Arginase II Inhibitory Activity of Phenolic Compounds from Caesalpinia sappan L.


  • Dao C. To Phenikaa University Nano Institute (PHENA), Phenikaa University, Yen Nghia, Ha Dong, Hanoi 12116, Vietnam
  • Manh H. Tran School of Medicine & Pharmacy, The University of Danang, Hoa Quy, Ngu Hanh Son, Da Nang City 550000, Vietnam
  • Phi H. Nguyen Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay district, Hanoi 122100, Vietnam
  • Nguyen T. Ai Nhung Department of Chemistry, University of Sciences, Hue University, Hue 530000, Vietnam
  • Tu T. T. Nguyen Faculty of Traditional Medicine, Hanoi Medical University, 01 Ton That Tung Street, Dong Da District, Hanoi, Vietnam


C57BL/6 mice, arginase, phenolic, Leguminosae, Caesalpinia sappan


Inhibition of arginase from natural compounds has been proposed as a therapeutic approach for the treatment of cardiovascular diseases. Therefore, this study aims to evaluate the arginase inhibitory activity of isolated compounds. Based on bioactivity-guided fractionation, the ethyl acetate fraction was further subjected to column chromatography to obtain seven compounds (17). The chemical structures of the isolated compounds were determined by analyzing NMR spectral data and referring to data from the literature. The arginase II inhibitory activity of compounds 17 were investigated in vitro using an enzyme solution prepared from the kidney of anesthetized C57BL/6 mice. Compounds 1, 2, and 7 potentially inhibit arginase II activity, with IC50 values ranging from 8.1 to 14.2 μM, whereas the remaining compounds were inactive. This study is the first to assess compounds isolated from C. sappan heartwood with regard to their arginase inhibitory activity. 


Ivanenkov YA, Chufarova NV. Small-molecule arginase inhibitors. Pharm Pat Anal. 2014; 3(1):65-85.

Jenkinson CP, Grody WW, Cederbaum SD. Comparative properties of arginases. Comp Biochem Phys. 1996; 114(1):107-132.

White AR, Ryoo S, Li D, Champion HC, Steppan J, Wang D, Nyhan D, Shoukas AA, Hare JM, Berkowitz DE. Knockdown of arginase I restores NO signaling in the vasculature of old rats. Hypertension. 2006; 47(2):245-251.

Ryoo S, Bhunia A, Chang F, Shoukas A, Berkowitz DE, Romer LH. OxLDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signaling. Atherosclerosis. 2011; 214(2):279-287.

Shin W, Cuong TD, Lee JH, Min B, Jeon BH, Lim HK, Ryoo S. Arginase inhibition by ethylacetate extract of Caesalpinia sappan Lignum contributes to activation of endothelial nitric oxide synthase. Korean J Physiol Pharmacol. 2011; 15(3):123-128.

Pournaghi N, Khalighi-Sigaroodi F, Safari E, Hajiaghaee R. A review of the genus Caesalpinia L.: emphasis on the cassane and norcassane compounds and cytotoxicity effects. J Med Plants. 2020; 19(76):1-20.

Ogbeide O, Okhomina OK, Omoregie IG, Unuigbe CA, Augustine I, Isacc A, Iheanacho M, Akubuiro P, Solomon A, Irabor EEI, Owolabi JB, Falodun A. Antimalarial, ferric reducing antioxidant power and elemental analysis of Caesalpinia pulcherrima leaf extract. J Chem Soc Nigeria.

; 45(4):704 -711.

Erharuyi O, Adhikari A, Falodun A, Aimas J, Ahmmad M, Rehan I, Choudhary MI. Cytotoxic, anti-inflmmatory, and leishmanicidal activities of diterpenes isolated from the roots of Caesalpinia pulcherrima. Planta Med. 2017; 83(1-02):100-110.

Erharuyi O, Adhikari A, Falodun A, Imad R, Choudhary MI. Derivatization of cassane diterpenoids from Caesalpinia pulcherrima (L.) Sw. and evaluation of their cytotoxic and leishmanicidal activities. Tetrahedron Lett. 2016; 57(20):2201-2206.

