Fabrication and optimization of naringin-loaded MOF-5 encapsulated by liponiosomes as smart drug delivery, cytotoxicity, and apoptotic on breast cancer cells.

INTRODUCTION: Cancers are regarded as hazardous due to their high worldwide death rate, with breast cancer (BC), which affects practically all cancer patients globally, playing a significant role in this statistic. The therapeutic approach for BC has not advanced using standard techniques, such as specialized naringin (NG) chemotherapy. Instead, a novel strategy has been utilized to enhance smart drug delivery (SDD) to tumors. SIGNIFICANCE: Herein, we established NG-loaded zinc metal-organic framework-5 (NG-MOF-5) coated with liponiosomes (LNs) to manufacture NG-MOF-5@LNs nanoparticles (NPs) for antibacterial and cancer treatment. METHODS: MOF-5, NG, and NG-MOF-5@LNs were evaluated with XRD, thermogravimetric analysis (TGA), FTIR, SEM, TEM, PDI, ZP, encapsulation efficiency (EE), loading efficiency (LE), and drug release (DR) kinetics. We examined the antibacterial activity involving minimum inhibitory concentration (MIC) and zone of inhibition by NG, MOF-5, and NG-MOF-5@LNs. The cell viability, necrosis, and total apoptosis (late and early) were evaluated for anti-cancer activity against MCF-7 BC cells. RESULTS: TEM results demonstrated that NG-MOF-5@LNs formed monodispersed spherical-like particles with a size of 122.5 nm, PDI of 0.139, and ZP of +21 mV. The anti-microbial activity results indicated that NG-MOF-5@LNs exhibited potent antibacterial effects, as evidenced by inhibition zones and MIC values. The Higuchi model indicates an excellent fit (R2 = 0.9988). The MTT assay revealed anti-tumor activity against MCF-7 BC cells, with IC50 of 21 µg/mL for NG-MOF-5@LNs and demonstrating a total apoptosis effect of 68.2% on MCF-7 cells. CONCLUSION: NG-MOF-5@LNs is anticipated to show as an effective antimicrobial and novel long-term-release antitumor agent and might be more suitable for MCF-7 cell therapy.

Synergistic Effects of New Curcumin Analog (PAC) and Cisplatin on Oral Cancer Therapy.

Oral cancer has traditionally been treated with surgery, radiotherapy, chemotherapy, or a combination of these therapies. Although cisplatin, a chemotherapy drug, can effectively kill oral cancer cells by forming DNA adducts, its clinical use is limited due to adverse effects and chemo-resistance. Therefore, there is a need to develop new, targeted anticancer drugs to complement chemotherapy, allowing for reduced cisplatin doses and minimizing adverse effects. Recent studies have shown that 3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidine (PAC), a new curcumin analog, possesses anticancer properties and could be considered a complementary or alternative therapy. In this study, we aimed to assess the potential complementary effects of PAC in combination with cisplatin for treating oral cancer. We conducted experiments using oral cancer cell lines (Ca9-22) treated with different concentrations of cisplatin (ranging from 0.1 µM to 1 µM), either alone or in conjunction with PAC (2.5 and 5 µM). Cell growth was measured using the MTT assay, while cell cytotoxicity was evaluated using an LDH assay. Propidium iodide and annexin V staining were employed to examine the impact on cell apoptosis. Flow cytometry was used to investigate the effects of the PAC/cisplatin combination on cancer cell autophagy, oxidative stress, and DNA damage. Additionally, a Western Blot analysis was performed to assess the influence of this combination on pro-carcinogenic proteins involved in various signaling pathways. The results demonstrated that PAC enhanced the efficacy of cisplatin in a dose-dependent manner, leading to a significant inhibition of oral cancer cell proliferation. Importantly, treatment with PAC (5 µM) alongside different concentrations of cisplatin reduced the IC50 of cisplatin tenfold. Combining these two agents increased apoptosis by further inducing caspase activity. In addition, the concomitant use of PAC and cisplatin enhances oral cancer cell autophagy, ROS, and MitoSOX production. However, combined PAC with cisplatin inhibits the mitochondrial membrane potential (ΔΨm), which is a marker for cell viability. Finally, this combination further enhances the inhibition of oral cancer cell migration via the inhibition of epithelial-to-mesenchymal transition genes, such as E-cadherin. We demonstrated that the combination of PAC and cisplatin markedly enhanced oral cancer cell death by inducing apoptosis, autophagy, and oxidative stress. The data presented indicate that PAC has the potential to serve as a powerful complementary agent to cisplatin in the treatment of gingival squamous cell carcinomas.

