Total phenolic contents, cytotoxic, free radicals, porcine pancreatic α-amylase, and lipase suppressant activities of Artemisia dracunculus plant from Palestine.

Artemisia dracunculus: L. (A. dracunculus) is a popular vegetable and spice cultivated across many Middle Eastern countries. The herb's aqueous extract has significant folkloric medicinal importance for treating various disorders. Hence, the present investigation aimed to investigate A. dracunculus hydrophilic extract phytochemical constituents and pleiotropic biological potentials, as no previous studies have investigated the antilipase and anti-α-amylase effects of the A. dracunculus plant. Total phenol content and phytochemical screening assays were performed utilizing standard analytical methods. While the α-amylase inhibition, free radical-scavenging, antilipase, and cytotoxic activities were determined using dinitrosalicylic acid (DNSA), DPPH, p-nitrophenyl butyrate (PNPB), and MTS assays, respectively. The standard phytochemical analysis of A. dracunculus aqueous extract shows that this extract contains only a phenolic group. The total phenol content was 0.146 ± 0.012 mg GAE/g of the plant dry extract. The A. dracunculus aqueous extract exhibited potent DPPH free radical inhibitory (IC50 dose of 10.71 ± 0.01 µg/mL) and anti-lipase activities (IC50 dose of 60.25 ± 0.33 µg/mL) compared with Trolox (IC50 = 5.7 ± 0.92 µg/mL) and Orlistat (IC50 = 12.3 ± 0.35 µg/mL), respectively. However, it showed a weak anti-α-amylase effect (IC50 value > 1,000 µg/mL) compared with Acarbose (IC50 = 28.18 ± 1.27 µg/mL). A. dracunculus has a cytotoxic effect against the HeLa cancer cell line compared with the chemotherapeutic agent Doxorubicin. The extract has the same percent of inhibition as Doxorubicin (99.9%) at 10 mg/mL. Overall, these results pointed out for the first time the importance of considering A. dracunculus effects as a favorite candidate for preventing and treating metabolic disorders. Also, our results confirm the findings of previous reports on the role of A. dracunculus in the management of cancer and disorders resulting from the accumulation of harmful free radicals. On the contrary, the current study concluded that the antidiabetic role of A. dracunculus could be minimal. Further in-depth investigations are urgently warranted to explore the importance of A. dracunculus in pharmaceutical production.

Exploring the phytoconstituents, antimicrobial potency, and cytotoxic effects of essential oil from Origanum punonense from Palestine.

BACKGROUND: Origanum punonense Danin is one of the old traditional medicinal plants Bedouins utilize in the Dead Sea region to treat a variety of illnesses, those caused by infections. The current study aimed to identify the phytochemical components of O. punonense essential oil (EO) and determine its antiproliferative and antimicrobial effects. METHODS: Gas chromatography and mass spectrometry were employed to detect the phytochemical constituents of O. punonense EO. Broth microdilution assay was utilized to determine the antimicrobial effects against various microbial species, including those causing diabetic foot infections. RESULTS: This study revealed that O. punonense EO contains 44 phytochemical compounds, of which 41 compounds were detectable and amounted to 99.78% of the total oil. The main chemical components of the oil were carvacrol (57.4%), p-cymene (6.66%), carvone (5.35%), pinene (4.9%), and terpinene (2.96%). The antiproliferative activity of different concentrations of O. punonense EO was noted in all of the investigated cell lines, with the best activity at the concentration of 500 µg/mL. The greatest antibacterial activity was against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus vulgaris, with MIC values of 1.56 µL/mL. In addition, and the O. punonense EO showed strong antifungal activity against Candida albicans with a MIC value of 0.8 µL/mL. In addition, the O. punonense EO showed potent antibacterial activity against all MRSA samples obtained from the diabetic foot with a MIC value of 3.13 µL/mL. The O. punonense EO demonstrated potent activity against Carbapenem-resistant Enterobacterales, Citrobacter freundii, and K. pneumoniae, with MICs value of 6.25 µL/mL. CONCLUSION: The potent antiproliferative and broad antimicrobial activity of O. punonense EO makes it an effective strategy for treating infections, especially in immunocompromised patients with chronic comorbidities such as cancer and diabetes mellitus.

Chemical composition, anticancer, antimicrobial activity of Aloysia citriodora Palau essential oils from four different locations in Palestine.

