Isolation of 6-gingerol and semi-synthesis of 1,4-benzodiazepines derivatives: An in-situ pharmacokinetics properties, molecular docking and molecular dynamics simulation assessments.

This paper outlines a methodical approach for isolating 6-gingerol (1a) from Zingiber officinale Roscoe rhizomes on a gram-scale, resulting in a product of high purity and significant yield. Further, 6-gingerol (1a) [SSG1] derivatives, including 1-(4-hydroxy-3-methoxyphenyl)decane-3,5-dione (1ab), were synthesized via a semi-synthetic pathway involving DMP-mediated fast oxidation and replication. Subsequently, a new series of 1,4-benzodiazepines (3a-c) was synthesized quantitatively using a basic technique. This synthesis necessitated the interaction of 1ab with various o-phenylenediamine (2a-c) compounds. Spectroscopic methods were employed to characterize the synthesized 1,4-benzodiazepines (3a-c)[SSG2, SSG3 & SSG4]. Despite extensive investments by pharmaceutical companies in traditional drug research and development for diseases like type 2 diabetes (T2D), successful treatments remain elusive. Medication repurposing has gained traction as a strategy to address not only diabetes but also other disorders. Leveraging existing molecular pharmacology data accelerates the development of new medications. This paper underscores the importance of repurposing traditional medicines to combat a range of communicable and non-communicable diseases, offering a promising avenue for therapeutic advancement. Additionally, molecular docking studies suggested that one derivative (SSG2) exhibited stronger binding affinity compared to the reference standards. Overall, the findings of this study highlight the potential of semi-synthetic gingerol derivatives for the development of novel therapeutic agents.

Hexaconazole exposure may lead to Parkinson via disrupting glucocerebrosidase and parkin: molecular interaction, dynamics, MMPBSA and DFT based in-silico predictive toxicology.

Hexaconazole is a known fungicide for agricultural purposes. It has bioaccumulation ability which makes it important for its toxicological characterization. There are various neurological impacts of pollutants on human health. Therefore, in this study, we have done predictive analyses of the interaction mechanism of hexaconazole by molecular interaction analysis, molecular dynamics simulation, and Poisson-Boltzmann surface area (MM-PBSA) to assess hexaconazole's potency to disrupt the homeostasis of glucocerebrosidase (-7.9 kcal/mol) and parkin (-5.67 kcal/mol) proteins which have significant roles in the manifestation of Parkinson disease. The findings reveal that hexaconazole has the potency to form stable interactions with glucocerebrosidase and parkin. This research provides a molecular and atomic-level understanding of how hexaconazole exposure may disrupt the homeostasis of glucocerebrosidase and parkin. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration, and hydrogen bonding exhibited the potent molecular interactions of hexaconazole, which may lead to neurological manifestations such as Parkinson disease.

The Combined Anti-Tumor Efficacy of Bioactive Hydroxyapatite Nanoparticles Loaded with Altretamine.

In the current study, the combined anti-tumor efficacy of bioactive hydroxyapatite nano- particles (HA-NPs) loaded with altretamine (ALT) was evaluated. The well-known fact that HA has great biological compatibility was confirmed through the findings of the hemolytic experiments and a maximum IC50 value seen in the MTT testing. The preparation of HA-NPs was performed using the chemical precipitation process. An in vitro release investigation was conducted, and the results demonstrated the sustained drug release of the altretamine-loaded hydroxyapatite nanoparticles (ALT-HA-NPs). Studies using the JURKAT E6.1 cell lines MTT assay, and cell uptake, as well as in vivo pharmacokinetic tests using Wistar rats demonstrated that the ALT-HA-NPs were easily absorbed by the cells. A putative synergism between the action of the Ca2+ ions and the anticancer drug obtained from the carrier was indicated by the fact that the ALT-HA-NPs displayed cytotoxicity comparable to the free ALT at 1/10th of the ALT concentration. It has been suggested that a rise in intracellular Ca2+ ions causes cells to undergo apoptosis. Ehrlich's ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half.

