GEO chip analysis combined with network pharmacology to explore the mechanism of Schisandra chinensis Goji berry in protecting against radiation-induced liver injury
Radiation induced liver injury (RILI) is a type of liver damage caused by radiation therapy or nuclear leakage, which results in a decrease in liver function, an increase in liver enzymes, and other damage to the liver after exposure to a certain amount of radiation. Under light microscopy, the early pathological manifestations of liver tissue mainly include congestion in the central region of the liver lobules, hepatocyte edema, and inflammatory reactions. In the late stage, it gradually develops into liver fibrosis and cirrhosis, which are irreversible. The main pathogenesis includes microvascular and connective tissue damage, excessive free radicals, excessive autoimmune response, and cytokine influence.

Schisandra Chinensis Fructus (SCF) refers to Schisandra chinensis, which has a warm nature and has been found to have good liver protection effects. Its mechanism of action is mainly through antioxidant and anti-inflammatory methods. Lycium barbarum (LF) has a neutral nature and pharmacological effects that have been shown to nourish the liver and kidneys. The combination of the two can effectively protect against liver damage. This article uses GEO chip analysis, network pharmacology, and molecular docking technology to predict the potential active ingredients, targets, and mechanisms of action of Schisandra chinensis combined with Goji berries in protecting RILI, providing reference for further in-depth research and clinical applications.

Radiation induced liver injury refers to the exposure of the liver to a certain dose of radiation during the process of radiation therapy or nuclear leakage in cancer patients. Early manifestations include edema of liver cells in the central lobules of the liver, accompanied by peripheral inflammatory reactions and affecting liver function. Later, it is prone to develop into liver fibrosis or cirrhosis. In recent years, there has been an increasing amount of research on the radiation protection of traditional Chinese medicine against liver damage. Traditional Chinese medicine has great potential due to its safety, convenience for oral administration, rapid absorption, and low cost.
Schisandra chinensis has excellent hepatoprotective effects. Research has found that Schisandra contains over 200 chemical components, mainly including volatile terpenes, lignans, organic acids, and polysaccharides, which have anti-inflammatory, antioxidant, immune enhancing, and substance metabolism regulating properties. Wang’s research found that crude Schisandra chinensis improved the treatment and prevention of acute alcoholic fatty liver by reducing inflammatory factors, reducing fat accumulation, lowering CYP2E1 expression, and enhancing Nrf2/ARE signaling pathways to protect against liver damage. Zhu’s in vitro research found that Schisandra polysaccharides can effectively scavenge hydroxyl radicals, 1,1-diphenyl-2-trinitrophenylhydrazine, and superoxide ions; In vivo experiments have found that Schisandra polysaccharides can alleviate liver damage caused by CCL4 induced hepatocyte vesicular degeneration and inflammatory response. Yang’s research found that Schisandra lignans have a protective effect against liver injury caused by acetaminophen, mainly by regulating the expression of EGFR and LPCAT1 related proteins in the ERBB signaling pathway, exerting anti-inflammatory and antioxidant effects. Chen et al. found that Schisandra chinensis lignans can reduce the activity of AST and ALT in serum, lower inflammatory factors such as IL-6 and IL1 β, and exhibit strong anti-inflammatory effects, thereby protecting against liver damage. Chen et al. found that polysaccharides from Schisandra chinensis can reduce the Bcl-2/Bax ratio and decrease the activation of CASP3, thereby reducing liver cell apoptosis.
Goji berry has the effects of nourishing essence, improving vision, nourishing liver and kidneys, etc. It is rich in polysaccharides, volatile oils, alkaloids, flavonoids and other components. Modern pharmacological research has shown that it can improve immunity, antioxidant, liver protection, and protect the retina. Tian’s research found that Lycium barbarum polysaccharides can prevent the reduction of protein thiols and the inactivation of SOD, and have good antioxidant effects on the membrane damage of mouse liver mitochondrial cells caused by free radicals generated by gamma radiation. The combination of goji berries and schisandra improves the efficacy of liver protection. Zhang’s research found that Lycium barbarum polysaccharides have a protective effect on radiation-induced small intestine damage, providing a reduction in oxidative reactions and an increase in the Bcl-2/Bax ratio to inhibit cell apoptosis. Gao et al. found that administering goji berry polyphenols to rats with liver injury can enhance their oxidative function, and the mechanism may play a role in reducing liver injury by increasing the expression of Nrf2 and its downstream proteins.
