Journal of Pharmacy and Pharmacology最新文献

Objectives: In diabetes mellitus, inflammation and apoptosis contribute to cardiovascular injury and oxidative damage. Dapagliflozin and Pio, beyond their hypoglycemic effects, mitigate organ damage. This study explored whether their combination provides enhanced protection against cardiac damage in streptozotocin-induced diabetic rats.

Methods: Wistar rats were divided into control, diabetic (STZ, 55 mg/kg, i.p.), dapagliflozin-treated (10 mg/kg, chow), pioglitazone-treated (12 mg/kg, chow), and combination groups. After six weeks, systolic blood pressure, glucose, and lipids were assessed; subsequently, the left ventricle was excised for real-time quantitative PCR and western blot analyses.

Key findings: Both drugs alleviated STZ-induced weight loss, water intake, and urine output without significant glucose reduction. The monotherapy also effectively modulated oxidative stress, inflammation, and apoptosis. The combination of drugs led to a more favourable lipid profile than the individual drugs. Dapagliflozin + pioglitazone additively upregulated MnSOD, normalized Bcl2 and Bax/Bcl2 ratios, and decreased tumour necrosis factor-α levels in the left ventricle. These effects were associated with improved cardiac damage markers (Myh6/Myh7 ratio) and systolic blood pressure compared to the administration of the drugs alone.

Conclusions: Combined dapagliflozin and pioglitazone protect diabetic rat hearts by reducing oxidative stress, inflammation, and apoptosis, independently of glycemic control. This combination therapy offers a promising approach to mitigate cardiovascular complications in diabetes.

Respiratory infectious diseases caused by viruses pose a serious threat to human and animal health. In the search for effective antiviral agents, natural polysaccharides have emerged as promising candidates with significant potential. As natural bioactive compounds with low toxicity, polysaccharides exert antirespiratory virus effects through multiple mechanisms, including regulating immune response, inhibiting virus replication, and preventing virus adsorption and invasion. These multifaceted properties endow natural polysaccharides with broad therapeutic prospects, warranting further investigation. This review comprehensively summarizes the current understanding of the antiviral effects of natural polysaccharides and their derivatives while illustrating their underlying mechanisms, thereby providing a scientific foundation for the development of novel antiviral drugs and the advancement of natural polysaccharide-based therapeutics.

Background: Clinical effectiveness of edoxaban is hindered by poor solubility and limited permeability due to P-glycoprotein (P-gp) efflux.

Aim: The aim was to hasten dissolution and intestinal permeability of edoxaban by loading into microemulsion system consisting of menthol as oil and inhibitor of P-gp.

Methods: Pseudo-ternary phase diagram was constructed at 37°C and microemulsion comprising menthol, tween 80, ethanol and water at ratio of 20:30:30:20 was selected and evaluated.

Results: Microemulsion's droplet size was 163.47 nm, its polydispersity index was 0.28, and its zeta potential was -16.43 mV. Edoxaban was loaded in water-free system for dissolution testing. This system underwent self microemulsification in dissolution medium to increase dissolution efficiency to 95.39%, compared with 66.64% for unprocessed edoxaban. Stability assessments demonstrated the system's stability against various stress conditions. In situ intestinal perfusion studies indicated improved permeability, with 2.96-fold increase in the duodenum and 2.06-fold increase in the ileum compared with edoxaban in aqueous solution. This enhanced absorption was attributed to inhibition of P-gp-mediated efflux by menthol and Tween 80, as well as increased membrane fluidity and permeability.

Conclusion: These encouraging outcomes highlight the potential of microemulsion in improving both solubility and intestinal permeability of edoxaban enhancing of its oral bioavailability and therapeutic effectiveness.

Objective: This research aimed to evaluate the beneficial impact of Cordyceps militaris (CM) on chronic obstructive pulmonary disease (COPD) and methodically clarify its underlying processes.

Methods: The fingerprint analysis and content determination of CM were carried out by HPLC. The effect of CM on COPD was evaluated by a COPD mouse model. Potential targets were further explored by combining metabolomics with network pharmacology. The binding capacity between the active ingredients of CM and potential targets was assessed by molecular docking.

Key findings: A total of five nucleosides in CM were identified, including uridine, guanosine, adenosine, cordycepin, and N6-(2-hydroxyethyl) adenosine. CM significantly improved lung function and ameliorated the pathological changes in COPD. Subsequently, eight shared differentially expressed metabolites were significantly altered following CM intervention via non-targeted metabolomics analysis, with the linoleic acid metabolic pathway enriched. Next, two potential targets involving IDH1 and CYP19A1 were identified by the metabolite-reaction-enzyme-gene network. Finally, molecular docking results further corroborated strong binding affinities between the six active ingredients and the two potential targets.

