Anti-Hepatofibrotic Effect of Xiao-Chaihu-Tang (Sho-Saiko-To)
Sheng-Li Pan in Bupleurum Species, 2006
Hepatic fibrosis is often associated with inflammation and cell death, which accompanies the repair processes, and is a consequence of severe liver damage that occurs in many patients with chronic liver disease, including chronic HCV infection. The main origin of the abnormal ECM proteins is a cell known as the hepatic stellate cell (HSC) (also known as the fat-storing cell, lipocyte, or the Ito cell). HSCs are located in the space of Disse in close contact with hepatocytes and sinusoidal endothelial cells. Their three-dimensional structure consists of the cell body and several long and branching cytoplasmic processes (Wake, 1999) (Figure 14.2). It is now evident that HSCs undergo proliferation and transformation under inflammatory and peroxidative stimuli into myofibroblast-like cells, which serve as the origin of much of the collagen hypersecretion and nodule formation that occurs during hepatic fibrosis and cirrhosis (Shimizu, 2001).
Advances in Nanonutraceuticals: Indian Scenario
Harishkumar Madhyastha, Durgesh Nandini Chauhan in Nanopharmaceuticals in Regenerative Medicine, 2022
Persistent inflammation, following liver damage, often results in the formation of fibrous tissue. Therefore, often, any medication which is given to reduce the inflammation ideally has an anti-fibrotic effect. The sequence of steps, which lead to fibrosis are outlined as oxidative stress caused by the generation of ROS followed by scar formation, leading to a reduced inflammatory response. This inflammation causes the crippling of hepatic stellate cell (HSC) activation causing fibrogenesis as seen in cirrhosis of the liver. In this context, it can be said, that certain natural compounds or Unani preparations which are identified as antioxidants, can be given as a therapy to reduce the ROS and in a way to prevent fibrosis of hepatic tissue. The effectiveness of this treatment depends upon the agility of the antioxidant reaching the target site i.e., liver (Kawada et al. 1998).
Fatty Liver Disease
David Heber, Zhaoping Li in Primary Care Nutrition, 2017
In hepatitis and cirrhosis, abnormal hepatic gene expression of methyl donor metabolism, specifically in methionine and glutathione metabolism, occurs and often contributes to decreased hepatic S-adenosylmethionine (SAM), cysteine, and glutathione levels (Lee et al. 2004). Rodent and primate studies demonstrate that SAM depletion occurs in the early stages of fatty liver infiltration, and decreased SAM concentration, liver injury, and mitochondrial damage can be reversed with SAM supplementation (Lieber 2002). SAM appears to attenuate oxidative stress and hepatic stellate cell activation in an ethanol-LPS-induced fibrotic rat model (Karaa et al. 2008). Clinical trial evidence is lacking.
Diagnostic accuracy and prognostic significance of osteopontin in liver cirrhosis and hepatocellular carcinoma: a Meta-analysis
Published in Biomarkers, 2022
Yingshi Zhang, Jiayue Gao, Yu Bao, Yang Liu, Yimeng Tong, Shuqing Jin, Qingchun Zhao
In summary, our research is the first to show that OPN was significant not only in HCC but also in LC. OPN plays an important role in cancer development by leading to cell migration in the ECM and is considered to cause tumour progression by affecting the receptors of different integrins and CD44 (Wesson et al.2003). Many studies have reported that increased OPN release is effective for determining the prognosis of HCC by analysing the phosphoinositide 3-kinase (PI3K)/AKT pathway (Yu et al.2018), activator of colony stimulating factor-1 (CSF1) and the CSF1 receptor (CSF1R), and the expansion of tumour-associated macrophages (Zhu et al.2019). Czepukojc B’s research revealed hepatic stellate cell activation, ECM deposition, and induction of the LPC markers Spp1, Cdh1, and AFP, suggesting the occurrence of dedifferentiated cells in transgenic livers (Czepukojc et al.2019). OPN explains the positive correlation between liver Notch activity and fibrosis stage in LC patients (Zhu et al.2018). The above evidence indicates that the combination of AFP and SPP1 may result in better diagnostic efficiency, which is similar to our results. In addition, the protein regulator of cytokinesis 1 aggravated LC by regulating Wnt/β-catenin (DKK1 as a marker)-mediated OPN expression, providing a mechanism for the diagnostic value of the three markers combined (OPN + AFP + DKK1).
Effects of lacto-ovo-vegetarian diet vs. standard-weight-loss diet on obese and overweight adults with non-alcoholic fatty liver disease: a randomised clinical trial
Published in Archives of Physiology and Biochemistry, 2023
Nazila Garousi, Babak Tamizifar, Makan Pourmasoumi, Awat Feizi, Gholamreza Askari, Cain C. T. Clark, Mohammad Hasan Entezari
The role of higher energy intake on NAFLD risks has been well-documented (Wehmeyer et al. 2016). However, the relationship between NAFLD and diet is complicated and is not solely limited to energy intake. Several studies have shown that NAFLD patients have higher carbohydrate intake, in comparison to healthy controls (Cortez-Pinto et al. 2006, Volynets et al. 2012). In addition, results have indicated that protein intake in NAFLD patients is higher than in healthy participants (Cortez-Pinto et al. 2006, Volynets et al. 2012, Wehmeyer et al. 2016). Diet with higher vegetables and fruits content provides lower energy density and can act as an essential factor in weight management. However, the role of vegetables and fruits is not limited to their associations with lower energy density. They also contain polyphenols and carotenoids, which can improve metabolic homeostasis, act as anti-inflammatory factors, and suppress hepatic stellate cell activation (Salomone et al. 2016).
Paeonol alleviates CCl4-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling
Published in Immunopharmacology and Immunotoxicology, 2019
Shengwang Wu, Laicheng Liu, Sen Yang, Ge Kuang, Xinru Yin, Yuanyuan Wang, Fangzhi Xu, Lingyi Xiong, Meixia Zhang, Jingyuan Wan, Xia Gong
TGF-β is highly expressed in patients with liver fibrosis, the expression of which is up-regulated as the condition worsens. For this reason, TGF-β is qualified to reflect inflammation, necrosis of liver tissue and severe liver fibrosis [28]. TGF-β is the most critical cytokine that promotes liver fibrosis and the inhibition of TGF-β signaling pathway could protect the liver against fibrosis [29]. The main reason is that it triggers the HSCs to induce the increasing synthesis of collagen [30]. The type I collagen can also lead to the secretion of TGF-β by a positive feedback mechanism [31]. Thus, TGF-β plays a crucial role in the progression of liver fibrosis by affecting hepatic stellate cell activation, collagen deposition, and extracellular matrix remodeling [32]. TGF-β stimulates, activates, and promotes the proliferation and differentiation of HSCs through the phosphorylation of a downstream signaling molecule Smad3, which is an important signal molecule to regulate the function of HSCs [33]. In short, the activation of TGF-β/Smad3 signaling pathway accelerates the progression of liver fibrogenesis [34,35]. By virtue of it, we hypothesized that the TGF-β/Smad3 signaling pathway involved the protection of paeonol against liver fibrosis and then we measured the mRNA and protein of TGF-β, as well as the expression of p-Smad3 by immunoblotting. The results showed that CCl4-induced the expression of TGF-β mRNA and protein and activation of p-Smad3 were markedly all decreased in the paeonol treatment group, indicating that paeonol suppressed the activation of HSCs by inhibiting TGF-β/Smad3 signaling pathway.
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