Skip to main content
Log in

Human Acyl-CoA:Cholesterol Acyltransferase-inhibiting Dammarane Triterpenes from Rhus chinensis

  • Bioactive Materials
  • Article
  • Published:
Journal of the Korean Society for Applied Biological Chemistry Submit manuscript

Abstract

In the process of screening for anti-human acyl-CoA:cholesterol acyltransferase (hACAT) agents from plant resources, we found that the 80% methanolic extract of Rhus chinensis (R. chinensis) exhibited significant antioxidative and hACAT activities in rats. Two compounds were isolated as active principles from the ethyl acetate soluble fraction of the branches of R. chinensis. The structures of compounds 1 and 2 were determined as hydroxydammarenone and semialactone, respectively, by means of MS and NMR spectroscopic analysis. Compound 1 has been isolated from this plant for the first time. Compounds 1 and 2 showed inhibitory activities on both human ACAT1 with IC50 values of 12.4, and 79.1 μM and on human ACAT2 with IC50 values of 30.5 and 76.9 μM, respectively. These results suggested that R. chinensis containing dammarane triterpenes 1 and 2 might be effective in the prevention and treatment of hypercholesterolemia or atherosclerosis via inhibitory effect on hACAT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Brecher P and Chan CT (1980) Properties of Acyl-CoA: cholesterol O-acyltransferase in aortic microsomes from atherosclerotic rabbits. Biochim Biophys Acta- Lipids and Lipid Metabolism 617, 458–471.

    Article  CAS  Google Scholar 

  • Cha BC, Lee SB, Rhim TJ, and Lee KH (2000) Constituents of antioxidative activity and free radical scavenging effect from Galla rhois (Rhus javanica Linne). Korean J Pharmacogn 31, 185–189.

    CAS  Google Scholar 

  • Cho KH, An S, Lee WS, Paik YK, Kim YK, and Jeong TS (2003) Mass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation. Biochem Biophys Res Commun 309, 864–872.

    Article  CAS  Google Scholar 

  • Choi I (2003) Antimicrobial activity of Rhus javanica extracts against animal husbandry disease-related bacteria. J Korean Soc Food Sci Nutr 32, 1214–1220.

    Article  Google Scholar 

  • Chung SC, Hwang BY, Oh GJ, Kang SJ, Kim MJ, Choi WH, Lee KS, and Ro JS (1999) Chemical components from the stem bark of Rhus javanica L. Korean J Pharmacogn 30, 295–300.

    CAS  Google Scholar 

  • Hua DH, Huang XD, Tamura M, Chen Y, Woltkamp M, Jin LW, Perchellet EM, Perchellet JP, Chiang PK, Namatame I, and Tomoda H (2003) Syntheses and bioactivities of tricyclic pyrones. Tetrahedron 59, 4795–4803.

    Article  CAS  Google Scholar 

  • Hutter-Paier B, Huttunen HJ, Puglielli L, Eckman CB, Kim DY, Hofmeister A, Moir RD, Domnitz SB, Frosch MP, Windisch M, and Kovacs DM (2004) The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer’s disease. Neuron 44, 227–238.

    Article  CAS  Google Scholar 

  • Jeong TS, Kim SU, Son KH, Kwon BM, Kim YK, Choi MU, and Bok SH (1995) GERI-BP001 compounds, new inhibitors of acyl-CoA: Cholesterol acyltransferase from Aspergillus fumigatus F37. J Antibio 48, 751–756.

    CAS  Google Scholar 

  • Kim HJ, Jang DI, and Choi SW (1997) Inhibitors of tyrosinase and melanogenesis from Galla rhois. J Food Sci Nutr 2, 285–290.

    CAS  Google Scholar 

  • Kurokawa M, Nakano M, Ohyama H, Hozumi T, Kageyama S, Namba T, and Shiraki K (1997) Prophylactic efficacy of traditional herbal medicines against recurrent herpes simplex virus type 1 infection from latently infected ganglia in mice. J Dermatol Sci 14, 76–84.

    Article  CAS  Google Scholar 

  • Lawrence LR and Gregory SS (2000) Cholesterol esters and atherosclerosis-a game of ACAT and mouse. Nat Med 6, 1341–1347.

    Article  Google Scholar 

  • Lee DY, Jung L, Lyu HN, Jeong TS, Lee YH, and Baek NI (2009) Triterpenoids from the Fruits of Cornus kousa Burg as Human Acyl-CoA: Cholesterol Acyltransferase Inhibitors. Food Sci Biotechnol 18, 223–227.

    CAS  Google Scholar 

  • Lee IS, Oh SR, Ahn KS, and Lee HK (2001) Semialactone, isofouquierone peroxide and fouquierone, three new dammarane triterpenes from Rhus javanica. Chem Pharm Bull (Tokyo) 49, 1024–1026.

    Article  CAS  Google Scholar 

  • Lee WS, Im KR, Park YD, Sung ND, and Jeong TS (2006) Human ACAT-1 and ACAT-2 Inhibitory Activities of pentacyclic triterpenes from the leaves of Lycopus lucidus TURCZ. Biol Pharm Bull 29, 382–384.

    Article  CAS  Google Scholar 

  • Lee YJ, Shin DH, Chang YS, and Kang WS (1993) Antioxidative effect of Rhus javanica Linne extract by various solvents. Korean J Food Sci Technol 25, 677–682.

    Google Scholar 

  • Liu J, Sun HB, Wang, XF, Mu DY, Liao H, and Zhang L (2007) Effects of oleanolic acid and maslinic acid on hyperlipidemia. Drug Dev Res 68, 261–266.

    Article  CAS  Google Scholar 

  • Nishimura K, Miyase T, and Noguchi H (1999) Triterpenoid saponins from Ilex kudincha. J Nat Prod 62, 1128–1133.

    Article  CAS  Google Scholar 

  • Puglielli L, Konopka G, Pack-Chung E, Ingano LAM, Berezovska O, Hyman BT, Chang T Y, Tanzi RE, and Kovacs DM (2001) Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid β-peptide. Nat Cell Biol 3, 905–912.

    Article  CAS  Google Scholar 

  • Puglielli L, Tanzi RE, and Kovacs DM (2003) Alzheimer’s disease: the cholesterol connection. Nat Neurosci 6, 345–351.

    Article  CAS  Google Scholar 

  • Rudel LL, Lee RG, and Cockman TL (2001) Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis. Curr Opin Lipidol 12, 121–127.

    Article  CAS  Google Scholar 

  • Runz H, Rietdorf J, Tomic I, de Bernard M, Beyreuther K, Pepperkok R, and Hartmann T (2002). Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells. J Neurosci 22, 1679–1689.

    CAS  Google Scholar 

  • Shim YJ, Do HK, Ah SY, Kim YS, Seong JK, Park IS, and Min BH (2003) Inhibitory effect of aqueous extract from the gall of Rhus chinensis on alpha-glucosidase activity and postprandial blood glucose. J Ethnopharmacol 85, 283–287.

    Article  Google Scholar 

  • Wahrle S, Das P, Nyborg AC, McLendon C, Shoji M, Kawarabayashi T, Younkin LH, Younkin S G, and Golde TE (2002) Cholesterol-dependent γ-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiol Dis 9, 11–23.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyung-Sik Song.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, GS., Jeong, TS., Kim, Y.O. et al. Human Acyl-CoA:Cholesterol Acyltransferase-inhibiting Dammarane Triterpenes from Rhus chinensis . J. Korean Soc. Appl. Biol. Chem. 53, 417–421 (2010). https://doi.org/10.3839/jksabc.2010.064

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.3839/jksabc.2010.064

Key words

Navigation