The primary aim of this investigation was to determine the anticancer and antimicrobial properties of essential oils (EOs) extracted from the leaves of Aloysia citriodora Palau, which were procured from four separate locations in Palestine, in addition to analyzing their chemical composition. These areas include Jericho, which has the distinction of being the lowest location on Earth, at 260 m below sea level. The EOs were acquired by hydrodistillation, and their chemical composition was examined utilizing gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentration (MIC) of EOs was assessed against six bacterial strains and one fungal species using 96-well microtiter plates. The primary components found in these oils are geranial (26.32-37.22%), neral (18.38-29.00%), and α-curcumene (7.76-16.91%) in three regions. α-Curcumene (26.94%), spathulenol (13.69%), geranial (10.79%), caryophyllene oxide (8.66%), and neral (7.59%) were found to be the most common of the 32 chemical components in the EO from Jericho. The EOs exhibited bactericidal properties, particularly against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and showed highly effective fungicidal activity. Nevertheless, the antifungal efficacy of the EO was found to surpass its antibacterial activity when administered at lower dosages. The EOs exhibited anticancer activities against melanoma cancer cells, as indicated by their IC50 values, which ranged from 4.65 to 7.96 µg/mL. A. citriodora EO possesses substantial antifungal and anticancer characteristics, rendering it appropriate for utilization in food-related contexts, hence potentially enhancing the sustainability of the food sector.

Multi-biological activity assessment and phytochemical characterization of an aqueous extract of the Cymbopogon citratus grown in Palestine.

BACKGROUND: Plants have historically been a rich source of medicinal compounds, with many modern pharmaceuticals derived from botanical origins. In contemporary healthcare, there is a resurgence in utilizing botanical substances as recognized medicinal agents. This study delved into understanding the phytochemical makeup and the multifaceted biological activities of an aqueous extract from Cymbopogon citratus (C. citratus). The investigated activities were its effect on AMPA receptors, antioxidant capacity, anti-lipase, anti-α-amylase actions, cytotoxicity, and antimicrobial properties. METHODS: The extract of C. citratus received a comprehensive investigation, which included the study of its phytochemical composition, assessment of its antioxidant and anti-lipase properties, evaluation of its capacity to inhibit α-amylase, analysis of its impact on cell viability, and assessment of its antimicrobial activity. The approaches are used to clarify the complex physiological and biochemical characteristics. RESULTS: The results were compelling; receptor kinetics had a marked impact, notably on the GluA2 subunit. Regarding its medicinal potential, the extract demonstrated potent antioxidant and anti-diabetic activities with IC50 values of 15.13 and 101.14 µg/mL, respectively. Additionally, it displayed significant inhibitory effects on the lipase enzyme and showed cytotoxicity against the Hep3B cancer cell line, with IC50 values of 144.35 and 148.37 µg/mL. In contrast, its effects on the normal LX-2 cell line were minimal, indicating selectivity. CONCLUSION: The aqueous extract of C. citratus shows promising therapeutic properties. The findings advocate for further research into its compounds for potential isolation, purification, and in-depth pharmacological studies, especially in areas like nervous system disorders, diabetes, obesity, and combating oxidative stress.

Assessing the therapeutic potential and safety of traditional anti-obesity herbal blends in Palestine.

The use of traditional herbal remedies has been a common practice for centuries across different cultures to treat various ailments. In Palestine, traditional herbal medicines are widely used, but their efficacy and safety have not been thoroughly investigated. Therefore, the purpose of this study was to assess the biological activity and toxicity of two traditional herbal blends often used to treat obesity in the West Bank region of Palestine. Two herbal blends with a total of eight plants were chosen based on their historic use and availability. The plant aqueous extracts were evaluated for their antioxidant, anti-fibrotic, anti-obesity, anti-diabetic, and cytotoxic activities. The results showed that these blends have potent antifibrotic, antioxidant, and anticancer activities. While their activities on α-amylase and lipase enzymes (main targets) showed moderate activities. Therefore, our results showed that Herbal Blend 2 was more potent than Herbal Blend 1 on all investigated targets. Herbal Blend 2 showed significant activities as an antioxidant, antifibrotic, and anticancer activities with IC50 values of 68.16 ± 2.45, 33.97 ± 1.14, and 52.53 ± 0.78 µg/mL against DPPH, LX-2, and MCF-7 cell lines, respectively. While it is IC50 values on α-amylase and lipase enzymes were 243.73 ± 1.57 and 1358.39 ± 2.04 µg/mL, respectively. However, the use of anti-cancer plants can be challenging due to their cytotoxic effects on the body. We urge individuals to exercise caution when using natural remedies and to seek medical advice before incorporating them into their health regimens. This study provides valuable insight into the potential health benefits of traditional herbal remedies and emphasizes the importance of responsible usage.

Eucalyptus camaldulensis Dehnh Leaf Essential Oil from Palestine Exhibits Antimicrobial and Antioxidant Activity but No Effect on Porcine Pancreatic Lipase and α-Amylase.

