Renal fibrosis is considered as the pathway of almost all kinds of chronic kidney diseases (CKD) to the end stage of renal diseases (ESRD). Ganoderic acid (GA) is a group of lanostane triterpenes isolated from Ganoderma lucidum , which has shown a variety of pharmacological activities. In this study we investigated whether GA exerted antirenal fibrosis effect in a unilateral ureteral obstruction (UUO) mouse model. After UUO surgery, the mice were treated with GA (3.125, 12.5, and 50 mg· kg −1 ·d − 1 , ip) for 7 or 14 days. Then the mice were sacrificed for collecting blood and kidneys. We showed that GA treatment dose-dependently attenuated UUO-induced tubular injury and renal fibrosis; GA (50 mg· kg −1 ·d − 1 ) significantly ameliorated renal disfunction during fibrosis progression. We further revealed that GA treatment inhibited the extracellular matrix (ECM) deposition in the kidney by suppressing the expression of fibronectin, mainly through hindering the over activation of TGF-β/Smad signaling. On the other hand, GA treatment significantly decreased the expression of mesenchymal cell markers alpha-smooth muscle actin (α-SMA) and vimentin, and upregulated E-cadherin expression in the kidney, suggesting the suppression of tubular epithelial-mesenchymal transition (EMT) partially via inhibiting both TGF-β/Smad and MAPK (ERK, JNK, p38) signaling pathways. The inhibitory effects of GA on TGF-β/Smad and MAPK signaling pathways were confirmed in TGF-β1-stimulated HK-2 cell model. GA-A, a GA monomer, was identified as a potent inhibitor on renal fibrosis in vitro. These data demonstrate that GA or GA-A might be developed as a potential therapeutic agent in the treatment of renal fibrosis.
Genetic marker technology designed to detect naturally occurring polymorphisms at the DNA level had become an invaluable and revolutionizing tool for both applied and basic studies of fungi. To eliminate the confusion on the taxonomy of Ganoderma strains, in this study, a collection of 31 accessions representative of morphotypes and some unclassified types was used for analyzing molecular diversity using a novel molecular marker sequence-related amplified polymorphism (SRAP). This collection included commercial cultivars and wild varieties that represented the great diversification of types from different countries and regions. The experimental results showed that 50 out of 95 combinations of primers turned out to be polymorphic, and 85 polymorphism bands were obtained using six combinations. Based on the appearances of markers, the genetic similarity coefficients were calculated, and genetic variations were observed (0 approximately 1) among the 31 different Ganoderma strains. The group of Ganoderma lucidum showed significant differences from the group of Ganoderma sinense. Moreover, G. lucidum in China was also different from G. lucidum in Yugoslavia. At the same time, cluster analysis successfully categorized these 31 Ganoderma strains into five groups. These results revealed the genetic diversity of Ganoderma strains and their correlation with geographic environments. It also suggested SRAP marker could be used in the taxonomic analysis of fungi. To our knowledge, this is the first application of SRAP marker on the systematics of Ganoderma strains within basidiomycetes.
Malignant gliomas are the most common brain tumors with high rates of recurrence and mortality. Novel approaches are in research, and immunotherapy emerges as a promising strategy. Recently, scientific attention has been focused on Ganoderma lucidum polysaccharides (GL-PS), one of the critical bioactive components of G lucidum, which have been recognized as a promising natural source of immunomodulatory and anticancer compounds. It remains unknown whether the GL-PS have any immunomodulatory and anticancer effects on brain glioma. This study was designed to identify and characterize the antitumor action and influence of immune system of GL-PS in glioma-bearing rats. Results showed that GL-PS increased the concentration of serum interleukin-2, tumor necrosis factor-α, and interferon-γ, and enhanced the cytotoxic activity of natural killer cells and T cells, promoting the functional maturation of dendritic cells, thus resulting in the inhibition of glioma growth and prolonged survival of rats. Therefore, GL-PS may be potentially useful as part of the treatment regimen to regulate host immune responses and increase the antitumor effects of immunotherapy for glioma.
Ganoderma lucidum polysaccharide peptide (GLPP) scavenges oxygen free radicals that are a key factor in the pathogenesis of renal ischemia reperfusion injury (RIRI). The aim of this study was to determine whether GLPP could attenuate RIRI by counteracting the oxidative stress. The mechanism involved was assessed by an in vivo mouse RIRI model and an in vitro hypoxia/reoxygenation model, and tunicamycin-stimulated NRK-52E cells were used to explore the GLPP-mediated alleviation of ER stress. Experimental results showed that renal dysfunction and morphological damage were reduced in GLPP-treated group. The imbalance of redox status was reversed and production of ROS was reduced by GLPP. RIRI-induced mitochondrial- and ER stress-dependent apoptosis were dramatically inhibited in GLPP-treated group. Intriguingly, JNK activation in the kidney with RIRI or hypoxia/reoxygenation was inhibited by GLPP. These results suggest that the protective effect of GLPP against RIRI may be due to reducing oxidative stress, alleviating the mitochondrial and ER stress-dependent apoptosis caused by excessive ROS.
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