Catharanthus roseus-assisted bio-fabricated zinc oxide nanoparticles for promising antibacterial potential against Klebsiella pneumoniae.

This study emphasized on the synthesis of zinc oxide nanoparticles (ZnO NPs) in an environmentally friendly manner from the extract of Catharanthus roseus leaves and its antibacterial assessment against the pneumonia-causing pathogen Klebsiella pneumoniae. This simple and convenient phytosynthesis approach is found to be beneficial over conventional methods, wherein plants serve as excellent reducing, capping, and stabilizing agents that enables the formation of ZnO NPs without the use of harmful chemicals. The formation of ZnO NPs was confirmed through several characterization techniques such as UV-visible spectroscopy, XRD, FT-IR, SEM, HR-TEM, and EDX. XRD analysis revealed high polycrystallinity with crystallite size of approximately 13 nm. SEM and HR-TEM revealed the hexagonal structure of ZnO NPs with the particle size range of 20-50 nm. The EDX shows the elemental purity without any impurity. Furthermore, the antibacterial efficacy by the technique of disc diffusion exhibited clear inhibition zones in ZnO NPs-treated discs. In addition, 125 µg/mL of ZnO NP concentration showed minimum inhibition by the microbroth dilution method. The potent inhibitory activity was further validated with trypan blue dye exclusion and fluorescence microscopy. Finally, SEM examination confirmed the efficient antibacterial potential of ZnO NPs through disruption of the intact morphology of Klebsiella pneumoniae.

In Silico Molecular Docking Analysis of Karanjin against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski's drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer's animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development.

Silibinin and Naringenin against Bisphenol A-Induced Neurotoxicity in Zebrafish Model-Potential Flavonoid Molecules for New Drug Design, Development, and Therapy for Neurological Disorders.

Bisphenol A (BPA), a well-known xenoestrogen, is commonly utilised in the production of polycarbonate plastics. Based on the existing evidence, BPA is known to induce neurotoxicity and behavioural issues. Flavonoids such as silibinin and naringenin have been shown to have biological activity against a variety of illnesses. The current research evaluates the neuropharmacological effects of silibinin and naringenin in a zebrafish model against neurotoxicity and oxidative stress caused by Bisphenol A. In this study, a novel tank diving test (NTDT) and light−dark preference test (LDPT) were used in neurobehavioural investigations. The experimental protocol was planned to last 21 days. The neuroprotective effects of silibinin (10 µM) and naringenin (10 µM) in zebrafish (Danio rerio) induced by BPA (17.52 µM) were investigated. In the brine shrimp lethality assay, the 50% fatal concentrations (LC50) were 34.10 µg/mL (silibinin) and 91.33 µg/mL (naringenin) compared to the standard potassium dichromate (13.15 µg/mL). The acute toxicity investigation found no mortality or visible abnormalities in the silibinin- and naringenin-treated groups (LC50 > 100 mg/L). The altered scototaxis behaviour in LDPT caused by BPA was reversed by co-supplementation with silibinin and naringenin, as shown by decreases in the number of transitions to the light zone and the duration spent in the light zone. Our findings point to BPA's neurotoxic potential in causing altered scototaxis and bottom-dwelling behaviour in zebrafish, as well as the usage of silibinin and naringenin as potential neuroprotectants.

Tilianin: A Potential Natural Lead Molecule for New Drug Design and Development for the Treatment of Cardiovascular Disorders.

Cardiovascular disorders (CVDs) are the leading risk factor for death worldwide, and research into the processes and treatment regimens has received a lot of attention. Tilianin is a flavonoid glycoside that can be found in a wide range of medicinal plants and is most commonly obtained from Dracocephalum moldavica. Due to its extensive range of biological actions, it has become a well-known molecule in recent years. In particular, numerous studies have shown that tilianin has cardioprotective properties against CVDs. Hence, this review summarises tilianin's preclinical research in CVDs, as well as its mechanism of action and opportunities in future drug development. The physicochemical and drug-likeness properties, as well as the toxicity profile, were also highlighted. Tilianin can be a natural lead molecule in the therapy of CVDs such as coronary heart disease, angina pectoris, hypertension, and myocardial ischemia, according to scientific evidence. Free radical scavenging, inflammation control, mitochondrial function regulation, and related signalling pathways are all thought to play a role in tilianin's cardioprotective actions. Finally, we discuss tilianin-derived compounds, as well as the limitations and opportunities of using tilianin as a lead molecule in drug development for CVDs. Overall, the scientific evidence presented in this review supports that tilianin and its derivatives could be used as a lead molecule in CVD drug development initiatives.