Eucalyptus camaldulensis Dehnh is a tree species that is commonly used for various purposes, including forestry, agroforestry, and conservation. The present investigation was designed to determine the composition of E. camaldulensis leaves essential oil and estimate its free radicals, porcine pancreatic lipase, α-amylase inhibitory, and antimicrobial properties in vitro. The chemical constituents were analyzed using the gas chromatography-mass spectrometry (GC-MS) technique. DPPH (2,2-diphenyl-1-picrylhydrazyl), p-nitrophenyl butyrate, and 3,5-dinitro salicylic acid (DNSA) methods were employed to estimate the antioxidant, antiobesity, and antidiabetic effects of the essential oil. The microdilution assay was employed to assess the antimicrobial efficacy of the substance against a total of seven distinct microbial species. The GC-MS results revealed that E. camaldulensis essential oil contains 52 components that makeup 100% of the entire oil. The main chemical constituents in E. camaldulensis essential oil are p-cymene (38.64%), followed by aromadendrene (29.65%), and 1,8-cineol (6.45%), with monocyclic monoterpene being the most abundant phytochemical group, followed by the sesquiterpene hydrocarbon group, representing 44.27 and 31.46%, respectively. The essential oil showed a weak antioxidant effect and had no antilipase or antiamylase effects. At the same time, the oil showed a strong antimicrobial effect against methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Proteus vulgaris, which was even more potent than the positive controls, ciprofloxacin and ampicillin, which had MIC doses of 0.2 ± 0.01, 0.2 ± 0.01, and 6.25 ± 0.1 µg/mL, respectively. It also has a strong anti-Candida albicans effect with a MIC of 0.2 ± 0.01 µg/mL. In light of these findings, in vivo studies should be conducted to determine the efficiency of the E. camaldulensis essential oil in treating microbial infections.

Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine.

Curcuma longa (turmeric) is a plant that has been extensively utilized in traditional medicine for centuries. Turmeric has a long history of use in both food and traditional medicine for the treatment of ailments such as diarrhea, cancer, flatulence, and dyspepsia. In Palestine, this plant was cultivated for the first time. The objective of this study was to characterize the extract of C. longa and assess its antimutagenic activity against a variety of cancer cells. Gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) methods were employed to identify the constituents of turmeric. The cytotoxic effects of C. longa were evaluated on cancer and normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. The results revealed the presence of 10 components in turmeric extract as identified by GC-MS. The major constituents comprising 78% of the total constituents were α-zingiberene (27.51%), tumeron (19.44%), ß-sesquiphellandrene (19.40%), and aromatic-tumeron (11.63%). HPLC analysis successfully separated the main constituent, curcumin (1.78%), along with two other curcumin derivatives. The cytotoxicity results demonstrated potent anticancer activity of the C. longa extract against HeLa and LX2 cell lines, with IC50 values of 46.84 ± 2.12 and 29.77 ± 1 µg/mL, respectively. Furthermore, the plant extract at a concentration of 250 µg/mL exhibited over 95% inhibition against all tested cancer cell lines. These findings highlight the promising potential of turmeric as a natural source with powerful anticancer activities. Moreover, the extract may possess other biological activities such as antioxidant and antimicrobial properties, which could be explored in future studies.

Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model.

In this study, we synthesized benzodioxol carboxamide derivatives and investigated their antidiabetic potential. The synthesized compounds (Ia-Ic and IIa-IId) underwent characterization via HRMS, 1H-, 13CAPT-NMR, and MicroED. Their efficacy against α-amylase was assessed in vitro, while MTS assays were employed to gauge cytotoxicity across cancer and normal cell lines. Additionally, the antidiabetic impact of compound IIc was evaluated in vivo using a streptozotocin-induced diabetic mice model. Notably, IIa and IIc displayed potent α-amylase inhibition (IC50 values of 0.85 and 0.68 µM, respectively) while exhibiting a negligible effect on the Hek293t normal cell line (IC50 > 150 µM), suggesting their safety. Compound IId demonstrated significant activity against four cancer cell lines (26-65 µM). In vivo experiments revealed that five doses of IIc substantially reduced mice blood glucose levels from 252.2 mg/dL to 173.8 mg/dL in contrast to the control group. The compelling in vitro anticancer efficacy of IIc and its safety for normal cells underscores the need for further in vivo assessment of this promising compound. This research highlights the potential of benzodioxol derivatives as candidates for the future development of synthetic antidiabetic drugs.

Qualitative and Quantitative Comparison of Aromatic Oil Components and Antifungal Effects of Cymbopogon flexuosus Obtained with Supercritical CO2, Microwave-Ultrasonic, Steam Distillation, and Hydrodistillation Extraction Techniques.

