I-Ta Lee1, Chwan-Fwu Lin2, Yu-Ling Huang3, Kowit-Yu Chong4, Ming-Fa Hsieh5, Tse-Hung Huang6, Ching-Yi Cheng7. 1. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. 2. Department of Cosmetic Science, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan. 3. Department of Cosmetic Science, Chang Gung University of Science and Technology, Taoyuan, Taiwan; National Research Institute of Chinese Medicine, Taipei, Taiwan. 4. Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. 5. Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan, Taiwan. 6. Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan. 7. Research Center for Food and Cosmetic Safety, and Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan; Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Ophthalmology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. Electronic address: Jennycheng@mail.cgust.edu.tw.
Abstract
INTRODUCTION: Resveratrol has been reported to alleviate inflammatory responses and oxidative stress in mesangial cells and in several types of renal injury in animal models. Previously, the active resveratrol derivatives from the roots of Vitis thunbergii Sieb. & Zucc. (Vitaceae) were shown to have significant anti-platelet and anti-oxidative activities. However, the anti-inflammatory mechanisms of these resveratrol derivatives in rat mesangial cells (RMCs) have not been clarified fully. METHODS: The protective mechanisms of resveratrol derivatives involved in tumor necrosis factor-α (TNF-α)-induced inflammatory responses were assessed by Western blot analysis, real-time PCR, and RT-PCR. The involvement of various signaling molecules in these responses was investigated using selective pharmacological inhibitors. RESULTS: Nontoxic concentrations of the resveratrol derivatives significantly attenuated cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2) expression in RMCs challenged by TNF-α. These resveratrol derivatives inhibited TNF-α-activated ERK1/2 and JNK1/2 without affecting p38 phosphorylation. Next, we demonstrated that TNF-α induced NF-κB activation, translocation, and promoter activity, which was inhibited by pretreatment with resveratrol derivatives in RMCs. CONCLUSION: The protective mechanisms of resveratrol derivatives against TNF-α-stimulated inflammatory responses via cPLA2/COX-2/PGE2 inhibition was caused by the attenuation of the JNK1/2, ERK1/2, and NF-κB signaling pathways in RMCs.
INTRODUCTION:Resveratrol has been reported to alleviate inflammatory responses and oxidative stress in mesangial cells and in several types of renal injury in animal models. Previously, the active resveratrol derivatives from the roots of Vitis thunbergii Sieb. & Zucc. (Vitaceae) were shown to have significant anti-platelet and anti-oxidative activities. However, the anti-inflammatory mechanisms of these resveratrol derivatives in rat mesangial cells (RMCs) have not been clarified fully. METHODS: The protective mechanisms of resveratrol derivatives involved in tumor necrosis factor-α (TNF-α)-induced inflammatory responses were assessed by Western blot analysis, real-time PCR, and RT-PCR. The involvement of various signaling molecules in these responses was investigated using selective pharmacological inhibitors. RESULTS: Nontoxic concentrations of the resveratrol derivatives significantly attenuated cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2) expression in RMCs challenged by TNF-α. These resveratrol derivatives inhibited TNF-α-activated ERK1/2 and JNK1/2 without affecting p38 phosphorylation. Next, we demonstrated that TNF-α induced NF-κB activation, translocation, and promoter activity, which was inhibited by pretreatment with resveratrol derivatives in RMCs. CONCLUSION: The protective mechanisms of resveratrol derivatives against TNF-α-stimulated inflammatory responses via cPLA2/COX-2/PGE2 inhibition was caused by the attenuation of the JNK1/2, ERK1/2, and NF-κB signaling pathways in RMCs.
Authors: Mona M Ahmed; Mohamed M A Hussein; Taisir Saber; Yasmina M Abd-Elhakim Journal: Int J Environ Res Public Health Date: 2022-07-04 Impact factor: 4.614