Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes

Cheng, Kur Ta; Wang, Yu Shiou; Chou, Hsiu Chu; Chang, Chih‐Cheng; Lee, Ching Kuo; Juan, Shu Hui

doi:10.1016/j.phymed.2015.04.001

Cited by 31 publications

(17 citation statements)

References 29 publications

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“…Our results showed that the linear dose‐effect relationship range for KD attenuating liver damage in mice was around 10‐30 mg/kg, and the linear dose‐response range for in vitro was around 2.5‐10.0 μg/mL (http://onlinelibrary.wiley.com/doi/10.1002/hep.28825/suppinfo). Other studies also reported that KD exhibited significant hepatoprotective, antihyperliposis, antihyperglycemic, and anti‐inflammatory activity in rodents with 5‐100 mg/kg in vivo or 0.1‐13.0 μg/mL in vitro . Because KD accounted for around 10% of A. roxburghii , the concentration of KD (10 mg/kg) used in our study corresponds to approximately 500 mg/day/per subject of A. roxburghii in humans, which is consistent with a report that oral A. roxburghii at 450 mg/day/per subject significantly decreased high ALT and AST levels in volunteer subjects .…”

Section: Discussionsupporting

confidence: 90%

“…Previous reports indicated that KD enhanced adipocyte lipolysis by activating adenosine monophosphate‐activated protein kinase (AMPK)‐dependent pathways in adipocytes . In order to find possible molecular targets of KD in liver disease, we performed in silico target identification by a combinational method of 2D fingerprint screen and three‐dimensional (3D) molecular docking.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies showed that KD possessed hepatoprotective activity in CCl 4 ‐treated mice or in samples of patients with liver disease, but the mechanism is not clear. Other reports indicated that KD exerted antihyperglycemic and ‐hyperliposis effects and could alleviate acute inflammation …”

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confidence: 99%

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Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells/CD8+T cells communication in mice

et al. 2016

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The central purpose of this study was to investigate therapeutic effects of the botanical derivative, kinsenoside (KD), in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and proinflammatory cytokines, in concanavalin A-induced T-cell-mediated hepatitis, and in dendritic cells (DCs) loaded with hepatocellular carcinoma cells (DC/Hepa1-6) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti-CD8 antibody blocking, CD8 1 T cell sorting, and vaccinated mice with KD-pretreated DCs in a DC/Hepa1-6 model. These results showed that KD inhibited the elevated expressions of CD86 and major histocompatibility complex II, densities of chemokine receptor C-C chemokine receptor type 7, and extensive migration to lymph nodes, and increased the programmed death ligand 1 level of DCs, followed by suppressing CD8 1 T cells, characterized as low differentiation and cytotoxicity, and eliciting cytokines balance. Furthermore, biochemical analysis, two-dimensional fingerprint screen and three-dimensional molecular docking results showed that KD bound to the vascular endothelial growth factor receptor 2 (VEGFR2) kinase domain, which inhibited the metabolism-related phosphatidylinositol 3 kinase/protein kinase B (PI3K-AKT) pathway in DCs and DC-modulated CD81 T cells to lower the mitochondrial membrane potential and glucose/lipid utilization ratio in both cells. KD reversed activation of the PI3K-AKT pathway by 740 Y-P (PI3K agonist), thereby impeding the translocation and dimerization of signal transducer and activators of transcription (STAT) 3 and synergistically blocking the inflammation-related Janus kinase (JAK) 2/STAT3 pathway in DCs and DCmodulated T cells. Conclusion: KD treatment elicits immunosuppression against autoimmune liver injury by targeting VEGFR2, followed by diminishing the cross-talk of metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 pathways, and thereby disrupts DC-induced cross-priming of CD8 1 T cell responses. (HEPATOLOGY 2016;64:2135-2150).

