wogonin and Body-Weight

The present study was conducted to identify possible health - promoting effects of wogonin (Wog) on testicular dysfunction in rats caused by cadmium. Pre-treatment of cadmium chloride (Cd: 5 mg/kg b.wt.) administered rats with wogonin (10 mg/kg b.wt) resulted in significant improvement in Cd-induced decrease in body and organ (testes and epididymides) weights. Wogonin treatment significantly improved Cd-induced reduction in sperm quality and quantity, steroidogenic gene (SFI, StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD) and protein (SF1, StAR and CYP17A1) expressions and serum testosterone levels. Wogonin treatment provided significant protection to Cd-induced aggression in testicular oxidative (elevated levels of MDA) and anti-oxidative (diminished activities of SOD, CAT and GPx) status. Wog significantly up-regulated mRNA levels of Nrf2, NQO1 and HO-1 and down-regulation of Keap1 in cadmium treated testes. Wogonin administration significantly suppressed Cd-stimulated increase in inflammatory reactions (increase in NF-κB p65 DNA, p-IKKβ, TNF-α levels and decrease in IL-10 levels). Wogonin prevented apoptotic damage by enhanced protein distribution of caspase-9, caspase-3, and Bax due to Cd exposure. Furthermore, Wogonin presented significant protection to histo-morphometric changes resulted after Cd administration. Taken together, the findings of this study provided clear evidence of the therapeutic potential of Cd-induced testicular toxicity at least partly due to its antioxidant, anti-inflammatory and anti-apoptotic properties.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biomarkers; Body Weight; Cadmium; Drinking; Epididymis; Feeding Behavior; Flavanones; Gene Expression Regulation; Hormones; Inflammation; Male; Oxidation-Reduction; Protective Agents; Rats, Wistar; RNA, Messenger; Signal Transduction; Spermatogenesis; Spermatozoa; Steroids; Testis

Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis Gerogi. We evaluated the therapeutic effects of wogonin using db/db mice.. Mice received wogonin or vehicle by oral gavage for 2 weeks. Blood glucose, insulin, and cholesterol levels were measured, and liver morphology was observed with histopathological analysis. The mRNA expression levels of PPARα, PPARγ, and adiponectin in the liver and white adipose tissue (WAT) were determined by real-time PCR. Immunoblotting for AMPK and PPARγ, and adipocyte differentiation were investigated in vitro using 3T3-L1 cells. A luciferase assay was used to measure PPARα and PPARγ binding activity.. The wogonin group showed decreased weight gain without a change in food intake and improved glucose tolerance. Serum insulin and cholesterol levels in the wogonin group were significantly decreased compared to those in the control group. The wogonin group also showed less accumulation of lipid droplets and glycogen in the liver. PPARα and PPARγ expression levels in the liver and WAT and adiponectin expression level in WAT in the wogonin group were higher than those in the control group. In 3T3-L1 cells, wogonin was shown to stimulate AMPK activation in a dose-dependent manner. The presence of wogonin did not affect adipocyte differentiation or PPARγ protein level during adipogenesis. Notably, wogonin enhanced PPARα but not PPARγ transactivation.. These indicate that wogonin may have beneficial effects on glucose and lipid metabolism related to enhanced PPARα and adiponectin expression via AMPK activation. Importantly, wogonin did not cause deleterious effects, such as weight gain and fatty liver. Wogonin might be a useful therapeutic agent to treat type 2 diabetes.

Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Adipose Tissue, White; AMP-Activated Protein Kinases; Animals; Blood Glucose; Body Weight; Cell Differentiation; Cholesterol; Dyslipidemias; Flavanones; Gene Expression; Hyperglycemia; Insulin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; PPAR alpha; PPAR gamma

Tumor growth and metastasis are associated with angiogenesis and lymphangiogenesis through the production of vascular endothelial growth factor (VEGF) or VEGF-C in tumors, and the phosphorylation of VEGF receptor (VEGFR)-2 or VEGFR-3 in vascular endothelial cells or lymphatic endothelial cells (LECs). Tumor-associated macrophages (TAMs) play an important role in tumor lymphangiogenesis, and consequently stimulate metastasis through the lymphatic system to lymph nodes. We examined the effects of wogonin isolated from Scutellaria baicalensis roots on tumor growth and metastasis using a highly metastatic model in osteosarcoma LM8-bearing mice. Wogonin (25 and 50 mg/kg, twice daily) reduced tumor growth and metastasis to the lung, liver and kidney, angiogenesis (CD31-positive cells), lymphangiogenesis (LYVE-1-positive cells), and TAM (F4/80-positive cell) numbers in the tumors of LM8-bearing mice. Wogonin (10-100 μM) also inhibited increases in IL-1β production and cyclooxygenase (COX)-2 expression induced by lipopolysaccharide in THP-1 macrophages. Wogonin had no effect on VEGF-C production in LM8 cells, or VEGFR-3 expression in human lymphatic endothelial cells (HLECs), however, it inhibited VEGF-C-induced VEGFR-3 phosphorylation in HLECs. The anti-tumor and anti-metastatic actions of wogonin may be associated with the inhibition of VEGF-C-induced lymphangiogenesis through a reduction in VEGF-C-induced VEGFR-3 phosphorylation by the inhibition of COX-2 expression and IL-1β production in TAMs.

Topics: Animals; Antineoplastic Agents, Phytogenic; Body Weight; Chemokine CCL2; Cyclooxygenase 2; Cytokines; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Endothelial Cells; Flavanones; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Lymphangiogenesis; Macrophages; Male; Mice; Mice, Inbred C3H; Neoplasm Metastasis; Phosphorylation; Phytotherapy; Plant Roots; Sarcoma, Experimental; Scutellaria baicalensis; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3

Wogonin, one active ingredient extract from the radix of Scutellaria baicalensis Georgi, is known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties, especially the anticancer activity studied recently. However, no extensive safety studies have been conducted to date. In this paper, the acute and sub-chronic toxicity of the agent were determined using albino mice and Sprague-Dawley rats as animal models. Histopathological examination and viscera parameter investigation were also carried out after autopsy. The LD(50) of wogonin administered by the intravenous injection was 286.15 mg/kg and the 95% confidence limit was 278.27-295.26 mg/kg. A long period of treatment with a high dose of wogonin (120 mg/kg) could induce heart injury in rats. These results provide a foundation for the further clinical investigation of this promising anticancer agent.

Topics: Animals; Antineoplastic Agents, Phytogenic; Body Weight; Dose-Response Relationship, Drug; Female; Flavanones; Injections, Intravenous; Lethal Dose 50; Male; Mice; Myocardium; Organ Size; Plant Extracts; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis; Toxicity Tests, Acute

The anti-inflammatory effect of three flavonoids from the root of Scutellaria baicalensis (baicalein, baicalin and wogonin) was evaluated in a murine model of acute experimental colitis induced by dextran sulfate sodium (DSS). Baicalein, but not baicalin or wogonin, given orally at 20 mg/kg for ten days, ameliorates all the considered inflammatory symptoms of the induced colitis, such as body weight loss, blood haemoglobin content, rectal bleeding and other histological and biochemical parameters. The effect of baicalein was similar to that of sulfasalazine, the reference drug given at 50 mg/kg.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Colitis; Dextran Sulfate; Female; Flavanones; Flavonoids; Inflammation; Lamiaceae; Mice; Mice, Inbred BALB C; Plant Extracts; Plant Roots; Sulfasalazine