New sesquiterpenoid derivatives from Ganoderma sinense with nitric oxide inhibitory activity

Highlights

• Two new sesquiterpenoid derivatives were isolated from Ganoderma sinense.

• They showed inhibitory effects on LPS-induced NO production in RAW264.7 macrophages.

• They may be used as anti-inflammatory agents and are worth being further researched.

Abstract

One new sesquiterpenoid, ganosinensol K (1) and one new norsesquiterpenoid, ganosinensol L (2) were isolated from 95 % EtOH extract of the fruiting bodies of Ganoderma sinense. Their structures were determined on the basis of extensive spectroscopic analyses including HRESIMS, 1D and 2D NMR, and optical rotation value. Compound 1 should be a mixture of two enantiomers. We attempted to resolve compound 1 into one pair of enantiomers by HPLC using a Daicel Chiralpak IE column, while each purified enantiomer of 1 rapidly converted back to racemates, which hampered the determination their steric structures. The absolute configuration of C-5 in 2 was confirmed by comparison of its experimental and calculated specific rotations. Both compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW264.7 macrophages, with IC₅₀ values of 1.15 ± 0.09 μM and 7.31 ± 0.52 μM, respectively.

Introduction

Ganoderma sinense (Chinese name: Lingzhi), a well-known traditional Chinese medicine, has been used as a folk medicine for thousands of years in China. G. sinense and G. lucidum are officially recorded in Chinese pharmacopoeia for treating asthma and hypertension (Chinese Pharmacopoeia Commission, 2015). There are about 100 species in Ganoderma genus widely distributed in China. The mushrooms of Ganoderma have been reported to possess antitumor (Gao et al., 2018; Liang et al., 2014; Sun et al., 2015; Yu et al., 2015; Zheng et al., 2018), anti-inflammation (Joseph et al., 2009; Ko et al., 2008), immune regulation (Jan et al., 2011; Shi et al., 2012), hepatoprotection (Liu et al., 2015), as well as anti-androgenic effect and therapy for benign prostatic hyperplasia (Fujita et al., 2005; Liu et al., 2007, 2009; Nahata and Dixit, 2012). More than 300 compounds including polysaccharides, triterpenes, sterols, and farnesyl phenols substances have been isolated from the Ganoderma genus (El Dine et al., 2009; Gao et al., 2017; Isaka et al., 2013; Kikuchi et al., 1985; Mothana et al., 2000; Niedermeyer et al., 2013; Niu et al., 2006; Paterson, 2016; Peng et al., 2014; Ríos et al., 2016; Satria et al., 2019; Wu et al., 2019).

Nitric oxide (NO) is produced by inducible nitric oxide synthase (iNOS) and excessive amounts of NO can cause various inflammation-related diseases, such as allergic rhinitis, arthritis, and bowel diseases (Coulter et al., 2008; Kaminska, 2005; Stein et al., 2017). Therefore, the regulation of NO production is pivotal for treating inflammation. As our ongoing research on finding more potential lead compounds with inhibitory effect against NO production from the Ganoderma genus (Wang et al., 2016; Wu et al., 2019), the EtOAc fraction from EtOH extract of G. sinense was investigated, resulting in the isolation and identification of one new sesquiterpenoid, ganosinensol K (1) and one new norsesquiterpenoid, ganosinensol L (2) (Fig. 1). Their inhibitory effects on NO production in LPS-stimulated RAW264.7 macrophages were evaluated herein.