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Published Online: 12 May 2020

Pharmacological Effects of 1′-Acetoxychavicol Acetate, a Major Constituent in the Rhizomes of Alpinia galanga and Alpinia conchigera

Publication: Journal of Medicinal Food
Volume 23, Issue Number 5


1′-Acetoxychavicol acetate (ACA) is found in the rhizomes or seeds of Alpinia galanga and Alpinia conchigera, which are used as traditional spices in cooking and traditional medicines in Southeast Asia. ACA possesses numerous medicinal properties. Those include anticancer, antiobesity, antiallergy, antimicrobial, antidiabetic, gastroprotective, and anti-inflammatory activities. ACA is also observed to exhibit antidementia activity. Recent studies have demonstrated that combining ACA with other substances results in synergistic anticancer effects. The structural factors that regulate the activity of ACA include (1) the acetyl group at position 1′, (2) the acetyl group at position 4, and (3) the unsaturated double bond between positions 2′ and 3′. ACA induces the activation of AMP-activated protein kinase (AMPK), which regulates the signal transduction pathways, and has an important role in the prevention of diseases, including cancer, obesity, hyperlipidemia, diabetes, and neurodegenerative disorders. Such findings suggest that AMPK has a central role in different pharmacological functions of ACA, and ACA is useful for the prevention of life-threatening diseases. However, more studies should be performed to evaluate the clinical effects of ACA and to better understand its potential.

