Total Flavonoids of <italic style="font-style: italic">Litchi chinensis</italic> Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis

TANG Yan; WANG Ting; FENG Min-chao; GONG Jun-wen; TANG Mei-wen; CHEN Guo-zhong; SI Ma-ling; FENG Jian-fang; LUO Wei-sheng

doi:10.1007/s11655-025-3839-4

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Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis

Original Article | Updated：2026-08-04

- Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis
- Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis
- 中国结合医学杂志（英文版） 2026年32卷第8期页码：709-719
- Affiliations：
  
  1.Department of Gastroenterology, the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning ( 530023), China
  2.The Graduate School, Guangxi University of Traditional Chinese Medicine, Nanning ( 530200), China
  3.The Second Clinical School, Guangzhou University of Chinese Medicine, Guangzhou ( 510405), China
  4.Xiangxing College, Hunan University of Traditional Chinese Medicine, Changsha ( 411105), China
  5.School of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning ( 530200), China
- Author bio：
  
  Prof. LUO Wei-sheng, E-mail: 4011188@qq.com
- Funds：
  
  the National Natural Science Foundation of China(82160834;81660779);Doctoral Research Initiation Fund Project of Guangxi University of Traditional Chinese Medicine(2023BS034)
- DOI：10.1007/s11655-025-3839-4
  中图分类号：
- 录用：2025-04-17，
  
  网络首发：2025-12-09，
  
  纸质出版：2026-08
- Accepted：
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TANG Yan, WANG Ting, FENG Min-chao, 等. Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis[J]. 中国结合医学杂志（英文版）, 2026,32(8):709-719. DOI: 10.1007/s11655-025-3839-4.

TANG Yan, WANG Ting, FENG Min-chao, et al. Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis[J]. Chinese Journal of Integrative Medicine, 2026, 32(8): 709-719. DOI: 10.1007/s11655-025-3839-4.
TANG Yan, WANG Ting, FENG Min-chao, 等. Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis[J]. 中国结合医学杂志（英文版）, 2026,32(8):709-719. DOI: 10.1007/s11655-025-3839-4. DOI：

TANG Yan, WANG Ting, FENG Min-chao, et al. Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis[J]. Chinese Journal of Integrative Medicine, 2026, 32(8): 709-719. DOI: 10.1007/s11655-025-3839-4. DOI：

摘要

Abstract

Objective:

To investigate the therapeutic benefits and possible mechanism of total flavonoids of

Litchi chinensis

Sonn. seed (TFLS) on hepatic fibrosis (HF)

in vivo

and

in vitro

Methods:

A carbon tetrachloride (CCl

)-induced rat HF model and transforming growth factor β1 (TGF-β1)-stimulated hepatic stellate cell (HSC)-T6 cells were employed. For

in vivo

study

rats were randomly divided into 6 groups using a random number table method

including vehicle

CCl

silybin (50 mg/kg)

and low-

medium-

high-dose (25

and 100 mg/kg) TFLS treatment groups. TFLS or silybin was administered daily by gavage for 8 weeks during CCl

induction period. For

in vitro

study

HSC-T6 cells were divided into 4 groups

including control

TGF-β1 (20 ng/mL)

TGF-β1 + Z-DNA binding protein 1 (ZBP1) siRNA (si-ZBP1)

TGF-β1 + low-dose (80 μg/mL) TFLS

and TGF-β1 + high-dose (160 μg/mL) TFLS groups. Serum levels of alanine transaminase (ALT)

aspartate aminotransferase (AST)

hydroxyproline (HYP)

total bile acid (TBA)

interleukin (IL)-1β

IL-18

IL-6

and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay. Hematoxylin-eosin and Masson's trichrome staining were employed to conduct a histological examination of the liver tissue. Apoptosis was assessed by TUNEL. Cysteine-aspartic acid protease (CASP)-8

NLR family pyrin domain containing 3 (NLRP3)

gasdermin D (GSDMD)

and receptor-interacting protein kinase (RIPK) 3 were immunohistochemically detected. CASP-8

NLRP3

GSDMD

CASP-3

BCL-2

BCL-2-associated X (BAX)

ZBP1

IPK1

and RIPK3 mRNA levels were measured by quantitative real-time polymerase chain reaction. PANoptosis-related proteins were detected by Western blot.

Results:

In CCl

-induced HF rats

TFLS improved liver function

inflammatory response

and liver tissue fibrosis (

0.05 or

0.01). TFLs inhibited the activation of PANoptosis initiator ZBP1

which subsequently regulated PANoptosis by increasing BAX

CASP-3

CASP-8 and decreasing BCL-2

NLRP3

GSDMD

CASP-1

RIPK1

RIPK3

and mixed lineage kinase domain-like expressions (

0.05 or

0.01).

In vitro

TFLS inhibited TGF-β1-induced HSC-T6 cells activation and PANoptosis (

0.05 or

0.01).

Conclusion:

TFLS might ameliorate HF by targeting ZBP1 to suppress PANoptosis

highlighting its multi-modal regulation of apoptosis

pyroptosis

and necroptosis.

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Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis

Total Flavonoids of Litchi chinensis Sonn. Seed Improves Hepatic Fibrosis by Inhibiting PANoptosis

DOI：10.1007/s11655-025-3839-4

摘要

Abstract

关键词

Keywords

references