RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Tongluo formula (YSTLF) is formulated based on traditional Chinese medicine theory for the treatment of Diabetic kidney disease (DKD) and has been shown to be effective in improving the symptoms of DKD according to the clinical observation. AIM OF THE STUDY: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-ß1/Smad2/3 pathway and promoting degradation of TGF-ß1. MATERIALS AND METHODS: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-ß1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-ß1 degradation was investigated in HG-stimulated SV40-MES-13 cells. RESULTS: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-ß1/Smad2/3 signaling pathway. TGF-ß1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment. CONCLUSIONS: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-ß1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-ß1.
Asunto(s)
Diabetes Mellitus , Nefropatías Diabéticas , Sirtuinas , Ratones , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Factor de Crecimiento Transformador beta1/metabolismo , Riñón , Fibrosis , Diabetes Mellitus/metabolismo , Sirtuinas/metabolismoRESUMEN
BACKGROUND: Eucheuma Cottonii is a type of red algae obtained from Sabah with main active component, sulfated polysaccharide or k-carrageenan. AIMS: The objective of this research was to evaluate the antioxidant, antibacterial and potential wound-healing properties in aqueous extraction of E cottonii in order to meet the increasing demand for halal and natural cosmeceutical products. METHODS AND RESULTS: Aqueous extract of E cottonii was investigated for active compounds by phytochemical screening and IR spectroscopy. Antioxidant activity was carried out using DPPH method, and the IC50 value was 1.99 mg/mL. Antibacterial activity was examined against Staphylococcus Aureus using Kirby-Bauer disk diffusion method and showed 10.03 ± 0.06 mm zone of inhibition, achieved by 200 mg/mL of extracts. A wound was made by skin excision of area around 100 mm2 on each mouse. Test group was treated with aqueous extract gel (10% w/w); meanwhile, the mice that were treated with honey acted as the positive control group and the untreated mice as negative control group. Results showed that the wound contraction rate inclined to aqueous extracts as compared to untreated group (P < .05). Percentage of wound healing for aqueous extracts and untreated group were 87.7% ± 2.0% and 57.6% ± 5.3%, respectively. CONCLUSION: Aqueous extract was found to be comparable to the honey in wound healing.