The Protective Effect of the Asystasia chelonoides Extracts on Hypertensive Nephropathy Rats.

BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.

The Chinese medicine Fufang Zhenzhu Tiaozhi capsule protects against renal injury and inflammation in mice with diabetic kidney disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown. AIM OF THE STUDY: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms. MATERIALS AND METHODS: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined. RESULTS: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80+ macrophage cell infiltration and Ly-6G+ neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ. CONCLUSION: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ.

Molecular mechanism of Fufang Zhenzhu Tiaozhi capsule in the treatment of type 2 diabetes mellitus with nonalcoholic fatty liver disease based on network pharmacology and validation in minipigs.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi formula (FTZ) of which a patented preparation of Chinese herbal medicine has been well documented with significant clinical curative effect for hyperglycemia and hyperlipidemia. Because of the complexity of the chemical constituents of Chinese herbal formulas, the holistic pharmacological mechanism of FTZ acting on type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) remains unclear. AIM OF THE STUDY: To investigate the pharmacological efficacy and mechanism of FTZ in the treatment of T2DM accompanied by NAFLD. MATERIALS AND METHODS: Network pharmacology and validation in minipigs were used in this study. First, potential bioactive compounds of FTZ were identified by the traditional Chinese medicine system pharmacology technology platform (TCMSP). Then, targets of compounds were gathered using DrugBank, SwissTargetPrediction and TCMSP, while targets for T2DM and NAFLD were collected from CTD (compounds-targets-diseases network) and GeneCards. Common targets were defined as direct therapeutic targets acting on T2DM with NAFLD. In addition, crucial targets were chosen by the protein-protein interaction (PPI) network and contribution to compound-therapeutic targets in T2DM with the NAFLD network. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by FTZ. Candidate patterns selected by network pharmacology were tested in the minipigs model of T2DM with NAFLD. Measurements of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and fasting blood glucose (FBG) in the blood and the expression levels of proteins, including PI3K-AKT and HIF-1α, in the livers of the minipigs were followed by the administration of FTZ. RESULTS: A total of 116 active compounds and 82 potential targets related to T2DM and NAFLD were found. Pathway and functional enrichment analysis showed that FTZ mainly regulates metabolism-related pathways, including PI3K-AKT, HIF-1α, TNFα and MAPK. Animal experiments showed that FTZ treatment significantly reduced the serum levels of TG, TC, LDL-C and FBG, increased serum levels of HDL-C, ameliorated systemic insulin resistance (IR), and attenuated liver damage in minipigs with T2DM and NAFLD. FTZ treatment has an obviously favorable influence on hepatic steatosis and liver lipid accumulation in the histopathologic features of HE, Oil red O staining, and electron microscopy. Mechanistically, FTZ improved liver metabolism by increasing the phosphorylation of PI3K-AKT and decreasing the expression of HIF-1α. CONCLUSION: Network pharmacology was supported by experimental studies, which indicated that FTZ has demonstrated therapeutic benefits in T2DM and NAFLD by regulating the PI3K-AKT and HIF-1α signaling pathways.

Renshen Shouwu extract enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 signaling pathway following ischemic stroke in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Renshen Shouwu extract (RSSW) is a patented Traditional Chinese Medicine included in Chinese Pharmacopoeia for neurasthenia, forgetfulness, insomnia, inappetence and excessive fatigue. Our previous study had demonstrated the neuroprotective effect of RSSW against ischemic stroke in rats with middle cerebral artery occlusion (MCAO). However, its underlying mechanism remains unknown. AIM OF THE STUDY: In this study, we investigated the neurogenesis and angiogenesis effects of RSSW in ischemic stroke rats, and further revealed its underlying mechanism focused on TLR4/NF-κB/NLRP3 signaling pathway. MATERIALS AND METHODS: Firstly, active compounds of RSSW were determined by High Performance Liquid Chromatography (HPLC). Secondly, Middle cerebral artery occlusion (MCAO) was performed to induce ischemic stroke in rats and 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was employed to evaluate whether MCAO surgery was successfully established. Neurological deficit evaluation was conducted according to the Zea Longa' method. Then, we explored the neurogenesis and angiogenesis effects after oral administration of RSSW (50 mg/kg, 100 mg/kg) in MCAO-induced rats by Immunofluorescence Staining. Moreover, the proteins involved in TLR4/NF-κB/NLRP3 signaling pathway (TLR4, p-NF-κB p65, NF-κB p65, NLRP3, pro-IL-1ß, IL-1ß, pro-Caspase-1, Caspase-1) were determined by western blotting. RESULTS: It was observed that RSSW treatment significantly increased the number of newborn neurons and brain microvessel density (MVD) after ischemic stroke. What's more, RSSW treatment significantly downregulated TLR4, p-NF-κB p65/p65, NLRP3, pro-IL-1ß, IL-1ß, pro-Caspase-1, Caspase-1 proteins involved in TLR4/NF-κB/NLRP3 signaling pathway. CONCLUSIONS: RSSW enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 inflammatory signaling pathway following ischemic stroke in rats. Hence, RSSW may be a promising Chinese Medicine for the treatment of ischemic stroke.