Naringin ameliorates type 2 diabetes mellitus-induced steatohepatitis by inhibiting RAGE/NF-κB mediated mitochondrial apoptosis

Syed, Anees A.; Reza, Mohammad Irshad; Shafiq, Mohammed; Kumariya, Sanjana; Singh, Punj Lata; Husain, Athar; Hanif, Kashif; Gayen, Jiaur R.

doi:10.1016/j.lfs.2020.118118

Cited by 72 publications

(41 citation statements)

References 41 publications

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“…Images were captured at 20 X magnification (Leica DM-5000). Lipid accumulation was calculated in terms of steatosis and hepatic ballooning score, as previously described ( Syed et al., 2020 ).…”

Section: Methodsmentioning

confidence: 99%

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Combination of Pancreastatin inhibitor PSTi8 with metformin inhibits Fetuin-A in type 2 diabetic mice

Singh

Garg

Goand

et al. 2020

Heliyon

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In the preceding study, we delineated that high-fat diet (HFD) consumption in mice increases the circulatory level of pancreastatin (PST), which additionally enhances the free fatty acid (FFA) concentration in circulation. Consequently, the aggravated FFA activates Fetuin-A, which facilitates hepatic lipid accumulation, insulin resistance (IR), and culminates in type 2 diabetes (T2D). Metformin (Met) is a widely known first-line drug for the treatment of T2D. We previously unveiled PSTi8, an inhibitor of PST, comprising antidiabetic property. Hence, we hypothesized that combination therapy of Met and PSTi8, at reduced therapeutic doses, would mitigate HFD-induced IR by inhibiting hepatic Fetuin-A in mice model of T2D. C57BL/6 mice were fed HFD for 12 weeks, followed by treatment with Met, PSTi8, and its combination for 10 days. Glucose and insulin tolerance tests were conducted. Circulatory levels of PST, Fetuin-A, and lipid markers were determined. Also, the mRNA and protein expression of Fetuin-A was assessed by qPCR, western blotting, and immunofluorescence. Moreover, the energy expenditure was measured by comprehensive laboratory animal monitoring system (CLAMS). Combination therapy displayed improved PST, Fetuin-A, and lipid profile in plasma. We also found reduced hepatic Fetuin-A, which reduced inhibitory phosphorylation of IRS and increased phosphorylation of AKT. Consequently, ameliorated hepatic lipogenesis, gluconeogenesis, and inflammation. Also, combination treatment attenuated Fetuin-A expression, lipid accumulation, and glucose production in palmitate-induced HepG2 cells. Altogether current study promulgates the beneficial effect of combination therapy of Met and PSTi8 (comparable to alone higher therapeutic doses) to ameliorate Fetuin-A activation, hepatic lipid accumulation, insulin resistance, and associated progressive pathophysiological alterations in T2D.

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Section: Methodsmentioning

confidence: 99%

“…To unravel the effect of combination therapy on Fetuin-A expression in Pal exposed HepG2 cells, we performed immunofluorescence as previously established in our lab ( Syed et al., 2020 ). HepG2 cells were grown in 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

Combination of Pancreastatin inhibitor PSTi8 with metformin inhibits Fetuin-A in type 2 diabetic mice

Singh

Garg

Goand

et al. 2020

Heliyon

Self Cite

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“…Additionally, naringin potentiated the viability and cytotoxic effect of MTX in HepG2 cells (Elsawy et al, 2020). In another study, naringin substantially reduced the viability and proliferation of HepG2 cells (Syed et al, 2020). Naringin treatment also significantly suppressed proliferation, upregulated the expression of microRNA (miR)-19b, and promoted apoptosis in HepG2 cells.…”

