Pharmacological and computer-aided studies provide new insights into Millettia peguensis Ali (Fabaceae)

Abstract

Millettia peguensis, popular for its ethnopharmacological uses, was employed to evaluate its different pharmacological properties in this study. The analgesic studies of the plant have been performed by acetic acid-induced writhing and formalin-induced licking tests respectively, whereas the antidiarrheal experiment was done by castor oil-induced diarrheal test. Besides, antioxidant, cytotoxic, antimicrobial, thrombolytic evaluations were performed by DPPH scavenging with phenol content determination, brine shrimp lethality, disc diffusion and clot lysis methods respectively. Moreover, in silico study of the phytoconstituents was carried out by molecular docking and ADME/T analysis. The methanol extract of Millettia peguensis (MEMP) revealed significant biological activity in the analgesic and antidiarrheal test (p < 0.001) compared to the standards. Antioxidant assay displayed promising IC₅₀ values (15.96 μg/mL) with the total phenol content (65.27 ± 1.24 mg GAE/g). In the cytotoxicity study, the LC₅₀ value was found to be 1.094 μg/mL. Besides, MEMP was highly sensitive to the bacteria but less liable to clot lysis. Furthermore, phytoconstituents exposed potential binding affinity towards the selected receptors, whereas the ADME/T properties indicated the drug likeliness of the plant. The outcomes of these findings suggest the therapeutic potential of this plant against pain, diarrhea, inflammation, and tissue toxicity.

Keywords: 5-HT3, 5-hydroxytryptamine 3; ASA, acetyl salicylic acid; Analgesic; Antidiarrheal; Antioxidant; Antitumor; BHT, butylated hydroxytoluene; CADD, computer-aided drug discovery; COX 1, cyclooxygenase-1; COX 2, cyclooxygenase-2; DPPH, 2,2-diphenyl-1-picryl-hydrazyl-hydrate; GABA, gamma-Aminobutyric acid; IC50, half maximal inhibitory concentration; IL-1, interleukin-1; LC50, Lethal Concentration 50; MEMP, methanol extract of Millettia peguensis; MMP 9, matrix metalloproteinase 9; Millettia peguensis; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; RONS, reactive oxygen and nitrogen species; ROS, reactive oxygen species; TNF-alpha, tumour necrosis factor alpha.

Fig. 1

Structure of selected phytoconstituents.

Fig. 2

Percentage of radical scavenging activities of methanol extract of M. peguensis leaves and standard drug.

Fig. 3

IC₅₀ value of butylated hydroxytoluene (BHT) and methanol extract of M. peguensis leaves.

Fig. 4

% Mortality and predicted regression line of vincristine sulphate and methanol extract of M. peguensis leaves.

Fig. 5

Clot lysis effects of methanol extract of M. peguensis leaves. Clot lysis values are presented as mean ± SEM (n = 5); One-way analysis of variance (ANOVA) was followed by Dunnett’s test. *p < 0.05, ** p < 0.01, ***p < 0.001 were considered as significant compared with the control, where # is designated as control. SW = Saline water, SK = streptokinase and MEMP = methanol extract of M. peguensis leaves.

Fig. 6

3D and 2D representation of docking interaction with standard drugs.A. Aspirin interaction with 2OYE; B. Aspirin interaction with 6COX; C. Loperamide interaction with 5AIN; D. Doxorubicin interaction with 1XKK; E. Streptokinase interaction with 1A5H.

Fig. 7

3D and 2D representation of the best key interactions in the binding pocket for selected ligands and receptors whether, (A and B) represents prostaglandin – 1 (PDB ID: 2OYE), pongamol; (C and D) represents prostaglandin – 2 (PDB ID: 6COX), lanceolatin – B; (E and F) represents 5-HT3 receptor (PDB ID: 5AIN) and milletenone; respectively.

Fig. 8

3D and 2D representation of the best key interactions in the binding pocket for selected ligands and receptors whether, (G and H) represents urate oxidase (PDB ID: 1R4U), lanceolatin – B; (I and J) represents protein tyrosine kinase (PDB: 1XKK), lanceolatin – B; (K and L) represents E. coli exonuclease I (PDB ID: 1FXX), ovalitenone; (M and N) represents human tissue-type plasminogen activator (PDB ID: 1A5H) and lanceolatin –B, respectively.