Efficacy of Sitagliptin on Nonalcoholic Fatty Liver Disease in High-fat-diet-fed Diabetic Mice

Zhou, Shu-Tong; Cui, Wen; Kong, Li; Yang, Xiaofeng

doi:10.1007/s11596-022-2573-9

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…Sitagliptin and pioglitazone are two commonly used clinical antidiabetic drugs. When they were used in HFD-induced diabetic mice, the same in vivo experimental model as ours, sitagliptin showed an approximately 20% and pioglitazone a 10% decline in FBGLs (Takada et al, 2014;Zhou et al, 2022). The above findings indicate that both LCA and ISL possess excellent hypoglycemic effects.…”

Section: Discussionsupporting

confidence: 71%

Licochalcone A alleviates abnormal glucolipid metabolism and restores energy homeostasis in diet‐induced diabetic mice

Wang,

Yang,

Ding

et al. 2023

Phytotherapy Research

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Licochalcone A (LCA) is a bioactive chalcone compound identified in licorice. This study aimed to investigate the effects of LCA on glucolipid metabolism and energy homeostasis, as well as the underlying mechanisms. Blood glucose levels, oral glucose tolerance, serum parameters, and histopathology were examined in high‐fat‐high‐glucose diet (HFD)‐induced diabetic mice, with metformin as a positive control. Additionally, changes in key markers related to glucolipid metabolism and mitochondrial function were analyzed to comprehensively assess LCA's effects on metabolism. The results showed that LCA alleviated metabolic abnormalities in HFD‐induced diabetic mice, which were manifested by suppression of lipogenesis, promotion of lipolysis, reduction of hepatic steatosis, increase in hepatic glycogenesis, and decrease in gluconeogenesis. In addition, LCA restored energy homeostasis by promoting mitochondrial biogenesis, enhancing mitophagy, and reducing adenosine triphosphate production. Mechanistically, the metabolic benefits of LCA were associated with the downregulation of mammalian target of rapamycin complex 1 and activation of adenosine monophosphate‐activated protein kinase, the two central regulators of metabolism. This study demonstrates that LCA can alleviate abnormal glucolipid metabolism and restore energy balance in diet‐induced diabetic mice, highlighting its therapeutical potential for the treatment of diabetes.

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Section: Discussionsupporting

confidence: 71%

Licochalcone A alleviates abnormal glucolipid metabolism and restores energy homeostasis in diet‐induced diabetic mice

Wang,

Yang,

Ding

et al. 2023

Phytotherapy Research

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“…Evogliptin exhibits an improved pharmacokinetic/pharmacodynamic (PK/PD) profile as well as related advantages: in in vitro studies, the DPP‐4 inhibitory activity of evogliptin was reversible, highly potent (half‐maximal inhibitory concentration 0.9 nM) and selective 9,10 . Evogliptin also displayed a relatively long half‐life (30‐40 hours), providing sustained inhibition of DPP‐4 7,11 . In a study in healthy volunteers, >80% inhibition of DPP‐4 activity was achieved within 1 hour after a single administration (5 mg, 10 mg or 20 mg), and the inhibitory effect was maintained for >24 hours after multiple administrations of once‐daily doses 13 .…”

Section: Introductionmentioning

confidence: 99%

“…9,10 Evogliptin also displayed a relatively long half-life (30-40 hours), providing sustained inhibition of DPP-4. 7,11 In a study in healthy volunteers, >80% inhibition of DPP-4 activity was achieved within 1 hour after a single administration (5 mg, 10 mg or 20 mg), and the inhibitory effect was maintained for >24 hours after multiple administrations of once-daily doses. 13 Evogliptin exhibits a linear PK profile, and its main route of elimination is the nonrenal route, primarily metabolized by CYP3A4.…”

Section: Introductionmentioning

confidence: 99%

“…9 In addition to their glucose-lowering effect, DPP-4 inhibitors have shown anti-inflammatory effects in both nondiabetic and diabetic models, suggesting potential novel therapeutic applications. 10,11 Evogliptin (DA-1229), a piperazine derivative, is a DPP-4 inhibitor developed by Dong-A ST Co., Ltd. The mechanism of action is proposed to occur through noncovalent binding with DPP-4, similar to linagliptin.…”

