Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells

Introduction: Among numerous triterpenoids of the Cucurbitaceae family, Cucurbitacin-B (Cur-B) is being explored for its pharmacological attributes. Reports from previous studies have explicitly shown that Cur-B possesses substantial anticancer effects. The present report focuses on exploring the anticancer attributes of Cur-B against androgen-dependent PCa LNCaP cells.Methods: LNCaP cells were exposed to commercially available purified Cur-B at varying concentrations that were selected as 5, 10, 15, 20, and 25 µM for some time of 24 h to perform various experimental studies.Results: Cytotoxicity evaluation revealed that Cur-B impeded the LNCaP cell’s viability at 5 µM (p <0.05) which increased considerably at a concentration of 25 µM (p <0.001). Cur-B was also efficacious in inducing the changes within nu-clear morphology followed by a concomitant increase in the activities of key caspases including caspase-3, -8, and -9 intriguingly in a dose-dependent trend. Cur-B treatment not only resulted in the augmentation of intracellular ROS levels within LNCaP cells at 5 µM (p <0.05) but also in-creased significantly at 25 µM concentration (p <0.001). Elevation in the ROS levels was also found to be correlated with dissipated mitochondrial membrane potential (ΔΨm) which culminated in the onset of significant apoptosis at 25 µM concentration (p <0.001). Cur-B exposure also resulted in the downregulation of cyclin D1, cyclin-dependent kinase 4 (CDK4) followed by amplified levels of p21Cip1 mRNA. Importantly, exposure of Cur-B competently reduced the expression of the Notch signaling cascade which may be the plausible cause behind Cur-B-instigated apoptotic cell death and cell cycle arrest in LNCaP cells.Discussion: These observations thus, explicitly indicated that Cur-B could be plausibly further explored as potent therapeutics against androgen-dependent PCa

ARTEMETHER LOADED ETHYLCELLULOSE NANOSUSPENSIONS: EFFECTS OF FORMULATION VARIABLES, PHYSICAL STABILITY AND DRUG RELEASE PROFILE

Objective: The aim of this study was to explore the individual and joint effects of drug: ethylcellulose ratio, content of tween 80 and chloroform: water volume ratio on particles' size and size distribution of artemether loaded ethyl cellulose nanosuspension formulations, aiming to achieve nanosuspension with desired particles properties, stability and drug release profile.Methods: Mixed levels design was used to generate a series of artemether loaded ethylcellulose nanosuspensions that produced by emulsification-solvent evaporation technique. Formulations were qualified for particle size and size distribution using dynamic light scattering technique. Best ranked formulation was then evaluated for stability and drug release rate and kinetics.Results: Drug: polymer ratio, content of surfactant and organic: water volume ratio were found to exert considerable influences (p<0.05) on particle size of produced nanosuspensions, either individually or as joint variables. Peak intensity property of nanosuspensions was found to be influenced by drug: polymer ratio (p<0.05) whereas the influences of different variables on the polydisperse index property appear inconsequential (p>0.05). Best ranked (optimal) artemether nanosuspension proved stable and capable to improve and maintain the release of loaded drug over 24 h, at least under the setting conditions of this study.Conclusion: Focusing on both the individual and joint influences of formulation variables assist in achieving nanosuspension with desired particles characteristics, stability and drug release profile

Image1_Cucurbitacin-B instigates intrinsic apoptosis and modulates Notch signaling in androgen-dependent prostate cancer LNCaP cells.TIF

Introduction: Among numerous triterpenoids of the Cucurbitaceae family, Cucurbitacin-B (Cur-B) is being explored for its pharmacological attributes. Reports from previous studies have explicitly shown that Cur-B possesses substantial anticancer effects. The present report focuses on exploring the anticancer attributes of Cur-B against androgen-dependent PCa LNCaP cells.Methods: LNCaP cells were exposed to commercially available purified Cur-B at varying concentrations that were selected as 5, 10, 15, 20, and 25 µM for some time of 24 h to perform various experimental studies.Results: Cytotoxicity evaluation revealed that Cur-B impeded the LNCaP cell’s viability at 5 µM (p Cip1 mRNA. Importantly, exposure of Cur-B competently reduced the expression of the Notch signaling cascade which may be the plausible cause behind Cur-B-instigated apoptotic cell death and cell cycle arrest in LNCaP cells.Discussion: These observations thus, explicitly indicated that Cur-B could be plausibly further explored as potent therapeutics against androgen-dependent PCa.</p

