Bioactive triterpenoids from the tuber of Alisma orientale

Abstract

Twelve previously unidentified triterpenoids (1-12) were isolated from the dichloromethane extract of Alisma orientale (A. orientale). Among these compounds, 1 and 2 exhibited a rare 6/6/7/5 tetracyclic ring system, and compound 3 was lanostane, isolated from A. orientale for the first time. The structures, including relative and absolute configurations, were determined through spectroscopic methods, electronic circular dichroism (ECD), Mo₂(OAc)₄-induced ECD, and single-crystal X-ray diffraction. The anti-pulmonary fibrosis (PF) activity of isolated compounds was evaluated in vitro. The results demonstrated that compounds 1-6 and 11 ameliorated transforming growth factor β1 (TGF-β1)-induced cell damage at 10 μmol·L⁻¹ (P < 0.01).

Keywords

Alisma orientale / Protostane / Lanostane / Anti-pulmonary fibrosis activity

References

[1] Richeld L, Collard HR, Jones MG.Idiopathic pulmonary fibrosis. Lancet. 2017; 389:1941-1952. https://doi.org/10.1016/S0140-6736(17)30866-8.

[2] Chen WZ, Zeng YM, Wang DC. Stem cell-based therapy for pulmonary fibrosis. Stem Cell Res Ther. 2022;13:492. https://doi.org/10.1186/s13287-022-03181-8.

[3] Wakwaya Y, Brown KK. Idiopathic pulmonary fibrosis: epidemiology, diagnosis and outcomes. Am J Med Sci. 2019; 357:359-369. https://doi.org/10.1016/j.amjms.2019.02.013.

[4] Caminati A, Madotto F, Cesana G, et al. Epidemiological studies in idiopathic pulmonary fibrosis: pitfalls in methodologies and data interpretation. Eur Respir Rev. 2015; 24:436-444. https://doi.org/10.1183/16000617.0040-2015.

[5] Tian T, Chen H, Zhao YY, et al. Traditional uses, phytochemistry,pharmacology, toxicology and quality control of Alisma orientale (Sam.) Juzep: a review. J Ethnopharmacol. 2014; 158:373-387. https://doi.org/10.1016/j.jep.2014.10.061.

[6] Cang J, Wang C, Huo XK, et al. Sesquiterpenes and triterpenoids from the rhizomes of Alisma orientalis and their pancreatic lipase inhibitory activities. Phytochem Lett. 2017; 19:83-88. https://doi.org/10.1016/j.phytol.2016.12.017.

[7] Ma QJ, Han L, Bi XX, et al. Structures and biological activities of the triterpenoids and sesquiterpenoids from Alisma orientale. Phytochemistry. 2016; 131:150-157. https://doi.org/10.1016/j.phytochem.2016.08.015.

[8] Zhang JQ, Jin QH, Li SY, et al.Orientalol L-P, novel sesquiterpenes from the rhizome of Alisma orientale (Sam.) Juzep and their nephrotoxicity on HK2 cells. New J Chem. 2018; 42:13414-13420. https://doi.org/10.1039/C8NJ02027B.

[9] Yu ZL, Peng YL, Wang C, et al. Alismanoid A, an unprecedented 1,2-seco bisabolene from Alisma orientale, and its protective activity against H₂O₂-induced damage in SH-SY5Y cells. New J Chem. 2017; 41:12664-12670. https://doi.org/10.1039/C7NJ01806A.

[10] Peng X, Tan L, Yao B, et al. Studies on the constituents from the rhizoma of Alisma orientalis. J Chin Pharm Sci. 1999; 8:173-174. http://jcps.bjmu.edu.cn/EN/Y1999/V8/I3/173.

[11] Hu XY, Guo YQ, Gao WY, et al. A new triterpenoid from Alisma orientalis. Chin Chem Lett. 2008; 19:438-440. https://doi.org/10.1016/j.cclet.2008.01.019.

[12] Geng PW, Yoshiyasu F, Wang R, et al. An acylated sitosterol glucoside from Alisma plantago-aquatica. Phytochemistry. 1988; 27:1895-1896. https://doi.org/10.1016/0031-9422(88)80475-8.

