Investigating the effects of four medicinal plants against dengue virus through QSAR modeling and molecular dynamics studies.

The Dengue virus (DENV) has been increasingly recognized as a prevalent viral pathogen responsible for global transmission of infection. It has been established that DENV's NS5 methyltransferase (MTase) controls viral replication. As a result, NS5 MTase is considered a potentially useful drug target for DENV. In this study, the two phases of virtual screening were conducted using the ML-based QSAR model and molecular docking to identify potential compounds against NS5 of DENV. Four medicinal plants [Aloe vera, Cannabis sativa (Hemp), Ocimum sanctum (Holy Basil; Tulsi), and Zingiber officinale (Ginger)] that showed anti-viral properties were selected for sourcing the phytochemicals and screening them against NS5. Additionally, re-docking at higher exhaustiveness and interaction analysis were performed which resulted in the identification of the top four hits (135398658, 5281675, 119394, and 969516) which showed comparable results with the control Sinefungin (SFG). Post molecular dynamics simulation, 135398658 showed the lowest RMSD (0.4-0.5 nm) and the maximum number of hydrogen bonds (eight hydrogen bonds) after the control while 5281675 and 969516 showed comparable hydrogen bonds to the control. These compounds showed direct interactions with the catalytic site residues GLU111 and ASP131, in addition to this these compounds showed stable complex formation as depicted by principal component analysis and free energy landscape. 135398658 showed lower total binding free energy (ΔGTotal = -36.56 kcal/mol) than the control, while 5281675 had comparable values to the control (ΔGTotal = -34.1 kcal/mol). Overall, the purpose of this study was to identify phytochemicals that inhibit NS5 function, that could be further tested experimentally to treat dengue virus (DENV).Communicated by Ramaswamy H. Sarma.

Identification of potential Escherichia coli DNA gyrase B inhibitors targeting antibacterial therapy: an integrated docking and molecular dynamics simulation study.

The alarming rise in the rate of antibiotic resistance is a matter of significant concern. DNA gyrase B (GyrB), a critical bacterial enzyme involved in DNA replication, transcription, and recombination, has emerged as a promising target for antibacterial agents. Inhibition of GyrB disrupts bacterial DNA replication, leading to cell death, making it an attractive candidate for antibiotic development. Although several classes of antibiotics targeting GyrB are currently in clinical use, the emergence of antibiotic resistance necessitates the exploration of novel inhibitors. In this study, we aimed to identify potential Escherichia coli GyrB inhibitors from a database of phytoconstituents sourced from Indian medicinal plants. Utilizing virtual screening, we performed a rigorous search to identify compounds with the most promising inhibitory properties against GyrB. Two compounds, namely Zizogenin and Cucurbitacin S, were identified based on their favorable drug likeliness and pharmacokinetic profiles. Employing advanced computational techniques, we analyzed the binding interactions of Zizogenin and Cucurbitacin S with the ATP-binding site of GyrB through molecular docking simulations. Both compounds exhibited robust binding interactions, evidenced by their high docking energy scores. To assess the stability of these interactions, we conducted extensive 100 ns molecular dynamics (MD) simulations, which confirmed the stability of Zizogenin and Cucurbitacin S when bound to GyrB. In conclusion, our study highlights Zizogenin and Cucurbitacin S as promising candidates for potential antibacterial agents targeting GyrB. Experimental validation of these compounds is warranted to further explore their efficacy and potential as novel antibiotics to combat antibiotic-resistant bacteria.Communicated by Ramaswamy H. Sarma.

Aegle marvels (L.) Correa Leaf Essential Oil and Its Phytoconstituents as an Anticancer and Anti-Streptococcus mutans Agent.