Kirenol: A Potential Natural Lead Molecule for a New Drug Design, Development, and Therapy for Inflammation.

Kirenol, a potential natural diterpenoid molecule, is mainly found in Sigesbeckia species. Kirenol has received a lot of interest in recent years due to its wide range of pharmacological actions. In particular, it has a significant ability to interact with a wide range of molecular targets associated with inflammation. In this review, we summarise the efficacy and safety of kirenol in reducing inflammation, as well as its potential mechanisms of action and opportunities in future drug development. Based on the preclinical studies reported earlier, kirenol has a good therapeutic potential against inflammation involved in multiple sclerosis, inflammatory bowel disorders, diabetic wounds, arthritis, cardiovascular disease, bone damage, and joint disorders. We also address the physicochemical and drug-like features of kirenol, as well as the structurally modified kirenol-derived molecules. The inhibition of pro-inflammatory cytokines, reduction in the nuclear factor kappa-B (NF-κB), attenuation of antioxidant enzymes, stimulation of heme-oxygenase-1 (HO-1) expression, and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation are among the molecular mechanisms contributing to kirenol's anti-inflammatory actions. Furthermore, this review also highlights the challenges and opportunities to improve the drug delivery of kirenol for treating inflammation. According to the findings of this review, kirenol is an active molecule against inflammation in numerous preclinical models, indicating a path to using it for new drug discovery and development in the treatment of a wide range of inflammations.

Chemistry, Biosynthesis and Pharmacology of Sarsasapogenin: A Potential Natural Steroid Molecule for New Drug Design, Development and Therapy.

Sarsasapogenin is a natural steroidal sapogenin molecule obtained mainly from Anemarrhena asphodeloides Bunge. Among the various phytosteroids present, sarsasapogenin has emerged as a promising molecule due to the fact of its diverse pharmacological activities. In this review, the chemistry, biosynthesis and pharmacological potentials of sarsasapogenin are summarised. Between 1996 and the present, the relevant literature regarding sarsasapogenin was obtained from scientific databases including PubMed, ScienceDirect, Scopus, and Google Scholar. Overall, sarsasapogenin is a potent molecule with anti-inflammatory, anticancer, antidiabetic, anti-osteoclastogenic and neuroprotective activities. It is also a potential molecule in the treatment for precocious puberty. This review also discusses the metabolism, pharmacokinetics and possible structural modifications as well as obstacles and opportunities for sarsasapogenin to become a drug molecule in the near future. More comprehensive preclinical studies, clinical trials, drug delivery, formulations of effective doses in pharmacokinetics studies, evaluation of adverse effects and potential synergistic effects with other drugs need to be thoroughly investigated to make sarsasapogenin a potential molecule for future drug development.

Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uropathogens-An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections.

Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis. This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in B. monnieri extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, -7.5 kcal/mol and -7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski's rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from B. monnieri can be a potent inhibitor for the effective killing of K. pneumoniae and P. mirabilis. Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.

Chemistry, Biosynthesis and Pharmacology of Viniferin: Potential Resveratrol-Derived Molecules for New Drug Discovery, Development and Therapy.