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells/CD8+T cells communication in mice

et al. 2016

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“…Lipid production and accumulation are important for tumor progression because these processes may produce energy for tumorigenesis and provide the building components of phospholipids to form cell membranes [ 47 ]. PGC-1, a transcriptional coactivator, is the major regulator of mitochondrial bioenergenesis associated with energy metabolism by interacting with the nuclear receptor PPAR- γ and C/EBPα [ 48 , 49 ]. PGC-1 β is pivotal to activate fatty acid β -oxidation [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrion-Directed Nanoparticles Loaded with a Natural Compound and a microRNA for Promoting Cancer Cell Death via the Modulation of Tumor Metabolism and Mitochondrial Dynamics

Lo¹,

Wang²,

Chen³

et al. 2020

Pharmaceutics

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Mitochondrial dysfunction may cause cancer and metabolic syndrome. Ellagic acid (abbreviated as E), a phytochemical, possesses anticancer activity. MicroRNA 125 (miR-125) may regulate metabolism. However, E has low aqueous solubility, and miR-125 is unstable in a biological fluid. Hence, this study aimed to develop nanoparticle formulations for the co-treatment of miR-125 and E. These nanoparticles were modified with one mitochondrion-directed peptide and a tumor-targeted ligand, and their modulating effects on mitochondrial dysfunction, antitumor efficacy, and safety in head and neck cancer (HNC) were evaluated. Results revealed that miR-125- and E-loaded nanoparticles effectively targeted cancer cells and intracellular mitochondria. The co-treatment significantly altered cellular bioenergetics, lipid, and glucose metabolism in human tongue squamous carcinoma SAS cells. This combination therapy also regulated protein expression associated with bioenergenesis and mitochondrial dynamics. These formulations also modulated multiple pathways of tumor metabolism, apoptosis, resistance, and metastasis in SAS cells. In vivo mouse experiments showed that the combined treatment of miR-125 and E nanoparticles exhibited significant hypoglycemic and hypolipidemic effects. The combinatorial therapy of E and miR-125 nanoparticles effectively reduced SAS tumor growth. To our best knowledge, this prospective study provided a basis for combining miRNA with a natural compound in nanoformulations to regulate mitochondrial dysfunction and energy metabolism associated with cancer.

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“…The phosphorylation of PPAR α and the protein level of PGC‐1 α are upregulated by an AMPK‐dependent mechanism in adipocytes (Cheng et al. ), and AMPK regulates PGC‐1 α expression and mitochondrial enzymes in eWAT (Wan et al. ).…”

Section: Discussionmentioning

confidence: 99%

Differential response of adipose tissue gene and protein expressions to 4- and 8-week administration of β -guanidinopropionic acid in mice

et al. 2018

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β‐Guanidinopropionic acid (β‐GPA) feeding inhibits growth‐associated gain of body mass. It remains unknown, however, whether and how β‐GPA feeding affects growth‐associated increase in white adipose tissue (WAT) mass. We examined the effects of 4‐ and 8‐week β‐GPA feeding on serum myostatin levels and expression of genes and proteins related to adipogenesis, lipolysis, and liposynthesis in epididymal WAT (eWAT) and brown adipose tissue (BAT) in 3‐week‐old, juvenile male mice. Body, eWAT, and muscle weights were significantly lower in β‐GPA‐fed mice than in controls after feeding. Four‐ but not 8‐week‐β‐GPA feeding increased the serum myostatin level. Incubation of C2C12 myotubes with β‐GPA (1 mM) significantly promoted myostatin mRNA expression. The protein expression of peroxisome proliferator‐activated receptor gamma coactivator 1 α (PGC‐1α) and peroxisome proliferator‐activated receptor α (PPAR α) was up‐regulated in GPAF eWAT at week 4, but down‐regulated at week 8. There was no significant difference in the protein expression of adipocyte triglyceride lipase (ATGL), hormone‐sensitive lipase (HSL), fatty acid synthase (FAS), and acetyl‐CoA carboxylase (ACC) between groups in eWAT. In BAT, no significant difference was found in the protein expression of PGC‐1α, PPAR α, ATGL, and HSL between β‐GPA‐fed and control mice, whereas that of FAS and ACC was significantly lower in β‐GPA‐fed mice at week 8. Uncoupling protein 1 was expressed higher in β‐GPA‐fed mice both at weeks 4 and 8 than that in controls. Thus, the mechanism by which β‐GPA feeding in early juvenile mice inhibits growth‐associated increase in eWAT mass may differ between early and later periods of growth.

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Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes

Cited by 31 publications

References 29 publications

Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells/CD8+T cells communication in mice

Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells/CD8+T cells communication in mice

Mitochondrion-Directed Nanoparticles Loaded with a Natural Compound and a microRNA for Promoting Cancer Cell Death via the Modulation of Tumor Metabolism and Mitochondrial Dynamics

Differential response of adipose tissue gene and protein expressions to 4- and 8-week administration of β -guanidinopropionic acid in mice

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