3713–3721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plengmuankhae W, Tantitadapitak C (2015) Low temperature and water dehydration increase the levels of asiaticoside and madecassoside in Centella asiatica (L.) Urban. South Afr J Bot 97:196–203

    Article  CAS  Google Scholar 

  • Prakash A, Kumar A (2013) Mitoprotective effect of Centella asiatica against aluminum-induced neurotoxicity in rats: possible relevance to its anti-oxidant and anti-apoptosis mechanism. Neurol Sci 34:1403–1409

    Article  PubMed  Google Scholar 

  • Rahajanirina V, Rakotondralambo Raoseta SO, Roger E, Razafindrazaka H, Pirotais S, Boucher M, Danthu P (2012) The influence of certain taxonomic and environmental parameters on biomass production and triterpenoid content in the leaves of Centella asiatica (L.) Urb. from Madagascar. Chem Biodivers 9:298–308

    Article  CAS  PubMed  Google Scholar 

  • Rakesh R, Sushma T, Sangeeta G, Gambir I (2013) Response of Centella asiatica in the management of age related problems among elderly with special reference to cognitive problems as per Prakriti. Int J Res Ayurveda Pharm 4(2):163–167

    Article  Google Scholar 

  • Ramesh B, Girish T, Raghavendra R, Naidu K, Rao U, Rao K (2014) Comparative study on anti-oxidant and anti-inflammatory activities of Caesalpinia crista and Centella asiatica leaf extracts. J Pharm Bioallied Sci 6:86–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rangel-Ordóñez L, Nöldner M, Schubert-Zsilavecz M, Wurglics M (2010) Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761®. Planta Med 76:1683–1690

    Article  PubMed  CAS  Google Scholar 

  • Rhein V, Baysang G, Rao S, Meier F, Bonert A, Müller-Spahn F, Eckert A (2009) Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells. Cell Mol Neurobiol 29:1063–1071

    Article  CAS  PubMed  Google Scholar 

  • Rush WR, Murray GR, Graham DJ (1993) The comparative steady-state bioavailability of the active ingredients of Madecassol. Eur J Drug Metab Pharmacokinet 18:323–326

    Article  CAS  PubMed  Google Scholar 

  • Sakina MR, Dandiya P (1990) A psycho-neuropharmacological profile of centellaasiatica extract. Fitoterapia 61:291–296

    Google Scholar 

  • Sangwan RS, Tripathi S, Singh J, Narnoliya LK, Sangwan NS (2013) De novo sequencing and assembly of Centella asiatica leaf transcriptome for mapping of structural, functional and regulatory genes with special reference to secondary metabolism. Gene 525:58–76

    Article  CAS  PubMed  Google Scholar 

  • Sasaki K, Han J, Shimozono H, Villareal M, Isoda H (2013) Caffeoylquinic acid-rich purple sweet potato extract, with or without anthocyanin, imparts neuroprotection and contributes to the improvement of spatial learning and memory of SAMP8 mouse. J Agric Food Chem 61:5037–5045

    Article  CAS  PubMed  Google Scholar 

  • Scherbl D, Renouf M, Marmet C, Poquet L, Cristiani I, Dahbane S, Emady-Azar S, Sauser J, Galan J, Dionisi F, Richling E (2017) Breakfast consumption induces retarded release of chlorogenic acid metabolites in humans. Eur Food Res Technol 243(5):791–806

    Article  CAS  Google Scholar 

  • Senger DR, Li D, Jaminet SC, Cao S (2016) Activation of the Nrf2 cell defense pathway by ancient foods: disease prevention by important molecules and microbes lost from the modern western diet. PLoS ONE 17:1–40

    Google Scholar 

  • Sharma PD, Surana SJ, Jadav RB, Patel PH (2011) Bioanalytical HPLC method development and validation for quantification of asiatic acid from centella asiatica linn. Int J Pharm Sci Rev Res 10:46–50

    CAS  Google Scholar 

  • Shinomol G (2008a) Effect of Centella asiatica leaf powder on oxidative markers in brain regions of prepubertal mice in vivo and its in vitro efficacy to ameliorate 3-NPA-induced oxidative stress in mitochondria. Phytomedicine 15:971–984