The core proteins identified through PPI network analysis include CASP3, EGFR, and ESR1. Caspases (CASP) play a crucial role in regulating cell apoptosis and trigger cascade reactions in response to pro apoptotic signals. CASP3 is a major executive protein in CASP, and apoptosis occurs in any cell. It can regulate the dynamic balance of cell growth and death through physical, chemical, and other molecular mechanisms. Cao et al. found that Schisandrin B has an inhibitory effect on radiation-induced apoptosis in Hacat cells, and its mechanism exerts a protective effect by reducing the expression of apoptotic genes such as CASP3, P53, and P21. Duan’s research found that goji berry water has antioxidant effects on irradiated mice, exerting a protective effect by reducing the expression of CASP3 and CASP6. CASP3 is involved in the apoptosis process of radiation-induced liver injury, by regulating the CASP3 protein through the active ingredients in Schisandra chinensis Goji berries, thereby inhibiting cell apoptosis and maintaining a dynamic balance between growth and death. The epidermal growth factor receptor (EGFR) is a member of the epidermal growth factor receptor family, widely distributed on the surface of epithelial cells, fibroblasts, and glial cells, and plays an important role in the growth, proliferation, and differentiation of cells. Li et al. found that Schisandrin A can inhibit liver cell apoptosis and promote liver cell regeneration after liver resection surgery by increasing the gene expression of EGFR and reducing the expression of apoptosis genes P53 and P21. Zhang’s research found that Lycium barbarum polysaccharides can regulate the expression of EGFR and phosphorylated protein levels to improve endothelial function damage caused by oxidative stress, and its mechanism of action may be through the PI3K Akt signaling pathway. The active ingredients in Schisandra chinensis goji berry may regulate the imbalance of cell numbers caused by apoptosis by acting on EGFR, leading the body towards a normal physiological level. Estrogen receptor 1 (ER1) is located on the nucleus of the cell and consists of important structural domains for hormone binding, DNA binding, and transcriptional activation. Zeng’s study found that the water extract of goji berries can regulate mRNA expression in PC12 cells, not only upregulating ESR1 but also downregulating CASP3 expression, providing a certain reference for goji berry targets. Liu et al. have shown that ESR1 can inhibit ionizing radiation induced iron death in breast cancer cells through the NEDD4L/CD71 signal pathway. When ESR1 is overexpressed, it can improve the survival rate of breast cancer patients. After ESR1 is knocked out, it enhances ionizing radiation mediated iron death. ESR1 may be a potential target to protect RILI.
This study predicted the mechanism of Schisandra chinensis Goji berry in protecting RILI through network pharmacology, and constructed a network diagram of active ingredients key protein targets of the drug. The results showed that the node degree values of quercetin, genistein, and deoxypurpurin were relatively high, suggesting that these active ingredients play an important role in protecting RILI. Through GO function enrichment and KEGG pathway analysis of 66 potential protein targets, it is speculated that the active components of Schisandra chinensis Wolfberry may play a role in protecting RILI by regulating chemical carcinogenesis receptor activation, lipid and arterial atherosclerosis, PI3K-Akt, MAPK, apoptosis and other signal pathways. This article integrates and predicts data. Due to the limited sample size, with the continuous deepening of research, it is believed that predictive analysis will bring more extensive and accurate results.
Using GEO chip analysis, network pharmacology, and molecular docking technology, a comprehensive and multi-dimensional study was conducted on Schisandra chinensis Goji berry, and the mechanism of Schisandra chinensis Goji berry in protecting against radiation-induced liver injury was preliminarily predicted. The effective substance basis of schisandra chinensis wolfberry for protecting against radiation liver injury predicted by the active ingredient gene target radiation liver injury network may be quercetin, daidzein and deoxysshikonin, which play a role in protecting radiation liver injury by regulating chemical carcinogenesis receptor activation, lipid and arterial atherosclerosis, PI3K-Akt, MAPK, apoptosis and other signal pathways through acting on the key targets CASP3, EFGR, ESR1, indicating that schisandra chinensis wolfberry plays a role in protecting radiation liver injury through “multi-component”, “multi target” and “multi pathway”, which can provide a certain reference basis for later research on the mechanism of action and clinical application.