Abstract
The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract’s ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.
Highlights
In ancient times, traditional systems of medicine were the fundamental source of herbal medications [1]
When the alcoholic fraction of S. mangifera extract was administered at a dose of 400 mg/kg in the Group VI animals, the results showed a significant (p < 0.05) reduction (68.83 ± 1.87) in the IL-6 concentration, whereas there was no reduction in the IL-6 concentration in groups IV and V (121.72 ± 3.71 and 76.51 ± 2.81, respectively) when compared to the group II animals (Figure 5)
This study showed that the ethanolic fraction of S. mangifera has greater scavenging activity than the other fractions in comparison to the standard
Summary
Traditional systems of medicine were the fundamental source of herbal medications [1]. ROS circulating in the blood stream affects the metabolic process because it reacts with the free electron molecules that are present in living systems, which can lead to various life-threating diseases like ischemia, respiratory distress, arthritis, cancer, and aging, and can damage various vital organs. It has an odour that resembles that of turpentine upon scrubbing and/or chewing It has numerous bioactive phytoconstituents in various parts of the plant: the fruits and aerial parts contain cycloartanone-24-methylene, daucosterol, lignoceric acid, stigmast-4-en-3-one, cystine, oleanolic acid and β-amyrin; and glycine and leucine respectively [14]. The ethanolic fraction of the plant extract was used for the estimation of pharmacological activity against inflammation and CFA-induced arthritis in an animal model
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