    Article  PubMed  Google Scholar 

  • Shinomol G (2008b) Prophylactic neuroprotective property of Centella asiatica against 3-nitropropionic acid induced oxidative stress and mitochondrial dysfunctions in brain regions of prepubertal mice. Neurotoxicology 29:948–957

    Article  CAS  PubMed  Google Scholar 

  • Shinomol G, Muralidhara MMB (2011) Exploring the role of “Brahmi” (Bocopa monnieri and Centella asiatica) in brain function and therapy. Recent Pat Endocr Metab Immune Drug Discov 5:33–49

    Article  CAS  PubMed  Google Scholar 

  • Singh J, Singh Sangwan R, Gupta S, Saxena S, Sangwan NS (2015) Profiling of triterpenoid saponin content variation in different chemotypic accessions of Centella asiatica L. Plant Genet Resour Charact Util 13:176–179

    Article  CAS  Google Scholar 

  • Sirichoat A, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Leksomboon R, Chaichun A, Wigmore P, Welbat J (2015) Effects of asiatic acid on spatial working memory and cell proliferation in the adult rat hippocampus. Nutrients 7:8413–8423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soumyanath A, Zhong YP, Gold SA, Yu X, Koop DR, Bourdette D, Gold BG (2005) Centella asiatica accelerates nerve regeneration upon oral administration and contains multiple active fractions increasing neurite elongation in vitro. J Pharm Pharmacol 57:1221–1229

    Article  CAS  PubMed  Google Scholar 

  • Soumyanath A, Zhang Y, Henson E, Wadsworth T, Bishop J, Gold B, Quinn J (2012) Centella asiatica extract improves behavioral deficits in a mouse model of Alzheimer’s disease: investigation of a possible mechanism of action. Int J Alzheimers Dis 381974

  • Srithongkul J, Kanlayanarat S, Srilaong V, Uthairatanakij A, Chalermglin P (2011) Effects of light intensity on growth and accumulation of triterpenoids in three accessions of Asiatic pennywort (Centella asiatica (L.) Urb.). J Food Agric Environ 9:360–363

    CAS  Google Scholar 

  • Srivastava S, Verma S, Gupta A, Rajan S, Rawat AKS (2014) Studies on chemotypic variation in Centella Asiatica (L.) Urban from Nilgiri Range of India. J Planar Chromatogr Mod TLC 27:454–459

    Article  CAS  Google Scholar 

  • Stalmach A, Mullen W, Barron D, Uchida K, Yokota T, Cavin C, Steiling H, Williamson G, Crozier A (2009) Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee by humans: Identification of biomarkers of coffee consumption. Drug Metab Dispos 37:1749–1758

    Article  CAS  PubMed  Google Scholar 

  • Stark TD, Angelov A, Hofmann M, Liebl W, Hofmann T (2013) Comparative direct infusion ion mobility mass spectrometry profiling of Thermus thermophilus wild-type and mutant cruC carotenoid extracts. Anal Bioanal Chem 405:9843–9848

    Article  CAS  PubMed  Google Scholar 

  • Su D, Huang J, Song Y, Feng Y (2014) Comparative pharmacokinetics and tissue distribution study of mono-, and di-caffeoylquinic acids isomers of Ainsliaea fragrans Champ by a fast UHPLC-MS/MS method. Fitoterapia 99:139–152

    Article  CAS  PubMed  Google Scholar 

  • Subash S, Essa M, Braidy N, Awlad-Thani K, Vaishnav R, Al-Adawi S, Al-Asmi A, Guillemin G (2015) Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer’s disease. J Ayurveda Integr Med 6:111–120

    Article  PubMed  PubMed Central  Google Scholar 

  • Subban R, Veerakumar A, Manimaran R, Hashim KM, Balachandran I (2008) Two new flavonoids from Centella asiatica (Linn.). J Nat Med 62:369–373

