ergosterol-5-8-peroxide and Fibrosis

Cicada flower, Isaria cicadae Miq., has been a traditional Chinese medicine for approximately 1600 years. Many works on its identification, bioactivities, and clinical use against some disorders have been published, but some inaccuracies and inconsistencies need to be further clarified. In combination with our > 20 years of research and application of cicada flower and examination of the literature and patents published in recent years, this article summarizes and reviews the life cycle and taxonomy, genome size and mating type, molecular systematic classification and cultivation, active ingredients, and pharmacological functions of I. cicadae.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antihypertensive Agents; Antineoplastic Agents; Antioxidants; Cordyceps; Ergosterol; Fatty Acids, Monounsaturated; Fibrosis; Genome, Fungal; Immunologic Factors; Kidney Failure, Chronic; Liver Cirrhosis; Medicine, Chinese Traditional; Nucleosides; Peptides, Cyclic; Polysaccharides

Chronic kidney disease is a growing public health problem with an urgent need for new pharmacological agents. Ergosterol peroxide (EP) is the major sterol produced by Cordyceps cicadae Shing (C. cicadae), a widely used traditional Chinese medicine. C. cicadae has been used to treat many kinds of diseases and has a potential benefit on renoprotection. This study aimed to investigate the anti-fibrotic effects of EP as well as the underlying mechanisms. A normal rat kidney fibroblast cell line (NRK-49F) was stimulated to undergo fibroblast activation by transforming growth factor-β1 (TGF-β1) and EP treatment was applied to explore its potential anti-fibrotic effects. Cell proliferation was investigated using MTT analysis. Fibrosis-associated protein expression was analyzed using immunohistochemistry and/or Western blotting. EP treatment attenuated TGF-β1-induced renal fibroblast proliferation, expression of cytoskeleton protein and CTGF, as well as ECM production. Additionally, EP blocked TGF-β1-stimulated phosphorylation of ERK1/2, p38 and JNK pathway. Moreover, the TGF-β1-induced expression of fibronectin was attenuated by either inhibition of MAPKs or by EP treatment. In conclusion, our findings demonstrate that EP is able to suppress TGF-β1-induced fibroblasts activation in NRK-49F. This new information provides a line of theoretical evidence supporting the use of C. cicadae in the intervention of kidney disease and suggests that EP has the potential to be developed as a therapeutic agent to prevent renal fibrosis.

Topics: Animals; Cell Line; Cell Proliferation; Cells, Cultured; Cordyceps; Drugs, Chinese Herbal; Ergosterol; Fibroblasts; Fibronectins; Fibrosis; Kidney; Kidney Diseases; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Transforming Growth Factor beta1