Modulation of NF-κB and MAPK signalling pathways by hydrolysable tannin fraction from Terminalia chebula fruits contributes to its anti-inflammatory action in RAW 264.7 cells

Abstract

Objectives Hydrolysable tannin fraction (HTF) derived from Terminalia chebula fruit pericarps was assessed for its anti-inflammatory potential in LPS-induced RAW 264.7 cells. Its molecular mechanism was also established and compared with individual tannins – chebulagic acid (CH) and corilagin (CO). Methods The effect of HTF on LPS-stimulated RAW 264.7 cells was studied by estimating the release of NO, ROS, cytokines and changes in nuclear morphology by DAPI staining. Furthermore, the effect of HTF, CO and CH was compared with the expression of p65, p38 and pERK proteins by immunoblotting and the mRNA transcript level of COX-2, iNOS and TNF-α by quantitative PCR. The in-silico interactions of various hydrolysable tannins present in HTF with molecular targets of inflammation were studied using Maestro software. Key findings HTF at the dose levels of 25, 50 and 100 µg/ml was able to decrease the release of NO, ROS and cytokines from LPS-induced RAW 264.7 cells without disturbing the cell nuclear morphology. Investigation of molecular mechanism revealed that inhibition of NF-κB and MAPK signalling pathways was responsible for its anti-inflammatory action. The effect of HTF was higher than the individual tannins CH and CO. Conclusion HTF can be developed as an effective anti-inflammatory agent.

Simultaneous quantitative analysis and in vitro anti-arthritic effects of five polyphenols from Terminalia chebula

“…Our previous network pharmacology analysis revealed that the NF-κB signaling pathway and MAPK signaling pathway play dominate role in the mechanism of T. chebula for RA treatment ( Fang et al, 2019 ). Other studies are consistent with our findings ( Ekambaram et al, 2022 ). The structural analysis revealed that both chebulanin and chebulagic acid contain 2,4-O-chebuloyl-β-d-glucose gallic acyl derivative structural domains, which are presumed to be key domains for anti-inflammatory activity.…”

NF‐κB mediates silica‐induced pulmonary inflammation by promoting the release of IL‐1β in macrophages

“…Yan et al 28 report that the inhibition of STAT3/NF‐κB can alleviate ROS‐dependent inflammatory response in atopic dermatitis. By targeting the NF‐κB and MAPK signaling pathways, the Terminalia chebula fruits‐derived hydrolyzable tannin fraction shows an antiinflammatory effect on LPS‐stimulated RAW 264.7 cells 29 . Similarly, triptolide, the main active ingredient of Tripterygium wilfordii Hook.f ., is a newly defined NF‐κB inhibitor that can alleviate Caerulein‐induced acute pancreatitis 30 …”

“…By targeting the NF-κB and MAPK signaling pathways, the Terminalia chebula fruits-derived hydrolyzable tannin fraction shows an antiinflammatory effect on LPS-stimulated RAW 264.7 cells. 29 Similarly, triptolide, the main active ingredient of Tripterygium wilfordii Hook.f., is a newly defined NF-κB inhibitor that can alleviate Caerulein-induced acute pancreatitis. 30 The pro-inflammatory effect of SiNPs is tightly associated with the upregulated cytokines such as IL-1β, IL-6, and IL-18, which are all potential downstream targets of NK-κB.…”

Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response

“…et al (2021) [ 202 ] Notopterol Inhibition of JAK 2/3-STAT signalling Wang Q. et al (2020) [ 203 ] Tannins Chebulagic acid, corilagin Inhibition of NFκB and MAPK signalling pathways Ekambaram S.P. et al (2022) [ 204 ] Emblicanin Binding to NFκB complex resulting in decrease of its activation Husain I. et al (2018) [ 205 ] Tannic acid (Gallotannin) Inhibition of JAK/STAT signalling pathway and NFκB signalling pathway Youness R.A. et al (2021) [ 206 ] Punicalagin Induction of Nrf2-HO-1 signalling through SIRT1 activation Yu L.M. et al (2019) [ 207 ] Punicalagin Reduction of the expression of p-STAT6, Jagged1, and GATA3 protein Yu L. et al (2022) [ 208 ] …”

“…Considering the low solubility of natural tannins in water and, accordingly, in intestinal juice, the systemic effect on transcription factors is specific only to those tannins that have a relatively high capacity to undergo hydrolysis. These compounds have an inhibitory effect on NFκB and MAPK cascades [ 204 ]. Some tannins (emblicanin) are capable to bind directly to NFκB protein complex [ 205 ].…”