Ophiocordyceps lanpingensis polysaccharides alleviate chronic kidney disease through MAPK/NF-κB pathway.

Ethnopharmacological Relevance: Ophiocordyceps lanpingensis (O. lanpingensis) is a traditional ethno-medicine distributed in Eastern Himalayas, which has been used by local minorities to prevent and treat urinary diseases for hundreds of years. However, the corresponding active components and related pharmacological mechanism of such medication are not clear yet.

Aims Of The Study: This study was performed to investigate the effects and potential mechanisms of O. lanpingensis polysaccharides (OLP) in the treatment of chronic kidney disease (CKD) based on our previous research results.

Materials And Methods: Methylation analysis was used to investigate the monosaccharide composition and glycosidic linkages in OLP. The animals were divided into the control group, CKD model group, losartan group and three different doses of OLP groups. The CKD mouse model was established by the adenine gavage. The histological changes of renal tissue were observed by Hematoxylin-eosin and Masson staining. Biochemical indicators, including blood urea nitrogen (BUN), serum creatinine (Scr), serum phosphorus (P), plasma calcium (Ca), reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) were measured to evaluate the alleviation of CKD by OLP. Moreover, the expression levels of a series of cytokines related to the inflammation, apoptosis and fibrosis were analyzed to explore the possible mechanisms of OLP to treat CKD.

Results: OLP is composed of three kinds of monosaccharides. There are eight kinds of glycosidic linkages in OLP, among which →4)-Glcp-(1→ is the main linkage. OLP could significantly attenuate CKD in mice and the tubulointerstitial damage was recovered to almost normal after the treatment of OLP. Compared with the CKD model group, the levels of Scr, BUN, MDA, P in OLP treatment groups were significantly decreased; and the levels of SOD and Ca were increased after OLP treatment. Furthermore, OLP could reduce the oxidative stress of the renal tissues, decrease the expression levels of pro-inflammatory factors through TLR4-mediated MAPK and NF-κB pathway, inhibit the apoptosis of renal cells by MAPK pathway, and relieve the renal fibrosis by down-regulating the expression of TGF-β1.

Conclusions: OLP is composed of three kinds of monosaccharides and →4)-Glcp-(1→ is the main glycosidic linkage in the polysaccharide. OLP could ameliorate CKD in mice by declining the oxidative stress, inflammation, apoptosis and fibrosis in the kidneys. The study provided some evidences for the potential application of OLP in alleviating CKD.