Timosaponin B-II Ameliorates Palmitate-Induced Insulin Resistance and Inflammation via IRS-1/PI3K/Akt and IKK/NF-κB Pathways

Yuan, Yanggang; Lin, Baoqin; Zhang, Chunfeng; Cui, Lingling; Ruan, Shi-Xia; Yang, Zhonglin; Li, Fēi; Ji, De

doi:10.1142/s0192415x16500415

Cited by 34 publications

(27 citation statements)

References 41 publications

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“…In the current study, Sar remarkably reduced the albuminuria, kidney weight index, serum uric acid level, and the protein expression of FN and CoIV in kidney of STZ‐induced diabetic rats, suggesting that Sar may be the final contributor of the effects of steroidal saponins from AA. Timosaponin BII, BIII, AIII, and Sar have anti‐inflammatory effects by negative regulation of the NF‐κB pathways (J. Y. Kim et al, ; Lim et al, ; Yuan et al, ), and the vitro and in vivo anti‐inflammatory effects of Sar are more potent than its glycoside timosaponin AIII (Lim et al, ). The present study showed that Sar could suppress NLRP3 inflammasome activation in rat model of DN, as evidenced by the decreased levels of markers of inflammasome activation (elevated NLRP3, caspase 1 cleavage, and IL‐18 overproduction) in the kidney of diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats

Liu

Hao

Chen

et al. 2018

Phytotherapy Research

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Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in albuminuria, kidney weight index, serum uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (fibronectin and collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in interleukin-18, NLRP3, and activated caspase 1 levels as well as advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate diabetic nephropathy in rats via inhibition of NLRP3 inflammasome activation and AGEs-RAGE interaction.

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Section: Discussionmentioning

confidence: 99%

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats

Liu

Hao

Chen

et al. 2018

Phytotherapy Research

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“…It was also reported to attenuate DN by reducing endoplasmic reticulum stress [28]. Similarly, A. asphodeloides Bunge was reported to reduce FG and improve impaired glucose tolerance in type 2 DM rats, and the flavonoids of A. asphodeloides Bunge are thought to reduce glucose and TGs [13]. Furthermore, TB-II, a main ingredient of A. asphodeloides Bunge, notably ameliorated IR and inflammation, and significantly improved cell viability decreased TNF-α and IL-6 levels, and the expression of p-NF-κBp65, p-IKKβ, p-IRS-1, p-PI3K, and p-Akt [13].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, A. asphodeloides Bunge was reported to reduce FG and improve impaired glucose tolerance in type 2 DM rats, and the flavonoids of A. asphodeloides Bunge are thought to reduce glucose and TGs [13]. Furthermore, TB-II, a main ingredient of A. asphodeloides Bunge, notably ameliorated IR and inflammation, and significantly improved cell viability decreased TNF-α and IL-6 levels, and the expression of p-NF-κBp65, p-IKKβ, p-IRS-1, p-PI3K, and p-Akt [13]. Coptis chinensis Franch was confirmed to significantly inhibit all the three periods of nonenzymatic protein glycation in vitro, including amadori products, dicarbonyl compounds, and AGEs formation [29].…”

Section: Discussionmentioning

confidence: 99%

“…Other studies of TCM also indicate that diabetes may be an inflammatory disease and the inhibition of inflammation might be useful to prevent its development [11]. Moreover, previous studies found that Chinese herbal medicine, such as berberine [11], astragaloside IV [11], salvianolic acid B [12], and timosaponin B-II [13], one of the main components of Coptis chinensis Franch , Astragalus mongholicus Bunge, Salvia miltiorrhiza Bunge, and Anemarrhena asphodeloides Bunge , respectively, might exert hypoglycemic effects that are partially mediated by anti-inflammatory mechanisms. JTD, a Chinese patented drug (Patent Number: 20141002188.3) containing Euphorbia humifusa Willd, S. miltiorrhiza Bunge, A. mongholicus Bunge, A. asphodeloides Bunge, and C. chinensis Franch was specifically formulated to clear heat, promote blood circulation, supplement the qi, and nourish the Yin, has been used clinically for decades to effectively treat DN; however, the mechanisms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Jiangtang decoction ameliorate diabetic nephropathy through the regulation of PI3K/Akt-mediated NF-κB pathways in KK-Ay mice

