Highly oxygenated isoryanodane diterpenoids from the leaves of Cinnamomum cassia and their immunomodulatory activities

Abstract

A total of twelve highly oxygenated isoryanodane (also known as cinncassiol D-type) diterpenoids including nine undescribed ones, named cinnacassins A−I, were isolated from the leaves of Cinnamomum cassia. Their chemical structures were elucidated by extensive spectrometric and spectroscopic techniques including HRESIMS, 1D and 2D NMR, single-crystal X-ray diffraction analysis, calculated 13C-NMR DP4+ analysis, and chemical methods. The absolute configuration of cinnacassin A was unambiguously delineated by single-crystal X-ray diffraction analysis. Cinnacassin H represents the first example of 16-O-glucosylated isoryanodane diterpenoid, and cinnacassin I is the first isoryanod-13(18)-ene diterpenoid. The relationship of the configuration C-18 and the chemical shifts of H2-19 and C-20 in the 19-hydroxy-isoryanodane diterpenoids was discussed, and the 18S-configuration of three known 19-hydroxy-isoryanodane diterpenoids, cinncassiol D1, 19-O-β-D-glucopyranosyl-cinncassiol D1, and cinncassiol D3 was assigned. All the isolated isoryanodane diterpenoids were evaluated for their immunomodulatory effects in vitro, and cinnacassin A and cinncassiol D1 enhanced the proliferation of Con A-induced murine T cells with enhancement rates ranging from 17.9% to 45.4%, which were more potent than the positive control, thymosin α1. In addition, cinncassiol D1 significantly promoted the proliferation of LPS-induced murine B cells with an enhancement rate up to 116.1%, two-fold more potent than thymosin α1 at a concentration of 1.5625 μM.