Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

OBJECTIVEThe present study was undertaken to evaluate the effect of diosmin in diabetic neuropathy in type 2 diabetic rats.

METHODSType 2 diabetes was induced in male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin (35 mg/kg) and high-fat diet. Four weeks after the confirmation of diabetes, diabetic rats were treated with diosmin (50 and 100 mg/kg, p.o.) for next 4 weeks. Rats were evaluated for biochemical, behavioral and oxidative stress parameters. Eddy's hot plate and tail immersion test were performed on 6th, 7th, 8th, 9th and 10th weeks of experiment to assess thermal hyperalgesia and cold allodynia respectively. Further, the walking function test was performed for assessing the motor responses at the end of the treatment schedule.

RESULTSRats were fed with high-fat diet throughout the experiment schedule and administration of low-dose streptozotocin induced significant elevation in blood glucose level and insulin resistance which was confirmed by oral glucose tolerance test. Treatment with diosmin at doses of 50 and 100 mg/kg significantly restored the reduced body weight, elevated blood sugar and lipid profiles. Further the dose-dependent improvement was observed in thermal hyperalgesia, cold allodynia and walking function in diabetic rats treated with diosmin. Elevated levels of malondialdehyde, and nitric oxide and decreased glutathione levels and superoxide dismutase activity in diabetic rats were restored significantly after the 4 weeks of diosmin treatment.

CONCLUSIONDiosmin has shown beneficial effect in preventing the progression of early diabetic neuropathy in rats.

Animals ; Blood Glucose ; metabolism ; Cholesterol ; metabolism ; Citrus ; chemistry ; Diabetic Neuropathies ; drug therapy ; metabolism ; prevention & control ; Diosmin ; administration & dosage ; Glutathione ; metabolism ; Humans ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; drug effects ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo establish a HPLC method for the determination of diosmin in Rats plasma and to study the pharmacokinetics of diosmin in Rats.

METHODRats were given diosmin with 3 doses as 225, 325, 425 mg x kg(-1). Blood samples were collected at different times after oral administration. The plasma concentration of diosmin was determined by HPLC, and the pharmacokinetics parameters were calculated by 3p97 program.

RESULTThe typical equation of diosmin in rats plasma was Y = 3.05 x 10(-3) C + 1.55 x 10(-3), the calibration curves of diosmin was linear in the range from 0.5-100 microg x mL(-1) (R =0. 996 4). The lowest concentration of diosmin in plasma was 0. 2 g x mL(-1). Its recoveries was more than 85%, and the interday and intraday precision, which was expressed as RSD, were all less than 15%. After 3 doses oral administration of diosmin in rats, the mean plasma concentration-time curves were found to fit one compartment model, and the main pharmacokinetics parameters were obtained.

CONCLUSIONIt is first time to establish the HPLC method to determine the concentration of diosmin in rats plasma, and the method described in this report has high sensitivity and selectivity, and it was suitable for pharmacokinetics studies of diosmin. The internal process of diosmin in rats is fit to one compartment model.

Administration, Oral ; Animals ; Area Under Curve ; Chromatography, High Pressure Liquid ; Diosmin ; administration & dosage ; blood ; pharmacokinetics ; Female ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar