Neuropharmacological assessment and identification of possible lead compound (apomorphine) from Hygrophila spinosa through in-vivo and in-silico approaches.

The aim of this research is to examine possible neurological activity of methanol, ethyl acetate, and aqueous extracts of Hygrophila spinosa and identify possible lead compounds through in silico analysis. In vivo, neuropharmacological activity was evaluated by using four distinct neuropharmacological assessment assays. Previously reported GC-MS data and earlier literature were utilized to identify the phytochemicals present in Hygrophila spinosa. Computational studies notably molecular docking and molecular dynamic simulations were conducted with responsible receptors to assess the stability of the best interacting compound. Pharmacokinetics properties like absorption, distribution, metabolism, excretion, and toxicity were considered to evaluate the drug likeliness properties of the identified compounds. All the in vivo results support the notion that different extracts (methanol, ethyl acetate, and aqueous) of Hygrophila spinosa have significant (*p = 0.05) sedative-hypnotic, anxiolytic, and anti-depressant activity. Among all the extracts, specifically methanol extracts of Hygrophila spinosa (MHS 400 mg/kg.b.w.) showed better sedative, anxiolytic and antidepressant activity than aqueous and ethyl acetate extracts. In silico molecular docking analysis revealed that among 53 compounds 7 compounds showed good binding affinities and one compound, namely apomorphine (CID: 6005), surprisingly showed promising binding affinity to all the receptors . An analysis of molecular dynamics simulations confirmed that apomorphine (CID: 6005) had a high level of stability at the protein binding site. Evidence suggests that Hygrophila spinosa has significant sedative, anxiolytic, and antidepressant activity. In silico analysis revealed that a particular compound (apomorphine) is responsible for this action. Further research is required in order to establish apomorphine as a drug for anxiety, depression, and sleep disorders.Communicated by Ramaswamy H. Sarma.

Natural defense against multi-drug resistant Pseudomonas aeruginosa: Cassia occidentalis L. in vitro and in silico antibacterial activity.

Cassia occidentalis L. is widely used in indigenous and traditional medicine, but its impact on multi-drug resistant (MDR) bacterial infections mostly remains unknown. Therefore, this study aimed to evaluate the in vitro antibacterial efficiency of methanol and ethyl acetate extracts of C. occidentalis L. leaves (MECOL and EAECOL) against multi-drug resistant Pseudomonas aeruginosa and to identify potential antibacterial agents through computational studies targeting the LasR protein. Initially, 82 compounds were identified using GC-MS analysis, and the functional groups were determined through FT-IR analysis. Both extracts of the plant exhibited dose-dependent antibacterial activity, with MICs of 104.16 ± 36.08 µg mL-1 for MECOL and 83.33 ± 36.08 µg mL-1 for EAECOL, and an MBC of 125 µg mL-1. Among the 82 compounds, 12 potential compounds were identified based on binding scores using molecular docking with the LasR protein and MM-GBSA analysis. Furthermore, screening for ADME properties, including physicochemical features, water solubility, lipophilicity, RO5 compliance, and toxicity, identified the top three compounds: methyl dihydrojasmonate, methyl benzoate, and 4a-methyl-4,4a,5,6,7,8-hexahydro-2(3H)-naphthalenone, which also demonstrated binding affinity with the active site residues of the LpxC protein of the bacteria. Additionally, molecular dynamics (MD) simulations confirmed the binding reliability of these three phytochemicals to LasR's active pocket, comparable to the protein native inhibitory ligands (C12-HSL). The study offers scientific support for the traditional use of C. occidentalis in treating bacterial infections, highlighting the potential of the three compounds as leads for developing LasR inhibitors to combat multi-drug resistant P. aeruginosa.

Evaluation of Senna tora (L.) Roxb. leaves as source of bioactive molecules with antioxidant, anti-inflammatory and antibacterial potential.

