Nephropathy 1st inhibits renal fibrosis by activating the PPARγ signaling pathway.

Renal fibrosis is a manifestation of kidney injury. Nephropathy 1st is a traditional Chinese herbal medicine that has been used as a therapy for kidney disease, but the underlying mechanisms remain elusive. The aim of this study was to investigate the role and underlying mechanisms of Nephropathy 1st on the progression of kidney disease. In the present study, unilateral ureteral obstruction was performed to establish the renal fibrosis rat model. By hematoxylin-eosin staining and immunohistochemical staining analysis, the severity of renal fibrosis was evaluated in vivo. Serum creatinine (CREA) and urea nitrogen (BUN) were measured by ELISA. The expression levels of Col-I, FN, PPARγ, and Klotho were measured by Western blot in rat NRK-49F cells and in fibrotic rats. GW9662 was used to inhibit PPARγ signaling. Metabonomic analysis showed metabolic differences among groups. Nephropathy 1st administration alleviated the progression of rat renal fibrosis and reduced serum creatinine (Scr) and BUN levels. Mechanistically, Nephropathy 1st promoted the expression of PPARγ and thus activated PPARγ signaling, thereby reducing the pro-fibrotic phenotypes of fibroblasts. The therapeutic effect of Nephropathy 1st was abrogated by the PPARγ inhibitor GW9662. Moreover, Nephropathy 1st normalized the dysregulated lipid metabolism in renal fibrosis rats. In conclusion, Nephropathy 1st alleviates renal fibrosis development in a PPARγ-dependent manner.

Therapeutic effects of traditional Chinese medicine (Maxingshigan-Weijing Decoction) on COVID-19: An open-label randomized controlled trial.

BACKGROUND: Wenzhou has achieved great progress in the prevention and control of the growing coronavirus disease 2019 (COVID-19) pandemic, and traditional Chinese medicine (TCM) has played an indispensable role in this fight. This study aimed to investigate the efficacy of Maxingshigan-Weijing decoction (MWD) in treating infected patients. METHODS: This study was an open-label randomized controlled trial. Inpatients with mild or moderate symptoms caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were randomly treated with routine supportive care alone or a combination of routine supportive care and MWD. The primary outcome was the rate of symptom (fever, fatigue, cough and difficulty breathing) recovery. RESULTS: Fifty-nine inpatients were enrolled, of whom 29 received routine supportive care alone (control group) and 30 received combination therapy (treatment group). The rate of symptom recovery was significantly higher in the treatment group than in the control group. The time to recovery of fever (3 vs. 7 days), fatigue (9 vs. 12 days), coughing (9 vs. 14 days) and difficulty breathing (4.5 vs. 9.5 days) was also significantly shorter in the treatment group (all p < 0.001). The syndrome score was lower after MWD treatment. However, neither group differed in the viral assay findings, hospitalization days, medication time or the rate of conversion to severe cases. CONCLUSIONS: MWD increased the rate of symptom recovery and shortened the time to recovery of clinical symptoms without deterioration to death or critical care. These findings may provide opportunities for the use of complementary medicine in treating this infection. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030759.