Appraising the therapeutical potentials of Alchornea laxiflora (Benth.) Pax & K. Hoffm., an underexplored medicinal herb: A systematic review.

Ethnopharmacological relevance: Alchornea laxiflora (Benth.) Pax & K. Hoffm. (Euphorbiaceae) is an important traditional medicinal plant grown in tropical Africa. The stem, leaves, and root have been widely used in the folk medicine systems in Nigeria, Cameroon, South Africa, and Ghana to treat various ailments, including inflammatory, infectious, and central nervous system disorders, such as anxiety and epilepsy. Material and methods: The scientific name of the plant was validated using the "The Plant List," "Kew Royal Botanic Gardens," and Tropicos Nomenclatural databases. The literature search on A. laxiflora was performed using electronic search engines and databases such as Google scholar, ScienceDirect, PubMed, AJOL, Scopus, and Mendeley. Results: To the best of our knowledge, no specific and detailed review has been reported on A. laxiflora. Consequently, this review provides an up-to-date systematic presentation on ethnobotany, phytoconstituents, pharmacological activities, and toxicity profiles of A. laxiflora. Phytochemical investigations disclosed the presence of important compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and fatty acids. Furthermore, various pharmacological activities and traditional uses reported for this botanical drug were discussed comprehensively. Conclusion: This systemic review presents the current status and perspectives of A. laxiflora as a potential therapeutic modality that would assist future researchers in exploring this African botanical drug as a source of novel drug candidates for varied diseases.

Molecular Docking and Green Synthesis of Bioinorganic TiO2 Nanoparticles against E.coli and S.aureus.

This study used a simple solution evaporation approach to make a bioinorganic titanium dioxide (Bi-TiO2) photocatalyst for dye contaminant degradation. A variety of techniques, including X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) coupled with energy dispersive X-ray analysis (EDAX), and differential reflectance spectroscopy, had been employed to classify the structural and optical properties of the prepared bioinorganic photocatalyst (UV-DRS). Using simulated solar irradiation, the photocatalytic activity of the produced Bi-TiO2 nanoparticles was examined by detecting the degradation of a solution of methylene blue (MB) as a model dye molecule. The developed Bi-TiO2 photocatalyst demonstrates superior photocatalytic action than commercially available powder TiO2, according to photo-degradation experiments. E.coli and S.aureus bacterial strains were employed to assess the antibacterial activity of Bi-TiO2 nanoparticles. The most active molecules that gain antibacterial activity were examined in isolated or extracted components from the tulsi plant. The chosen compounds were docked with thymidylate kinase (TMPK), a potential therapeutic goal for the preparation of novel antibacterial drugs with the PDB ID of 4QGG. Five compounds, namely rosmarinic acid, vicenin-2, orientin, vitexin, and isoorientin, out of the 27 chosen compounds, showed a higher docking score and may aid in boosting antibacterial activity. The synthesized Bi-TiO2 nanoparticles produced antibacterial activity that was effective against Gram-positive bacteria. The nanomaterials that have been synthesized have a lot of potential in wastewater treatment and biomedical management technologies.

Medicinal Plants of Solanum Species: The Promising Sources of Phyto-Insecticidal Compounds.

Several medicinal plants have the potential to be a promising alternative pharmacological therapy for a variety of human illnesses. Many insects, including mosquitoes, are important vectors of deadly pathogens and parasites, which in the world's growing human and animal populations can cause serious epidemics and pandemics. Medicinal plants continue to provide a large library of phytochemicals, which can be used to replace chemically synthesized insecticides, and utilization of herbal product-based insecticides is one of the best and safest alternatives for mosquito control. Identifying new effective phyto-derived insecticides is important to counter increasing insect resistance to synthetic compounds and provide a safer environment. Solanum genus (Solanaceae family or nightshades) comprises more than 2500 species, which are widely used as food and traditional medicine. All research publications on insecticidal properties of Solanaceae plants and their phytoconstituents against mosquitoes and other insects published up to July 2020 were systematically analyzed through PubMed/MEDLINE, Scopus, EBSCO, Europe PMC, and Google Scholar databases, with focus on species containing active phytoconstituents that are biodegradable and environmentally safe. The current state of knowledge on larvicidal plants of Solanum species, type of extracts, target insect species, type of effects, name of inhibiting bioactive compounds, and their lethal doses (LC50 and LC90) were reviewed in this study. These studies provide valuable information about the activity of various species of Solanum and their phytochemical diversity, as well as a roadmap for optimizing select compounds for botanical repellents against a variety of vectors that cause debilitating and life-threatening human diseases.

