Exploring the potential of Ziziphus nummularia and luteolin-7-O-glucoside as tubulin inhibitors in cancer therapy and survival.

Cancer is responsible for approximately 10 million deaths worldwide, with 70% of the deaths occurring in low- and middle-income countries; as such safer and more effective anti-cancer drugs are required. Therefore, the potential benefits of Ziziphus nummularia and Ziziphus spina-christi as sources of anti-cancer agents were investigated. Z. nummularia and Z. spina-christi extracts were prepared using chloroform, ethanol, ethyl acetate, and water. The extracts' anti-cancer properties were determined using the MTT Cell Viability Assay in four cancer cell lines: breast (KAIMRC2 and MDA-MB-231), colorectal (HCT8), and liver (HepG2). The ApoTox-Glo Triplex Assay and high-content imaging (HCI)-Apoptosis Assay were used to assess KAIMRC2 and HCT8 cells further. In addition, KAIMRC2 cells were tested for microtubule staining, and AKT/mTOR protein expression was determined by western blot analysis. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the secondary metabolites in the ethanol and ethyl acetate extracts, followed by in silico techniques to predict molecular targets and interactions, safety, and pharmacokinetic profile for identified metabolites. Out of the eight extracts, the ethanolic extract of Z. nummularia, exhibited the most potent activity against KAIMRC2 cells with an IC50 value of 29.2 µg/ml. Cancer cell treatment with the ethanolic extract of Z. nummularia resulted in a dose-dependent decrease in cell viability with increased apoptosis and cytotoxic effects. Microtubule staining showed a disrupted microtubular network. The ethanolic extract treatment of KAIMRC2 cells led to upregulated expression of pAKT and pmTOR. In silico studies predicted luteolin-7-O-glucoside to be a ligand for tubulin with the highest docking score (- 7.686) and similar binding interactions relative to the native ligand. Further computational analysis of the metabolites showed acceptable pharmacokinetic and safety profiles, although ethanolic extract metabolites were predicted to have cardiotoxic effects. Ethanolic extraction is optimal for solubilizing active anticancer metabolites from Z. nummularia, which may act by causing M-phase arrest via inhibition of tubulin polymerization. Luteolin-7-O-glucoside is the lead candidate for further research and development as an anti-cancer agent. In addition, this study suggests that herbal treatment could switch on mechanisms of adaptation and survival in cancer cells.

Exploring in vitro and in silico Biological Activities of Calligonum Comosum and Rumex Vesicarius: Implications on Anticancer and Antibacterial Therapeutics.

Introduction: The adverse effects of clinically used anti-cancer medication and the rise in resistive micro-organisms have limited therapeutic options. Multiple anti-cancer drugs are derived from medicinal herbs which also have shown anti-bacterial effects. This study aimed to identify the optimal extraction solvent for detecting the cytotoxic and anti-bacterial effects of Calligonum comosum (C. Comosum) and Rumex vesicarius (R. Vesicarius) extracts. Additionally, the study aimed to identify active metabolites and assess their potential as future drug candidates for anti-cancer and anti-bacterial therapeutics. Methods: Leaves from both plants were extracted using ethanol, ethyl acetate, chloroform, and water. The cytotoxic effects of the extracts were tested on liver, colon, and breast cancer cell lines. Apoptosis was assessed using High Content Imaging (HCI) and the ApoTox triplex Glo assay. The anti-bacterial effects were determined using agar-well diffusion. Liquid chromatography-mass spectrometry (LC-MS) was used to tentatively identify the secondary metabolites. In silico computational studies were conducted to determine the metabolites' mode of action, safety, and pharmacokinetic properties. Results: The ethanolic extract of C. Comosum exhibited potent cytotoxicity on breast cancer cell lines, with IC50 values of 54.97 µg/mL and 58 µg/mL for KAIMRC2 and MDA-MB-231, respectively. It also induced apoptosis in colon and breast cancer cell lines. All tested extracts of C. Comosum and R. Vesicarius demonstrated anti-bacterial activity against Staphylococcus aureus and Escherichia coli. Seven active metabolites were identified, one of which is Kaempferol 3-O-Glucoside-7-O-Rhamnoside, which showed strong (predicted) anti-cancer activity. Kaempferol 3-O-Glucoside-7-O-Rhamnoside and Quercetin-3-O-Glucuronide also exhibited potential anti-bacterial effects on gram-positive and negative bacteria. Conclusion: Ethanol extraction of C. Comosum solubilizes active metabolites with potential therapeutic applications in cancer treatment and bacterial infections. Kaempferol 3-O-Glucoside-7-O-Rhamnoside, in particular, shows promise as a dual therapeutic drug candidate for further research and development to improve its efficacy, safety, and pharmacokinetic profile.

Assessing the Perception of Pharmacy Students on Launching a Doctor of Pharmacy/Master of Public Health Dual Degree Program in Saudi Arabia: A Multi-Institutional Cross-Sectional Study.

There is a lack of Doctor of Pharmacy (PharmD) and Master of Public Health (MPH) dual degree programs in Saudi Arabia. This study aims to examine current pharmacy students' perceptions regarding establishing such a program and the perceived limitations and advantages of pursuing such a degree. We conducted a cross-sectional web-based short survey to assess the feasibility of establishing a PharmD/MPH dual degree program in several randomly selected pharmacy schools in Saudi Arabia. Our cohort consisted of 657 students. Almost 56% were males, and nearly 58% were fourth-year pharmacy students. Close to 85% had a "very well" or "well" understanding regarding the pharmacist's role in the public health area, and almost 70% stated that they see themselves playing a role in public health as a future pharmacist. Nearly 93% reported that they are either "very likely" or "likely" to enroll in such a program if given the opportunity. Almost 80% felt it would increase their job opportunities. On the other hand, close to 70% felt it would increase workload and stress. This study highlights pharmacy students' positive perceptions regarding establishing a PharmD/MPH dual degree program in Saudi Arabia. The study results could be utilized as the starting point to propose and establish this program to health education policymakers in Saudi Arabia.