Huaiqihuang Granules () reduce proteinuria by enhancing nephrin expression and regulating necrosis factor κB signaling pathway in adriamycin-induced nephropathy.

OBJECTIVE: To investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms. METHODS: Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers. RESULTS: HQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis. CONCLUSION: HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

Dahuang Fuzi Decoction ameliorates tubular epithelial apoptosis and renal damage via inhibiting TGF-ß1-JNK signaling pathway activation in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Fuzi Decoction (DFD) is a traditional well-prescribed formula for the treatment of chronic kidney disease (CKD) in China. This study was carried out to examine the effects of DFD in adenine-induced tubular epithelial apoptosis and renal damage, in comparison with allopurinol (AP), then to clarify the therapeutic mechanisms in vivo. MATERIALS AND METHODS: A rat model of renal damage was created by adenine. Rats in Normal and Vehicle groups received distilled water, while rats in DFD and AP groups received DFD and AP, respectively. Proteinuria; urinary N-acetyl-ß-D-glucosaminidase (NAG) levels; the blood biochemical parameters; renal histopathology damage; transferase-mediated dUTP nick-end labeling (TUNEL)-staining; the key molecular protein expressions in mitochondrial and transforming growth factor (TGF)-ß1-c-JunNH2-terminal kinase (JNK) pathways were examined, respectively. RESULTS: Adenine administration induced severe renal damages, as indicated by the mass proteinuria, the heavy urinary NAG, and the marked histopathological injury in tubules and interstitium. This was associated with the activation of TGF-ß1-JNK signaling pathway and tubular epithelial apoptosis. DFD treatment, however, significantly prevented proteinuria and urinary NAG elevation, and attenuated tubular epithelial apoptosis. It suppressed the protein expressions of Bax and cleaved caspase-3, whereas it enhanced the protein expression of Bcl-2. Furthermore, it also suppressed the protein levels of TGF-ß1 as well as phosphorylated-JNK (p-JNK). CONCLUSION: DFD alleviated adenine-induced tubular epithelial apoptosis and renal damage in vivo, presumably through the suppression of TGF-ß1-JNK pathway activation.

[Regulative mechanisms of tubular epithelial to mesenchymal transition and interventional effects of Chinese herbal medicine].

Epithelial to mesenchymal transition (EMT) has been proposed as a key role leading to the progressive tubulo-interstitial fibrosis (TIF). The tubular EMT is an highly regulated process involving four key steps including: loss of epithelial cell adhesion, de novo smooth muscle actin expression and actin reorganization, disruption of tubular basement membrane,and enhanced cell migration and invasion. These crucial processes are closely connected to the relative actions on many signaling pathways in EMT. Additionally, increasing evidences suggest that some Chinese herbal medicines and their extracts, such as Astragali Radix, Cordyceps, Salvia miltiorrhiza, as well as Chinese. herbal prescriptions including Astragalus Angelica mixture and Supplementing Qi and activating blood circulation decoction, could intervene the related events controlling EMT both in vitro and in vivo. Chinese herbal medicines could ameliorate TIF by intervening the course of EMT.

[Regulatory mechanism of NF-kappaB signaling pathway on renal tissue inflammation in chronic kidney disease and interventional effect of traditional Chinese medicine].

In chronic kidney disease (CKD), inflammatory responses during the progression of renal tissue and tissue injury related causes its progression to end-state renal disease. Among them, nuclear factor (nuclear factor, NF)-kappaB signaling pathway by regulating the corresponding nuclear expression of target gene transcription, as well as affecting the synthesis of inflammatory mediators, induction of inflammation lead to kidney damage and renal fibrosis. Some single herbs and their extracts (such as Astragali Radix, Scutellariae Radix, Ginkgo Folium) and some traditional Chinese medicine (such as Danggui Buxue decoction, Qilian decoction) can reduce the inflammatory damage induced by renal tissue NF-kappaB signaling pathway and delay the progression of CKD.