Kaempferol attenuated largemouth bass virus caused inflammation via inhibiting NF-κB and ERK-MAPK signaling pathways

Largemouth bass virus (LMBV) has caused significant economic losses in the largemouth bass (Micropterus salmoides) industry due to its unclear pathophysiology and lack of accessible treatment. In this investigation, we aimed to explore the corresponding molecular mechanisms for LMBV-caused inflammation and the anti-inflammatory effects of kaempferol both in vitro and in vivo. We demonstrated that LMBV infection caused a severe inflammatory response by up-regulating the levels of pro-inflammatory cytokines including interleukin-1β (il1β), il8, tumor necrosis factor alpha (tnfα), interferon gamma (ifng), and cyclooxygenase-2 (cox2) both in fish and in FHM cells. Further, LMBV-induced inflammation involved the NF-κB and ERK-MAPK signaling pathways since the inflammatory response could be blocked by specific inhibitors of NF-κB (PDTC) and ERK (U0126), respectively. Additionally, pretreatment with kaempferol dramatically decreased cell death and suppressed LMBV replication in FHM cells, with 50 % effective concentration (EC₅₀) values of 10.89 μM. It is noteworthy that feeding largemouth bass with 50 mg/kg of kaempferol enhanced their survival rate from LMBV infection by 53.33 %. By mechanically blocking NF-κB (p65) nuclear translocation and ERK phosphorylation, kaempferol reduced the expression of pro-inflammatory cytokines (il1β, il8, il10, tnfα, ifng, and cox2). According to these results, kaempferol and other bioactive elements of herbal plants may be able to regulate the inflammatory response and control LMBV in the aquaculture industry.