Journal of Pharmacy and Pharmacology最新文献

Objectives: Increased intraocular pressure (IOP) is a significant risk factor for primary open-angle glaucoma (POAG). Physiologically, the trabecular meshwork (TM) controls IOP and the secretion of aqueous humor. A change in resistance to aqueous outflow is related to the phagocytic ability of trabecular meshwork cells (TMCs); in addition, alterations in extracellular matrix can also affect the function of TMCs. However, their application has certain limitations due to the nondirected differentiation and tumorigenic effect of stem cells, while their exosomes can reduce side effects and exert the same effects.

Methods: The effects of mesenchymal stem cell exosomes on the extracellular environment and the function of human trabecular meshwork cells were observed, and glaucomato-related proteins as well as the NRF2 signaling pathway were detected.

Key findings and conclusions: The exosomes could improve the phagocytosis of TMCs, reduce the damage, and lead to some changes in the pathways related to oxidative stress.

Background: Kidney diseases affect over 850 million people globally and are a significant cause of morbidity and mortality. Traditional biomarkers like serum creatinine, blood urea nitrogen, and proteinuria have limited sensitivity and specificity, often detecting damage only after substantial renal function loss. Even U.S. Food and Drug Administration (FDA)-approved biomarkers, such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and cystatin C, have limitations because their levels can be influenced by inflammation, infections, or disease stage. There is an urgent need for reliable, non-invasive biomarkers for early diagnosis and treatment guidance.

Objective: This review provides an updated overview of emerging biomarkers for early detection and monitoring of kidney diseases (acute kidney injury, chronic kidney disease, diabetic kidney disease, polycystic kidney disease, lupus nephritis, renal cell carcinoma).

Methods: A comprehensive literature review focused on studies from the past decade on urine and blood-based biomarkers that reflect key pathological processes, including inflammation, tubular injury, fibrosis, and immune activation.

Results: Promising biomarkers include collectrin, olfactomedin 4, activin A, follistatin, USP18, galectin-3, fetuin-A, sestrin-2, podocalyxin, copeptin, anti-C1q, p-cresol glucuronide, serum CD206, lncRNAs, and miRNAs.

Conclusions: These biomarkers may enhance early diagnosis, enable personalized therapy, and improve kidney disease outcomes. Their integration into clinical practice may bridge the gap between early detection and effective intervention, potentially improving long-term outcomes in patients with kidney disease.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a Gram-positive bacterium found in hospital-acquired infections, particularly in immunosuppressed individuals. Brazilian red propolis is a beekeeping product with antimicrobial and immunomodulatory properties. Its composition includes flavonoids and benzophenones, such as oblongifolin B (OBLB). This study investigated the antibacterial activity of OBLB isolated from Brazilian red propolis against MRSA in vitro and its modulatory effects on macrophages.

Methods: The activity of OBLB was assessed both alone and in combination with antimicrobials. The minimum inhibitory and minimum bactericidal concentrations were determined for the USA300 MRSA strain and for a clinical isolate. The interaction between OBLB and the antimicrobials against MRSA was analysed using the checkerboard method. The effects of OBLB on THP-1 cells differentiated into macrophages were analysed regarding cytokine and eicosanoid production, cell surface marker expression, bactericidal activity, and hydrogen peroxide production.

Key findings: OBLB exhibited anti-MRSA activity and had no synergistic effects with antimicrobials or cytotoxic effects on macrophages. It stimulated tumor necrosis factor-α and interleukin-1β production, CD80 expression, and increased the bactericidal activity of macrophages suppressed or not by dexamethasone against MRSA.

Conclusions: OBLB exerted anti-MRSA properties and modulated macrophage activity, suggesting it is a potential candidate in new therapeutic approaches for MRSA infections.

Objectives: Tamoxifen is an endocrine therapy for breast cancer that works by competing with estradiol for estrogen receptors, but continued use of tamoxifen by patients can lead to resistance and metastasis. Studies have shown that 4-hydroxytamoxifen (4-OH-TAM), the active product of tamoxifen, promotes the malignant biological behavior of breast cancer cells, but the mechanism is not fully understood.

Methods: We investigated the effects of 4-OH-TAM on breast cancer cell stemness, paclitaxel (PTX) resistance and metastasis. Molecular mechanism studies were used to investigate the pro-cancer effects of 4-OH-TAM.

Key findings: Treatment with low-dose 4-OH-TAM increased the resistance of ER-positive (MCF-7 and T47D cells) and triple-negative (4T1 and MDA-MB-231 cells) breast cancer cells to PTX. In vitro and in vivo experiments showed that 4-OH-TAM enhanced stemness in T47D and 4T1 cells by upregulating the stem cell markers CD44 and CD133. Mechanistically, 4-OH-TAM enhanced breast cancer cell stemness by upregulating estrogen-related receptor alpha (ERRα) protein expression via neuropilin-1 (NRP-1). Notably, inhibition of the NRP-1/ERRα signaling pathway reversed 4-OH-TAM-induced PTX resistance and tumor metastasis.

