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. 2021 Nov 26:12:775563.
doi: 10.3389/fphar.2021.775563. eCollection 2021.

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats

Zhi-Hao Zhang  1 , Juan Li  2 , Jun Li  1 , Zhaowu Ma  3 , Xian-Ju Huang  1
Affiliations

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats

Zhi-Hao Zhang et al. Front Pharmacol. .

Abstract

Type 2 diabetes mellitus (T2DM) is a complex and polygenic disorder with diverse complications. Veratrilla baillonii Franch (V. baillonii) has been applied in the intervention and treatment a diverse range of diseases, including diabetes. In this study, we revealed that water extracts of V. baillonii (WVBF) can ameliorate liver injury and insulin resistance in T2DM rat model. To elucidate the anti-diabetic mechanisms of WVBF, we performed liver transcriptome analysis that displayed WVBF treatment significantly suppressed many gene expressions involved in insulin resistance. Furthermore, functional experiments showed that WVBF treatment reduced the pathological damages of liver and pancreas, which may be regulated by Foxo1, Sirt1, G6pc, c-Met, Irs1, Akt1, Pik3r1. These results indicated that WVBF improves diabetic liver injury and insulin resistance in diabetic rats. Therefore, this study demonstrated WVBF could be used as a promising therapeutic agent for intervention and treatment of diabetes.

Keywords: Veratrilla baillonii franch; diabetes mellitus; diabetic liver injury; insulin resistance; transcriptome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Effects of WVBF treatment on weight, blood glucose and insulin resistance of diabetic rats. (A) overview of the experimental process. (B, C) The effect of WVBF on the body weight of diabetic rats. (D, E) The level of FBG from one to 6 weeks (D) and at the end of 6 weeks (E). (F, G) The levels of blood glucose (F) and areas under curves AUC (G) in oral glucose tolerance test (OGTT) at the end of 6 weeks (H–J) WVBF intervention influenced insulin sensitivity and insulin resistance in diabetic rats. HFD: high-fat diet, L-WVBF: WVBF 12.5 mg/kg, H-WVBF: WVBF 25 mg/kg, WVBF 12.5 mg/kg, NC: normal control, MC: mellitus control, PC: positive control, 12.5: WVBF 12.5 mg/kg/day, 25: 25 mg/kg/day. Date were shown as mean ± SEM; *p < 0.05, **p < 0.01 vs. NC group; #p < 0.05, ##p < 0.01, vs. MC group. B-E, n = 8 in each group; F-J, n = 6 in each group.
FIGURE 2
FIGURE 2
Effect of WVBF treatment on the hepatic and pancreatic morphology in diabetic rats (A). H&E staining of liver from different groups. Upper panel, hematoxylin and eosin, 100×; middle panel, hematoxylin and eosin, 200×; Bottom panel, hematoxylin and eosin, 400×. CV indicates central vein; Red arrow indicates edema; Yellow arrow, inflammatory cells infiltration; Black arrow head indicates hyperemia. Bottom panel, (B). H&E staining of pancreas from different groups. Red arrow, pancreatic acini; green arrow, intralobular duct of the pancreas; black arrow head, inflammatory cells. Hematoxylin and eosin, 100×. NC: normal control, MC: mellitus control, PC: positive control, 12.5: WVBF 12.5 mg/kg/day, 25: 25 mg/kg/day.
FIGURE 3
FIGURE 3
Screening and verification of differentially expressed genes in diabetic rats. (A) Venn diagram of differentially expressed genes (DEGs) in the different groups. (B) Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation signaling pathway (WVBF 25 mg/kg-treated versus MC). (C–I) The key gene (c-Met, G6pc, Foxo1, pik3r1, Sirt1, Akt1, Irs1) expression in liver tissues from different groups. NC: normal control, MC: mellitus control, PC: positive control, 12.5: WVBF 12.5 mg/kg/day, 25: 25 mg/kg/day. Date were shown as mean ± SEM; *p < 0.05, **p < 0.01 vs. NC group; #p < 0.05, ##p < 0.01, vs. MC group. n = 3 in each group.
FIGURE 4
FIGURE 4
WVBF-mediated pathways in diabetic liver injury.
See this image and copyright information in PMC

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