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. 2022 Nov 28:13:1084435.
doi: 10.3389/fphar.2022.1084435. eCollection 2022.

Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet

Meng Liang  1 , Mohan Huo  2 , Yi Guo  1 , Yuyi Zhang  1 , Xiao Xiao  1 , Jianwen Xv  1 , Lixue Fang  1 , Tianqi Li  1 , Huan Wang  1 , Siyu Dong  1 , Xiaowen Jiang  1 , Wenhui Yu  1   3   4
Affiliations

Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet

Meng Liang et al. Front Pharmacol. .

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and is a nutritional metabolic disease. Artemisia capillaris (AC) is the above-ground dried part of Artemisia capillaris Thunb. or Artemisia scoparia Waldst. et Kit., a natural medicinal plant with pharmacological effects of heat-clearing and biliary-promoting. In order to evaluate the therapeutic effect of Artemisia capillaris on NAFLD and obesity, experiments were conducted using aqueous extracts of Artemisia capillaris (WAC) to intervene in NAFLD models in vivo and in vitro. In vivo experiments were performed using HFD-fed (high fat diet) C57BL/6 mice to induce NAFLD model, and in vitro experiments were performed using oleic acid to induce HepG2 cells to construct NAFLD cell model. H.E. staining and oil red O staining of liver tissue were used to observe hepatocytes. Blood biochemistry analyzer was used to detect serum lipid levels in mice. The drug targets and mechanism of action of AC to improve NAFLD were investigated by western blotting, qRT-PCR and immunofluorescence. The results showed that C57BL/6 mice fed HFD continuously for 16 weeks met the criteria for NAFLD in terms of lipid index and hepatocyte fat accumulation. WAC was able to reverse the elevation of serum lipid levels induced by high-fat diet in mice. WAC promoted the phosphorylation levels of PI3K/AKT and AMPK in liver and HepG2 cells of NAFLD mice, inhibited SREBP-1c expression, reduced TG and lipogenesis, and decreased lipid accumulation. In summary, WAC extract activates PI3K/AKT pathway, reduces SREBP-1c protein expression by promoting AMPK phosphorylation, and decreases fatty acid synthesis and TG content in hepatocytes. AC can be used as a potential health herb to improve NAFLD and obesity.

Keywords: AMPK; NAFLD; PI3K/AKT; SREBP-1c; aqueous extracts of Artemisia capillaris; lipid metabolism.

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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
LC-MS analysis. (A) positive mode (B) negative mode. 1) 1-Caffeoylquinic acid (rt = 5.46 min), 2) Isoferulic Acid (rt = 7.008 min),3) Costunolide (rt = 12.083 min), 4) Neochlorogenic acid (rt = 4.879 min), 5) Chlorogenic Acid (rt = 5.37 min), 6) 3-O-Feruloylquinic acid (rt = 5.55 min), 7) Caffeic acid (rt = 5.801 min), 8) Isochlorogenic acid B (rt = 6.768 min), 9) 1,5-Dicaffeoylquinic acid (rt = 7.676 min), 10) Isochlorogenic acid C (rt = 7.053 min), 11) Scoparone (rt = 7.935 min).
FIGURE 2
FIGURE 2
Effect of WAC on obesity and hepatic steatosis in HFD-induced NAFLD mice. (A) Animal experimentation process. (B) Pictures of liver morphology, HE staining and oil red O staining of liver sections after 6 weeks of WAC gavage. (C) Body condition of mice in each group after 6 weeks of WAC gavage. (D) Body weight changes in mice over 22 weeks. (E) Body weight gain in mice over 22 weeks. (F) Mouse liver index. (G) Index of inguinal adipose tissue in mice. (H) Adipose tissue index of mouse epididymis. (I) The positive areas of oil-red O staining were analyzed using ImageJ. Compared with HFD, * indicates p < 0.05 and ** indicates p < 0.01.
FIGURE 3
FIGURE 3
Effect of WAC on metabolic disorders in HFD-induced NAFLD mice. (A) Serum triglyceride levels. (B) Serum cholesterol levels. (C) Serum glucose levels. (D) Serum HDL levels. (E) Serum LDL levels. (F) Liver triglyceride levels in mice. (G) Liver cholesterol levels in mice. Compared with HFD, * indicates p < 0.05 and ** indicates p < 0.01.
FIGURE 4
FIGURE 4
Effect of WAC on lipid accumulation in OA-induced HepG2 cells. (A) Cellular experimental procedures. (B) Cell viability. (C,D) Triglyceride and cholesterol levels in HepG2 cells. (E) Graph of oil red O staining results. (F) Graph of BODIPY staining results. Compared with OA, * indicates p < 0.05 and ** indicates p < 0.01.
FIGURE 5
FIGURE 5
Effect of WAC on PI3K, AKT, AMPK phosphorylation and SREBP-1c protein expression in HFD-induced NAFLD mice. (A,B) Phosphorylation and total protein levels of PI3K, AKT, and AMPK in mouse liver. (C,D) Protein levels of SREBP-1c in mouse liver. (E) The mRNA levels of mouse liver FASN, ACC, SREBP-1c and SCD-1. Compared with HFD, * indicates p < 0.05 and ** indicates p < 0.01.
FIGURE 6
FIGURE 6
Effect of WAC on OA-induced PI3K, AKT, AMPK phosphorylation and SREBP-1c protein expression in HepG2 cells. (A,B) Phosphorylation of PI3K, AKT, AMPK and total protein levels in HepG2 cells. (C,D) Protein levels of SREBP-1c in HepG2 cells. (E) Graph of SREBP-1c immunofluorescence results. (F) mRNA levels of FASN, ACC, SREBP-1c and SCD-1 in HepG2 cells. Compared with OA, * indicates p < 0.05 and ** indicates p < 0.01.
FIGURE 7
FIGURE 7
Effect of WAC on SREBP-1c in HepG2 cells. (A) Experimental procedure of cells after the addition of FATO. (B,C) Triglyceride and cholesterol levels in HepG2 cells. (D) Graph of oil red O staining results. (E) Graph of BODIPY staining results. (F) Graph of SREBP-1c immunofluorescence results. (G) SREBP-1c, SCD1, FAS, DGAT2 protein levels in HepG2 cells. Different letters represent significant differences.
FIGURE 8
FIGURE 8
Schematic diagram of the mechanism by which WAC improves NAFLD. WAC activates PI3K/AKT pathway, activates AMPK to promote SREBP-1c expression, thereby reducing hepatic TG synthesis and lipid synthesis.
See this image and copyright information in PMC

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