Wang

et al. 2017

Chin Med

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BackgroundJiangtang decoction (JTD) is a China patented drug which contains Euphorbia humifusa Willd, Salvia miltiorrhiza Bunge, Astragalus mongholicus Bunge, Anemarrhena asphodeloides Bunge, and Coptis chinensis Franch. For decades, it has also been used clinically to treat diabetic nephropathy (DN) effectively; however, the associated mechanisms remain unknown. Thus, the present study aimed to examine the protective efficacy of JTD in DN and elucidate the underlying molecular mechanisms.MethodsA diabetic model using KK-Ay mice received a daily administration of JTD for 12 weeks. Body weight, blood glucose, triglycerides (TGs), total cholesterol (TC), urea nitrogen (UN), creatinine (Cr), and microalbumin/urine creatinine (MA/UCREA) was measured every 4 weeks. Furthermore, on the day of the sacrifice, blood, urine, and kidneys were collected to assess renal function according to general parameters. Pathological staining was performed to evaluate the protective renal effect of JTD. In addition, the levels of inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6 and intercellular adhesion molecule [ICAM]-1), insulin receptor substrate [IRS]-1, advanced glycation end products [AGEs], and receptor of glycation end products [RAGE] were assessed. Finally, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and involvement of nuclear factor-κB (NF-κB) was further analyzed.ResultsAfter 12 weeks of metformin and JTD administration, the mice exhibited a significant amelioration in glucose and lipid metabolism dysfunction, reduced morphological changes in the renal tissue, decreased urinary albumin excretion, and normalized creatinine clearance. JTD treatment also reduced the accumulation of AGEs and RAGE, up-regulated IRS-1, and increased the phosphorylation of both PI3K (p85) and Akt, indicating that the activation of the PI3K/Akt signaling pathway was involved. Additionally, JTD administration reduced the elevated levels of renal inflammatory mediators and decreased the phosphorylation of NF-κB p65.ConclusionsThese results demonstrate that JTD might reduce inflammation in DN through the PI3K/Akt and NF-κB signaling pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s13020-017-0134-0) contains supplementary material, which is available to authorized users.

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“…The activated AKT can then activate or deactivate its myriad of substrates through its kinase activity. Recent studies have shown that the activation of the PI3K-AKT pathway reduces TNF-α production and suppresses inflammation [10,11]. Activation of the PI3K/AKT pathway limits JNK-mediated apoptosis by phosphorylating and inactivating ASK1 during the Enterovirus 71 (EV71) infection [12].…”

Section: Introductionmentioning

confidence: 99%

PI3K–AKT Pathway Protects Cardiomyocytes Against Hypoxia-Induced Apoptosis by MitoKATP-Mediated Mitochondrial Translocation of pAKT

Song

Chu

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The phosphatidylinositol-3-kinase -AKT (PI3K-AKT) is an important intracellular signal pathway in regulating cell proliferation, differentiation and apoptosis. In previous studies, we’ve demonstrated that PI3K–AKT pathway protects cardiomyocytes from ischemic and hypoxic apoptosis through mitochondrial function. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis via PI3K-AKT pathway remain ill-defined. Here, we addressed this question. Methods: Cardiomyocytes were exposed to hypoxia, with/without different inhibitors and then protein levels were assessed by Western blotting. Results: We found that the PI3K–AKT pathway was activated in cardiomyocytes that were exposed to hypoxia. Moreover, the phospho-AKT (pAKT) translocated from cytosol to mitochondria via mitochondrial adenosine triphosphate-dependent potassium (mitoKATP), leading to an increase in cytochrome c oxidase (CcO) activity to suppress apoptosis. On the other hand, the mitoKATP specific blocker, 5-hydroxydecanote (5-HD), or suppression of CcO using siRNA, inhibited the pAKT mitochondrial translocation to maintain the CcO activity, resulting in mitochondrial dysfunction and cellular apoptosis induced by hypoxia. Conclusion: These findings suggest that the anti-apoptotic effect of the PI3K-AKT pathway through pAKT translocation to mitochondrial via mitoKATP may be conducted through modification of CcO activity.

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Timosaponin B-II Ameliorates Palmitate-Induced Insulin Resistance and Inflammation via IRS-1/PI3K/Akt and IKK/NF-κB Pathways

Cited by 34 publications

References 41 publications

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats

Jiangtang decoction ameliorate diabetic nephropathy through the regulation of PI3K/Akt-mediated NF-κB pathways in KK-Ay mice

PI3K–AKT Pathway Protects Cardiomyocytes Against Hypoxia-Induced Apoptosis by MitoKATP-Mediated Mitochondrial Translocation of pAKT

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