Section: Liver Cancermentioning

confidence: 96%

A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies

et al. 2021

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Background: Natural product-based cancer preventive and therapeutic entities, such as flavonoids and their derivatives, are shown to have a noticeable capability to suppress tumor formation and cancer cell growth. Naringin, a natural flavanone glycoside present in various plant species, has been indicated to modulate different signaling pathways and interact with numerous cell signaling molecules, which allows for an extensive variety of pharmacological actions, such as amelioration of inflammation, oxidative stress, metabolic syndromes, bone disorders, and cancer. The purpose of this systematic review is to present a critical and comprehensive assessment of the antitumor ability of naringin and associated molecular targets in various cancers.Methods: Studies were identified through systematic searches of Science Direct, PubMed, and Scopus as well as eligibility checks according to predefined selection criteria.Results: Eighty-seven studies were included in this systematic review. There was strong evidence for the association between treatment with naringin alone, or combined with other drugs and antitumor activity. Additionally, studies showed that naringin-metal complexes have greater anticancer effects compared to free naringin. It has been demonstrated that naringin employs multitargeted mechanisms to hamper cancer initiation, promotion, and progression through modulation of several dysregulated signaling cascades implicated in cell proliferation, autophagy, apoptosis, inflammation, angiogenesis, metastasis, and invasion.Conclusion: The results of our work show that naringin is a promising candidate for cancer prevention and treatment, and might offer substantial support for the clinical application of this phytocompound in the future. Nevertheless, further preclinical and clinical studies as well as drug delivery approaches are needed for designing novel formulations of naringin to realize the full potential of this flavonoid in cancer prevention and intervention.

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“…Naringin is another major compound in DOFP. Naringin ameliorates high-fat diet-induced lipid metabolic disorder, hepatic dysfunction, and steatohepatitis [44,45]. Jung previously reported that naringin regulated fatty acid metabolism to improve hyperlipidemia in a type II diabetes mouse model by significantly reducing the levels of plasma FFAs, plasma and liver triglycerides, liver carnitine palmitoyltransferase, and liver FAS [46].…”

Section: Discussionmentioning

confidence: 99%

Dendrobium officinale Regulates Fatty Acid Metabolism to Ameliorate Liver Lipid Accumulation in NAFLD Mice

Lei

Zhang

Zhou

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Dendrobium officinale (DOF) is a traditional Chinese edible and officinal plant. Ultrafine DOF powder (DOFP) can regulate lipids and histopathology in the liver, but the underlying mechanisms of hepatic fatty acid (FA) metabolism, which is generally correlated with the development of nonalcoholic fatty liver disease (NAFLD), remain unclear. The purpose of the present study was to investigate whether DOFP treatment alters hepatic FA metabolism in NAFLD mice by using multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) and analyse the underlying mechanisms. A 3-week DOFP treatment prevented lipid deposition and improved hepatic histopathology in NAFLD mice after withdrawal from the high-sucrose, high-fat (HSHF) diet, and it decreased triglyceride and FA content in the liver. Furthermore, the C16 : 0/C14 : 0 and C18 : 1/18 : 0 ratios in FAs were significantly decreased in the DOFP treatment group, and the C20 : 4/C20 : 3 and C22 : 4/C22 : 3 ratios were increased, and saturated FA was inhibited. Additionally, DOFP treatment significantly increased the content of two FA β-oxidation-related proteins (carnitine palmitoyltransferase 1-α and acyl-coenzyme A oxidase 1). It also decreased the content of a FA synthesis-related protein (fatty acid synthase), a FA desaturation-related protein (stearoyl-coenzyme A desaturase-1), and a FA uptake-related protein (fatty acid transport protein 2). Moreover, DOFP treatment improved dysregulated levels of major phospholipids in the livers of model mice. The results of this study confirm that DOFP treatment in NAFLD mice has liver recovery effects by regulating FA metabolism.

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Naringin ameliorates type 2 diabetes mellitus-induced steatohepatitis by inhibiting RAGE/NF-κB mediated mitochondrial apoptosis

Cited by 72 publications

References 41 publications

Combination of Pancreastatin inhibitor PSTi8 with metformin inhibits Fetuin-A in type 2 diabetic mice

Combination of Pancreastatin inhibitor PSTi8 with metformin inhibits Fetuin-A in type 2 diabetic mice

A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies

Dendrobium officinale Regulates Fatty Acid Metabolism to Ameliorate Liver Lipid Accumulation in NAFLD Mice

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