Regulation of the redox signaling and inflammation by Terminalia myriocarpa leaves and the predictive interactions of it's major metabolites with iNOS and NF-ĸB

Ano: 2021

Journal of Ethnopharmacology, 2021, 280, 114459.


Autores/as: Md Afjalus Siraj, Md Sariful Islam Howlader, Md Arman Islam, Tanzira Irin, Jesus Simal-Gandara.


Ethnopharmacological relevance

The present study was designed to investigate the regulation of the redox signaling and inflammation by ethanolic leaf extract of Terminalia myriocarpa Van Heurck & Müller (ETM), inspired by the reported antioxidant potential of the plant bark and the anti-edema effect of the same genus.

Materials and methods

HPLC-DAD dereplication study was conducted to detect the major polyphenolic secondary metabolites. In-vitro DPPH free radical scavenging assay, nitric oxide (NO) scavenging assay, Fe2+ ion chelating ability assay and reducing power assay were conducted to evaluate the antioxidant capacity. The molecular mechanism of anti-inflammation was investigated via assessing the NO and NF-ĸB inhibiting properties in different cell lines. In-vivo carrageenan and histamine-induced edema tests were conducted using established animal models. Pro-inflammatory proteins iNOS and NF-κB were docked against the major metabolites of ETM in the in-silico study.


HPLC dereplication analysis revealed the presence of considerable amount of ellagic acid, where methyl-(S)-flavogallonate was previously reported in T. myriocarpa. Significant antioxidant activity was found in every in- vitro redox assay conducted. NO was reduced in RAW 264.7 cells, showing 83.67 ± 4.18% inhibitory activity at the highest tested concentration. TNF-α induced NF-κB was also observed to be reduced in 293/NF-кB-luc cells with an inhibitory activity of 66.23 ± 0.81% at the highest dose tested. In-vivo carrageenan-induced edema test demonstrated significant anti-inflammatory activity (p < 0.05; p < 0.01) at both doses of 250 and 500 mg/kg with 60.10% highest reduction in rat paw volume. Using same doses, histamine-induced edema test exhibited mentionable anti-inflammatory potential (p < 0.05; p < 0.01) with 67.91% highest reduction in rat paw volume. Moreover, ellagic acid and methyl-(S)-flavogallonate showed significant binding affinity with iNOS (−8.5 and −8.7 Kcal/moL, respectively) and NF-κB (−7.3 and −7.3 Kcal/moL, respectively).


Mentionable basis was found on behalf of the anti-inflammatory and antioxidant potentials of ETM which might be correlated with its NF-ĸB inhibiting properties.

Jesús Simal Gándara

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