ABSTRACT
Bupleurum polysaccharides (BPs) is isolated from Bupleurum smithii var. parvifolium, a key traditional Chinese medicine. The study was to investigate the effects of BPs on diabetic kidney injury. After two intraperitoneal injections of streptozotozin (STZ) 100 mg·kg-1, renal injury in diabetic mice was induced and BPs was orally administrated at dosages of 30 and 60 mg·kg-1·d-1. The STZ injected mice developed renal function damage, renal inflammation and fibrosis known as diabetic kidney disease (DKD). BPs significantly reduced serum creatinine level and urinary albumin excretion rate, with the attenuated swelling of kidneys. BPs treatment obviously alleviated the pathological damage of renal tissue. The progression of renal injury in BPs treated mice was inhibited with less expression of type IV collagen (Col IV), fibronectin (FN) and α-smooth muscle actin (α-SMA). The inhibition of inflammation in kidney was associated with the reduced level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). BPs administration suppressed the over-expression of toll like receptor 4 (TLR4) and high-mobility group box 1 (HMGB1) with lowered activity of nuclear factor kappa B (NF-κB) in renal tissue of diabetic mice. Oral administration of BPs effectively prevented the development ofrenal injury in diabetic mice. This study suggested that the protection provided by BPs might affect through the interruption of HMGB1-TLR4 pathway, leading to the inhibition of renal inflammation and fibrotic process.
Subject(s)
Bupleurum/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , HMGB1 Protein/metabolism , Polysaccharides/therapeutic use , Toll-Like Receptor 4/metabolism , Animals , Cytokines/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/chemically induced , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Inflammation/metabolism , Inflammation/prevention & control , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Mice, Inbred C57BL , Plant Roots/chemistry , Polysaccharides/administration & dosage , Polysaccharides/pharmacology , Signal Transduction/drug effects , Streptozocin/toxicity , Transcription Factor RelA/metabolismABSTRACT
PURPOSE: Yanghe Pingchuan granules (YPG), a hospital preparation developed by The First Affiliated Hospital, Anhui University of Chinese Medicine, has been used for the clinical treatment of bronchial asthma (BA) for several decades. This study aimed to explore the mechanism of action of YPG in the treatment of BA. MATERIALS AND METHODS: Male Sprague Dawley rats (n=60) were randomly divided into six groups (n=10 per group): control, a BA model, positive drug control (Guilong Kechuanning capsules; a proven effective treatment for BA), and model rats treated with a high, medium, or low dose of YPG. H&E staining was used to detect pathological changes in the bronchial tubes. The mRNA expression levels of PI3K, PKB, PCNA, and AR were determined by real-time PCR, and the protein levels of phospho- (p-)PI3K, p-PKB, p-PCNA, and p-AR were detected by Western blotting. ELISAs were used to detect the expression of PIP2, PIP3 IL-6, IL-8, IL-1ß, and epinephrine (EPI). RESULTS: H&E staining demonstrated that BA can be ameliorated using YPG. Real-time PCR, Western blotting, and ELISA indicated that use of YPG decreased expression of the phosphoinositide 3-kinase (PI3K) signaling pathway and PCNA, and can also ameliorate the condition kidney Yang deficiency, which is associated with BA in Chinese traditional medicine. CONCLUSION: YPG can attenuate BA therapeutically in a dose-dependent manner. The mechanism underlying its therapeutic effect comprises influences on three features that contribute to BA: the PI3K signaling pathway, cell proliferation, and "kidney-Yang deficiency".
Subject(s)
Airway Remodeling/drug effects , Asthma/drug therapy , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional , Animals , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/therapeutic use , Male , Phosphatidylinositol 3-Kinases/physiology , Proliferating Cell Nuclear Antigen/analysis , Proto-Oncogene Proteins c-akt/physiology , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effectsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata (HC) has been used as a folk therapy to treat pulmonary infections. This study aimed to determine the role and mechanism of action of polysaccharides isolated from HC (HCP) in lipopolysaccharide (LPS)-induced ALI in the mice. MATERIALS AND METHODS: LPS was delivered by the intratracheal route to Balb/c mice 2h before HCP (40, 80 and 160mg/kg) administration. RESULTS: The number of total cells, protein and tumor necrosis factor-α (TNF-α) concentrations in bronchoalveolar lavage fluid, the wet/dry weight ratio (w/d) of lungs and pulmonary pathology of each mouse were analyzed, it was found that HCP significantly alleviated ALI induced by LPS. Moreover, in lungs of mice, it was found that the infiltration of inflammatory cells, the expression of Toll-like receptor 4 and complement deposition were significantly decreased by HCP treatment. In vitro assays showed that C5a, a complement activation product, induced significant macrophage migration and treatment with HCP prevented it. The in vitro results also proved that LPS increased nitric oxide and pro-inflammatory cytokines (TNF-α, interleukin-6, and interleukin-1ß) production, and HCP antagonized these effects of LPS. It was also found that HCP alone augmented secretion of some pro-inflammatory cytokines. CONCLUSION: These results indicate that HCP may alleviate LPS induced lung inflammatory injury, which may be associated with its inhibitory effect on the over activation of complement and macrophages. This suggests a potential role to treat ALI.