Clinical prognostic role of bioimpedance phase angle in diabetic and non-diabetic hemodialysis patients.

BACKGROUND AND OBJECTIVES: Bioelectrical-impedance analysis (BIA) is frequently used to estimate dry weight in hemodialysis (HD) patients. However, the clinical prognostic significance of BIA indicators is unclear. As a nutritional index, low phase angle (PA) might be an independent risk factor for predicting death in multiple chronic diseases. We performed this study to find relative influence factors of PA and other clinical prognostic significance. METHODS AND STUDY DESIGN: The study involved 87 HD patients, 33 of whom were diabetic and 54 of whom were not. We measured body composition index, body water index and nutritional indicators and collected biochemical criteria. Then, we statistically analyzed the associations of these indices. After 1 year of follow- up, we recorded death, heart failure, hospitalization, cerebrovascular and cardiovascular events and other clinical outcomes. RESULTS: We found a significant difference between the two groups in visceral-fat area, extracellular water/total body water (ECW/TBW) ratio and PA value. Two factors were negatively associated with PA: ECW/TBW ratio and HCO3- before HD. At 1 year, we noted that PA was associated with events such as heart failure or hospitalization. By further stratification and multivariate analysis adjusting for age, sex and months of dialysis, we found that low PA was an independent predictor of heart failure for diabetic HD patients. CONCLUSIONS: PA value was lower in Diabetic nephropathy (DN) HD patients, than that in non-DN HD patients. PA was mainly negatively associated with ECW/TBW ratio. It is a useful index for predicting heart failure in diabetic HD patients.

Artemether attenuates renal tubular injury by targeting mitochondria in adriamycin nephropathy mice.

Chronic kidney disease (CKD) is complex and current treatment remains limited. As we know, glomerular injury plays a dominant role in kidney disease progression. However, accumulating evidence demonstrated that renal tubules, rather than being victims or bystanders, are major initiators in renal fibrosis progression. Renal tubules are rich in mitochondria and mitochondrial dysfunction may participate in renal tubular phenotypic changes and ultimately promote renal fibrosis. Previous studies have proved that artemether displayed renal protective effects, but the mechanisms remain unclear. In this experiment, we showed that artemether reduced urinary protein/creatinine ratio and attenuated renal tubular injury. Both in vivo and in vitro results indicated that artemether could restore renal tubular phenotypic alterations. Meanwhile, the unbalanced expressions of Bax and Bcl-xL in renal tubules were restored by artemether. In addition, artemether also regulated mitochondrial pyruvate metabolism, increased mitochondrial biogenesis, and improved mitochondrial function. Taken together, this study suggested that artemether could attenuate renal tubular injury by regulating mitochondrial biogenesis and function. It has great potential to be translated to the clinic as a therapeutic agent for treating kidney diseases, especially those associated with renal tubular injury.

Artemether ameliorates type 2 diabetic kidney disease by increasing mitochondrial pyruvate carrier content in db/db mice.

Diabetic kidney disease (DKD), the leading cause of kidney failure, is characterized by albuminuria and renal hypertrophy. Metabolic alterations and mitochondrial dysfunction play critical roles in DKD initiation and progression. Artemether, a methyl ether derivative of artemisinin used for the treatment of malaria, has been identified as a putative candidate for treating diabetes, but its effect on DKD has not been studied. The goal of this study was to examine the effect of artemether on type 2 diabetic db/db mice. Our results show that artemether reduced urinary albumin excretion, prevented diabetic kidney hypertrophy, attenuated glomerular basement membrane and tubular basement membrane thickening, and ameliorated foot process effacement in type 2 diabetic db/db mice. Artemether also protected against hyperglycemia and improved diabetic symptoms. In addition, it increased serum insulin level and restored the normal ratio of insulin, glucagon, and somatostatin levels in islets. Specifically, artemether increased the respiratory exchange ratio and regulated mitochondrial function and the redox state in the kidney. In conclusion, this experiment confirmed the renal protection ability of artemether in DKD. The mechanisms of this effect might be associated with the ability of artemether to increase mitochondrial pyruvate carrier content.

Metabolomics Reveals Effect of Zishen Jiangtang Pill, a Chinese Herbal Product on High-Fat Diet-Induced Type 2 Diabetes Mellitus in Mice.

