## 1 Introduction  
Liver inflammation is one common initiator of liver illness and is considered as the main contributor of hepatic tissue damage [1]. Consequently, inflammation leads to tissue modifications with the developing of fibrosis, cirrhosis, and finally, in many cases ending in primary liver cancer, and death [2, 3]. Worldwide, more than 1 million deaths each year are due to the chronic liver inflammation associated with fibrosis and cirrhosis [4]. Inflammation of injured hepatocytes activates immune processes in liver. Inflammatory signaling of the liver is regulated by the action of immune cells, including Kupffer cells and inflammatory cells, such as infiltrating macrophages, T lymphocytes, neutrophils, and dendritic cells [5]. Consequently, such processes initiate and maintain the hepatic inflammation through the release of cytokines, such as zinc finger e-box binding protein 2 (ZEB-2), phosphatase and tension homolog (PTEN), tumor necrosis factor (TNF-\(\alpha\)), interleukins (IL-1 and IL-6), as well as interferon gamma (IFN-\(\gamma\)) [6, 7, 8, 9, 10]. These inflammatory mediatorsactivate hepatic stellate cells (HSCs), which are the major source of the development of fibrosis in liver after interaction with HSCs via transforming growth factor (TGF-\(\beta\)) [1].  
Flavonoids are a group of natural products which are important for human health [11]. Flavonoids exhibit broad therapeutic potential in cardiovascular, gastric, and liver diseases. Furthermore, flavonoids exhibited anti-inflammatory properties through regulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and other inflammatory-related factors [12; 13; 14; 15; 16; 17; 18]. Among these flavonoids, the C-glycosated type including orientin, isoorientin, vitexin, and isovitexin are reported to possess anxiolytic, antioxidative activities [19; 20]. Orientin is one in this bioactive category isolable from many medicinal plants such as basil, bamboo, passion flower, golden queen, flax, dayflower, and lavender. Orientin exhibits a diversity of medicinal properties, which comprise anti-inflammation, antioxidant, antimicrobial, neuroprotective, vasodilation, and cardio-protective effects [19; 21]. Carbon tetrachloride (CCI\({}_{4}\)) is commonly used in industries as a solvent and in medicine as an anthelmittic. CCl\({}_{4}\) is a well-known hepatotoxic in both humans and experimental animals. Previous studies reported its wide application in scientific research including flavonoids, as a model of hepatotoxicity associated with the release of TNF-\(\alpha\) from activated hepatic macrophages [22; 23; 24]. Lipopolysaccharide (LPS) is an endotoxin made up of a polysaccharide and induces inflammation in various organs, including the liver, kidney, and brain, as well as murine macrophages and HSCs. Most of the toxicities observed in LPS-induced injury have been attributed to toxic mediators produced by activated cells, including TNF-\(\alpha\), iNOS, IL-1\(\beta\), IL-6, ZEB-2, PTEN, and other pro-inflammatory molecules [25; 26; 27; 28; 29]. However, to the best of our knowledge, there was no previous detailed information about the effects of orientin on LPS-mediated pro-inflammatory responses on HSCs, as well as its anti-inflammatory activity towards CCl\({}_{4}\)-induced liver inflammation on experimental mice. Hence, the current study was designed to assess the effect of orientin on anti-inflammatory activity and its molecular mechanisms towards a CCl\({}_{4}\)-induced in vivo model and inflamed in vitro model including an in silico docking approach.