Cymbopogon flexuosus is a highly valued botanical species with significant applications in the food and food supplement industries, medicine, and cosmetics. The effects of four extraction techniques, supercritical CO2, microwave-ultrasonic, steam distillation, and hydrodistillation techniques, on the yield, phytochemical constituents, and antifungal activity against nine fungal species of Cymbopogon flexuosus aromatic oil (AO) were explored in this investigation. Gas chromatography connected with a mass spectrometry apparatus was employed for the qualitative and quantitative analyses of the investigated plant AOs. In addition, using the broth microdilution method, minimum inhibitory concentrations (MICs) were calculated for several fungi species. The supercritical CO2 method gave the highest yield of AO (11.62 ± 0.03 (w/w)) followed by the microwave-ultrasonic method (1.55 ± 0.05% (w/w)) and the steam distillation method (1.24 ± 0.04% (w/w)), while the hydrodistillation methods gave the lowest yield (1.17 ± 0.01 (w/w)). In addition, eighteen molecules were specified in the AOs obtained with the supercritical CO2, microwave-ultrasonic, steam distillation, and hydrodistillation techniques, which constituted 99.36, 98.6, 98.21, and 98.31% (v/v) of the total oils, respectively. Additionally, linalyl acetate was the trending molecule in the microwave-ultrasonic and steam distillation methods, representing 24.61 and 24.34% (v/v), respectively, while geranial was the dominant molecule in the AOs extracted with the hydrodistillation and supercritical CO2 extraction techniques (27.01 and 25.6% (v/v), respectively). The antifungal screening results revealed that the tested C. flexuosus AOs have potential antifungal effects against all the screened fungi species. The antifungal effect of the AOs extracted with the steam distillation and microwave-ultrasonic methods was remarkable compared with that of the commercial antifungal drug Fluconazole. However, the AOs extracted with these two methods have a more potent antifungal effect against Candida parapsilosis than that of Fluconazole with MICs of 3.13 ± 0.01, 3.13 ± 0.01, and 6.25 ± 0.91 µg/mL, respectively. The same effects were also observed against Trichophyton rubrum with MICs of 6.25 ± 0.91 µg/mL, respectively. The results of this investigation demonstrated that the steam distillation and microwave-ultrasonic methods are promising processes for the extraction of C. flexuosus AO with a potent antifungal effect. This may be an advantage for the utilization of C. flexuosus AO over some antifungal synthetic agents commonly utilized as medicines, preservatives, food additives, cosmetics, and nutrient supplements.

New Thiazole Carboxamide Derivatives as COX Inhibitors: Design, Synthesis, Anticancer Screening, In Silico Molecular Docking, and ADME Profile Studies.

The goal of this work was to create and test a new series of thiazole carboxamide derivatives for their cyclooxygenase (COX) suppressor and anticancer effects. The compounds were characterized using 1H, 13C NMR, and HRMS spectrum analysis, and their selectivity toward COX-1 and COX-2 was assessed using an in vitro COX inhibition assay kit. Cytotoxicity was assessed using an MTS assay against a panel of cancer and normal cell lines. The docking studies were aided by the Prime MM-GBSA method for estimating binding affinities. The density functional theory (DFT) analysis was performed to assess compound chemical reactivity, which was calculated by computing the border orbital energy of both HOMO and LUMO orbitals, as well as the HOMO-LUMO energy gap. For ADME-T analysis, the QiKProp module was employed. Furthermore, using human X-ray crystal structures, molecular docking studies were carried out to discover the probable binding patterns of these drugs within both COX-1 and COX-2 isozymes. The results demonstrated that the most effective compound against the COX-1 enzyme was 2b with an IC50 of 0.239 µM. It also showed potent activity against COX-2 with an IC50 value of 0.191 µM and a selectivity ratio of 1.251. The highest selectivity ratio was 2.766 for compound 2a against COX-2 with an IC50 dose of 0.958 µM relating to the celecoxib ratio of 23.8 and its IC50 against COX-2 of 0.002 µM. Compound 2j also showed good selectivity toward COX-2 (1.507) with an IC50 value of 0.957 µM. All compounds showed negligible cytotoxic activity against the evaluated normal cell lines, and the IC50 values were more than 300 µM, except for compound 2b, whose IC50 values were 203.71 ± 1.89 and 116.96 ± 2.05 µM against LX-2 and Hek293t cell lines, respectively. Moreover, compound 2b showed moderate anticancer activity against COLO205 and B16F1 cancer cell lines with IC50 values of 30.79 and 74.15 µM, respectively.

Assessment of anticancer, antimicrobial, antidiabetic, anti-obesity and antioxidant activity of Ocimum Basilicum seeds essential oil from Palestine.