Sadaf S, Erharuyi O, Falodun A, Choudhary MI, Sammer Y. Crystal structure of (3S*,4S*,4aS*,5R*,6R*,6aS*,7R*,11aS*,11bR*)-5,6-bis-

(benzoyloxy)-3,4a-dihydroxy-4,7,11btrimethyl-1,2,3,4,4a,5,6,6a,7,11,11a,-11bdodecahydrophenanthro[3,2-b]-furan-4-carboxylic acid methanol monosolvate. Acta Crystallogr. 2015; E71:739-740.

Bich DH. Selected Medicinal Plants in Vietnam. (1st ed.). Hanoi: Science and Technology Publishing House; 1999. 151-154 p.

Cuong TD, Hung TM, Kim JC, Kim EH, Woo MH, Choi JS, Lee JH, Min BS. Phenolic compounds from Caesalpinia sappan heartwood and their anti-inflammatory activity. J Nat Prod. 2012; 75(12):2069-2075.

Min BS, Cuong TD, Hung TM, Min BK, Shin BS, Woo MH. Compounds from the heartwood of Caesalpinia sappan and their anti-inflammatory activity. Bioor Med Chem Lett. 2012; 22(24):7436-7439.

Wan YJ, Xu L, Song WT, Liu YQ, Wang LC, Zhao MB, Jiang Y, Liu LY, Zeng KW, Tu PF. The ethanolic extract of Caesalpinia sappan heartwood inhibits cerebral ischemia/reperfusion injury in a rat model through a multitargeted pharmacological mechanism. Front Pharmacol.

; 10:29.

Hung TM, Hai NX, Nhan NT, Quang TT, Quan TL, Cuong TD, Dang NH, Dat NT. Cytotoxic activity of new phenolics compounds from Vietnamese Caesalpinia sappan. Biosci Biotechnol Biochem. 2013; 77(12):2378-2382.

Widodo N, Puspitarini S, Widyananda MH, Alamsyah A, Wicaksono ST, Masruri M, Jatmiko DW. Anticancer activity of Caesalpinia sappan by downregulating mitochondrial genes in A549 lung cancer cell line. F1000Res. 2022; 11:169.

Bukke AN, Hadi FN, Babu KS, Shankar PC. In vitro studies data on anticancer activity of Caesalpinia sappan L. heartwood and leaf extracts on MCF7 and A549 cell lines. Data Brief. 2018; 19:868-877.

Astirin OP, Prayitno A, Artanti AN, Herawati E, Dewi AR, Aryani VR, Dewangga VS. Synergistic cytotoxic effect of Anonna muricata and Caesalpinia sappan nanoparticles via expression of BAD pro-apoptotic protein in HeLa cervical cancer cells. Trop J Nat Prod Res. 2021; 5(12):2108-2114.

Acero LH, Cruz MEP, Tuy FS. Termiticidal potential of sappan (Caesalpinia sappan) seeds. Int J Chem Eng Appl. 2018; 9(6):216-220.

Laksmiani NPL, Leliqia NPE, Armita PMN, Arijana NIGK, Saputra AABI, Prananingtyas KI. In-silico and In-vitro studies of antioxidant and sun protection activities of Sappan wood (Caesalpinia sappan L.). Trop J Nat Prod Res. 2020; 4(12):1072-1080.

Yim DG, Seo JK, Yum HW, Zahid MA, Park JY, Parvin R, Go J, Jin SK, Koo OK, Yang HS. Effects of Caesalpinia sappan L. extract on the color stability, antioxidant and antimicrobial activity in cooked pork sausages during cold storage. LWT Food Sci Technol. 2019; 112:108235.

Puttipan R, Chansakaow S, Khongkhunthian S, Okonogi S. Caesalpinia sappan: A promising natural source of antimicrobial agent for inhibition of cariogenic bacteria. Drug Discov Ther. 2018; 12(4):197-205.

Panthong S, Sakpakdeejaroen I, Kuropakornpong P, Jaicharoensub J, Itharat A. Antibacterial activity and stability evaluation of “Apo-taat” remedy extract for inhibiting diarrhoea-causing bacteria. Trop J Nat Prod Res. 2020; 4(12):1101-1107.