Viniferin is a resveratrol derivative. Resveratrol is the most prominent stilbenoid synthesized by plants as a defense mechanism in response to microbial attack, toxins, infections or UV radiation. Different forms of viniferin exist, including alpha-viniferin (α-viniferin), beta-viniferin (ß-viniferin), delta-viniferin (δ-viniferin), epsilon-viniferin (ε-viniferin), gamma-viniferin (γ-viniferin), R-viniferin (vitisin A), and R2-viniferin (vitisin B). All of these forms exhibit a range of important biological activities and, therefore, have several possible applications in clinical research and future drug development. In this review, we present a comprehensive literature search on the chemistry and biosynthesis of and the diverse studies conducted on viniferin, especially with regards to its anti-inflammatory, antipsoriasis, antidiabetic, antiplasmodic, anticancer, anti-angiogenic, antioxidant, anti-melanogenic, neurodegenerative effects, antiviral, antimicrobial, antifungal, antidiarrhea, anti-obesity and anthelminthic activities. In addition to highlighting its important chemical and biological activities, coherent and environmentally acceptable methods for establishing vinferin on a large scale are highlighted to allow the development of further research that can help to exploit its properties and develop new phyto-pharmaceuticals. Overall, viniferin and its derivatives have the potential to be the most effective nutritional supplement and supplementary medication, especially as a therapeutic approach. More researchers will be aware of viniferin as a pharmaceutical drug as a consequence of this review, and they will be encouraged to investigate viniferin and its derivatives as pharmaceutical drugs to prevent future health catastrophes caused by a variety of serious illnesses.

Solubility Determination, Hansen Solubility Parameters and Thermodynamic Evaluation of Thymoquinone in (Isopropanol + Water) Compositions.

This article studies the solubility, Hansen solubility parameters (HSPs), and thermodynamic behavior of a naturally-derived bioactive thymoquinone (TQ) in different binary combinations of isopropanol (IPA) and water (H2O). The mole fraction solubilities (x3) of TQ in various (IPA + H2O) compositions are measured at 298.2-318.2 K and 0.1 MPa. The HSPs of TQ, neat IPA, neat H2O, and binary (IPA + H2O) compositions free of TQ are also determined. The x3 data of TQ are regressed by van't Hoff, Apelblat, Yalkowsky-Roseman, Buchowski-Ksiazczak λh, Jouyban-Acree, and Jouyban-Acree-van't Hoff models. The maximum and minimum x3 values of TQ are recorded in neat IPA (7.63 × 10-2 at 318.2 K) and neat H2O (8.25 × 10-5 at 298.2 K), respectively. The solubility of TQ is recorded as increasing with the rise in temperature and IPA mass fraction in all (IPA + H2O) mixtures, including pure IPA and pure H2O. The HSP of TQ is similar to that of pure IPA, suggesting the great potential of IPA in TQ solubilization. The maximum molecular solute-solvent interactions are found in TQ-IPA compared to TQ-H2O. A thermodynamic study indicates an endothermic and entropy-driven dissolution of TQ in all (IPA + H2O) mixtures, including pure IPA and pure H2O.

Haloperidol-induced painless legs and moving toe syndrome in a schizophrenia patient: a case report.

Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient's PoLMT is unknown. We present a case of PoLMT in 45-year-old woman with a history of haloperidol intake for 10 months. Haloperidol was discontinued, and aripiprazole (15 mg) was initiated. After this switch, a reduction in movement was observed in the third and fourth toes; however, the second toe showed no discernible change.

Painless Legs and Moving Toe Syndrome (PoLMT) is a rare condition in which the toe moves on its own without any pain. No one knows for sure what causes PoLMT in patients. In this case report, we discuss a 45-year-old woman with PoLMT who was taking a drug called haloperidol for 10 months prior to their visit to hospital. Another drug, aripiprazole, was started after haloperidol was stopped. It was noticed that the third and fourth toes moved less after this switch in medication, but no change was noticed in the second toe.

Green Synthesis of Cerium Oxide Nanoparticles, Characterization, and Their Neuroprotective Effect on Hydrogen Peroxide-Induced Oxidative Injury in Human Neuroblastoma (SH-SY5Y) Cell Line.

