Anti-Inflammatory Triterpenoids from the Caulophyllum robustum Maximin LPS-Stimulated RAW264.7 Cells.

Caulophyllum robustum Maxim is widely distributed in China and used as a traditional herbal medicine to induce childbirth, ease the pain of labor, rectify delayed or irregular menstruation, alleviate heavy bleeding and pain during menstruation, and treat external injuries and irregular menses. According to our detailed chemical investigation, three new triterpene derivatives (1⁻3), together with seven known compounds, were isolated from the root and rhizome of C. robustum Maxim. Their structures were elucidated by 1D- and 2D-NMR spectroscopic analysis and physio-chemical methods. They were identified as (1) 23-hydroxy-3,19-dioxo-olean-12-en-28-oic-acid; (2) 23-hydroxy-3,11-dioxo-olean-12-en-28-oic acid; and (3) 16α,23-dihydroxy-3-oxo-olean-12-en-28-oic acid. Compounds (1⁻10) inhibited the LPS-activated NO production in RAW264.7 cells. Furthermore, the anti-inflammatory characteristics of these compounds were confirmed on the basis of decreases in iNOS and NF-κB protein expression in RAW264.7 cells.

Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF-ß1
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OBJECTIVE: Renal fibrosis generally results in renal failure during the end stage of chronic renal diseases. There are many cell factors including E-cadherin, α-SMA, and TGF-ß1 influencing deposition of extracellular matrix and leading to renal fibrosis. As the most important and widely-used therapy for various diseases in China for thousands of years, traditional Chinese medicine (TCM) provides a novel treatment for renal fibrosis. For clinical application, we explore the effect of Bu-Shen-Huo-Xue formula (BSHX), a traditional Chinese herbal formula, on E-cadherin and α-SMA in rats with 5/6 nephrectomy. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to 5/6 nephrectomy to induce chronic renal failure (CRF); they were divided into three groups including a CRF control group, a BSHX group, and a Cozaar group, and compared with a normal control group. After 8 weeks of therapy with the respective drug, E-cadherin, α-SMA, and TGF were detected by immunohistochemistry assays in renal tissues. RESULTS: As the immunohistochemistry assays indicated, BSHX could significantly enhance the expression of E-cadherin and depress the levels of α-SMA and TGF-ß1 expression in rats' renal tissues with 5/6 nephrectomy. CONCLUSION: BSHX can effectively relieve the renal fibrosis in rats with 5/6 nephrectomy via the change of cell factor levels including enhancement of the expression of E-cadherin and depression of the levels of α-SMA and TGF-ß1 expression.
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Berberine protects HK-2 cells from hypoxia/reoxygenation induced apoptosis via inhibiting SPHK1 expression.

Renal ischemia reperfusion injury (RIRI) refers to the irreversible damage for renal function when blood perfusion is recovered after ischemia for an extended period, which is common in clinical surgeries and has been regarded as a major risk for acute renal failures (ARF) that is accompanied with unimaginably high morbidity and mortality. Hypoxia during ischemia followed by reoxygenation via reperfusion serves as a major event contributing to cell apoptosis, which has been widely accepted as the vital pathogenesis in RIRI. Preventing apoptosis in renal tubular epithelial cell has been considered as effective method for blocking RIRI. In this paper, we established a hypoxia/reoxygenation (H/R) injury model in human proximal tubular epithelial HK-2 cells. Here, we found increased SPHK1 levels in H/R injured HK-2 cells, which could be significantly down regulated after berberine treatment. Berberine has been reported to exert a protective effect on H/R-induced apoptosis of HK-2 cells. So, in our present study, we planned to investigate whether SPHK1 participated in the anti-apoptosis process of berberine in H/R injured HK-2 cells. Our study confirmed the protective effect of berberine against H/R-induced apoptosis in HK-2 cells through promoting cells viability, inhibiting cells apoptosis, and down-regulating p-P38, caspase-3, caspase-9 as well as SPHK1, while up regulating the ratio of Bcl-2/Bax. However, SPHK1 overexpression in HK-2 cells induced severe apoptosis, which can be significantly ameliorated with additional berberine treatment. We concluded that berberine could remarkably prevent H/R-induced apoptosis in HK-2 cells through down-regulating SPHK1 expression levels, and the mechanisms included the suppression of p38 MAPK activation and mitochondrial stress pathways.

Huangqi Decoction Ameliorates Streptozotocin-Induced Rat Diabetic Nephropathy through Antioxidant and Regulation of the TGF-ß/MAPK/PPAR-γ Signaling.

BACKGROUND/AIMS: Huangqi Decoction (HQD) has been traditionally used to treat diabetes mellitus in China. The present study was carried out to assess the protective effect of HQD on diabetic nephropathy (DN) using the streptozotocin-induced (STZ) diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Wistar rats. 40 diabetic rats were divided into 5 groups: vehicle-treated (DN group), 0.45, 0.15, 0.05 g/kg HQD-treated diabetic group (HQD group) and 1 mg/kg rosiglitazone-treated diabetic group (RGZ group). 16 normal rats were randomly divided into 2 groups: vehicle-treated normal control group (NC) and 0.45 g/kg HQD-treated normal control group (NC+0.45 g/kg HQD). At the end of 8-week experiment, we measured changes of renal pathological morphology, function, antioxidant enzyme levels and the activation of TGF-ß/PPAR-γ/MAPK signaling pathway. RESULTS: After HQD treatment, renal function, including blood urea nitrogen (BUN), 24-h albuminuria and blood glucose level were improved significantly; meanwhile, impaired kidney redox balance was diminished in diabetic rats. The activation of TGF-ß, phospho-JNK, phospho-p44/42, p47 and p42 phox was blocked and the decrease in PPAR-γ in diabetic rats was attenuated by treatment with HQD in a dose-dependent manner. CONCLUSION: These results suggest that HQD shows therapeutic efficacy in DN characterized by renal dysfunction and pathological changes through hypoglycemic and antioxidant effects.

Protective Effects of Bu-Shen-Huo-Xue Formula against 5/6 Nephrectomy-Induced Chronic Renal Failure in Rats.

Chronic renal failure (CRF) is a serious disease related to increasing incidence and prevalence as well as decline in quality of life. Bu-Shen-Huo-Xue formula (BSHX), one of traditional herbal formulations, has been clinically employed to treat CRF for decades, but the mechanisms involved have not been investigated. In the present study, we investigated the effects of BSHX on some closely related parameters in 5/6 nephrectomy CRF rats. Rats with CRF were divided into five groups, namely, one control group, one enalapril group, and three BSHX treatment groups (0.25, 0.5, and 1 g/kg·d). The rats subjected to sham operation were used as a normal control. After eight weeks of treatment, BSHX significantly decreased the levels of Scr and BUN, downregulated the mRNA expression levels of TGF-ß 1, CTGF, NF-κB, TNF-α, and OPN, upregulated the mRNA expression of PPARγ, and reduced in situ expression of fibronectin and laminins. Histological findings also showed significant amelioration of the damaged renal tissue. BSHX protects 5/6 nephrectomy rats against chronic renal failure probably via regulating the expression of TNF-α, NF-κB, TGF-ß 1, CTGF, PPARγ, OPN, fibronectin, and laminins and is useful for therapy of CRF.