Pattananandecha T, Apichai S, Julsrigival J, Ogata F, Kawasaki N, Saenjum C. Antibacterial activity against foodborne pathogens and inhibitory effect on antiinflammatory mediators production of brazilin-enriched extract from Caesalpinia sappan Linn. Plants (Basel). 2022;


Namikoshi M, Nakata H, Yamada H, Nagai M, Saitoh T. Homoisoflavonoids and related compounds: II. Isolation and absolute configurations of 3,4-dihydroxy lated homoisoflavans and brazilins from Caesalpinia sappan L. Chem Pharm Bull. 1987; 35(7):2761-2773.

Nguyen MTT, Awale S, Tezuka Y, Tran QL, Kadota S. Xanthine oxidase inhibitors from the heartwood of Vietnamese Caesalpinia sappan. Chem Pharm Bull. 2005; 53(8):984-988.

Li F, Awale S, Tezuka Y, Kadota S. Cytotoxic constituents from Brazilian red propolis and their structure–activity relationship. Bioorg Med Chem. 2008; 16(10):5434-5440.

Namikoshi M, Nakata H, Nuno M, Ozawa T, Saitoh T. Homoisoflavonoids and related compounds. III. Phenolic constituents of Caesalpinia japonica SIEB. et ZUCC. Chem Pharm Bull. 1987; 35(9):3568-3575.

Lim CJ, Cuong TD, Hung TM, Ryoo SW, Lee JH, Kim EH, Woo MH, Choi JS, Min BS. Arginase II inhibitory activity of phenolic compounds from Saururus chinensis. Bull Korean Chem Soc. 2012; 33(9):3079-3082.

Kim SW, Cuong TD, Hung TM, Ryoo S, Lee JH, Min BS. Arginase II inhibitory activity of flavonoid compounds from Scutellaria indica. Arch Pharm Res. 2013; 36(8):922-926.

Woo A, Shin W, Cuong TD, Min B, Lee JH, Jeon BH, Ryoo S. Arginase inhibition by piceatannol-3′-O-β-Dglucopyranoside improves endothelial dysfunction via activation of endothelial nitric oxide synthase in ApoE-null mice fed a high-cholesterol diet. Int J Mol Med. 2013;


Anadozie SO, Akinyemi JA, Agunbiade S, Ajiboye BO, Adewale OB. Bryophyllum pinnatum inhibits arginase II activity and prevents oxidative damage occasioned by carbon tetrachloride (CCl4) in rats. Biomed Pharmacother. 2018; 101:8-13.

Arraki K, Totoson P, Decendit A, Zedet A, Maroilley J, Badoc A, Demougeot C, Girard C. Mammalian arginase inhibitory activity of methanolic extracts and isolated compounds from Cyperus species. Molecules. 2021; 26(6):1694.

Arraki K, Totoson P, Attia R, Zedet A, Pudlo M, Messaoud C, Demougeot C, Girard C. Arginase inhibitory properties of flavonoid compounds from the leaves of Mulberry (Morus alba, Moraceae). J Pharm Pharmacol. 2020; 72(9):1269-1277.

Hidayati AA, Sauriasari R, Elya B. Arginase inhibitory and antioxidant activities in Syzygium cumini (L.) Skeels leaves extracts collected from three different locations of java. Pharm Sci Asia. 2020; 47(1):65-73.

Indriani D, Elya B, Noviani A. Arginase inhibitory activity and total flavonoid content on Caesalpinia ferrea C. Mart stem bark extracts. Pharmacogn J. 2018; 10(6):1180-1183.

Najid A, Elya B, Noviani A. Arginase inhibitory activity of stem bark extracts of Caesalpinia tortuosa Roxb. Int J Appl Pharm. 2018; 10(1):130-132.

Wulansari A, Elya B, Noviani A. Arginase inhibitory and antioxidant activities of Caesalpinia coriaria (Jacq.) Willd. bark extract. Pharmacogn J. 2018; 10(6):1174-1179.



How to Cite

To, D. C., Tran, M. H., Nguyen, P. H., Ai Nhung, N. T., & Nguyen, T. T. T. (2023). Arginase II Inhibitory Activity of Phenolic Compounds from Caesalpinia sappan L.: Tropical Journal of Natural Product Research (TJNPR), 7(4), 2744–2748. Retrieved from

Most read articles by the same author(s)

1 2 > >>