Four Isosteroidal Alkaloids from <italic style="font-style: italic">Fritillaria</italic> Alleviate Lipopolysaccharide-Induced Inflammation <italic style="font-style: italic">in vitro</italic> and <italic style="font-style: italic">in vivo</italic> through MyD88- and TRIF-Dependent Signaling Pathways

AGA Er-bu; PAI Ming-xin; ZHANG Meng-rui; TSE Wai Ming; TSE Kathy Wai Gaun; LUO You-fu; YE Ben-gui

doi:10.1007/s11655-025-4025-4

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Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways

Original Article | Updated：2026-02-14

- Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways
- Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways
- Chinese Journal of Integrative Medicine 2026年32卷第1期页码：54-63
- Affiliations：
  
  1.State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu (610041), China
  2.Medical College of Xizang University, Lhasa (850002), China
  3.Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu (610041), China
  4.Nin Jiom Medicine Manufactory (H.K.) Limited, Hong Kong SAR (999077), China
- Author bio：
  
  Prof. YE Ben-gui, E-mail: benguiye513@163.com
- Funds：
  
  the Major Science and Technology Research Project in the Science and Technology Projects of Xizang Axtonomoxs Region, China(XZ202301ZY0009G;XZ202201ZD0001G01/06)
- DOI：10.1007/s11655-025-4025-4
  中图分类号：
- 录用：2025-07-11，
  
  网络首发：2025-11-18，
  
  纸质出版：2026-01
- Accepted：
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AGA Er-bu, PAI Ming-xin, ZHANG Meng-rui, 等. Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways[J]. Chinese Journal of Integrative Medicine, 2026,32(1):54-63.

AGA Er-bu, PAI Ming-xin, ZHANG Meng-rui, et al. Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways[J]. Chinese Journal of Integrative Medicine, 2026, 32(1): 54-63.
AGA Er-bu, PAI Ming-xin, ZHANG Meng-rui, 等. Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways[J]. Chinese Journal of Integrative Medicine, 2026,32(1):54-63. DOI： 10.1007/s11655-025-4025-4.

AGA Er-bu, PAI Ming-xin, ZHANG Meng-rui, et al. Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways[J]. Chinese Journal of Integrative Medicine, 2026, 32(1): 54-63. DOI： 10.1007/s11655-025-4025-4.

摘要

Abstract

Objective:

To investigate the anti-inflammatory effects and mechanisms of action of 4 steroidal alkaloids (ebeiedinone

imperialine

chuanbeinone

and peimisine) in

Fritillaria

Methods:

This study established a lipopolysaccharide (LPS)-induced inflammatory model using mouse leukemia cells of monocyte macrophage (RAW 264.7) cells. The cell toxicity

nitric oxide (NO) release

expression levels of inflammatory factors

and expression levels of anti-inflammatory mechanism proteins and mRNA of ebeiedinone

imperialine

chuanbeinone

and peimisine on RAW 264.7 cells were detected by cell counting kit-8 (CCK8) assay

Griess assay

enzyme-linked immunosorbent assay

Western blot

and real-time quantitative PCR

respectively. An acute lung injury (ALI) rat model was established. Hematoxylin and eosin staining was used to observe the morphological and pathological characteristics of lung tissue in each group of rats. The expression levels of inflammatory factors and anti-inflammatory mechanism proteins and mRNA in the ALI rat model induced by the 2 alkaloids (ebeiedinone

peimisine) were detected.

Results:

The 4 alkaloids reduced the release of NO

downregulated the expression of pro-inflammatory factors

regulated the expressions of the TIR domain-containing adapter protein inducing interferon-beta (TRIF)

myeloid differentiation factor 88 (MyD88)

nuclear factor kappa-B (NF-κB)

and mitogen-activated protein kinases (MAPKs) signaling pathways in LPS-induced RAW 264.7 cells

exerting an anti-inflammatory effect (

0.05 or

0.01). Ebeiedinone and peomisine improved pulmonary edema and inflammation levels

regulated the expressions of MyD88

NF-κB

and MAPKs signaling pathways in the ALI rat model

exerting anti-inflammatory effects (

0.05 or

0.01).

Conclusion:

The 4 alkaloids of

Fritillaria

exert anti-inflammatory effects

in vivo

and

in vitro

through MyD88- and TRIF-dependent signaling pathways

thereby protecting rats from ALI.

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Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways

Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo through MyD88- and TRIF-Dependent Signaling Pathways

DOI：10.1007/s11655-025-4025-4

摘要

Abstract

关键词

Keywords

references