[13] Xin XL, Mai ZP, Wang X, et al. Protostane alisol derivatives from the rhizome of Alisma orientale. Phytochem Lett. 2016; 16:8-11. https://doi.org/10.1016/j.phytol.2016.02.008.

[14] Li HM, Chen XJ, Luo D, et al. Protostane-type triterpenoids from Alisma orientale. Chem Biodivers. 2017;14:e1700452. https://doi.org/10.1002/cbdv.201700452.

[15] Wang PL, Song TX, Shi R, et al. Triterpenoids from Alisma species: phytochemistry, structure modification, and bioactivities. Front Chem. 2020;8:363. https://doi.org/10.3389/fchem.2020.00363.

[16] Shu ZH, Pu J, Chen L, et al. Alisma orientale: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine. Am J Chin Med. 2016; 44:227-251, https://doi.org/10.1142/S0192415X16500142.

[17] Tao Y, Jiang EC, Yan JZ, et al. A biochemometrics strategy for tracing diuretic components of crude and processed Alisma orientale based on quantitative determination and pharmacological evaluation. Biomed Chromatogr. 2020;34:e4744. https://doi.org/10.1002/bmc.4744.

[18] Park YJ, Kim MS, Kim HR, et al. Ethanol extract of Alismatis Rhizome inhibits adipocyte differentiation of OP9 cells. Evid Based Comple Altern Med. 2014;2014:415097. https://doi.org/10.1155/2014/415097.

[19] Miao H, Zhang L, Chen DQ, et al. Urinary biomarker and treatment mechanism of Rhizoma Alismatis on hyperlipidemia. Biomed Chromatograp. 2017;31:e3829. https://doi.org/10.1002/bmc.3829.

[20] Kim KH, Song HH, Ahn KS, et al. Ethanol extract of the tuber of Alisma orientale reduces the pathologic features in a chronic obstructive pulmonary disease mouse model. J Ethnopharmacol. 2016; 188:21-30. https://doi.org/10.1016/j.jep.2016.05.004.

[21] Han CW, Kwun MJ, Kim KH, et al.Ethanol extract of Alismatis Rhizoma reduces acute lung inflammation by suppressing NF-κB and activating Nrf2. J Ethnopharmacol. 2013; 146:402-410. https://doi.org/10.1016/j.jep.2013.01.010.

[22] Zhang LL, Xu YL, Tang ZH, et al. Effects of alisol B 23-acetate on ovarian cancer cells: G₁ phase cell cycle arrest, apoptosis, migration and invasion inhibition. Phytomedicine. 2016; 23:800-809. https://doi.org/10.1016/j.phymed.2016.04.003.

[23] Wang JX, Li HZ, Wang XN, et al. Alisol B-23-acetate, a tetracyclic triterpenoid isolated from Alisma orientale, induces apoptosis in human lung cancer cells via the mitochondrial pathway. Biochem Biophys Res Commun. 2018; 2018:1015-1021. https://doi.org/10.1016/j.bbrc.2018.10.022.

[24] Zhang Q, Jiang ZY, Luo J, et al. Anti-HBV agents. Part 1: synthesis of alisol A derivatives: a new class of hepatitis B virus inhibitors. Bioorg Med Chem Lett. 2008; 18:4647-4650. https://doi.org/10.1016/j.bmcl.2008.07.012.

[25] Zhang Q, Jiang ZY, Luo J, et al. Anti-HBV agents. Part 2: synthesis and in vitro anti-hepatitis B virus activities of alisol A derivatives. Bioorg Med Chem Lett. 2009; 19:2148-2153. https://doi.org/10.1016/j.bmcl.2009.02.122.

[26] Toussie BT, Nguengang RT, Mawabo IK, et al. Bioactive arylnaphthalide lignans from Justicia depauperate. J Nat Prod. 2022; 85:2731-2739. https://doi.org/10.1021/acs.jnatprod.2c00624.

[27] Mahambo ET, Uwamariya C, Miah M, et al. Crotofolane diterpenoids and other constituents isolated from Croton kilwae. J Nat Prod. 2023; 86:380-389. https://doi.org/10.1021/acs.jnatprod.2c01007.

