Journal of Pharmacy and Pharmacology最新文献

Objectives: Asthma is a heterogeneous disease characterized by chronic airway inflammation. Huashanshen dripping pills (HSS) are commonly utilized for relieving asthma, relieving cough, and expelling phlegm. At present, the molecular mechanism against airway inflammation remains unclear.

Methods: In this study, network pharmacology, molecular docking technology, and molecular dynamic simulation were used to predict the therapeutic pathways of HSS for asthma. The ovalbumin-induced mouse model was used to further validate the prediction by RT-qPCR, western blot, immunofluorescence, and related methods.

Key findings: The findings indicate that HSS improves lung function and relieves lung inflammation by reducing inflammatory cell infiltration around the bronchus and reducing eosinophilic counts in bronchoalveolar lavage fluid (BALF). In addition, it lowers the levels of inflammatory cytokines and the expression levels of interleukin-4, interleukin-5, and interleukin-13 mRNA. HSS also inhibits the phosphorylation and nuclear translocation of NF-κB p65 protein.

Conclusions: All results suggested that HSS can decrease airway inflammation in asthmatic mice by inhibiting NF-κB signaling pathway. This finding will shed light on how it can be used to treat asthma.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a nutritional and metabolic disease with a high prevalence today. Artemisia capillaris has anti-inflammatory, antioxidant, and other effects. However, the mechanism of A. capillaris in treating NAFLD is still poorly understood.

Methods: This study explored the mechanism of A. capillaris in the treatment of NAFLD through network pharmacology and molecular docking, and verified the results through in vivo experiments using a high-fat diet-induced mouse model and in vitro experiments using an oleic acid-induced HepG2 cell model.

Key findings: Aqueous extract of A. capillaris (AEAC) can reduce blood lipids, reduce liver lipid accumulation and liver inflammation in NAFLD mice, and improve NAFLD. Network pharmacology analysis revealed that 51 drug ingredients in A. capillaris correspond to 370 targets that act on NAFLD. GEO data mining obtained 93 liver differentially expressed genes related to NAFLD. In the UHPLC-MS detection results, 36 components were characterized and molecular docked with JNK. Verified in vitro and in vivo, the results show that JNK and the phosphorylation levels of IL-6, IL-1β, c-Jun, c-Fos, and CCL2 are key targets and pathways.

Conclusions: This study confirmed that AEAC reduces lipid accumulation and inflammation in the liver of NAFLD mice by inhibiting the JNK/AP-1 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.

Lipotoxicity is defined as a prolonged metabolic imbalance of lipids that results in ectopic fat distribution in peripheral organs such as the liver, heart, and kidney. The harmful consequences of excessive lipid accumulation in cardiomyocytes cause cardiac lipotoxicity, which alters the structure and function of the heart. Obesity and diabetes are linked to lipotoxic cardiomyopathy. These anomalies might be caused by a harmful metabolic shift that accumulates toxic lipids and shifts glucose oxidation to less fatty acid oxidation. Research has linked fatty acids, fatty acyl coenzyme A, diacylglycerol, and ceramide to lipotoxic stress in cells. This stress can be brought on by apoptosis, impaired insulin signaling, endoplasmic reticulum stress, protein kinase C activation, p38 Ras-mitogen-activated protein kinase (MAPK) activation, or modification of peroxisome proliferator-activated receptors (PPARs) family members. Curcuma longa is used to extract curcumin, a hydrophobic polyphenol derivative with a variety of pharmacological characteristics. Throughout the years, curcumin has been utilized as an anti-inflammatory, antioxidant, anticancer, hepatoprotective, cardioprotective, anti-diabetic, and anti-obesity drug. Curcumin reduces cardiac lipotoxicity by inhibiting apoptosis and decreasing the expression of apoptosis-related proteins, reducing the expression of inflammatory cytokines, activating the autophagy signaling pathway, and inhibiting the expression of endoplasmic reticulum stress marker proteins.

Background: In this study, Schisandrin B (SCHB), the main active component of Schisandra chinensis extract (SCE), was taken as the research object. From gene, microRNA (miR-124), and the level of protein expression system to study the influences of microglia phenotype to play the role of nerve inflammation.

