Hypoglycaemic activity of Ganoderma triterpenoids

A series of in vitro studies have showed that Ganoderma lucidum (fruiting bodies) extract, including reishi spore oil and reishi spore powder, has a strong inhibitory effect on human aldose reductase activity. Ganoderic acid Df, a lanostane-type triterpenoid, exhibited potent aldose reductase inhibitory activity with an IC50 value of 22.8µM. It was subsequently demonstrated that ganoderol B, which was isolated from Ganoderma lucidum extract, was effective in inhibiting α-glucosidase activity with an IC50 value of 119.8µM and the inhibitory effect was stronger than that of acarbose, which is commonly used as a medication to inhibit α-glucosidase in patients with T2DM. Structure-activity studies were carried out to identify the structural requirements of lanostane-type triterpenoids from Ganoderma lucidum, which were necessary to increase α-glucosidase inhibitory activity.

Hypoglycaemic activity of Ganoderma proteoglycans/peptidoglycans

Inhibition of PTP1B activity has been treated as a potential therapy for T2DM for many years. Ganoderma lucidum, which is a water soluble macromolecular proteoglycan extracted from the fruiting bodies of Ganoderma lucidum, inhibits PTP1B activity with an IC50 value of 5.12±0.05µg/mL. Ganoderma lucidum enhances glycogen synthesis and inhibits the expression of glycogen synthase kinase-3β in liver tissues of ob/ob mice and HepG2 cells probably via modulating insulin receptor substrate 1/phosphatidylinositol-3 kinase/protein kinase B/AMP-activated protein kinase/GSK3β cascades. In rat myoblast PTP1B-transfected L6 cells, Ganoderma lucidum improves insulin resistance by regulating IRS1-glucose transporter type 4 cascades in the insulin signalling pathway. In streptozotocin-induced T2DM mice, Ganoderma lucidum reduces plasma glucose levels with an effect comparable with metformin and rosiglitazone, through inhibiting the PTP1B expression and activity, and consequently modulating the tyrosine phosphorylation level of the insulin receptor 13-subunit.

Furthermore, Ganoderma lucidum improves the plasma biochemistry indexes associated with T2DM-accompanied metabolic disorders, including triglycerides, total cholesterol, free fatty acids, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Further studies in db/db mice found that the hypoglycaemic effect of Ganoderma lucidum is related with its ability to enhance insulin secretion, decrease hepatic glucose output, and increase adipose and skeletal muscle glucose disposal.

In normal and alloxan-induced hyperglycaemic mice, water extraction yielded from the fruiting bodies of Ganoderma lucidum and the two peptidoglycans, ganoderans A and B, subsequently produced through fractionation have all shown hypoglycaemic activity. Administration of ganoderan B increases plasma insulin levels in normal and glucose-loaded mice; it also increases the activities of hepatic glucokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase, decreases hepatic glucose-6-phosphatase and glycogen synthetase activities and does not affect the activities of hexokinase and glycogen phosphorylase.