Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors.

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 µM) and 11 (IC50 = 28.4 ± 0.5 µM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 µM to 64.4 ± 0.3 µM. On the other hand, 5 (IC50 = 22.0 ± 1.1 µM) and 27 (IC50 = 31.3 ± 1.3 µM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 µM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.

Herbal remedies in the management of hyperuricemia and gout: A review of in vitro, in vivo and clinical evidences.

Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.

Innovative Encapsulation Strategies for Food, Industrial, and Pharmaceutical Applications.

Bioactive metabolites obtained from fruits and vegetables as well as many drugs have various capacities to prevent or treat various ailments. Nevertheless, their efficiency, in vivo, encounter many challenges resulting in lower efficacy as well as different side effects when high doses are used resulting in many challenges for their application. Indeed, demand for effective treatments with no or less unfavorable side effects is rising. Delivering active molecules to a particular site of action within the human body is an example of targeted therapy which remains a challenging field. Developments of nanotechnology and polymer science have great promise for meeting the growing demands of efficient options. Encapsulation of active ingredients in nano-delivery systems has become as a vitally tool for protecting the integrity of critical biochemicals, improving their delivery, enabling their controlled release and maintaining their biological features. Here, we examine a wide range of nano-delivery techniques, such as niosomes, polymeric/solid lipid nanoparticles, nanostructured lipid carriers, and nano-emulsions. The advantages of encapsulation in targeted, synergistic, and supportive therapies are emphasized, along with current progress in its application. Additionally, a revised collection of studies was given, focusing on improving the effectiveness of anticancer medications and addressing the problem of antimicrobial resistance. To sum up, this paper conducted a thorough analysis to determine the efficacy of encapsulation technology in the field of drug discovery and development.

Chemistry, Biological Activities, and Pharmacological Properties of Gastrodin: Mechanism Insights.

Gastrodin, a bioactive compound derived from the rhizome of the orchid Gastrodia elata, exhibits a diverse range of biological activities. With documented neuroprotective, anti-inflammatory, antioxidant, anti-apoptotic, and anti-tumor effects, gastrodin stands out as a multifaceted therapeutic agent. Notably, it has demonstrated efficacy in protecting against neuronal damage and enhancing cognitive function in animal models of Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Additionally, gastrodin showcases immunomodulatory effects by mitigating inflammation and suppressing the expression of inflammatory cytokines. Its cytotoxic activity involves the inhibition of angiogenesis, suppression of tumor growth, and induction of apoptosis. This comprehensive review seeks to elucidate the myriad potential effects of Gastrodin, delving into the intricate molecular mechanisms underpinning its pharmacological properties. The findings underscore the therapeutic potential of gastrodin in addressing various conditions linked to neuroinflammation and cancer.

Nutritional, medicinal and functional properties of different parts of the date palm and its fruit (Phoenix dactylifera L.) - A systematic review.

Appraised for being one of the oldest staple nutritive foods mainly in the Arabian Peninsula, the date palm tree (Phoenix dactylifera L.), is a crop native to the subtropical and tropical regions of Southern Asia and Africa. Different parts of the date tree have been extensively studied for their nutritional and therapeutic properties. Despite an array of publications on the date tree, there has been no attempt to compile in a single study the traditional uses, nutritive value, phytochemical profile, the medicinal properties as well as the potential of the different plant parts as a functional food. Therefore, this review endeavors to systematically review the scientific literature to highlight the traditional uses of date fruit and parts around the world, the nutritional profile of several parts and the medicinal properties. A total of 215 studies was retrieved (traditional uses (n = 26), nutritional (n = 52), and medicinal (n = 84)). Scientific articles were further categorized as in vitro (n = 33), in vivo (n = 35), and clinical (n = 16) evidences. Date seeds were found to be effective against E. coli and Staphylococcus aureus. Aqueous date pollen was used to manage hormonal problems and boost fertility. Palm leaves showed anti-hyperglycemic effects via inhibition of α-amylase and α-glucosidase. Unlike previous studies, this study highlighted the functional roles of all the plant parts of the palm tree and provided insights into the various mechanism of action of their bioactive compounds. Although scientific shreds of evidence have been growing over the years, there is still a dearth of studies concerning the clinical validation of the date fruit and other plant parts to provide strong evidence on their medicinal uses. In conclusion, P. dactylifera can be regarded as a potent medicinal plant with prophylactic potential and should be further explored to alleviate the burden of both communicable and non-communicable diseases.