Cerium oxide nanoparticles (CeO2NPs) have a broad scale of applications in the biomedical field due to their excellent physicochemical and catalytic properties. The present study aims to synthesize the CeO2NPs from Centella asiatica (C. asiatica) leaf extract, which has been used in Indian traditional medicine for its neuroprotective properties. The CeO2NPs were characterized by ultraviolet-visible, X-ray diffraction, Fourier transform infrared, Raman spectroscopy, scanning electron microscopy- energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. The antioxidant property was evaluated by 2,2-di (4-tert-octyl phenyl)-1-picrylhydrazyl and OH radical assays. The neuroprotective potential was assessed against the oxidative stress (OS) induced by H2O2 in the human neuroblastoma (SH-SY5Y) cell line. CeO2NPs exhibited significant DPPH and OH radical scavenging activity. Our results revealed that CeO2NPs significantly increased H2O2-induced cell viability, decreased lactate dehydrogenase, protein carbonyls, reactive oxygen species generation, apoptosis, and upregulated antioxidant enzyme activity. Our findings suggest that the CeO2NPs protect the SH-SY5Y cells from OS and apoptosis, which could potentially counter OS-related neurodegenerative disorders.

Computational intelligence modeling of hyoscine drug solubility and solvent density in supercritical processing: gradient boosting, extra trees, and random forest models.

This work presents the results of using tree-based models, including Gradient Boosting, Extra Trees, and Random Forest, to model the solubility of hyoscine drug and solvent density based on pressure and temperature as inputs. The models were trained on a dataset of hyoscine drug with known solubility and density values, optimized with WCA algorithm, and their accuracy was evaluated using R2, MSE, MAPE, and Max Error metrics. The results showed that Gradient Boosting and Extra Trees models had high accuracy, with R2 values above 0.96 and low MAPE and Max Error values for both solubility and density output. The Random Forest model was less accurate than the other two models. These findings demonstrate the effectiveness of tree-based models for predicting the solubility and density of chemical compounds and have potential applications in determination of drug solubility prior to process design by correlation of solubility and density to input parameters including pressure and temperature.

Encapsulation of Leptadenia pyrotechnica (Khip) Extract in Carbomer Based Emulgel for Its Enhanced Antioxidant Effects and Its In Vitro Evaluation.

BACKGROUND: The use of natural products in skin care has been valued for their tremendous therapeutic benefits since ancient times. The current study was aimed at exploring the Leptadenia pyrotechnica plant extract and development of a stable emulgel loaded with the same extract to assess its cosmeceutical potentials. METHODOLOGY: A stable emulgel loaded with methanolic plant extract along with its control gel was prepared by homogenization. The antioxidant potential of extracts prepared in different solvents (methanol MLP, ethanol ELP, n-hexane nLP, ethyl acetate EALP, and petroleum ether PLP) was determined by DPPH scavenging activity. The presence of phytochemicals was confirmed by total phenolic and flavonoid content analysis (TPC/TFC). HPLC was used for quantification of bioactive components. FTIR analysis was performed for confirmation of functional groups. SPF was calculated via spectroscopic analysis for extract, control gel, and extract loaded emulgel. Stability studies included physical evaluation, pH, conductivity, spreadability, and rheological testing of both control and test emulgels at different temperatures, i.e., 8 °C ± 1, 25 °C ± 1, 40 °C ± 1, 40 °C ± 1 with RH of 75% for a period of 90 days. RESULTS: DPPH radical scavenging activity showed the highest antioxidant activity of 85.5% ± 2.78 for MLP. TPC and TFC were also found to be highest for the methanolic fraction, i.e., 190.98 ± 0.40 mgGAE/g and 128.28 ± 2.64 mgQE/g, respectively. The SPF of methanolic extract, placebo gel, and LPEG was 13.43 ± 0.46, 2.37 ± 0.33, and 7.28 ± 0.56, respectively. HPLC assay confirmed the presence of catechin, vanillic acid, caffeic acid, and sinapinic acid. Rheological analysis showed that formulation has pseudo-plastic flow behavior. Other stability tests also revealed that prepared emulgel is a stable one. CONCLUSION: A stable emulgel loaded with Leptadenia pyrotechnica plant extract was successfully prepared and characterized for its cosmetic effects.

A phenylpropanoid dimer from the leaves of Piper betle.

