Ganoderma lucidum polysaccharide ameliorated diabetes mellitus-induced erectile dysfunction in rats by regulating fibrosis and the NOS/ERK/JNK pathway

Abstract

Background: Diabetes mellitus-induced erectile dysfunction (DMED) is a frequent complication of diabetes mellitus (DM), with limited therapy at present. This study aimed to explore the role and mechanism of Ganoderma lucidum polysaccharide (GLP) on DMED.Methods: DMED was induced in the experimental rats [male 12-week-old Sprague-Dawley (SD) rats] by treatment with streptozotocin (60 mg/kg) and apomorphine (APO). Next, rats in the GLP low dose (GLP-L)/GLP high dose (GLP-H) groups were treated with GLP (100 or 400 mg/kg/d, respectively) for 8 weeks. Subsequently, erectile function was assessed by APO and electrostimulation of the cavernous nerve (CN). Serum or penile testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cyclic guanosine monophosphate (cGMP) contents were evaluated by enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress indicators in the corpus cavernosum (CC) were measured by corresponding kits, and histological changes in the CC were observed by hematoxylin-eosin (HE) and Masson staining. Additionally, the apoptosis index, caspase-3, caspase-9, and eNOS expression, and mitochondrial membrane potential (MMP) were also detected. Furthermore, quantitative polymerase chain reaction (qPCR) and western blot assays were conducted to determine the NOS, TGF-β1 mRNA expression, ERK1/2, eNOS, JNK phosphorylation, and arginase II protein expression. Results:The erectile function test revealed that erectile dysfunction (ED) was alleviated in the DMED rats following treatment with GLP. Moreover, GLP upregulated the T and cGMP content, improved the oxidative stress and histological injuries of CC, and also inhibited the apoptosis and MMP loss of penile tissues in DMED rats. Furthermore, GLP treatment enhanced the mRNA expression of NOS and TGF-β1 and suppressed the phosphorylation of ERK1/2, eNOS, and JNK, as well as the protein expression of arginase II in DMED rats.Conclusions: GLP ameliorated DMED by repairing the CC pathological damage and upregulating NOS expression and ERK/JNK phosphorylation, indicating that GLP may be a candidate drug for DMED therapy.

Polysaccharides from natural resource: ameliorate type 2 diabetes mellitus via regulation of oxidative stress network

“…More data on the role of MP in diabetes treatment can be obtained from another review ( Arunachalam et al, 2022 ). Furthermore, GLP improved the OS and inhibited apoptosis by increasing the expression of TGF-β1, GSH, SOD, and NOS and suppressing the phosphorylation of MDA, JNK, eNOS and ERK in DM rats ( Yao et al, 2022 ). In addition, GLP-treatment reversed the levels of fasting plasma lipids, hepatic lipid accumulation, and higher blood glucose levels ( Li et al, 2020 ), increased SOD, CAT, and GSH-Px expression, as well as promoted Nrf2 and HO-1expression in db/db mice, by contrast, the content of MDA and TNF-a decreased in these mice.…”