Blocking the major inflammatory pathways by newly synthesized thiadiazine derivatives via in-vivo, in-vitro and in-silico mechanism.

A series of new thiadiazine derivatives including 2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) propanoic acids (a) and 4-methyl-2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) pentanoic acids (b) were synthesized by reacting primary alkyl/aryl amines with CS2, followed by reaction with formaldehyde and amino acids. The chemical structures of synthesized compounds were confirmed by 13C- NMR and 1H- NMR techniques. The inhibitory potential of major inflammatory enzymes, COX-2 and 5-LOX was examined. Moreover, anti-nociceptive and anti-inflammatory activities were evaluated in the in vivo thermally induced nociceptive, and carrageenan induced paw edema models in mice. The in-vitro results reflect that these compounds exhibited concentration dependent inhibition of COX-2 and 5-LOX. The tested compounds at 50 mg/kg showed significant effect on thermally induced pain, and reduced latency time (seconds) as compared to the vehicle treated animals. Moreover, tested compounds exhibited percent inhibition of paw edema in the carrageenan induced paw edema model in mice. Furthermore, the binding modes of the most active COX-2 and 5-LOX inhibitors were determined through computational methods. The computational study reflects that the docked compounds have high binding affinities for COX-2 and 5-LOX enzymes, which leads to inhibition of these enzymes.

Chemical Characterization and Multidirectional Biological Effects of Different Solvent Extracts of Arum elongatum: in Vitro and in Silico Approaches.

Arum elongatum (Araceae) is widely used traditionally for the treatment of abdominal pain, arterial hypertension, diabetes mellitus, rheumatism and hemorrhoids. This study investigated the antioxidant properties, individual phenolic compounds, total phenolic and total flavonoid contents (HPLC/MS analysis), reducing power and metal chelating effects of four extracts obtained from A. elongatum (ethyl acetate (EA), methanol (MeOH), methanol/water (MeOH/water) and infusion). The inhibitory activity of the extracts were also determined against acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase enzymes. The MeOH/water extracts contained the highest amount of phenolic contents (28.85 mg GAE/g) while the highest total flavonoid content was obtained with MeOH extract (36.77 mg RE/g). MeOH/water demonstrated highest antioxidant activity against DPPH⋅ radical at 38.90 mg Trolox equivalent per gram. The infusion extract was the most active against ABTS+ ⋅ (133.08 mg TE/g). MeOH/water extract showed the highest reducing abilities with the CUPRAC value of 102.22 mg TE/g and the FRAP value of 68.50 mg TE/g. A strong metal chelating effect was observed with MeOH/water extract (35.72 mg EDTAE/g). The PBD values of the extracts ranged from 1.01 to 2.17 mmol TE/g. EA extract displayed the highest inhibitory activity against AChE (2.32 mg GALAE/g), BChE (3.80 mg GALAE/g), α-amylase (0.56 mmol ACAE/g) and α-glucosidase (9.16 mmol ACAE/g) enzymes. Infusion extract was the most active against tyrosinase enzyme with a value of 83.33 mg KAE/g. A total of 28 compounds were identified from the different extracts. The compounds present in the highest concentration were chlorogenic acids, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, isoquercitrin, delphindin 3,5-diglucoside, kaempferol-3-glucoside and hyperoside. The biological activities of A. elongatum extracts could be due to the presence of compounds such as gallic acid, chlorogenic acids, ellagic acid, epicatechin, catechin, kaempferol, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, quercetin, isoquercitrin, and hyperoside. Extracts of A. elongatum showed promising biological activities which warrants further investigations in an endeavor to develop biopharmaceuticals.