A Chinese herbal decoction, Zishen Jiangtang Pill (ZJP), has been clinically prescribed to diabetic patients to prevent excessive blood sugar levels for decades. However, the potential mechanisms of this action have not been well investigated. The purpose of this study was to explore the metabolic variations in response to ZJP treatment for an animal model of obese type 2 diabetes. An UHPLC-Orbitrap/MS-based metabolomics tool was conducted to reveal the potential mechanisms of ZJP on diabetic mice. The treatment with ZJP significantly restored the increased levels of insulin, glucose and total cholesterol in high-fat diet mice. A total of 26 potential biomarkers were found and identified in serum samples, amongst which 24 metabolites were robustly affected and driven back to the control-like levels after ZJP treatment. By analyzing the metabolic pathways, glutathione metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism were suggested to be closely involved in diabetes disease. From the above outcomes, it can be concluded that ZJP exhibits a promising anti-diabetic activity, largely due to the regulation of phospholipid metabolism, including phosphatidylcholines, lysophosphatidylcholines, and phosphatidylinositol.

Jian-Pi-Yi-Shen Decoction Relieves Renal Anemia in 5/6 Nephrectomized Rats: Production of Erythropoietin via Hypoxia Inducible Factor Signaling.

Jian-Pi-Yi-Shen (JPYS) is one of the herbal medicines for treatment of anemic patients with chronic kidney disease (CKD). However, less of scientific evidence to support JPYS involved in treating anemia has been revealed. Here, an animal study was performed to investigate its hematopoietic activities and the underlying mechanism. The 5/6 nephrectomized inductions of CKD anemic rats were randomly divided into two groups: CKD group and JPYS group. Sham-operated rats served as sham group. JPYS (1.36 g/kg/d) was administered orally to CKD rats daily for six consecutive weeks. Results showed that JPYS treatment notably improved renal function and pathological injury in CKD rats. JPYS also restored the hematological parameters, including red blood cells, hemoglobin, and hematocrit. In parallel, the reduction level of EPO was reversed by JPYS. Furthermore, JPYS induced the accumulation of hypoxia inducible factor (HIF)-α protein expression. Collectively, these results provide convincing evidence for JPYS decoction in ameliorating CKD-associated anemia, and its mechanism might be related to regulate EPO production via HIF signaling pathway.

Niclosamide ethanolamine protects kidney in adriamycin nephropathy by regulating mitochondrial redox balance.

Chronic kidney disease (CKD) is commonly characterized by proteinuria and leads to progressive glomerulosclerosis and tubulointerstitial fibrosis. Accumulating evidence implicates mitochondrial dysfunction including reactive oxygen species (ROS) overproduction in the pathogenesis of CKD. Mitochondrial function and ROS production are regulated by mitochondrial uncoupling. Niclosamide ethanolamine salt (NEN) is a mild mitochondrial uncoupler, which reduces urinary albumin excretion in mice with diabetic kidney disease. However, its role in nondiabetic kidney disease has not been investigated. Here we show that NEN exerts renoprotective effects in adriamycin induced nondiabetic kidney disease. It reduces urinary protein excretion, restores podocyte function, ameliorates renal pathological injury, and decreases the excretion of the urinary tubular injury biomarkers NGAL and Kim-1. Specifically, NEN uncouples isolated kidney mitochondria, and dose-dependently decreases the renal production and urinary excretion of H2O2. Moreover, NEN increases catalase and PGC-1α expression, which might accelerate H2O2 scavenging. The results of this study provide the first evidence that NEN protects kidney in nondiabetic kidney disease by regulating redox balance.

A novel mutation in a Chinese family with autosomal recessive Alport syndrome: a case report.

Alport syndrome (AS) is a familial hereditary nephropathy which is characterized by molecular abnormalities in Collagen IV a345. As more gene mutations are discovered, it has been reported that autosomal recessive disease accounts for a smaller proportion (about 4%) of AS patients than previously recognized. We report here a novel mutation in COL4A4 in a Chinese family with autosomal recessive AS. Patient 1 was a 24-year-old Chinese man. He and his brother (patient 2) had a history of proteinuria and hematuria with renal dysfunction and sensorineural deafness. Pathologic findings were consistent with Alport syndrome, and genetic analysis revealed that both patients had two heterozygous mutations, c.1423 G>T (p.Gly475Cys) in EX21/CDS20 and c.735 G>A (p.Pro245Pro) in EX12/CDS11, and that each mutation originated from their mother or father who were carriers for one of these two mutations. Both patients showed similar results by laboratory examination and histopathologic assessment. Patient 1 received ACEI treatment and ran a stable clinical course, whereas patient 2 refused ACEI treatment and had progressive deterioration of renal function. This is the first report of a novel mutation in the collagen domain of COL4A4 gene. The results add to the spectrum of mutations in COL4A4 of Alport syndrome.

