Oridonin: A Mini Review on the Anti-Cancer, Anti-Inflammatory, Cardioprotective, Hepatoprotective, Renoprotective and Lung Protective Properties
DOI:
https://doi.org/10.26538/tjnpr/v8i4.1Keywords:
pharmacological properties, diterpenoid, Donglingcao, Rabdosia rubescens, Isodon rubescensAbstract
Oridonin (ORI), an ent-kaurane tetracyclic diterpenoid from Isodon rubescens, is renowned for its anti-cancer properties. Known as Donglingcao, I. rubescens is a traditional Chinese herbal medicine that is widely used to treat sore throat, inflammation and gastrointestinal disorders. This mini-review is focused on the pharmacological activities of ORI other than anti-cancer properties. They include cardioprotective, hepatoprotective, renoprotective and lung protective properties of ORI. The pharmacological properties of ORI have not been reviewed before. Information on the effects and mechanisms of ORI in each pharmacological activity are tabulated with some explanations of technical terms used. The anti-asthmatic, anti-inflammatory, neuroprotective, immuno-suppressive, osteoblast protective and analgesic properties of ORI deserve more in-depth investigation. References used in this review are derived from Google, Google Scholar, PubMed and JStage, with search words based on the title and keywords.
References
Chen X, He X. Isodon rubescens (Hemls.) Hara.: A comprehensive review on traditional uses, phytochemistry, and pharmacological activities. Front Pharmacol. 2022; 13:766581.
Li XW, Hedge IC. Isodon. Flora of China. 1994;17:269-291.
Wiarts C. Isodon rubescens (Hemsl.) H. Hara. In: Lead Compounds from Medicinal Plants for the Treatment of Cancer. Academic Press & Elsevier, 2013.
Ye S, Sun S, Cai J, Jiang J. Research progress and future development potential of oridonin in pharmacological activities. Curr Mol Pharmacol. 2023;16(7):691-706.
Fujita E, Fujita T, Katayama H, Shibuya M. Oridonin, a new diterpenoid from Isodon species. Chem Commun. 1967; 6:252-254.
Zhang W, Huang Q, Hua ZC. Oridonin: A promising anticancer drug from China. Front Biol. 2010;5:540-545.
Zhang YH, Wu YL, Tashiro SI, Onodera S, Ikejima T. Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in human cervical carcinoma HeLa cells. Acta Pharmacol Sin. 2011;32(10):1266-1275.
Tian W, Chen SY. Recent advances in the molecular basis of anti-neoplastic mechanisms of oridonin. Chin J Integr Med. 2013;19(4):315-320.
Liu X, Xu J, Zhou J, Shen Q. Oridonin and its derivatives for cancer treatment and overcoming therapeutic resistance. Genes Dis. 2021;8(4):448-462.
Ali MA, Khan N, Ali A, Akram H, Zafar N, Imran K, Khan T, Khan K, Armaghan M, Palma‐Morales M, Rodríguez‐Pérez C. Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy – A comprehensive review. Food Sci Nutr. 2024; http://doi.org/10.1002/fsn3.3986
Hu X, Huang S, Ye S, Jiang J. The natural product oridonin as an anticancer agent: current achievements and problems. Curr Pharm Biotechnol. 2024;25(6):655-664.
Chen J, Wang S, Chen D, Chang G, Xin Q, Yuan S, Shen Z. The inhibitory effect of oridonin on the growth of fifteen human cancer cell lines. Chin J Clin Oncol. 2007;4:16-20.
Cheng W, Huang C, Ma W, Tian X, Zhang X. Recent development of oridonin derivatives with diverse pharmacological activities. Mini Rev Med Chem. 2019; 19(2):114-124.
Li J, Wu Y, Wang D, Zou L, Fu C, Zhang J, Leung GP. Oridonin synergistically enhances the anti-tumor efficacy of doxorubicin against aggressive breast cancer via pro-apoptotic and anti-angiogenic effects. Pharmacol Res. 2019;146:104313.
Yao J, Liu L, Sun Q, Shen X. Direct cellular targets and anticancer mechanisms of the natural product oridonin. MedComm–Futur Med. 2023;2(1):e35.