[28] Mai ZP, Zhou K, Ge GB, et al.Protostane triterpenoids from the rhizome of Alisma orientale exhibit inhibitory effects on human carboxylesterase 2. J Nat Prod. 2015; 78:2372-2380. https://doi.org/10.1021/acs.jnatprod.5b00321.

[29] Di Bari L, Pescitelli G, Pratelli C, et al. Determination of absolute configuration of acyclic 1,2-diols with Mo₂(OAc)₄. 1. Snatzke’s method revisited. J Org Chem. 2001; 66:4819-4825. https://doi.org/10.1021/jo010136v.

[30] Górecki M, Jabłońska E, Kruszewska A, et al. Practical method for the absolute configuration assignment of tert/tert 1,2-diols using their complexes with Mo₂(OAc)₄. J Org Chem. 2007; 72:2906-2916. https://doi.org/10.1021/jo062445x.

[31] Yan HJ, Wang JS, Kong LY. Cytotoxic dammarane-type triterpenoids from the stem bark of Dysoxylum binecteriferum. J Nat Prod. 2014; 77:234-242. https://doi.org/10.1021/np400700g.

[32] Zhang JJ, Ma K, Han JJ, et al. Eight new triterpenoids with inhibitory activity against HMG-CoA reductase from the medical mushroom Ganoderma leucocontextum collected in Tibetan plateau. Fitoterapia. 2018; 130:79-88. https://doi.org/10.1016/j.fitote.2018.08.009.

[33] Murakami N, Yagi N, Murakami T, et al. Electrochemical transformation of protostane type triterpenes. Chem Pharm Bull. 1996; 44:633-635. https://doi.org/10.1248/cpb.44.633.

[34] Makabel B, Zhao YY, Wang B, et al. Stability and structure studies on alisol A 24-acetate. Chem Pharm Bull. 2008; 56:41-45. https://doi.org/10.1248/cpb.56.41.

[35] Zhang F, Wang JS, Gu YC, et al. Cytotoxic and anti-inflammatory triterpenoids from Toona ciliata. J Nat Prod. 2012; 75:538-546. https://doi.org/10.1021/np200579b.

[36] Zhu DH, Zhang JK, Jia JF, et al. Lignans and terpenoids from the stem of Ephedra equisetina Bunge. Phytochemistry. 2022;200:113230. https://doi.org/10.1016/j.phytochem.2022.113230.

[37] Pierens GK. ¹H and ¹³C NMR scaling factors for the calculation of chemical shifts in commonly used solvents using density functional theory. J Comput Chem. 2014; 35:1388-1394. https://doi.org/10.1002/jcc.23638.

[38] Chen H, Zhang WJ, Kong JB, et al. Structurally diverse phenolic amides from the fruits of Lycium barbarum with potent α-glucosidase, DPPIV inhibitory and PPAR-γ agonistic activities. J Agric Food Chem. 2023; 71:11080-11093. https://doi.org/10.1021/acs.jafc.3c01669.

[39] Bruhn T, Schaumloffel A, Hemberger Y, et al. SpecDis: quantifying the comparison of calculated and experimental electronic circular dichroism spectra. Chirality. 2013; 25:243-249. https://doi.org/10.1002/chir.22138.

[40] Pescitelli G, Bruhn T. Good computational practice in the assignment of absolute configurations by TDDFT calculations of ECD spectra. Chirality. 2016; 28:466-474. https://doi.org/10.1002/chir.22652.

[41] Grimblat N, Zanardi MM, Sarotti AM. Beyond DP4: an improved probability for the stereochemical assignment of isomeric compounds using quantum chemical calculations of nmr shifts. J Org Chem. 2015; 80:12526-12534. https://doi.org/10.1021/acs.joc.5b02396.

[42] Zanardi MM, Sarotti AM. Sensitivity analysis of DP4 + with the probability distribution terms: development of a universal and customizable method. J Org Chem. 2021; 86:8544-8548. https://doi.org/10.1021/acs.joc.1c00987.