Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease <italic style="font-style: italic">in vivo</italic> and <italic style="font-style: italic">in vitro</italic> via IRE1α/XBP1s Signaling Pathway

ZHENG An-ni; LIN Meng-yu; ZHENG Ji-xian; XU Qiu-ling; LIU Tao

doi:10.1007/s11655-025-3836-7

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Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway

Original Article | Updated：2026-02-14

- Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway
- Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway
- Chinese Journal of Integrative Medicine 2026年32卷第3期页码：232-240
- Affiliations：
  
  1.Department of Traditional Chinese Medicine, the First Affiliated Hospital of Hainan Medical University, Haikou (571199), China
  2.College of Traditional Chinese Medicine, Hainan Medical University, Haikou (571199), China
- Author bio：
  
  Prof. LIU Tao, E-mail: hy0204026@hainmc.edu.cn
- Funds：
  
  the Youth Qi Huang Scholar Project of State Administration of Traditional Chinese Medicine([2022] 256);the Natural Science Foundation of Hainan Province(821RC579);the National Natural Science Foundation of China(81760795)
- DOI：10.1007/s11655-025-3836-7
  中图分类号：
- 录用：2025-03-31，
  
  网络首发：2026-01-07，
  
  纸质出版：2026-03
- Accepted：
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ZHENG An-ni, LIN Meng-yu, ZHENG Ji-xian, 等. Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2026,32(3):232-240.

ZHENG An-ni, LIN Meng-yu, ZHENG Ji-xian, et al. Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2026, 32(3): 232-240.
ZHENG An-ni, LIN Meng-yu, ZHENG Ji-xian, 等. Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2026,32(3):232-240. DOI： 10.1007/s11655-025-3836-7.

ZHENG An-ni, LIN Meng-yu, ZHENG Ji-xian, et al. Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway[J]. Chinese Journal of Integrative Medicine, 2026, 32(3): 232-240. DOI： 10.1007/s11655-025-3836-7.

摘要

Abstract

Objective:

To investigate therapeutic effects of Huanglian Jiedu Decoction (HLJDD) on metabolic-associated fatty liver disease (MAFLD) and explore its underlying mechanisms.

Methods:

Q-Orbitrap liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the incoming blood compounds of HLJDD.

In vivo

high-fat diet (HFD)-induced MAFLD rats received HLJDD (5.4

2.7

1.35 g/kg) or silybin (37.8 mg/kg) once daily for 6 weeks. The rats fed with normal diets were served as control. Serum lipids were biochemically determined; and hepatic steatosis and lipid accumulation were evaluated with H

E and Oil red O stainings.

In vitro

palmitic acid (PA)-treated HepG2 cells were co-incubated with 10% HLJDD drug-containing serum. Intracellular triglyceride (TG)

total cholesterol (TC) and nonesterified fatty acids (NEFA) levels were detected and lipid droplet changes in HepG2 cells were observed by Oil red O staining. RT-qPCR and Western blot were employed to assess the expressions of lipid metabolic-related genes [diacylglycerol acyltransferase 2 (DGAT2)

stearoyl-coenzyme A desaturase 1 (SCD1)

]

and components of the inositol-requiring enzyme 1alpha/X-box-binding protein-1 spliced (IRE1α/XBP1s) signaling pathway.

Results:

A total of 43 active compounds of HLJDD were identified. In HFD-fed rats

HLJDD treatment significantly improved hepatic TG and TC and increased

HDL-C level (

0.05 or

0.01)

and also markedly reduced serum levels of TG

LDL-C

ALT

and AST (

0.05 or

0.01). H

E and Oil red O stainings further revealed that HLJDD effectively alleviated hepatic steatosis and attenuated lipid accumulation in the liver tissues. In PA-treated HepG2 cells

HLJDD treatment significantly reduced intracellular levels of TG

and NEFA (

0.05 or

0.01)

as well as lipid accumulation. More importantly

HLJDD treatment exerted therapeutic effects in both HFD-fed rats and PA-induced HepG2 cells by down-regulating lipid metabolic-related genes DGAT2

SCD1 and suppressing the IRE1α/XBP1s pathway related protein expressions (

0.05 or

0.01).

Conclusion:

HLJDD ameliorates MAFLD by modulating lipid metabolism through IRE1α/XBP1s signaling pathway

providing pharmacological evidence for its clinical application.

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Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway

Huanglian Jiedu Decoction Alleviates Metabolic-Associated Fatty Liver Disease in vivo and in vitro via IRE1α/XBP1s Signaling Pathway

DOI：10.1007/s11655-025-3836-7

摘要

Abstract

关键词

Keywords

references