Pakistan journal of pharmaceutical sciences最新文献

Beta blockers (BB) and calcium channel blockers (CCB) are highly effective to suppress angina attacks. Current observational study is designed to investigate the effectiveness of BB, CCB and its combination in angina patients. Angina patients from different tertiary care hospital cardiology OPDs were recruited from June 2022 to June 2023. Patient's history and suspected adverse drug effects (ADE) observed by manual chart review. Results showed baseline demographics and comorbidities were similar. Medication assessment revealed that most patients were on CCB (54.4%) and BB (36.36%) than combination (9.8%). Compared with BB, CCB and combination drugs taking patients represented stable heart rate and blood pressure (P<0.05). There were insignificant differences were observed in electrolytes and lipid profile in each groups. In addition, the Seattle questionnaire for angina (SQA) showed improved symptoms in 83 patients out of 110 (P<0.05). Further ADE were observed by using Naranjo scale that represented BB taking patients were found to have more ADRs than CCB and combination therapy. In conclusion, patients using BB, CCB or a combination of CCB+BB had improved angina symptoms and represented same efficacy however CCB exhibited lesser number of ADRs that shows CCB is more effective than BB in prolong use of angina control.

This study introduces an innovative, and rapid HPLC method using reverse phase elution for the simultaneous analysis of Sitagliptin and Metformin HCl in pharmaceutical formulations. This combination was explored in bulk and solid dosage forms using Luna Phenomenex C8 column (4.6 x 250 mm, 5 µm) at ambient temperature in isocratic elution. It was found that the mobile phase comprising of 0.1% ortho-phosphoric acid, potassium dihydrogen phosphate buffer (pH 3.0) and acetonitrile in ratios 35:35:30, showed a symmetrical peak for Sitagliptin and Metformin HCl. The detection was carried out at 210nm, using a flow rate of 1.0mL/min. The method was linear over the concentration range for Sitagliptin 2.5-7.5 ppm and Metformin HCl 25-75 ppm. The assay recoveries of Sitagliptin and Metformin were found to be 100.36% and 100.20%, respectively. The LOD and LOQ for the Sitagliptin were found to be 0.201 ppm and 0.301 ppm and for Metformin HCl 0.101 ppm and 0.303 ppm, respectively. The proposed methods can be implemented for controlling quality in bulk and solid dosage forms. The analytical methods were validated as per the guideline of ICH Q2 (R2). The developed HPLC methods were effectively employed for the determination of combined dosage forms in pharmaceutical formulations.

Olive leaf extracts contain several phytochemical and pharmacological properties. This study evaluated the cytotoxic, antioxidant, α-amylase inhibitory activities of aqueous, ethanol and ethyl acetate extracts from the Nabali, Muhassan and wild olive leaves grown in Jordan. Total polyphenols, flavonoids and flavonols contents, chelating power activity, total antioxidant activity and DPPH free radical scavenging activity of each extract were evaluated. The α-amylase inhibitory activity of each extract was evaluated using CNP-G3 assay while cytotoxicity was assessed against viability of MCF7 and MB-MDA-231 breast cancer cell lines by MTT. The results showed that total polyphenol content was the highest in the ethanolic wild leaf extract (113.97 mg gallic acid equivalent/g of dry extract). At a concentration of 100µg/ml, the extracts from ethanolic wild leaf, ethyl acetate of wild leaf, and ethanolic Nabali leaf exhibited the highest chelating activity for ferrous ions (52.4%, 50.5%, and 47.2%). All olive leaf extracts significantly reduced MCF7 cell growth, while ethyl acetate wild leaf extract decreased MB-MDA-231 viability. The findings revealed a robust correlation between the antioxidant, cytotoxic and α-amylase inhibitory activities of various olive leaf extracts. Further investigations are needed to identify cytoprotective effects of olive leaf extracts and the evaluation of its efficacy in vivo.

