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. 2025 Jun 30;26(13):6324.
doi: 10.3390/ijms26136324.

Investigating Protective Effect of Suspension of Paeoniflorin in Combination with Curcumin Against Acute Liver Injury Based on Inhibition of TLR4/NF-κB/NLRP3 Inflammatory Pathway

Zhengkun Wu  1 , Yinquan Zhao  1 , Yang Wang  1 , Haohuan Li  1 , Funeng Xu  1 , Wei Zhang  1 , Hualin Fu  1 , Lizi Yin  1 , Felix Kwame Amevor  1 , Juchun Lin  1 , Danqin Li  2 , Gang Shu  1
Affiliations

Investigating Protective Effect of Suspension of Paeoniflorin in Combination with Curcumin Against Acute Liver Injury Based on Inhibition of TLR4/NF-κB/NLRP3 Inflammatory Pathway

Zhengkun Wu et al. Int J Mol Sci. .

Abstract

The objective of this study was to formulate a compound suspension comprising paeoniflorin and curcumin, assess its quality characteristics, and investigate its protective efficacy against acute liver injury in mice. The prescriptions were screened using a single-factor test, and nine groups of suspensions were prepared using the dispersion method. Fifty KM mice (four weeks old) were selected and randomly divided into five groups: the CON, LD, PF, CUR, and PC groups. The doses of both paeoniflorin and curcumin were 100 mg/kg BW, and different suspensions were given to different groups by gavage for 14 days. All the groups except the CON group were injected intraperitoneally with 20 μg/kg LPS and 700 mg/kg D-GalN on the last day. According to the results, the suspension prepared using the optimal prescriptions was orange-yellow in color, with homogeneous turbidity and good re-dispersibility. The combination treatment could reduce the severity of pathological injuries of liver, improve the ultrastructure of hepatocytes, increase the activities of T-SOD, GSH-Px, and CAT, decrease the levels of IFN-γ, TNF-α, and IL-1, and down-regulate the expression of genes such as TLR4, MyD88, IκBα, and NLRP3. The underlying mechanism might be associated with the enhancement of antioxidant enzyme activities, inhibition of the TLR4/NF-κB/NLRP3 signaling pathway, and suppression of inflammasome assembly and release in hepatic tissues.

Keywords: TLR4/NF-κB/NLRP3; acute liver injury; curcumin; paeoniflorin; suspension.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Weights and organ indexes. (A) Average weight; (B) heart index; (C) liver index; (D) spleen index; (E) lung index; (F) kidney index. Data are presented as means ± SD. ** p < 0.01 vs. CON group; ## p < 0.01 vs. LD group. CON: control group; LD: LPS/D-GalN (model) group; PF: paeoniflorin; CUR: curcumin; PC: paeoniflorin combined with curcumin.
Figure 1
Figure 1
Weights and organ indexes. (A) Average weight; (B) heart index; (C) liver index; (D) spleen index; (E) lung index; (F) kidney index. Data are presented as means ± SD. ** p < 0.01 vs. CON group; ## p < 0.01 vs. LD group. CON: control group; LD: LPS/D-GalN (model) group; PF: paeoniflorin; CUR: curcumin; PC: paeoniflorin combined with curcumin.
Figure 2
Figure 2
Liver morphology histopathological observation. Left magnification: 200 μm; right magnification: 100 μm. (A,B) CON group liver; (C,D) LD group liver; (E,F) PF group liver; (G,H) CUR group liver; (I,J) PC group liver. HL: hepatic lobule; HS: hepatic sinusoid; HC: hepatic cell; ICI: inflammatory cell infiltration; RBC: red blood cell.
Figure 3
Figure 3
Liver ultrastructure observation. Left magnification: 2 μm; right magnification: 500 nm. (A,B) CON group liver; (C,D) LD group liver; (E,F) PC group liver. CRN: cell nuclei; ACRN: apoptotic cell nuclei; MC: mitochondria; SMC: swollen mitochondria; WMC: wrinkled mitochondria.
Figure 3
Figure 3
Liver ultrastructure observation. Left magnification: 2 μm; right magnification: 500 nm. (A,B) CON group liver; (C,D) LD group liver; (E,F) PC group liver. CRN: cell nuclei; ACRN: apoptotic cell nuclei; MC: mitochondria; SMC: swollen mitochondria; WMC: wrinkled mitochondria.
Figure 4
Figure 4
Biochemical indicator testing. (A) Serum ALT/AST; (B) liver T-SOD; (C) liver GSH-Px; (D) liver CAT; (E) liver MDA. * p < 0.05 vs. CON group; ** p < 0.01 vs. CON group; # p < 0.05 vs. LD group; ## p < 0.01 vs. LD group; ++ p < 0.01 vs. PC group.
Figure 4
Figure 4
Biochemical indicator testing. (A) Serum ALT/AST; (B) liver T-SOD; (C) liver GSH-Px; (D) liver CAT; (E) liver MDA. * p < 0.05 vs. CON group; ** p < 0.01 vs. CON group; # p < 0.05 vs. LD group; ## p < 0.01 vs. LD group; ++ p < 0.01 vs. PC group.
Figure 5
Figure 5
Serum ELISA testing. (A) ET; (B) IFN-γ; (C) TNF-α; (D) IL-1; (E) IL-2; (F) IgM; (G) IgG. ** p < 0.01 vs. CON group; ## p < 0.01 vs. LD group; ++ p < 0.01 vs. PC group.
Figure 6
Figure 6
Liver—relative gene expression. (A) TLR4; (B) MyD88; (C) NF-κB; (D) IκBα; (E) TNF-α; (F) IL-1β; (G) IL-6; (H) NLRP3; (I) ASC. ** p < 0.01 vs. CON group; ## p < 0.01 vs. LD group.
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