Annual review of plant physiology and plant molecular biology

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1260 

Capsaicin ( trans -8-methyl- N -vanillyl-6-nonenamide), a major pungent ingredient of red pepper, is reported to have anti-mutagenic and anti-carcinogenic properties. However, the mechanisms underlying its chemoprotective effects remain largely unresolved. In the present study, we found capsaicin induced expression of heme oxygenase-1 (HO-1) in HepG2 cells. Capsaicin treatment resulted in a transient increase in the phosphorylation of Akt and subsequently nuclear translocation of NF-E2-related factor 2 (Nrf2) and its binding to antioxidant response element (ARE). HepG2 cells treated with capsaicin exhibited increased production of reactive oxygen species (ROS). Prior exposure of cells with N -acetyl-L-cysteine (NAC) not only blocked the ROS production but also the Akt phosphorylation, nuclear translocation of Nrf2 and Nrf2-ARE binding, as well as HO-1 induction. Moreover, immunoblot analysis showed that while the level of HO-1 protein was elevated, that of NAD(P)H:quinone oxidoreductase (NQO1) was decreased with capsaicin or the inhibitor of NQO1, dicumarol. These results suggested that generation of reactive quinone metabolites of capsaicin that may bind covalently to NQO1 and thereby inhibit its activity may have been responsible for the overproduction of ROS. This, in turn, triggers the phosphorylation of Akt, increases the nuclear translocation of Nrf2 and its binding to ARE and upregulates the expression of HO-1.

Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3k-Nrf2 signaling

Biochimica et biophysica acta. Proteins and proteomics

Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin is still not fully understood. This review provides an overview of the existing literature concerning the beneficial mitochondrial and vascular effects of metformin, which it exerts by diminishing oxidative stress and reducing leukocyte-endothelium interactions. Specifically, we describe the molecular mechanisms involved in metformin's effect on gluconeogenesis, its capacity to interfere with major metabolic pathways (AMPK and mTORC1), its action on mitochondria and its antioxidant effects. We also discuss potential targets for therapeutic intervention based on these molecular actions.

https://digital.csic.es/bitstream/10261/230875/1/metformin.pdf

Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.

Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin's efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin's beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis.

Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects

Capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) is the active ingredient of chilli peppers and is responsible for the characteristic pungency. The ubiquitous human consumption of chilli peppers indicates their influence on human health. The effect of capsaicin through sensory neurons via TRPV1 activation has been well studied, but its non-neuronal effects are still not extensively explored. The purpose of this study was to investigate the in vivo antioxidant effect of capsaicin on erythrocytes of male Wistar rats. Markers of oxidative stress in blood were determined by assessing the plasma total antioxidant potential, activity of plasma membrane redox system, intracellular glutathione (GSH) level, ROS level, protein oxidation and lipid peroxidation. Results of this study suggest a significant protective effect of capsaicin against oxidative stress by enhancing FRAP, GSH level, PMRS activity and ameliorating ROS, MDA, PCO and AOPP.

Capsaicin has potent anti-oxidative effects in vivo through a mechanism which is non-receptor mediated

The anti-diabetic medicine metformin has been reported as an anti-ageing drug candidate as it mimics the benefits of caloric restriction and reduces ageing-related oxidative stress in various exper...

Metformin protects red blood cells against rotenone induced oxidative stress and cytotoxicity.

Different class of spiders spin silk to construct different web architectures. Spider’s silk is an extraordinary semi-crystalline biopolymer, which is highly tough and elastic. In the present study we have assessed the total protein content in spider webs produced by young and old cellar spiders (family pholcidae) inhabiting different environments. Data revealed that the total protein content in webs spun by young spiders was higher compared to old spiders of the same spider family. Also, the total protein content in webs spun by garden spiders was significantly higher compared to house spiders of the same spider family.

Ankita Chaudhary

Papers

Capsaicin has potent anti-oxidative effects in vivo through a mechanism which is non-receptor mediated

Metformin protects red blood cells against rotenone induced oxidative stress and cytotoxicity.

Protein Content in Silken Webs of Cellar Spiders (Family-Pholcidae): Effect of Habitat and Senescence