Unveiling the Antioxidant, Clinical Enzyme Inhibitory Properties and Cytotoxic Potential of Tambourissa peltata Baker-An Understudied Endemic Plant.

This study documents for the first time the phytochemical composition and biological activities of Tambourissa peltata Baker, an endemic plant from Mauritius. Phytochemical extraction was performed using ethyl acetate, methanol and distilled water as solvents. The phytochemical composition was determined through HPLC-MS and other standard assays. The DPPH, ABTS, FRAP, CUPRAC and phosphomolybdenum assays were employed for the determination of the antioxidant potential, whereas cell viability assays were used to determine the cytotoxicity. The highest phenolic and phenolic acid contents were obtained in the aqueous extract (179.91 ± 0.67 gallic acid equivalents/g and 55.74 ± 1.43 caffeic acid equivalents/g). The highest quantity of flavonoids was obtained in the ethyl acetate extract (28.97 ± 0.46 rutin equivalents/g). The methanolic extract was the highest source of flavonols (33.71 ± 0.13 mg catechin equivalents/g). A total of 34 phytochemicals were identified, mainly proanthocyanidins and flavonoid glycosides. The highest antioxidant activity in DPPH (973.40 ± 5.65 mg TE (Trolox equivalents)/g), ABTS (2030.37 ± 40.83 mg TE/g), FRAP (1461.39 ± 5.95 mg TE/g), CUPRAC (1940.99 ± 20.95 mg TE/g) and phosphomolybdenum (8.37 ± 0.23 mmol TE/g) assays was recorded for the aqueous extract. The ethyl acetate extract was the most active metal chelator. The highest acetylcholinesterase inhibitor was the methanolic extract, whereas the ethyl acetate extract was the most active against BChE. The tyrosinase enzyme was most inhibited by the methanolic extract. Alpha-amylase and glucosidase were most inhibited by the aqueous extract. The methanolic extract was capable of inducing cell cytotoxicity to the human colorectal carcinoma without damaging normal cells. T. peltata warrants further attention from the scientific community given its multifaceted biological properties.

A Novel Approach to Develop New and Potent Inhibitors for the Simultaneous Inhibition of Protease and Helicase Activities of HCV NS3/4A Protease: A Computational Approach.

Infection of hepatitis C (HCV) is a major threat to human health throughout the world. The current therapy program suffers from restricted efficiency and low tolerance, and there is serious demand frr novel medication. NS3/4A protease is observed to be very effective target for the treatment of HCV. A data set of the already reported HCV NS3/4A protease inhibitors was first docked into the NS3/4A protease (PDB ID: 4A92A) active sites of both protease and helicase sites for calculating the docking score, binding affinity, binding mode, and solvation energy. Then the data set of these reported inhibitors was used in a computer-based program "RECAP Analyses" implemented in MOE to fragment every molecule in the subset according to simple retrosynthetic analysis rules. The RECAP analysis fragments were then used in another computer-based program "RECAP Synthesis" to randomly recombine and generate synthetically reasonable novel chemical structures. The novel chemical structures thus produced were then docked against HCV NS3/4A. After a thorough validation of all undertaken steps, based on Lipinski's rule of five, docking score, binding affinity, solvation energy, and Van der Waal's interactions with HCV NS3/4A, 12 novel chemical structures were identified as inhibitors of HCV NS3/4A. The novel structures thus designed are hoped to play a key role in the development of new effective inhibitors of HCV.

A Comprehensive Review of the Pharmacological Properties and Bioactive Components of Retama monosperma.

Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), known locally as "R'tam", is a spontaneous and annual herb that belongs to the Fabaceae family. It is native to the Mediterranean regions, specifically in the desert areas and across the Middle Atlas in Morocco. This plant has been extensively used in folk medicine and it is rich in bioactive compounds, including polyphenols, flavonoids, and alkaloids. Current research efforts are focusing on the development of novel natural drugs as alternatives to various organic and non-organic chemical products from Retama monosperma. In addition, extract, and isolated compounds obtained from different parts of the chosen plant have been described to exhibit multiple biological and pharmacological properties such as antioxidant, anti-aging, anti-inflammatory, antihypertensive, anti-helminthic, disinfectant, diuretic, and hypoglycemic effects. The plant-derived extract also acts as an antimicrobial agent, which is highly efficient in the treatment of bacterial, viral, and fungal infections. Its antiproliferative effects are associated with some mechanisms, such as the inhibition of cell cycle arrest and apoptosis. In light of these assessments, we critically highlight the beneficial effects of the flowers, stems, seeds extracts, and isolated compounds from R. monosperma (L.) Boiss in human health care, industrial, and other applications, as well as the possible ways to be employed as a potential natural source for future drug discovery.

Isoxazole analogues of dibenzazepine as possible leads against ulcers and skin disease: In vitro and in silico exploration.

Utilizing multi-target drugs shows great promise as an effective strategy against polygenic diseases characterized by intricate patho-mechanisms, such as ulcers, skin dermatitis, and cancers. The current research centers around the creation of hybrid compounds, connecting dibenzazepine and isoxazole, with the aim of exploring their potential as inhibitors for urease and tyrosinase enzymes. Analogs 6a, 6b, 6d, 6 h-6j, and 6 l demonstrated strong inhibitory potential against tyrosinase enzyme with IC50 values of 4.32 ± 0.31-12.36 ± 0.48. Whereas analogs 6a, 6c, 6e, 6f, 6h-6m, and 6r exhibited potent inhibitory activities against urease enzyme with IC50 values of 3.67 ± 0.91-15.60 ± 0.18 µM. Furthermore, compounds 6i, 6n, and 6r showed weak toxic effect in BJ-cell line, whereas the remaining compounds were found non-toxic to normal cell line. The mechanistic studies of potent inhibitors of both the enzymes showed competitive mode of inhibition. Molecular docking was employed to establish the relationship between structure and activity and to elucidate the interaction mechanism. This analysis revealed that the active analogs exhibited crucial interactions with the active site residues of urease and tyrosinase, thus corroborating our experimental results. Hence, the generated derivatives of dibenzazepine-linked isoxazoles present intriguing starting points for further investigations into their potential as inhibitors of urease and tyrosinase, with the potential for future modification and enhancement.

Explicit mechanistic insights of Prosopis juliflora extract in streptozotocin-induced diabetic rats at the molecular level.

Background: The Ancient system of medicine showed the limelight on the use of herbal remedies and was found to possess minimal side effects and acceptable therapeutic outcomes. In this context, Prosopis juliflora gained importance in managing chronic diseases such as cancer, dermatological diseases, and chronic inflammatory disorders. Hence, P. juliflora was selected for further investigation associated with diabetes and inflammation. Aim: The present study aimed to evaluate the anti-diabetic activity in chemically induced experimental rats and explore the nature of phytocomponents that may produce this activity. Methods: Experimentally, diabetes was induced by a single administration of streptozotocin at 50 mg/kg intraperitoneally in Wistar rats. The animals were treated orally with P. juliflora at low and high doses (200 and 400 mg/kg) for 10 days. Blood collected from the retro-orbital plexus was analyzed for parameters like blood glucose levels, insulin, adiponectin, Keap1 and Nrf2. PPAR-γ, AMPK and GLUT 2 levels were analyzed in the pancreatic tissue. Besides, at the end of the experiment, animals were sacrificed, and the pancreatic tissue sections were subjected for histopathological, morphometrical and immune histochemical exploration. The phytochemical composition of the plant was investigated by GC-MS. Results: The administration of P. juliflora higher dose showed a significant decrease (**p< 0.001) in blood glucose levels with a rise in adiponectin, PPARγ, Keap1, Nrf2, Glut 2, and AMPK significantly (**p< 0.001). The inflammatory cytokine TNFα was also estimated and was found to be lowered significantly (**p< 0.001) in test drug-treated animals. Furthermore, in the pancreatic tissue, the number of Islets, the area, and the number of ß-cells were improved significantly with the sub-chronic treatment of P. juliflora extract. The structure and function of ß-cells were also revamped. Conclusion: The study results demonstrated a significant effect of P. juliflora on glycemic status, inflammatory condition, and the architecture of pancreatic tissue. In the identification and isolation process by GC MS, it was noticed that P. juliflora contained few phytochemical constituents from which it might be considered a promising drug for type 2 diabetes mellitus.