BACKGROUND: Many modern pharmaceutical researchers continue to focus on the discovery and evaluation of natural compounds for possible therapies for obesity, diabetes, infections, cancer, and oxidative stress. Extraction of Ocimum basilicum seed essential oil and evaluation of its antioxidant, anti-obesity, antidiabetic, antibacterial, and cytotoxic activities were the goals of the current study. METHOD: O. basilicum seed essential oil was extracted and evaluated for its anticancer, antimicrobial, antioxidant, anti-obesity, and anti-diabetic properties utilizing standard biomedical assays. RESULTS: O. basilicum seed essential oil showed good anticancer activity against Hep3B (IC50 56.23 ± 1.32 µg/ml) and MCF-7 (80.35 ± 1.17 µg/ml) when compared with the positive control, Doxorubicin. In addition, the essential oil showed potent antibacterial (against Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Proteus mirabilis, and Pseudomonas aeruginosa) and antifungal (against Candida albicans) activities. Moreover, as for the anti-amylase test, IC50 was 74.13 ± 1.1 µg/ml, a potent effect compared with the IC50 of acarbose, which was 28.10 ± 0.7 µg/ml. On the other hand, for the anti-lipase test, the IC50 was 112.20 ± 0.7 µg/ml a moderate effect compared with the IC50 of orlistat, which was 12.30 ± 0.8 µg/ml. Finally, the oil had a potent antioxidant effect with an IC50 of 23.44 ± 0.9 µg/ml compared with trolox (IC50 was 2.7 ± 0.5 µg/ml). CONCLUSION: This study has provided initial data that supports the importance of O. basilcum essential oil in traditional medicine. The extracted oil not only exhibited significant anticancer, antimicrobial, and antioxidant properties but also antidiabetic and anti-obesity effects, which provided a foundation for future research.

Arum palaestinum delays hepatocellular carcinoma proliferation through the PI3K-AKT-mTOR signaling pathway and exhibits anticoagulant effects with antimicrobial properties.

Background: Arum palaestinum Boiss (AP) is a wild plant in Palestine whose leaves have a long history as food and medicine in Middle Eastern countries. The current study aimed to evaluate the biological characteristics of AP flower extract, including its antimicrobial and coagulation cascade activities and its effects on anticancer molecular pathways. Methods: The antimicrobial activity of the aqueous extract of AP flowers was assessed using a microdilution assay against eight pathogens. The coagulation properties were assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) tests using standard hematological methods. The biological effects of AP on hepatocellular carcinoma were measured by assessing the impact of AP on cell cycle, proliferation (CFSE), apoptosis (annexin-v+/PI), and tumorigenicity (αFP and HBsAg), as well as its effects on the PI3K-AKT-mTOR molecular signaling pathway. Results: The antimicrobial screening results revealed that the aqueous extract of AP had potent antibacterial effects against P. vulgaris and E. faecium compared to ampicillin, with MIC values of 6.25, 6.25, and 18 µg/mL, respectively. Moreover, the AP aqueous extract exerted anticoagulant activity, with significant prolonged results in the aPTT and TT tests (25 µg/mL and 50 µg/mL, respectively) and slightly prolonged results in the PT test (50 µg/mL). The anticancer results indicated a delay in the cell cycle through decreased cell proliferation rates following incubation with AP fractions. The effect of the aqueous fraction was most evident in a delay in the S phase. The aqueous and DMSO fractions maintained the cells in the G2-M phase, similar to the DOX, while the flower extract in methanol accelerated the cells in the G2-M phase, suggesting that AF flower extracts may have anti-cancer properties. The aqueous extract of AP 1) reduced secretions of HCC αFP by 1.55-fold and 3.3-fold at the 50 and 100 µg/mL concentrations, respectively (p = 0.0008); 2) decreased phosphorylation in the PI3K-AKT-mTOR signaling pathway (p < 0.05); and 3) shifted cells from necrosis to apoptosis by 50% and 70% at the 50 and 100 µg/mL concentrations, respectively (p < 0.05). Conclusion: The results of this study showed the activities of the bioactive components for the treatment of infectious diseases and blood coagulation disorders, which could also be a potential therapeutic approach for delaying HCC tumorigenicity.

Design, synthesis, molecular docking and biological evaluation of new carbazole derivatives as anticancer, and antioxidant agents.