    Article  CAS  PubMed  Google Scholar 

  • Sun T, Liu B, Li P (2015) Nerve protective effect of asiaticoside against ischemia-hypoxia in cultured rat cortex neurons. Med Sci Monit 21:3036–3041

    Article  PubMed  PubMed Central  Google Scholar 

  • Tabassum R, Vaibhav K, Shrivastava P, Khan A, Ejaz Ahmed M, Javed H, Islam F, Ahmad S, Saeed Siddiqui M, Safhi M, Islam F (2013) Centella asiatica attenuates the neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion rats. Neurol Sci 34:925–933

    Article  PubMed  Google Scholar 

  • Thomas MT, Kurup R, Johnson AJ, Chandrika SP, Mathew PJ, Dan M, Baby S (2010) Elite genotypes/chemotypes, with high contents of madecassoside and asiaticoside, from sixty accessions of Centella asiatica of south India and the Andaman Islands: for cultivation and utility in cosmetic and herbal drug applications. Ind Crops Prod 32:545–550

    Article  CAS  Google Scholar 

  • Thongnopnua P (2008) High-performance liquid chromatographic determination of Asiatic acid in human plasma. Thai J Pharm Sci 32:10–16

    CAS  Google Scholar 

  • Tian X, An L, Gao L, Bai J, Wang J, Meng W, Ren T, Zhao Q (2015) Compound MQA, a caffeoylquinic acid derivative, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro. CNS Neurosci Ther 21:575–584

    Article  CAS  PubMed  Google Scholar 

  • Tiwari S, Singh S, Patwardhan K, Ghlot S, Gambhir I (2008) Effect of Centella asiatica on mild cognitive impairment (MCI) and other common age-related clinical problems. Digst J Nanomater Biostruct 3(4):215–220

  • Tugizimana F, Ncube EN, Steenkamp PA, Dubery IA (2015) Metabolomics-derived insights into the manipulation of terpenoid synthesis in Centella asiatica cells by methyl jasmonate. Plant Biotechnol Rep 9:125–136

    Article  Google Scholar 

  • Umka Welbat J, Sirichoat A, Chaijaroonkhanarak W, Prachaney P, Pannangrong W, Pakdeechote P, Sripanidkulchai B, Wigmore P (2016) Asiatic acid prevents the deleterious effects of valproic acid on cognition and hippocampal cell proliferation and survival. Nutrients 8:E303

    Article  PubMed  CAS  Google Scholar 

  • Upadhyaya S, Saikia LR (2012) Evaluation of phytochemicals, antioxidant activity and nutrient content of Centella asiatica (L.) urban leaves from different localities of Assam. Int Pharm Bio Sci 3:656–663

    Google Scholar 

  • USDA (2016) National plant germplasm system, germplasm resources information network (GRIN database)

  • Visweswari G, Prasad K, Chetan P, Lokanatha V, Rajendra W (2010) Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in pentylenetetrazol-induced seizures with respect to cholinergic neurotransmission. Epilepsy Behav 17:332–335

    Article  PubMed  Google Scholar 

  • Vogel H, De Souza N, D’Sa A (1990) Effect of terpenoids isolated from centella asiatica on granuloma tissue. Acta Ther 16(4):285–298

    CAS  Google Scholar 

  • Wanakhachornkrai O, Pongrakhananon V, Chunhacha P, Wanasuntronwong A, Vattanajun A (2013) Neuritogenic effect of standardized extract of Centella asiatica ECa233 on human neuroblastoma cells. BMC Complement Altern Med 13:204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wanasuntronwong A, Tantisira M, Tantisira B, Watanabe H (2012) Anxiolytic effects of standardized extract of Centella asiatica (ECa 233) after chronic immobilization stress in mice. J Ethnopharmacol 143:579–585

    Article  PubMed  Google Scholar 

  • Wang T, Leng DD, Gao FF, Jiang CJ, Xia YF, Dai Y (2014) A LC-ESI-MS method for the simultaneous determination of madecassoside and its metabolite madecassic acid in rat plasma: comparison pharmacokinetics in normal and collagen-induced arthritic rats. Chin J Nat Med 12:0943–0951