Aegle mamelons (A. marmelos) or Indian Bael leaves possess anti-cancerous and antibacterial properties and are used in the traditional medicine system for the treatment of oral infections. In the present study, the essential oil of the leaves of A. marmelos was explored for its anticancer, antioxidant, and anti-cariogenic properties. The hydro-distilled oil of A. marmelos leaves was analyzed using gas chromatography coupled with mass spectrometry (GC-MS). Monoterpene limonene (63.71%) was found to have the highest percentage after trans-2-Hydroxy-1,8-cineole and p-Menth-2,8-dien-1-ol. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to investigate the anticancer activity of the extracted oil against human oral epidermal carcinoma (KB), and the results showed significantly higher (**** p < 0.0001) anticancer activity (45.89%) in the doxorubicin (47.87%) when compared to the normal control. The antioxidant activity of the essential oil was evaluated using methods of DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)). The results showed a significant (*** p < 0.001) percentage of inhibition of DPPH-induced free radical (70.02 ± 1.6%) and ABTS-induced free radical (70.7 ± 1.32%) at 100 µg/mL with IC50, 72.51 and 67.33 µg/mL, respectively, comparatively lower than standard compound ascorbic acid. The results of the molecular docking study of the significant compound limonene with the receptors tyrosinase and tyrosine kinase 2 supported the in vitro antioxidant potential. The anti-cariogenic activity was evaluated against Streptococcus mutans (S. mutans). Results showed a significant minimum inhibitor concentration of 0.25 mg/mL and the killing time was achieved at 3 to 6 h. The molecular-docking study showed that limonene inhibits the surface receptors of the S. mutans c-terminal domain and CviR protein. The study found that A. marmelos leaves have potential anti-carcinoma, antioxidant, and anti-cariogenic effects on human oral epidermal health, making them a valuable natural therapeutic agent for managing oral cancer and infections.

Ex Vivo Antiplatelet and Thrombolytic Activity of Bioactive Fractions from the New-Fangled Stem Buds of Ficus religiosa L. with Simultaneous GC-MS Examination.

Different parts of Ficus religiosa are the common components of various traditional formulations for the treatment of several blood disorders. The new-fangled stem buds' powder was extracted with 80% ethanol and successively fractionated by chloroform and methanol. Chloroform and methanol fractions of Ficus religiosa (CFFR and MFFR) were tested for antiplatelet, antithrombotic, thrombolytic, and antioxidant activity in ex vivo mode. The MFFR was particularly investigated for GC-MS and toxicity. The antiplatelet activity of the CFFR, MFFR, and standard drug aspirin at 50 µg/mL was 54.32%, 86.61%, and 87.57%, and a significant delay in clot formation was noted. CFFR at different concentrations did not show a significant effect on the delay of clot formation, antiplatelet, and free radical scavenging activity. The most possible marker compounds for antiplatelet and antioxidant activity identified by GC-MS in the MFFR are salicylate derivatives aromatic compounds such as benzeneacetaldehyde (7), phenylmalonic acid (13), and Salicylic acid (14), as well as Benzamides derivatives such as carbobenzyloxy-dl-norvaline (17), 3-acetoxy-2(1H)-pyridone (16), and 3-benzylhexahydropyrrolo [1,2-a] pyrazine-1,4-dione (35). A toxicity study of MFFR did not show any physical indications of toxicity and mortality up to 1500 mg/kg body weight and nontoxic up to 1000 mg/kg, which is promising for the treatment of atherothrombotic diseases.

Oxidative free radicals scavenging activity (in vitro and in vivo assay) of standardized fractions from the seeds of Argyreia speciosa (Ghav-patta) a traditional Indian medicine.

TRADITIONAL PERTINENCE: Argyreia speciosa Sweet (Linn.), belongs to the family convolvulaceae, a traditional Indian medicinal herb, has been used to treat acute/chronic ulcers, gonorrhea, rheumatoid arthritis and several nervous disorders having a long history. AIM OF THE STUDY: A broad spectrum approach of this work was to find out the antioxidant activity of Argyreia speciosa seeds, in vitro and in vivo antioxidant assay were performed. MATERIAL AND METHODS: Total phenolic content (TPC), reducing power (RP), antioxidant activity (AOA), O 2 · - (superoxide anion), DPPH (1,1-diphenyl-2-picrylhydrazyl) and ˙OH (hydroxyl) radicals scavenging activities, GSH (glutathione), CAT (catalase), SOD (superoxide dismutase) and LPO (lipid peroxidase) are the major parameters which were studied for determining in vitro and in vivo antioxidant property of seed extract & their six fractions obtained from A. speciosa. Carbon tetrachloride (CCl4) induced rat model was used to determine in vivo antioxidant assay of extract and its fractions. RESULTS: Butanol fraction (AS-BF) showed strong antioxidant property and protected oxidative DNA damage. AS-BF was found best as compared to all other fraction for determining antioxidant property of seeds with the reduction in lipid peroxide formation and increment in GSH, CAT and SOD. AS-BF showed the presence of phenolic compounds viz. gallic acid, chlorogenic acid, and ellagic acid. CONCLUSION: From these results, it was proved that A. speciosa seeds prevent tissue damage due to oxidative stress with strong antioxidant activity.

