Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway
Type 2 diabetes mellitus (T2DM) is a multisystem and complex metabolic disorder which is associated with insulin resistance and impairments of pancreatic β-cells. Previous studies have shown that icariside II (ICS II), one of the main active ingredients of <i>Herba Epimedii</i>, exerts p...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/9/1705 |
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| author | Yiqi Li Yeli Li Nana Chen Linying Feng Jianmei Gao Nan Zeng Zhixu He Qihai Gong |
| author_facet | Yiqi Li Yeli Li Nana Chen Linying Feng Jianmei Gao Nan Zeng Zhixu He Qihai Gong |
| author_sort | Yiqi Li |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is a multisystem and complex metabolic disorder which is associated with insulin resistance and impairments of pancreatic β-cells. Previous studies have shown that icariside II (ICS II), one of the main active ingredients of <i>Herba Epimedii</i>, exerts potent anti-inflammatory and anti-oxidative properties. In this study, we investigated whether ICS II exerted anti-T2DM profile and further explored its possible underlying mechanism both in vivo and in vitro. db/db mice were administered ICS II (10, 20, 40 mg·kg<sup>−1</sup>) for 7 weeks. We found that ICS II dose-dependently attenuated hyperglycemia and dyslipidemia, as well as inhibited hepatic steatosis and islet architecture damage in db/db mice. Moreover, ICS II not only dramatically reduced inflammatory cytokines and oxidative stress, but also up-regulated PPARα/γ protein expressions, phosphorylation of Akt, GSK3β and IR, meanwhile, down-regulated phosphorylation of NF-κB(p65) and IRS1 in db/db mice. In palmitic acid (PA)-treated HepG2 or MIN6 cells, ICS II (5−20 μM) concentration-dependently promoted the cell viability via mediating PPARα/γ/NF-κB signaling pathway. PPARα/γ knockout by CRISPR-Cas9 system partly abolished the protective effects of ICS II on HepG2 or MIN6 cells following PA insults. These findings reveal that ICS II effectively confer anti-T2DM property by targeting PPARα/γ through mediation of ROS/NF-κB/IRS1 signaling pathway. |
| first_indexed | 2024-03-10T00:53:59Z |
| format | Article |
| id | doaj.art-92201fb833e445cb8144d5bea4e95792 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T00:53:59Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-92201fb833e445cb8144d5bea4e957922023-11-23T14:47:33ZengMDPI AGAntioxidants2076-39212022-08-01119170510.3390/antiox11091705Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling PathwayYiqi Li0Yeli Li1Nana Chen2Linying Feng3Jianmei Gao4Nan Zeng5Zhixu He6Qihai Gong7School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi 563000, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi 563000, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaThe Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi 563000, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaType 2 diabetes mellitus (T2DM) is a multisystem and complex metabolic disorder which is associated with insulin resistance and impairments of pancreatic β-cells. Previous studies have shown that icariside II (ICS II), one of the main active ingredients of <i>Herba Epimedii</i>, exerts potent anti-inflammatory and anti-oxidative properties. In this study, we investigated whether ICS II exerted anti-T2DM profile and further explored its possible underlying mechanism both in vivo and in vitro. db/db mice were administered ICS II (10, 20, 40 mg·kg<sup>−1</sup>) for 7 weeks. We found that ICS II dose-dependently attenuated hyperglycemia and dyslipidemia, as well as inhibited hepatic steatosis and islet architecture damage in db/db mice. Moreover, ICS II not only dramatically reduced inflammatory cytokines and oxidative stress, but also up-regulated PPARα/γ protein expressions, phosphorylation of Akt, GSK3β and IR, meanwhile, down-regulated phosphorylation of NF-κB(p65) and IRS1 in db/db mice. In palmitic acid (PA)-treated HepG2 or MIN6 cells, ICS II (5−20 μM) concentration-dependently promoted the cell viability via mediating PPARα/γ/NF-κB signaling pathway. PPARα/γ knockout by CRISPR-Cas9 system partly abolished the protective effects of ICS II on HepG2 or MIN6 cells following PA insults. These findings reveal that ICS II effectively confer anti-T2DM property by targeting PPARα/γ through mediation of ROS/NF-κB/IRS1 signaling pathway.https://www.mdpi.com/2076-3921/11/9/1705Icariside IIType 2 diabetes mellitusperoxisome proliferator-activated receptors α and γoxidative stressinflammation |
| spellingShingle | Yiqi Li Yeli Li Nana Chen Linying Feng Jianmei Gao Nan Zeng Zhixu He Qihai Gong Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway Antioxidants Icariside II Type 2 diabetes mellitus peroxisome proliferator-activated receptors α and γ oxidative stress inflammation |
| title | Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway |
| title_full | Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway |
| title_fullStr | Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway |
| title_full_unstemmed | Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway |
| title_short | Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway |
| title_sort | icariside ii exerts anti type 2 diabetic effect by targeting pparα γ involvement of ros nf κb irs1 signaling pathway |
| topic | Icariside II Type 2 diabetes mellitus peroxisome proliferator-activated receptors α and γ oxidative stress inflammation |
| url | https://www.mdpi.com/2076-3921/11/9/1705 |
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