The beneficial effects of Ganoderma lucidum on cardiovascular and metabolic disease risk

Figures & data

Table 1. In vitro studies on the hypoglycaemic effects of G. lucidum.

References	Model	Interventions	Findings
Zhang et al. 2003	Alloxan-induced pancreatic islet damage	Gl-PS polysaccharides from the fruiting body of G. lucidum	Gl-PS showed a protective effect
Fatmawati et al. 2009	Human aldose reductase activity	Methanol extracts of 17 medicinal and edible mushrooms	G. lucidum showed the highest aldose reductase inhibitory activity
Fatmawati et al. 2010	Human aldose reductase activity	Ganoderic acid Df isolated from the fruiting body of G. lucidum	Ganoderic acid Df showed potent human aldose reductase inhibitory activity
Fatmawati et al. 2011a	Human α-glucosidase activity	Chloroform extract of the fruiting body of G. lucidum	Ganoderol B identified as an active α-glucosidase inhibitor
Pan et al. 2015	PTP1B activity	FYGL proteoglycan isolated from G. lucidum	Competitive inhibitor of PTP1B
Yang et al. 2018a	Liver tissues of ob/ob mice and HepG2 cells	FYGL proteoglycan isolated from G. lucidum	Inhibited PTP1B overexpression, improved IRS1 phosphorylation, activated PI3K/Akt cascades, increased phosphorylation of GSK3β, enhanced insulin-stimulated glycogen synthesis
Yang et al. 2018b	Rat myoblast L6 cells	FYGL proteoglycan isolated from G. lucidum	Increased insulin-stimulated glucose uptake, inhibited PTP1B expression, increased IRS1 phosphorylation, activated PI3K/Akt, increased phosphorylation of AMPK and up-regulated expression of GLUT4

Akt: protein kinase B; AMPK: adenosine monophosphate-activated protein kinase; FYGL: Fudan-Yueyang Ganoderma lucidum; GLUT4: glucose transporter type 4; GSK3β: glycogen synthase kinase-3β; IRS1: insulin receptor substrate 1; PI3K: phosphatidylinositol-3 kinase; PTP1B: protein tyrosine phosphatase 1B.

Table 2. Animal studies on the hypoglycaemic effects of G. lucidum.

References	Animal model	Interventions	Findings
Hikino et al. 1985	Normal and alloxan-induced hyperglycaemic mice	Water extracts (10^4 mg/kg crude drug equivalent, i.p.) of the fruiting bodies of G. lucidum for 7 or 27 h	Reduced plasma glucose and 2 glycans, ganoderans A and B, with hypoglycaemic action isolated
Hikino et al. 1989	Normal and glucose-loaded mice	Ganoderan B	Increased insulin and altered enzyme activities
Kino et al. 1990	Autoimmune diabetes model in non-obese mice	Ling Zhi-8 immunomodulatory protein (10.3 − 12.6 mg/kg twice weekly) from 4 weeks of age, followed up to 42 weeks of age	Prevented development of autoimmune diabetes by immunosuppressive mechanism
Zhang et al. 2003	Alloxan-induced diabetic mice	Pre-treatment with intragastric Gl-PS (50 − 200 mg/kg) for 10 days	Gl-PS partly protected beta cells from necrosis
Zhang & Lin 2004	Normal fasted mice	Gl-PS (25 − 100 mg/kg) given by single intraperitoneal injections	Reduced serum glucose and increased insulin levels
He et al. 2006	Streptozotocin-induced diabetic mice	Gl-PS (125 and 250 mg/kg) given for 8 weeks	Reduced serum glucose, increased insulin levels and delayed progression of diabetic renal disease
Seto et al. 2009	Genetically obese/diabetic (+db/+db) and lean (+db/+m) mice	Water extract of G. lucidum (0.003, 0.03 and 0.3 g/kg) for 4 weeks, oral gavage	Extract reduced serum glucose and liver PEPCK expression
Li et al. 2011	Streptozotocin-induced diabetic mice	Gl-PS at low (50 mg/kg) and high (150 mg/kg) dose for 28 days	Reduced serum glucose, increased insulin levels and improvements in blood lipids
Teng et al. 2011	Streptozotocin-induced diabetic mice	FYGL proteoglycan from G. lucidum (50 and 150 mg/kg, oral dose) for up to 4 weeks	Reduced plasma glucose with effect comparable with metformin
Teng et al. 2012	Streptozotocin-induced diabetic rats	FYGL proteoglycan from G. lucidum (40 and 120 mg/kg, oral dose) for 30 days	Reduced plasma glucose, increased insulin and inhibited PTP1B
Zheng et al. 2012	Streptozotocin-induced diabetic rats	Low-molecular-weight Gl-PS (200 mg/kg) orally for 8 weeks	Reduced serum glucose appeared related to protection of pancreatic β-cells
Xiao et al. 2012	Streptozotocin-induced diabetic mice	Polysaccharides from G. lucidum (50 or 100 mg/kg/day) given for 7 days	Reduced fasting serum glucose and insulin levels
Pan et al. 2013	Obese/diabetic (+db/+db) mice	FYGL proteoglycan from G. lucidum (75, 250, or 450 mg/kg) for 8 weeks	Reduced HbA1c, increased insulin and C-peptide levels, increased glucokinase and lowered PEPCK activities
Sarker 2015	Rats with alloxan- or corticosteroid-induced diabetes	A petroleum ether extract and a methanol extract of G. lucidum (200, 400, 600 and 800 mg/kg/day) for 7 days	Reduced fasting and postprandial plasma glucose and HbA1c, increased plasma insulin levels and improved lipid profile
Xiao et al. 2017	Streptozotocin-induced diabetic mice	F31 polysaccharide from G. lucidum (50 mg/kg/day)	Decreased fasting serum glucose, fasting serum insulin and liver glucose regulatory enzymes
Ratnaningtyas et al. 2018	Alloxan-induced diabetic rats	Ethanol extract of G. lucidum powdered fruiting bodies (250, 500 and 1000 mg/kg) for 14 days	Dose-dependent reduction in blood glucose, reduction in HbA1c, and increase in insulin
Bach et al. 2018	Streptozotocin-induced diabetic rats	Hydroethanolic extract of G. lucidum (1 mL/kg/day) for 30 days	Reduced plasma glucose and lipid levels

