Bio-/chem-equivalence of polysaccharies of G. lucidum and G. sinense evaluated with a novel systematic approach

This is a resubmission of grant application after revision as reviewers suggested. The proposed project aims to evaluate the bio-/chem-equivalence of Ganoderma lucidum and G. sinense through a new approach.

The quality assessment of Lingzhi is challenging. Lingzhi is a popularly used anticancer fungus. According to Chinese Pharmacopeia, it includes two species: G. lucidum and G. sinense. Its anti-cancer ingredients are commonly thought to be ganoderic acids (GAs), however, only G. lucidum contains GAs. If this is true, G. sinense should not be certified as Lingzhi. Instead, the anticancer components may be polysaccharides, as indicated by a number of publications and our own work.

In order to solve this problem, the chemical nature of these two species, and the active anticancer components need to be determined and compared. People think GAs are the active components because they are bioavailable; however, Gas are not water soluble and the two species have different GA profiles. On the other hand, both species are rich in polysaccharides; polysaccharides are water-soluble, hence abundant in the decoctions—which is the usual form in which they are consumed. However, these polysaccharides appear to be poorly bioavailable.

In collaboration with pharmacologists, we have proven that oral feeding with the crude polysaccharide of both Lingzhi species signicantly suppressed the growth of different tumors in mice. And decoctions of both speices showed identical molecular distribution patterns in HPGPC (high performance gel permeation chromatography) examination. We hypothesize that the polysaccharides of two Ganoderma species are biologically and chemically equivalent.

Further separation has yielded 20+ purified polysaccharides. Some have been tested and exhibit significant inducing effects on the cytokine secretion of PBMCs (peripheral blood mononuclear cells), macrophages, and DCs (dendric cells), especially inducing the maturation of DCs via TLR-4 pathway. It is hypothesized that these polysaccharides, without entering blood, might work as immunotherapy agents to sensitize the DCs in the intestine which is known as trigger to activate cytoxotic T lymphocytes against cancer cells.

This project will provide substantial scientific evidences to determine the Ganoderma chem-/bio-equivalence by 1) qualitative and quantitative analysis of their polysaccharide profiles using innovative recycling HPGPC and purified/characterized polysaccharide markers and by 2) evaluation of the bio-equivalence of these polysaccharides’ anti-cancer effects using modified cell models based on step co-culture of polysaccharide-DCs-T lymphocyte-cancer cell, in three aspects: a. anticancer effects of polysaccharide alone; b. interaction with chemotherapy; c. reaction to TLR-4 antagonist. This project will offer a successful example for polysaccharide-based quality control of many Chinese medicines that are rich in saccharides and traditionally used in the form of decoction.