The vicious cycle between hyperinsulinemia and insulin resistance results in the progression of atherosclerosis in the vessel wall. The complex interaction between hyperglycemia and lipoprotein abnormalities promotes the development of atherogenesis. In the early phase of atherosclerosis, macrophage‐derived foam cells play an important role in vascular remodeling. Mechanistic target of rapamycin (mTOR) signaling pathway has been identified to play an essential role in the initiation, progression, and complication of atherosclerosis. Recently sestrin2, an antioxidant, was shown to modulate TOR activity and thereby regulating glucose and lipid metabolism. But the role of sestrin2 in monocyte activation is still not clearly understood. Hence, this study is focussed on investigating the role of sestrin2 in monocyte activation under hyperglycemic and dyslipidemic conditions. High‐glucose and oxidized low‐density lipoprotein (LDL) treatments mediated proinflammatory cytokine production (M1) with a concomitant decrease in the anti‐inflammatory cytokine (M2) levels in human monocytic THP1 cells. Both glucose and oxidized LDL (OxLDL) in a dose and time‐dependent manner increased the mTOR activation with a marked reduction in the levels of pAMPK and sestrin2 expression. Both high‐glucose and OxLDL treatment increased foam cell formation and adhesion of THP1 cells to endothelial cells. Experiments employing activator or inhibitor of adenosine monophosphate kinase (AMPK) as well as overexpression or silencing of sestrin2 indicated that high‐glucose mediated monocyte polarization and adhesion of monocytes to the endothelial cells were appeared to be programmed via sestrin2‐AMPK‐mTOR nexus. Our results evidently suggest that sestrin2 plays a major role in regulating monocyte activation via the AMPK–mTOR‐pathway under diabetic and dyslipidemic conditions and also AMPK regulates sestrin2 in a feedback mechanism.

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We previously reported that the circulatory level of Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, was increased in diabetic kidney disease patients. However, the mechanism and the role of ADMA in diabetic kidney injury remain unclear. Hence, our principal aim is to investigate the causal role of ADMA in the progression of renal cell fibrosis under high glucose (HG) treatment and to delineate its signaling alterations in kidney cell injury. High Glucose/ADMA significantly increased fibrotic events including cell migration, invasion and proliferation along with fibrotic markers in the renal cells; whereas ADMA inhibition reversed the renal cell fibrosis. To delineate the central role of ADMA induced fibrotic signaling pathway and its downstream signaling, we analysed the expression levels of fibrotic markers, NOX4, ROS and ERK activity by using specific inhibitors and genetic manipulation techniques. ADMA stimulated the ROS generation along with a significant increase in NOX4 and ERK activity. Further, we observed that ADMA activated NOX-4 and ERK are involved in the extracellular matrix proteins accumulation. Also, we observed that ADMA induced ERK1/2 phosphorylation was decreased after NOX4 silencing. Our study mechanistically demonstrates that ADMA is involved in the progression of kidney cell injury under high glucose condition by targeting coordinated complex mechanisms involving the NOX4- ROS-ERK pathway.

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Introduction: Sarapenthira  vaithiya murailkal (Neerilivu chikitchai) (SVM-NC) is a classic book written in a poetic form. It mentioned the treatment of Neerilivu (Diabetic Mellitus (DM)). According to the mode of administration, Siddha medicines are categorized into two classes; Internal medicine & external medicine. Medicinal plants, Metals and Minerals are used to prepare medicines from ancient times for the treatment of Neerilivu (DM). According to the Siddha literatures signs & symptoms of Neerilivu can be compared with Diabetic Mellitus in modern aspect. Diabetic Mellitus is a chronic metabolic disorder. Many drugs are mentioned for the treatment of Neerilivu (DM) in SVM-NC. Aim: The aim of the study is to identify the types of Siddha drugs and its ingredients from SVM-NC and research article. Data were collected, tabulated and analysed. This information was used to identify the medicinal plants that are being used in the management of Neerilivu (DM) in the traditional medicine. Results and Discussion: Eighty-five drugs were identified from the analysis. Out of 85 drugs, 83 drugs (98%) are used as internally and 2 drugs (2%) are externally. Among the 85 Internal medicine, 28 (33%) are chooranum, 20 (24%) are home remedy, 12 (14%) are kudineer and 8 (9%) are vizhuthu. Two external medicines are oil. 124 medicinal plants were identified from 83 internal medicines. 63 Families were identified in 124 medicinal plants. 10% (26) Medicinal plants are belonging to Fabaceae family. From these plants, 34 (27%) plants are used as root, 19 (15%) plants are used as leaves and seeds and 17 (14%) plants are used as bark. These plants have siddha properties; taste (Astringent: 41 (33%), Bitter: 32 (26%), Sweet: 28 (23%)), Potency (Hot: 81 (61%), Cool: 37 (30%)) and Efficacy (Pungent: 68 (55%), Sweet: 50(40%)). Among the 85 drugs, Cassia auriculata, Phyllanthus emblica, Strychnos potatorum, Terminalia chebula, Terminalia bellirica, Sysygium aromaticum and Salacia reticulata are used many times in medicine preparation.  Previous researches showed that these ingredients have antidiabetic activity, hepatoprotectives and anti-oxidant. Conclusion: This review provides useful documented evidence and scientific evidence on the treatment of Neerilivu (DM) in traditional medicine.

Introduction: Diabetes is a group of metabolic disorders characterized by hyperglycemia and associated chronic complications including cardiovascular diseases. Hyperglycemia induces various stress conditions including oxidative /endoplasmic reticulum (ER) stress, leading to inflammatory disorders in vascular system. Sestrin2, an antioxidant, is involved in the glucose and lipid homeostasis by regulating mTOR activity. However, the roles of sestrin2 in the regulation of ER stress and pro-inflammation in diabetic patients remains unclear. Hence, the present study is focused on evaluating the status of sestrin2 and its effect on ER stress and pro-inflammation in the diabetic dyslipidemia.Methods: Human subjects with diabetes and/or dyslipidemia were recruited to study the status of sestrin2, ER stress markers, andpro-inflammatory markers in peripheral mononuclear cells (PBMC) and monocytes. Human monocytic cell line (THP1) was over expressed with sestrin2 and treated with high glucose and then analyzed the expression levels of oxidative stress, ER stress and pro-inflammatory markers.Observations: The expressions of ER stress/pro-inflammatory markers were significantly increased in the PBMC of patients with diabetes or dyslipidemia, and those with both the conditions. Sestrin2 expression was also significantly reduced in the monocytes of persons with metabolic disorder. In in vitro conditions, high glucose induction increased the expression levels of ER stress, oxidative stress, pro-inflammatory markers and decreased the sestrin2 levels. Sestrin2 overexpression reverted all the ill effects of high glucose in THP1 cells. Conclusion:Sestrin2 is involved in the regulation of pro-inflammation, ER stress and oxidative stress in diabetes condition.