Anti-Struvite, Antimicrobial, and Anti-Inflammatory Activities of Aqueous and Ethanolic Extracts of Saussurea costus (Falc) Lipsch Asteraceae.

Saussurea costus (Falc) Lipsch is a traditional herb used to treat kidney stone problems because it contains several molecules used to treat this health problem, such as quercitrin. Infectious stones are the most painful of all urinary tract disorders, with ammonium phosphate (struvite) and carbapatite stones being the most common, caused by a bacterial infection with urease activity. These stones are treated with antibiotics, but antibiotic resistance is on the rise. The current study investigated the anti-urolithic activities of S. costus aqueous and ethanolic extracts of against struvite crystals synthesized using microscopic crystallization and turbidimetric methods, respectively. The utilized methods indicated that the ethanolic extract of this plant has a significant inhibitory effect on struvite crystallization, with a percentage inhibition of (87.45 ± 1.107) (p < 0.001) for a concentration of 1 mg mL−1 and a decrease in the number of struvite crystals, reaching values less than 100/mm3. For the number of struvite crystals inhibited by cystone, we found a value of 400/mm3 and with the aqueous extract we found 700/mm3. The antibacterial activity of the plant extracts studied was examined against several urease-producing bacteria, and this activity was evaluated by qualitative and quantitative evaluation methods; the highest minimum inhibitory concentration was seen in the ethanolic extract, with an MIC of 50 mg mL−1 for Staphylococcus aureus followed by an MIC of 200 mg mL−1 for Klebsiella pneumoniae. It showed a minimal bactericidal concentration (MBC) against S. aureus and K. pneumoniae (>50 mg mL−1 and >200 mg mL−1, respectively). Furthermore, to determine the extract's anti-inflammatory activity, in vivo anti-inflammatory activity was investigated in rats. The results show that at a dose of 400 mg kg−1, the ethanolic extract has a maximum edema inhibition of 66%.

Berberine enhances the sensitivity of radiotherapy in ovarian cancer cell line (SKOV-3).

Berberine, a well-known isoquinoline alkaloid derivative, has a varied range of pharmacological effects. Herein, we notice the radio-modulatory outcome of berberine in cultured ovarian cancer (SKOV-3) cells exposed to γ-rays as radiotherapy (RT). Cells pre-treated with berberine were irradiated by γ-irradiation and the liberation of reactive oxygen species (ROS) was analyzed by flow cytometry. Apoptotic cell death along with the DNA damage associated with protein expressions was projected by flow cytometry and confocal microscopy. Experimental findings established that berberine might be a capable radiosensitizer for treating SKOV-3, because of oxidative DNA damage. Moreover, the in-silico study of the compound, berberine suggests free energy of binding (ΔG) -7.5 kcal/mol with SKOV-3 and -8.8 kcal/mol of PALB/BRCA2, which proves an effective and compact binding of the complex and is safe for future clinical trials. Thus, our approach is probably to widen the field of study of SKOV-3 and PALB/BRCA2 from the inhibition of these targets as a prospective nutraceutical for the anti-cancer theragnostic candidate.

Chemical profile, antiproliferative and pro-apoptotic activities of essential oils of Pulicaria arabica against A549 lung cancer cell line.

Pulicaria arabica has been traditionally utilized in folk medicine for various purposes such as ulcer treatments as well as antidiarrheal agent. Herein, the chemical profiles of Pulicaria arabica essential oils (PAEOs) and the in vitro antiproliferative effect of PAEOs were investigated. Hydrodistillation was employed to prepare PAEOs which were then characterized by GC/MS, while the antiproliferative effects were investigated by MTT assay as well as flow cytometric and RT-PCR analysis. Sixty-four (99.99 %) constituents were recognized from PAEOs. Carvotanacetone (36.97 %), (-)-carvomenthone (27.20 %) and benzene, 2-(1,1-dimethylethyl)-1,4-dimethoxy- (6.92 %) were the main components. PAEOs displayed IC50 values ranging from 30 to 50 µg/mL. DNA content analysis revealed that A549 cells exposed to PAEOs exhibited an increase in G1 cells population. The flow cytometry analysis results also showed that the PAEOs antiproliferative effect was mediated via apoptosis induction. Furthermore, a modulation in the pro-apoptotic markers (caspase-3 and Bax) and anti-apoptotic (Bcl-2) was also observed. In conclusion, PAEOs exhibited a moderate anti-proliferative effect on A549 cells through modulating the cell cycle progression and apoptosis initiation. These findings could offer a potential therapeutic use of PAEOs in lung cancer treatment.

FNDC5/Irisin: Physiology and Pathophysiology.

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

Efficacy of ivermectin against colon cancer induced by dimethylhydrazine in male wistar rats.

Colon cancer (CC) is a common form of cancer worldwide. According to growing incidence of cancer and little information about the possible protective role of Ivermectin (IVM) on colon cancer, this study aimed to investigate the chemoprotective role of IVM against colon cancer induced by Dimethylhydrazine (DMH) in Male Wistar Rats. Based on LD50, three doses of IVM (0.25, 0.5, and 1 mg/kg) were applied before assayingthe antioxidant status, apoptotic markers, and microscopic analysis. Our result showed that glutathione (GSH) level was significantly increased in low dose of IVM-treated rats. Hight levels of oxidative stress and tissue damage consumed GSH and catalase (CAT), and dismutase (SOD) as indicated by significant drop in the treated groups. mRNA levels of Bax and caspase-3 were upregulated in rats treated with the high dose. Contrastingly, the expression of Bcl-2 was significantly downregulated with high dose. Changes in genes expression proved that IVM triggered apoptosis in treated groups compared to untreated control group. Microscopic analysis showed that rats treated with DMH exhibited high development of colorectal tumor. After induction of colorectal tumor, medium and high dose of DMH induced reduction in medullary carcinoma with great incidence of lymphoid nodules and desmoplastic reaction. In conclusion, this study demonstrates the potential of IVM as an anticancer drug against colon cancer in male Wistar rats.

Antioxidant and anti-inflammatory activities of lycopene against 5-fluorouracil-induced cytotoxicity in Caco2 cells.

5-fluorouracil (5FU) is widely used to treat colorectal cancer (CC) and its main mechanisms of anticancer action are through generation of ROS which often result in inflammation. Here, we test the effect of Lycopene against 5FU in Caco2 cell line. Caco2 cells were exposed to 3 µg/ml of 5FU alone or with 60, 90, 120 µg/ml of lycopene. This was followed by assessment of cytotoxicity, oxidative stress, and gene expression of inflammatory genes. Our findings showed that Lycopene and 5FU co-exposure induced dose-dependent cytotoxic effect without compromising the membrane integrity based on the LDH assay. Lycopene also significantly enhanced 5FU-induced SOD activity and GSH level compared to control for all mixture concentrations (p < 0.01). Lycopene alone and combination with 5FU-induced expression of IL-1ß, TNF-α, and IL-6. Furthermore, IFN-γ expression was significantly enhanced by only mixture of lycopene (90 µg/ml) and 5FU (p < 0.05). In conclusion, Lycopene supplementation with 5FU therapy resulted in improvement in antioxidant parameters such as catalase and GSH levels giving the cell capacity to cope with 5FU-mediated oxidative stress. Lycopene also enhanced IFN-γ expression in the presence of 5FU, which may activate antitumor effects further enhancing the cancer killing effect of 5FU.

Antioxidant, Anti-Inflammatory and Antidiabetic Proprieties of LC-MS/MS Identified Polyphenols from Coriander Seeds.

Coriandrum sativum L. seeds are traditionally used to treat diabetes and its complications (inflammation and formation of reactive oxygen species) around the world. The present study investigates the antidiabetic, anti-inflammatory, and antioxidant effects of the polyphenol fraction of Coriandrum sativum seeds (PCS). Diabetic mice were orally administered with PCS (25 and 50 mg/kg b.w.) for 28 days. Oral glucose tolerance (OGTT) was also evaluated along with the anti-inflammatory effect, assessed by measuring paw edema development induced with carrageenan in Wistar rat and the antioxidant activity assessed using two tests (ß-carotene discoloration and DPPH). Treatment of diabetic mice with PCS for four weeks managed their high fasting blood glucose levels, improved their overall health, also revealed an excellent antihyperlipidemic activity. The OGTT result showed a potent antihyperglycemic activity, and following the anti-inflammatory and antioxidant effects, the PCS exhibited a perfect activity. LC-MS/MS result revealed the presence of 9 polyphenols. This modest work indicates that the PCS have an important antidiabetic, antihyperglycemic, antihyperlipidemic, anti-inflammatory, and antioxidant effect that can be well established treatment of diabetes and its complications.

Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action.

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO's effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.

Apoptotic Induction and Anti-Migratory Effects of Rhazya Stricta Fruit Extracts on a Human Breast Cancer Cell Line.

Rhazya stricta is a medicinal plant that is widely used in Saudi folklore medicine for treatment of various diseases. R. stricta fruit powder was sequentially extracted with n-hexane, chloroform, ethyl acetate, and methanol using a Soxhlet extractor. The cytotoxic effects of these fractions on human breast cancer cells (MDA-MB-231 and MCF-7) and non-tumorigenic control cells (MCF-10A) were evaluated via cell viability measurements, microscopy, gene expression, and migration assays. Moreover, the effect of the most promising extract on 7,12-dimethyl-benz[a]anthracene (DMBA)-induced breast cancer was investigated in rats. The promising extract was also subjected to gas chromatography-mass spectrometry. Fruit extracts of R. stricta were significantly cytotoxic toward all tested cell lines, as demonstrated by MTT and LDH assays. Treatment of MDA-MB-231 cells with fruit ethyl acetate fraction (RSF EtOAc) increased expression 11of P53, Bax and activation of caspase 3/7. A cell migration scratch assay demonstrated that extracts at non-cytotoxic concentrations exerted a potent anti-migration activity against the highly invasive MDA-MB-231 cell line. Moreover, RT-PCR results showed that RSF EtOAc significantly downregulated MMP-2 and MMP-9 expression, which play an important role in breast cancer metastasis. Histological studies of breast tissue in experimental animals showed a slight improvement in tissue treated with fruit ethyl acetate extract. GC-MS chromatogram showed thirteen peaks with major constituents were camphor, trichosenic acid and guanidine. Our current study demonstrates that fruit extracts of R. stricta are cytotoxic toward breast cancer cell lines through apoptotic mechanisms.

Analysis of Chemical Composition and Assessment of Cytotoxic, Antimicrobial, and Antioxidant Activities of the Essential Oil of Meriandra dianthera Growing in Saudi Arabia.

The essential oil of Meriandra dianthera (Konig ex Roxb.) Benth. (Synonym: Meriandra bengalensis, Lamiaceae) collected from Saudi Arabia was studied utilizing GC and GC/MS. Forty four constituents were identified, representing 96.8% of the total oil. The M. dianthera essential oil (MDEO) was characterized by a high content of oxygenated monoterpenes (76.2%). Camphor (54.3%) was the major compound in MDEO followed by 1,8-cineole (12.2%) and camphene (10.4%). Moreover, MDEO was assessed for its cytotoxic, antimicrobial, and antioxidant activities. MDEO demonstrated an interesting cytotoxic activity against all cancer cell lines with IC50 values of 83.6 to 91.2 µg/mL, especially against MCF-7 cancer cells. Using labeling with annexin VFITC and/or propidium iodide (PI) dyes and flow cytometer analysis, the apoptosis induction was quantitatively confirmed for MCF-7 cells. The MDEO exhibited a considerable antimicrobial activity against all bacterial and fungal strains with minimum inhibitory concentration (MIC)-values of 0.07 to 1.25 mg/mL. The most sensitive microbial strain was Staphylococcus aureus (MIC: 0.07 mg/mL). Minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) values were determined one time higher than that of MIC's. Additionally, the MDEO revealed a strong activity for reducing ß-carotene bleaching with a total antioxidant value of 72.6% and significant DPPH free radical scavenging activity (78.4%) at the concentration 1000 µg/mL.

Growth inhibitory effect of Leptospermum scoparium (manuka) chloroform extract on breast and liver cancer cell lines.

Objective: Research has demonstrated that Leptospermum scoparium possesses various therapeutic benefits. This study set out to determine whether or not L. scoparium extracts had any effect on the ability of HepG2 and MCF-7 breast cancer cells to survive. Materials and Methods: The antiproliferative activity of L. scoparium extracts was explored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. The most active fraction was selected to investigate its effects on apoptosis induction using flow cytometry and quantitative real-time polymerase chain reaction. The constituents of this fraction were characterized using GC-MS analysis. Results: Research demonstrated that the chloroform fraction of L. scoparium (LSCF) significantly impacted the HepG2 and MCF-7 cancer cell lines. Treatment with LSCF led to a notable rise in both early and late apoptotic cells. Furthermore, there was an upregulation in the mRNA levels of P53, Bax, and caspases, while the expression of Bcl-2 mRNA saw a decrease. The analysis of LSCF revealed the primary components to be cis-calamenene, beta-eudesmol, cyclododecane, and alpha-muurolene. Conclusion: The study showed the promising antiproliferative activity of L. scoparium, suggesting its potential application for cancer treatment.

3D computer modeling of inhibitors targeting the MCF-7 breast cancer cell line.

This study focused on developing new inhibitors for the MCF-7 cell line to contribute to our understanding of breast cancer biology and various experimental techniques. 3D QSAR modeling was used to design new tetrahydrobenzo[4, 5]thieno[2, 3-d]pyrimidine derivatives with good characteristics. Two robust 3D-QSAR models were developed, and their predictive capacities were confirmed through high correlations [CoMFA (Q2 = 0.62, R 2 = 0.90) and CoMSIA (Q2 = 0.71, R 2 = 0.88)] via external validations (R2 ext = 0.90 and R2 ext = 0.91, respectively). These successful evaluations confirm the potential of the models to provide reliable predictions. Six candidate inhibitors were discovered, and two new inhibitors were developed in silico using computational methods. The ADME-Tox properties and pharmacokinetic characteristics of the new derivatives were evaluated carefully. The interactions between the new tetrahydrobenzo[4, 5]thieno[2, 3-d]pyrimidine derivatives and the protein ERα (PDB code: 4XO6) were highlighted by molecular docking. Additionally, MM/GBSA calculations and molecular dynamics simulations provided interesting information on the binding stabilities between the complexes. The pharmaceutical characteristics, interactions with protein, and stabilities of the inhibitors were examined using various methods, including molecular docking and molecular dynamics simulations over 100 ns, binding free energy calculations, and ADME-Tox predictions, and compared with the FDA-approved drug capivasertib. The findings indicate that the inhibitors exhibit significant binding affinities, robust stabilities, and desirable pharmaceutical characteristics. These newly developed compounds, which act as inhibitors to mitigate breast cancer, therefore possess considerable potential as prospective drug candidates.

Actinobacterium-Mediated Green Synthesis of CuO/Zn-Al LDH Nanocomposite Using Micromonospora sp. ISP-2 27: A Synergistic Study that Enhances Antimicrobial Activity.

Bacterial resistance to conventional antibiotics has created an urgent need to develop enhanced alternatives. Nanocomposites combined with promising antibacterial nanomaterials can show improved antimicrobial activity compared to that of their components. In this work, green synthesized CuO nanoparticles (NPs) supported on an anionic clay with a hydrotalcite-like structure such as Zn-Al layered double hydroxide (LDH) nanocomposite were investigated as antimicrobial agents. This nanocomposite was synthesized using Micromonospora sp. ISP-2 27 cell-free supernatant to form CuO NPs on the surface of previously synthesized LDH. The prepared samples were characterized using UV-Vis spectrophotometry, XRD, FTIR, Field emission scanning electron microscopy with EDX, zeta potential, and hydrodynamic particle size. UV-vis spectral analysis of the biosynthesized CuO NPs revealed a maximum peak at 300 nm, indicating their successful synthesis. The synthesized CuO NPs had a flower-like morphology with a size range of 43-78 nm, while the LDH support had a typical hexagonal layered structure. The zeta potentials of the CuO NPs, Zn-Al LDH, and CuO NPs/LDH nanocomposite were -21.4, 22.3, and 30.8 mV, respectively, while the average hydrodynamic sizes were 687, 735, and 528 nm, respectively. The antimicrobial activity of the produced samples was tested against several microbes. The results demonstrated that the nanocomposite displayed superior antimicrobial properties compared to those of its components. Among the microbes tested, Listeria monocytogenes ATCC 7644 was more sensitive (30 ± 0.34) to the biosynthesized nanocomposite than to CuO NPs (25 ± 0.05) and Zn-Al LDH (22 ± 0.011). In summary, the use of nanocomposites with superior antimicrobial properties has the potential to offer innovative solutions to the global challenge of antibiotic resistance by providing alternative treatments, reducing the reliance on traditional antibiotics, and contributing to the development of more effective and targeted therapeutic approaches.

Anti-MRSA and cytotoxic activities of different solvent extracts from Artemisia herba-alba grown in Shubak, Jordan.

