Standardised Ethanol Extract of Tithonia diversifolia (Hemsley) A Gray Leaves Improve Insulin Sensitivity and Increase Mitochondrial DNA Copy Numbers in Skeletal Muscles of Streptozotocin-Nicotinamide-Induced Rats

BACKGROUND: In this study, we examined the anti-diabetic activity of standardised extracts of Tithonia diversifolia (Hemsley) A Gray (T. diversifolia) leaves for their effects on insulin resistance and mitochondrial DNA (mtDNA) copy number. METHODS: T. diversifolia leaves were extracted using an ultrasound-assisted method and standardised using Tagitinin C. There were six groups: i) normal control; ii) diabetic group; iii) metformin group (300 mg/kg) and iv) groups treated with three different doses of extract (50 mg/kg, 100 mg/kg and 150 mg/kg). Blood samples were taken before and after 28 days of treatment for fasting plasma glucose (FPG) and insulin analysis, which were used for a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) calculation. The soleus and gastrocnemius muscles were harvested after 28 days of treatment for the measurement of mtDNA copy number. RESULTS: The results showed an improvement in blood glucose levels and HOMA-IR scores in all treatment groups. The results of mtDNA copy number analysis also revealed significant improvement with the highest number observed at an extract dose of 100 mg/kg in which the mtDNA copy number increased up to 3 times in the soleus muscles (P < 0.001). CONCLUSION: T. diversifolia extract has the potential to be used as an anti-diabetic agent that improves insulin resistance, possibly by increasing mtDNA content.