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Potent immunosuppressive and anti-inflammatory bisindole alkaloids from Melodinus fusiformis

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journal contribution
posted on 2021-02-11, 09:40 authored by Lu Liu, Ming-Jun Xie, Wen-Bing Zhou, Jin-Tang Wang, Jia-Yi Wang, Afsar Khan, Ya-Ping Liu, Jian-Xin Cao, Gui-Guang Cheng, Wen-Yuan Mao

Phytochemical investigation of Melodinus fusiformis led to a new aspidosperma-aspidosperma bisindole alkaloid (BIA), bis-19β-hydroxyvenalstonidine (1), together with three known BIAs (24). The structures were established by extensive analysis of their HRESIMS, NMR data, and comparing with the reported data. BIA 1 is an almost symmetrical structure, linked by C3–C14’ bond, while BIAs 24 are reported for the first time from the plant. The cytotoxic, immunosuppressive and anti-inflammatory activities of BIAs 14 were evaluated in vitro. BIAs 1, 3 and 4 showed good toxicity against MOLT-4 cell lines with IC50 values in the range of 1.5–17.5 M. BIA 2 exhibited the strongest inhibitory effect against MCF-7 cell lines with an IC50 value of 7.1 μM. BIA 1 significantly inhibited Con A-stimulated mice splenocytes proliferation equal to that of the positive control (DXM) in a concentration-dependent manner. BIAs 1 and 2 were able to decrease the NO production in LPS-induced RAW 264.7 cells at 30 μM concentration. BIA 2 showed similar inhibition of nitric oxide release, compared to that of DXM. Furthermore, BIA 2 remarkably inhibited the levels of IL-6 and TNF-α compared to the LPS induced group. Interestingly, BIA 2 displayed an inhibitory effect on TNF-α production similar to that of dexamethasone at a concentration of 20 μM.

Funding

This work was financially supported by Applied Basic Research Project of Yunnan Province (2018FB036), the National Natural Science Foundation of China (31600274 and 31872676), the Open Program of State Key of Phytochemistry and Plant Resources in West China (P2018-KF08), China Postdoctoral Science Foundation (2018M633419), Open Research Fund Program of Yunnan Provincial Key Laboratory of Molecular Biology for Sinomedicine (Yunnan University of Chinese Medicine) and Key science and technology plan projects of Yunnan Province (2018530000241012).

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