Two new flavonoid–triterpene saponin meroterpenoids from Clinopodium chinense and their protective effects against anoxia/reoxygenation-induced apoptosis in H9c2 cells
Graphical abstract
Introduction
Clinopodium is a genus in the family Lamiaceae, which contains approximately 22 species occurring in tropical and subtropical regions of Southeast Asia [1]. The aerial parts of C. chinense, couple with Clinopodium polycephalum, which are known as “duanxueliu” in China, have been used as a traditional folk medicine for the treatment of hematuria, skin trauma, influenza and allergic dermatitis [2]. Numerous chemical constituents have been reported from the genus Clinopodium including flavonoids [3], triterpenoid saponins [4], phenylpropanoids [5], diterpenes [6] and quinoids [7], as well as volatile and fatty oils, and these components exhibit diverse biological activities, including helostatic [8], anti-hyperglycemic [9], anti-tumour [10] and cardioprotective activity [11].
Our previous studies proved that total flavonoids from Clinopodium chinense (Benth.) O. Kuntze showed significantly protective effect against doxorubicin-induced cardiotoxicity and ischemic heart disease [12]. Further chemical studies found six novel favonoid-triterpene saponin meroterpenoids with unprecedented structures in the aerial parts of Clinopodium chinense [13]. In the present study, we examined the protective effects of two new flavonoid–triterpene saponin meroterpenoids, clinoposides G (1) and H (2) (Fig. 1), against anoxia/reoxygenation(A/R)-induced H9c2 cells injury in vitro. This function relies on the activation of Nrf2 and inhibition of NF-κB.
Section snippets
General experimental procedures
Optical rotation values were determined on a Perkin-Elmer 341 digital polarimeter equipped with a sodium lamp (589 nm) and a 1-dm microcell in MeOH. UV spectra were recorded on a Shimadzu UV2550 spectrometer in MeOH. ECD spectra were measured in MeOH on a JASCO J-815 spectropolarimeter. NMR spectra were acquired on Bruker AV III 600 MHz (the chemical shift values are reported as δ values with TMS as an internal standard). HR-ESI-MS spectra were measured on a LTQ Orbitrap XL mass spectrometer
Results and discussion
Two new flavonoid–triterpene saponin meroterpenoids, clinoposides G (1) and H (2), were obtained from C. chinense after successive separations and purifications using various column chromatography methods.
Clinoposide G (1) possesses a molecular formula of C63H90O23, as was established by the analysis of its HR-ESI-MS (m/z 1213.5829 [M - H]−, calculated as 1213.5795 for C63H89O23) and 13C NMR data. The 1H NMR spectrum (Table 1) showed the presence of seven methyl groups at δH 1.12 (s, H3-24),
Conflict of interest
The authors declare no competing financial interest.
Acknowledgements
This work was supported by grants (No. 81703689) from the National Natural Sciences Foundation of China and Wenzhou Medical University Research Initiation Fund (No. QTJ16015). Yongxiao Mou from School of Pharmacy, Wenzhou Medical University was also thanked for optimizing spatial structure of compound 1.
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These authors contribute equally to this work.