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1. Kondo A, Ohigashi H, Murakami A, Suratwadee J, Koshimizu K: 1’-Acetoxychavicol acetate as a potent inhibitor of tumor promoter-induced Epstein-Barr virus activation from Languas galangal, a traditional Thai condiment. Biosci Biotech Biochem 1993;57:1344–1345.
2. Ohigashi H, Murakami A, Koshimizu K: Antitumor promoters from edible plants. In: Food Phytochemicals for Cancer Prevention II. Tea, Spices and Herbs, Vol. 547 (Ho CT, Osawa T, Huang MT, Rosen RT, eds.). American Chemical Society, Washington, DC, 1994, pp. 251–261.
3. Ohnishi M, Tanaka T, Makita H, Kawamori T, Mori H, Satoh K, Hara A, Murakami A, Ohigashi H, Koshimizu K: Chemopreventive effect of a xanthine oxidase inhibitor, 1’-acetoxychavicol acetate, on rat oral carcinogenesis. Jpn J Cancer Res 1996;87:349–356.
4. Murakami A, Ohura S, Nakamura Y, Koshimizu K, Ohigashi H: 1′-Acetoxychavicol acetate, a superoxide anion generation inhibitor, potently inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in ICR mouse skin. Oncology 1996;53:386–391.
5. Tanaka T, Kawabata K, Kakumoto M, Makita H, Matsunaga K, Mori H, Satoh K, Hara A, Murakami A, Koshimizu K, Ohigashi H: Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1′-acetoxychavicol acetate. Jpn J Cancer Res 1997;88:821–830.
6. Kobayashi Y, Nakae D, Akai H, Kishida H, Okajima E, Kitayama W, Denda A, Tsujiuchi T, Murakami A, Koshimizu K, Ohigashi H, Konishi Y: Prevention by 1’-acetoxychavocol acetate of the induction but not grown of putative preneoplastic, glutathione S-transferase placental form-positive, focal lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet. Carcinogenesis 1998;19:1809–1814.
7. Miyauchi M, Nishikawa A, Furukawa F, Nakamura H, Son HY, Murakami A, Ohigashi H, Hiroe M: Inhibitory effects of 1’-acetoxychavicol acetate on N-nitrosobis(2-oxopropyl)-amine-induced initiation of cholangiocarcinogenesis in Syrian hamster. Jpn J Cancer Res 2000;91:477–484.
8. Kawabata K, Tanaka T, Yamamoto T, Ushida J, Hara A, Murakami A, Koshimizu K, Ohigashi H, Stoner GD, Mori H: Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1’-acetoxychavicol acetate. Jpn J Cancer Res 2000;91:148–155.
9. Mori H, Niwa K, Zheng Q, Yamada Y, Sakata K, Yoshimi N: Cell proliferation in cancer prevention: Effects of preventive agents on estrogen-related endometrial carcinogenesis model and on an in vitro model in human colorectal cells. Mutat Res 2001;480:201–207.
10. Ito K, Nakazato T, Murakami A, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Ohigashi H, Ikeda Y, Kizaki Y: Induction of apoptosis in human myeloid leukemic cells by 1’-acetoxychavicol acetate through a mitochondrial- and Fas-mediated dual mechanism. Clin Cancer Res 2004;10:2120–2130.
11. Ito K, Nakazato T, Xian MJ, Yamada T, Hozumi N, Murakami A, Ohigashi H, Ikeda Y, Kizaki M: 1’-Acetoxuchavicol acetate is a novel nuclear factor kB inhibitor with significant activity against multiple myeloma in vitro and in vivo. Cancer Rec 2005;65:4417–4424.
12. Ichikawa H, Takada Y, Murakami A, Aggarwal BB: Identification of a novel blocker of I kappa B alpha kinase that enhances cellular apoptosis and inhibits cellular invasion through suppression of NF-kappa B-regulated gene products. J Immunol 2005;174:7383–7392.
13. Batra V, Sted Z, Gill JN, Coburn MA, Adegboyega P, DiGiovanni J, Mathis JM, Shi RH, Clifford JL, Kleiner-Hsncock HE: Effect of the tropical ginger compound, 1’-acetoxychavicol acetate, against tumor promotion in K5.Stat3C transgenic mice. J Exp Clin Cancer Res 2012;31:57.
14. Ito K, Nakazato T, Murakami A, Ohigashi H, Ikeda Y, Kizaki M: 1’-Acetoxychavicol acetate induces apoptosis of myeloma cells via induction of TRAIL. Biochem Biophys Res Commun 2005;338:1702–1710.
15. Campbell CT, Prince M, Landry GM, Greg M, Kha V, Kleiner HE: Pro-apoptotic effects of 1’-acetoxychavicol acetate in human breast carcinoma cells. Toxicol Lett 2007;173:151–160.
16. Moffatt J, Hashimoto M, Kojima A, Kennedy DO, Murakami A, Koshimizu K, Ohigashi H, Matsui-Yuasa I: Apoptosis induced by 1’acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation. Carcinogenesis 2000;21:2151–2157.
17. Xu SH, Kojima-Yuasa A, Azuma H, Huang XD, Norikura T, Kennedy DO, Matsui-Yuasa I: (1’S)-Acetoxychavicol acetate and its enantiomer inhibit tumor cells proliferation via different mechanisms. Chem Biol Interact 2008;172:216–223.
18. Higashida M, Xu SH, Kojima-Yuasa A, Kennedy DO, Murakami A, Ohigashi H, Matsui-Yuasa I: 1’-Acetoxychavicol acetate-induced cytotoxicity is accompanied by a rapid and drastic modulation of glutathione metabolism. Amino Acids 2009;36:107–113.
19. Moffatt J, Kennedy DO, Kojima A, Hasuma T, Yano Y, Otani S, Murakami A, Koshimizu K, Ohigashi H, Matsui-Yuasa I: Involvement of protein tyrosine phosphorylation and reduction of cellular sulfhydryl groups in cell death induced by 1’-acetoxychavicol acetate in Ehrlich ascites tumor cells. Chem Biol Interact 2002;139:215–230.
