Natural food products have been used for combating human diseases for thousands of years. Naturally occurring flavonoids including flavones, flavonols, flavanones, flavonols, isoflavones and anthocyanidins have been proposed as effective supplements for management and prevention of diabetes and its long-term complications based on in vitro and animal models. To summarize the roles of dietary flavonoids in diabetes management and their molecular mechanisms. Tremendous studies have found that flavonoids originated from foods could improve glucose metabolism, lipid profile, regulating the hormones and enzymes in human body, further protecting human being from diseases like obesity, diabetes and their complications. In the current review, we summarize recent progress in understanding the biological action, mechanism and therapeutic potential of the dietary flavonoids and its subsequent clinical outcomes in the field of drug discovery in management of diabetes mellitus.

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Antidiabetic properties of dietary flavonoids: a cellular mechanism review

Neuroprotection is the preservation of function and networks of neural tissues from damages caused by various agents, as well as neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Huntington’s diseases, and multiple sclerosis. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases. Our review discusses neuropharmacological mechanisms for preventive and therapeutic effects of hesperidin in neurodegenerative diseases. In addition, the review examines clinical evidence confirming its neuroprotective function. Various cellular and animal models specific to neurodegenerative diseases have been conducted to evaluate the underlying neuropharmacological mechanisms of hesperidin. Neuroprotective potential of this flavonoid is mediated by improvement of neural growth factors and endogenous antioxidant defense functions, diminishing neuro-inflammatory and apoptotic pathways. Despite the various preclinical studies on the role of hesperidin in the neurodegenerative diseases, less is known about its definite effect on humans. A limited number of clinical trials showed that hesperidin-enriched dietary supplements can significantly improve cerebral blood flow, cognition, and memory performance. Further clinical trials are also required for confirming neuroprotective efficacy of this natural flavonoid and evaluating its safety profile.

https://www.mdpi.com/1420-3049/24/3/648/pdf

Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence

Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: An experimental approach.

Diabetes mellitus (DM) is a group of metabolic disorders in which high blood sugar levels occur over a prolonged period. Approximately 4% of the global population is affected by DM. Western medical treatment methods for diabetes including injection or oral hypoglycemic drugs have some toxic or side effects, economic pressures, and so on. Many researchers turn to discover new drugs from natural products or Traditional Chinese Medicine (TCM). Flavonoids are widely distributed in plants, and many studies have shown that flavonoids possess antidiabetic properties, exhibiting not only well-recognized antidiabetic and hypoglycemic activities but also activity in the treatment of diabetic complications. In this review, we systematically summarized anti-diabetic flavonoid compounds based on structure classification by examining the PubMed, Springer Link, Web of Science, and CNKI databases. There are 13 flavonoid compounds listed which have been studied extensively and have antidiabetic features respectively. Apigenin, baicalein, and catechin mainly reduces blood glucose via anti-oxidation; hesperidin is good for diabetic neuropathy; glycyrrhiza flavonoids have a significant effect on gestational DM; quercetin takes advantage of crossing the blood-brain barrier and improving renal function. Some compounds have protective and preventive effects on diabetic complications, such as kaempferol and puerarin which are beneficial to cardiomyopathy; myricetin has therapeutic potential in the treatment of DN; dihydromyricetin might improve CI. It is a pity or might be a pointcut that most studies remain in the animal experimental stage, and further investigation should be carried out.

https://www.worldscientific.com/doi/pdf/10.1142/S0192415X19500496

Antidiabetic Potential of Flavonoids from Traditional Chinese Medicine: A Review.

Hesperidin ameliorates heavy metal induced toxicity mediated by oxidative stress in brain of Wistar rats.

Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ-) induced diabetes mellitus and its complication in central nervous system (CNS). Recent studies have provided insights on antioxidants and their emergence as potential therapeutic and nutraceutical. The present study examined the hypothesis that hesperidin (HP) ameliorates oxidative stress and may be a limiting factor in the extent of CNS complication following diabetes. To test this hypothesis rats were divided into four groups: control, diabetic, diabetic-HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by a single injection of STZ (65 mg/kg body weight). Three days after STZ injection, HP was given (50 mg/kg b.wt. orally) once daily for four weeks. The results of the present investigation suggest that the significant elevated levels of oxidative stress markers were observed in STZ-treated animals, whereas significant depletion in the activity of nonenzymatic antioxidants and enzymatic antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker activity was also altered significantly. HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers. Our results demonstrate that HP exhibits potent antioxidant and neuroprotective effects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model.

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Neuromodulatory effects of hesperidin in mitigating oxidative stress in streptozotocin induced diabetes.

Carbon tetrachloride (CCl4) is a highly toxic industrial solvent with pronounced systemic toxicity including brain. Neurotoxicity may be a direct result of hepatic dysfunction from CCl4 intoxication. Over the years CCl4 has been used as an excellent model for studying experimentally induced neurotoxicity in murine models. Hesperidin (HP) is a known cytoprotectant with comprehensive anti-oxidant and neuroprotective properties. The aim of the present study was to evaluate experimentally induced neurotoxicity by CCl4 and its abrogation by using antioxidant potential of HP. CCl4 caused a significant enhancement in the lipid peroxidation (LPO) levels and protein carbonyl (PC) content. HP supplementation significantly restored the LPO levels and PC content. It also replenished the altered enzymatic and non-enzymatic antioxidants in brain tissues of rats. The neurotoxicity markers were also restored to normalcy with HP treatment. It is suggested that HP, by attenuating neuronal oxidative stress, holds promise that can ameliorate CCl4-induced neurotoxicity. HP has the potential to be explored as a universal neuroprotectant in xenobiotically induced neurotoxicity mediated by oxidative stress.

Mehar Naseem

Papers

Neuromodulatory effects of hesperidin in mitigating oxidative stress in streptozotocin induced diabetes.

Hesperidin restores experimentally induced neurotoxicity in Wistar rats