Abstract

Both Ganoderma lucidum (GL) and G. sinense (GS) are used as Lingzhi in China. Their functions are assumed to mainly derive from triterpenes and polysaccharides; however, the two species have very different triterpenes profiles, if this was the case, then the bioactivity of these two species should differ. Instead, could the polysaccharides be similar, contributing to the shared therapeutic basis? In this study, two main polysaccharide fractions from different batches of GL and GS were systematically compared by a series of chemical and biological experiments. The results showed that the polysaccharides from two species shared the same structural features in terms of mono-/oligo-saccharide profiles, molecular size, sugar linkages, and IR/NMR spectra. In addition, these polysaccharides showed similar tumor-suppressive activity in mice. Further study on RAW264.7 cells indicated that these polysaccharides exhibited similar inducing effects to macrophages, as evaluated in the phagocytosis function, NO/cytokines production, inhibition against the viability and migration of cancer cells. Mechanistic investigation revealed the identical activation via TLR-4 related MAPK/NF-κB signaling pathway and gut-microbiota modulatory effects. In summary, GL and GS polysaccharides presented similar chemical features, antitumor/immunomodulating activities and mechanism; this establishes polysaccharides as the active principles and supports the official use of both species as Lingzhi.

Highlights

  • Lingzhi is a functional food and herbal medicine well-known for its anti-carcinogenic properties[1,2]

  • As the further purified polysaccharides from water/sodium fraction showed closely similar chemistry, chemical comparison in this study will focus on these two major fractions, in terms of the molecular weight distribution pattern, monosaccharide profiles produced by complete hydrolysis, and oligosaccharides profiles produced by partial hydrolysis

  • We focused on the two major polysaccharides from each species, characterizing them, assessing their antitumor activity and exploring the potential mechanism, involving immune stimulation and gut microbiota alteration

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Summary

Introduction

Lingzhi is a functional food and herbal medicine well-known for its anti-carcinogenic properties[1,2]. Triterpenes called ganoderic acids have been found cytotoxic towards a variety of cancer cell lines[3,4], and are assumed to be responsible for the antitumor activity. If polysaccharides are responsible for Lingzhi’s biological activity, GS and GL, having the similar range and amounts of polysaccharides, could be used as more or less equivalent This possibility is further supported by the fact that Lingzhi is typically used in water decoctions. Using eight batches of two major polysaccharide fractions-GLW and GLA isolated from crude polysaccharides of GL, and seven batches of GSW and GSA from GS, we determined their chemical similarity We evaluated these polysaccharides’ antitumor effects in vivo and in vitro.

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