Pharmacology Papers & Publications

Metformin, a widely prescribed biguanide for type 2 diabetes, has emerged as a promising candidate in skin cancer therapy due to its diverse anticancer mechanisms. Beyond its glucoselowering effects, metformin inhibits key oncogenic pathways, including the PI3K/AKT/mTOR and insulin/IGF-1 signaling pathways, activates AMP-activated protein kinase, and disrupts mitochondrial complex I function. These mechanisms are presumed to contribute to metformin's antiproliferative, pro-apoptotic, and anti-inflammatory effects, potentially reducing tumor growth and metastasis in melanoma and non-melanoma skin cancers. Predictive molecular docking studies reveal that metformin interacts with critical proteins in melanoma pathophysiology. Against PI3K/mTOR (PDB: 5OQ4), PTPN2 (PDB: 7UAD), and TRIP13 (PDB: 5VQA), metformin exhibited docking scores of -4.4, -4.6, and -5.6 kcal/mol, respectively, interacting via hydrogen bonding with residues such as ASP-836, ASP-964 (5OQ4), ASP-50 (7UAD), and SER-187, SER-138 (5VQA). Compared to standard inhibitors, PQR309 (-9.4 kcal/mol), ABBV-CLS-484 (-7.5 kcal/mol), and ATP (-10.8 kcal/mol), metformin displayed moderate binding affinity, suggesting potential but weaker inhibition of these targets. Preclinical and clinical studies support metformin's potential to reduce skin cancer risk, particularly in diabetic patients. However, challenges regarding bioavailability, optimal dosing, and patient selection persist, necessitating further investigation. Therefore, given its affordability, safety, and multitargeted action, metformin represents an attractive candidate for repurposing in skin cancer pharmacotherapy. Focusing future research on optimizing its therapeutic application, refining drug combinations, and identifying biomarkers would enhance clinical outcomes.

Karishma

Background: Although statins are considered safe, they do have side effects with a wide range of hepatic adverse effects. The present study aims to estimate the frequency of liver injury in patients treated with various statins and to describe their clinical characteristics and outcomes. Materials and Methods: We carried out a secondary post hoc analysis of collected data from our previous study entitled “Frequency of Rhabdomyolysis in Patients Treated with Statins in Hamad General Hospital, Qatar.” Results: We identified 10 cases (1.0%) of statin-induced liver injury during the study period. Their mean age was 62±10.09 years, with 6 (60%) males and 4 (40%) females. Of the 10 patients, six patients received rosuvastatin, two patients received atorvastatin, and other two cases received simvastatin. The mean duration between the initiation of statin and the development of liver injury (latency period) was 20.40±6.91 months. Five of our patients were asymptomatic, and liver injury was discovered incidentally during routine testing of the patients during routine follow-up, while four patients developed painless jaundice and one developed muscle pain attributed to rhabdomyolysis. Statins were stopped in all patients. Nine of them were managed on an outpatient basis, while one patient with rhabdomyolysis was admitted. In all patients, other statins were reintroduced after a mean time of 7.4±3 months without recurrence of liver injury. No mortality has been reported. Conclusion: Our study demonstrated that statin-induced liver injury is a rare clinical entity that occurs regardless of the dose and type of statin, with rosuvastatin being the most causative drug. Statin-induced liver injury was asymptomatic and was discovered incidentally in 50% of our cases during routine testing, underscoring the importance of routine follow-up of liver function tests in asymptomatic patients.

Karishma

The leaves of khat (Catha edulis) are chewed as a social habit for the central stimulant action of their cathinone content. There is growing concern about the health hazards of chronic khat chewing. Many authors have addressed the adverse effects of khat chewing on the cardiovascular and other systems. Based on a limited number of case reports and few prospective controlled studies, associations between khat chewing and the occurrence of myocardial infarction, dilated cardiomyopathy, and vascular diseases such as hypertension and cerebrovascular ischemia have been proposed. This review outlines the current knowledge on the adverse health effects of khat chewing on the cardiovascular system, assesses the strength and the limitations of the studies, and identifies the questions that the future studies should address.