Phytochemical analyses of the chloroform extract of Piper betle L. var. Sanchi, Piperaceae, leaves led to the isolation of a new phenylpropanoid analogue for the first time: hydroxychavicol dimer, 2-(γ'-hydroxychavicol)-hydroxychavicol (S1), on the basis of spectroscopic data 1 D (1H and 13C) and 2 D (1H-1H COSY and HMBC) NMR, as well as ESI-MS, FT-IR, HR-ESI-MS and LC-ESI-MS. Compound S1 exhibited excellent antioxidant DPPH radical scavenging activity with IC50 values of 9.07 µg/mL, compared to ascorbic acid as a standard antioxidant drug with IC50 value of 3.41 µg/mL. Evaluation of cytotoxic activity against two human colon cancer cell lines (HT 29 and COLO-205) showed significant effect with GI50 values of 73.81 and 64.02 µmol/L, compared to Doxorubicin® as a standard cytotoxic drug with GI50 value of <10 µmol/L.

Antidepressant and Anxiolytic Potentials of the Chewing Stick, Salvadora persica.

Materials and Methods: Salvadora persica stem bark was extracted with two different solvents, i.e., ethyl acetate and water, and preliminary phytochemical screening was performed. Two behavioral models were used: an elevated plus maze test (EPM) and the light and dark model test for anxiolytic parameters, and a forced swim test (FST) for antidepressant effects. Healthy mice weighing 18-40 gms were treated orally in four groups (n = 6), i.e., negative control treated with normal saline and positive control with 1 mg/kg diazepam (EPM) and 30 mg/kg fluoxetine (FST), and the test groups were treated with 500 mg/kg of aqueous and ethyl acetate Sp extract. The number of entries and duration spent in the open arm for 5 minutes were the parameters for evaluating the anxiolytic activity (EPM). Duration of immobility was measured for 5 min in the FST model. Results: In EPM, both the Sp extracts significantly (p < 0.005) increased the number of entries and the time spent in the open arms and was much similar to those of diazepam. Similarly, these extracts and fluoxetine significantly (p < 0.005) decreased the immobility time in FST. Conclusion: The results suggest the therapeutic potential of Salvadora persica an alternative in the management of comorbid anxiety and depression.

Development and Characterization of Gel-Based Buccoadhesive Bilayer Formulation of Nifedipine.

A promising controlled drug delivery system has been developed based on polymeric buccoadhesive bilayered formulation that uses a drug-free backing layer and a polymeric hydrophilic gel buccoadhesive core layer containing nifedipine. The DSC thermogravimetric analysis confirms the drug's entrapment in the gel layer and reveals no evidence of a potential interaction. Various ratios of bioadhesive polymers, including HPMC K100, PVP K30, SCMC, and CP 934, were combined with EC as an impermeable backing layer to ensure unidirectional drug release towards the buccal mucosa. The polymeric compositions of hydrophilic gel-natured HPMC, SCMC, and CP formed a matrix layer by surrounding the core nifedipine during compression. Preformulation studies were performed for all of the ingredients in order to evaluate their physical and flow characteristics. Ex vivo buccoadhesive strength, surface pH, swelling index, in vitro and in vivo drug release, and ex vivo permeation investigations were performed to evaluate the produced gel-based system. Rapid temperature variations had no appreciable impact on the substance's physical properties, pharmacological content, or buccoadhesive strength during stability testing using actual human saliva. It was clear from a histological examination of the ex vivo mucosa that the developed system did not cause any irritation or inflammation at the site of administration. The formulation NT5 was the best one, with a correlation coefficient of 0.9966. The in vitro and in vivo drug release profiles were well correlated, and they mimic the in vitro drug release pattern via the biological membrane. Thus, the developed gel-based formulation was found to be novel, stable, and useful for the targeted delivery of nifedipine.

Influence of solvent selection and extraction methods on the determination of polyphenols, antioxidant, lipoxygenase and tyrosinase inhibition activities of Opuntia ficus-indica fruits peel and pulp collected from the Kingdom of Saudi Arabia (KSA).