Methods: In this study, we investigated the role of miR-124 in regulating microglial polarization alteration and NF-κB/TLR4 signaling and MAPK signaling in the LPS-induced BV2 by PCR, western blot, ELISA, immunofluorescence, and cytometry.

Results: SCE and SCHB significantly reduced the NO-releasing, decreased the levels of TNF-α, iNOS, IBA-1, and ratio of CD86+/CD206+, and increased the levels of IL-10, Arg-1. In addition, SCE and SCHB inhibited the nucleus translocation of NF-κB, decreased the expressions of IKK-α, and increased the expressions of IκB-α. Besides, the expressions of TLR4 and MyD88, and the ratios of p-p38/p38, p-ERK/ERK, and p-JNK/JNK were reduced by SCE and SCHB treatments. Furthermore, SCHB upregulated the mRNA levels of miR-124. However, the effects of SCHB were reversed by the miR-124 inhibitor.

Conclusions: These findings suggested SCHB downregulated NF-κB/TLR4/MyD88 signaling pathway and MAPK signaling pathway via miR-124 to restore M1/M2 balance and alleviate depressive symptoms.

Aims: The aim of the present review was to highlight natural product investigations in silico and in vitro to find plants and chemicals that inhibit or stimulate angiotensin-converting enzyme 2 (ACE-2).

Background: The global reduction of incidents and fatalities attributable to infections with SARS-CoV-2 is one of the most public health problems. In the absence of specific therapy for coronavirus disease 2019 (COVID-19), phytocompounds generated from plant extracts may be a promising strategy worth further investigation, motivating researchers to evaluate the safety and anti-SARS-CoV-2 effectiveness of these ingredients.

Objective: To review phytochemicals in silico for anti-SARS-CoV-2 activity and to assess their safety and effectiveness in vitro and in vivo.

Methods: The present review was conducted using various scientific databases and studies on anti-SARS-CoV-2 phytochemicals were analyzed and summarized. The results obtained from the in silico screening were subjected to extraction, isolation, and purification. The in vitro studies on anti-SarcoV-2 were also included in this review. In addition, the results of this research were interpreted, analyzed, and documented on the basis of the bibliographic information obtained.

Results: This review discusses recent research on using natural remedies to cure or prevent COVID-19 infection. The literature analysis shows that the various herbal preparations (extracts) and purified compounds can block the replication or entrance of the virus directly to carry out their anti-SARS-CoV-2 effects. It is interesting to note that certain items can prevent SARS-CoV-2 from infecting human cells by blocking the ACE-2 receptor or the serine protease TMPRRS2. Moreover, natural substances have been demonstrated to block proteins involved in the SARS-CoV-2 life cycle, such as papain- or chymotrypsin-like proteases.

Conclusion: The natural products may have the potential for use singly or in combination as alternative drugs to treat/prevent COVID-19 infection, including blocking or stimulating ACE-2. In addition, their structures may provide indications for the development of anti-SARS-CoV-2 drugs.

Objectives: To explore the effective components of Guishao Yigong decoction (GYD) in the treatment of colorectal cancer and reveal its potential mechanism of action.

Methods: Through network pharmacology, the main target and signaling pathway of GYD therapy for colorectal cancer (CRC) were found. Subsequently, the effect of GYD was verified by in vitro cell viability measurements, colony formation, and scratch healing tests. The effects of GYD on metabolic pathways in vivo were found through plasma metabolomics. Finally, flow cytometry and qPCR experiments were used to verify the cycle-blocking effect of GYD on CRC cells.

Key findings: Based on the network pharmacological analysis and molecular docking technology, it was found that GYD could restrain the growth of CRC cells by affecting lipid metabolic pathways and mitogen-activated protein kinase (MAPK) signaling pathways. A series of cell experiments showed that GYD could inhibit the proliferation, migration and clonogenic ability of CRC cells. Furthermore, the plasma metabolomics results showed that GYD could affect the production of unsaturated fatty acids in mice. Flow cytometry and qPCR experiments further proved that GYD blocked the CRC cells in the G1 phase and modulated the expression of cell cycle-related targets, such as AKT, TP53, CDKN1A, and CDK2.

Conclusions: All the results indicated that GYD could regulate the related metabolism of unsaturated fatty acids. Thus, the cell cycle was blocked and the expressions of the key proteins such as AKT and TP53 were regulated, which achieved the purpose of intervention in colorectal cancer.