Efficacy of Traditional Chinese Medicine, Maxingshigan-Weijing in the management of COVID-19 patients with severe acute respiratory syndrome: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We aimed to test our expectation that additional administration of Traditional Chinese medicine (TCM), maxingshigan-weijing decoction, is more effective in the management of COVID-19 patients compared to those treated with routine supportive care alone. TRIAL DESIGN: This is a multicenter, open-label 2-arm (1:1 ratio) randomized controlled trial. PARTICIPANTS: Patients will be recruited from 3 hospitals in Wenzhou China: the First Affiliated Hospital of Wenzhou Medical University, the Second Affiliated Hospital of Wenzhou Medical University and Wenzhou Center Hospital. The inclusion and exclusion criteria are as follows: Inclusion criteria 1. Participants are 18-85 years of age, either male or female. 2. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3. Symptomatic. Mild (mild clinical symptoms without signs of pneumonia in chest X-ray) and Moderate (fever or respiratory symptom with signs of pneumonia in chest X-ray) . 1. Signed the informed consent before treatment. 2. Agreed not to enroll in any other clinical trials. 3. Inpatients Exclusion criteria 1. < 18 or > 85 years old. 2. Pregnancy and lactation. 3. Serious heart, liver, kidney and hematopoietic system diseases, abnormal liver or kidney function. 4. Suffering from other known virus pneumonia. 5. Allergic to Chinese herbal medicine or suffering from allergies. 6. Critical patients (respiratory failure treated by mechanical ventilation or shock or multiple organ failure). INTERVENTION AND COMPARATOR: Patients in the control group will receive routine supportive clinically care including the therapies of anti-viral, anti-bacterial and ameliorating the related symptoms, while patients in TCM group will be asked to take maxingshigan-weijing decoction (composed of 14 Chinese herbal medicines), orally 200 mL 2 times daily, for 14 consecutive days in addition to routine supportive care as mentioned above. Maxingshigan-weijing decoction consists of 10 g of Herba Ephedra (Mahuang), 10 g of Amygdalus Communis Vas (Xingren), 45 g of Gypsum Fibrosum (Shigao), 30 g of Rhizoma phragmitis (Lugen), 20 g of Peach kernel (Taoren), 20 g of Winter Melon kernel (Dongguaren), 30 g of Trichosanthes Kirilowii Maxim (Gualou), 12 g of Pericarpium Citri Reticulatae (Chenpi), 12 g of Rhizoma Pinelliae (Jiangbanxia), 12 g of caulis bambusae in taeniis (Zhuru), 30 g of semen lepidii (Tingliz), 15 g of semen lepidii (Shichangpu), 10 g of curcuma zedoary (ezhu) and 5 g of Radix Glycyrrhizae (Gancao). MAIN OUTCOMES: The primary outcome will be the number of days until the clinical symptom of fever improves in the first 14 days of treatment following randomisation. Fever will be defined as an improvement when the temperature is less than 37°C. Secondary outcomes will be TCM Syndrome Scores, the time it takes until individuals have negative test results for SARS-CoV-2 nucleic acid, the proportion of cases with chest X-ray improvements and the rate of symptom (fever, cough, malaise, shortness of breath) recovery. TCM Syndrome Scoring System is a checklist covering 4 main, 7 secondary and 13 accompanying items. The 4 main items consisting of fever, cough, malaise and shortness of breath, use a four-point scale (0, 2, 4 and 6) depending on the severity; the 7 secondary items including dysphoria, diarrhea, pharyngalgia, expectoration, muscular soreness, nasal obstruction and rhinorrhoea use 0-3-point scale; the 13 accompanying items contain chest pain, headache, aversion to cold, dizziness, nausea and vomiting, anorexia, abdominal distension, dry mouth, anxiety, spontaneous sweating, insomnia, wheezing and blood tinged sputum, and each item is rated on 0-1 scale ( 0 stands for asymptomatic, 1 stands for symptomatic ). The total scores sum up to a range from 0 to 58, with higher scores indicating more severe levels of disease. RANDOMIZATION: Minimization method will be used, balancing the two arms for pneumonia severity. Patients are randomized (1:1 ratio) to each group. Clinical researchers will get a random sequence number which is automatically generated by a random number generator (IBM Corp., Armonk, NY, USA), and sequentially number them in an opaque envelope. Researchers will open random allocation envelopes and assign participants accordingly. Eligible patients will be randomly divided into a routine supportive care group and a routine supportive care plus oral administration of traditional Chinese medicine group, with 70 patients in each group. BLINDING (MASKING): This is an open-label study. The statistical analysis will be carried out by the Professor of Statistics at Wenzhou Medical University, who is blinded to patient allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The previous study reported the efficacy of TCM for COVID-19 and H1N1 influenza patients, the median survival time in the TCM group is estimated as 3 days; this time will be 1.5 times longer in the control group. Accordingly, Kaplan-Meier method and log-rank test will be used. And assuming a statistical power of 70% (one-sided type-1 error of α = 5%, ß = 30%) and a rate of withdrawal and loss to follow-up of 10%, we plan to include 140 participants in both groups ( TCM group = 70, control group = 70). TRIAL STATUS: The trial protocol is Version 2.0, October 14, 2020. Recruitment began March, 2020, and is anticipated to be completed by December 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030759 . Registered on 13 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

[Protective effect of curcumin derivative B06 on kidney of type 2 diabetic rats].

OBJECTIVE: To observe the effect and mechanism of curcumin derivative B06 on kidney from rats with hyperlipidemia and type 2 diabetes. METHODS: Thirty five male SD rats were randomly divided into five groups(n = 7): the normal control group, high-fat group, high-fat + B06-treatd group, diabetic group, diabetic + B06-treated group. After fed with high-fat diet for 4 weeks, the later two groups were in- jected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. B06-treated groups were given B06 by gavage at a dosage of 0.2 mg/kg . d for 8 weeks. After the treatment, the serum creatinine, blood urea nitrogen and uric acid were detected biochemically, the morphology of kidney was observed with light and transmission electron microscopy, the expression of collagen fibers was observed with Masson staining, the protein expression of collogen IV and fibronectin in kidney were determined by Immunohistochemistry. RESULTS: It was showed that the levels of the serum creatinine and blood urea nitrogen elevated significantly in diabetic group. In high-fat and diabetic groups, increased glomerular mesangial matrix and collagen fiber and thicken glomerular basal membrane were observed under light microscopy, swelling and fusion of foot process were found under electron microscope; increased green matrix within glomeruli was observed under Masson staining. collogen IV and fibronectin protein expression were significantly enhanced in high-fat group and diabetic group. After B06's intervention, the levels of serum creatinine and blood urea nitrogen were decreased in diabetic groups, the morphological change of kidney was obviously relieved, Collogen IV and fibronectin protein expression reduced. CONCLUSION: Curcumin derivative B06 exerts a protective effect on kidney in type 2 diabetic rats, reduced expressions of collogen IV and fibronectin, inhibition of the accumulation of extracellular matrix and glomerular mesangial proliferation, and then prevention of renal fibrosis may be the mechanism.