In vitro wound healing activity of 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC) and other isolates of Aegle marmelos L.: Enhances keratinocytes motility via Wnt/ß-catenin and RAS-ERK pathways.

Wound healing is a complex process in which injured skin and tissues repaired by interaction of a complex cascade of cellular events that generates resurfacing, reconstitution and restoration of the tensile strength of injured skin. It follows ß-catenin, extracellular signal regulated kinase (ERK) and Akt signaling pathways. Aegle marmelos L., generally known as bael is found to act as anti-inflammatory, antioxidant and anti-ulcer agent. Furthermore, studies have demonstrated that this Indian traditional medicinal plant, A. marmelos flower extract (AMF) was used for wound injury. Henceforth, the current study was investigated to ascertain the effect of its active constituents in vitro wound healing with mechanism involve in migration of cells and activation of ß-catenin in keratinocytes, inhibition of PGE2 in macrophages and production of collagen in fibroblasts. We have taken full thickness wound of rats and applied AMF for 2 weeks. Cutaneous wound healing activity was performed using HaCaT keratinocytes, Hs68 dermal fibroblasts and RAW264.7 macrophages to determine cell viability, nitric oxide production, collagen expression, cell migration and ß-catenin activation. Results shows that AMF treated rats demonstrated reduced wound size and epithelisation was improved, involved in keratinocytes migration by regulation of Akt signaling, beta-catenin and extracellular signal-regulated kinase (ERK) pathways. AMF and its active constituent's increased mRNA expression, inhibited nitric oxide, PGE2 release, mRNA expression of mediators in RAW 264.7 macrophages and enhances the motility of HaCaT keratinocytes in vitro wound healing of rats.

Evaluation of Cucurbita maxima extract against scopolamine-induced amnesia in rats: implication of tumour necrosis factor alpha.

Cucurbita maxima (CM) seed oil is commonly used in Indian folk medicine to treat various ailments. We have investigated the effect of CM seed oil on memory impairment induced by scopolamine in rats. Male adult Wistar rats were administered scopolamine 1 mg/kg body weight, i.p. or 1.25 mg/kg body weight, s.c. to induce memory impairment. The nootropic agent piracetam 100 mg/kg body weight, i.p. and CM seed oil 100 and 200 mg/kg body weight, p.o. were administered daily for five consecutive days. The memory function was evaluated in the Morris water maze (MWM) test, the social recognition test (SRT), the elevated plus maze (EPM) test, and the pole climbing test (PCT). Acetylcholinesterase (AChE) activity and oxidative stress parameters were estimated in the cortex, hippocampus, and cerebellum of the brains after completion of the behavioural studies. The effects of scopolamine on the levels of the tumour necrosis factor alpha (TNF-α) transcript were also investigated. Scopolamine caused memory impairment in all the behavioural paradigms along with a significant increase in the AChE activity and oxidative stress in the brain. Scopolamine also caused a significant increase in the expression of TNF-α in the hippocampus. CM seed oil exhibited antiamnesic activity as indicated by a significant reduction in the latency time in the MWM test and decreased social interaction during trial 2 in the SRT. Further, treatment with CM seed oil significantly decreased the AChE activity and malondialdehyde levels and increased the glutathione level in brain regions. CM seed oil also significantly decreased the expression of TNF-α in the hippocampus. The effect of CM seed oil on behavioural and biochemical parameters was comparable to that observed in rats treated with piracetam. These results indicate that CM seed oil may exert antiamnesic activity which may be attributed to the inhibition of AChE and inflammation as well as its antioxidant activity in the brain.