Jian-Pi-Yi-Shen Formula ameliorates chronic kidney disease: involvement of mitochondrial quality control network.

BACKGROUND: Jian-Pi-Yi-Shen Formula (JPYSF), a Chinese herbal decoction with the efficacies of 'fortify the spleen and tonify the kidney' and 'activate blood and resolve stasis', is effective for the treatment of chronic kidney disease in clinic. However, the underlying mechanism remains unclear. The aim of this study was to investigate the therapeutic effects and possible mechanisms of JPYSF on retarding chronic kidney disease progression in 5/6 nephrectomized (5/6 Nx) rats. METHODS: Perindopril (4 mg/kg/d) and JPYSF (2.72 g/kg/d) were administrated by gavage to 5/6 Nx rats daily for 6 weeks. The therapeutic effects of JPYSF were evaluated by renal function, pathological injury, and fibrosis. The protein levels associated with mitochondrial quality control network were measured by Western blot and immunofluorescence analysis. RESULTS: 5/6 Nx rats showed obvious decline in renal function as evidenced by increased serum creatinine, blood urea nitrogen, and urinary protein excretion, and significant injury in kidney structure as evidenced by glomerular hypertrophy, tubular atrophy, and interstitial fibrosis. Administration of JPYSF for 6 weeks could improve renal function and ameliorate kidney structure injury in 5/6 Nx rats. Furthermore, the remnant kidneys of 5/6 Nx rats showed unbalanced mitochondrial quality control network manifested as decreased mitochondrial biogenesis, fusion, and mitophagy, and increased mitochondrial fission. Treatment of JPYSF could restore aforesaid aspects of mitochondrial quality control network. CONCLUSIONS: These results indicate that JPYSF can notably ameliorate 5/6 Nx-induced chronic kidney disease, which may be related with modulation of mitochondrial quality control network.

Angelica sinensis Supercritical Fluid CO2 Extract Attenuates D-Galactose-Induced Liver and Kidney Impairment in Mice by Suppressing Oxidative Stress and Inflammation.

Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose (D-gal)-elicited senescent mice brain, its effects on liver and kidney injury have not yet been explored. In this work, mice were subjected to hypodermic injection with D-gal (200 mg/kg) and orally gavaged with AS (20, 40, or 80 mg/kg) once a day for 8 successive weeks. Results revealed that AS significantly improved liver and kidney function as assessed by organ index and functional parameters. In addition, AS pretreatment effectively ameliorated the histological deterioration. AS attenuated the MDA level and markedly enhanced the activities and gene expressions of antioxidative enzymes, namely Cu, Zn-SOD, CAT, and GPx. Furthermore, AS markedly inhibited the D-gal-mediated increment of expressions of inflammatory cytokines iNOS, COX-2, IκBα, p-IκBα, and p65 and promoted the IκBα expression level in both hepatic and renal tissues. In sum, AS pretreatment could effectively guard the liver and kidney of mice from D-gal-induced injury, and the underlying mechanism was deemed to be intimately related to attenuating oxidative response and inflammatory stress.

Niclosamide ethanolamine improves kidney injury in db/db mice.

AIMS: Early diabetic kidney disease (DKD) is characterized by renal hypertrophy and albuminuria. The mTOR signal pathway is closely related to DKD. This study was performed to determine the renal protection of niclosamide ethanolamine salt (NEN) which was identified as mTOR inhibitor. METHODS: Type 2 diabetes (T2D) db/db mice were used and divided into db/db and db/db + NEN groups. Lean wild type mice served as T2D-control. NEN treatment lasted for 12 weeks. The kidney morphological changes, urine indices, blood glucose and metabolic symptoms were evaluated. In addition, the effects of NEN on kidney mitochondria and mTOR/4E-BP pathway were also measured. RESULTS: NEN could prevent diabetic kidney hypertrophy and alleviate glomerular mesangial expansion, attenuate GBM and TBM thickening in db/db mice. It also restored podocyte dysfunction, reduced urinary albumin, NAG, NGAL, and TGF-ß1 excretion. Specifically, it could uncouple kidney mitochondria and significantly inhibit renal cortical activation of mTOR/4E-BP1 pathway. CONCLUSIONS: This study demonstrated that NEN could improve kidney injury in db/db mice and has the potential to translate to future clinical studies.

