Material Basis of Entada phaseoloides Against Neuropathic Pain Based on in vitro Chemical Profiling and in vivo Absorbed Constituents
10.13422/j.cnki.syfjx.20252343
- VernacularTitle:基于体外化学成分-体内移行成分探究榼藤子治疗神经病理性疼痛的物质基础
- Author:
Sensen LI
1
;
Hanxue WU
1
;
Yuanbin LI
2
;
Limin ZHAO
1
;
Xiaohui SU
1
;
Hui XIONG
3
;
Weihua MA
4
;
Chao WANG
1
;
Zhaochen MA
1
;
Na LIN
1
Author Information
1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China
2. Dongzhimen Hospital， Beijing University of Chinese Medicine， Beijing 100700， China
3. School of Pharmaceutical Sciences， South-Central Minzu University， Wuhan 430074， China
4. Tengzhou Traditional Chinese Medical Hospital， Tengzhou 277500， China
- Publication Type:Journal Article
- Keywords:
Entada phaseoloides;
neuropathic pain;
ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS）;
component identification;
network pharmacology
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(18):88-97
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo systematically characterize the in vitro chemical constituents of Entada phaseoloides and its absorbed prototype compounds and metabolites in a neuropathic pain （NP） model， thereby elucidating the potential pharmacological material basis underlying its analgesic activity. MethodsUltra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to analyze the constituents of the 80% methanol extract of E. phaseoloides. Thirty-six mice were divided into a blank group， low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg-1， respectively）， an aspirin group （400 mg·kg-1）， and a morphine group （10 mg·kg-1）， with six mice in each group. The tail-flick threshold was measured. Twenty-four mice were randomly divided into a blank group and low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg-1， respectively）， with six mice in each group， and motor coordination was evaluated. A spinal nerve ligation （SNL） model was established in mice. Twenty-four mice were randomly divided into a sham-operated （Sham） group， an SNL group， an SNL + E. phaseoloides extract group （750 mg·kg-1）， and an SNL + pregabalin group （20 mg·kg-1）， with 6 mice in each group. Mechanical allodynia and thermal hyperalgesia were evaluated. Behavioral assessments were combined to determine the optimal onset time of the analgesic effect， and plasma samples were collected at this time point. Absorbed components and metabolites were systematically identified based on accurate mass， MS/MS fragmentation patterns， retention time， and comparisons with literature data and reference standards. Meanwhile， network pharmacology， target similarity analysis， and molecular docking validation were integrated to evaluate the potential effects of absorbed components on disease intervention. ResultsCompared with the blank group， the high-dose E. phaseoloides extract group and morphine group showed significantly increased pain response thresholds （P<0.01）， without affecting motor coordination in normal mice. Compared with the Sham group， the SNL group exhibited significantly decreased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. Compared with the SNL group， the SNL + E. phaseoloides extract group and SNL + pregabalin group showed significantly increased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. The analgesic effect of E. phaseoloides was most significant at 2 h after administration. A total of 70 constituents were identified in vitro， and 22 prototype compounds and 29 metabolites were detected in plasma. The targets of the absorbed components were mainly enriched in biological processes associated with pain signal perception and transmission and showed a high degree of overlap with disease genes related to neuropathic pain. In addition， multiple components exhibited strong binding energies with core pain-related targets. Based on integrated analysis of in vitro content， plasma exposure levels， and target associations， ketanthamide A-β-D-pyranoside and ketengzide were identified as the most representative pharmacologically active substances responsible for the analgesic effect. ConclusionThis study systematically elucidates the material basis of E. phaseoloides intervention in neuropathic pain from three aspects， including chemical constituent characteristics， in vivo behavioral characteristics， and potential targets， providing important theoretical foundations and experimental support for further studies on its pharmacological mechanism and analgesic drug development.