Conclusions: This study suggested that CM could ameliorate COPD by modulating linoleic acid metabolism and influencing IDH1 and CYP19A1, which would provide a scientific basis for the treatment of COPD with CM.

Objectives: Inflammation, oxidative harm, and degradation of mitochondria ultimately contribute to the initiation neurodegenerative changes. This study investigated the inhibitory effects of rosavin and salidroside on neuroinflammation induced by β-amyloid oligomers using primary microglia derived from the cerebral tissue of C57BL/6 J mice.

Key findings: Following β-amyloid oligomers' production, a series of continuous neurological deterioration takes place. Rosavin and salidroside exhibited distinct inhibitory effects on different neurodegenerative damage. Subsequent studies indicated that the protective mechanism of rosavin was associated with nuclear factor к-B phosphorylation.

Lay summary: Rhodiola rosea L., with its natural small molecule compounds like rosavin may be potential candidates for the treatment of AD.

Purpose: Cardiac microvascular impairment serves a function in cardiac hypertrophy (CH). Oleanolic acid (OA), a bioactive pentacyclic triterpenoid substance, has been extensively investigated for its anti-inflammatory and antioxidant characteristics. This investigation sought to elucidate the involvement of pyroptosis and mitochondrial malfunction in microvascular damage and examine the potential of OA in inhibiting pyroptosis and mitigating endothelial injury.

Methods: We utilized a rat CH model and performed several experiments, encompassing network pharmacology, molecular docking, western blot, morphological analysis, mitochondrial membrane potential detection, mitochondrial oxygen consumption rate assay and enzyme-linked immunosorbent assay kit detection.

Results: Network pharmacology approaches were employed to forecast the potential molecular targets of OA. The results showed that OA interacts with signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-B (NF-κB), peroxisome proliferator-activated receptor gamma (PPARG), and Interleukin-1β (IL-1β). Echocardiography data showed that OA remarkably improves cardiac function, and inhibits CH in rats. Mechanistically, upregulation of p-STAT3 expression, NF-κB p65 and IL-1β, but downregulation of PPARG could be detected in the hearts of CH rat and in cardiac microvascular endothelial cells (CMECs) exposed to Ang II. In addition, OA decreased STAT3 and NF-κB phosphorylation and up-regulated PPARG, thereby inhibiting pyroptosis and improving mitochondrial function.

Conclusion: OA rescued mitochondrial function and inhibited CMEC pyroptosis by directly interacting with PPARG, STAT3, NF-κB, and IL-1β, and then suppressed CH.

Objectives: Ziziphus jujuba var. spinosa, commonly known as sour jujube, has been utilized for millennia in traditional Chinese medicine and functional foods. This review comprehensively summarizes the phytochemistry, pharmacology, and resource utilization of its multiple medicinal-edible parts, aiming to bridge research gaps and promote integrated applications.

Methods: A systematic literature search was conducted across PubMed, Web of Science, Google Scholar, and CNKI, using keywords such as "Sour jujube" and "Z. jujuba var. spinosa," covering publications up to December 2024.

Key findings: Phytochemical analysis identified 354 bioactive compounds, including 164 flavonoids and 74 triterpenoids, underlying the plant's broad-spectrum pharmacological activity. The seeds, a well-documented herbal medicine, are used alone, in polyherbal formulations, or as an adjuvant to acupuncture, with sedative-hypnotic effects extensively studied via neurotransmitter regulation, specifically by upregulating GABA receptor expression and inhibiting 5-HT degradation and signaling pathway modulation. Nonseed tissues, such as fruits, leaves, and roots, exhibit underutilized potential due to their high content of antioxidants and nutrients, yet remain understudied, leading to resource waste.

Conclusions: This review highlights the need to prioritize research on nonseed parts to maximize their medicinal and nutritional value. The findings provide a scientific basis for advancing sour jujube's applications in healthcare and functional food industries.

Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options. Cannabidiol (CBD) has demonstrated anticancer potential, but its clinical application is hindered by poor solubility and nonspecific distribution. This study aimed to develop a folic acid-modified chitosan (FA-CS) nanoparticle system to enhance the targeted delivery and therapeutic efficacy of CBD against TNBC.

Methods: FA-CS@CBD nanoparticles were synthesized and characterized for morphology, size distribution, zeta potential, and stability. Their in vitro anticancer effects were evaluated through cytotoxicity, cellular uptake, apoptosis, and reactive oxygen species (ROS) assays in 4T1 breast cancer cells. The in vivo antitumour efficacy and systemic toxicity were assessed using a TNBC mouse model.