A Chinese Herbal Preparation, Xiao-Er-An-Shen Decoction, Exerts Neuron Protection by Modulation of Differentiation and Antioxidant Activity in Cultured PC12 Cells.

Xiao-Er-An-Shen Decoction (XEASD), a Chinese herbal formula, has been used in clinic for treating insomnia and mental excitement in children and adolescents. However, less of scientific data supports its effectiveness in clinic. Here, we aim to study the role of XEASD in regulating neuron differentiation and antioxidant activity. An HPLC-MS was used to chemically standardize herbal extract of XEASD. The standardized herbal extracts of XEASD (0.3-3.0 mg/mL) were applied onto cultured PC12 cells for 48 hours. The treatment with XEASD extract induced neurite outgrowth of PC12 cells in a dose-dependent manner, having the highest response by ~50% of differentiated cells. Application of XEASD extract dose dependently stimulated expressions of NF68, NF160, and NF200 in cultured PC12 cells. Furthermore, XEASD activated the phosphorylation of cAMP responsive element binding protein on PC12 cells, the effect of which was blocked by H89, a protein kinase A inhibitor. Moreover, XEASD showed free radical scavenging activity and stimulated the transcriptional activity of ARE. These results supported the neurobeneficial effects of XEASD in the induction of neurite outgrowth and protection against oxidative stress and could be useful for neurological diseases, in which neurotrophin deficiency and oxidation insult are involved.

Astragaloside IV ameliorates early diabetic nephropathy by inhibition of MEK1/2-ERK1/2-RSK2 signaling in streptozotocin-induced diabetic mice.

Objective The aim of this study was to investigate the renoprotective effects and molecular mechanisms of astragaloside IV (AS-IV) in streptozotocin (STZ)-induced diabetic mice. Methods Male C57BL/6 mice were injected intraperitoneally with STZ at 200 mg/kg body weight. AS-IV was administered for 8 consecutive weeks, beginning 1 week after STZ injection. Body weight, 24-hour urinary albumin excretion, and fasting blood glucose were measured. Kidney tissues were examined by histopathological analyses. Total levels and phosphorylation of mitogen-activated protein kinase 1/2 (MEK1/2), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and ribosomal S6 kinase 2 (RSK2) were determined by Western blotting analysis. Results AS-IV treatment significantly reduced albuminuria and serum creatinine levels, ameliorated mesangial matrix expansion and greater foot process width, and decreased the levels of urinary N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, and transforming growth factor-beta 1 in STZ-induced diabetic mice. AS-IV also inhibited renal cortical phosphorylation of MEK1/2, ERK1/2 and RSK2. Conclusion Our results suggest that AS-IV attenuates renal injury in STZ-induced diabetic mice. This effect might be partially associated with inhibition of the activation of the MEK1/2-ERK1/2-RSK2 signaling pathway.

Niclosamide ethanolamine improves diabetes and diabetic kidney disease in mice.

Diabetes and its renal complications are major medical challenges worldwide. There are no effective drugs currently available for treating diabetes and diabetic kidney disease (DKD), especially in type 1 diabetes (T1D). Evidence has suggested that niclosamide ethanolamine salt (NEN) could improve diabetic symptoms in mice of type 2 diabetes (T2D). However, its role in T1D and DKD has not been studied to date. Here we report that NEN could protect against diabetes in streptozotocin (STZ) induced T1D mice. It increased serum insulin levels, corrected the unbalanced ratio of α-cells to ß-cells, and induced islet morphologic changes under diabetic conditions. In addition, NEN could impede the progression of DKD in T1D. Specifically, it reduced urinary albumin levels, NAG, NGAL and TGF-ß1 excretion, ameliorated renal hypertrophy, alleviated podocyte dysfunction, and suppressed the renal cortical activation of mTOR/4E-BP1 signaling pathway. Moreover, it is hepatoprotective and does not exhibit heart toxicity. Therefore, these findings open up a completely novel therapy for diabetes and DKD.

Octahydrocurcumin, a final hydrogenated metabolite of curcumin, possesses superior anti-tumor activity through induction of cellular apoptosis.