Karishma

We reported a case of cyclophosphamide (CYP)-induced posterior reversible encephalopathy syndrome (PRES) in a 26-year-old previously healthy male patient who was presented to the emergency department with a history of fever, shortness of breath, and hemoptysis. After extensive investigations, including bronchoscopy and autoimmune screening, he was diagnosed with renalpulmonary syndrome. The diagnosis of CYP-related PRES was based on the development of neurological clinical picture supported by magnetic resonance imaging findings. The dose of CYP was decreased to 75 mg/day, and the patient’s symptoms improved after 3 days.

Karishma

The global burden of metabolic disorders, including obesity and type 2 diabetes, necessitates innovative therapeutic strategies. SLU-PP-332, a synthetic agonist of estrogen-related receptor α (ERRα), has emerged as a promising exercise mimetic, demonstrating preclinical efficacy in enhancing mitochondrial biogenesis, insulin sensitivity, and energy expenditure. This brief review synthesizes current knowledge on SLU-PP-332 and related ERRα agonists, highlighting their molecular mechanisms, preclinical outcomes, translational challenges, and ethical considerations. ERRα activation by SLU-PP-332 upregulates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), driving fatty acid oxidation and mimicking exercise-induced metabolic adaptations. However, pan-ERR activity raises concerns about off-target effects such as cardiac hypertrophy and hepatotoxicity. Despite robust preclinical data, clinical translation remains hindered by the absence of human trials and undefined long-term safety. Future research must prioritize isoform-selective agonist design, rigorous clinical validation, and equitable access frameworks.

Mostafa Eissa

High-Performance Liquid Chromatography (HPLC) is a frequently utilized analytical method that has numerous characteristics, including high selectivity, sensitivity, and a reduced time requirement. Upon using this fabulous technique, the limit of detection is reduced, and the accuracy, precision, reliability, and specificity can be expanded. This technique plays a crucial role in both qualitative and quantitative analysis throughout the various stages of drug production, from the initial discovery of the drug to its excretion from the body. The role of High-Performance Liquid Chromatography (HPLC) in pharmaceutical analysis during various stages of drug discovery, production, and clinical use, including drug pharmacokinetics, is reviewed and discussed in detail. This provides an overview of the benefits of High-Performance Liquid Chromatography from the chemical, pharmaceutical, and clinical perspectives.

Mediterranean Journal of Pharmacy and Pharmaceutical Sciences

Self-medication, the practice of using medications without professional guidance, is a significant public health concern globally, particularly among medical students who, despite their pharmacological training, often engage in this practice at high rates. This cross-sectional study aimed to assess the prevalence and patterns of self-medication among medical students at the University of Tripoli, Libya. A sample of 121 undergraduate medical students was surveyed using a semi-structured questionnaire. The results revealed a high prevalence of self-medication (82.6%), with analgesics (51.2%) and vitamins (31.4%) being the most commonly used medications. Headache (80.4%), pain (79.9%), and respiratory issues (73.2%) were the primary health complaints prompting self-medication. Key determinants included pharmacist advice (43.8%), prior medical knowledge (32.2%), and recommendations from family or friends (12.4%). Factors such as residing in Tripoli and higher parental education levels were significantly associated with increased self-medication practices. Notably, 62.0% of the students reported using antibiotics without a prescription, raising concerns about antimicrobial resistance. The study highlights the need for educational interventions to promote responsible self-medication practices among medical students, emphasizing the risks associated with inappropriate drug use. Addressing these issues early in medical education could help mitigate the public health implications of widespread self-medication.