Xu J, Wold EA, Ding Y, Shen Q, Zhou J. Therapeutic potential of oridonin and its analogs: from anticancer and anti-inflammation to neuroprotection. Molecules. 2018; 23(2):474.
Li X, Zhang CT, Ma W, Xie X, Huang Q. Oridonin: A review of its pharmacology, pharmacokinetics and toxicity. Front Pharmacol. 2021;12:645824.
Ding C, Zhang Y, Chen H, Yang Z, Wild C, Ye N, Ester CD, Xiong A, White MA, Shen Q, Zhou J. Oridonin ring A-based diverse constructions of enone functionality: Identification of novel dienone analogues effective for highly aggressive breast cancer by inducing apoptosis. J Med Chem. 2013; 56(21):8814-8825.
Li J, Zhang D, Wu X. Synthesis and biological evaluation of novel exo-methylene cyclopentanone tetracyclic diterpenoids as antitumor agents. Bioorg Med Chem Lett. 2011;21(1):130-132.
Liang ST, Chen C, Jiang GH. Michael acceptor molecules in natural products and their mechanism of action. Front Pharmacol. 2022;13:1033003.
Du X, Que W, Hu X, Yu X, Guo WZ, Li XK. Oridonin prolongs the survival of mouse cardiac allografts by attenuating the NF-κB/NLRP3 pathway. Front Immunol. 2021; 12:719574.
Fu M, Xie D, Sun Y, Pan Y, Zhang Y, Chen X, Shi Y, Deng S, Cheng B. Exosomes derived from MSC pre‐treated with oridonin alleviates myocardial IR injury by suppressing apoptosis via regulating autophagy activation. J Cell Mol Med. 2021;25(12):5486-5496.
Gao RF, Li X, Xiang HY, Yang H, Lv CY, Sun XL, Chen HZ, Gao Y, Yang JS, Luo W, Yang YQ, Tang YH. The covalent NLRP3-inflammasome inhibitor Oridonin relieves myocardial infarction induced myocardial fibrosis and cardiac remodeling in mice. Int Immunopharmacol. 2021; 90:107133.
Lin J, Lai X, Fan X, Ye B, Zhong L, Zhang Y, Shao R, Shi S, Huang W, Su L, Ying M. Oridonin protects against myocardial ischemia–reperfusion injury by inhibiting GSDMD-mediated pyroptosis. Genes. 2022;13(11):2133.
Lu C, Chen C, Chen A, Wu Y, Wen J, Huang F, Zeng Z. Oridonin attenuates myocardial ischemia/reperfusion injury via down-regulating oxidative stress and NLRP3 inflammasome pathway in mice. Evid-Based Complement Altern Med. 2020; Article ID 7395187: 9 pp.
Xu M, Wan CX, Huang SH, Wang HB, Fan D, Wu HM, Wu Q, Ma Z, Deng W, Tang QZ. Oridonin protects against cardiac hypertrophy by promoting P21-related autophagy. Cell Death Dis. 2019;10(6):403.
Yu D, Li J, Wang Y, Guo D, Zhu C, Sun B, Zhou Z. Oridonin ameliorates doxorubicin induced-cardiotoxicity via the E2F1/Sirt6/PGC1α pathway in mice. Food Chem Toxicol. 2023;181:114050.
Chen Y, Jiang H, Zhan Z, Lu J, Gu T, Yu P, Liang W, Zhang X, Zhong X, Tang L. Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner. J Pharm Anal. 2023;13(11):1281-1295.
Cummins CB, Wang X, Sommerhalder C, Bohanon FJ, Nunez Lopez O, Tie HY, Rontoyanni VG, Zhou J, Radhakrishnan RS. Natural compound oridonin inhibits endotoxin-induced inflammatory response of activated hepatic stellate cells. BioMed Res Int. 2018; Article ID 6137420, 10 pp.