The biological activity of curcumin (CUR), a promising naturally occurring dietary compound for the treatment of hepatocellular carcinoma (HCC), was closely associated with its metabolite. Octahydrocurcumin (OHC) is the final hydrogenated metabolite of CUR and has been reported to have potential biological activities. However, difficulties in access have hampered its biological studies. In the current investigation, we designed an efficient synthesis method to produce OHC, and comparatively explored the anti-cancer effect and potential mechanism of OHC and CUR in an H22 ascites tumor-bearing mice model. The results indicated that OHC had a relatively wide margin of safety, and exhibited superior effects to CUR in suppressing the tumor growth, including ascending weight, abdominal circumference, ascites volume and cancer cell viability. OHC significantly induced H22 cell apoptosis by upregulating the p53 expression and downregulating the MDM2 expression. OHC also remarkably decreased the Bcl-2 and Bcl-xl protein expressions, and increased the Bax and Bad expressions in ascitic cells. Furthermore, THC substantially induced the release of cytochrome C, caspase-3, caspase-9 and the cleavage of PARP to induce H22 cell apoptosis. Taken together, OHC was more effective than CUR in suppressing H22-induced HCC through the activation of the mitochondrial apoptosis pathway. OHC may thus be a promising anti-HCC agent.

A Chinese herbal decoction, Jian-Pi-Yi-Shen, regulates the expressions of erythropoietin and pro-inflammatory cytokines in cultured cells.

BACKGROUND: A Chinese herbal formula, namely Jian-Pi-Yi-Shen (JPYS), has been clinically prescribed for patients with chronic kidney disease associated-anemia, and which can improve the patient's immunological system. However, the mechanisms of JPYS involved in anemia and immune response have not been investigated. To study the role of JPYS in regulating hematopoietic and immunological functions, we investigated its activities on the expressions of erythropoietin and pro-inflammatory cytokines in cultured cells. METHODS: The standardized herbal extracts of JPYS (0-30 µg/ml) were applied onto cultured cells for 24-48 h. Total RNA was collected from the treated cells and subjected to real-time quantitative PCR analysis. Cultured HEK293T cells, transfected with a construct composed of hypoxia response element tagged with a luciferase gene, i.e. pHRE-Luc, were treated with JPYS extracts (1-30 µg/ml) for 24 h. The cell lysates were subjected to luciferase assay. RESULTS: The treatment with JPYS extract onto cultured HEK293T cells induced erythropoietin expression in a dose-dependent manner, having the highest response by ~ 50% of increase. In parallel, application of JPYS extract for 24 h stimulated expressions of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in cultured RAW 264.7 macrophages. In contrast, the pretreatment with JPYS extract suppressed expressions of IL-1ß, IL-6, and TNF-α in lipopolysaccharide-induced macrophages. CONCLUSIONS: These results confirmed the hematopoietic function of JPYS in regulating erythropoietin expression, as well as the bidirectional immune-modulatory roles of JPYS by regulating the expression of pro-inflammatory cytokines in cultures.

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice.

Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1ß, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC.

Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis.

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.

A Chinese herbal formula, Jian-Pi-Yi-Shen decoction, improves muscle atrophy via regulating mitochondrial quality control process in 5/6 nephrectomised rats.

Muscle atrophy is one of the serious complications of chronic kidney disease (CKD). Dysregulation of mitochondrial quality control (MQC) process, including decrease mitochondrial biogenesis, impair mitochondrial dynamics and induce activation of mitophagy, play an important role in mediating muscle wasting. This study aimed to observe effects of Jian-Pi-Yi-Shen (JPYS) decoction on muscle atrophy in CKD rats and explore its possible mechanism on regulation of MQC processes. The 5/6 nephrectomised rats were randomly allocated into 2 groups: CKD group and JPYS group. Besides, a sham-operated rats as sham group. All rats were treated for 6 weeks. Results showed that administration of JPYS decoction prevented body weight loss, muscle loss, muscle fiber size decrease, muscle protein degradation, and increased muscle protein systhesis. In addition, JPYS decoction increased the mitochondrial content and biogenesis proteins, and down-regulated the autophagy and mitophagy proteins. Furthermore, JPYS decoction increased mitochondrial fusion proteins, while decreased mitochondrial fission proteins. In conclusion, JPYS decoction increased mitochondrial content and biogenesis, restore the balance between fission and fusion, and inhibited autophagy-lysosome pathway (mitophagy). Collectively, our data showed that JPYS decoction to be beneficial to muscle atrophy in CKD, which might be associated with the modulation of MQC process.

Astragaloside IV ameliorates renal injury in db/db mice.

Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-ß1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways.