Computational approach to decode the mechanism of curcuminoids against neuropathic pain

Xiang, Chunxiao; Chen, Chunlan; Li, Xi; Wu, Yating; Xu, Qing; Wen, Lingmiao; Xiong, Wei; Liu, Yanjun; Zhang, Tinglan; Dou, Chongyang; Ding, Xian; H, Lin; Chen, Fangfang; Yan, Zhiyong; Liang, Lingli; Wei, Guihua

doi:10.1016/j.compbiomed.2022.105739

Cited by 8 publications

(4 citation statements)

References 63 publications

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“…Molecular dynamics simulation provided insight into the stability of protein-ligand complexes. The RMSD is typically regarded as a key sign of a system's stability [ 23 ]. As shown in Figure 11 , the RMSD values of escin with the core targets fluctuated in a small range (RMSD <0.3 nm) during the simulation.…”

Section: Resultsmentioning

confidence: 99%

“…NP-associated target genes were collected through the databases, including Therapeutic Targets Database ( https://db.idrblab.net/ttd/ ), DisGeNet ( https://www.disgenet.org/ ), GeneCards ( https://www.genecards.org ), DrugBank ( https://www.drugbank.ca ), and OMIM ( https://omim.org/ ). After discarding the duplicate targets, we obtained NP-related targets [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

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Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study

Li,

Wu,

Wang

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Background. Escin is the main active component in Aesculus hippocastanum. It has been demonstrated that escin has anti-inflammatory properties. This study combined the methods of network pharmacology, molecular docking, and molecular dynamics to explore the molecular mechanism of escin against neuropathic pain (NP). Methods. The Swiss Target Prediction and the Pharm Mapper database were employed for predicting the targets of escin. Also, the candidate targets of NP were gathered via the databases including Therapeutic Targets, DisGeNet, GeneCards, DrugBank, and OMIM. Subsequently, the network of protein-protein interaction was screened for the key targets by the software Cytoscape 3.8.0. Then, the intersection of these targets was analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Additionally, we further investigated the ligand-target interactions by molecular docking and molecular dynamics simulations. Results. In total, 94 escin targets were predicted by network pharmacology. Among them, SRC, MMP9, PTGS2, and MAPK1 were the core candidate targets. Subsequently, the analysis of GO and KEGG enrichment revealed that escin affected NP by regulating protein kinase C, MAP kinase, TRP channels, the T-cell receptors signaling pathway, and the TNF signaling pathway. The results of molecular docking and molecular dynamics simulation confirmed that escin not only had a strong binding activity with the four core target proteins but also stably combined in 50 ns. Conclusions. Our study revealed that escin acts on the core targets SRC, MMP9, PTGS2, MAPK1, and associated enrichment pathways to alleviate neuronal inflammation and regulate the immune response, thus exerting anti-NP efficacy. This study provided innovative ideas and methods for the promising treatment of escin in relieving NP.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study

Li,

Wu,

Wang

et al. 2023

Evidence-Based Complementary and Alternative Medicine

Self Cite

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“…Curcuminoids (components of turmeric) have been previously investigated in treatment of neuropathic pain, and previous studies found that a possible mechanism of action in alleviating neuropathic pain was via modulating nitrogen metabolism 63 . Although ME/CFS summary statistics were not used in this analysis, changes in nitrogen metabolism have been implicated in this condition 64 , and our findings suggest these metabolic changes may not be unique to ME/CFS but instead shared across COPCs through influence on nociplastic pain in particular.…”

Section: Discussionmentioning

confidence: 99%

Chronic Overlapping Pain Conditions and Nociplastic Pain

Johnston

Signer

Huckins

2023

Preprint

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Background: Chronic Overlapping Pain Conditions (COPCs) are a subset of chronic pain conditions commonly comorbid with one another and more prevalent in women and assigned female at birth (AFAB) individuals. Pain experience in these conditions may better fit with a new mechanistic pain descriptor, nociplastic pain, and nociplastic type pain may represent a shared underlying factor among COPCs. Methods: We applied GenomicSEM common-factor genome wide association study (GWAS) and multivariate transcriptome-wide association (TWAS) analyses to existing GWAS output for six COPCs in order to find genetic variation associated with nociplastic type pain, followed by genetic correlation (linkage-disequilibrium score regression), gene-set and tissue enrichment analyses. Results: We found 24 independent single nucleotide polymorphisms (SNPs), and 127 unique genes significantly associated with nociplastic type pain, and showed nociplastic type pain to be a polygenic trait with significant SNP-heritability. We found significant genetic overlap between multisite chronic pain and nociplastic type pain, and to a smaller extent with rheumatoid arthritis. Tissue enrichment analyses highlighted cardiac and thyroid tissue, and gene set enrichment analyses emphasized potential shared mechanisms in cognitive, personality, and metabolic traits and nociplastic type pain along with distinct pathology in migraine and headache. Conclusions: We use a well-powered network approach to investigating nociplastic type pain using existing COPC GWAS output, and show nociplastic type pain to be a complex, heritable trait, in addition to contributing to understanding of potential mechanisms in development of nociplastic pain.

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“…Ticagrelor (-6.883 ± 0.276 Kcal/mol), in turn, showed higher a nity than γ-TPN and Prasugrel. Interaction energy and a nity of the ligand-target complex are inversely proportional quantities, therefore, the lower the binding energy, the greater the stability of the interaction between ligand and protein (Trott & Olson 2010;Zhang et al 2021;Xiang et al 2022).…”

Section: Docking Molecular Of γ-Tpnmentioning

confidence: 99%

Non-clinical investigations about cytotoxic and anti-platelet activities of gamma-terpinene

Souza,

Pimentel,

de Sousa

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Gamma-terpinene (γ-TPN) is a cyclohexane monoterpene, isolated from essential oils of pharmacologically active plant species, such as tea tree (Melaleuca alternifolia), oregano (Origanum vulgare), rosemary (Rosmarinus o cinalis L.), thyme (Thymus vulgaris Marchand) and eucalyptus (Eucalyptus sp.). Terpenes are widely studied for their recognized pharmacological actions on the cardiovascular system, hemostasis and antioxidant actions. The objective of this study was to investigate the cytotoxic and antiplatelet activity of γ-TPN in non-clinical study models. For the in silico evaluation, the PreADMET, SwissADME and SwissTargetPrediction software were used. Molecular docking was performed using the AutoDockVina and BIOVIA Discovery Studio databases. The cytotoxicity of γ-TPN was analyzed by the MTT assay with normal murine endothelial (SVEC4-10) and broblast (L929) lines. Platelet aggregation was evaluated with platelet-rich (PRP) and platelet-poor (PPP) plasma from spontaneously hypertensive rats (SHR), in addition to SVEC4-10 cells pre-incubated with γ-TPN (50, 100 and 200 µM) for 24 h. In in vivo tests, SHR animals were also used, pre-treated by gavage with γ-TPN for 7 days, distributed into four groups (control, 25, 50 and 100 mg/Kg). At the end, blood samples were collected to measure nitrites using the Griess reagent. γ-TPN proved to be quite lipid-soluble (Log P = + 4.50), with a quali ed pro le of similarity to the drug, good bioavailability, and adequate pharmacokinetics. The monoterpene exhibited a nity mainly for the P2Y12 receptor (6.450 ± 0.232 Kcal/mol), moderate cytotoxicity for L929 (CC 50 = 333.3 µM) and SVEC 4-10 (CC 50 = 366.7 µM). The presence of γ-TPN in SVEC 4-10 cells was also able to reduce platelet aggregation by 51.57 and 44.20%, respectively, at the lowest concentrations (50 and 100 µM). It was concluded that γ-TPN has a good a nity with purinergic receptors and an effect on the reversal of platelet aggregation and oxidative stress, being promising and safe for therapeutic targets and subsequent studies in the control of thromboembolic diseases.

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Computational approach to decode the mechanism of curcuminoids against neuropathic pain

Cited by 8 publications

References 63 publications

Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study

Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study

Chronic Overlapping Pain Conditions and Nociplastic Pain

Non-clinical investigations about cytotoxic and anti-platelet activities of gamma-terpinene

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