The molecular mechanism of rhein in diabetic nephropathy.

Diabetic nephropathy (DN) is characterized by unclear pathogenesis. Recent medical data shows that the incidence of DN rises year by year. Rhein is the main compositions of rhubarb, a traditional Chinese medicinal plant, which plays an active role in kidney protection. The prophylaxis and phytotherapeutic effects of rhein are due to its anti-inflammatory and antifibrosis properties. Here, we shed light on the renal protective role of rhein in diabetes mellitus (DM) with a particular focus on the molecular basis of this effect.

[Effect of Curcuma aromatica on epithelial-myofibroblast transdifferentiation of NRK-52E cells induced by TGF-beta1].

OBJECTIVE: To observe the antagonist effect of Curcuma Aromatica (CA) on renal tubular epithelial-myofibroblast transdifferentiation (EMT) induced by transforming growth factor-beta1 (TGF-beta1). METHODS: Normal renal tubular epithelial NRK-52E cells in vitro cultured were randomly divided into 6 groups, i.e., the normal control group (Group C), the TGF-beta1 induced model group (Group T), the low dose CA treated group (Group E1), the moderate dose CA treated group (Group E2), the high dose CA group (Group E3), and the Benazepril Hydrochloride Tablet treated group (Group Y). Except Group C, corresponding medication (with an action of 48 h) was administered to cells in the rest groups after they were induced by TGF-beta1 for 24 h. The morphological changes were observed by inverted phase contrast microscope. The distribution of beta-actin protein was detected by immunohistochemical assay. The mRNA expressions of alpha-smooth muscle actin (alpha-SMA) and E-cadherin (E-cad) were detected by real-time PCR. The concentration of fibronectin (FN) was detected by ELISA. RESULTS: After induced by TGF-beta1 for three days, hypertrophy and elongated cells in fusiform-shape occurred,with increased expressions of beta-actin protein in the cytoskeletal structure (P < 0.05), bundle fibrous structure occurred inside cytoplasm with significantly up-regulated intracellular alpha-SMA mRNA expressions (P < 0.05), E-cad mRNA expression decreased (P < 0.05), the FN content in the supernate increased (P < 0.05) in Group T. Compared with Group T, partial cells in Group E1, E2, and E3 showed fibrous changes, accompanied with decreased expression of beta-actin protein and FN concentration (P < 0.05). The expression of alpha-SMA mRNA increased and the expression E-cad mRNA decreased in Group E2 and E3 (both P < 0.05). But there was no statistical difference in the expression levels of E-cad and alpha-SMA mRNA (P > 0.05). Compared with Group E1, the expression of beta-actin protein and FN concentration decreased in Group E2 and E3 (P < 0.05). The expressions of alpha-SMA mRNA decreased and E-cad mRNA increased in Group E3 (P < 0.05). Compared with Group Y, the expression of beta-actin mRNA and FN concentration increased in Group E1 (P < 0.05); the expression of beta-actin mRNA increased in Group E3 (P < 0.05); the expression of E-cad mRNA decreased in Group E3 (P < 0.05). There was no statistical difference in the expression of alpha-SMA mRNA among Group E1, E2, and E3 (P > 0.05). CONCLUSION: CA could inhibit the occurrence of TGF-beta1 induced EMT, which could be used as an effective drug for treating chronic renal insufficiency.

The clinical research on serum cystatin-C alteration on stage II chronic kidney disease with gubenquduyishen decoction treatment.

AIM OF THE STUDY: Gubenquduyishen (GBQDYS) decoction, the modified remedy of a classical Chinese prescription named Liuweidihuang decoction, has been clinically employed to treat nephrotic syndrome and chronic nephritis in chronic kidney disease (CKD). The present study was designed to examine whether GBQDYS decoction has a protective effect on renal function associated with the raised level of cystatin-C (Cys-C), serum creatinine (Scr), blood urea nitrogen (BUN) and decreased Glomerular filtration rate (GFR) in stage-II CKD. MATERIALS AND METHODS: A total of 68 stage-II CKD patients were randomly divided into two groups, the control group and the treatment group who received GBQDYS decoction as an additional therapy supplement. RESULTS: Following up on a period of 48 months, levels of serum Cys-C, Scr, and BUN were significantly reduced by the treatment of GBQDYS decoction and GFR was elevated in the treated group. Whereas not achieved in the control group, suggesting the nephro-protective activity of GBQDYS decoction. CONCLUSIONS: Taken together, these results demonstrated that GBQDYS decoction is able to protect renal function by delaying the progression of renal failure, and this may be used as an effective alternative treatment for CKD patients.