Obesity is a major health hazard, suppressing the immune system and complicating inflammatory symptoms treatment. Traditional Chinese medicine emphasizes holistic principles and syndrome-based diagnosis/therapy. Its primary focus is on enhancing overall well-being, rather than solely aiming for weight loss. Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, has demonstrated promising effects in enhancing the health status of obese individuals. Therefore, this study employed DIO mouse model to explore the immunomodulatory effects of APS in obese mice. The findings revealed a dose-dependent effect of APS on obesity prevention in DIO mice. Specifically, a 4% concentration of APS significantly reduced body weight, whereas a 2% concentration tended to increase it. Furthermore, APS effectively modulated blood glucose and lipid profiles, demonstrating varying degrees of improvement in blood glucose and blood lipid-related factors. Notably, APS also facilitated the reactivation of suppressed immune function in obese mice, regulating a range of immunological variables associated with obesity and thereby maintaining homeostasis. In conclusion, the functional benefits of APS were dose-related, with a 4% concentration demonstrating promising results in obesity prevention and immune system modulation. These findings provide a potential reference for treating inflammatory conditions associated with obesity, contributing academic understanding of obesity management and immunomodulation.

In this study, in order to further search anti-inflammatory drugs with high efficiency and low toxicity, this study took the ring of indoles and imidazole [2,1-b] thiazole as the main skeleton. A total of nine new N-1-substituted derivatives of indole-2-carboxyamide-phenylimidazoles [2,1-b] thiazole (13-20) was synthesized through the processes of cyclization, amino reduction, ester hydrolysis, dehydration condensation and acyl chloride substitution. These derivatives were then tested for their ability to reduce inflammation in RAW 264.7 macrophages. There was a significant majority of these compounds that effectively suppressed the production of NO, IL-6 and TNF-α in RAW 264.7 cells that were stimulated by LPS. One of these compounds, compound 19, was shown to be capable of efficiently lowering the levels of LPS-induced over expression of a number of inflammatory mediators. The inhibition rates for compound 19 were 54.66%, 68.82% and 43.74%, respectively. Additionally, an initial structure-activity relationship evaluation was carried out. The findings indicate that the incorporation of substituted benzyl moieties at the same position provided N-benzylation compounds with a positive anti-inflammatory effect. The electrophilicity of the substituent on the benzyl group had the potential to have an effect on the anti-inflammatory effect, which is something that calls for further investigation.

Cinnamomi Cortex is a commonly used herb with a variety of pharmacological effects. We investigated the molecular mechanisms by which Cinnamomi Cortex antagonises morphine addiction (MA) using network pharmacology and molecular docking techniques in a morphine-dependent rat withdrawal model. The antagonistic effect of Cinnamomi Cortex was observed by inducing withdrawal symptoms in morphine-dependent rats through a dose-escalation method. Network pharmacology and molecular docking techniques were further employed to analyze the substance basis and mechanism of Cinnamomi Cortex in antagonizing MA. Cinnamomi Cortex was screened to contain 10 active ingredients, 127 active targets and 1724 MA-related targets. Among them, 52 targets overlapped between Cinnamomi Cortex and MA and 13 core targets were identified by metric analysis. Cinnamomi Cortex had a significant inhibitory effect on withdrawal symptoms in MA rats, with the most pronounced effect at a moderate dose. The active ingredients of Cinnamomi Cortex (including oleic acid) can act on multiple targets related to MA and regulate multiple pathways to treat MA. The present study reveals the material basis and mechanism of cinnamon's action on MA, and provides insights and references for subsequent experiments exploring the potential therapeutic approach of Cinnamomi Cortex on MA.