Deng Y, Chen C, Yu H, Diao H, Shi C, Wang Y, Li G, Shi M. Oridonin ameliorates lipopolysaccharide/D-galactosamine-induced acute liver injury in mice via inhibition of apoptosis. Am J Translat Res. 2017;9(9):4271-4279.
Hong MK, Liu HH, Chen GH, Zhu JQ, Zheng SY, Zhao D, Diao J, Jia H, Zhang DD, Chen SX, Gao L, Li J. Oridonin alters hepatic urea cycle via gut microbiota and protects against acetaminophen-induced liver injury. Oxid Med Cell Longev. 2021; Article ID 3259238, 15 pp.
Liu D, Qin H, Yang B, Du B, Yun X. Oridonin ameliorates carbon tetrachloride‐induced liver fibrosis in mice through inhibition of the NLRP3 inflammasome. Drug Devel Res. 2020;81(4):526-533.
Shi M, Deng Y, Yu H, Xu L, Shi C, Chen J, Li G, Du Y, Wang Y. Protective effects of oridonin on acute liver injury via impeding post-translational modifications of interleukin-1 receptor-associated kinase 4 (IRAK4) in the toll-like receptor 4 (TLR4) signaling pathway. Mediators Inflamm. 2019; Article ID 7634761: 11 pp.
Wang X, Gao M, Wang Z, Cui W, Zhang J, Zhang W, Xia Y, Wei B, Tang Y, Xu X. Hepatoprotective effects of oridonin against bisphenol A induced liver injury in rats via inhibiting the activity of xanthine oxidase. Sci Total Environ. 2021;770:145301.
Yu D, Li J, Wang Y, Guo D, Zhang X, Chen M, Zhou Z. Oridonin ameliorates acetaminophen‐induced acute liver injury through ATF4/PGC‐1α pathway. Drug Devel Res. 2023;84(2):211-225.
Zhang YW, Bao MH, Lou XY, Cheng Y, Yu J, Zhou HH. Effects of oridonin on hepatic cytochrome P450 expression and activities in PXR-humanized mice. Biol Pharm Bull. 2018;41(5):707-712.
Zhang T, Chen Y, Zhan Z, Mao Z, Wen Y, Liu S, Tang L. Oridonin alleviates d‐GalN/LPS‐induced acute liver injury by inhibiting NLRP3 inflammasome. Drug Devel Res. 2021; 82(4):575-580.
Gu H, Gwon MG, Kim JH, Leem J, Lee SJ. Oridonin attenuates cisplatin-induced acute kidney injury via inhibiting oxidative stress, apoptosis, and inflammation in mice. BioMed Res Int. 2022; Article ID 3002962, 10 pp.
Huang JH, Lan CC, Hsu YT, Tsai CL, Tzeng IS, Wang P, Kuo CY, Hsieh PC. Oridonin attenuates lipopolysaccharide-induced ROS accumulation and inflammation in HK-2 cells. Evid-based Complement Altern Med. 2020; Article ID 9724520, 8 pp. Huang G, Zhang Y, Zhang Y, Zhou X, Xu Y, Wei H,
Ma Y. Oridonin attenuates diabetesinduced renal fibrosis via inhibition of the TXNIP/NLRP3 and NFκB pathway in rats. Research Square. 2021; https://doi.org/10.21203/rs.3.rs-1144780/v1
Li J, Bao L, Zha D, Zhang L, Gao P, Zhang J, Wu X. Oridonin protects against the inflammatory response in diabetic nephropathy by inhibiting the TLR4/p38-MAPK and TLR4/NF-κB signaling pathways. Int Immuno-pharmacol. 2018;55:9-19.
Tan RZ, Yan Y, Yu Y, Diao H, Zhong X, Lin X, Liao Y, Wang L. Renoprotective effect of oridonin in a mouse model of acute kidney injury via suppression of macrophage involved inflammation. Biol Pharm Bull. 2021;44(5):714-723.
Yan Y, Tan RZ, Liu P, Li JC, Zhong X, Liao Y, Lin X, Wei C, Wang L. Oridonin alleviates IRI-induced kidney injury by inhibiting inflammatory response of macrophages via Akt-related pathways. Int Med J Exper Clin Res. 2020; 26:e921114-1.
Gao J, Li C, Wang X, Sun X, Zhang R, Yu M, Liu Y, Zhu Y, Chen J. Oridonin attenuates lung inflammation and fibrosis in silicosis via covalent targeting iNOS. Biomed Pharmacother. 2022;153:113532.
Jiang J, Shan X, Zhu L. Effects and mechanisms of oridonin in the treatment of acute respiratory distress syndrome mice. Int J Clin Exp Med. 2017;10:6191-6197.
Liu Y, Zhang PX, Han CH, Wei D, Qiao T, Peng B, Liu K, Zheng J, Liu W. Oridonin protects the lung against hyperoxia-induced injury in a mouse model. Undersea Hyperb Med. 2017;44(1):33.
Liu Q, Shang W, Zhang J, Chen R, Wei L, Wang H, Zhang M, Yue M. Oridonin alleviates lipopolysaccharide-induced acute lung injury in mice through inhibiting apoptosis, oxidative stress, and inflammation by modulating VIP/cAMP/PKA/AQPs signaling pathway. Research Square. 2023; https://doi.org/10.21203/rs.3.rs-3022672/v1
Wang J, Li F, Ding J, Tian G, Jiang M, Gao Z, Tuyghun E. Investigation of the antiasthmatic activity of oridonin on a mouse model of asthma. Mol Med Rep. 2016; 14(3):2000-6.
Wang W, Ming D. Oridonin attenuates apoptosis and NLRP3 inflammasome activation in IL-4-stimulated human bronchial epithelial cells in an in vitro pediatric asthma model. Adv Clin Exper Med. 2024;33(2):163-170.
Yang H, Lv H, Li H, Ci X, Peng L. Oridonin protects LPS-induced acute lung injury by modulating Nrf2-mediated oxidative stress and Nrf2-independent NLRP3 and NF-κB pathways. Cell Commun Signal. 2019;17:1-5.
Yang H, Wang L, Yang M, Hu J, Zhang E, Peng L. Oridonin attenuates LPS-induced early pulmonary fibrosis by regulating impaired autophagy, oxidative stress, inflammation and EMT. Eur J Pharmacol. 2022;923:174931.
Zhao G, Zhang T, Ma X, Jiang K, Wu H, Qiu C, Guo M, Deng G. Oridonin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-induced RAW264.7 cells and acute lung injury. Oncotarget. 2017;8(40):68153.
Zhao Y, Jin H, Bai LP, Pan H, Wang C, Tang Y, Guo Z, Cai J, Li T. Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury. Front Immunol. 2023;14:1163397.
Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, Lieberman J. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016; 535 (7610):153-158.
Tan Y, Chen Q, Li X, Zeng Z, Xiong W, Li G, Li X, Yang J, Xiang B, Yi M. Pyroptosis: A new paradigm of cell death for fighting against cancer. J Exper Clin Cancer Res. 2021; 40(1):153.
Zhang D, Qian J, Zhang P, Li H, Shen H, Li X, Chen G. Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro. J Neurosci Res. 2019;97(6):645-660.
You W, Zheng W, Weiss S, Chua KF, Steegborn C. Structural basis for the activation and inhibition of Sirtuin 6 by quercetin and its derivatives. Sci Rep. 2019;9(1):19176.
Leung CC, Yu IT, Chen W. Silicosis. Lancet. 2012; 379(9830):2008-2018.
Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. J Clin Investig. 2012;122(8): 2731-2740.
Clark NM, Brown RW, Parker E, Robins TG, Remick Jr DG, Philbert MA, Keeler GJ, Israel BA. Childhood asthma. Environ Health Perspect. 1999;107(suppl 3):421-429.
Kikkawa R, Koya D, Haneda M. Progression of diabetic nephropathy. Am J Kidney Dis. 2003;41(3):19-21.
Xie W, Barwick JL, Downes M, Blumberg B, Simon CM, Nelson MC, Neuschwander-Tetri BA, Brunt EM, Guzelian PS, Evans RM. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature. 2000; 406 (6794):435-439.
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