Synergistic mechanism of Curcuma phaeocaulis genuine regional materia medica from Sichuan Province processing with vinegar to invade liver via "gut-liver axis"
Objective Based on "gut-liver axis" theory,the regulatory effects of raw and vinegar-processed Curcuma phaeocaulis on liver and intestine were studied from the perspectives of "liver protective effect" and "intestinal barrier effect",in order to study the processing synergistic mechanism of vinegar-processed C. phaeocaulis leading into liver. Method Kunming mice were randomly divided into the control group,model group,positive group (0.06 g/kg),high-dose,medium-dose and low-dose groups (3,2,1 g/kg) of raw and vinegar-processed C. phaeocaulis decoction,with 10 mice in each group. Each group was administered intragastrically once a day for four consecutive days (10 mL/kg). One hour after administration on the 4th day,except for the control group,all groups were intraperitoneally injected with thioacetamide (TAA) at a dose of 100 mg/kg to establish the liver injury model. The liver wet weight and liver index of mice were detected. The levels of aspartate aminotransferase (AST),alanine aminotransferase (ALT),superoxide dismutase (SOD),malondialdehyde (MDA),lipopolysaccharide (LPS) and the contents of tumor necrosis factor-α (TNF-α),interleukin-6(IL-6),IL-1β,IL-10,IL-17A and secretory immunoglobulin A (sIgA) were detected by biochemical kits. The morphology of liver and ileum tissues was observed by hematoxylin-eosin (HE) staining. The expressions of zonula occludens proteins-1 (ZO-1) and occludin in ileum tissues were detected by immunohistochemistry. 16S rDNA gene sequencing was used to analyze the changes of intestinal flora in mice. The expressions of Toll-like receptor4 (TLR4),myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B-p65 (NF-κB-p65) proteins were detected by Western blotting. Results After treatment with C. phaeocaulis,the liver inflammatory cell infiltration and swelling of liver cells were improved,and the liver index,ALT,AST and MDA were significantly decreased (P<0.05,0.001) while SOD was significantly increased (P<0.001) after treatment with vinegar-processed C. phaeocaulis. After treatment with C. phaeocaulis,the changes of ileum villus atrophy and tight junction gap widening of epithelial cells were alleviated in mice with liver injury,and the expression of occludin (P<0.05) was significantly increased after treatment with vinegar-processed C. phaeocaulis. 16S rDNA sequencing analysis showed that vinegar-processed C. phaeocaulis could significantly reverse the increase of Firmicutes abundance (P<0.05),the decrease of Bacteroidetes abundance (P<0.05) and the increase of Firmicutes/Bacteroidetes ratio (P<0.05) caused by liver injury. The levels of IL-17A and sIgA were increased (P<0.01,0.001),and the levels of TNF-α,IL-1β and IL-6 were decreased (P<0.05). The expression of key proteins MyD88,NF-κB-p65 and TLR4 (P<0.05) in the TLR4/MyD88/NF-κB pathway were inhibited to varying degrees in all drug administration groups. In vinegar-processed C. phaeocaulis groups,the levels of IL-10 were increased (P<0.05),the LPS levels were significantly decreased (P<0.01),and the TLR4 protein expression was significantly inhibited (P<0.05). Conclusion The vinegar-processing C. phaeocaulis can play a better role in liver protection. It can regulate the three intestinal barriers by inhibiting the key pathway TLR4/MyD88/NF-κB of "gut-liver axis",so as to play the synergistic effect of vinegar-processing C. phaeocaulis leading into liver to alleviate liver injury based on "gut-liver axis".
Curcuma phaeocaulis Val.processing with vinegar to invade livergut-liver axisTLR4/MyD88/NF-κB signal pathwayintestinal barrierhepatoprotective effectsbisdemethoxycurcumingermacrone
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