Gymnemic Acid Alleviates Type 2 Diabetes Mellitus and Suppresses Endoplasmic Reticulum Stress <i>in Vivo</i> and <i>in Vitro</i>

Li, Yumeng; Sun, Mingzhe; Liu, Yaping; Liang, Jianying; Wang, Tianxin; Zhang, Zesheng

doi:10.1021/acs.jafc.9b00431

Cited by 40 publications

(27 citation statements)

References 37 publications

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“…Curcumin [52], berberine [53], glycyrrhizin [54], and scutellarin [55] were found to activate glucose and lipid metabolism by activating PPAR-α in the adipose tissue; while, naringenin [56], myricetin [57], quercetin [58], mangiferin [59], ferulic acid [60], bixin [61], silymarin [62], α-eleostearic acid [63], glycyrrhizin [54], and asiatic acid [64] can endorse hepatic lipid metabolism via endorsing PPAR-α activation. Gymnemic acid was found to endorse fatty acid oxidation and reciprocate insulin resistance in the liver, skeletal muscle and adipose tissue through PPAR-δ activation [65]. Plant phenolics can maintain energy homeostasis by triggering PPAR-δ activation [66].…”

Section: Plant-derived Small Molecules As Antidiabetic Agentsmentioning

confidence: 99%

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

Dewanjee

Chakraborty

Mukherjee

et al. 2020

IJMS

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Diabetes mellitus is a life-threatening metabolic syndrome. Over the past few decades, the incidence of diabetes has climbed exponentially. Several therapeutic approaches have been undertaken, but the occurrence and risk still remain unabated. Several plant-derived small molecules have been proposed to be effective against diabetes and associated vascular complications via acting on several therapeutic targets. In addition, the biocompatibility of these phytochemicals increasingly enhances the interest of exploiting them as therapeutic negotiators. However, poor pharmacokinetic and biopharmaceutical attributes of these phytochemicals largely restrict their clinical usefulness as therapeutic agents. Several pharmaceutical attempts have been undertaken to enhance their compliance and therapeutic efficacy. In this regard, the application of nanotechnology has been proven to be the best approach to improve the compliance and clinical efficacy by overturning the pharmacokinetic and biopharmaceutical obstacles associated with the plant-derived antidiabetic agents. This review gives a comprehensive and up-to-date overview of the nanoformulations of phytochemicals in the management of diabetes and associated complications. The effects of nanosizing on pharmacokinetic, biopharmaceutical and therapeutic profiles of plant-derived small molecules, such as curcumin, resveratrol, naringenin, quercetin, apigenin, baicalin, luteolin, rosmarinic acid, berberine, gymnemic acid, emodin, scutellarin, catechins, thymoquinone, ferulic acid, stevioside, and others have been discussed comprehensively in this review.

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Section: Plant-derived Small Molecules As Antidiabetic Agentsmentioning

confidence: 99%

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

Dewanjee

Chakraborty

Mukherjee

et al. 2020

IJMS

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“…When the random blood glucose was 16.7 mmol/L and remained stable for 4 weeks, the rats were identified as Type 2 diabetes. 16 The rats were fasted for 12 h before surgery, and were anesthetized with isoflurane inhalation, then supine on the operating table.…”

