Extraction, purification, and characterisation of biologically active compounds from Ganoderma lucidum and their effects on diabetes and cancer

Abstract

Ganoderma lucidum is a medicinal mushroom with centuries of use. Polysaccharides and triterpenoids from the fruiting bodies and spores and mycelium have interested researchers over the last 40 years. Cancer and diabetes impose a significant burden on health services globally with rising cases. Numerous treatments exist; however, with significant side effects in many cases generally managing one aspect of the condition. In this thesis, novel extraction and purification protocols using G. lucidum fruiting bodies produced two polysaccharide extracts (GLP) varying in composition compared to those reported in the literature, with higher β-glucan and total protein content than most marketed extracts. Extracts produced by ionic liquid extraction (GLP-IL) and fractional precipitation (GLP-FR) showed no signs of toxicity in rodent or human pancreatic beta cells in vitro. GLP-FR displayed significant in vitro insulin release which has not been reported with GLP. GLP-IL and GLP-FR demonstrated inhibitor effects on starch digestion and improved glucose tolerance in healthy lean mice in vivo. However, longer term effects in a diabetic mouse model were not as promising at the dose employed. All extracts inhibited cell proliferation of human cervical, colorectal, and pancreatic cancers in vitro. GLP-IL showed notable results in reducing pancreatic tumour growth in vivo by inducing apoptosis and necrosis along with stimulation of components of the innate and adapt immune system. Crude triterpenoid extracts of the sporoderm-broken spores increased beta cell proliferation, protection from cytokine damage and improved glucose tolerance in lean mice. Additionally, these extracts demonstrated inhibition of human cancer cell lines in vitro and stimulation of the immune system in vivo. These findings are the first demonstrated effects of G. lucidum extracts on pancreatic cancer in vivo and reinforces their use in the development of novel therapies in the treatment of diabetes and cancer due to their multitargeted effects and safety profiles.

Date of Award	May 2023
Original language	English
Sponsors	Hughes Group
Supervisor	Victor Gault (Supervisor), Peter Flatt (Supervisor) & Keith Thomas (Supervisor)