Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes and the primary cause of end-stage renal disease. At present, renin–angiotensin–aldosterone system (RAAS) blockers have been applied as first-class drugs to restrain development of DN; however, its long-term effect is limited. Recent evidence has shown definite effects of Chinese medicine on DN. Yishen Huashi (YSHS) granule is a traditional Chinese Medicine prescription that has been used in the clinic to treat DN, but its mechanism is not understood.Methods: In the present study, both in vitro and in vivo studies were carried out. The DN model was induced by STZ in Wistar rats, and GEnC and HPC cell lines were applied in the in vitro study. Quality of YSHS was evaluated by LC-MS/MS. A metabolomic study of urine was carried out by LC-MS; influence of YSHS on composition of DN was analyzed by network pharmacology. Mechanism of the YSHS on DN was analyzed by Q-PCR, Western Blot, and multi-immunological methods.Results: We found YSHS administration significantly reduced levels of HbA1c and mALB. Histopathological analysis found that YSHS preserved integrity of glomerular filtration barrier by preserving viability of glomerular endothelial cells and podocytes, inhibiting glomerular fibrosis, reducing oxidative stress damage, and enhancing cross-talk among glomerular endothelial cells and podocytes. Network pharmacology, differential metabolite analysis, as well as intracellular pathway experimental study demonstrated that the PI3K/AKT/mTOR signaling pathway played a pivotal role in it.Conclusion: Our present findings supplied new understanding toward the mechanism of YSHS on inhibiting DN.
Background/aims: Hypertensive nephropathy (HN) is a kind of renal diseases caused by essential hypertension, eventually worsens into end-stage renal disease (ESRD). HN could damage the renal tubules, induce kidney damage, renal failure, and increase the risk of stroke, heart disease or death, but there are few ideal drugs for HN treatment. Methods: In this study, we explored the therapeutic effect of bajijiasu (a compound from Morinda officinalis how and a common traditional Chinese medicine for tonifying the kidney) on the HN rat model. Biochemical analysis, HE staining, and PAS staining were used to assess the effects of bajijiasu on HN rat model, western blotting was used to analyze the potential mechanisms. Results: The results of HE staining and PAS staining showed that bajijiasu could alleviate the pathological changes in HN rat models; biochemical analysis found that the concentration of Malondialdehyde (MDA), total protein (TP), albumin (ALB), microalbuminuria (MALB), blood urea nitrogen (BUN), creatinine (Cr), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) were significantly decreased compared with model group after bajijiasu treatment; and bajijiasu could regulate the expression of TNF-α, IL-6, MDA, SOD1 and AGEs in HN rats; the result of western blotting demonstrated that bajijiasu could down-regulate the expression of TGFβ1, NOX4, JNK, p-JNK and up-regulate the expression PPARγ and SOD 1 in HN rats. Conclusion: Those results demonstrated that bajijiasu could alleviate the pathological changes, physiological and biochemical symptoms of HN rat models by regulating the expression of TGFβ1, PPARγ, JNK, p-JNK, NOX4 and SOD1, but could not lower the blood pressure of HN rats. Those evidences may provide a new therapeutic method for HN treatment.
Background/aims: Hypertensive nephropathy (HN) is a kind of renal diseases which caused by a long term uncontrolled hypertension, usually result in severe kidney damage including inflammation and oxidative stress no matter in cells or tissues from patients with nephropathy. In recent years, Nephropathy accompanied with hypertension is becoming one of main causes for kidney replacement therapy, but there are no ideal drugs for HN treatment. Asystasia chelonoides (AC) is a kind of plants which has the lowering blood pressure, anti-inflammation and anti-oxidative stress effect, but the therapeutic effect of AC in HN rat 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 TGFβ1 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.
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