Molecular Mechanisms Molecular Docking of Three Mitragyna speciosa Alkaloids with iNOS, TNF-α, and IL-6 and In Silico Toxicity Prediction

DOI

10.2991/978-94-6239-836-8_16How to use a DOI?

Keywords

Mitragyna speciosa; mitragynine; 7-hydroxymitragynine; speciociliatine; sepsis; iNOS; TNF-α; IL-6; molecular docking; toxicity prediction

Abstract

Sepsis involves a dysregulated host response to infection, in which inflammatory mediators contribute to organ dysfunction. This exploratory study compared the docking scores and predicted interactions of mitragynine, 7-hydroxymitragynine, and speciociliatine with inducible nitric oxide synthase (iNOS; PDB ID 1M8E), tumor necrosis factor-alpha (TNF-α; 6X86), and interleukin-6 (IL-6; 4NI9), together with toxicity predictions from pkCSM and ProTox-III. Within the applied docking protocol, 7-hydroxymitragynine yielded the most negative scores against iNOS (−9.0 kcal/mol) and IL-6 (−9.2 kcal/mol), whereas mitragynine yielded the most negative score against TNF-α (−6.6 kcal/mol). Speciociliatine produced scores of − 8.5, − 6.1, and − 7.5 kcal/mol against iNOS, TNF-α, and IL-6, respectively. pkCSM predicted negative classifications for Ames mutagenicity, hERG I inhibition, and skin sensitization for all three compounds, but identified shared hepatotoxicity alerts and predicted hERG II inhibition for mitragynine and speciociliatine. ProTox-III predicted acute oral LD₅₀ values of 300 mg/kg for mitragynine and speciociliatine and 1,000 mg/kg for 7-hydroxymitragynine. However, the latter prediction had lower average similarity and prediction accuracy. These findings describe target-dependent computational patterns and predicted toxicity concerns that may inform subsequent experiments. The lack of reported docking protocol validation and experimental confirmation limits confidence in the predicted poses and rankings. The results do not establish binding affinity, functional inhibition, efficacy in sepsis, or safety.

Copyright

© 2026 The Author(s)

Open Access

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TY  - CONF
AU  - Mumya Camary
AU  - Binawati Ginting
AU  - Rosnani Nasution
AU  - Bastian Lubis
PY  - 2026
DA  - 2026/11/11
TI  - Molecular Mechanisms Molecular Docking of Three Mitragyna speciosa Alkaloids with iNOS, TNF-α, and IL-6 and In Silico Toxicity Prediction
BT  - Proceedings of the3rd Malikussaleh International Conference on Health and Disaster Medicine 2026  (MICOHEDMED 2026)
PB  - Atlantis Press
SP  - 170
EP  - 184
SN  - 2468-5739
UR  - https://doi.org/10.2991/978-94-6239-836-8_16
DO  - 10.2991/978-94-6239-836-8_16
ID  - Camary2026
ER  -