RETRACTED: Combination of carvacrol and rosiglitazone ameliorates high fat diet induced changes in lipids and inflammatory markers in C57BL/6J mice

Ezhumalai, Muthukrishnan; Ashokkumar, Natarajan; Pugalendi, Kodukkur Viswanathan

doi:10.1016/j.biochi.2014.12.005

Cited by 16 publications

(13 citation statements)

References 50 publications

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“…The remarkable feature of monoterpenes is that they have shown promising antidiabetic effect in vivo despite their rather simplistic structural appearance [ 35 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. The list of monoterpenes with good effects on in vivo antidiabetic models including in the streptozotocin (STZ)-induced diabetic, high fat diet (HFD) fed and spontaneously obese mouse models are shown in Table 2 .…”

Section: Antidiabetic Potential Of Monoterpenesmentioning

confidence: 99%

“…It is important to note the effect of the studied compounds on gross weight of the animals especially given administration of STZ-induced diabetes is associated with weight loss. For example, administration of borneol [ 67 ], carvacrol [ 68 ] and swertiamarin [ 94 ] have shown to reverse the body weight loss in diabetes. On the other hand, the body weight gain in HFD-obese model could be ameliorated by monoterpenes.…”

Section: Antidiabetic Potential Of Monoterpenesmentioning

confidence: 99%

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Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight

Habtemariam

2017

IJMS

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Monoterpenes belong to the terpenoids class of natural products and are bio-synthesized through the mevalonic acid pathway. Their small molecular weight coupled with high non-polar nature make them the most abundant components of essential oils which are often considered to have some general antioxidant and antimicrobial effects at fairly high concentrations. These compounds are however reported to have antidiabetic effects in recent years. Thanks to the ingenious biosynthetic machinery of nature, they also display a fair degree of structural complexity/diversity for further consideration in structure-activity studies. In the present communication, the merit of monoterpenes as antidiabetic agents is scrutinized by assessing recent in vitro and in vivo studies reported in the scientific literature. Both the aglycones and glycosides of these compounds of rather small structural size appear to display antidiabetic along with antiobesity and lipid lowering effects. The diversity of these effects vis-à-vis their structures and mechanisms of actions are discussed. Some key pharmacological targets include the insulin signaling pathways and/or the associated PI3K-AKT (protein kinase B), peroxisome proliferator activated receptor-γ (PPARγ), glucose transporter-4 (GLUT4) and adenosine monophosphate-activated protein kinase (AMPK) pathways; proinflammatory cytokines and the NF-κB pathway; glycogenolysis and gluconeogenesis in the liver; glucagon-like-1 receptor (GLP-1R); among others.

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Section: Antidiabetic Potential Of Monoterpenesmentioning

confidence: 99%

Section: Antidiabetic Potential Of Monoterpenesmentioning

confidence: 99%

Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight

Habtemariam

2017

IJMS

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“…The plasma level of carvacrol may reach 20-30 μM (1, 10). In animals with liver or kidney disorders, this level may go much higher (1,10). Our results show that at a concentration of 200 μM carvacrol could induce slight cell death.…”

Section: Discussionmentioning

confidence: 66%

“…To the best of our knowledge, the effect of carvacrol on toxicity has not been explored in human; therefore, no data of the achievable plasma level is available. However, in animal research, previous studies were performed to explore the protective effects of carvacrol in D-galactosamine (D-GalN)-induced hepatotoxicity and oxidative damage in male albino Wistar rats (1) and high-fat-diet (HFD)-induced C57BL/ 6J diabetic mice (10). The plasma level of carvacrol may reach 20-30 μM (1, 10).…”