Metformin Therapy and Breast Cancer Incidence in the Ha&rsquo;il Region

Background: Metformin is a drug used to treat patients with type 2 diabetes, especially those who suffer from obesity. It is also used in the treatment of women with polycystic ovary syndrome (PCOS). This disease is related to insulin resistance and multiplied blood sugar ranges. Furthermore, it has been established that the use of metformin improves the menstrual cycles and ovulation rates of these women. Methods: A structured questionnaire was conducted to determine the prevalence of breast cancer among women using metformin in the Ha&rsquo;il region. Result: The incidence of breast cancer among women using metformin in the Ha&rsquo;il region is very low. Thus, it can be said that breast cancer cases declined among diabetics taking metformin. This means that metformin use is associated with a lower risk of breast cancer in women with type 2 diabetes, even in cases where these women have a family history of breast cancer. Conclusions: According to previous findings, metformin has been linked to lower breast cancer risk in women with type 2 diabetes. Furthermore, the findings of this study corroborate the literature on this subject by indicating that there is a substantial connection between metformin use and a lower risk of breast cancer in women with type 2 diabetes. However, further in vitro and in vivo experiments are crucial to investigate the protective effect of metformin against breast cancer and to confirm our findings

Development of Tea Tree Oil Based Nanoemulgel Loaded with Azithromycin for Enhancing the Antibacterial Activity

Azithromycin (AZ) is an azalide macrolide antibiotic that is frequently employed for treating bacterial skin infections. It suffers from limited oral bioavailability, which results from incomplete absorption or extensive first-pass metabolism. Therefore, preparing azithromycin formulations for topical administration is highly recommended to avoid first-pass metabolism and to boost the concentration of the drug on the skin. The objective of our investigation was to formulate and evaluate the efficacy of AZ-loaded nanoemulgel as an antimicrobial drug. The physical appearance, spreadability, viscosity, particle size, in vitro drug release, ex vivo permeation investigations, and antimicrobial efficiency of the prepared formulations were evaluated. The prepared formulation loaded with AZ exhibited good physical quality. AZ-loaded nanoemulgel had a greater ex vivo drug permeation across rabbit skin than other formulations (AZ-loaded gel and AZ-loaded emulgel), revealing improved drug permeation and greater transdermal flux in addition to enhanced antibacterial efficacy (p < 0.05). Overall, our findings imply that tea-tree-oil-based nanoemulgel would be a promising delivery system for enhancing the antimicrobial efficiency of azithromycin

Development and Optimization of Erythromycin Loaded Transethosomes Cinnamon Oil Based Emulgel for Antimicrobial Efficiency

Erythromycin (EM) is a macrolide antibiotic that is frequently used to treat skin bacterial infections. It has a short half-life (1–1.5 h), instability in stomach pH, and a low oral bioavailability. These foregoing factors limit its oral application; therefore, the development of topical formulations loaded with erythromycin is an essential point to maximize the drug’s concentration at the skin. Accordingly, the current study’s goal was to boost the antimicrobial activity of EM by utilizing the advantages of natural oils such as cinnamon oil. Erythromycin-loaded transethosomes (EM-TE) were generated and optimized using a Box–Behnken design employing, phospholipid concentration (A), surfactant concentration (B), and ethanol content (C) as independent variables. Their effects on entrapment efficiency, EE, (Y1) and the total amount of erythromycin that penetrated the skin after 6 h, Q6h (Y2), were assessed. The optimized transethosome showed a particle size of 256.2 nm, EE of 67.96 ± 0.59%, and Q6h of 665.96 ± 5.87 (µg/cm2) after 6 h. The TEM analysis revealed that, the vesicles are well-known packed structures with a spherical shape. The optimized transethosomes formulation was further transformed into a cinnamon oil-based emulgel system using HPMC as a gelling agent. The generated EM-TE-emulgel was characterized by its physical features, in vitro, ex vivo studies, and antimicrobial activities. The formulation showed sufficient characteristics for effective topical application, and demonstrated a great stability. Additionally, EM-TE-Emulgel had the highest transdermal flux (120.19 μg/cm2·h), and showed considerably (p < 0.05) greater antimicrobial activity, than EM-TE-gel and placebo TE-Emulgel. The action of EM was subsequently augmented with cinnamon oil, which eventually showed a notable effect against bacterial growth. Finally, these results demonstrate that the transethosomes-loaded cinnamon oil-based emulgel is an alternative way to deliver erythromycin for the treatment of topical bacterial infections