20. Unahara Y, Kojima-Yuasa A, Higashida M, Kennedy DO, Murakami A, Ohigashi H, Matsui-Yuasa I: Cellular thiol status-dependent inhibition of tumor cell growth via modulation of p27(kip1)stop translocation and retinoblastoma protein phosphorylation by 1’-acetoxychavicol acetate. Amino Acids 2007;33:469–476.
21. Xu SH, Kojima-Yuasa A, Azuma H, Kennedy DO, Konishi Y, Matsui-Yuasa I: Comparison of glutathione reductase activity and the intracellular glutathione reducing effects of 13 derivatives of 1’-acetoxychavicol acetate in Ehrlich ascites tumor cells. Chem Biol Interact 2010;185:235–240.
22. Baradwaj RG, Rao MV, Kumar TS: Novel purification of 1’S-1’-Acetoxychavicol acetate from Alpinia galanga and its cytotoxic plus antiproliferative activity in colorectal adenocarcinoma cell line SW 480. Biomed Pharmacother 2017;91:485–493.
23. Pang X, Zhang L, Lai L, Chen J, Wu Y, Yi Z, Zhang J, Qu W, Aggarwal BB, Liu M: 1’-Acetoxychavicol acetate suppresses angiogenesis-mediated human prostate tumor growth by targeting VEGF-mediated Src-FAK-Rho GTPase-signaling pathway. Carcinogenesis 2011;32:904–912.
24. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T: Identification of novel genes coding for small expressed RNAs. Science 2001;294:853–858.
25. Wu S, Huang S, Ding J, Zhao Y, Liang L, Liu T, Han R, He X: Multiple microRNAs modulate p21Cip1/waf1 expression by directly targeting its 3’ untranslated region. Oncogene 2010;29:2302–2308.
26. Phuah NH, La In L, Azmi MN, Ibraim H, Awang K, Nagoor NH: Alteration of microRNA expression patterns in human cervical carcinoma cells (Ca Ski) toward 1’S-1’-acetoxychavicol acetate and cisplatin. Reprod Sci 2013;20:567–578.
27. Wang H, Shen L, Li X, Sun M: MicroRNAs contribute to anticancer effect of 1’acetoxychavicol acetate in human head and neck squamous cell carcinoma cell line HN4. Biosci Biotechnol Biochem 2013;77:2348–2355.
28. Phuah NH, Azmi MN, Awang K, Nagoor NH: Down-regulation of microRNA-210 confers sensitivity towards 1’S-1’-acetoxychavicol acetate [ACA] in cervical cancer cells by targeting SMAD4. Mol Cells 2017;40:291–298.
29. Phuah NH, Azmi MN, Awang K, Nagoor NH: Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1’S-1’-acetoxychavicol acetate via regulating RSUI. Onco Targets Ther 2017;10:1695–1705.
30. Farnsworth NR, Bunyapraphatsara N: The medicinal plants. Recommended for primary health care system. In: Thai Medicinal Plants: Recommendation for Primary Health Care System, (Farnsworth NR, ed.). Medicinal Plant Information Center, Bangkok, 1992. pp. 409.
31. Narukawa M, Koizumi K, Iwasaki Y, Kubota K, Watanabe T: Galangal pungent component, 1’-acetoxychavicol acetate, activates TRPA1. Biosci Biotechnol Biochem 2010;74:1694–1696.
32. Lieder B, Zaunschirm M, Holik AK, Ley JP, Hans J, Krammer G, Somoza V: The alkamide trans-pellitorine targets PPARγ via TRPV1 and TRPA1 to reduce lipid accumulation in developing 3T3-L1 adipocytes. Front Pharmacol 2017;8:316.
33. Ohnishi R, Matsui-Yuasa I, Deguchi Y, Yaku K, Tabuchi M, Munakata H, Akahoshi Y, Kojima-Yuasa A: 1’-Acetoxychavicol acetate inhibits adipogenesis in 3T3-L1 adipocytes and in high fat-fed rats. Am J Chin Med 2012;40:1189–1204.
34. Xie J, Wang Y, Jiang WW, Luo XF, Dai TY, Peng L, Song S, Li LF, Tao L, Shi CY, Sheng J: Moringa oleifera leaf petroleum ether extractiInhibits lipogenesis by activating the AMPK Signaling Pathway. Front Pharmacol 2018;9:1447.
35. Wang ZY, Hu JM, Hamzah SS, Ge SH, Lin YL, Zheng BD, Zeng SX, Lin SL: n-Butanol extract of lotus seeds exerts antiobesity effects in 3T3-L1 preadipocytes and high-fat diet-fed mice via activating adenosine monophosphate-activated protein kinase. J Agric Food Chem 2019;67:1092–1103.
36. Kang MC, Ding YL, Lee SH: Inhibition of adipogenesis by diphlorethohydroxycarmalol (DPHC) through AMPK activation in adipocytes. Marin Drugs 2019;17:E44.
37. Mitsui S, Kobayashi S, Nagahori H, Ogiso A: Constituents from seeds of Alpinia galangal Wild. And their anti-ulcer activities. Chem Pharm Bull 1976;24:2377–2382.
38. Matsuda H, Pongpiriyadacha Y, Morikawa T, Ochi M, Yoshikawa M. Gastroprotective effects of phenylpropanoids from the rhizomes of Alpinia galangal in rats: Structural requirements and mode of action. Eur J Pharmacol 2003;471:59–67.
39. Yaku K, Matsui-Yuasa I, Azuma H, Kojima-Yuasa A: 1’-Acetoxychavicol acetate enhances the phase II enzyme activities via the increase in intracellular Nrf-2 level and cytosolic p21 level. Am J Chin Med 2011;39:789–802.
40. Matsuda H, Morikawa T, Managi H, Yoshikawa M: Antiallergic principles from Alpinia galangal: Structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-a and IL-4 in RBL-2H3 cells. Bioorg Med Chem Lett 2003;13:3197–3202.
