Abstract
Objective Pain is a common symptom among patients, and pain management is an important clinical practice topic. The mechanism of Huajiao (HJ; Zanthoxylum bungeanum Maxim.) and its effective components for treating pain was explored using network pharmacology and molecular docking to verify its pain relief function in traditional medical practice. Methods HJ's components were collected via the Traditional Chinese Medicine Systems Pharmacology platform and published studies. HJ-associated target proteins were predicted using the drug similarity rule via Swiss Target Prediction. Online Mendelian Inheritance in Man was used to search for pain-related genes and proteins, and the Database of Interacting Proteins was used to obtain the human interactive target proteins. The compound-target-disease network of HJ for pain relief was constructed with protein-protein interaction networks. The obtained target proteins were uploaded on the Database for Annotation, Visualization, and Integrated Discovery to annotate, visualize, and integrally discover the related signaling pathway, and semiflexible molecular docking by Autodock Vina was applied to verify the potential mechanism. Results A total of 157 molecules in HJ were obtained, and the top 20 active components or active groups were mainly focused on the amide alkaloids (e.g., [6RS]-[2E,7E,9E]-6-hydroxy-N-[2-hydroxy-2-methylpropyl]-11-oxo-2,7,9-dodecatrienamide and [2E,7E,9E]-N-[2-hydroxy-2-methylpropyl]-11-ethoxy-6-hydroxy-dodeca-2,7,9-trienamide). Also, the 66 main targets were filtered from 746 predicted targets and 928 pain-related targets through module Network Analyzer in Cytoscape 3.6.0. Finally, there were 3 critical signaling pathways, including mitogen-activated protein kinase, phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin, and IκB kinase-nuclear factor κB-cyclooxygenase 2 based on integrated discovery with 54 enriched signaling pathways. Conclusions HJ is used as a pain relief and has multicomponents, multitargets, and multiapproaches. Amide alkaloids are important substance bases, and HJ is more suitable for treating inflammatory pain.
Highlights
Pain is a complex pathophysiological and psychological phenomenon that is commonly manifested in clinical practice, including pain sensation and the body’s response to harmful stimulation
A total of 746 predicted targets and 928 pain-related targets were obtained from Online Mendelian Inheritance in Man (OMIM) and Database of Interacting Proteins (DIP)
It was shown that HJ components with an analgesic effect were mainly amide alkaloids, which could be absorbed in the gastrointestinal tract with high bioavailability, indicating its potential property in drug likeness (Table 1)
Summary
Pain is a complex pathophysiological and psychological phenomenon that is commonly manifested in clinical practice, including pain sensation and the body’s response to harmful stimulation. Current medications for pain management have been limited due to inevitable adverse reactions. Erefore, it is important to develop a candidate drug and alternative therapy for pain management. It was reported that the α-sanshool in HJ could decrease the frequency of Evidence-Based Complementary and Alternative Medicine body torsion, and fagaramide could remarkably relieve the pain induced by formalin and capsaicin [4]. Studies on the underlying mechanisms have revealed that fagaramide could develop the analgesic effect by suppressing the voltage-dependent Na+ channel in the Aδ mechanic analgesic receptor and reducing the excitation output from the nociceptor [5]. Transient receptor potential (TRP)A1 and TRPV1, which belong to the TRP family, could be stimulated by hydroxy-alpha-sanshool in HJ to relieve pain [6]. Given that the material basis is complex with multicomponents, multitargets, and multiapproaches, the conventional pharmacological study might be insufficient to elucidate the mechanism and scientific connotation underlying the analgesic effects HJ
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