Background: Globally, resistance to antimicrobial drugs is a major hazard to public health. Infections that were once easily treatable with antibiotics are becoming harder to control, leading to prolonged illnesses, increased mortality rates, and higher healthcare costs. Aim: This study intended to assess the antimicrobial, specifically the anti-Methicillin resistant Staphylococcus aureus (MRSA), and anticancer properties of different extracts obtained from A. herba-alba (AHA). Methods: The antibacterial tests of AHA were performed on two Gram-negative bacterial strains (Escherichia coli and Klebsiella pneumonia), two Gram-positive bacterial strains (Methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus aureus). Initial screening for antibacterial activities was conducted using the well diffusion technique. Subsequently, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined through the broth-dilution assay. The anticancer test was carried out in vitro on a human colorectal carcinoma cell line (HCT-116) using MTT assay. Results: Among all extracts, n-hexane extract of AHA was the most effective against S. aureus with the highest inhibition zone (24.67 mm ± 0.58) compared to standard antibiotic (erythromycin, 24.00 mm) followed by the methanolic extract against MRSA (24.00 mm ± 1.73). The methanol extract of AHA showed the highest antibacterial activity against MRSA. The results of MIC and MBC of the AHA methanol extract against MRSA were 1.17 ± 1.09 and 9.375 ± 0.0 mg/ml, respectively, demonstrating therapeutically significant antibacterial activity. Ethyl acetate extract has no antibacterial activity against E. coli and K. pneumonia. The findings indicated that the methanol extract of AHA exhibited the highest efficacy against the colorectal carcinoma cell line (HCT-116), with an IC50 value of 126.61 ± 13.35 µg/ml. Conclusion: These findings suggest that the methanol extract of AHA could be considered as a potential agent to serve as a source of antibacterial and anticancer compounds.

Novel composite of nano zinc oxide and nano propolis as antibiotic for antibiotic-resistant bacteria: a promising approach.

This study proposes an innovative approach to combat the escalating threat of antibiotic resistance in bacteria by introducing a novel ZnO-propolis nanocomposite (ZnO-P NCs). The overuse of antibiotics, particularly during events like the COVID-19 pandemic, has intensified bacterial resistance, necessitating innovative solutions. The study employs a cost-effective and controllable biosynthesis method to produce ZnO nanoparticles (ZnO-NPs), with propolis extract crucially contributing to the reduction and stabilization of Zn2+ ions. A biodegradable nano-propolis matrix is then created by incorporating ZnO-NPs, forming the ZnO-P NCs. Structural stability is confirmed through FT-IR and Zeta potential analysis, while nanoscale properties are validated via TEM, SEM, and XRD analyses. The antimicrobial efficacy of various substances, including propolis, nano propolis, ethanolic propolis extract, ZnO-NPs, and ZnO-P NCs, is assessed against Gram-negative and Gram-positive bacteria, alongside a comparison with 28 antibiotics. Among the bacteria tested, Pseudomonas aeruginosa PAO1 ATCC15692 was more sensitive (40 mm) to the biosynthesized nanocomposite ZnO-P NCs than to ZnO-NPs (38 mm) and nanopropolis (32 mm), while Escherichia coli was resistant to nanopropolis (0 mm) than to ZnO-NPs (31 mm), and ZnO-P NCs (34 mm). The study reveals a synergy effect when combining propolis with green-synthesized ZnO-NPs in the form of ZnO-P NCs, significantly improving their efficiency against all tested bacteria, including antibiotic-resistant strains like E. coli. The nanocomposite outperforms other materials and antibiotics, demonstrating remarkable antibacterial effectiveness. SEM imaging confirms the disruption of bacterial cell membranes by ZnO-NPs and ZnO-P NCs. The study emphasizes the potential applications of ZnO-NPs integrated into biodegradable materials and underscores the significance of the zinc oxide-propolis nanocomposite in countering antimicrobial resistance. Overall, this research offers a comprehensive solution to combat multidrug-resistant bacteria, opening avenues for novel approaches in infection control.

