Figure 9.

Schematic models of molecular targets affected by ISE to attenuate inflammatory signaling pathways. On the one hand, LPS- and free fatty acid (FFA)-induced inflammatory responses are regulated by both NF-κB and MAPK signaling pathways. In activated macrophages, ISE decreases pro-inflammatory cytokine production via inhibiting the ERK and p38 MAPK pathways, not NF-κB signals. On the other hand, ISE markedly suppresses the phosphorylation of STAT3 to reduce cytokines transcription. Subsequently, the lipolysis of adipocytes is suppressed and proinflammatory M1 macrophages are less recruited via the MCP-1-CCR2 pathway. And the decrease of inflammatory cytokine IL-6 further restrains the IL-6/STAT3 activation and the inflammatory mediator production. In a word, treatment with ISE reduces the levels of these pro-inflammatory mediators, thereby disrupting the crosstalk between macrophages and adipocytes in a coculture. ISE apparently exerted anti-inflammatory ability, possibly diminishing the obesity-induced inflammatory diseases.