Network pharmacology-based analysis on geniposide, a component of gardenia jasminoides, beneficial effects to alleviate LPS-induced immune stress in piglets

•Network pharmacology to investigate the effects of geniposide on changes in inflammatory pathways and cytokine levels in lymphocytes of inflammation-stressed piglets.•In the inflammatory pathways of immune stress in weaned piglets were explored from the perspective of lymphocyte assay, and the mechanism of Geniposide's action on the body's immune system was clarified.•Immune stress were established by using LPS-induced method, and the regulatory mechanism of Geniposide on the activation of NF-κB/IAP signaling pathway in piglets induced by LPS. Geniposide is the main medicinal component of Gardenia jasminoides, and its content is approximately 3–8% depending on its origin. Geniposide is a class of cyclic enol ether terpene glucoside compounds with strong antioxidant, free radical quenching and cancer-inhibiting activities. Many studies have reported that geniposide has hepatoprotective, cholestatic, neuroprotective, blood sugar and blood lipid regulation, soft tissue damage treatment, antithrombotic, antitumor and other effects. As a traditional Chinese medicine, gardenia, whether used as gardenia alone, as the monomer geniposide or as the effective part of cyclic either terpenoids, has been reported to have anti-inflammatory effects when used in the right amounts. Recent studies have found that geniposide has important roles in pharmacological activities such as anti-inflammation activity, inhibition of the NF-κB/IκB pathway, and cell adhesion molecule production. In this study, we predicted the anti-inflammatory and antioxidant effects of geniposide in piglets through network pharmacology based on the LPS-induced inflammatory response-regulated signaling pathway. The effects of geniposide on changes in inflammatory pathways and cytokine levels in the lymphocytes of inflammation-stressed piglets were investigated using in vivo and in vitro models of piglet lipopolysaccharide-induced oxidative stress. Network pharmacology identified 23 target genes, of which the main pathways of action were lipid and atherosclerosis, fluid shear stress and atherosclerosis, and Yersinia infection. The main relevant target genes were VEGFA, ROCK2, NOS3, and CCL2. Validation experiments showed that the interventional effects of geniposide reduced the relative expression of NF-κB pathway proteins and genes, restored the expression of COX-2 genes to normal levels, and increased the relative expression of tight junction proteins and genes in IPEC-J2 cells. This indicates that th