Section: Discussionmentioning

confidence: 99%

Effect of Carvacrol on Ca^(2+) Movement and Viability in PC3 Human Prostate Cancer Cells

et al. 2017

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Carvacrol, a monoterpenic phenol compound, has been shown to possess various biological effects in different models. However, the effect of carvacrol on intracellular Ca²⁺ and its related physiology in human prostate cancer is unknown. This study explored the effect of carvacrol on cytosolic free Ca²⁺ levels ([Ca²⁺]i) and viability in PC3 human prostate cancer cells. Fura-2, a Ca²⁺- sensitive fluorescent dye, was used to assess [Ca²⁺]i. Cell viability was measured by the detecting reagent WST-1. Carvacrol at concentrations of 200-800 μM caused [Ca²⁺]i rises in a concentration-dependent manner. Removal of extracellular Ca²⁺ reduced carvacrol’s effect by approximately 60%. Carvacrol-induced Ca²⁺ entry was confirmed by Mn²⁺ entry-induced quench of fura-2 fluorescence, and was inhibited by approximately 30% by nifedipine, econazole, SKF96365, and the protein kinase C (PKC) inhibitor GF109203X. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin (TG) abolished carvacrol-induced [Ca²⁺]i rises. Treatment with carvacrol also abolished TG-induced [Ca²⁺]i rises. Carvacrol-induced Ca²⁺ release from the endoplasmic reticulum was abolished by inhibition of phospholipase C (PLC). Carvacrol killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelating cytosolic Ca²⁺ with BAPTA/AM did not prevent carvacrol’s cytotoxicity. Together, in PC3 cells, carvacrol induced [Ca²⁺]i rises by inducing PLC-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via PKC-sensitive store-operated Ca²⁺ channels and other unknown channels. Carvacrol also induced Ca²⁺-dissociated cell death.

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“…An excessive amount of fatty acids in plasma promote the production of phospholipids and cholesterol in STZ-induced diabetic animals [37]. Antihyperglycemic treatment that improves insulin resistance can improve the lipid profile [38]. Treatment with carvacrol for 7 days has been shown to reduce the TC level significantly in STZ-induced diabetic mice [34].…”

Section: Discussionmentioning

confidence: 99%

Effect of long-term treatment of Carvacrol on glucose metabolism in Streptozotocin-induced diabetic mice

Mai

Qiu

et al. 2020

BMC Complement Med Ther

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Background: Carvacrol is a food additive with various bioactivities, including reducing the blood glucose level as well as improvement of heart function, in diabetic mice. We explored the antihyperglycemic effect of carvacrol and its effect on the key hepatic enzymes accounting for glucose metabolism. Methods: A streptozotocin (STZ)-induced diabetes-mellitus model in mice was used. Mice were divided randomly into a control group, diabetic group, low dose carvacrol-treated diabetic group (10 mg/kg body weight [BW]), and high dose carvacrol-treated diabetic group (20 mg/kg BW). Carvacrol was injected intraperitoneally (i.p.) in each carvacrol-treated group daily for 4 weeks and 6 weeks, respectively. The level of random plasma glucose, fasting plasma glucose, and plasma insulin was determined at 4 weeks and 6 weeks after carvacrol administration. The plasma level of total cholesterol (TC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and the activity of hepatic key enzymes related to glucose metabolism were determined. Results: Carvacrol treatment decreased the levels of random plasma glucose and fasting plasma glucose, significantly in a dose-dependent manner. A significant improvement in glucose tolerance and a significant decrease in the plasma level of TG were observed in carvacrol-treated diabetic mice at a dose of 20 mg/kg BW compared with that in vehicle-treated diabetic mice. There was no significant difference in the plasma level of TC and insulin between vehicle-treated diabetic mice and carvacrol-treated diabetic mice. Carvacrol treatment at a dose of 20 mg/kg BW significantly reduced the plasma level of LDH but not AST, ALT, or ALP, compared with that in the vehicle-treated diabetic group. The activity of hexokinase (HK), 6-phosphofructokinase (PFK), and citrate synthetase (CS) was increased by carvacrol treatment in diabetic mice. Conclusions: Carvacrol exerted an anti-hyperglycemic effect in STZ-induced diabetic mice. This was achieved through regulating glucose metabolism by increasing the activity of the hepatic enzymes HK, PFK, and CS.

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RETRACTED: Combination of carvacrol and rosiglitazone ameliorates high fat diet induced changes in lipids and inflammatory markers in C57BL/6J mice

Cited by 16 publications

References 50 publications

Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight

Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight

Effect of Carvacrol on Ca^(2+) Movement and Viability in PC3 Human Prostate Cancer Cells

Effect of long-term treatment of Carvacrol on glucose metabolism in Streptozotocin-induced diabetic mice

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