BACKGROUND: The carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities. OBJECTIVES: This study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities. METHODS: The synthesized compounds were characterized utilizing HRMS, 1H-, and 13CAPT-NMR, and assessed for their anticancer, antifibrotic, and antioxidant effects utilizing reference biomedical procedures. In addition, the AutoDock Vina application was used to perform in-silico docking computations. RESULTS: A series of carbazole derivatives were synthesized and characterized in the current study. Compounds 10 and 11 were found to have a stronger antiproliferative effect than compounds 2-5 against HepG2, HeLa, and MCF7 cancer cell lines with IC50 values of 7.68, 10.09, and 6.44 µM, respectively. Moreover, compound 9 showed potent antiproliferative activity against HeLa cancer cell lines with an IC50 value of 7.59 µM. However, except for compound 5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC50 values in the range of 43.7-187.23 µM. All of these values were compared with the positive control anticancer drug 5-Fluorouracil (5-FU). In addition, compound 9 showed the most potent anti-fibrotic compound, and the cellular viability of LX-2 was found 57.96% at 1 µM concentration in comparison with the positive control 5-FU. Moreover, 4 and 9 compounds showed potent antioxidant activities with IC50 values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively. CONCLUSION: Most of the synthesized carbazole derivatives showed promising antiproliferative, antioxidant, and antifibrotic biological effects, and further in-vivo investigations are needed to approve or disapprove these results.

The effect of Lavandula Coronopifolia essential oil on the biophysical properties of desensitization and deactivation gating currents in ionotropic receptors.

The rising incidence of cancer and the lack of effective therapeutic interventions for many neurological illnesses like Alzheimer's and epilepsy has prompted us to investigate the composition and effects of the Lavandula coronopifolia oil from Palestine on cancer cells and AMPA receptor subunits in the brain due to the vast range of beneficial properties of Lavandula coronopifolia essential oil (EO). GC/MS was used to analyze L. coronopifolia's EO chemistry. EO's cytotoxicity and biophysical effects on AMPA receptors were investigated using MTS and electrophysiological techniques. The GC-MS results revealed that L. coronopifolia EO has a high content of eucalyptol (77.23%), ß-pinene (6.93%), and α-pinene (4.95%). The EO showed more significant antiproliferative selectivity activities against HepG2 cancer cell lines than HEK293T cell lines with IC50 values of 58.51 and 133.22 µg/mL, respectively. The EO of L. coronopifolia affected AMPA receptor kinetics (desensitization and deactivation) and preferred homomeric GluA1 and heteromeric GluA1/A2 receptors. These findings indicate the potential therapeutic use of L. coronopifolia EO in the selective treatment of HepG2 cancer cell lines and neurodegenerative diseases.

Antibacterial and Anti-Acne Activity of Benzoyl Peroxide Nanoparticles Incorporated in Lemongrass Oil Nanoemulgel.

PURPOSE: The goal of this study was to make Benzoyl Peroxide (BPO) nanoemulgel to improve its ability to kill bacteria. BPO has trouble getting into the skin, being absorbed by the skin, staying stable, and being spread out. METHODS: A BPO nanoemulgel formulation was prepared by combining BPO nanoemulsion with Carbopol hydrogel. The drug was tested for solubility in various oils and surfactants in order to select the best oil and surfactant for the drug, and then the drug nanoemulsion formulation was prepared using a self-nano-emulsifying technique with Tween 80, Span 80, and lemongrass oil. The drug nanoemulgel was looked at in terms of its particle size, polydispersity index (PDI), rheological behavior, drug release, and antimicrobial activity. RESULTS: Based on the solubility test results, lemongrass oil was the best solubilizing oil for drugs, while Tween 80 and Span 80 demonstrated the highest solubilizing ability for drugs among the surfactants. The optimum self-nano-emulsifying formulation had particle sizes of less than 200 nm and a PDI of close to zero. The results showed that incorporating the SNEDDS formulation of the drug with Carbopol at various concentrations did not cause a significant change in the particle size and PDI of the drug. The zeta potential results for drug nanoemulgel were negative, with more than 30 mV. All nanoemulgel formulations exhibited pseudo-plastic behavior, with 0.4% Carbopol exhibiting the highest release pattern. The drug nanoemulgel formulation worked better against bacteria and acne than the product on the market. CONCLUSION: Nanoemulgel is a promising way to deliver BPO because it makes the drug more stable and increases its ability to kill bacteria.

