Cytotoxic activity of Thymus capitatus collected from Hail region in Saudi Arabia with mechanistic study via induction of caspase-dependent apoptosis and S-phase arrest

Thymus capitatus is a plant grows in Mediterranean area and some Arab countries such as Saudi Arabia. It possesses numerous medicinal values. Its common name is Zaatar and it belongs to family Lamiaceae Thymus capitatus leaves and stem were collected from Hail region, Saudi Arabia. Then both leaves and stem were extracted with ethanol. This study was performed to evaluate cytotoxic activity of Thymus capitatus leaves and stem ethanolic extract in details. Doxorubicin was used as a standard and the relevant half maximal inhibitory concentration (IC50) values were computed for each cell line by 3-(4,5- diemthylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. In addition, further mechanistic study was carried out by using Apoptosis assay to explore cytotoxic activity of plant extract. Both leaves and stems extracts were screened against HepG2, A-549, HCT-116 and   MCF-7 cancer cell lines. It was found that leaves’ extract shows high and moderate cytotoxic activity against both A-549 and HepG2 cancer cell lines, respectively (with IC50 = 13.6 and 21.5 μg/ml, respectively), while stem’s extract exerted moderate cytotoxic activity against A-549 cancer cell lines (with IC50 = 21.38 μg/ml).  Further mechanistic study was carried out on A-549 cells by using apoptosis assay. It showed that leaves’ extract resulted in arrest of S-phase and caused apoptosis through activation of caspase-3, p53 and Bax, in addition to down regulation of Bcl-2

Anti-ulcer properties, cytokines, and apoptosis regulatory effects of Olea europaea leaves from Hail Province, Saudi Arabia

This study investigated the anti-ulcer properties of raw olive leaf powder (OLP) and its immunomodulatory potential through the cytokine network. The efficacy of OLP extract in treating stomach ulcers in rats in ethanol-induced models was examined using a single dosage (100, 200, 400 mg/kg) in groups 4, 5, and 6. The OLP demonstrated substantial anti-ulcer action even at 100 mg/kg. The activity was better at 400 mg/kg and almost equivalent to the conventional omeprazole treatment at 20 mg/kg in group 3. The cytokine network was studied in groups 1, 2, 3, and 6. The cytokine network was efficiently regulated by reducing the production of cytokines such as IL-1β, IL-2, IL-4, IL-6, IL-10, and TNF-α. The levels of caspase-3 and caspase-9 were also lowered in groups 3 and 4 considerably at p < 0.05. It is interesting to note that the expression of IFN was greater in animals treated with OLP in group 4, as compared to animals treated with omeprazole in group 3, as well as animals from the disease control group 2, when analyzed at a significance level of p < 0.05. The results revealed that OLP has intriguing potential for anti-ulcer action, and possesses immunomodulatory capabilities to control inflammatory cytokines and apoptotic markers

Synthesis, molecular docking, and dynamic simulation targeting main protease (Mpro) of new, Thiazole clubbed pyridine scaffolds as potential COVID-19 inhibitors

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N′-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = −8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19

Cytotoxic activity of Thymus capitatus collected from Hail region in Saudi Arabia with mechanistic study via induction of caspase-dependent apoptosis and S-phase arrest

Thymus capitatus is a plant grows in Mediterranean area and some Arab countries such as Saudi Arabia. It possesses numerous medicinal values. Its common name is Zaatar and it belongs to family Lamiaceae Thymus capitatus leaves and stem were collected from Hail region, Saudi Arabia. Then both leaves and stem were extracted with ethanol. This study was performed to evaluate cytotoxic activity of Thymus capitatus leaves and stem ethanolic extract in details. Doxorubicin was used as a standard and the relevant half maximal inhibitory concentration (IC50) values were computed for each cell line by 3-(4,5- diemthylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. In addition, further mechanistic study was carried out by using Apoptosis assay to explore cytotoxic activity of plant extract. Both leaves and stems extracts were screened against HepG2, A-549, HCT-116 and   MCF-7 cancer cell lines. It was found that leaves’ extract shows high and moderate cytotoxic activity against both A-549 and HepG2 cancer cell lines, respectively (with IC50 = 13.6 and 21.5 μg/ml, respectively), while stem’s extract exerted moderate cytotoxic activity against A-549 cancer cell lines (with IC50 = 21.38 μg/ml).  Further mechanistic study was carried out on A-549 cells by using apoptosis assay. It showed that leaves’ extract resulted in arrest of S-phase and caused apoptosis through activation of caspase-3, p53 and Bax, in addition to down regulation of Bcl-2

GC–MS analysis, molecular docking, and pharmacokinetic studies of Multidentia crassa extracts’ compounds for analgesic and anti-inflammatory activities in dentistry