Pharmacological Validation for the Folklore Use of Ipomoea nil against Asthma: In Vivo and In Vitro Evaluation.

Oxidative stress is the key factor that strengthens free radical generation which stimulates lung inflammation. The aim was to explore antioxidant, bronchodilatory along with anti-asthmatic potential of folkloric plants and the aqueous methanolic crude extract of Ipomoea nil (In.Cr) seeds which may demonstrate as more potent, economically affordable, having an improved antioxidant profile and providing evidence as exclusive therapeutic agents in respiratory pharmacology. In vitro antioxidant temperament was executed by DPPH, TFC, TPC and HPLC in addition to enzyme inhibition (cholinesterase) analysis; a bronchodilator assay on rabbit's trachea as well as in vivo OVA-induced allergic asthmatic activity was performed on mice. In vitro analysis of 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) expressed as % inhibition 86.28 ± 0.25 with IC50 17.22 ± 0.56 mol/L, TPC 115.5 ± 1.02 mg GAE/g of dry sample, TFC 50.44 ± 1.06 mg QE/g dry weight of sample, inhibition in cholinesterase levels for acetyl and butyryl with IC50 (0.60 ± 0.67 and 1.5 ± 0.04 mol/L) in comparison with standard 0.06 ± 0.002 and 0.30 ± 0.003, respectively, while HPLC characterization of In.Cr confirmed the existence with identification as well as quantification of various polyphenolics and flavonoids i.e., gallic acid, vanillic acid, chlorogenic acid, quercetin, kaempferol and others. However, oral gavage of In.Cr at different doses in rabbits showed a better brochodilation profile as compared to carbachol and K+-induced bronchospasm. More significant (p < 0.01) reduction in OVA-induced allergic hyper-responses i.e., inflammatory cells grade, antibody IgE as well as altered IFN-α in airways were observed at three different doses of In.Cr. It can be concluded that sound mechanistic basis i.e., the existence of antioxidants: various phenolic and flavonoids, calcium antagonist(s) as well as enzymes' inhibition profile, validates folkloric consumptions of this traditionally used plant to treat ailments of respiration.