Design, synthesis, molecular docking studies and biological evaluation of thiazole carboxamide derivatives as COX inhibitors.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the most commonly used class of medications worldwide for the last three decades. OBJECTIVES: This study aimed to design and synthesize a novel series of methoxyphenyl thiazole carboxamide derivatives and evaluate their cyclooxygenase (COX) suppressant and cytotoxic properties. METHODS: The synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and were evaluated for their selectivity towards COX-1 and COX-2 using an in vitro COX inhibition assay kit. Besides, their cytotoxicity was evaluated using the Sulforhodamine B (SRB) assay. Moreover, molecular docking studies were conducted to identify the possible binding patterns of these compounds within both COX-1 and COX-2 isozymes, utilizing human X-ray crystal structures. The density functional theory (DFT) analysis was used to evaluate compound chemical reactivity, which was determined by calculating the frontier orbital energy of both HOMO and LUMO orbitals, as well as the HOMO-LUMO energy gap. Finally, the QiKProp module was used for ADME-T analysis. RESULTS: The results revealed that all synthesized molecules have potent inhibitory activities against COX enzymes. The percentage of inhibitory activities at 5 µM concentration against the COX2 enzyme was in the range of 53.9-81.5%, while the percentage against the COX-1 enzyme was 14.7-74.8%. That means almost all of our compounds have selective inhibition activities against the COX-2 enzyme, and the most selective compound was 2f, with selectivity ratio (SR) value of 3.67 at 5 µM concentration, which has a bulky group of trimethoxy on the phenyl ring that could not bind well with the COX-1 enzyme. Compound 2h was the most potent, with an inhibitory activity percentage at 5 µM concentration of 81.5 and 58.2% against COX-2 and COX-1, respectively. The cytotoxicity of these compounds was evaluated against three cancer cell lines: Huh7, MCF-7, and HCT116, and negligible or very weak activities were observed for all of these compounds except compound 2f, which showed moderate activities with IC50 values of 17.47 and 14.57 µM against Huh7 and HCT116 cancer cell lines, respectively. Analysis of the molecular docking suggests 2d, 2e, 2f, and 2i molecules were bound to COX-2 isozyme favorably over COX-1 enzyme, and their interaction behaviors within COX-1 and COX-2 isozymes were comparable to celecoxib, as an ideal selective COX-2 drug, which explained their high potency and COX-2 selectivity. The molecular docking scores and expected affinity using the MM-GBSA approach were consistent with the recorded biological activity. The calculated global reactivity descriptors, such as HOMO and LUMO energies and the HOMO-LUMO gaps, confirmed the key structural features required to achieve favorable binding interactions and thus improve affinity. The in silico ADME-T studies asserted the druggability of molecules and have the potential to become lead molecules in the drug discovery process. CONCLUSION: In general, the series of the synthesized compounds had a strong effect on both enzymes (COX-1 and COX-2) and the trimethoxy compound 2f was more selective than the other compounds.

Anticancer Activity of Thiophene Carboxamide Derivatives as CA-4 Biomimetics: Synthesis, Biological Potency, 3D Spheroid Model, and Molecular Dynamics Simulation.

The present study aimed to synthesize thiophene carboxamide derivatives, which are considered biomimetics of the anticancer medication Combretastatin A-4 (CA-4), and compare the similarity in the polar surface area (PSA) between the novel series and CA-4. Our results showed that the PSA of the most synthesized structures was biomimetic to CA-4, and similar chemical and biological properties were observed against Hep3B cancer cell line. Among the synthesized series 2b and 2e compounds were the most active molecules on Hep3B (IC50 = 5.46 and 12.58 µM, respectively). The 3D results revealed that both 2b and 2e structures confuse the surface of Hep3B cancer cell lines' spheroid formation and force these cells to aggregate into a globular-shaped spheroid. The 2b and 2e showed a comparable interaction pattern to that observed for CA-4 and colchicine within the tubulin-colchicine-binding pocket. The thiophene ring, due to holding a high aromaticity character, participated critically in that observed interaction profile and showed additional advanced interactions over CA-4. The 2b and 2e tubulin complexes showed optimal dynamics trajectories within a time scale of 100 ns at 300 K temperature, which asserts their high stability and compactness. Together, these findings revealed the biomimetic role of 2b and 2e compounds in CA-4 in preventing cancer progression.

The Formation of Self-Assembled Nanoparticles Loaded with Doxorubicin and d-Limonene for Cancer Therapy.

Self-assembled nanoparticles present unique properties that have potential applications in the development of a successful drug delivery system. Doxorubicin (DOX) is an important anti-neoplastic anthracycline chemotherapeutic drug widely described. However, it suffers from serious dose-dependent cardiotoxicity. d-Limonene is a major constituent of numerous citrus oils that is considered a specific monoterpene against free radicals producing antioxidant activity. Herein, we aimed to design three types of self-assembled nanodelivery systems (nanoemulsion, niosomes, and polylactide nanoparticles) for loading both DOX and d-limonene to enhance the solubilization of d-limonene and provide antioxidant activity with excellent anticancer activity. As confirmed by dynamic light scattering and transmission electron microscopy, the nanoparticles were prepared successfully with diameter sizes of 52, 180, and 257 nm for the DOX-loaded nanoemulsion, niosomes, and polylactide nanoparticles, respectively. The zeta potential values were above -30 mV in all cases, which confirms the formation of stable nanoparticles. The loading efficiency of DOX was the highest in the case of the DOX-loaded nanoemulsion (75.8%), followed by niosomes (62.8%), and the least was in the case of polylactide nanoparticles with a percentage of 50.2%. The in vitro release study of the DOX-loaded nanoparticles showed a sustained release profile of doxorubicin with the highest release in the case of DOX-loaded PDLLA nanoparticles. The kinetic release model for all developed nanoparticles was the Peppas-Sahlin model, demonstrating DOX release through Fickian diffusion phenomena. Moreover, all developed nanoparticles maintain the antioxidant activity of d-limonene. The cytotoxicity study of the DOX-loaded nanoparticles showed concentration-dependent anticancer activity with excellent anticancer activity in the case of the DOX-loaded nanoemulsion and polylactide nanoparticles. These nanoparticles will be further studied in vivo to prove the cardioprotective effect of d-limonene in combination with DOX.

