RESUMO
Introduction: Nobiletin is a polymethoxyflavonoid abundant in citrus peels and has been reported to have various bioactive effects. We have previously reported that nobiletin inhibits endoplasmic reticulum stress-induced apoptosis in the pancreatic ß-cell line INS-1 and that continuous subcutaneous administration of nobiletin suppresses the progression of diabetes by protecting ß-cells in type 2 diabetic db/db mice. In the present study, we investigated effects of oral ingestion of Shiikuwasha extract rich in nobiletin on the pathogenesis of type 2 diabetes in db/db mice. Materials and methods: A Shiikuwasha extract was dissolved in MediDrop sucralose. Twenty-four mice were equally divided in three groups and fed with vehicle or low or high dose of Shiikuwasha extract for 4 weeks. Blood glucose levels, pancreatic ß-cell mass, serum insulin levels, pancreatic insulin content, and other biomarkers were measured and compared between the groups. Results: The group that freely ingested the Shiikuwasha extract containing higher concentration of nobiletin (Shiikuwasha H) showed lower blood glucose levels. At the end of the experiment, the Shiikuwasha H group exhibited improved glucose tolerance, lower serum glycoalbumin levels, and an increase in ß-cell area per pancreas compared with the control group. Body weight, food intake, and serum biomarkers related to liver function and lipid metabolism of the Shiikuwasha H group were not different from those of the control group, although water intake of the former was significantly decreased than that of the latter. Conclusion: Our results suggest that the oral ingestion of Shiikuwasha extract preserves pancreatic ß-cell mass in diabetic mice, which might be attributed to ameliorating the progression of diabetes.
RESUMO
Osteoarthritis (OA), also called degenerative joint disease, is characterized by joint cartilage loss and is strongly linked to obesity. Medicine to alleviate pain is currently the only treatment. Shiikuwasha extract (SE) has been reported to possess valuable bioactive substances exhibiting anti-inflammatory, antiobesity, and anticancer effects. Research is limited to the use of SE in the treatment of OA and obesity. We performed both anterior cruciate ligament transections and medial meniscectomies to induce OA on Sprague-Dawley rats after 11 weeks of a high fat diet followed by 9 weeks of oral SE administration (300, 600, and 1500 mg/kg). This study showed that SE treatment could reduce weight gain and joint pain. Additionally, SE significantly decreased triglycerides and total cholesterol in plasma of the S1500 group but increased high-density lipoprotein cholesterol in the plasma of the S600 group. Meanwhile, plasma levels of tumor necrosis factor alpha (TNF-α) was significantly reduced in the S1500 groups. Histopathological findings confirmed administration of SE attenuated cartilage degeneration. Immunohistochemistry examination demonstrated that caspase 3 and phospho-Janus kinase 2 (p-JAK2) expression levels on chondrocytes were downregulated by SE treatment. Our findings demonstrate that SE can alleviate OA progression by improving obesity.