Evidence map›Paper›PMID 42423989›Full record

ArticleArchives of toxicology2026

Integrated quantitative proteomics reveals stress-associated network remodeling induced by mitragynine in RSC96 Schwann cells.

Hasriadi Hasriadi, Dasuni Wasana Peththa Wadu, Thorsang Weerakul, Chutichot Pattamadilok, Boonchoo Sritularak, Pasarapa Towiwat

Abstract read
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Article in Archives of toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Hasriadi HasriadiDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Dasuni Wasana Peththa WaduDepartment of Pharmacy, Faculty of Allied Health Sciences, University of Ruhuna, Galle, 80000, Sri Lanka.
Thorsang WeerakulInter-Department of Pharmacology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand.
Chutichot PattamadilokDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Boonchoo SritularakDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Pasarapa TowiwatDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand. pasarapa.c@chula.ac.th.ORCID http://orcid.org/0000-0001-9394-4622

Funding

Ratchadaphiseksomphot Endowment Fund for Animal Models of Chronic Inflammation-associated Diseases for Drug Discovery Research Unit, Chulalongkorn University Ratchadaphiseksomphot Endowment Fund for Animal Models of Chronic Inflammation-associated Diseases for Drug Discovery Research Unit, Chulalongkorn UniversitySecond Century Fund (C2F), Chulalongkorn University Second Century Fund (C2F), Chulalongkorn UniversityThailand Science Research and Innovation (TSRI) Fund, Chulalongkorn University No. 68A101000214
6 · The paper itself

Abstract

Mitragynine, the principal alkaloid of Mitragyna speciosa (kratom), exhibits opioid-like analgesic effects but is associated with tolerance following prolonged exposure. Schwann cells are particularly vulnerable to chemically induced toxicity, and disruption of their homeostatic functions has been implicated in neurotoxic injury. The cellular mechanisms underlying this adaptive response remain poorly understood. In this study, an integrated quantitative proteomics and systems biology approach was performed to investigate mitragynine-induced molecular remodeling in RSC96 Schwann cells. Cells were exposed to 20 µM mitragynine, the highest non-cytotoxic concentration, for 72 h and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic profiling. Differentially expressed proteins were characterized through Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway mapping, InterPro domain annotation, and protein-protein interaction network reconstruction using STRING and BioGRID. Proteomic profiling identified 91 significantly altered proteins, comprising 60 downregulated and 31 upregulated proteins. Functional enrichment revealed coordinated suppression of translational machinery, cytoskeletal organization, and metabolic pathways associated with Schwann cell homeostasis. Network reconstruction highlighted AMP-activated protein kinase (AMPK) as a high-centrality node within the downregulated interaction network. Upregulated proteins were enriched in xenobiotic stress responses, aminoacyl-tRNA biosynthesis, and chromatin remodeling pathways. Structural similarity analysis revealed limited overlap between the mitragynine scaffold and morphine despite their shared receptor target. These findings suggest that chronic mitragynine exposure induces coordinated proteomic and network-level remodeling in Schwann cells, identifying regulatory pathways consistent with tolerance-related cellular adaptation and peripheral neurotoxic risk.

Indexed as

Analgesic toleranceMitragynineNeurotoxicityQuantitative proteomicsSchwann cells

Identifiers

PMID42423989

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.