Gundelia tournefortii inhibits hepatocellular carcinoma progression by lowering gene expression of the cell cycle and hepatocyte proliferation in immunodeficient mice.

Gundelia (G.) tournefortii has antibacterial, anti-inflammatory, and hypolipemic effects. We evaluated the anticancer effect of G. tournefortii in an hepatocellular carcinoma (HCC) mouse model of an HCC cell line (Hep3B) injected into NOD.CB17-Prkdc-SCID/NCrHsD male mice. Tumorigenicity was assessed by tumor size, histology, serum α-fetoprotein (αFP), and glypican 3 (GPC3). HCC-related gene expression of the cell cycle (Cyclin-dependent kinase inhibitor 2A (CDNK2A)), proliferation (MKI67), and platelet-derived growth factor receptor α (PDGFA) were measured. HCC cell cycle alterations, apoptosis, and antioxidant markers in serum and liver following treatment with G. tournefortii were determined. Signaling pathways of liver p53 and phosphorylated PI3K, AKT, and mTOR were also evaluated. Results indicate a significant increase in tumor size in HCC animals associated with elevated αFP, GPC3, and MKI67. Tumor markers of p53 and phosphorylated AKT/PI3K/mTOR signaling pathway were diminished, with less proliferating cells and reduced PDGFRA gene expression following G. tournefortii infection. H&E staining showed a remarkable reduction in inflammatory lesions in HCC mice treated with G. tournefortii. This result was in line with a significant delay in the G2/M phase of HCC-primary hepatocytes by 1.39- to 2.4-fold and reduced HCC necrosis associated with inhibited CDNK2A gene expression. Antioxidant activity was significantly lower in the HCC mice than in the control group. Moreover, G. tournefortii inhibited the HCC formation of 3D MCTS spheroids. G. tournefortii treatment markedly restored antioxidant levels and displayed anticancer and antiproliferative effects and could be a promising cancer therapy.

Chemical Markers and Pharmacological Characters of Pelargonium graveolens Essential Oil from Palestine.

Pelargonium graveolens leaves are widely used in traditional medicine for relieving some cardiovascular, dental, gastrointestinal, and respiratory disorders. They are also used as food and tea additives in Palestine and many other countries. Consequently, this investigation aimed to describe the chemical markers, cytotoxic, antioxidant, antimicrobial, metabolic, and cyclooxygenase (COX) enzymes inhibitory characteristics of P. graveolens essential oil (PGEO) from Palestine utilizing reference methods. There were 70 chemicals found in the GCMS analysis, and oxygenated terpenoids were the most abundant group of the total PGEO. Citronellol (24.44%), citronellyl formate (15.63%), γ-eudesmol (7.60%), and iso-menthone (7.66%) were the dominant chemical markers. The EO displayed strong antioxidant activity (IC50 = 3.88 ± 0.45 µg/mL) and weak lipase and α-amylase suppressant effects. Notably, the PGEO displayed high α-glucosidase inhibitory efficacy compared with Acarbose, with IC50 doses of 52.44 ± 0.29 and 37.15 ± 0.33 µg/mL, respectively. PGEO remarkably repressed the growth of methicillin-resistant Staphylococcus aureus (MRSA), even more than Ampicillin and Ciprofloxacin, and strongly inhibited Candida albicans compared with Fluconazole. The highest cytotoxic effect of the PGEO was noticed against MCF-7, followed by Hep3B and HeLa cancer cells, with IC50 doses of 32.71 ± 1.25, 40.71 ± 1.89, and 315.19 ± 20.5 µg/mL, respectively, compared with doxorubicin. Moreover, the screened EO demonstrated selective inhibitory activity against COX-1 (IC50 = 14.03 µg/mL). Additionally, PGEO showed a weak suppressant effect on COX-2 (IC50 = 275.97 µg/mL). The current research can be considered the most comprehensive investigation of the chemical and pharmacological characterization of the PGEO. The results obtained in this study demonstrate, without doubt, that this plant represents a rich source of bioactive substances that can be further investigated and authenticated for their medicinal potential.