Exploring LIPIDs for their potential to improves bioavailability of lipophilic drugs candidates: A review.

This review aims to provide a thorough examination of the benefits, challenges, and advancements in utilizing lipids for more effective drug delivery, ultimately contributing to the development of innovative approaches in pharmaceutical science. Lipophilic drugs, characterized by low aqueous solubility, present a formidable challenge in achieving effective delivery and absorption within the human body. To address this issue, one promising approach involves harnessing the potential of lipids. Lipids, in their diverse forms, serve as carriers, leveraging their unique capacity to enhance solubility, stability, and absorption of these challenging drugs. By facilitating improved intestinal solubility and selective lymphatic absorption of porously permeable drugs, lipids offer an array of possibilities for drug delivery. This versatile characteristic not only bolsters the pharmacological efficacy of drugs with low bioavailability but also contributes to enhanced therapeutic performance, ultimately reducing the required dose size and associated costs. This comprehensive review delves into the strategic formulation approaches that employ lipids as carriers to ameliorate drug solubility and bioavailability. Emphasis is placed on the critical considerations of lipid type, composition, and processing techniques when designing lipid-based formulations. This review meticulously examines the multifaceted challenges that come hand in hand with lipid-based formulations for lipophilic drugs, offering an insightful perspective on future trends. Regulatory considerations and the broad spectrum of potential applications are also thoughtfully discussed. In summary, this review presents a valuable repository of insights into the effective utilization of lipids as carriers, all aimed at elevating the bioavailability of lipophilic drugs.

Chalcone Scaffolds Exhibiting Acetylcholinesterase Enzyme Inhibition: Mechanistic and Computational Investigations.

This study was aimed to perform the mechanistic investigations of chalcone scaffold as inhibitors of acetylcholinesterase (AChE) enzyme using molecular docking and molecular dynamics simulation tools. Basic chalcones (C1-C5) were synthesized and their in vitro AChE inhibition was tested. Binding interactions were studied using AutoDock and Surflex-Dock programs, whereas the molecular dynamics simulation studies were performed to check the stability of the ligand-protein complex. Good AChE inhibition (IC50 = 22 ± 2.8 to 37.6 ± 0.75 µM) in correlation with the in silico results (binding energies = -8.55 to -8.14 Kcal/mol) were obtained. The mechanistic studies showed that all of the functionalities present in the chalcone scaffold were involved in binding with the amino acid residues at the binding site through hydrogen bonding, π-π, π-cation, π-sigma, and hydrophobic interactions. Molecular dynamics simulation studies showed the formation of stable complex between the AChE enzyme and C4 ligand.

Sarcorucinine-D Inhibits Cholinesterases and Calcium Channels: Molecular Dynamics Simulation and In Vitro Mechanistic Investigations.