Section: Methodsmentioning

confidence: 99%

Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus

Su¹,

Cheng²,

Wang³

2021

DMSO

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Background: Roux-en-Y gastric bypass (RYGB) is the most effective treatment for type 2 diabetes mellitus (T2DM). Previous studies have reported that silent information regulator 1 (Sirt1) closely relates to many pathological processes of glucose metabolism and insulin resistance (IR). However, it is unclear whether Sirt1 is involved in the hepatic glucose metabolism of T2DM after RYGB. Methods: T2DM rats were randomly divided into four groups: Control, DM, Diet and RYGB. Normal rats were served as the control group. Hematoxylin and eosin (H&E) staining and Masson staining assays were performed to explore the changes of liver fibrous tissue after RYGB. The effect of RYGB on the protein expression of Sirt1 was detected by the Western blotting assay and immunohistochemical assay. Next, we built the insulin resistance model of human hepatocyte cell lines (FL62891 and HHL5) using the human recombinant insulin. Western blotting assay was applied to determine the expression of Sirt1 and the expression change of IRS1/mTOR2 /PKB pathway-related proteins in FL62891 and HHL5 cells. Additionally, the effects of Sirt1 on the expression of PTP1B and FGF-21 in insulin-resistant FL62891 and HHL5 cells were investigated using Western blotting and immunofluorescence assay. Results: Our results showed that following RYGB improved the pathological changes of liver and increased the expression of Sirt1 in rats with T2DM compared with the diabetic rats. In experiments in vitro, the expression of Sirt1 was downregulated in insulin-resistance FL62891 and HHL5 cells. Moreover, overexpression of Sirt1 significantly increased the expression of FGF-21 whereas decreased the expression of PTP1B in insulin-resistance FL62891 and HHL5 cells. These above changes were alleviated in RYGB and Diet groups. Furthermore, RYGB could improve the glucose metabolism through activating IRS1/ mTOR2/PKB pathways by regulating Sirt1 in rats with T2DM. Conclusion: RYGB could significantly improve hepatic glucose metabolism and increase the expression of Sirt1 in T2DM rats, which is related to the IRS1/mTOR2 /PKB pathway.

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“…Additionally, the absorptive external layers of the intestine exhibit receptors for GM molecules that prevent the absorption of sugar molecules, lowering blood glucose levels (19). GM improves glucose and lipid metabolism in type two DM model rats, enhances glucose uptake by regulating the amelioration of endoplasmic reticulum stress and insulin transduction in insulin resistant HepG2 cells (20), and inhibits GAPDH during glycerol metabolism in rabbits (21).…”

Section: Efficiency Of Gymnema Sylvestre-derived Gymnemic Acid On the Restoration And Improvement Of Brain Vascular Characteristics In DImentioning

confidence: 99%

Efficiency of Gymnema sylvestre‑derived gymnemic acid on the restoration and improvement of brain vascular characteristics in diabetic rats

et al. 2021

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The brain is a vital organ that requires a constant blood supply. Stroke occurs when the blood supply to specific parts of the brain is reduced; diabetes is an autonomous risk factor for stroke. The present study aimed to investigate the potential vascular protective effect of gymnemic acid (GM) by assessing the morphological changes of microvasculature, along with VEGFA and angiopoietin-1 (Ang-1) protein expression in the brains of diabetic rats. Rats were divided into five groups, including control, gymnemic control rats (CGM), rats that were rendered diabetic by single injection of 60 mg/kg streptozotocin (STZ), diabetic rats treated with 400 mg/kg GM (STZ + GM) and diabetic rats treated with 4 mg/kg glibenclamide (GL; STZ + GL). After 8 weeks, brain tissues were collected to examine the three-dimensional morphology of the anterior cerebral arteries by vascular corrosion casting. Western blotting was performed to determine VEGFA and Ang-1 expression. Cerebral arteries, arterioles and capillaries were depicted the diameter, thickness and collagen accumulation of the wall, and the results demonstrated narrow diameters, thickened walls and collagen accumulation in the STZ group. After receiving GM, the histopathological changes were similar to that of the control group. Through vascular corrosion casting and microscopy, signs of vessel restoration and improvement were exhibited by increased diameters, and healthy and nourished arterioles and capillaries following treatment with GM. Furthermore, VEGF expression and Ang-1 secretion decreased in the STZ + GM group compared with STZ rats. The results of the present study revealed that GM treatment decreased blood vessel damage in the brain, suggesting that it may be used as a therapeutic target for the treatment of diabetes.

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Gymnemic Acid Alleviates Type 2 Diabetes Mellitus and Suppresses Endoplasmic Reticulum Stress in Vivo and in Vitro

Cited by 40 publications

References 37 publications

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy

Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Upregulation of Sirt1 in Type 2 Diabetes Mellitus

Efficiency of Gymnema sylvestre‑derived gymnemic acid on the restoration and improvement of brain vascular characteristics in diabetic rats

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