Structure-based virtual screening methods for the identification of novel phytochemical inhibitors targeting furin protease for the management of COVID-19.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a highly contagious respiratory disease with widespread societal impact. The symptoms range from cough, fever, and pneumonia to complications affecting various organs, including the heart, kidneys, and nervous system. Despite various ongoing efforts, no effective drug has been developed to stop the spread of the virus. Although various types of medications used to treat bacterial and viral diseases have previously been employed to treat COVID-19 patients, their side effects have also been observed. The way SARS-CoV-2 infects the human body is very specific, as its spike protein plays an important role. The S subunit of virus spike protein cleaved by human proteases, such as furin protein, is an initial and important step for its internalization into a human host. Keeping this context, we attempted to inhibit the furin using phytochemicals that could produce minimal side effects. For this, we screened 408 natural phytochemicals from various plants having antiviral properties, against furin protein, and molecular docking and dynamics simulations were performed. Based on the binding score, the top three compounds (robustaflavone, withanolide, and amentoflavone) were selected for further validation. MM/GBSA energy calculations revealed that withanolide has the lowest binding energy of -57.2 kcal/mol followed by robustaflavone and amentoflavone with a binding energy of -45.2 kcal/mol and -39.68 kcal/mol, respectively. Additionally, ADME analysis showed drug-like properties for these three lead compounds. Hence, these natural compounds robustaflavone, withanolide, and amentoflavone, may have therapeutic potential for the management of SARS-CoV-2 by targeting furin.

Cannabinoid Mixture Affects the Fate and Functions of B Cells through the Modulation of the Caspase and MAP Kinase Pathways.

Cannabis use is continuously increasing in Canada, raising concerns about its potential impact on immunity. The current study assessed the impact of a cannabinoid mixture (CM) on B cells and the mechanisms by which the CM exerts its potential anti-inflammatory properties. Peripheral blood mononuclear cells (PBMCs) were treated with different concentrations of the CM to evaluate cytotoxicity. In addition, flow cytometry was used to evaluate oxidative stress, antioxidant levels, mitochondrial membrane potential, apoptosis, caspase activation, and the activation of key signaling pathways (ERK1/2, NF-κB, STAT5, and p38). The number of IgM- and IgG-expressing cells was assessed using FluoroSpot, and the cytokine production profile of the B cells was explored using a cytokine array. Our results reveal that the CM induced B-cell cytotoxicity in a dose-dependent manner, which was mediated by apoptosis. The levels of ROS and those of the activated caspases, mitochondrial membrane potential, and DNA damage increased following exposure to the CM (3 µg/mL). In addition, the activation of MAP Kinase, STATs, and the NF-κB pathway and the number of IgM- and IgG-expressing cells were reduced following exposure to the CM. Furthermore, the exposure to the CM significantly altered the cytokine profile of the B cells. Our results suggest that cannabinoids have a detrimental effect on B cells, inducing caspase-mediated apoptosis.

Synergistic Effect of Anethole and Platinum Drug Cisplatin against Oral Cancer Cell Growth and Migration by Inhibiting MAPKase, Beta-Catenin, and NF-κB Pathways.

Cisplatin is a common drug used to treat patients with oral squamous cell carcinoma. However, cisplatin-induced chemoresistance poses a major challenge to its clinical application. Our recent study has shown that anethole possesses an anti-oral cancer effect. In this study, we examined the combined effect of anethole and cisplatin on oral cancer therapy. Gingival cancer cells Ca9-22 were cultured in the presence of various concentrations of cisplatin with or without anethole. The cell viability/proliferation and cytotoxicity were evaluated, respectively, by MTT, Hoechst staining, and LDH assay, while colony formation was measured by crystal violet. Oral cancer cell migration was evaluated by the scratch method. Apoptosis, caspase activity, oxidative stress, MitoSOX, and mitochondrial membrane potential (ΔΨm) levels were evaluated by flow cytometry, and the inhibition of signaling pathways was investigated by Western blot. Our results show that anethole (3 µM) potentiates cisplatin-induced inhibition of cell proliferation and decreases the ΔΨm on Ca9-22 cells. Furthermore, drug combination was found to inhibit cell migration and enhanced cisplatin cytotoxicity. The combination of anethole and cisplatin potentiates cisplatin-induced oral cancer cell apoptosis through the activation of caspase, while we also found anethole and cisplatin to enhance the cisplatin-induced generation of reactive oxygen species (ROS) and mitochondrial stress. In addition, major cancer signaling pathways were inhibited by the combination of anethole and cisplatin such as MAPKase, beta-catenin, and NF-κB pathways. This study reports that the combination of anethole and cisplatin might provide a beneficial effect in enhancing the cisplatin cancer cell-killing effect, thus lowering the associated side effects.