Fahd A. Nasr

Catha edulis Forsk., commonly known as Khat, is a stimulant plant that is chewed in the Horn of Africa and the southern regions of the Arabian Peninsula. It is often used alongside conventional drugs, but there is a lack of research on its interactions with other drugs. In this study, our aim was to investigate the possibility of an herb–drug interaction between KT extract and metformin (MT) by exploring the effect of KT on the in vivo pharmacokinetics of MT in diabetic Wistar albino rats and monitoring blood glucose levels through time intervals, comparing when MT was given alone and co-administered with KT. Rats were given 500 mg/kg of KT extract and 300 mg/kg of MT daily for 7 days. The pharmacokinetic parameters of MT were analyzed using UPLC-MS/MS. The quantification was conducted using multiple reaction monitoring (MRM) in positive ion mode. The transitions used were (m/z) 130.006→59.939 for MT and 260.125→116.018 for propranolol as an internal standard (IS). An Acquity UPLC BEH HSS T3 C18 column was used with isocratic elution, and the mobile phase was formic acid (0.1%): acetonitrile (70:30 v/v) at a flow rate of 0.25 mL/min. In addition, the study delved into the in vitro impact of KT on the CYP3A4 enzyme, seeking to identify any potential disruptions in MT’s metabolism that could alter its pharmacokinetics. The effect of KT extract on CYP3A4 enzyme activity was investigated using fluorescence-based enzyme assays and a CYP3A4 Inhibitor Screening Kit. The results indicated that the combined treatment showed increased systemic exposure to MT, with Cmax and AUC levels increasing by 33.42% and 45.23%, respectively. Additionally, the combination treatment led to significantly lower fasting blood glucose (FBG) levels compared to the groups treated with MT alone. It was found that at a concentration of 500 µg/mL, the CYP3A4 enzyme activity was maximally suppressed by approximately 57%, while at 250 µg/mL, it was inhibited by almost 50%. In comparison, the standard Ketoconazole only inhibited CYP3A4 activity by approximately 58%. Therefore, the in vitro results suggest that KT extract has the potential to affect CYP3A4 activity at high doses. In conclusion, the combination treatment resulted in a significant increase in MT’s blood sugar-lowering effects. Therefore, it is important to be aware of this potential interaction and to monitor blood sugar levels closely when using KT alongside MT.

Lung cancer is a formidable challenge in clinical practice owing to its metastatic nature and resistance to conventional treatments. The codelivery of anticancer agents offers a potential solution to overcome resistance and minimize systemic toxicity. The encapsulation of these agents within nanostructured lipid carriers (NLCs) provides a promising strategy to enhance lymphatic delivery and reduce the risk of relapse. This study aimed to develop an NLC formulation loaded with Gefitinib and Azacitidine (GEF-AZT-NLC) for the treatment of metastatic-resistant lung cancer. The physicochemical properties of the formulations were characterized, and in vitro drug release was evaluated using the dialysis bag method. The cytotoxic activity of the GEF-AZT-NLC formulations was assessed on a lung cancer cell line, and hemocompatibility was evaluated using suspended red blood cells. The prepared formulations exhibited nanoscale size (235–272 nm) and negative zeta potential values (−15 to −31 mV). In vitro study revealed that the GEF-AZT-NLC formulation retained more than 20% and 60% of GEF and AZT, respectively, at the end of the experiment. Hemocompatibility study demonstrated the safety of the formulation for therapeutic use, while cytotoxicity studies suggested that the encapsulation of both anticancer agents within NLCs could be advantageous in treating resistant cancer cells. In conclusion, the GEF-AZT-NLC formulation developed in this study holds promise as a potential therapeutic tool for treating metastatic-resistant lung cancer.

The accumulation of body fat due to an imbalance between calorie intake and energy expenditure is called obesity. Metabolic syndrome increases the risk of heart disease, type 2 diabetes, and stroke. The purpose of this study was to determine the effect of Jatropha tanjorensis (J.T.) and Fraxinus micrantha (F.M.) leaf extracts on high-fat diet-induced obesity in rats. Normal control, high-fat diet (HFD) control, orlistat standard, and test groups were created using male Albino Wistar rats (n = 6 per group) weighing 190 ± 15 g. Except for the control group, all regimens were administered orally and continued for 6 weeks while on HFD. Evaluation criteria included body weight, food intake, blood glucose, lipid profile, oxidative stress, and liver histology. High-Performance Thin Layer Chromatography (HPTLC) analysis was performed using a solvent system (7:3 hexane: ethyl acetate for sitosterol solution and Jatropha tanjorensis extracts and 6:4 hexane: ethyl acetate: 1 drop of acetic acid for esculetin and Fraxinus micrantha extracts). There were no deaths during the 14 days before the acute toxicity test, indicating that aqueous and ethanolic extracts of both J.T. and F.M. did not produce acute toxicity at any dose (5, 50, 300, and 2000 mg/kg). The ethanolic and aqueous extracts of J.T. and F.M. leaves at 200 and 400 mg/kg/orally showed a reduction in weight gain, feed intake, and significant decreases in serum glucose and lipid profile. As compared to inducer HFD animals, co-treatment of aqueous and ethanolic extract of both J.T. and F.M. and orlistat increased the levels of antioxidant enzymes and decreased lipid peroxidation. The liver’s histological findings showed that the sample had some degree of protection. These results indicate that ethanolic samples of J.T. have antidiabetic potential in diabetic rats fed an HFD. The strong antioxidant potential and restoration of serum lipid levels may be related to this. Co-treatment of samples JTE, JTAQ, FME, FMAQ and orlistat resulted in an increase in antioxidant enzymes and reduction in lipid peroxidation as compared to inducer HFD animals. We report, for the first time, on using these leaves to combat obesity.

Euphorbia plants have a significant place in traditional medicine due to their numerous therapeutic properties, including their anti-tumor effects, which have been observed in several species. In the current study, a phytochemical investigation of Euphorbia saudiarabica methanolic extract led to the isolation and characterization of four secondary metabolites from the chloroform (CHCl3) and ethyl acetate (EtOAc) fractions, which are reported for the first time in this species. One of the constituents, saudiarabicain F (2), is a rare C-19 oxidized ingol-type diterpenoid that has not been previously reported. The structures of these compounds were determined by extensive spectroscopic (HR-ESI-MS, 1D and 2D NMR) analyses. The anticancer properties of the E. saudiarabica crude extract, its fractions and its isolated compounds were examined against several cancer cells. The active fractions were evaluated for their effects on cell-cycle progression and apoptosis induction using flow cytometry. Furthermore, RT-PCR was employed to estimate the gene-expression levels of the apoptosis-related genes. It was demonstrated that the E. saudiarabica CHCl3 and EtOAc fractions suppressed the proliferation of the cancer cells. The MCF-7 cells were the most sensitive to both fractions, with IC50 values of 22.6 and 23.2 µg/mL, respectively. Notably, both fractions caused cell-cycle arrest in the G2/M phase of the treated MCF-7 cells. The inhibition of the MCF-7 cells’ proliferation was also linked with apoptosis induction by flow-cytometry analysis. Additionally, the activation of apoptosis by both fractions was demonstrated by an increase in the ratio of Bax to Bcl-2, with an increase in the expression of caspase-7. Among the isolated compounds, glutinol (1) showed potent activity against the MCF-7 cell line, with an IC50 value of 9.83 µg/mL. Our findings suggest that E. saudiarabica has apoptosis-inducing effects and shows promise as a potential source of new chemotherapeutic drugs.