Psoriasis is a chronic inflammatory immune-related skin disease. According to literature reports, the leaves of Broussonetia papyrifera exhibit antioxidant, immune-enhancing and antibacterial effects. These leaves are not only used clinically for the treatment of superficial fungal infections and hepatitis, but also used in the development of health food. However, the treatment of psoriasis with the leaves of B. papyrifera has not been reported yet. The in vitro antioxidant activity of B. papyrifera leaf extract was investigated by DPPH, OH and ABTS assays. Furthermore, IMQ was used to induce a mouse psoriasis-like model and HE staining, enzyme-linked immunosorbent assay and biochemical kits were used to measure relevant pathological indexes. The results showed that the B. papyrifera leaf extract has certain antioxidant capacity in vitro, which was positively correlated with its concentration. In addition, the extract can not only improve IMQ-induced skin damage on the back of mice, inhibit TNF-α and IL-6 factor secretion, but also regulate activity of SOD and the serum levels of MDA. Its mechanism of action related to inhibiting the secretion of inflammatory factors and the regulation of oxidative stress in vivo.

The core intent of the existing effort was to explore a triple therapy to eradicate Helicobacter pylori. A hard gelatin capsule filled with metronidazole (MNZ) floating microspheres aided with Plantago ovata seed mucilage (POSM) and Clarithromycin (CMN) floating microspheres aided with Abelmoschus esculentus fruit mucilage (AEFM). These mucilages were adopted as they have gastro-protective actions. These microspheres were designed by a central composite design. The influence of polymers used was checked towards the drug entrapment efficacy and floating time was tallied as a response. The capsule also contains Pantoprazole sodium (PZS) enteric-coated mini-tablets. These mini-tablets were checked for the coating thickness as a response (Design Expert). The microspheres and the mini-tablets were gauged for tests and a positive response was reported. The study summarizes that microspheres of MNZ & CMN and PZS enteric-coated mini-tablets can be used to eradicate H. pylori effectively. POSM and AEFM can aid MNZ and CMN microspheres formulations and have ulcer-curing and gastric-protective abilities.

The mechanisms of the anticancer effect of Tanshinone IIA (Tan IIA) on Bladder urothelial carcinoma (BUC) remain mostly unknown. In this study, BUC T24 cells were treated with Tan IIA at different concentrations and durations. The apoptosis, proliferation and invasion of T24 cells were evaluated using MTT assays, Annexin V-FITC Staining, Hoechst staining and Trans well assay. One group of T-24 cell xenograft mice was treated with Tan IIA, while the other group received normal saline for 25 days. Subsequently, the size of tumors as well as mRNA and protein expression of Aurora A, HIF-1α and Bcl-2 were measured both in vitro and in vivo. Tan IIA induced apoptosis, inhibited proliferation, suppressed invasion of T24 cells in a time- and dose-dependent manner in vitro and attenuated growth in vivo. The decreasing of mRNA and protein expression of Aurora A, HIF-1α and Bcl-2 in T-24 cells treated with Tan IIA were detected in a time- and dose-dependent manner both in vitro and in vivo. The pro-apoptotic, anti-proliferative and anti-invasive effects of Tan IIA on T-24 cells may be derived from inhibition of mRNA and protein expression of Aurora A, HIF-1α and Bcl-2. Tan IIA could potentially serve as a novel potential anti-cancer agent for BUC.

The dysregulation of mitochondrial dynamics in cardiac fibroblasts (CFs) is closely linked to myocardial fibrosis, which can induce cardiac dysfunction and even lead to heart failure. As an essential multifunctional zinc-finger transcriptional factor of cardiovascular remodeling, the role of KLF6 mediating the link between mitochondrial fission and myocardial fibrosis remains unclear. Next, we want to explore whether the effect of KLF6 on mitochondrial fission might influence cardiac fibroblasts, we established a model of Transforming growth factor β1 (TGF-β1) and Isoprenaline (ISO)-induced myocardial fibrosis. Here, we found that KLF6 up-regulation in CFs is correlated with myocardial fibrosis. While knockdown of KLF6 suppresses mitochondrial fission and the Keap1/Nrf2 pathway molecules, which alleviates myocardial fibrosis induced by TGF-β1. Our findings not only clarified the regulation mechanism of mitochondrial fission by KLF6 but also provided a potential therapeutic target for cardiovascular disease.