Forsythiae Fructuse water extract attenuates liver fibrosis via TLR4/MyD88/NF-kappa B and TGF-beta/smads signaling pathways
JOURNAL OF ETHNOPHARMACOLOGY
Authors: Hu, Naihua; Guo, Chaocheng; Dai, Xuyang; Wang, Cheng; Gong, Lihong; Yu, Lingyuan; Peng, Cheng; Li, Yunxia
Abstract
Ethnopharmacological relevance: Forsythiae Fructuse water extract (FSE) is a water-soluble component extracted from the traditional Chinese medicine Forsythiae Fructuse (The fruit of Forsythia suspensa (Thunb.) Vahl) usually used to treat inflammatory diseases. However, little is known about the therapeutic effect of FSE on liver fibrosis. Aim of the study: The purpose of our study was to investigate the therapeutic effect of FSE on liver fibrosis and reveal the underlying mechanism. Materials and methods: Liver fibrosis model was established by subcutaneous injection of olive oil containing 40% CCl4. Rat liver tissue morphologic pathology was investigated by using HE staining, Masson staining and Sirius red staining. Several biochemical markers including liver (ALT, AST, AKP, gamma-GT), fibrosis (HA, LN, PC III, Col IV) and inflammation (IL-6, IL-1 beta, TNF-alpha) were determined by using Elisa kits. Immunohistochemistry was used to observe the distribution of alpha-SMA and COL1 in liver tissue. Effects of FSE on inflammatory pathway (TLR4/MyD88/NF-kappa B) and fibrotic pathway (TGF-beta/smads) were detected by western blot and qPCR. Results: The results showed that hepatic histopathological injury, abnormal liver function, fibrosis and inflammation induced by CCl4 were improved by FSE (2.5, 5 g/kg). Immunohistochemistry and western blot results indicated that the expression of alpha-SMA and COL1 in liver tissue was inhibited by FSE (2.5, 5 g/kg). Western blot and qPCR results further proved that FSE (2.5, 5 g/kg) inhibited the transduction of TLR4/MyD88/NF-kappa B and TGF-beta/smads signaling pathways. Conclusion: FSE can inhibit the expression of inflammatory factors and fibrotic cytokines, reduce liver injury, and inhibit the development of liver fibrosis through TLR4/MyD88/NF-kappa B and TGF-beta/smads signaling pathways.
Long-term exercise from adolescence to adulthood reduces anxiety- and depression-like behaviors following maternal immune activation in offspring
PHYSIOLOGY & BEHAVIOR
Authors: Rahimi, Samira; Peeri, Maghsoud; Azarbayjani, Mohammad Ali; Anoosheh, Leila; Ghasemzadeh, Elham; Khalifeh, Niloofar; Noroozi-Mahyari, Safoora; Deravi, Salome; Saffari-Anaraki, Shadi; Zangeneh, Fatemeh Hemat; Salari, Ali-Akbar
Abstract
Maternal immune activation is an environmental risk factor for the development of neuropsychiatric disorders such as anxiety and depression later in life. There is an urgent need to develop therapeutic strategies for treating or preventing psychiatric disorders with developmental origins. There is important information that physical exercise is a therapeutic strategy for treating anxiety and depression-related disorders. This study set out to determine the long-term effects of exercise on anxiety and depression-like behaviors following maternal immune activation in adult offspring. Pregnant mice were treated with lipopolysaccharides (LPS) or vehicle. Then offspring were subjected to a combination of different exercise protocols including voluntary running wheel, swimming, and treadmill exercises from adolescence to adulthood. Anxiety and depression-related symptoms in adult offspring were evaluated using open field, elevated plus maze, sucrose preference test, and forced swim test. The hypothalamic-pituitary-adrenal (HPA) axis reactivity was assessed by measuring corticosterone in serum. We also measured oxytocin, malondialdehyde, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, and IL-10 in the brain of adult offspring. Our findings indicated that long-term exercise significantly decreased anxiety- and depression-like behaviors in offspring prenatally exposed to maternal immune activation. The exercise also decreased corticosterone levels in the serum, and increased oxytocin and IL-10 levels in the brain of these offspring; whereas no significant alterations in TNF-alpha, IL-1 beta, IL-6 were found. Taken together, this study suggests that exercise might be a therapeutic strategy for the treatment of anxiety and depression-related behaviors following maternal immune activation in offspring.