Key findings: FA-CS@CBD nanoparticles exhibited uniform morphology, stable physicochemical properties, and efficient cellular uptake. Compared to free CBD, the nanoparticles significantly enhanced ROS production, induced apoptosis, and inhibited migration in 4T1 cells. In vivo studies demonstrated strong tumour-targeting capability and a tumour inhibition rate of 68.07%, with minimal systemic toxicity.

Conclusions: The FA-CS@CBD nanoparticle system improved the targeted delivery and therapeutic effects of CBD against TNBC while maintaining favorable biocompatibility. These findings highlight the potential of FA-CS-based nanocarriers for enhancing CBD clinical application in breast cancer therapy.

Objective: The current study assessed the pharmacological potential of syringol and guaiacol, both separately and in combination, in hyperglycemia linked to dicarbonyl stress (DS).

Methods: The control group (n = 5) received a standard diet with Tween 20 and disease group received high-fat high-fructose diet. The remaining four groups received metformin, syringol (100 μg/kg), guaiacol (100 μg/kg), or a combination of both (50 + 50 μg/kg) starting on the 29th day and lasting 30 days. After study completion, glucose intolerance, oxidative stress markers, glycated products, liver, renal, lipid markers along with liver and pancreatic histology were assessed. NF-κB, TNF-α, IL-6, IL-1β, and nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels were estimated using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR).

Key findings: Combination therapy markedly decreased weight (31.30%), fasting blood glucose (74.92%), glucose intolerance (65.42%), and improved biochemical markers of lipid, hepatic, and renal function. The combination therapy significantly reduced (P < .05) malondialdehyde, nitric oxide, expression of NF-κB, TNF-α, IL-6, and IL-1β while increasing superoxide dismutase, catalase and reduced glutathione levels. Combination therapy significantly (P < .05) reduced HbA1c levels and increased Glo1, Glo2, and Nrf-2 levels. Histopathological variations showed reduced cellular damage in the treatment groups.

Conclusion: Combination of syringol and guaiacol exhibits significant pharmacological efficacy for managing DS associated with hyperglycemia.

Background: Preclinical studies have demonstrated that the edible arboreal medicinal mushroom Hericium erinaceus (HE) mitigates high corticosterone levels and enhances stress-coping strategies in rodents, with emerging evidence suggesting similar neuroprotective potential for Fomitopsis officinalis (FO) and Pleurotus djamor (PDJ). However, comparative dose-dependent effects, including comprehensive anxiety and depression assessments, remain underexplored.

Purpose: This study investigates the dose-dependent effects of dietary supplementation with HE, FO, or PDJ on anxiety-like behaviors and stress-coping strategies in rats, building on prior findings of their anxiolytic and antidepressant-like properties, and compares these effects to fluoxetine (FLX; 20 mg/kg), a standard treatment for stress-related psychiatric disorders.

Study design: Male Wistar rats received 0, 100, 250, or 500 mg/kg (per os) of HE, FO, or PDJ lyophilizate from in vitro cultures for 3 weeks.

Methods: Behavioral outcomes were assessed using the open field test (OFT), elevated plus maze (EPM), and forced swim test (FST). Pearson's correlations explored relationships between FST parameters.

Results: A middle dose of FO (250 mg/kg) increased rearing in the OFT, indicating reduced anxiety-like behavior. In the EPM, FO (100-250 mg/kg) and PDJ (100 mg/kg) increased open arm entries and time while reducing closed arm time, indicating anxiolytic-like effects consistent with prior studies on HE and extending novel insights to PDJ. In the FST, FO (250 mg/kg) reduced immobility, increased swimming, and decreased climbing, suggesting serotonergic-mediated antidepressant-like effects comparable or superior to FLX. HE and PDJ (250-500 mg/kg) reduced immobility and increased climbing or swimming, indicating dose-specific antidepressant effects. Immobility was strongly negatively correlated with swimming (r = -0.75, P < .0001) and moderately with climbing (r = -0.43, P < .001), with no significant correlation between swimming and climbing (r = -0.18, P = .06).

Conclusion: This study advances prior research by demonstrating that dietary supplementation with HE, FO, and PDJ exerts dose-dependent anxiolytic and antidepressant-like effects in rats, likely via serotonergic, noradrenergic, GABAergic, and anti-inflammatory pathways. The FST correlations highlight distinct coping mechanisms, supporting their potential as dietary interventions for stress-related disorders, comparable to FLX, warranting further investigation into underlying mechanisms and clinical applicability.