Formulation and Evaluation of Amikacin Sulfate Loaded Dextran Nanoparticles against Human Pathogenic Bacteria

Amikacin sulfate-loaded dextran sulfate sodium nanoparticles were formulated, lyophilized (LADNP), and then analyzed. The LADNP had a −20.9 ± 8.35 mV zeta potential, PDI of 0.256, and % PDI of 67.7. The zeta average nano size of LADNP was 317.9 z. d.nm, while the dimension of an individual particle was 259.3 ± 73.52 nm, and nanoparticle conductivity in colloidal solution was 2.36 mS/cm. LADNP has distinct endothermic peaks at temperatures at 165.77 °C, according to differential scanning calorimetry (DSC). The thermogravimetric analysis (TGA) showed the weight loss of LADNP, which was observed as 95% at 210.78 °C. XRD investigation on LADNP exhibited distinct peaks at 2θ as 9.6°, 10.4°, 11.4°, 18.9°, 20.3°, 24.4°, 28.2°, 33.2°, 38.9°, and 40.4° confirming crystalline structure. The amikacin release kinetics from LADNP revealed zero order kinetics with a linear release showed zero order kinetics with 37% of drug release in 7 h and had an R2 value of 0.99. The antibacterial effect of LADNP showed broad-spectrum activity against tested human pathogenic bacteria. The preset study demonstrated that LADNP is a promising antibacterial agent

A comprehensive assessment of phytochemicals from Phyla nodiflora (L.) Greene as a potential enzyme inhibitor, and their biological potential: An in-silico, in-vivo, and in-vitro approach

This work explored Phyla nodiflora (L.) Greene as a potential source of the bioactive medicinal agent. In this aspect, methanol (PN-M) and dichloromethane (PN-D) extracts were prepared from the whole plant and evaluated for phytochemical composition (total bioactive contents, UHPLC-MS analysis, and HPLC-PDA polyphenolic quantification), biological (antioxidant and enzyme inhibition) potential and in-vivo toxicity. The PN-M was found to contain higher phenolic (26.08 mg GAE/g extract) and flavonoid (50.25 mg QE/g extract) contents which might correlate to the higher radical scavenging (DPPH: 52.94 mg TE/g extract; ABTS: 72.11 mg TE/g extract) and reducing power (FRAP: 71.96 mg TE/g extract; CUPRAC: 142.65 mg TE/g extract) antioxidant potential, as well as AChE (4.33 mg GALAE/g extract), tyrosinase (125.36 mg KAE/g extract), and amylase (1.86 mmol ACAE/g extract) inhibition activity of this extract. In contrast, the PN-D extract was found to be most active for phosphomolybdenum (1.30 mg TE/ g extract) and metal chelation (54.84 mg EDTAE/g extract) assays in addition to BChE (4.70 mg GALAE/g extract) and glucosidase (0.62 mmol ACAE/g extract) enzyme inhibition activity. The PN-M extract on UHPLC-MS analysis revealed the tentative identification of 24 different secondary metabolites, most of which belonged to the flavonoid, glycoside, and terpenoid classes of phytochemicals. The polyphenolic composition of the extracts was appraised by HPLC-PDA. Seven phenolic compounds were identified in the extracts. PN-M was found to be rich in catechin (0.25 µg/extract) and 3-OH benzoic acid (0.64 µg/extract), while PN-D contained epicatechin (0.30 µg/extract), 3-OH-4-MeO benzaldehyde (0.21 µg/extract), and 2,3-Di-Meo benzoic acid (0.97 µg/extract) in higher amounts. The methanol extract was found to be non-toxic even at higher doses. Furthermore, the relationship between the phytochemicals and the tested enzymes was highlighted by molecular docking studies. In sum, this research showed that the studied extracts were effective as enzyme inhibitors and antioxidants, suggesting it would be worth investigating in more depth for further advanced studies to explore its pharmacological properties