Nowadays, the incidence of liver injury remains high. To date, approximately 300 million people worldwide are infected with the hepatitis B virus and 170 million with the hepatitis C virus, as well as many other liver-like diseases, mostly caused by alcohol, chemical toxins, drugs, and metabolic diseases (Wang et al., 2014; Zhou et al., 2022). Currently, the most frequently prescribed liver-protective medications in clinical practice, such as adefovir dipivoxil tablets and entecavir tablets, are successful in treating hepatitis, but they work on a single target, and some of them even have severe side effects like nausea, fatigue, headache and nephrotoxicity (Tao et al., 2020; Fontana R. J., 2009; Chen et al., 2014). Traditional Chinese Medicine (TCM) has a long history of practice as a complementary and alternative medicine for a variety of diseases. According to TCM, the main pathogenesis of liver injury is “dampness and heat fighting each other, Qi deficiency, dampness obstruction, and blood stasis”. Modern pharmacological investigations have demonstrated that the appropriate use of drugs that improve blood circulation, enhance blood flow, and dilate blood vessels has a protective effect on the liver (Zhang et al., 2018; Zhao et al., 2014). However, there are relatively few studies on liver protection with herbs that activate blood circulation and resolve blood ischemia.

L. chuanxiong is derived from the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae), which is warm and enters the liver meridians. It is a blood circulation activator and blood stasis resolver, and it is also commonly used to regulate Qi and relieve pain, and it is effective in chest pain caused by liver Qi stagnation, as well as trauma caused by blood stasis and liver-blood stagnation (Xu et al., 2021; Chen et al., 2018). Modern pharmacological studies have shown that L. chuanxiong is sedative, analgesic, antispasmodic, and antibacterial, increases renal blood flow, inhibits lipid peroxidation, and inhibits pulmonary fibrosis. Recent studies have found that L. chuanxiong can inhibit hepatic lipid deposition, improve lipid profiles, and have a protective effect on liver and vascular damage in the ovariectomy-induced menopausal rat. The mechanism may be related to the active antioxidants in L. chuanxiong increasing the levels of hepatic antioxidant enzymes and the upregulation of endothelial nitric oxide synthase mRNA expression by chemical components that promote vasodilation (Li et al., 2013). The Chinese herbal intravenous injection Xuebijing (XBJ; China Food and Drug Administration Patent No.: Z20040033), consisting of Ligusticum chuanxiong (Chuanxiong), Paeonia lactiflora (Chishao), Carthamus tinctorius (Honghua), Angelica sinensis (Danggui), and Salvia miltiorrhiza (Danshen), inhibits the production of pro-inflammatory factors, elevates the level of anti-inflammatory factors by promoting the expression of glycogen synthase kinase-3β (GSK-3β), thereby inhibiting the expression of nuclear factor kappa-B (NF-κB) and activating the cAMP-response element-binding protein signaling pathway, which may be the mechanism of the protective effect of XBJ on lipopolysaccharide-induced acute liver injury model of RAW264.7 cells (Cao et al., 2021). The drug pair Chuanxiong-Angelicae significantly reduced the hepatic inflammatory response, bile acid accumulation, and collagen deposition induced by CCl4-induced liver fibrosis model by modulating the extracellular signal-regulated kinase 1/2 -protein kinase B signaling pathway, providing a new idea on the pharmacological mechanism of preventing and ameliorating the development of liver fibrosis (Jian-Zhi et al., 2021). However, so far, the effective material basis and mechanism of chemotherapy alone for liver protection are still vague.

This study first predicted the material basis and mechanism of action (active ingredient integration site) of L. chuanxiong to alleviate liver injury utilizing network pharmacology technique and found that its active site was concentrated inorganic acid. It then isolated and extracted each major active site and qualitatively analyzed the active site components using LC-MS with GC-MS. In the end, the mechanism of effect was verified by investigating molecular docking to study the action of the main active ingredients with the core targets, and the material basis was verified by investigating the protective effect of the active parts of the correlation on the acute liver injury model induced by CCl4 in mice.