Senna tora (L.) Roxb. is an ethno-medicinal herb used by rural and tribal people of the Satpura region of Madhya Pradesh in India and the Phatthalung Province of Thailand for treating rheumatism, bronchitis, ringworm, itches, leprosy, dyspepsia, liver disorders and heart disorders. It is also used in Chinese and Ayurvedic medicine. This study was conducted to investigate the potential of Senna tora (L.) Roxb. as a source of drug candidates against oxidants, inflammation, and bacterial infection. Preliminary phytochemical screening (PPS) and GC-MS were performed to identify the phytochemicals in the ethyl acetate extract of Senna tora (L.) Roxb. leaves (EAESTL). The in vitro antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH)- and H2O2-scavenging tests; the in vitro anti-inflammatory activity was determined by bovine serum albumin (BSA) denaturation and red blood cell (RBC) hemolysis inhibition; and the antibacterial activity was evaluated by agar-well diffusion methods. Cytotoxicity was estimated by Artemia salina larvae lethality, while acute toxicity was evaluated by oral delivery of the extract to mice. In silico antioxidant, anti-inflammatory, and antibacterial activities were predicted by the Prediction of Activity Spectra for Substances (PASS) program. The pharmacokinetics related to ADME and toxicity tests were determined by the admetSAR2 and ADMETlab2 web servers, and drug-able properties were assessed by the SwissADME server. GC-MS detected fifty-nine phytochemicals that support the types of compounds (phenols, flavonoids, tannins, terpenoids, saponins, steroids, alkaloids, glycosides and reducing sugar) identified by phytochemical screening. EAESTL exhibited dose-dependent antioxidant, anti-inflammatory, and antibacterial activities without any adverse effects or fluctuations in body weight. The PASS program predicted that the identified phytochemicals have antioxidant, anti-inflammatory and antibacterial activities. Among 51 phytochemicals, 16 showed good ADME, and 8 fulfilled drug-able properties without toxicity. Altogether, four phytochemicals, viz., benzyl alcohol, 3-(hydroxy-phenyl-methyl)-2,3-dimethyl-octan-4-one, phenylethyl alcohol and 2,6,6-trimethylbicyclo [3.1.1] heptane-3-ol, showed good pharmacokinetics and drug-able properties without toxicity, along with antioxidant, anti-inflammatory, and antibacterial activities. The obtained results suggest that Senna tora (L.) Roxb. leaves contain bioactive phytochemicals that have the potential to fight against oxidants, inflammation, and bacterial infection as potential drug candidates.

Genomic analysis and in vivo efficacy of Pediococcus acidilactici as a potential probiotic to prevent hyperglycemia, hypercholesterolemia and gastrointestinal infections.

Lactic acid bacteria are the well acknowledged probiotics that can cure a variety of diseases. In this study, we observed the in vivo potentials of Pediococcus to treat hyperglycemia, hypercholesterolemia and gastrointestinal infections. A total of 77 Lactobacillus were isolated from the milk of 10 cows and 10 goats, four of those strains inhibited both carbohydrates-hydrolyzing enzymes, α-glucosidase, and α-amylase. They all showed antagonistic effects on pathogenic E. coli and S. Typhimurium which were confirmed by performing pathogen challenge test and visualizing on Electron microscopy. 16S rRNA gene sequence identified that all four strains belong to Pediococcus genus which were further distinguished as Pediococcus acidilactici by pheS gene sequence. Whole genome sequence analysis revealed their non-pathogenic properties for human and the presence of probiotic genes responsible for stress resistance, immunomodulation, adhesion, metal and drug resistance. In vivo trial with diabetes-induced mice ascertained that all Pediococcus acidilactici had significant potentials to reduce elevated glucose and low-density lipoprotein level in blood. Interestingly, two out of four strains were significantly more effective (p < 0.0001 each) than metformin in reducing the blood glucose level. This in vivo study demonstrated that Pediococcus acidilactici might be a promising probiotic to prevent hyperglycemia, hypercholesterolemia and gastrointestinal infections.

Curcuma longa L. Prevents the Loss of ß-Tubulin in the Brain and Maintains Healthy Aging in Drosophila melanogaster.

Loss of tubulin is associated with neurodegeneration and brain aging. Turmeric (Curcuma longa L.) has frequently been employed as a spice in curry and traditional medications in the Indian subcontinent to attain longevity and better cognitive performance. We aimed to evaluate the unelucidated mechanism of how turmeric protects the brain to be an anti-aging agent. D. melanogaster was cultured on a regular diet and turmeric-supplemented diet. ß-tubulin level and physiological traits including survivability, locomotor activity, fertility, tolerance to oxidative stress, and eye health were analyzed. Turmeric showed a hormetic effect, and 0.5% turmeric was the optimal dose in preventing aging. ß-tubulin protein level was decreased in the brain of D. melanogaster upon aging, while a 0.5% turmeric-supplemented diet predominantly prevented this aging-induced loss of ß-tubulin and degeneration of physiological traits as well as improved ß-tubulin synthesis in the brain of D. melanogaster early to mid-age. The higher concentration (≥ 1%) of turmeric-supplemented diet decreased the ß-tubulin level and degenerated many of the physiological traits of D. melanogaster. The turmeric concentration-dependent increase and decrease of ß-tubulin level were consistent with the increment and decrement data obtained from the evaluated physiological traits. This correlation demonstrated that turmeric targets ß-tubulin and has both beneficial and detrimental effects that depend on the concentration of turmeric. The findings of this study concluded that an optimal dosage of turmeric could maintain a healthy neuron and thus healthy aging, by preventing the loss and increasing the level of ß-tubulin in the brain.