The effect of extracting solvents used by two methods on the TPC, TFC, antioxidant as well as lipoxygenase, and tyrosinase inhibition activities of O. ficus-indica fruit (peel and pulp) were studied. The results manifest that extracts with solvent polarities showed different levels of polyphenols contents and antioxidant activities. The extracts acquired by the Soxhlet method were the most fascinating. Interestingly, peel extracts contain more polyphenols than pulp and showed activities. Lipoxygenase and tyrosinase inhibitory activity of the fruit peel and pulp extracts was reported for the first time. The promising results obtained prompted to the formulation of a stable phytocosmetic emulsion system loaded with 1% pre-concentrated peel extract, aiming to revive facial skin properties. The efficacy of the formulations was determined through SPF and UVA protection factors. To the in vitro safety assessment CAM-TBS, HET-CAM, and red blood cell tests were achieved. Importantly, the formulation did not induce any toxicity.

Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats.

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.

Phytochemical characterization of Typha domingensis and the assessment of therapeutic potential using in vitro and in vivo biological activities and in silico studies.

Typha domingensis, a medicinal plant with significant traditional importance for curing various human diseases, has potentially bioactive compounds but was less explored previously. Therefore, this study aims to investigate the therapeutic potential of T. domingensis by evaluating the phytochemical profile through high-performance liquid chromatography (HPLC) techniques and its biological activities (in vitro and in vivo) from the methanolic extract derived from the entire plant (TDME). The secondary metabolite profile of TDME regulated by reverse phase ultra-high-performance liquid chromatography-mass spectrometry (RP-UHPLC-MS) revealed some bioactive compounds by -ve and +ve modes of ionization. The HPLC quantification study showed the precise quantity of polyphenols (p-coumaric acid, 207.47; gallic acid, 96.25; and kaempferol, 95.78 µg/g extract). The enzyme inhibition assays revealed the IC50 of TDME as 44.75 ± 0.51, 52.71 ± 0.01, and 67.19 ± 0.68 µgmL-1, which were significant compared to their respective standards (indomethacin, 18.03 ± 0.12; quercetin, 4.11 ± 0.01; and thiourea, 8.97 ± 0.11) for lipoxygenase, α-glucosidase, and urease, respectively. Safety was assessed by in vitro hemolysis (4.25% ± 0.16% compared to triton × 100, 93.51% ± 0.36%), which was further confirmed (up to 10 g/kg) by an in vivo model of rats. TDME demonstrated significant (p < 0.05) potential in analgesic activity by hot plate and tail immersion tests and anti-inflammatory activity by the carrageenan-induced hind paw edema model. Pain latency decreased significantly, and the anti-inflammatory effect increased in a dose-dependent way. Additionally, in silico molecular docking revealed that 1,3,4,5-tetracaffeoylquinic acid and formononetin 7-O-glucoside-6″-O-malonate possibly contribute to enzyme inhibitory activities due to their higher binding affinities compared to standard inhibitors. An in silico absorption, distribution, metabolism, excretion, and toxicological study also predicted the pharmacokinetics and safety of the chosen compounds identified from TDME. To sum up, it was shown that TDME contains bioactive chemicals and has strong biological activities. The current investigations on T. domingensis could be extended to explore its potential applications in nutraceutical industries and encourage the isolation of novel molecules with anti-inflammatory and analgesic effects.

Celastrol: A Potential Natural Lead Molecule for New Drug Design, Development and Therapy for Memory Impairment.

Celastrol is a naturally occurring chemical isolated from Tripterygium wilfordii Hook. f., root extracts widely known for their neuroprotective properties. In this review, we focus on the efficacy of celastrol in mitigating memory impairment (MI) in both in vivo and in vitro models. Scopus, PubMed and Web of Science databases were utilised to locate pertinent literatures that explore the effects of celastrol in the brain, including its pharmacokinetics, bioavailability, behavioral effects and some of the putative mechanisms of action on memory in many MI models. To date, preclinical studies strongly suggest that celastrol is highly effective in enhancing the cognitive performance of MI animal models, particularly in the memory domain, including spatial, recognition, retention and reference memories, via reduction in oxidative stress and attenuation of neuro-inflammation, among others. This review also emphasised the challenges and potential associated enhancement of medication delivery for MI treatment. Additionally, the potential structural alterations and derivatives of celastrol in enhancing its physicochemical and drug-likeness qualities are examined. The current review demonstrated that celastrol can improve cognitive performance and mitigate MI in several preclinical investigations, highlighting its potential as a natural lead molecule for the design and development of a novel neuroprotective medication.