Abstract Plant extracts have been useful for oral health or dentistry. However, only a few evidence-based justifications exist. This study evaluated Multidentia crassa (Hiern) Bridson & Verdc, one of the oral health-used plants in Malawi. Gas chromatography-mass spectrometry (GC-MS) and Fourier transform infrared (FT-IR) identified the extracts’ compounds. The pharmacokinetics of the identified compounds were studied using pkCSM and SwissADME, and molecular docking studies were used to identify potential drug candidates for oral health by predicting the binding affinity of the compounds to cyclooxygenases, interleukin-1 beta receptors, odontoblast cold sensor proteins, and purinergic receptor P2X3. FT-IR analysis showed characteristic peaks of phenols, carboxylic acids, alkenes, alkyl halides, amines, esters, ethers, aromatics, and lipids. GC–MS results showed the presence of 58 bioactive phytocompounds, some of which have various pharmacological activities relevant to oral health. Molecular docking further validated stigmastan-3,5-diene’s potency for analgesic and anti-inflammatory purposes. Based on a literature review, this is the first report on the bioactive compounds of M. crassa extracts showing analgesic and anti-inflammatory effects. This study's results can lead to new herbal and conventional medicines. Therefore, we recommend in vivo and in vitro studies to elucidate the pharmacological effects of the plant extracts

In Vivo and In Silico Analgesic Activity of Ficus populifolia Extract Containing 2-O-β-D-(3′,4′,6′-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3′,4′,6′-triacetylated-glucoside, 2-O-β-D-(3′,4′,6′-tri-acetyl)-glucopyranosyl-3-methyl pentanoic acid was obtained from Ficus populifolia, and characterized through a detailed NMR spectroscopic analysis, i.e., 1H-NMR, 13C-DEPT-135, and the 2D nuclear magnetic resonance (NMR) correlations. The product was in silico investigated for its analgesic prowess, COX-2 binding feasibility and scores, drug likeliness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, possible biosystem’s toxicity using the Discovery Studio®, and other molecular studies computational software programs. The glycosidic product showed strong potential as an analgesic agent. However, an in vivo evaluation, though at strong levels of pain-relieving action, was estimated on the compound’s extract owing to the quantity and yield issues of the glycosidic product. Nonetheless, the F. populifolia extract showed the analgesic potency in eight-week-old male mice on day seven of the administration of the extract’s dose in acetic acid-induced writhing and hot-plate methods. Acetic acid-induced abdominal writhing for all the treated groups decreased significantly (p < 0.0001), as compared to the control group (n = 6) by 62.9%, 67.9%, and 70.9% of a dose of 100 mg/kg (n = 6), 200 mg/kg (n = 6), and 400 mg/kg (n = 6), respectively. Similarly, using the analgesia meter, the reaction time to pain sensation increased significantly (p < 0.0001), as compared to the control (n = 6). The findings indicated peripheral and central-nervous-system-mediated analgesic action of the product obtained from the corresponding extract

In Vivo and In Silico Analgesic Activity of <i>Ficus populifolia</i> Extract Containing 2-O-β-D-(3′,4′,6′-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3′,4′,6′-triacetylated-glucoside, 2-O-β-D-(3′,4′,6′-tri-acetyl)-glucopyranosyl-3-methyl pentanoic acid was obtained from Ficus populifolia, and characterized through a detailed NMR spectroscopic analysis, i.e., 1H-NMR, 13C-DEPT-135, and the 2D nuclear magnetic resonance (NMR) correlations. The product was in silico investigated for its analgesic prowess, COX-2 binding feasibility and scores, drug likeliness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, possible biosystem’s toxicity using the Discovery Studio®, and other molecular studies computational software programs. The glycosidic product showed strong potential as an analgesic agent. However, an in vivo evaluation, though at strong levels of pain-relieving action, was estimated on the compound’s extract owing to the quantity and yield issues of the glycosidic product. Nonetheless, the F. populifolia extract showed the analgesic potency in eight-week-old male mice on day seven of the administration of the extract’s dose in acetic acid-induced writhing and hot-plate methods. Acetic acid-induced abdominal writhing for all the treated groups decreased significantly (p p < 0.0001), as compared to the control (n = 6). The findings indicated peripheral and central-nervous-system-mediated analgesic action of the product obtained from the corresponding extract

A generalization of Jeffrey-Hamel problem to Reiner-Rivlin model for energy and thermodynamic analysis using Keller-Box computational framework

This study addresses the heat transport and irreversible mechanisms associated with energy and frictional losses in the Jeffery-Hamel flow of a non-Newtonian fluid adapting the Reiner-Rivlin model. The Reiner-Rivlin model is frequently used to tackle the impact of yield-stresses among the multiple rheological models suggested for constructing the flow of yield-stresses materials. The non-creeping flow between convergent and divergent plates (Jeffrey-Hamel flow), the viscoelastic characteristics of incompressible Reiner-Rivlin liquid are examined by adapting the Navier-Stokes flow. The flow of a Reiner-Rivlin fluid is caused by pressure differential at the inlet. The second law of thermodynamics ultimately provide entropy manifestation. Using a comprehensive Keller-Box approach, self-similar numerical solutions for the velocity and associated fields are provided. The distribution of velocities for fluid-specific characteristics reveals an impedance formed by interaction between wall and diverging flow orientations. Viscous dissipation has a notable impact on the irreversible process and subsequently enhance the transmission of heat. Irrespective of the conduit structure, the Eckert number raises both the centerline and wall temperatures. The wall temperature gradient show a dominant trend for diverging channel. Higher Brinkman number, particularly in the context of the Reiner-Rivlin fluid, render the effect of viscous dissipation on the development of entropy apparent

Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N&prime;-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = &minus;8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19

Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N′-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = −8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19