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Context: As a major active iridoid glycoside from Gardenia jasminoides J. Ellis (Rubiaceae), geniposide possesses various pharmacological activities, including anti-platelet aggregation and anti-inflammatory action. Objectives: This study explores the effect of geniposide in diabetic wound model by anti-inflammatory action. Materials and methods: Diabetic rodent model in Wistar rats was induced by streptozotocin combined with high-fat feed. The selected rats were divided into control group, the diabetic model group and geniposide subgroups (200, 400 and 500 mg/kg), and orally administrated once daily with saline or geniposide. Wound area and histochemical indicators were measured on day 7 after continuous administration, to assess lesion retraction, inflammatory cells and fibroblasts. Results: Geniposide notably enhanced lesion retraction by 1.06-1.84 times on day 7 after surgical onset in diabetic rats (p<0.05). In the pathological experiment by HE staining, geniposide significantly reduced inflammatory cell infiltration and proliferation of fibroblasts in the central lesion regions. In diabetic rats treated with geniposide, the levels of pro-inflammatory factors (tumour necrosis factor-a (TNF-a), interleukin-1b (IL-1b)) and IL-6 were significantly reduced (p<0.05), followed with the increment of IL-10 in a dose-dependent manner. The IC50 of geniposide on TNF-a, IL-1b and IL-6 could be calculated as 1.36, 1.02 and 1.23 g/kg, respectively. It assumed that geniposide-induced IL-10 expression contributed to inhibiting the expression of pro-inflammatory factors. Discussion and conclusions: Geniposide promoted diabetic wound healing by anti-inflammation and adjusting blood glucose. Further topical studies are required to evaluate effects on antibacterial activity and skin regeneration. [ABSTRACT FROM AUTHOR]

Context: Jinlida (JLD) as a traditional Chinese medicine formula has been used to treat type 2 diabetes mellitus (T2DM) and studies have shown its anti-obesity effect. Objective: To investigate the therapeutic effects of JLD in a mouse model of non-alcoholic fatty liver (NAFL). Materials and methods: C57BL/6J mice were divided into three groups and fed a low-diet diet (LFD), high-fat diet (HFD), or HFDþJLD (3.8 g/kg) for 16 weeks, respectively. The free fatty acids-induced lipotoxicity in HepG2 cells were used to evaluate the anti-pyroptotic effects of JLD. The pharmacological effects of JLD on NAFL were investigated by pathological examination, intraperitoneal glucose and insulin tolerance tests, western blotting, and quantitative real-time PCR. Results: In vivo studies showed that JLD ameliorated HFD-induced liver injury, significantly decreased body weight and enhanced insulin sensitivity and improved glucose tolerance. Furthermore, JLD suppressed both the mRNA expression of caspase-1 (1.58 vs. 2.90), IL-1β (0.93 vs. 3.44) and IL-18 (1.34 vs. 1.60) and protein expression of NLRP3 (2.04 vs. 5.71), pro-caspase-1 (2.68 vs. 4.92) and IL-1β (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2mM FFA (IC50 = 2.727mM), reduced the protein expression of NLRP3 (0.74 vs. 2.27), caspase-1 (0.57 vs. 2.68), p20 (1.67 vs. 3.33), and IL-1β (1.44 vs. 2.41), and lowered the ratio of p-IKB-α/IKB-α (0.47 vs. 2.19). Conclusion: JLD has a protective effect against NAFLD, which may be related to its anti-pyroptosis, suggesting that JLD has the potential as a novel agent in the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Rosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear. This study explores the RA protective effect on APAP-induced ALI and its mechanism. Sixty Kunming mice 6–8 weeks old were randomly separated into six groups (n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-α were measured by western blot. Compared with the APAP group, different dosages RA significantly decreased ALT (52.09 ± 7.98, 55.13 ± 10.19, 65.08 ± 27.61 U/L, p < 0.05), AST (114.78 ± 19.87, 115.29 ± 31.91, 101.78 ± 21.85 U/L, p < 0.05), MDA (2.37 ± 0.87, 2.13 ± 0.87, 1.86 ± 0.39 nmol/mg, p < 0.01) and increased SOD (306.178 ± 90.80, 459.21 ± 58.54, 444.01 ± 78.09 U/mg, p < 0.05). With increasing doses of RA, RACK1 and TNF-α expression decreased. Moreover, the RACK1 and TNF-α levels were positively correlated with MDA (r = 0.8453 and r = 0.9391, p < 0.01). Our findings support RA as a hepatoprotective agent to improve APAP-induced ALI and the antioxidant effect mediated through RACK1/TNF-α pathway. [ABSTRACT FROM AUTHOR]