Acetylcholinesterase (AChE) inhibitors and calcium channel blockers are considered effective therapies for Alzheimer's disease. AChE plays an essential role in the nervous system by catalyzing the hydrolysis of the neurotransmitter acetylcholine. In this study, the inhibition of the enzyme AChE by Sarcorucinine-D, a pregnane type steroidal alkaloid, was investigated with experimental enzyme kinetics and molecular dynamics (MD) simulation techniques. Kinetics studies showed that Sarcorucinine-D inhibits two cholinesterases-AChE and butyrylcholinesterase (BChE)-noncompetitively, with Ki values of 103.3 and 4.66 µM, respectively. In silico ligand-protein docking and MD simulation studies conducted on AChE predicted that Sarcorucinine-D interacted via hydrophobic interactions and hydrogen bonds with the residues of the active-site gorge of AChE. Sarcorucinine-D was able to relax contractility concentration-dependently in the intestinal smooth muscles of jejunum obtained from rabbits. Not only was the spontaneous spasmogenicity inhibited, but it also suppressed K+-mediated spasmogenicity, indicating an effect via the inhibition of voltage-dependent Ca2+ channels. Sarcorucinine-D could be considered a potential lead molecule based on its properties as a noncompetitive AChE inhibitor and a Ca2+ channel blocker.

Expression, Purification, and Comparative Inhibition of Helicobacter pylori Urease by Regio-Selectively Alkylated Benzimidazole 2-Thione Derivatives.

The urease enzyme has been an important target for the discovery of effective pharmacological and agricultural products. Thirteen regio-selectively alkylated benzimidazole-2-thione derivatives have been designed to carry the essential features of urease inhibitors. The urease enzyme was isolated from Helicobacter pylori as a recombinant urease utilizing the His-tag method. The isolated enzyme was purified and characterized using chromatographic and FPLC techniques showing a maximal activity of 200 mg/mL. Additionally, the commercial Jack bean urease was purchased and included in this study for comparative and mechanistic investigations. The designed compounds were synthesized and screened for their inhibitory activity against the two ureases. Compound 2 inhibited H. pylori and Jack bean ureases with IC50 values of 0.11; and 0.26 mM; respectively. While compound 5 showed IC50 values of 0.01; and 0.29 mM; respectively. Compounds 2 and 5 were docked against Helicobacter pylori urease (PDB ID: 1E9Y; resolution: 3.00 Å) and exhibited correct binding modes with free energy (ΔG) values of -9.74 and -13.82 kcal mol-1; respectively. Further; the in silico ADMET and toxicity properties of 2 and 5 indicated their general safeties and likeness to be used as drugs. Finally, the compounds' safety was authenticated by an in vitro cytotoxicity assay against fibroblast cells.

In Vitro and In Silico Pharmacological and Cosmeceutical Potential of Ten Essential Oils from Aromatic Medicinal Plants from the Mascarene Islands.

In this study, 10 essential oils (EOs), from nine plants (Cinnamomum camphora, Curcuma longa, Citrus aurantium, Morinda citrifolia, Petroselinum crispum, Plectranthus amboinicus, Pittosporum senacia, Syzygium coriaceum, and Syzygium samarangense) were assessed for their antimicrobial, antiaging and antiproliferative properties. While only S. coriaceum, P. amboinicus (MIC: 0.50 mg/mL) and M. citrifolia (MIC: 2 mg/mL) EOs showed activity against Cutibacterium acnes, all EOs except S. samarangense EO demonstrated activity against Mycobacterium smegmatis (MIC: 0.125-0.50 mg/mL). The EOs were either fungistatic or fungicidal against one or both tested Candida species with minimum inhibitory/fungicidal concentrations of 0.016-32 mg/mL. The EOs also inhibited one or both key enzymes involved in skin aging, elastase and collagenase (IC50: 89.22-459.2 µg/mL; 0.17-0.18 mg/mL, respectively). Turmerone, previously identified in the C. longa EO, showed the highest binding affinity with the enzymes (binding energy: -5.11 and -6.64 kcal/mol). Only C. aurantium leaf, C. longa, P. amboinicus, P. senacia, S. coriaceum, and S. samarangense EOs were cytotoxic to the human malignant melanoma cells, UCT-MEL1 (IC50: 88.91-277.25 µg/mL). All the EOs, except M. citrifolia EO, were also cytotoxic to the human keratinocytes non-tumorigenic cells, HaCat (IC50: 33.73-250.90 µg/mL). Altogether, some interesting therapeutic properties of the EOs of pharmacological/cosmeceutical interests were observed, which warrants further investigations.