41. Schwartz LB, Levis RA, Seldin D, Austen KF: Acid-hydrolases and tryptase from secretory granules of dispersed human-lung mast-cells. J Immunol 1981;126:1290–1294.
42. Seo JW, Cho SC, Park SJ, Lee EJ, Lee JH, Han SS, Pyo BS, Park DH, Kim BH: 1’-Acetoxychavicol acetate isolated from Alpinia galangal ameliorates ovalbumin-induced asthma in mice. PLoS One 2013;8:e56447.
43. Phongpaichit S, Vuddhakul V, Subhadhirasakul S, Wattanapiromsakul C: Evaluation of antimycobacterial activity of extracts from plants used as self-medication by AIDS patients in Thailand. Pharm Biol 2006;44:71–75.
44. Warit S, Rukseeree K, Prammananan T, Hongmanee P, Billamas P, Jaitrong S, Chaiprasert A, Jaki BU, Pauli GF, Franzblau SG, Palittapongarnpim P: In vitro activities of enantiopure and racemic 1’-acetyoxychavicol acetate against clinical isolates of Mycobacterium tuberculosis. Sci Pharm 2017:85:32.
45. Latha C, Shriram VD, Jahagirdar SS, Dhakephalkar PK, Rojatkar SR: Antiplasmid activity of 1’-acetoxychavicol acetate from Alpinia galanga against multi-drug resistant bacteria. J Ethenopharmacol 2009;123:522–525.
46. Niyomkam P, Kaewburmrung S, Kaewnpparat S, Panichayupakaranant P: Antibacteral activity of Thai herbal extracts on acne involved microorganism. Pharm Biol 2010;48:375–380.
47. Yaku K, Matsui-Yuasa I, Kojima-Yuasa A: 1’-Acetoxychavicol acetate increases proteasome activity by activating cAMP-PKA signaling. Planta Med 2018;84:153–159.
48. Kojima-Yuasa A, Yamamoto T, Yaku K, Hirota H. Takenaka S, Kawabe K, Matsui-Yuasa I: 1’Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells. Chem Biol Interact 2016;257:101–109.
49. Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, Ulja D, Karuppagounder SS, Holson EB, Ratan RR, Ninan I, Chao MV: Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. Elife 2016;5:e15092.
50. Kojima-Yuasa A, Huang X, Matsui-Yuasa I: Synergistic anticancer activities of natural substances in human hepatocellular carcinoma. Diseases 2015;3:260–281.
51. In LLa, Ardhad NM, Ibrahim H, Azmi MN, Awang K, Nagoor NH: 1’-Acetoxychavicol acetate inhibits growth of human oral carcinoma xenograft in mice and potentiates cisplatin effect via proinflammatory. BCM Complement Altern Med 2012;12:179,
52. Kato R, Matsui-Yuasa I, Azuma H, Kojima-Yuasa A: The synergistic effect of 1’-acetoxychavicol acetate and sodium butyrate on the death of human hepatocellular carcinoma cells. Chem Biol Interact 2014;212:1–10.
53. Yaku K, Matsui-Yuasa I, Konishi Y, Kojima-Yuasa A: AMPK synergizes with the combined treatment of 1’-acetoxychavicol acetate and sodium butyrate to upregulate phase II detoxifying enzyme activities. Mol Nutr Food Res 2013;57:1198–1208.
54. Arshad NM, La In L, Soh TL, Azmi MN, Ibrahim H, Awang H, Dudich E, Tatulov E, Nagoor NH: Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1’-S-1’-acetoxychavicol acetate when used as a coplex against human tumours harbouring AFP-receptors. Oncotarget 2015;6:16151–16167.
55. Murakami A, Toyota K, Ohura S, Koshimizu K, Ohigashi H: Structure-activity relationships of (1’S)-1’-acetoxychavicol acetate, a major constituent of a southeast Asian condimiment plant Languasgalanga, on the inhibition of tumor-promoter-induced Epstein-Barr virus activation. J Agric Food Chem 2000;48:1518–1523.
56. Matsuda H, Ando S, Morikawa T, Kataoka S, Yoshikawa M: Structure-activity relationships of 1’S-1-acetoxychavicol acetate for inhibitory effect on NO production in lipopolysaccharide-activated mouse peritoneal macrophages. Bioorg Med Chem Lett 2005;15:1949–1953.
57. Azuma H, Miyasaka K, Yokotani T, Tachibana T, Kojima-Yuasa A, Matsui-Yuasa I, Ogino K: Lipase-catalyzed preparation of optically active 1’-accetoxychavicol acetates and their structure-activity relationships in apoptotic activity against human leukemia HL-60 cells. Bioorg Med Chem 2006;14:1811–1818.
58. Liu Y, Murakami A, Zhang S, Xu T: Structure-activity relationships of 1’-acetoxychavicol acetate homologues as new nuclear export signal inhibitors. Phamazie 2007;62:659–662.

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Published In

cover image Journal of Medicinal Food
Journal of Medicinal Food
Volume 23Issue Number 5May 2020
Pages: 465 - 475
PubMed: 32069429


Published online: 12 May 2020
Published in print: May 2020
Published ahead of print: 18 February 2020
Accepted: 9 January 2020
Received: 20 May 2019


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Akiko Kojima-Yuasa [email protected]
Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan.
Isao Matsui-Yuasa
Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan.


Address correspondence to: Akiko Kojima-Yuasa, PhD, Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan. [email protected]

Author Disclosure Statement

No competing financial interest exists.

Funding Information

This work was supported by JSPS KAKENHI (Grant Nos. JP 24500987 and JP15K00832).

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