Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade
Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223010703 |
| _version_ | 1797744071749402624 |
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| author | Yuhui He Huan Wang Shiling Lin Tao Chen Dennis Chang Yibin Sun Chenxiang Wang Yang Liu Yusheng Lu Jianyuan Song Shaohua Li Wen Xu Yanxiang Lin Yanfang Zheng Xian Zhou Qiumei Huang Mingqing Huang |
| author_facet | Yuhui He Huan Wang Shiling Lin Tao Chen Dennis Chang Yibin Sun Chenxiang Wang Yang Liu Yusheng Lu Jianyuan Song Shaohua Li Wen Xu Yanxiang Lin Yanfang Zheng Xian Zhou Qiumei Huang Mingqing Huang |
| author_sort | Yuhui He |
| collection | DOAJ |
| description | Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated individually, their combined use and the potential for a synergistic or augmented effect remain unexplored. This study aims to investigate the effect of curcumin (Cur) and resveratrol (Res) as a potential combination therapy on MAFLD. Cur, Res and Cur+Res were tested in palmitic acid (PA)-induced-HepG2 cells. MAFLD model was established using Goto-Kakizaki rats. The animals were treated with vehicle control (model group), Cur (150 mg/kg), Res (150 mg/kg), Cur+Res (150 mg/kg, 8:2, w/w), or metformin (Met, positive control, 400 mg/kg/day) via oral gavage for 4 weeks. Wistar rats were used as the control group. Network pharmacology was conducted to elucidate the molecular actions of Cur and Res, followed by q-PCR and immunoblotting in vivo. Cur+Res exhibited synergistic effects in reducing triglyceride, total cholesterol and lipid accumulation in PA-induced HepG2 cells. The combination also markedly attenuated hepatic steatosis in the MAFLD rats. Network pharmacology illustrated that the interaction of Cur and Res was associated with the modulation of multiple molecular targets associated with the PI3K/AKT/mTOR and HIF-1 signaling pathways. Experimental results confirmed that Cur+Res nomalised the gene targets and protein expressions in the PI3K/AKT/mTOR and HIF-1 signaling pathways, including PI3K, mTOR, STAT-3, HIF-1α, and VEGF. The present study demonstrated an advanced effect of Cur and Res in combination to attenuate MAFLD, and the mechanism is at least partly associated with the modulation of the PI3K/AKT/mTOR and HIF-1 signaling pathways. |
| first_indexed | 2024-03-12T15:04:29Z |
| format | Article |
| id | doaj.art-8511884e3ac54c9494dd01b23bb7b763 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-12T15:04:29Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-8511884e3ac54c9494dd01b23bb7b7632023-08-13T04:53:17ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-09-01165115279Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascadeYuhui He0Huan Wang1Shiling Lin2Tao Chen3Dennis Chang4Yibin Sun5Chenxiang Wang6Yang Liu7Yusheng Lu8Jianyuan Song9Shaohua Li10Wen Xu11Yanxiang Lin12Yanfang Zheng13Xian Zhou14Qiumei Huang15Mingqing Huang16College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaNICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, AustraliaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaNICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, AustraliaFujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou 350108, ChinaDepartment of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, ChinaCollege of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, China; Correspondance to: College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou 350100, China.NICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, Australia; Correspondence to: NICM Health Research Institute, Western Sydney University, 158 Hawkesbury Rd, Westmead NSW 2145, Australia.Guangdong Food and Drug Vocational College, Guangzhou 510520, China; Corresponding author.College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou 350100, China; Correspondence to: NICM Health Research Institute, Western Sydney University, 158 Hawkesbury Rd, Westmead NSW 2145, Australia.Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease that has no viable treatment. Curcumin (Cur) and resveratrol (Res) are two natural products that have been studied for their potential to ameliorate MAFLD. However, while these compounds have been investigated individually, their combined use and the potential for a synergistic or augmented effect remain unexplored. This study aims to investigate the effect of curcumin (Cur) and resveratrol (Res) as a potential combination therapy on MAFLD. Cur, Res and Cur+Res were tested in palmitic acid (PA)-induced-HepG2 cells. MAFLD model was established using Goto-Kakizaki rats. The animals were treated with vehicle control (model group), Cur (150 mg/kg), Res (150 mg/kg), Cur+Res (150 mg/kg, 8:2, w/w), or metformin (Met, positive control, 400 mg/kg/day) via oral gavage for 4 weeks. Wistar rats were used as the control group. Network pharmacology was conducted to elucidate the molecular actions of Cur and Res, followed by q-PCR and immunoblotting in vivo. Cur+Res exhibited synergistic effects in reducing triglyceride, total cholesterol and lipid accumulation in PA-induced HepG2 cells. The combination also markedly attenuated hepatic steatosis in the MAFLD rats. Network pharmacology illustrated that the interaction of Cur and Res was associated with the modulation of multiple molecular targets associated with the PI3K/AKT/mTOR and HIF-1 signaling pathways. Experimental results confirmed that Cur+Res nomalised the gene targets and protein expressions in the PI3K/AKT/mTOR and HIF-1 signaling pathways, including PI3K, mTOR, STAT-3, HIF-1α, and VEGF. The present study demonstrated an advanced effect of Cur and Res in combination to attenuate MAFLD, and the mechanism is at least partly associated with the modulation of the PI3K/AKT/mTOR and HIF-1 signaling pathways.http://www.sciencedirect.com/science/article/pii/S0753332223010703CurcuminResveratrolMetabolism-related fatty liver diseaseHepatic steatosisSynergyPI3K/AKT/mTOR |
| spellingShingle | Yuhui He Huan Wang Shiling Lin Tao Chen Dennis Chang Yibin Sun Chenxiang Wang Yang Liu Yusheng Lu Jianyuan Song Shaohua Li Wen Xu Yanxiang Lin Yanfang Zheng Xian Zhou Qiumei Huang Mingqing Huang Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade Biomedicine & Pharmacotherapy Curcumin Resveratrol Metabolism-related fatty liver disease Hepatic steatosis Synergy PI3K/AKT/mTOR |
| title | Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade |
| title_full | Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade |
| title_fullStr | Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade |
| title_full_unstemmed | Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade |
| title_short | Advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the PI3K/AKT/mTOR and HIF-1/VEGF cascade |
| title_sort | advanced effect of curcumin and resveratrol on mitigating hepatic steatosis in metabolic associated fatty liver disease via the pi3k akt mtor and hif 1 vegf cascade |
| topic | Curcumin Resveratrol Metabolism-related fatty liver disease Hepatic steatosis Synergy PI3K/AKT/mTOR |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223010703 |
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