AUTHOR=Sajid-ur-Rehman Muhammad , Ishtiaq Saiqa , Aati Hanan Y. , Sherif Asmaa E. , Abbas Khan Mohsin , Hussain Mussadique , Sohaib Khan Muhammad , Ahmed Maqsood , Naseem Muhammad Jawad , Khan Kashif-ur-Rehman 

TITLE=Antiarthritic potential of the butanol fraction of Sesuvium sesuvioides: An in vitro, in vivo, and in silico evaluation

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1136459

DOI=10.3389/fphar.2023.1136459

ISSN=1663-9812

ABSTRACT=Sesuvium sesuvioides has been traditionally used in inflammation, arthritis, and gout. However, its anti-arthritic potential has not been evaluated scientifically. The current study was designed to assess the anti-arthritic properties of the n-butanol fraction of S. sesuvioides (SsBu) by phytochemical analysis, in-vitro and in-vivo pharmacological activities, as well as in-silico studies. Phytochemical analysis showed TPC (90.7±3.02 mg GAE/g), and TFC (23.7±0.69 mg RE/g), further analysis by GCMS identified possible bioactive phytocompounds belonging to phenols, flavonoids, steroids, and fatty acids. In-vitro antioxidant potential of SsBu was assessed by DPPH (175.5±7.35 mg TE/g), ABTS (391.6±17.1 mg TE/g), FRAP (418.2±10.8 mg TE/g), CUPRAC (884.8±7.97 mg TE/g), phosphomolybdenum (5.7±0.33 mmol TE/g), and metal chelating activity (9.04±0.58 mg EDTAE/g). Moreover, the in-vitro egg albumin denaturation inhibition assay showed the anti-inflammatory effect of SsBu was comparable to the standard. The in-vivo anti-arthritic activity was performed to determine the curative impact of SsBu against the formalin-induced (dose dependant peak effect 72.2 % inhibition at 750mg/kg, compared to standard; 69.1 % inhibition) and Complete Freund’s adjuvant induced arthritis (40.8 % inhibition compared to inhibition by the standard; 42.3 %). SsBu significantly controlled the PGE-2 level compared to the control group (p < 0.001) and restored the hematological parameters in RA. Treatment with SsBu significantly subdued the oxidative stress by reinstating SOD, GSH, and MDA along with pro-inflammatory markers (Il-6 and TNF-α) in arthritic rats. Molecular docking revealed the anti-arthritic role of major identified compounds. Kaempferol-3-rutinoside was found to be more potent for COX-1(-9.2 kcal/mol) and COX-2 inhibition (-9.9 kcal/mol) compared to diclofenac sodium (COX-1; -8.0, and COX-2; -6.5 kcal/mol). Out of twelve docked compounds, two for COX-1 and seven for COX-2 inhibition showed a more potent binding than standard drug. It finally concluded that the n-butanol fraction of S. sesuvioides had antioxidant and anti-arthritic potential investigated through in-vitro, in-vivo, and in silico approaches, which may be due to the quantified and identified bioactive compounds.