Mediterranean Journal of Pharmacy and Pharmaceutical Sciences

Background: Cannabis sativa has garnered significant attention due to its complex phytochemistry and diverse pharmacological properties. Given the rising interest in medicinal cannabis, understanding its physicochemical properties is crucial for drug development, quality control, and abuse prevention. This study aimed to analyze its phytoconstituents, with a focus on the isolation and profiling of cannabinoids. Methods: Fresh C. sativa leaves were macerated in ethanol to obtain a crude extract, which underwent phytochemical screening to detect alkaloids, flavonoids, cardiac glycosides, terpenes, steroids, and resins. Thin-layer chromatography (TLC) was performed using a n-hexane/diethyl ether (8:2) ratio as the mobile phase to separate cannabinoids, with visualization under UV light. Column chromatography further purified the extract, and subsequent TLC confirmed cannabinoid-rich fractions. Hydrogen peroxide-modified TLC was employed to assess oxidation effects on cannabinoid stability. Results: Phytochemical screening confirmed the presence of alkaloids, flavonoids, terpenes, and resins, while saponins and tannins were absent. TLC analysis revealed distinct Rf values for tetrahydrocannabinol (THC = 0.94) and cannabidiol (CBD = 0.90), with color differentiation indicating successful separation and a more polar nature of CBD. Column chromatography yielded enriched fractions, validated by TLC. Hydrogen peroxide exposure altered Rf values of 0.78 to 0.8, suggesting oxidative degradation. The study identified THC and CBD as dominant markers, alongside minor cannabinoids, reinforcing C. sativa’s complex chemical profile. These findings give clues to further research into standardized extraction protocols and stability testing to optimize medicinal applications of the plant and its phytoconstituents. Conclusions: This study highlights the efficacy of TLC and column chromatography for cannabinoid isolation and profiling. The presence of THC, CBD, and other bioactive compounds underscores C. sativa’s dual therapeutic and psychoactive potential.

Karishma

Background: Shilajit is a historically valued natural substance with promising but still preliminary scientific support for urinary and diabetic health, yet its growing popularity risks exploitation and exaggerated claims without rigorous human clinical validation. This study investigates the therapeutic effects of Yemeni Shilajit sourced from Dhamar, Ma’rib, and Raymah on hemolytic anemia experimentally induced in rabbits using phenylhydrazine. Methods: Twelve male rabbits were divided into four groups: a control group and three treatment groups, each receiving Shilajit from one of the three regions. Anemia was induced via subcutaneous injection of phenylhydrazine hydrochloride, and treatment was administered orally at a dose of 125 to 250 mg/kg twice daily. Hematological parameters—including packed cell volume (PCV), hemoglobin concentration (Hb), red blood cell (RBC) count, and glucose-6- phosphate dehydrogenase (G-6-PD) activity—were evaluated at various intervals. Results: showed that Shilajit from Dhamar and Raymah significantly increased PCV, Hb, RBC count, and G-6-PD enzyme activity (p < 0.05), suggesting notable anti-anemic effects and potential for restoring hematological parameters to near-normal levels. In contrast, Ma’rib Shilajit exhibited limited efficacy, with significant improvement only in hemoglobin levels. Phytochemical analysis confirmed the presence of essential amino acids and bioactive compounds, such as fulvic acid and dibenzo-α-pyrones, which likely contribute to Shilajit’s therapeutic action. Conclusions: The study concludes that purified Shilajit from Dhamar and Raymah holds promise as a natural remedy for hemolytic anemia, supporting its traditional use and warranting further investigation for pharmacological applications.

Karishma

Background: Previously, Ocimum sanctum (Lamiaceae), commonly known as holy basil, has been noted for its anti-ulcer properties, primarily attributed to its oil and leaf extracts. However, the anti-ulcer activity of an ethanolic extract derived from the whole plant has not been reported. This study aimed to evaluate the antiulcer effect of the ethanolic extract of O. sanctum whole plant (OSWP) in an experimental ulcer model. Methods: The study, conducted at PCSIR Labs Complex in Karachi in August 2024, was approved by the Ethical Use of Experimental Animals Committee (IEC/OSWP-05). This study investigates the anti-ulcer activity of an ethanolic extract of OSWP in a rat model of ethanol-induced gastric mucosal damage at 200, 300, and 400 mg/kg body weight, with ranitidine (50 mg/kg) used as a positive control. Outcome measures included ulcer index (UI), percentage protection, and gastric pH. Results: The ethanolic extract of OSWP demonstrated dose-dependent gastroprotective effects. At 200, 300, and 400 mg/kg, the UIs were 9.49 ± 2.40, 4.55 ± 1.44, and 2.5 ±2.25, respectively, with corresponding protection ranging from 48.9% to 86.54% for the 200 to 400 mg/kg doses (p < 0.05). Gastric pH increased from 5.6 to 7.6. In comparison, ranitidine (50 mg/kg) resulted in a UI of 4.0 ± 0.88, 78.47% protection (p < 0.05), and a pH of 7.0. Conclusions: The study demonstrates the dose-dependent anti-ulcer activity in the ethanolic extract of OSWP, which may be further developed as a potential anti-ulcer agent. A graphical presentation of the whole experimental process is shown in Figure 1.

Karishma