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Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N 6 -(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK-2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex ® LH-20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK-2 cells. The HK-2 cells were pretreated with HEA (10-20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production ( p < 0.001) and gene expression of ATF-6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.

Extracts derived from Cordyceps have been demonstrated to possess various pharmacological effects, including immunomodulatory, antitumor, hypoglycemic, and antioxidant activities. This study was aimed to clarify the role of CS-P, a polysaccharide fraction isolated from Cordyceps sobolifera, in modulating nephrofunctional damage in a rat model of endotoxemia. CS-P (500 mg/kg body weight) was orally administered to rats for 4 weeks before the peritoneal injection of lipopolysaccharide (LPS, 10 mg/kg body weight). Pre-treatment with CS-P significantly attenuated the deleterious renal functions caused by LPS, i.e., elevated blood urea nitrogen and creatinine as well as urine protein. Histopathological examination of kidney tissues also demonstrated that CS-P improved LPS-induced pathological abnormalities. The induction of inducible nitric oxide synthase and the overproduction of nitric acid by LPS were also significantly reduced by CS-P via inhibiting nuclear factor-κB activation. In addition, CS-P pre-treatment suppressed the plasma levels of tumor necrosis factor-alpha and interleukin-6. Concurrently, CS-P supplementation potently suppressed the LPS-induced rise of lipid peroxidation and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney. The present results suggested that CS-P pre-treatment could protect against LPS-triggered inflammatory responses and renal injury in rats., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity. [ABSTRACT FROM AUTHOR]

Abstract: A herbal preparation “Compound Codyceps-TCM-700C (CC-700C)” was tested for hepatoprotective effect against the carbon tetrachloride induced liver damages in Sprague-Dawley rat model for a period of 6-weeks. Two dosage levels of CC-700C, respectively 286.2 mg/kg-bw (L-TCM) and 2862 mg/kg-bw (H-TCM), and a positive control Silymarin (Sigma) were used to compare their therapeutic effect. Both CC-700C''s and Silymarin showed nontoxic in nature, as evidenced by body weight gain, organ weights and appearance including liver, spleen, and kidney. The activities of aspartate aminotransferase (AST) and alanine-aminotransferase (ALT) were more effectively suppressed by CC-700C than Silymarin. In addition, all levels of serum bilirubin, serum albumin, triglyceride (TG), total cholesterol (TC), platelet count (PLT), and prothombin time (PT) except TG were shown effectively restored to normal values by CC-700C and Silymarin. Moreover, although levels of glutathione (GSH), glutathione reductase (GSH-Rd), and superoxide dismutase (SOD) were equally maintained by these three preparations, glutathione peroxidase (GSH-Px) was suppressed only by H-TCM, and SOD only by Silymarin. In contrast, the activity of catalase efficiently recovered to control level on administration of CC-700C, being far better than Silymarin. Finally the liver collagen content, an indication of fibrosis, was also significantly suppressed by CC-700C, better effect was by L-TCM, but both levels were superior to Silymarin. Conclusively, the herbal preparation “Compound Cordyceps TCM-700C” is a potent hepatoprotective preparation. For therapeutic use, a dosage of 286.2 mg/kg-bw would be sufficiently effective. [Copyright &y& Elsevier]