Gentiopicroside alleviates cardiac inflammation and fibrosis in T2DM rats through targeting Smad3 phosphorylation.

BACKGROUND: Cardiac fibrosis is a major structural change observed in the heart of patients with type 2 diabetes mellitus (T2DM), ultimately resulting in heart failure (HF). Suppression of inflammation is an effective therapeutic strategy for treating cardiac fibrosis and HF. Gentiopicroside (GPS), the primary component of Gentiana manshurica Kitagawa, possess potent anti-inflammatory activity. However, its cardioprotective role remains elusive. PURPOSE: We explored the potential cardioprotective role of GPS in T2DM rats and its underlying mechanisms. METHODS: T2DM rats built by high-fat diet and streptozotocin were orally administered 25, 50, or 100 mg/kg GPS, daily for 8 weeks. The positive control drug was Metformin (200 mg/kg/day). Primary cardiac fibroblasts (CFs) were induced by high glucose (30 mM) and subsequently treated with GPS (100 µM). Cardiac function and pathological changes were analyzed using echocardiography and histological staining. Potential targets of GPS were predicted using Molecular docking. Real-time PCR as well as western blotting were applied to verify the expression of objective genes. RESULTS: All three doses reduced fasting blood glucose levels, but only 50 and 100 mg/kg GPS improved cardiac function and alleviated inflammation and fibrosis in T2DM rats. GPS (100 mg/kg) exhibited a better effect, similar to that of metformin. Mechanistically, binding between GPS and the MH2 domain of Smad3 blocked high glucose-induced Smad3 phosphorylation, thus attenuating inflammation, oxidative stress, and activation in CFs. CONCLUSION: We, for the first time, demonstrated that GPS improved cardiac function in T2DM rats and elucidated the underlying mechanism through which GPS targeted Smad3 phosphorylation to suppress inflammation and activation in CFs, thereby revealing the potential application of GPS in HF therapy.

[Rationality of the processing methods of aconiti lateralis radix (Fuzi) based on chemical analysis].

In this study, we explored the rationality of processing methods and mechanism of Aconiti Lateralis Radix (Fuzi) through comparing the chemical contents of diester alkaloids (DAs) and monoester alkaloids (MAs) in the raw material of Fuzi and its processed products. The results showed that the toxicity potency of MAs is at least lower than 1/64 to 1/180 of the toxicity potency of DAs. The contents of DAs in processed Fuzi decreased to 1/76.5 to 1/38.3 of the value of raw Fuzi. The contents of MAs in processed Fuzi significantly increased by 4.6 to 5.2 fold or basically the same as that of the raw Fuzi. The values of MAs/DAs of processed Fuzi were enhanced by 30 to 390 fold of the raw Fuzi. It was found that the contents of DAs were insignificantly different between "Wu dan fu pian" (steaming or stir-frying without Danba) and "Dan fu pian" (steaming or stir-frying with Danba). The result suggested that the abilities of "eliminating toxicity" of different processing methods were equivalent at all. In contrast, the contents of MAs contained in "Wu dan fu pian" were of 5.3 to 8.7 fold higher than the values in "Dan fu pian". This result suggested the processing method by steaming or stir-frying without Danba might have better effect for "conserving property" than the method processed with Danba stipulated by China Pharmacopoeia. We believe that the new processing method without Danba can be recommended in further application due to it offers a simple procedure and it will not introduce inorganic impurities in the products.

Research on fuzi based on animal thermotropism behavior to discover if it has fewer "hot" characteristics without Ganjiang.

OBJECTIVE: To investigate whether fuzi (Radix Aconiti Praeparata) has fewer "hot" characteristics when administered without Ganjiang (Rhizoma Zingiberis). METHODS: Differences in the thermotropism behaviors of mice treated either with fuzi (Radix Aconiti Praeparata), Ganjiang (Rhizoma Zingiberis) or the combination of the two given intragastrically were investigated using the Animal Thermotropism Behavior Surveillance System. The water intake volume, oxygen consumption volume, adenosine triphosphatase (ATPase) activity, total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) activity were determined during the investigation. RESULTS: When fuzi and ganjiang were administered together, the rate at which mice remained on a warm plate ("remaining rate") and the times and distances of their movement were all significantly reduced (P < 0.05). Compared with the Normal group, the reduction was 55.1%, 48.3% and 44.8%, while compared with the Fuzi group, the reduction was 57.6%, 34.3% and 36.0%, indicating that "cold" tropism was significantly increased. Compared with the normal and fuzi groups, the ATPase activity and the respiratory oxygen consumption volume of the fuzi + ganjiang group were significantly increased (P < 0.05), suggesting an improvement in energy metabolism and showing a "hot" characteristic when Fuzi and Ganjiang are present together. Additionally, the T-AOC and T-SOD activity were significantly enhanced (P < 0.05). CONCLUSION: The behavior of mice tending toward "cold" tropism can be regarded as a quantitative reflection of Fuzi having fewer characteristics consistent with a "hot" nature when not used with Ganjiang, the functional mechanism of which may be a change in the ATPase activity in liver tissue.