Journal of Pharmacy and Pharmacology最新文献

Introduction: The Bruguiera cylindrica L. is a mangrove plant that is typically found in coastal areas of Asia, including India. It has been known for its medicinal properties, which have been utilized for generations. For example, in Thailand, it has been used to treat wounds and diarrhoea, while in India, it has been effective in addressing diabetes, ulcers, and other health issues. This particular study sought to investigate the potential of B. cylindrica bark extract in reducing the symptoms of diabetes in rats.

Methods: In this study, we examined the potential of B. cylindrica bark extract as an inhibitor of α-amylase and α-glucosidase enzymes in vitro. We also evaluated the effects of the extract and Metformin on rats fed high-fat diets and measured their lipid profiles and biochemical parameters. Furthermore, we conducted a network pharmacology analysis to identify proteins and pathways involved in the amelioration of diabetes.

Results: Through metabolite profiling, we identified 58 compounds in B. cylindrica hydroalcoholic extract. These compounds include alkaloids, phenolics, flavonoids, and fatty acids. The extract was found to have a dose-dependent inhibition activity against α-amylase and α-glucosidase, with IC50 values similar to acarbose. In rats, oral administration of 200-400 mg/kg of B. cylindrica led to reduced blood glucose levels and normalized serum biochemical parameters.

Conclusions: Bruguiera cylindrica bark may reduce blood sugar levels in rats with diabetes. The study found metabolites that interact with protein targets associated with different types of diabetes.

Statins, also known as HMG-CoA reductase inhibitors, are widely prescribed drugs for the prevention and treatment of cardiovascular diseases. In addition to their lipid-lowering effects, these compounds have been found to possess immune-modulating properties. Macrophages, which are crucial phagocytic cells in the body, can be divided into two main subsets: M1 (proinflammatory) and M2 (anti-inflammatory). While there is evidence suggesting that statins exert an anti-inflammatory action on macrophages and promote their polarization towards the M2 subset, recent studies have identified the proinflammatory impact of statins on macrophages, leading to polarization towards the M1 subset. For example, statins have been shown to inhibit NF-κB activation to promote anti-inflammatory responses. On the other hand, statins can induce NFκB/AP-1 activation and increase IL-1β secretion in macrophages to promote pro-inflammatory responses. This review aims to provide a comprehensive overview of both in vivo and in vitro studies that have investigated the effects of statins on macrophage polarization and inflammatory responses in various diseases. Furthermore, this review seeks to evaluate the underlying mechanisms involved in these effects. By summarizing the existing evidence, this review contributes to our understanding of the complex interactions between statins and macrophages in different disease contexts.

Objectives: Intestinal ischemia reperfusion (IIR) is a critical emergency situation that needs immediate intervention. Small intestine is one of the most sensitive tissues to IR injury and it remains a highly morbid condition, with reported mortality rates ranging from 30% to 90%. Thus, we aimed to evaluate the suspected protective role of sacubitril/valsartan (SAC/VAL) on IIR injury.

Methods: Thirty-two adult male Wistar rats were used in our model and divided into four groups: sham group, SAC/VAL treated group without IIR, IIR group, and SAC/VAL treated group with IIR. SAC/VAL in a dose of 30 mg/kg was administered orally just before induction of IIR.

Key findings: SAC/VAL significantly ameliorated IIR-induced changes as it decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), angiotensin II (ANG II), interleukin 6 (IL 6), active caspase 3, and signal transducer- and activator-of transcription (STAT1). However, SAC/VAL administration significantly increased antioxidant parameters such as total antioxidant capacity (TAC), superoxide dismutase (SOD), and reduced glutathione (GSH). Moreover, alteration of the histological structure was observed in IIR group that was improved by SAC/VAL.

Conclusions: SAC/VAL prevents IIR-induced damage via modulation of renin angiotensin aldosterone system, antioxidant, anti-apoptotic, anti-inflammatory properties, and regulation of IL6/STAT1 pathway.

