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. 2018 Dec 11;9:1399. doi: 10.3389/fphar.2018.01399

Figure 8.

Figure 8

Protection on intestinal barrier function contributes to the therapeutic effects of GC combination on NASH. Overgrowth of the Gram-negative bacteria leads to increased content of LPS in the intestine and gut barrier dysfunction. LPS activates RhoA/ROCK signaling which induces activation of MLC2 via direct phosphorylation or phosphorylation of MYPT. The increased phosphorylation of MLC2 leads to the rearrangement of TJ proteins and increase of TJ permeability. The gut-derived LPS go into liver via portal circulation and activate KCs to produce inflammatory factors participating in the onset of NASH. GC combination was found to restore the TJs protein expression and down-regulate RhoA/ROCK signaling while ameliorated NASH. GC, Geniposide and chlorogenic acid combination, IL-1β, interleukin-1β, LBP, lipopolysaccharide binding protein, LPS, lipopolysaccharide, MLC, myosin light chain, MYPT, myosin phosphatase target subunit, NASH, non-alcoholic steatohepatitis, ROCK, Rho-associated kinase, TNF, tumor necrosis factor, TLR, Toll-like receptor, TJ, tight junction.