    CAS  Google Scholar 

  • Wang Y, Wang Y, Li J, Hua L, Han B, Zhang Y, Yang X, Zeng Z, Bai H, Yin H, Lou J (2016) Effects of caffeic acid on learning deficits in a model of Alzheimer’s disease. Int J Mol Med 38:869–875

    Article  CAS  PubMed  Google Scholar 

  • Wattanathorn J, Mator L, Muchimapura S, Tongun T, Pasuriwong O, Piyawatkul N, Yimtae K, Sripanidkulchai B, Singkhoraard J (2008) Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol 116:325–332

    Article  PubMed  Google Scholar 

  • Wijeweera P, Arnason J, Koszycki D, Merali Z (2006) Evaluation of anxiolytic properties of Gotukola–(Centella asiatica) extracts and asiaticoside in rat behavioral models. Phytomedicine 13:668–676

    Article  CAS  PubMed  Google Scholar 

  • Williamson G, Dionisi F, Renouf M (2011) Flavanols from green tea and phenolic acids from coffee: critical quantitative evaluation of the pharmacokinetic data in humans after consumption of single doses of beverages. Mol Nutr Food Res 55:864–873

    Article  CAS  PubMed  Google Scholar 

  • Winkel-Shirley B (2001) Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology. Plant Physiol 126:485–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wittemer SM, Veit M (2003) Validated method for the determination of six metabolites derived from artichoke leaf extract in human plasma by high-performance liquid chromatography-coulometric-array detection. J Chromatogr B: Anal Technol Biomed Life Sci 793:367–375

    Article  CAS  Google Scholar 

  • Wittemer SM, Ploch M, Windeck T, Muller SC, Drewelow B, Derendorf H, Veit M (2005) Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans. Phytomedicine 12:28–38

    Article  CAS  PubMed  Google Scholar 

  • Wong KC, Tan GL (1994) Essential oil of Centella asiatica (L.) Urb. J Essent Oil Res 6:307–309

    Article  CAS  Google Scholar 

  • Wong CC, Meinl W, Glatt HR, Barron D, Stalmach A, Steiling H, Crozier A, Williamson G (2010) In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans. J Nutr Biochem 21:1060–1068

    Article  CAS  PubMed  Google Scholar 

  • Xia B, Bai L, Li X, Xiong J, Xu P, Xue M (2015) Structural analysis of metabolites of asiatic acid and its analogue madecassic acid in zebrafish using LC/IT-MSn. Molecules 20:3001–3019

    Article  PubMed  CAS  Google Scholar 

  • Xie C, Yu K, Zhong D, Yuan T, Ye F, Jarrell JA, Millar A, Chen X (2011) Investigation of isomeric transformations of chlorogenic acid in buffers and biological matrixes by ultraperformance liquid chromatography coupled with hybrid quadrupole/ion mobility/orthogonal acceleration time-of-flight mass spectrometry. J Agric Food Chem 59:11078–11087

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Cao Z, Khan I, Luo Y (2008) Gotu Kola (Centella Asiatica) extract enhances phosphorylation of cyclic AMP response element binding protein in neuroblastoma cells expressing amyloid beta peptide. J Alzheimer’s Dis 13:341–349

    Article  Google Scholar 

  • Xu M, Xiong Y, Liu J, Qian J, Zhu L, Gao J (2012) Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells. Acta Pharmacol Sin 33:578–587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang J, Qian D, Jiang S, Shang EX, Guo J, Duan JA (2012) Identification of rutin deglycosylated metabolites produced by human intestinal bacteria using UPLC-Q-TOF/MS. J Chromatogr B Anal Technol Biomed Life Sci 898:95–100

    Article  CAS  Google Scholar 

  • Yin MC, Lin MC, Mong MC, Lin CY (2012) Bioavailability, distribution, and antioxidative effects of selected triterpenes in mice. J Agric Food Chem 60:7697–7701

