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【Diosmin】Main Citrus Flavonoids with Antidiabetic Effects



Diosmin】Main Citrus Flavonoids with Antidiabetic Effects

Diosmin (3′,5,7-trihydroxy-4′-methoxyflavone-7-ramnoglucoside) is a flavone found in citrus fruits and the leaves of oranges and lemons. This flavone has some important biological activities, such as antioxidant, anti-inflammatory, and anti-apoptotic effects. Diosmin was isolated for the first time in 1925 from Scrophularia nodosa Linn. (a perennial herbaceous plant from the family Scrophulariaceae) and used for the first time in 1969 as a therapeutic agent for inflammatory disorders. Currently, it is a medication mainly used for the treatment of diseases, such as chronic venous insufficiency and hemorrhoids. The effect of diosmin on lipid metabolism was evaluated using an animal model of streptozotocin (STZ)-induced diabetes. Interestingly, it was shown to attenuate biochemical markers, such as fasting plasma glucose concentrations, glycosylated hemoglobin (HbA1c), and C-reactive protein (CRP). In addition, it decreased the levels of plasma lipids, including triglycerides (TG), free fatty acids, phospholipids, low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Besides, the activity of 3-hydroxy-3-methyl-glutaril-CoA reductase (HMG-CoA reductase), an important enzyme of the metabolic pathway that produces cholesterol, was enhanced in the liver and kidneys of diabetic rats but was inhibited by diosmin treatment. Finally, the activities of the lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) enzymes were also altered by diabetes and normalized by diosmin.

Jain, Bansal, Dalvi, Upganlawar, and Somani showed protective effects of diosmin against biochemical, behavioral, and oxidative stress parameters related to diabetic neuropathy in type 2 diabetic rats fed with an HFD. Diosmin also increased the threshold of nociception in thermal hyperalgesia and tail-flick tests, and improved motor capacity in diabetic rats. In addition, this flavonoid demonstrated a protective effect against oxidative stress, reducing markers of lipid peroxidation (malondialdehyde (MDA) and NO) levels. It also increased the activity of antioxidant enzymes, such as superoxide dismutase (SOD) and reduced glutathione (GSH), suggesting that it may help prevent the early development of diabetic neuropathy in rats.

Hsu, Lin, Cheng, and Wu concluded that diosmin has a beneficial effect through the activation of the imidazoline I-2 receptor (I-2R) and opioid secretion. Diosmin induced β-endorphin-like immunoreactivity secretion in isolated adrenal glands in vitro via calcium-dependent reactions, which evidenced its utility as an antidiabetic drug via inducing opioid secretion. In addition, diosmin attenuated increased plasma glucose concentrations and increased hepatic glycogen levels in diabetic rats. It also activated the I-2R to promote metabolic homeostasis, resulting in reduced blood glucose and lipids in diabetic rats. It is worth mentioning that the administration of diosmin did not produce changes in body weight, food intake, or plasma insulin levels.

Furthermore, diosmin has been reported to have therapeutic potential for behavioral parameters, such as the antinociceptive response and locomotor activity, as well as for the regulation of nociceptive biomarkers linked to the neuropathy caused by diabetes. Taken together, it is suggested that diosmin can attenuate primary effects of diabetes, such as disturbances in plasma glucose and lipoproteins, by modulating key enzymes that regulate glucose metabolism and antioxidant activity.

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