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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Pharmacokinetic Studies of Gypenoside XLVI in Rat Plasma using UPLC-MS/MS Method

Author(s): Han Li, Aiping Yang, Meng Yang, Fengjuan Zhou, Rui Zhang, Zongping Zheng and Xiachang Wang*

Volume 20, Issue 2, 2024

Published on: 26 January, 2024

Page: [143 - 151] Pages: 9

DOI: 10.2174/0115734129286658240111093745

Abstract

Background: Gynostemma pentaphyllum (Thunb.) Makino has been linked to a number of pharmacological benefits, including hepatoprotective, anti-inflammatory, antioxidative, and antihyperlipidemic activities. Gypenoside XLVI (Gyp XLVI) was a significant triterpenoid saponin reported from a sweet-taste varietas G. pentaphyllum, which has inhibitory effects and causes apoptosis on human hepatocytes and hepatoma cells.

Methods: A quick, precise, and sensitive method for the quantification and pharmacokinetic research of Gyp XLVI in rats was developed utilizing UPLC-MS/MS. When extracting blood samples, protein was precipitated using methanol. An internal standard (IS) was employed, which was tolbutamide. For the chromatographic separation, a C18 column (Waters Acquity) was used with mobile phases as 0.1% formic acid and acetonitrile. Multiple reaction monitoring was used as MS detection manner with electrospray ionization in negative mode.

Results: Gyp XLVI had good linearity in the 1.36‒1000.00 ng/mL concentration range. The intra- day and inter-day precisions (RSD%) and accuracy (RE%) were less than 12.7% or 8.29%, respectively. Gyp XLVI’s extraction recovery ranged from 89.5% to 104.2%. The matrix effects ranged from 75.3%‒94.3%. The outcomes of matrix interference and recovery investigations complied with the necessary variability limitations. After three hours at room temperature (25°C), 24 hours in an auto-sampler (4°C), three freeze-thaw cycles, and 30 days of storage at -20°C, the analyte in rat plasma remained stable. Gyp XLVI pharmacokinetic investigations and quantification were conducted using the validated method. The AUC0-∞ values for intravenous administration (1 mg/kg) and oral administration (10 mg/kg) were 2213.9 ± 561.5 ng·h/mL and 1032.8 ± 334.8 ng·h/mL, respectively. Gyp XLVI had a half-life (t1/2z) of 2.5 ± 0.4 h in the rats after intravenous injection and 4.2 ± 0.9 h after oral administrations. Gyp XLVI had a comparatively low oral bioavailability of 4.56%.

Conclusion: This is the first time that Gyp XLVI’s pharmacokinetic properties have been investigated through various administration routes. These findings will aid in our understanding of how Gyp XLVI was metabolized in rats and how it behaved pharmacologically in vivo.

Keywords: Gypenoside XLVI, pharmacokinetics, UPLC-MS/MS, triterpene saponin, bioavailability, rat plasma.

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[1]
Chao, J.; Dai, Y.; Verpoorte, R.; Lam, W.; Cheng, Y.C.; Pao, L.H.; Zhang, W.; Chen, S. Major achievements of evidence-based traditional Chinese medicine in treating major diseases. Biochem. Pharmacol., 2017, 139, 94-104.
[http://dx.doi.org/10.1016/j.bcp.2017.06.123] [PMID: 28636884]
[2]
Gu, X.; Hao, D.; Xiao, P. Research progress of Chinese herbal medicine compounds and their bioactivities: Fruitful 2020. Chin. Herb. Med., 2022, 14(2), 171-186.
[http://dx.doi.org/10.1016/j.chmed.2022.03.004] [PMID: 36117669]
[3]
Qiu, S.; Cai, Y.; Yao, H.; Lin, C.; Xie, Y.; Tang, S.; Zhang, A. Small molecule metabolites: Discovery of biomarkers and therapeutic targets. Signal Transduct. Target. Ther., 2023, 8(1), 132.
[http://dx.doi.org/10.1038/s41392-023-01399-3] [PMID: 36941259]
[4]
Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov., 2021, 20(3), 200-216.
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[5]
Perez de Souza, L.; Alseekh, S.; Scossa, F.; Fernie, A.R. Ultra high performance liquid chromatography high-resolution mass spectrometry variants for metabolomics research. Nat. Methods, 2021, 18(7), 733-746.
[http://dx.doi.org/10.1038/s41592-021-01116-4] [PMID: 33972782]
[6]
Sarangdhar, V.A.; Kachave, R.N. Overview of UHPLC-MS: An effective and sensitive hyphenated technique. J. Anal. Chem., 2022, 77(11), 1386-1398.
[http://dx.doi.org/10.1134/S1061934822110119]
[7]
Su, C.; Li, N.; Ren, R.; Wang, Y.; Su, X.; Lu, F.; Zong, R.; Yang, L.; Ma, X. Progress in the medicinal value, bioactive compounds, and pharmacological activities of Gynostemma pentaphyllum. Molecules, 2021, 26(20), 6249.
[http://dx.doi.org/10.3390/molecules26206249] [PMID: 34684830]
[8]
Nguyen, N.H.; Ha, T.K.Q.; Yang, J.L.; Pham, H.T.T.; Oh, W.K. Triterpenoids from the genus Gynostemma: Chemistry and pharmacological activities. J. Ethnopharmacol., 2021, 268, 113574.
[http://dx.doi.org/10.1016/j.jep.2020.113574] [PMID: 33186700]
[9]
Xie, P.; Luo, H.T.; Pei, W.J.; Xiao, M.Y.; Li, F.F.; Gu, Y.L.; Piao, X.L. Saponins derived from Gynostemma pentaphyllum regulate triglyceride and cholesterol metabolism and the mechanisms: A review. J. Ethnopharmacol., 2024, 319(Pt 1), 117186.
[http://dx.doi.org/10.1016/j.jep.2023.117186] [PMID: 37722515]
[10]
Liu, Y.; Yang, Y.; Wang, H.; Li, H.; Lv, Q.; Wang, X.; Wu, D.; Hu, L.; Zhang, Y. Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix. Chin. J. Nat. Med., 2023, 21(8), 599-609.
[http://dx.doi.org/10.1016/S1875-5364(23)60395-4] [PMID: 37611978]
[11]
Li, K.; Ma, C.; Li, H.; Dev, S.; He, J.; Qu, X. Medicinal value and potential therapeutic mechanisms of Gynostemma pentaphyllum (Thunb.) Makino and its derivatives: An overview. Curr. Top. Med. Chem., 2020, 19(31), 2855-2867.
[http://dx.doi.org/10.2174/1568026619666191114104718] [PMID: 31724506]
[12]
Xiang, W.J.; Guo, C.Y.; Ma, L.; Hu, L.H. Dammarane-type glycosides and long chain sesquiterpene glycosides from Gynostemma yixingense. Fitoterapia, 2010, 81(4), 248-252.
[http://dx.doi.org/10.1016/j.fitote.2009.09.009] [PMID: 19781603]
[13]
Takemoto, T.; Arihara, S.; Yoshikawa, K.; Kawasaki, J.; Nakajima, T.; Okuhira, M. Studies onthe constituents of Cucurbitaceae plants. XI. On the saponin constituents of Gynostemma pentaphyllum Makino (7). Yakugaku Zasshi, 1984, 104(10), 1043-1049.
[http://dx.doi.org/10.1248/yakushi1947.104.10_1043]
[14]
Shen, C.Y.; Jiang, J.G.; Shi, M.M.; Yang, H.L.; Wei, H.; Zhu, W. Comparison of the effects and inhibitory pathways of the constituents from Gynostemma pentaphyllum against LPS-induced inflammatory response. J. Agric. Food Chem., 2018, 66(43), 11337-11346.
[http://dx.doi.org/10.1021/acs.jafc.8b03903] [PMID: 30301351]
[15]
Li, Y.; Lin, W.; Huang, J.; Xie, Y.; Ma, W. Anti-cancer effects of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan). Chin. Med., 2016, 11(1), 43.
[http://dx.doi.org/10.1186/s13020-016-0114-9] [PMID: 27708693]
[16]
Wang, T.X.; Shi, M.M.; Jiang, J.G. Bioassay-guided isolation and identification of anticancer and antioxidant compounds from Gynostemma pentaphyllum (Thunb.) Makino. RSC Advances, 2018, 8(41), 23181-23190.
[http://dx.doi.org/10.1039/C8RA02803F] [PMID: 35540147]
[17]
Li, H.; Wang, H.; Yang, A.; Xue, M.; Wang, J.; Lv, Q.; Liu, J.; Hu, L.; Zhang, Y.; Wang, X. Gypenosides synergistically reduce the extracellular matrix of hepatic stellate cells and ameliorate hepatic fibrosis in mice. Molecules, 2023, 28(14), 5448.
[http://dx.doi.org/10.3390/molecules28145448] [PMID: 37513321]
[18]
Liu, W.; Zeng, K.; Zhou, X.; Zhang, Y.; Nie, C. Comparative study on brain pharmacokinetics of Buyang Huanwu Decoction in normal and cerebral ischemia rats using brain microdialysis combined with LC-MS/MS. Chin. Herb. Med., 2022, 14(4), 630-637.
[http://dx.doi.org/10.1016/j.chmed.2022.03.007] [PMID: 36405053]
[19]
Hu, T.; Ge, X.; Wang, J.; Zhang, N.; Diao, X.; Hu, L.; Wang, X. Metabolite identification of iridin in rats by using UHPLC-MS/MS and pharmacokinetic study of its metabolite irigenin. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2021, 1181, 122914.
[http://dx.doi.org/10.1016/j.jchromb.2021.122914] [PMID: 34492510]
[20]
He, Y.; Liang, Q.; Luo, L.; He, Y.; Huang, X.; Wen, C. Determination of gypenoside A and gypenoside XLIX in rat plasma by UPLC-MS/MS and applied to the pharmacokinetics and bioavailability. Int. J. Anal. Chem., 2022, 2022, 1-7.
[http://dx.doi.org/10.1155/2022/6734408] [PMID: 35992562]
[21]
Yang, A.; Dong, J.; Zhao, H.; Zhang, Q.; Zhu, X.; Gao, L.; Ding, N.; Li, C.; Peng, R.; Lu, T.; Hu, L.; Wang, X. Quantification and pharmacokinetics study of pedunculoside in rats by using UPLC MS/MS. Curr. Pharm. Anal., 2021, 17(6), 731-737.
[http://dx.doi.org/10.2174/1573412916999200423105153]
[22]
Pecho, T.; Zeitlinger, M. Preclinical pharmacokinetic/ pharmacodynamic studies and clinical trials in the drug development process of EMA-approved antifungal agents: A review. Clin. Pharmacokinet., 2024, 63(1), 13-26.
[http://dx.doi.org/10.1007/s40262-023-01327-2] [PMID: 37971649]

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