    Article  CAS  PubMed  Google Scholar 

  • Yoshida M, Fuchigami M, Nagao T, Okabe H, Matsunaga K, Takata J, Karube Y, Tsuchihashi R, Kinjo J, Mihashi K, Fujioka T (2005) Antiproliferative constituents from Umbelliferae plants VII. Active triterpenes and rosmarinic acid from Centella asiatica. Biol Pharm Bull 28:173–175

    Article  CAS  PubMed  Google Scholar 

  • Yuan Y, Zhang H, Sun F, Sun S, Zhu Z, Chai Y (2015) Biopharmaceutical and pharmacokinetic characterization of asiatic acid in Centella asiatica as determined by a sensitive and robust HPLC-MS method. J Ethnopharmacol 163:31–38

    Article  CAS  PubMed  Google Scholar 

  • Zhang FL, Wei YJ, Zhu J, Gong ZN (2008) Simultaneous quantitation of three major triterpenoid glycosides in Centella asiatica extracts by high performance liquid chromatography with evaporative light scattering detection. Biomed Chromatogr 22:119–124

    Article  CAS  PubMed  Google Scholar 

  • Zhang XG, Han T, Zhang QY, Zhang H, Huang BK, Xu LL, Qin LP (2009) Chemical fingerprinting and hierarchical clustering analysis of Centella asiatica from different locations in China. Chromatographia 69:51–57

    Article  CAS  Google Scholar 

  • Zhang X, Wu J, Dou Y, Xia B, Rong W, Rimbach G, Lou Y (2012a) Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis. Eur J Pharmacol 679:51–59

    Article  CAS  PubMed  Google Scholar 

  • Zhang XG, Han T, He ZG, Zhang QY, Zhang L, Rahman K, Qin LP (2012b) Genetic diversity of Centella asiatica in China analyzed by inter-simple sequence repeat (ISSR) markers: combination analysis with chemical diversity. J Nat Med 66:241–247

    Article  PubMed  Google Scholar 

  • Zhang L, Foreman DP, Grant PA, Shrestha B, Moody SA, Villiers F, Kwak JM, Vertes A (2014) In situ metabolic analysis of single plant cells by capillary microsampling and electrospray ionization mass spectrometry with ion mobility separation. Analyst 139:5079–5085

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Li D, Leng A, Ai J, Du Y, Meng Y, Gao Y, Ying X (2015) Tissue distribution and excretion of the five components of Portulaca oleracea L. extract in rat assessed by UHPLC. Braz J Pharm Sci 51:643–652

    Article  Google Scholar 

  • Zheng XC, Wang SH (2009) Determination of asiatic acid in beagle dog plasma after oral administration of Centella asiatica extract by precolumn derivatization RP-HPLC. J Chromatogr B Anal Technol Biomed Life Sci 877:477–481

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge the following sources of grant support: NIH-NCCIH K99 AT008831 (NG), NIH-NCCIH R01AT008099 (AS, AA, CSM, JFS, JQ, PL), NIH-NCRR S10RR027878 (JFS), NIH-NCRR S10RR025628 (CSM), NIH-NCCIH T32 AT002688 (KW), Department of Veterans Affairs Merit Review grant (JQ).

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  1. Department of Neurology, Oregon Health and Science University, Portland, OR, 97239, USA

    Nora E. Gray, Kirsten M. Wright, Joseph Quinn & Amala Soumyanath

  2. Department of Chemistry, Oregon State University, Corvallis, OR, 97331, USA

    Armando Alcazar Magana, Parnian Lak & Claudia S. Maier

  3. Linus Pauling Institute, Oregon State Univeristy, Corvallis, OR, 97331, USA

    Armando Alcazar Magana, Parnian Lak, Jan F. Stevens & Claudia S. Maier

  4. Department of Neurology and Parkinson’s Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, 97239, USA

    Joseph Quinn

  5. Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, 97331, USA

    Jan F. Stevens

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Gray, N.E., Alcazar Magana, A., Lak, P. et al. Centella asiatica: phytochemistry and mechanisms of neuroprotection and cognitive enhancement. Phytochem Rev 17, 161–194 (2018). https://doi.org/10.1007/s11101-017-9528-y

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