The management of asthma and chronic obstructive pulmonary disease (COPD) poses considerable challenges due to the intricate nature of these respiratory conditions. Fostair™ and Trimbow™, two pressurized metered dose inhalers, have emerged as noteworthy therapeutic options for treating both asthma and COPD. Fostair combines an inhaled corticosteroid, specifically beclometasone dipropionate, with a long-acting beta2-agonist, formoterol fumarate dihydrate, offering a dual-action approach to mitigate airway inflammation and bronchoconstriction. Conversely, Trimbow integrates a tri-particulate formulation consisting of beclometasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide, providing a comprehensive strategy to target the pathophysiology of COPD and asthma. Recent clinical trials have underscored Trimbow's superior efficacy compared with Fostair, particularly in terms of reducing exacerbation rates and enhancing lung function. However, despite their therapeutic promise, both inhalers encounter challenges, including limited generalizability of study findings and a disparity between in vitro and human trial results. This literature review offers an in-depth analysis of Fostair and Trimbow, delving into their mechanisms of action, clinical applications, and outcomes in human studies for asthma and COPD. Additionally, the review discusses the role of combination therapy in managing respiratory diseases and underscores the necessity for further research to address existing knowledge gaps and optimize therapeutic outcomes.

Aim: This study investigates the molecular mechanisms through which Panax ginseng and Panax notoginseng saponin (PNS) mitigate neuroinflammatory damage and promote neural repair postischemic stroke, utilizing bioinformatics, and experimental approaches.

Background: Cerebral infarction significantly contributes to disability worldwide, with chronic neuroinflammation worsening cognitive impairments and leading to neurodegenerative diseases. Addressing neuroimmune interactions is crucial for slowing disease progression and enhancing patient recovery, highlighting the need for advanced research in neuroimmune regulatory mechanisms and therapeutic strategies.

Objective: To elucidate the effects of the traditional Chinese medicine components Panax ginseng and PNS on neuroinflammatory damage following ischemic stroke, focusing on the molecular pathways involved in mitigating inflammation and facilitating neural repair.

Methods: The study employs single-cell sequencing and transcriptomic analysis to investigate gene expression changes associated with cerebral infarction. Gene set enrichment analysis and weighted gene co-expression network analysis are used to identify key molecular markers and core genes. Furthermore, pharmacological profiling, including functional assays, assesses the impact of Ginsenoside-Rc, a PNS derivative, on microglial cell viability, cytokine production, and reactive oxygen species (ROS) levels.

Results: Our analysis revealed that MAPK14 is a critical mediator in the neuroinflammatory response to ischemic stroke. Ginsenoside-Rc potentially targets and modulates MAPK14 activity to suppress inflammation. Experimental validation showed that Ginsenoside-Rc treatment, combined with MAPK14 silencing, significantly alters MAPK14 expression and mitigates neuroinflammatory damage, evidenced by reduced microglial cell death, inflammatory factor secretion, and ROS production.

Conclusion: Ginsenoside-Rc's modulation of MAPK14 offers a promising therapeutic strategy for reducing neuroinflammation and potentially improving cognitive recovery post-ischemic stroke. This supports the therapeutic application of the traditional Chinese medicine Sanqi in ischemic stroke care, providing a theoretical and experimental foundation for its use.

Others: Future work will focus on extending these findings through clinical trials to evaluate the efficacy and safety of Ginsenoside-Rc in human subjects, aiming to translate these promising preclinical results into practical therapeutic interventions for ischemic stroke recovery.

Objectives: We examined the antirheumatoid effects of piperlongumine (PLM) on rat adjuvant-induced arthritis (AIA) and explored the underlying mechanisms involved.

Methods: PLM (2.5, 5, and 10 mg/kg) was administered intraperitoneally to AIA rats to assess its effectiveness. Blood, thymus, spleen, ankle joint, and synovial tissue samples were gathered for subsequent analyses, like enzyme-linked immunosorbent assay, thymus/spleen index measurement, ankle joint pathological examination, immunohistochemistry assay, polymerase chain reaction, and western blot assay. Moreover, the involvement of osteoprotegerin (OPG)/receptor activators of nuclear factor κB ligand (RANKL)/nuclear factor-κB (NF-κB) signaling was investigated.

Key findings: PLM effectively relieved inflammation and joint destruction in AIA rats, as indicated by reductions in hind paw swelling, arthritis index, thymus/spleen index, ankle joint pathological damage, production of TNF-α, IL-1β, and IL-6 in both serum and synovium, and osteoclast formation. Also, PLM treatment raised OPG production, reduced RANKL expression, and elevated the OPG/RANKL ratio in synovial tissues. Furthermore, PLM prevented IκBα degradation and phosphorylation, resulting in a reduced expression of the nuclear NF-κB p65 protein in AIA rat synovial tissues.

