Identification of apposite antagonist for androgen receptor in prostate cancer: an in silico study of fenugreek compounds.

Benign Prostate Cancer (BPC), a prevalent condition predominantly affecting elderly males, manifests with voiding difficulties and urinary retention. A library of compounds from Trigonella foenum-graecum, commonly known as fenugreek was used in this study. We aimed to explore its potential anti-cancer effects by computationally assessing its inhibitory activity on the androgen receptor (AR). For in-silico drug assessment, we employed Maestro 12.8, part of the Schrödinger Suite, to identify the most promising candidates acting as androgen receptor antagonists in the treatment of BPC. Subsequently, 59 fenugreek compounds were retrieved from the PubChem database and subjected to molecular docking against the active site of the target protein, 1E3G. 100-nanosecond molecular dynamics (MD) simulations were performed to assess the stability and compactness of the AR-ligand complexes. Notably, the AR-kaempferol complex exhibited the least fluctuation within the AR active site throughout the simulation trajectory, followed by chlorogenic acid and the reference ligand, hydroxyflutamide. The MM/GBSA values revealed the compounds' maximum free binding energy (-103.3 ± 6, -87.4 ± 23, -68.5 ΔGbind) for chlorogenic acid, kaempferol, and hydroxyflutamide, respectively. These findings suggest their potential as promising leads for drug development. Further lead optimization and comprehensive studies on the top-ranked ligands identified in this investigation are warranted to advance their potential as therapeutic agents for BPC treatment.Communicated by Ramaswamy H. Sarma.

Antidiabetes study of Spondias mombin (Linn) stem bark fractions in high-sucrose diet-induced diabetes in Drosophila melanogaster.

Objective: The onset of insulin resistant diabetes has been associated with a high-sucrose diet in vertebrates and invertebrates. However, various parts of Spondias mombin reportedly possess antidiabetic potential. However, the antidiabetic efficacy of S. mombin stem bark in high-sucrose diet-induced Drosophila melanogaster model has not been explored. In this study, the antidiabetic and antioxidant effects of the solvent fractions of S. mombin stem bark were evaluated using in vitro, in vivo, and in silico methods. Methods: Successive fractionation of S. mombin stem bark ethanol extract was performed; the resulting fractions were subjected to in vitro antioxidant and antidiabetic assays using standard protocols. The active compounds identified from the high-performance liquid chromatography (HPLC) study of the n-butanol fraction were docked against the active site of Drosophila α-amylase using AutoDoc Vina. The n-butanol and ethyl acetate fractions of the plant were incorporated into the diet of diabetic and nondiabetic flies to study the in vivo antidiabetic and antioxidant properties. Results: The results obtained revealed that n-butanol and ethyl acetate fractions had the highest in vitro anti-oxidant capacity by inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power, and hydroxyl radical followed by significant inhibition of α-amylase. HPLC analysis revealed the identification of eight compounds with quercetin having the highest peak followed by rutin, rhamnetin, chlorogenic acid, zeinoxanthin, lutin, isoquercetin, and rutinose showing the lowest peak. The fractions restored the glucose and antioxidant imbalance in diabetic flies, which is comparable with the standard drug (metformin). The fractions were also able to upregulate the mRNA expression of insulin-like peptide 2, insulin receptor, and ecdysone-inducible gene 2 in diabetic flies. The in silico studies revealed the inhibitory potential of active compounds against α-amylase with isoquercetin, rhamnetin, rutin, quercetin, and chlorogenic acid having higher binding affinity than the standard drug (acarbose). Conclusion: Overall, the butanol and ethyl acetate fractions of S. mombin stem bark ameliorate type 2 diabetes in Drosophila. However, further studies are needed in other animal models to confirm the antidiabetes effect of the plant.

Modulatory effects of stonebreaker (Phyllanthus amarus) and bitter gourd (Momordica charantia) on enzymes linked with cardiac function in heart tissue of doxorubicin-stressed rats.

Doxorubicin (DOX) has been linked with impairment in cardiovascular function and redox balance. In the present study, the effect of Phyllanthus amarus (PA) and Momordica charantia (MC) leaves on some biomolecules [Angiotensin-I converting enzyme (ACE), arginase, acetylcholinesterase (AChE), adenosine deaminase (ADA), lactate dehydrogenase (LDH)] and antioxidant [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA)] linked with cardiac function in DOX-stressed rats was evaluated. Animals were grouped and pretreated with PA and MC leaf extracts at different doses (200 and 400 mg/kg/bwt orally), while DOX (15 mg/kg/bwt) was administered intraperitoneally on the last day of the experiment. Result revealed an increase of ACE, arginase, AChE, ADA, LDH activities and MDA level as well as a significant reduction in CAT and SOD activities, and GSH level in the rats treated with DOX compared to the control. However, these were significantly mitigated in the rats pretreated with PA and MC dose dependently. Chemical characterization of the leaf extracts via high performance liquid chromatography revealed the presence of some phenolic compounds which included kaempferol, catechin, epicatechin, ellagic acid, gallic acid quercetin, isoquercitrin and rutin. These findings revealed a significant improvement in redox imbalance and other biomolecules associated with cardiac function, which was altered by DOX. This improvement could be linked to the presence of cardioprotective agents present in PA and MC, thereby making these plants therapeutic agents for the treatment of cardiovascular complications associated with drugs such as DOX.

Effect of dietary supplementation of Padauk (Pterocarpus soyauxii) leaf on high fat diet/streptozotocin induced diabetes in rats' brain and platelets.

BACKGROUND: This study investigated the effects of Padauk leaf on brain malondialdehyde (MDA) content, acetylcholinesterase (AChE) activities, ectonucleotidases and adenosine deaminase (ADA) activities in the platelet of high fat diet and streptozotocin (STZ)-induced diabetic rats. METHODS: The animals were divided into six groups (n=7): normal control rats; diabetic rats+high fat diet (HFD); diabetic rats+HFD+Metformin; diabetic rats+HFD+acarbose; diabetic rats+HFD+10% Padauk leaf; normal rats+basal diet+10% Padauk leaf. After 30days of experiment comprising of acclimatization, dietary manipulation, pre-treatment with STZ and supplementation with Padauk leaf, the animals were sacrificed and the rats' brain and blood were collected for subsequent analysis. RESULTS: The results demonstrated that the elevated MDA content and AChE activity in the diabetic rats were significantly reduced when compared with the control rats. Furthermore, the increased NTPDases, 5'-nucleotidase and ADA activities in the diabetic rats were significantly reduced when compared with the control rats. CONCLUSION: This study demonstrated that Padauk leaf exhibited modulatory effects on purinergic and cholinergic enzymes involved in the prevention of platelet abnormality and consequent vascular complications in diabetic state.