FYGL: Fudan-Yueyang Ganoderma lucidum; HbA1c: Glycosylated Haemoglobin Level; Gl-PS: Ganoderma lucidum polysaccharides; PEPCK: phosphoenolpyruvate carboxykinase; PTP1B: protein tyrosine phosphatase.

Table 3. Human studies on the hypoglycaemic effects of G. lucidum.

References	Subjects	Interventions	Findings
Gao et al. 2004b	62 patients with T2DM	Multi-centered randomised controlled trial of Ganopoly^TM 1800 mg 3 times daily versus placebo for 12 weeks	Reduced HbA1c and fasting and postprandial plasma glucose levels with Ganopoly^TM
Wang et al. 2008	46 patients with T2DM	Randomised, double-blind, placebo-controlled dry extract of G. lucidum 3000 mg or placebo for 12 weeks	No changes in fasting glucose or HbA1c but the plasma glucose area under the curve during a meal tolerance test was reduced more with G. lucidum extract
Chu et al. 2012	23 subjects with borderline elevations of blood pressure and/or cholesterol	Randomised, double-blind, cross-over study with a Lingzhi product 1.44 g daily or placebo for 12 weeks	No significant effect on HbA1c, fasting plasma glucose, blood pressure or lipids. Plasma insulin and HOMA-IR reduced with Lingzhi compared to placebo
Klupp et al. 2016	84 patients with T2DM and metabolic syndrome	Randomised controlled trial of G. lucidum 3 g/day or G. lucidum plus Cordyceps sinensis capsules, versus placebo for 16 weeks	No significant effect on HbA1c, fasting plasma glucose, blood pressure or lipids

HbA1c: Glycosylated Haemoglobin Level; HOMA-IR: homeostasis model assessment-insulin resistance; T2DM: type 2 diabetes mellitus.

Figure 1. Chemical structure of ganoderic acid Df. The hydroxyl group at C-11 and the carbonyl group at C-15 along with the hydroxyl group at C-7 are thought to be important for inhibition of aldose reductase (Fatmawati et al. 2010, 2011b).

Figure 2. Chemical structure of ganoderol B. The hydroxyl group at C-3 and the double-bond in the side chain are thought to be important for α-glucosidase inhibitory activity (Fatmawati et al. 2013).

Figure 3. Chemical structure of ganomycin B. Ganomycin B showed strong inhibitory activity against HMG-CoA reductase with an IC₅₀ of 14.3 μM (Chen et al. 2017).

Figure 4. Potential mechanisms for cardiovascular disease prevention and therapy with constituents of Ganoderma lucidum.

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