Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes
The flower of Edgeworthia gardneri (Wall.) Meisn is commonly used in beverage products in Tibet and has potential health benefits for diabetes. However, the mechanisms underlying anti-insulin resistance (IR) action of the flower of E. gardneri are not fully understood. This study aims to investigate...
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01666/full |
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| author | Yi Zhang Li Shan Yan Yu Ding Brian Chi Yan Cheng Brian Chi Yan Cheng Gan Luo Jing Kong Tong Hua Liu Tong Hua Liu Shuo Feng Zhang Shuo Feng Zhang |
| author_facet | Yi Zhang Li Shan Yan Yu Ding Brian Chi Yan Cheng Brian Chi Yan Cheng Gan Luo Jing Kong Tong Hua Liu Tong Hua Liu Shuo Feng Zhang Shuo Feng Zhang |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | The flower of Edgeworthia gardneri (Wall.) Meisn is commonly used in beverage products in Tibet and has potential health benefits for diabetes. However, the mechanisms underlying anti-insulin resistance (IR) action of the flower of E. gardneri are not fully understood. This study aims to investigate the effects of the water extract of the flower of E. gardneri (WEE) on IR in palmitate (PA)-exposed HepG2 hepatocytes. WEE was characterized by UPLC analysis. PA-treated HepG2 cells were selected as the IR cell model. The cell viability was determined using MTT assay. Moreover, the glucose consumption and production were measured by glucose oxidase method. The glucose uptake and glycogen content were determined by the 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose) glucose uptake assay and anthrone-sulfuric acid assay, respectively. The intracellular triglyceride content was detected by oxidative enzymic method. Protein levels were examined by Western blotting. Nuclear localization of FoxO1 was detected using immunofluorescence analyses and Western blotting. The expression of FoxO1 target genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The viability of PA-treated HepG2 cells was concentration-dependently increased by incubation with WEE for 24 h. WEE treatment remarkably increased the consumption and uptake of glucose in PA-exposed HepG2 cells. Moreover, treatment with WEE significantly decreased the PA-induced over-production of glucose in HepG2 cells. After exposure of HepG2 cells with PA and WEE, the glycogen content was significantly elevated. The phosphorylation and total levels of IRβ, IRS1, and Akt were upregulated by WEE treatment in PA-exposed HepG2 cells. The phosphorylation of GSK3β was elevated after WEE treatment in PA-treated cells. WEE treatment also concentration-dependently downregulated the phosphorylated CREB, ERK, c-Jun, p38 and JNK in PA-exposed HepG2 cells. Furthermore, the nuclear protein level and nuclear translocation of FoxO1 were also suppressed by WEE. Additionally, PA-induced changes of FoxO1 targeted genes were also attenuated by WEE treatment. The GLUT2 and GLUT4 translocation were also promoted by WEE treatment in PA-treated HepG2 cells. Taken together, WEE has potential anti-IR effect in PA-exposed HepG2 cells; the underlying mechanism of this action may be associated with the regulation of IRS1/GSK3β/FoxO1 signaling pathway. This study provides a pharmacological basis for the application of WEE in the treatment of metabolic diseases such as type 2 diabetes mellitus. |
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| spelling | doaj.art-43499edf2a524d968f7df39785dce4d72022-12-22T00:58:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-01-011010.3389/fphar.2019.01666495926Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 HepatocytesYi Zhang0Li Shan Yan1Yu Ding2Brian Chi Yan Cheng3Brian Chi Yan Cheng4Gan Luo5Jing Kong6Tong Hua Liu7Tong Hua Liu8Shuo Feng Zhang9Shuo Feng Zhang10School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaCollege of Professional and Continuing Education, Hong Kong Polytechnic University, Hong Kong, ChinaChinese Medicine Department of Quality Healthcare Medical Services , Hong Kong, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaTibetan Medicine Department of Tibetan Traditional Medical College, Lhasa, ChinaSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, ChinaTibetan Medicine Department of Tibetan Traditional Medical College, Lhasa, ChinaThe flower of Edgeworthia gardneri (Wall.) Meisn is commonly used in beverage products in Tibet and has potential health benefits for diabetes. However, the mechanisms underlying anti-insulin resistance (IR) action of the flower of E. gardneri are not fully understood. This study aims to investigate the effects of the water extract of the flower of E. gardneri (WEE) on IR in palmitate (PA)-exposed HepG2 hepatocytes. WEE was characterized by UPLC analysis. PA-treated HepG2 cells were selected as the IR cell model. The cell viability was determined using MTT assay. Moreover, the glucose consumption and production were measured by glucose oxidase method. The glucose uptake and glycogen content were determined by the 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose) glucose uptake assay and anthrone-sulfuric acid assay, respectively. The intracellular triglyceride content was detected by oxidative enzymic method. Protein levels were examined by Western blotting. Nuclear localization of FoxO1 was detected using immunofluorescence analyses and Western blotting. The expression of FoxO1 target genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The viability of PA-treated HepG2 cells was concentration-dependently increased by incubation with WEE for 24 h. WEE treatment remarkably increased the consumption and uptake of glucose in PA-exposed HepG2 cells. Moreover, treatment with WEE significantly decreased the PA-induced over-production of glucose in HepG2 cells. After exposure of HepG2 cells with PA and WEE, the glycogen content was significantly elevated. The phosphorylation and total levels of IRβ, IRS1, and Akt were upregulated by WEE treatment in PA-exposed HepG2 cells. The phosphorylation of GSK3β was elevated after WEE treatment in PA-treated cells. WEE treatment also concentration-dependently downregulated the phosphorylated CREB, ERK, c-Jun, p38 and JNK in PA-exposed HepG2 cells. Furthermore, the nuclear protein level and nuclear translocation of FoxO1 were also suppressed by WEE. Additionally, PA-induced changes of FoxO1 targeted genes were also attenuated by WEE treatment. The GLUT2 and GLUT4 translocation were also promoted by WEE treatment in PA-treated HepG2 cells. Taken together, WEE has potential anti-IR effect in PA-exposed HepG2 cells; the underlying mechanism of this action may be associated with the regulation of IRS1/GSK3β/FoxO1 signaling pathway. This study provides a pharmacological basis for the application of WEE in the treatment of metabolic diseases such as type 2 diabetes mellitus.https://www.frontiersin.org/article/10.3389/fphar.2019.01666/fullEdgeworthia gardneriinsulin resistancepalmitateIRS1/GSK3β/FoxO1 signaling pathwayHepG2 cells |
| spellingShingle | Yi Zhang Li Shan Yan Yu Ding Brian Chi Yan Cheng Brian Chi Yan Cheng Gan Luo Jing Kong Tong Hua Liu Tong Hua Liu Shuo Feng Zhang Shuo Feng Zhang Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes Frontiers in Pharmacology Edgeworthia gardneri insulin resistance palmitate IRS1/GSK3β/FoxO1 signaling pathway HepG2 cells |
| title | Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes |
| title_full | Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes |
| title_fullStr | Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes |
| title_full_unstemmed | Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes |
| title_short | Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes |
| title_sort | edgeworthia gardneri wall meisn water extract ameliorates palmitate induced insulin resistance by regulating irs1 gsk3β foxo1 signaling pathway in human hepg2 hepatocytes |
| topic | Edgeworthia gardneri insulin resistance palmitate IRS1/GSK3β/FoxO1 signaling pathway HepG2 cells |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01666/full |
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