Carey, Hannah V., Matthew T. Andrews, and Sandra L. Martin. Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature. Physiol Rev 83: 1153-1181, 2003; 10....

https://www.physiology.org/doi/pdf/10.1152/physrev.00008.2003

Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities. In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

A review on the dietary flavonoid kaempferol.

Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus (T2DM) and this appears to underlie the development of cardiovascular disease, T2DM and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM.

Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus

The morbidity and mortality associated with diabetes is the result of the myriad complications related to the disease One of the most explored hypotheses to explain the onset of complications is a hyperglycemia-induced increase in oxidative stress Reactive oxygen species (ROS) are produced by oxidative phosphorylation, nicotinamide adenine dinucleotide phosphate oxidase (NADPH), xanthine oxidase, the uncoupling of lipoxygenases, cytochrome P450 monooxygenases, and glucose autoxidation Once formed, ROS deplete antioxidant defenses, rendering the affected cells and tissues more susceptible to oxidative damage Lipid, DNA, and protein are the cellular targets for oxidation, leading to changes in cellular structure and function Recent evidence suggests ROS are also important as second messengers in the regulation of intracellular signaling pathways and, ultimately, gene expression This review explores the production of ROS and the propagation and consequences of oxidative stress in diabetes

The role of oxidative stress in diabetic complications.

Increased oxidative stress in obesity: Implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer

Influence of cytotoxic doses of 4-hydroxynonenal on selected neurotransmitter receptors in PC-12 cells.

Aldose Reductase Mediates Mitogenic Signaling in Vascular Smooth Muscle Cells

In the last few years there has been an exponential growth in the field of herbal medicine, and these drugs are gaining popularity in both developing and developed countries because of their natural origin and lesser side effects. Syzygium cumini (syn. Eugenia jambolana, Syzygium jambolana, Eugenia cumini, Syzygium jambos), commonly known as jamun in India, is an evergreen tree distributed throughout the Indian subcontinent, Southeast Asia and East Africa. It is mainly utilised as a fruit producer and for its timber. Medicinally, the fruit is reported to have antidiabetic, antihyperlipidaemic, antioxidant, antiulcer, hepatoprotective, antiallergic, antiarthritic, antimicrobial, anti-inflammatory, antifertility, antipyretic, antiplaque, radioprotective, neuropsychopharmacological, nephroprotective and antidiarrhoeal activities. Among these beneficial physiological effects, the antidiabetic property of S. cumini has the most promising nutraceutical value. The health-beneficial effects of S. cumini are mainly attributed to various phytoconstituents such as tannins, alkaloids, steroids, flavonoids, terpenoids, fatty acids, phenols, minerals, carbohydrates and vitamins present in the fruit. This review paper presents an overview of experimental evidence for the pharmacological potential of S. cumini.

Pharmacological potentials of Syzygium cumini: a review

Increased reduction of glucose via the polyol pathway enzyme aldose reductase (AR) has been linked to the development of secondary diabetic complications. Because AR is a redox-sensitive protein, which in vitro is readily modified by NO donors, we tested the hypothesis that NO may be a physiological regulator of AR. We found that administration of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) increased sorbitol accumulation in the aorta of nondiabetic and diabetic rats, whereas treatment with L-arginine (a precursor of NO) or nitroglycerine patches prevented sorbitol accumulation. When incubated ex vivo with high glucose, sorbitol accumulation was increased by L-NAME and prevented by L-arginine in strips of aorta from rats or wild-type, but not eNOS-deficient, mice. Exposure to NO donors also inhibited AR and prevented sorbitol accumulation in rat aortic vascular smooth muscle cells (VSMC) in culture. The NO donors also increased the incorporation of radioactivity in the AR protein immunoprecipitated from VSMC in which the glutathione pool was prelabeled with [35S]-cysteine. Based on these observations, we suggest that NO regulates the vascular synthesis of polyols by S-thiolating AR; therefore, increasing NO synthesis or bioavailability may be useful in preventing diabetes-induced changes in the polyol pathway.

Nitric oxide regulates the polyol pathway of glucose metabolism in vascular smooth muscle cells.

Increased glucose utilization by aldose reductase (AR) has been implicated in the development of diabetes complications. However, the mechanisms that regulate AR during diabetes remain unknown. Herein we report that several nitric oxide (NO) donors prevent ex vivo synthesis of sorbitol in erythrocytes obtained from diabetic or nondiabetic rats. Compared with erythrocytes of nondiabetic rats, the AR activity in the erythrocytes of diabetic rats was less sensitive to inhibition by NO donors or by AR inhibitors-sorbinil or tolrestat. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, enhanced AR activity and sorbitol accumulation in tissues of nondiabetic rats. Application of transdermal nitroglycerin patches or treatment with L-arginine did not inhibit AR activity or sorbitol accumulation in the tissues of nondiabetic animals. Treatment with L-NAME increased, whereas treatment with L-arginine or nitroglycerine patches decreased AR activity and sorbitol content in tissues of diabetic rats. These observations suggest that NO maintains AR in an inactive state and that this repression is relieved in diabetic tissues. Thus, increasing NO availability may be a useful strategy for inhibiting the polyol pathway and preventing the development of diabetes complications.

https://diabetes.diabetesjournals.org/content/diabetes/51/10/3095.full.pdf

Deepak Chandra

Papers

Influence of cytotoxic doses of 4-hydroxynonenal on selected neurotransmitter receptors in PC-12 cells.

Aldose Reductase Mediates Mitogenic Signaling in Vascular Smooth Muscle Cells

Pharmacological potentials of Syzygium cumini: a review

Nitric oxide regulates the polyol pathway of glucose metabolism in vascular smooth muscle cells.

Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes.