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

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-ß1 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-ß1 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.

Ganoderma lucidum polysaccharide inhibits UVB-induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways.

Ultraviolet (UV)-induced pigmentation is very common in clinical practice, but the current treatments are rarely effective, accompanied by some side effects. Ganoderma lucidum polysaccharide (GLP) is a natural antioxidant with no toxic side effects, which can antagonize UVB-induced fibroblast photo aging. The study aims to explore the role of GLP in inhibiting UVB-induced melanogenesis and its possible mechanism. The expression of melanogenesis genes such as microphthalmia-associated transcription factor (MITF), tyrosine (TYR), tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2), ras-related protein Rab-27A (Rab27A), and Myosin shows an upward trend after exposure of B16F10 and PIG1 cells to UVB irradiation, but GLP can downregulate the expression of genes related to UVB-induced melanogenesis. GLP can inhibit UVB-activated protein kinase A (PKA) and mitogen-activated protein kinase (MAPK) signaling pathways. Besides, GLP protects mitochondria from UVB damage and inhibits reactive oxygen species (ROS) production. Also, UVB-induced cyclic adenosine monophosphate (cAMP) can be inhibited. It has been found in the experiments of UVB-induced skin pigmentation in zebrafish that GLP is capable of inhibiting UVB-induced skin pigmentation. Meanwhile, it can greatly relieve erythema reaction in guinea pig skin caused by high-dosage UVB irradiation. In conclusion, this study shows that GLP can inhibit UVB-induced melanogenesis by antagonizing cAMP/PKA and ROS/MAPK signaling pathways and is a potential natural safe whitening sunscreen additive.

Ganoderma lucidum polysaccharides promote Th1 cell differentiation of human peripheral blood lymphocytes through the upregulation of STAT4 / 中华微生物学和免疫学杂志

Objective To study the effects of Ganoderma lucidum polysaccharide (GLP) on PBMCs and the related immune mechanism.Methods PBMCs from cancer patients and healthy donors were isolated and treated with different doses of Ganoderma lucidum polysaccharides (10 ng/ml,50 ng/ml and 100 ng/ml).DC cell costimulatory molecules (HLA-DR,CD83,and CD11 c),Th1 (CD3 + CD8-IFN-γ+) cells,Th2 (CD3 + CD8-IL-4+) cells and NK (CD3-CD56+) were analyzed by FCM.Furthermore,The CD3+ CD4+ Th ceils were separated by immunomagnetic beads and stimulated with Ganoderma lucidum polysaccharides at different concentrations in culture.After 24 h,the cytokine expression levels of Th1 and Th2were detected by RT-PCR.The expressions of Th1 differentiation-related transcription factor,STAT4,were analyzed by Western blot.Results Ganoderma lucidum polysaccharides can significantly stimulate in vitro Thl cell differentiation (P＜0.01) in a dose depend manner.It correlates with an increased expression of STAT4 and the elevated mRNA expression levels of Th1 cytokineincluding IL-12,IFN-γ and TNF-α (P＜0.01).Conclusion Ganoderma lucidum polysaccharides may promote Th1 differentiation and increase the secretion of Th1 cvtokines through the upregulation of STAT4.

Ganoderma lucidum polysaccharides combined with low-dose cisplatin inhibits tumor growth and enhances the immune function of tumor-bearing mice / 国际中医中药杂志

Objective To study the effects on inhibit tumor growth and enhance immune function of Ganoderma lucidum polysaccharide(GLP)combined with low-dose cisplatin in tumor-bearing mice.Methods 2 × 106 Lewis cells in 0.1 mL PBS were injected subcutaneously into the flanks of healthy female BALB/c nude mice (5～6 weeks old).When the tumor volume reached 100 mm3,mice were randomly assigned to 4 groups,control group (Oral gavage of 0.5 ml PBS and intraperitoneal injection of 0.5 ml),GLP group (gavage once every two days,40 mg/kg GLP in 0.5 ml),cisplatin group (intraperitoneal injection once every two days,2 mg/kg cisplatin in 0.5 ml) and the combination group (such as the above dose of cisplatin and GLP).After the treatment regimen was complete,the mice were sacrificed,and the tumors were removed,photographed,weighed,and prepared for histological analysis.The immune cells in spleen and peripheral blood were analyzed by flow cytometry.Results GLP can effectively increase anti-tumor effect of the small dose cisplatin,improve the survival of tumor-bearing mice,promote Th cells convert to Th1 in peripheral blood,increased the expression of CD 11c + on DC cell surface (GLP group 4.59％ VS the control group 1.06％,the combined group 7.21％ VS the cisplatin group 2.8％).Conclusion GLP can improve the immune function of tumor-bearing mice,had synergistic anti-tumor growth with low dose cisplatin,moreover,reduce renal toxic effects of cisplatin.