Conclusions: PLM demonstrated strong antiarthritic effects in rats with AIA by influencing the OPG/RANKL/NF-κB signaling pathway, highlighting its potential clinical relevance in treating rheumatoid arthritis.

Objectives: This study was designed to investigate the pharmacological activity and therapeutic mechanism of Mahuang Xixin Fuzi decoction (MXFD) on migraine.

Methods: Migraine model rats induced by nitroglycerin were established, and then orally administered with MXFD for 7 days. Blood and urine samples were collected to identify differential metabolites with metabolomics. To integrate the findings from network pharmacology and metabolomics analysis, the metabolites and targets related to MXFD therapy for migraine were filtered.

Key findings: MXFD was found to alleviate the symptoms of migraines in rats. After treatment with MXFD, nine metabolites were found to be regulated and returned to normal levels. MXFD acted directly on nine key targets including MAOB, MAOA, ADRB1, ADRB2, ADRB3, ADORA2A, ADORA2B, DRD5, and HTR4 and regulated two out of nine metabolites, namely deoxycholic acid and 5-methoxyindoleacetate.

Conclusions: The study found that MXFD can alleviate migraines through multitarget and multicomponent interaction networks.

Background: We administered Bushen Huoxue Huazhuo Formula (BSHXHZF) and transplanted bone marrow mesenchymal stem cells (BMSCs) into mice with Wilson's disease (WD)-related liver fibrosis to evaluate the liver-protecting mechanism of this prescription.

Methods: Mice, randomly divided into different treatment groups, showed histopathological changes and degree of hepatocyte apoptosis. For hepatic hydroxyproline (Hyp) determination, transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7) mRNA and protein were measured. Chemical profiling of the extract of BSHXHZF using The liquid chromatography-mass spectrometry (LC-MS/MS) and revealing its antifibrosis mechanism using metabolomics.

Results: TCM+BMSC group livers exhibited few inflammatory cells. TUNEL revealed abundant brown apoptotic cells in model control groups, while the TCM+BMSC groups showed a significant increase in blue negative expression of liver cells. Hyp in toxic milk (TX) mice groups was significantly lower than that in model control groups (MG). Compared with MG, TGF-β1 expression was significantly lower than all other groups, while BMP-7 expression was significantly higher. Metabolic analysis identified 20 potential biomarkers and 10 key pathways, indicating that BSHXHZF+BMSC intervention has a significant regulatory effect on metabolic disorders of these small molecule substances.

Conclusion: BSHXHZF combined with BMSCs can inhibit liver fibrosis and hepatocyte apoptosis by improving related metabolic disorders, and achieving therapeutic effects in WD-related liver fibrosis.

Objectives: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa.

Methods: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy.

Key findings: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG.

Conclusion: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.

Objectives: Schisandrin B (Sch B) has been shown to possess anti-inflammatory and antioxidant properties, however, its antirheumatoid arthritis properties and potential mechanism remain unexplored. This study evaluated the potential of Sch B in adjuvant-induced arthritic (AIA) rats.

Methods: AIA was induced by injecting 0.1 ml of CFA into the paw of rats and the animals were administered with Sch B (50 mg/kg) for 28 days. The effects of Sch B were evaluated using arthritis severity, serum levels of oxido-inflammatory, and metabolic index parameters.

Key findings: Sch B eased arthritic symptoms by significantly reducing paw swelling and arthritic score and increased body weight gain. Moreover, Sch B alleviated the levels of oxido-inflammatory markers including interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, nuclear factor kappa B, transforming growth factor β1, inducible nitric oxide synthase and malonaldehyde, as well as increased the levels of superoxide dismutase, glutathione, and Nrf2. Sch B also remarkably restored the altered levels of triglyceride, aspartate aminotransferase, lactic acid, pyruvate, phosphoenolpyruvate carboxylase, glucose, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor. In addition, Sch B markedly alleviated p65 expression in the treated AIA rats.

Conclusion: This study suggests that Sch B alleviated AIA by reducing oxidative stress, inflammation, and angiogenesis.