RESUMEN
Objective To explore the effects of Yiqi Yangyin Tongluo Recipe (YYTR) on the expressions of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) and aquaporin 2(AQP2) in diabetic renal tissue and its mechanism. Methods Sixty Wistar rats were randomly divided into the blank group, model group, valsartan (20 mg/kg) group, YYTR (4 mg/kg or 1 mg/kg), 4 mg/kg YYTR combined with 0.5 µmol/kg 740Y-P group, with 10 rats in each group. Except the blank group, the rats in other groups were fed with high-glucose and high-fat diet and injected with streptozocin to create diabetic nephropathy (DN) rat models. The day after successful modeling, the rats were administrated intragastrically for 8 weeks. At the end of the experiment, renal function indexes were measured, and glomerular sclerosis index and renal interstitial injury index were evaluated according to the results of HE staining and Masson staining. Western blot analysis was used to detect the levels of AQP2, PI3K, AKT, p-PI3K and p-AKT. Immunohistochemical staining was used to detect the expression and distribution of AQP2 in renal tissue. Results Compared with the normal group, urine protein quantitation in 24 hours (24 h UTP), serum creatinine, urea nitrogen and ß2-microglobulin (ß2-MG) content in model group were increased. It also reported a rise of kidney index, glomerulo sclerosis index, renal interstitial injury index, AQP2 protein and PI3K, AKT, p-PI3K and p-AKT protein expressions in model group. But compared with model group, the above indexes all decreased in 4 mg/kg YYTR group. In addition, compared with 4 mg/kg YYTR group, the above indexes in YYTR combined with 740Y-P group were increased. Conclusion YYTR can protect renal function by down-regulating AQP2 protein expression and inhibiting PI3K/AKT signaling pathway activation.
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Diabetes Mellitus , Nefropatías Diabéticas , Animales , Acuaporina 2 , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Medicamentos Herbarios Chinos , Riñón , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas WistarRESUMEN
BACKGROUND: Many studies have demonstrated that acupuncture combined with Chinese herbal medicine (CHM) effectively treats knee osteoarthritis (KOA), with few side effects. However, few systematic reviews have offered evidence-based support. Here we conducted a meta-analysis on the combination of acupuncture with CHM in treating KOA. METHODS: Databases including CNKI, Wanfang, VIP, PubMed, EMBASE, and Cochrane library were systematically searched for articles on the treatment of KOA by acupuncture combined with CHM from the establishment of the database to May 2021. Three researchers independently searched, screened, extracted, and included articles that met the inclusion standards. The primary outcome measure was overall response rate (ORR), and the secondary outcome measures included Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Lysholm score. ORR was a binary variable, while other indicators were continuous variables. The quality of literature was assessed with a modified Jadad scale. The RevMan 5.3 software provided by the Cochrane Collaboration was used for statistical analysis. RESULTS: Thirty-three randomized controlled trials involving 3,954 patients were included. Meta-analysis showed that ORR [odds ratio (OR) =5.41; 95% confidence interval (CI): (4.38, 6.68); P<0.00001], VAS score [mean difference (MD) =-1.86; 95% CI: (-2.44, -1.29); P<0.00001], WOMAC score [MD =-13.05; 95% CI: (-21.70, -4.41); P=0.003], and Lysholm score [MD =10.47; 95% CI: (5.21, 15.72); P<0.0001] in the combination group were significantly superior to those in the control group. DISCUSSION: Compared with acupuncture alone or CHM/Western drug alone, acupuncture combined with CHM can effectively alleviate knee pain, improve knee function, and increase the quality of life. Thus, this combination can be used as a conservative treatment for KOA. However, due to the small number of high-quality articles and possible biases in our analysis, our conclusions need to be further verified in more and higher-quality studies.
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Terapia por Acupuntura , Medicamentos Herbarios Chinos , Osteoartritis de la Rodilla , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Osteoartritis de la Rodilla/terapia , Dolor , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Podocyte injury is associated with albuminuria and the progression of diabetic nephropathy (DN). NADPH oxidase 4 (NOX4) is the main source of reactive oxygen species (ROS) in the kidney and NOX4 is up-regulated in podocytes in response to high glucose. In the present study, the effects of Salvianolate on DN and its underlying mechanisms were investigated in diabetic db/db mice and human podocytes. We confirmed that the Salvianolate administration exhibited similar beneficial effects as the NOX1/NOX4 inhibitor GKT137831 treated diabetic mice, as reflected by attenuated albuminuria, reduced podocyte loss and mesangial matrix accumulation. We further observed that Salvianolate attenuated the increase of Nox4 protein, NOX4-based NADPH oxidase activity and restored podocyte loss in the diabetic kidney. In human podocytes, NOX4 was predominantly localized to mitochondria and Sal B treatment blocked HG-induced mitochondrial NOX4 derived superoxide generation and thereby ameliorating podocyte apoptosis, which can be abrogated by AMPK knockdown. Therefore, our results suggest that Sal B possesses the reno-protective capabilities in part through AMPK-mediated control of NOX4 expression. Taken together, our results identify that Salvianolate could prevent glucose-induced oxidative podocyte injury through modulation of NOX4 activity in DN and have a novel therapeutic potential for DN.
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Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/patología , NADPH Oxidasa 4/metabolismo , Estrés Oxidativo , Extractos Vegetales/farmacología , Podocitos/patología , Adenilato Quinasa/metabolismo , Animales , Apoptosis/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Glucosa/toxicidad , Humanos , Masculino , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Podocitos/efectos de los fármacos , Podocitos/ultraestructura , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the safety profiles of Motherwort injection (MI). METHODS: A multi-center, prospective and drug- derived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications. This study was based on a very large population after the injection was approved and marketed in China. All patients using the injection in participating hospitals were monitored to determine the incidence, pattern, severity and outcome of associated adverse events. RESULTS: The post-marketing surveillance was performed in 10 094 female patients from April to December, 2015. The incidence of adverse drug reactions (ADRs) was 0.79¡ë(8/10 094). Among the 8 patients, the reported adverse events mainly included systemic abnormalities, such as fever, chills and eyelid edema; skin and appendages disorders, such as pruritus and rash; gastrointestinal disorders, such as nausea, abdominal distension and pain; heart rate and rhythm disorders, such as palpitation and increased heart rate. All of these ADRs were mild in severity. CONCLUSION: In this study the ADRs incidence rate of MI is very low, which supports that it is generally safe for use in obstetric and gynecological diseases. However, the total number of 8 ADRs recorded over a relatively short time span seems limited, and the low number of reports could not represent an absolute guarantee of safety.