Medicinal plants used against hepatic disorders in Bangladesh: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver disease is a major cause of illness and death worldwide which accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1 million due to viral hepatitis and hepatocellular carcinoma. That's why it is seeking the researchers' attention to find out the effective treatment strategies. Phytochemicals from natural resources are the main leads for the development of noble hepatoprotective drugs. The majority of the natural sources whose active compounds are currently employed actually have an ethnomedical use. Ethnopharmacological research is essential for the development of these bioactive compounds. These studies not only provide scientific evidence on medicinal plants utilized for particular therapeutic purposes, but they also ensure cultural heritage preservation. Plenty of experimental studies have been well-documented that the ethnomedicinal plants are of therapeutics' interest for the advanced pharmacological intervention in terms of hepatic disorders. AIM OF THE STUDY: This study summarizes the processes of hepatotoxicity induced by various toxins and explores identified hepatoprotective plants and their phytoconstituents, which can guide the extraction of novel phytochemical constituents from plants to treat liver injury. This review aimed to summarize the hepatoprotective activity of Bangladeshi medicinal plants where the bioactive compounds may be leads for the drug discovery in future. MATERIALS AND METHODS: Literature searches in electronic databases, such as Web of Science, Science Direct, SpringerLink, PubMed, Google Scholar, Semantic Scholar, Scopus, BanglaJOL, and so on, were performed using the keywords 'Bangladesh', 'ethnomedicinal plants', 'Hepatoprotective agents' as for primary searches, and secondary search terms were used as follows, either alone or in combination: traditional medicine, medicinal plants, folk medicine, liver, hepatitis, therapeutic uses, and anti-inflammatory. Besides, several books, including the book entitled "Medicinal plants of Bangladesh: chemical constituents and uses" authored by Abdul Ghani, were carefully considered, which contained pharmacological properties and phytoconstituents of many medicinal plants growing and traditionally available in Bangladesh. Among them, the most promising plant species with their latest therapeutic effects against hepatic disorders were deeply considered in this review. RESULTS: The results of this study revealed that in most cases, therapy using plant extracts stabilized altered hepatic biochemical markers induced by hepatotoxins. Initially, we investigated 32 plant species for hepatoprotective activity, however after extensive literature searching; we observed that 20 plants offer good pharmacological evidence of hepatoprotective function. Consequently, most bioactive compounds derived from the herbs including berberine, thymoquinone, andrographolide, ursolic acid, luteolin, naringenin, genistein, quercetin, troxerutin, morin, epigallocatechin-3-gallate, chlorogenic acid, emodin, curcumin, resveratrol, capsaicin, ellagic acid, etc. are appeared to be effective against hepatic disorders. CONCLUSIONS: Flavonoids, phenolic acids, monoterpenoids, diterpenoids, triterpenoids, alkaloids, chromenes, capsaicinoids, curcuminoids, and anthraquinones are among the phytoconstituents were appraised to have hepatoprotective activities. All the actions displayed by these ethnomedicinal plants could make them serve as leads in the formulation of drugs with higher efficacy to treat hepatic disorders.

Unsuccessful Progression of Sacral Neuromodulation From the Evaluation to the Implantation Stage: A Single-Center Experience.

Introduction Over the years, sacral neuromodulation (SNM) has become an established and effective treatment for chronic urinary system retention and incontinence. The process of SNM is performed in two stages, the first is an evaluation phase and the second an implant phase. This study aimed to assess the rate of failure of progression from the evaluation to the implantation stage and the factors predicting the outcome of this commonplace procedure. Materials and methods This retrospective cross-sectional study took place at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. All the patients who underwent SNM implantation from January 1, 2016 to January 1, 2021 were included. Patients younger than 14 years and patients who had the SNM implantation in a different hospital and were only followed-up at KAMC were excluded. Patient-related information were extracted from the BESTCare system. Frequency and percentage were used for the categorical variables, and the mean, median, and standard deviation to display the continuous variables. Chi-square test and Mann-Whitney U test were used to test for the association of the categorical variables. Results Among 28 patients, 46.4% (n=13) failed to progress from the evaluation phase to the implantation phase. Gender, age, having a co-morbidity, and SNM indication were not significant factors for predicting the outcome of the SNM evaluation phase. Conclusion The observed failure rate was marginally higher than the ones detected in other studies. Although no significant association was detected between evaluation stage failure and the assigned predictors, the results need to be interpreted with caution due to the small population size. Larger multicenter studies need to be done in order to investigate the link between patient characteristics and the efficacy of SNM. Establishing a concrete evidence would further refine the targeted patient population and indications for SNM.

Sacral Neuromodulation in a Pregnant Patient With Fowler's Syndrome: A Case Report.

Fowler's syndrome (FS) is a condition in which females face chronic urinary retention with abnormal electromyography (EMG) findings in the absence of structural anomalies. A sacral neuromodulation (SNM) device that restores urinary discharge is often used for treatment. It is advised to turn the device off during pregnancy. This is a case report of a 37-year-old pregnant female suffering from FS. The patient was on SNM and underwent two uneventful pregnancies despite the device being kept on throughout both pregnancies. There were no complications, and a healthy term baby was born on both occasions.