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Objective(s): Diabetic cardiomyopathy is a leading factor of high morbidity and mortality in diabetic patients. Our previous results revealed that ginkgolide B alleviates endothelial dysfunction in diabetic rats. This study aimed to investigate the effect of ginkgolide B on cardiac dysfunction and its mechanism in diabetic rats.Materials and Methods: Diabetes was induced in rats through the intraperitoneal injection of streptozotocin (STZ). Hemodynamics was monitored to assess cardiac function. Oxidative stress was examined by detecting levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum, and expression of sirtuin (SIRT)1, heme oxygenase (HO)-1, and phosphorylated AMPK in the heart. Masson’s trichrome staining and expression of transforming growth factor (TGF)-β1, smooth muscle actin (α-SMA), and phosphorylated (p-) Smad2 and Smad3 were used to evaluate cardiac fibrosis. Inflammatory cytokine in serum and levels of p-PI3K, p-Akt, p-p38, and p-JNK in the heart were determined.Results: Ginkgolide B significantly improved hemodynamics in diabetic rats. Compared with diabetic rats, treatment with ginkgolide B significantly decreased levels of inflammatory cytokines, improved oxidative stress via reducing MDA concentration, and elevating SOD activity in serum and increasing expression of SIRT1, HO-1, and p-AMPK. Further, ginkgolide B alleviated cardiac fibrosis by decreasing expression of TGF-β1, α-SMA, and p-Smad2 and p-Smad3. Meanwhile, ginkgolide B reduced Levels of p-P38, and p-JNK, and increased levels of p-PI3K and p-Akt.Conclusion: The results suggested that ginkgolide B alleviated cardiac dysfunction by reducing oxidative stress and cardiac fibrosis.

Objective(s): It has been demonstrated that hydrogen sulfide plays a vital role in physiological and pathological processes such as regulating inflammation, oxidative stress, and vessel relaxation. The aim of the study was to explore the effect of hydrogen sulfide on angiogenesis in the ischemic adductor muscles of type 2 diabetic db/db mice and ischemic diabetic wound healing.Materials and Methods: The femoral arteries of diabetic db/db mice were isolated and ligated for preparation of ischemic hind limb model. Round incision was made on ischemic and non-ischemic limbs. The wounds were treated with sodium bisulfide (hydrogen sulfide donor). Real-time PCR and Western blotting were used to measure transcription of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet derived growth factor (PDGF), hypoxia inducible factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) and protein expression of VEGF, VEGF receptor (VEGFR) and PDGF, PDGF receptor (PDGFR), respectively. Angiogenesis and morphological changes in adductor muscles were observed.Results: Hydrogen sulfide significantly increased transcription of VEGF, EGF, PDGF, HIF-1α, eNOS and protein expression of VEGF, PDGF, and phosphorylated VEGFR and PDGFR. Treatment with hydrogen sulfide significantly improved ischemic wound healing and formation of granulation tissue, and increased the number of small vessels in the ischemic adductor muscles.Conclusion: Our data suggested that hydrogen sulfide attenuated injury of ischemic adductor muscle, and promoted the ischemic diabetic wound healing via modulating angiogenesis in type 2 diabetic db/db mice.

Aim: This study aimed to investigate the effect of lycopene on LPS-induced liver injury in mice and its mechanisms. Methods: Male C57bl/6 mice were randomly assigned to three groups: sham control group (S-C), LPS control group (L-C), lycopene treatment group (L-T). The mice from the L-T were treated with lycopene for 2 weeks, and the remaining mice with solvent. Afterwards, the mice from the L-C and the L-T received an intraperitoneal injection of LPS (20 mg/kg, dissolved in sterile saline), and the S-C mice were injected with sterile saline. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were determined for analysis of liver function. Levels of inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-6, malondialdehyde (MDA) content, and the activity of superoxide dismutase (SOD), were detected in serum. Liver tissues were operated for morphologic analysis and determination of protein by western blot. Results: Pretreatment with lycopene significantly decreased levels of ALT, AST, and TNF-α and IL-6, reduced MDA content, and increased activity of SOD in serum compared with the L-C mice. Lycopene increased expression of nuclear factor-erythroid 2 related factor 2 (Nrf2), and reduced expression of cyclooxygenase (COX)-2, and phosphorylation of nuclear factor-kappa B (NF-κB) and extracellular regulated protein kinases 1/2 (ERK1/2). Conclusion: The results showed that lycopene attenuates LPS-induced liver injury by reducing NF-κB/COX-2 signaling by upregulation of Nrf2/HO-1 activation.