Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice.

Since lycopene has antioxidant activity, its combination with metformin may be useful to contrast diabetic complications related to oxidative stress. This study aimed to investigate the effects of metformin combined with lycopene on high-fat diet (HFD)-induced obese mice. Seventy-two C57BL-6J mice were divided into six groups: C (control diet-fed mice), H (HFD-fed mice for 17 weeks), H-V (HFD-fed mice treated with vehicle), H-M (HFD-fed mice treated with 50 mg/kg metformin), H-L (HFD-fed mice treated with 45 mg/kg lycopene), and H-ML (HFD-fed mice treated with 50 mg/kg metformin + 45 mg/kg lycopene). Treatments were administered for 8 weeks. Glucose tolerance, insulin sensitivity, fluorescent AGEs (advanced glycation end products), TBARS (thiobarbituric acid-reactive substances), and activities of antioxidant enzymes paraoxonase-1 (PON-1; plasma), superoxide dismutase, catalase and glutathione peroxidase (liver and kidneys) were determined. Metformin plus lycopene reduced body weight; improved insulin sensitivity and glucose tolerance; and decreased AGEs and TBARS in plasma, liver and kidneys. Combined therapy significantly increased the activities of antioxidant enzymes, mainly PON-1. Lycopene combined with metformin improved insulin resistance and glucose tolerance, and caused further increases in endogenous antioxidant defenses, arising as a promising therapeutic strategy for combating diabetic complications resulting from glycoxidative stress.

Siolmatra brasiliensis stem extract ameliorates antioxidant defenses and mitigates glycoxidative stress in mice with high-fat diet-induced obesity.

BACKGROUND: Obesity is accompanied by insulin resistance and glucose intolerance, which favor the onset of complications related to oxidative stress. The aim of this study was to investigate the effects and underlying mechanisms of hydroethanolic extract from Siolmatra brasiliensis stems on insulin resistance, glucose intolerance, advanced glycation end product (AGE) formation, and oxidative stress in mice with induced obesity. METHODS: C57BL-6 J mice were fed a high-fat diet for 14 weeks and treated with 125 or 250 mg/kg S. brasiliensis extract during the last 7 weeks. The study assessed glucose tolerance and insulin sensitivity, lipid profile, plasma levels of thiobarbituric acid reactive substances (TBARS, biomarkers of oxidative damage), fluorescent AGEs (biomarkers of advanced glycation), and paraoxonase 1 (PON1) activity (antioxidant enzyme). The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys were also investigated. RESULTS: Siolmatra brasiliensis extract had antiobesogenic effects; improved insulin sensitivity and glucose tolerance; decreased the total plasma cholesterol levels; decreased the levels of glycoxidative stress biomarkers, including AGEs (plasma, liver, kidneys) and TBARS (liver, kidneys); and also improved endogenous antioxidant defenses by increasing the activities of PON1 (plasma), SOD (kidneys), CAT (liver, kidneys), and GSH-Px (kidneys). CONCLUSION: This study expands on our knowledge about the pharmacological properties of S. brasiliensis and substantiates the potential of this plant species to be used as a complementary therapeutic agent to alleviate the metabolic dysfunctions resulting from dyslipidemia and glycoxidative stress.

Croton urucurana Baillon stem bark ointment accelerates the closure of cutaneous wounds in knockout IL-10 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton urucurana Baill. (Euphorbiaceae) is a plant used in Brazilian popular medicine for the treatment of wound healing, inflammatory diseases, gastritis, infections, and hemorrhoids. AIM: The present study aimed to evaluate the in vivo wound healing activity of an ointment based on ethanolic extract of C. urucurana stem bark, at concentrations of 5% and 10%, and to relate it with compounds that could be associated with this activity. MATERIALS AND METHODS: Analyses by FIA-ESI-IT-MSn were carried out to investigate the chemical composition of C. urucurana. Knockout IL-10 (n = 60) mice and wild type C57 (n = 12) mice were separated into 6 groups to evaluate the wound healing activity. Knockout IL-10 mice: SAL (0.9% saline); BAS (ointment base); SS (1% silver sulfadiazine); CR1 (ointment with extract of C. urucurana 5%); CR2 (ointment with extract of C. urucurana 10%); and wild mice C57: SALC57 (Saline 0.9%). A circular wound with 10 mm in diameter was generated on the dorsal of the animals. Tissue specimen of the wounds were removed on days 7 and 14 of the treatment for histopathological, oxidative status and analyses of pro-and anti-inflammatory cytokines in scar tissue. RESULTS: In the phytochemical profile, twelve proanthocyanidins were identified (in the form of monomers, dimers, trimers, and tetramers), based on (epi)catechin and (epi)gallocatechin. Furthermore, two quercetin derivatives and two alkaloids were detected. The groups treated with CR1 and CR2 ointments presented higher rate of wound closure, increased total number of cells, mast cells, blood vessels and higher deposition of type III and I collagen. In addition, they showed increased amount of pro-inflammatory cytokines (IL- 2 and IFN-γ), and anti-inflmatory cytokines (IL-4), on the 7th day of treatment. CONCLUSION: The results presented support the popular use of preparations based on the bark of C. urucurana as a healing compound.