Section: Introductionmentioning

confidence: 99%

“…DPP‐4 inhibitors may be used in combination therapy or as monotherapy to achieve euglycaemia in type 2 DM patients 9 . In addition to their glucose‐lowering effect, DPP‐4 inhibitors have shown anti‐inflammatory effects in both nondiabetic and diabetic models, suggesting potential novel therapeutic applications 10,11 …”

Section: Introductionmentioning

confidence: 99%

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Effect of haemodialysis on the pharmacokinetics and pharmacodynamics of evogliptin

Kim

Won

et al. 2023

Diabetes Obesity Metabolism

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Aim:To investigate the possible effect of haemodialysis (HD) on the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor.Methods: A single-dose, open-label, parallel-group study of eight end-stage renal disease (ESRD) patients and eight matched healthy subjects was conducted. ESRD patients received a single oral dose of evogliptin 5 mg after and before HD with a 2-week washout between each dose, and healthy subjects received a single oral dose of evogliptin 5 mg. Serial blood, dialysate, and urine samples were collected to assess the PK and PD profiles of evogliptin. To compare PK parameters before and after HD, geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were calculated. Results:The GMRs for the maximum concentration and area under the concentration-time curve from time 0 to the last measurable timepoint (AUC last ) of evogliptin when administered before HD compared with after HD were 0.7293 (90% CI 0.6171-0.8620) and 0.9480 (90% CI 0.8162-1.1010), respectively. The maximum DPP-4 inhibitory effect, area under the DPP-4 inhibitory effect-time curve, and time duration of more than 80% DPP-4 inhibition were comparable when evogliptin was administered before and after HD. Compared with healthy subjects, the mean AUC last of evogliptin was approximately 1.4-fold greater in ESRD patients, but the difference is unlikely to affect the safety and efficacy of evogliptin. Conclusion:The effect of HD on the PK and PD characteristics of evogliptin was not clinically significant; therefore, dose adjustment according to HD status is not necessary.

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Protective effects of syringic acid in nonalcoholic fatty liver in rats through regulation of Nrf2/HO‐1 signaling pathway

Zhang,

Zheng,

et al. 2024

J Biochem & Molecular Tox

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Nonalcoholic fatty liver disease (NAFLD) is an alarming ailment that leads to severe liver damage and increases the risk of serious health conditions. The prevalence of NAFLD due to oxidative stress could be mitigated by plant‐derived antioxidants. This study aims to investigate the effects of syringic acid (SA) on NAFLD in a high‐fat diet (HFD) rat model. Twenty‐four rats were randomly divided into four groups (n = 6): normal control, HFD, SA‐administered HFD, and positive control SA on a normal diet. Rats in the normal control and positive control groups received a normal diet, and the remaining groups received an HFD for 8 weeks. SA (20 mg/kg b.w.) was orally (gavage) administered for 8 weeks. Lipid profiles were controlled by SA against HFD‐fed rats (p < 0.05). SA reduced the serum aspartate aminotransferase and alanine aminotransferase levels by 70%–190%. SA also suppressed pro‐inflammatory cytokines and attenuated histopathological and immunohistochemical changes against HFD‐fed rats. SA reversed oxidative stress by suppressing the malondialdehyde formation by 82% and replenished the nonenzymatic and enzymatic antioxidant activities (p < 0.05). Gene expressions of nuclear factor‐erythroid 2‐related factor/heme oxygenase 1 (Nrf2/HO‐1) were elevated in SA‐treated rats. Ameliorative effects of SA on NAFLD induced by an HFD in rats were prominent through the reversal of oxidative stress and inflammation, regulated by an intrinsic mechanism of defense against oxidative stress, the Nrf2/HO‐1 pathway.

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Efficacy of Sitagliptin on Nonalcoholic Fatty Liver Disease in High-fat-diet-fed Diabetic Mice

Cited by 8 publications

References 21 publications

Licochalcone A alleviates abnormal glucolipid metabolism and restores energy homeostasis in diet‐induced diabetic mice

Licochalcone A alleviates abnormal glucolipid metabolism and restores energy homeostasis in diet‐induced diabetic mice

Effect of haemodialysis on the pharmacokinetics and pharmacodynamics of evogliptin

Protective effects of syringic acid in nonalcoholic fatty liver in rats through regulation of Nrf2/HO‐1 signaling pathway

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