Protective Effect of the Total Alkaloid Extract from Bulbus Fritillariae pallidiflorae in a Mouse Model of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Int J Chron Obstruct Pulmon Dis. 2024 Jun 10:19:1273-1289. doi: 10.2147/COPD.S459166. eCollection 2024.

Abstract

Purpose: In recent years, the incidence of chronic obstructive pulmonary disease (COPD) has been increasing year by year, but therapeutic drugs has no breakthrough. The total alkaloid extract from Bulbus Fritillariae pallidiflorae (BFP-TA) is widely used in treating lung diseases. Therefore, this study aimed to investigate the protective effect and mechanism of BFP-TA in COPD mice.

Methods: BFP-TA was prepared by macroporous adsorbent resin, and the material basis of BFP-TA was analyzed by HPLC-ELSD and UHPLC-MS/MS. Then, the COPD mouse model was induced by cigarette smoke (CS) for 12 weeks, administered at weeks 9-12. Subsequently, the body weight, lung-body ratio, pulmonary function, histopathology, and the levels of pro-inflammatory cytokines, matrix metalloproteinases (MMPs) and oxidative stress markers in the serum of mice were determined. The expressions of related protein of EMT and MAPK signaling pathways in the lung tissues of mice were detected by Western blot.

Results: The alkaloid relative content of BFP-TA is 64.28%, and nine alkaloids in BFP-TA were identified and quantified by UHPLC-MS/MS. Subsequently, the animal experiment showed that BFP-TA could improve pulmonary function, and alleviate inflammatory cell infiltration, pulmonary emphysema, and collagen fiber deposition in the lung of COPD mice. Furthermore, BFP-TA could decrease the levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), MMPs (MMP-9 and MMP-12) and MDA, while increase the levels of TIMP-1 and SOD. Moreover, BFP-TA could decrease the protein expressions of collagen I, vimentin, α-SMA, MMP-9, MMP-9/TIMP-1, Bax, p-JNK/JNK, p-P38/P38, and p-ERK/ERK, while increase the level of E-cadherin.

Conclusion: This study is the first to demonstrate the protective effect of BFP-TA in CS-induced COPD mouse model. Furthermore, BFP-TA may improve airway remodeling by inhibiting the EMT process and potentially exert anti-inflammatory effect by inhibiting the MAPK signaling pathway.

Keywords: Bulbus Fritillariae pallidiflorae; COPD; EMT; MAPK; total alkaloid.

MeSH terms

  • Airway Remodeling / drug effects
  • Alkaloids* / pharmacology
  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Cigarette Smoking / adverse effects
  • Cytokines* / metabolism
  • Disease Models, Animal*
  • Epithelial-Mesenchymal Transition / drug effects
  • Fritillaria* / chemistry
  • Inflammation Mediators / metabolism
  • Lung* / drug effects
  • Lung* / metabolism
  • Lung* / pathology
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress* / drug effects
  • Plant Extracts* / pharmacology
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / etiology
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • Pulmonary Disease, Chronic Obstructive* / prevention & control
  • Signal Transduction / drug effects
  • Smoke / adverse effects

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Plant Extracts
  • Cytokines
  • Smoke
  • Inflammation Mediators
  • Antioxidants

Grants and funding

This research was supported by the major science and technology research project in 2021 from Tibet Science and Technology Department (NO. XZ202101ZD0021G), the science and technology major project of Tibetan Autonomous Region of China (NO. XZ202201ZD0001G01, NO. XZ202201ZD0001G06), the Funds for local scientific and technological development guided by the central government in 2023 from Tibet Science and Technology Department (NO. XZ202301YD0014C), the Major science and technology research project in 2023 from Tibet Science and Technology Department (NO. XZ202301ZY0009G), the Key support projects of the central government for local transfer payment funds (inheritance and development of traditional Chinese medicine) in the Xizang Autonomous Region in 2023 (NO. 2023-XZ-ZYYJ-01-LH).