Effect and Mechanism of Ganoderma lucidum Spores on Alleviation of Diabetic Cardiomyopathy in a Pilot in vivo Study

• Main Authors: Shaher F, Wang S, Qiu H, Hu Y, Zhang Y, Wang W, AL-Ward H, Abdulghani MAM, Baldi S, Zhou S
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-12-01
• Series: Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
• Subjects: ganoderma lucidum spore; pi3k/akt/mtor signaling pathway; diabetic cardiomyopathy
• Online Access: https://www.dovepress.com/effect-and-mechanism-of-ganoderma-lucidum-spores-on-alleviation-of-dia-peer-reviewed-article-DMSO

Fahmi Shaher,1,* Shuqiu Wang,1,* Hongbin Qiu,1 Yu Hu,1 Yu Zhang,2 Weiqun Wang,3 Hisham AL-Ward,4 Mahfoudh AM Abdulghani,5 Salem Baldi,6 Shaobo Zhou7 1Department of Pathophysiology, College of Basic Medicine, Jiamusi University, Jiamusi, People’s Republic of China; 2Department of Pharmacology, College of Pharmacy, Jiamusi University, Jiamusi, People’s Republic of China; 3Department of Physiology, College of Basic Medicine, Jiamusi University, Jiamusi, People’s Republic of China; 4Department of Biochemistry and Molecular Biology, College of Basic Medicine, Jiamusi University, Jiamusi, People’s Republic of China; 5Department of Pharmacology and Toxicology, Unaizah College Pharmacy, Qassim University, Qassim, Saudi Arabia; 6Department of Clinical Laboratory Diagnostics, College of Basic Medicine, Dalian Medical University, Dalian, People’s Republic of China; 7School of Life Sciences, Institute of Biomedical and Environmental Science and Technology (iBEST), University of Bedfordshire, Luton LU1 3JU, UK*These authors contributed equally to this workCorrespondence: Hongbin QiuDepartment of Pathophysiology, College of Basic Medicine, Jiamusi University, Jiamusi, People’s Republic of ChinaEmail [e-mail]: Ganoderma lucidum spores (GLS) exhibit disease prevention properties, but no study has been carried out on the anti-diabetic cardiomyopathy property of GLS. The aim of this study was to evaluate the hyperglycemia-mediated cardiomyopathy protection and mechanisms of GLS in streptozotocin (STZ)induced diabetic rats.Methods: Male SD rats were randomly divided into three groups. Two groups were given STZ (50 mg/kg, i.p.) treatment and when their fasting plasma glucose was above 16.7 mmol/L, among them, one group was given placebo, as diabetic group, and another group was given GLS (300 mg/kg) treatment. The group without STZ treatment was given placebo as a control group. The experiment lasted 70 days. The histology of myocardium and biomarkers of antioxidants, myocardial injury, pro-inflammatory cytokines, pro-apoptotic proteins and phosphorylation of key proteins in PI3K/AKT pathway were assessed.Results: Biochemical analysis showed that GLS treatment significantly reduced the blood glucose (− 20.3%) and triglyceride (− 20.4%) levels compared to diabetic group without treatment. GLS treatment decreased the content of MDA (− 25.6%) and activity of lactate dehydrogenase (− 18.9%) but increased the activity of GSH-Px (65.4%). Western blot analysis showed that GLS treatment reduced the expression of both alpha-smooth muscle actin and brain natriuretic peptide. Histological analysis on the cardiac tissue micrographs showed that GLS treatment reduced collagen fibrosis and glycogen reactivity in myocardium. Both Western blot and immunohistochemistry analyses showed that GLS treatment decreased the expression levels of pro-inflammatory factors (cytokines IL-1β, and TNF-α) as well as apoptosis regulatory proteins (Bax, caspase-3 and − 9), but increased Bcl-2. Moreover, GLS treatment significantly increased the phosphorylation of key proteins involved in PI3K/AKT pathway, eg, p-AKT p-PI3K and mTOR.Conclusion: The results indicated that GLS treatment alleviates diabetic cardiomyopathy by reducing hyperglycemia, oxidative stress, inflammation, apoptosis and further attenuating the fibrosis and myocardial dysfunction induced by STZ through stimulation of the PI3K/Akt/mTOR signaling pathway.Keywords: Ganoderma lucidum spore, PI3K/Akt/mTOR signaling pathway, diabetic cardiomyopathy