Khat Chewing Induces a Floral Shift in Dental Material-Associated Microbiota: A Preliminary Study.

BACKGROUND The habit of khat (Catha Edulis Forskal) chewing is widely practiced in the southern regions of Saudi Arabia, Yemen, and East Africa. This social habit has tremendous effects on oral and general health of khat chewers. Khat may affect bacterial species in plaque biofilms on oral rehabilitation materials. This preliminary case-controlled study aimed to assess and compare the effect of khat chewing on bacterial biodiversity between non-khat chewers (NKC) and khat chewers (KC) in oral biofilms on oral rehabilitation materials using polymerase chain reaction (PCR). MATERIAL AND METHODS Fifty participants were organized into 2 equal groups of NKC and KC, each containing 5 subgroups related to filling material type. Some participants had amalgam (A) or composite (C) restorations, while others had feldspathic porcelain (FP), nickel chromium (NC), and zirconia ceramic (ZC) crowns or bridges. Oral biofilm samples were collected from all participants, DNA was extracted, and samples were subjected to PCR. Bacterial species were then identified and counted. PCR products were sequenced to detect similarity. Partial 16S rRNA gene sequences of the current study samples were compared with 16S rRNA gene sequences from GenBank using BLAST on the National Center for Biotechnology Information website. RESULTS The Streptococcus sp. was the most common bacterial species among our participants (40; 80%), followed by Lactobacillus and Veillonella spp., accounting for 12% (6) and 8% (4), respectively. Streptococcus sp. was observed equally among NKC and KC, but Lactobacillus and Veillonella spp. were higher in KC and NKC, respectively. Lactobacillus was associated mainly with prosthetic materials, and Streptococcus was found among all examined dental restorative materials. CONCLUSIONS This research concluded that khat chewing significantly affects bacterial biodiversity in oral biofilms in the presence of different restorative and prosthetic dental materials.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.

Effects of Khat on Surface Roughness and Color of Feldspathic and Zirconia Porcelain Materials under Simulated Oral Cavity Conditions.

Background and Objectives: Khat chewing is considered as a daily habit that is practiced by more than five million people globally. The effect of khat chewing on the surface roughness and the color stability of natural teeth and the material used in the fabrication of dental prosthesis remains unknown. This study was conducted to explore and compare the effect of khat homogenate (KH) on the surface roughness (Ra) and the average color changes (ΔE*) amongst natural teeth and selected shades from different porcelain types, namely, feldspathic metal ceramic (MC) VM13, computer-aided design/computer assisted manufacture (CAD/CAM) feldspathic (Vitablocs Mark II), and multilayer zirconia (Ceramill Zolid PS) porcelains. Materials and Methods: Seventy samples were prepared from natural teeth, feldspathic MC, CAD/CAM Vitablocs Mark II, and zirconia porcelain. The Ra values were measured using a profilometer and expressed in micrometers, whereas the ΔE* values were measured using VITA Easyshade® V spectrophotometer for all samples before and after frequent immersion and thermocycling in KH for 30 days. The surface topography was used to assess the materials surfaces (glazed or polished) after KH immersion by using a white light interferometry machine. Results: Results revealed that the Ra and the ΔE* values of the different types of tested porcelain were influenced by KH. The order of surface roughness values was glazed or polished MC > polished Zircon > polished Vitablocs Mark II > natural teeth. The lowest ΔE* values were recorded for glazed Vitablocs Mark II and MC, and the values could be arranged as polished zircon > natural teeth > glazed zircon > polished MC > polished Vitablocs Mark II. P values were significantly varied (< 0.001) among all the tested groups, except the zircon group (>0.05) for both Ra and ΔE*. Conclusion: KH significantly affected both surface parameter and color of glazed or polished porcelain materials and natural teeth.