Conclusion: 4-hydroxytamoxifen enhances stemness through the NRP/ERRα pathway to enhance breast cancer cell PTX resistance and metastasis.

Objectives: Propolis is a bee-derived product traditionally used in folk medicine to treat inflammatory diseases. Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that occurs during pregnancy and presents systemic inflammation, leading to adverse maternal and fetal outcomes. The present study evaluated the immunomodulatory role of a Brazilian green propolis extract on monocytes from women with early-onset (EOPE) and late-onset (LOPE) preeclampsia.

Methods: Peripheral blood was collected from 16 women with EOPE, 16 with LOPE, and 20 normotensive pregnant women. Monocytes were treated with Brazilian green propolis extract. The expression of p65NF-κB, ERK1/2, the CD192 receptor, and cytokines (IL-1β, IL-6, IL-10, IL-12, TNF-α) were analyzed by flow cytometry. Antioxidant capacity was assessed using the ferric reducing antioxidant power assay, and levels of heat shock protein (Hsp70), high mobility group box 1 protein (HMGB1), monocyte chemotactic protein-1 (MCP-1), and heme-oxigenase-1 were measured by enzyme-linked immunosorbent assay.

Key findings: PE groups, especially EOPE, showed higher plasma levels of HMGB1, Hsp70, and MCP-1. Monocytes from PE women exhibited increased expression of p65NF-κB, ERK1/2, and CD192, as well as proinflammatory cytokines, accompanied by reduced IL-10 expression. Propolis treatment significantly reduced inflammatory markers and upregulated IL-10 expression.

Conclusion: These findings support its potential as an adjunctive therapy to modulate the inflammatory profile in women with preeclampsia, particularly in those with EOPE disease.

Objectives: This study examined the effects of the noncatechin flavonoids (NCFs), a mixture of a range of flavonoids obtained from Camellia sinensis (L.) Kuntze seeds on Type 2 diabetes mellitus (T2DM).

Methods: Thirty-two 10-week-old SHR rats were randomly assigned to four groups. The RD group was fed a regular diet. The DM group was injected with 'streptozotocin (STZ, 50 mg/kg)' and nicotinamide '(NA, 100 mg/kg)' and fed a high-fat diet (HFD). The NCF0.5 group or NCF5 group was injected with 'STZ/NA' and fed HFD plus oral gavage NCF 0.5 or 5 mg/kg/day for four weeks, respectively.

Key findings: T2DM was successfully induced as evidenced by lower body weight and higher blood pressure, blood glucose, HbA1c; lower insulin, GLP-1; and higher IL-6, TNF-α, and MDA and deterioration of proteins regulating vasocontraction and vasodilation (AGTR1, AGTR2, ETB, eNOS), regulating glucose metabolism (AMPK, IRB, IRS-1, PI3K, Akt/PKB, PPAR-γ, GLUT-4, HKase, PKase, GSK-3α, PEPCK, G6Pase) and free radical scavengers (catalase, GPx). These biochemical parameters were improved dose dependently by NCFs, suggesting that association with NCFs had anti-T2DM, antiperoxidation, and anti-inflammatory effects.

Conclusions: NCFs possessing total flavonoids (42.5 ± 3.4 μg/mg), not saponins and catechins, could efficiently control T2DM. Thus, NCF could potentially develop into an agent for controlling T2DM and related complications.

Objective: This study investigated the protective mechanisms of Qian Yang Yu Yin Granule (QYYYG) against hypertensive renal injury.

Methods: A hypertensive renal injury model was established in Spontaneous hypertensive rat (SHR) rats using angiotensin II infusion combined with unilateral nephrectomy. Rats were assigned to model, valsartan, and high-/low-dose QYYYG groups and treated for 8 weeks. Blood pressure (BP), blood urea nitrogen (BUN), renal histopathology, and related biochemical indicators were evaluated. In vitro, HK-2 cells pretreated with QYYYG or valsartan were subjected to hypoxic conditions. The expression levels of HIF-1α, NOX4, HO-1, Nrf2, and SESN2 were quantified.

Key findings: QYYYG markedly reduced BP and BUN levels and ameliorated renal histopathological damage. It upregulated SESN2, activated AMPKα, inhibited mTOR phosphorylation, and suppressed NOX4 expression, thereby reducing HIF-1α accumulation. QYYYG also enhanced the expression of SESN2, Nrf2, and HO-1. Consistently, in vitro, QYYYG significantly increased SESN2, Nrf2, and HO-1 expression while reducing NOX4 and HIF-1α levels.

Conclusion: QYYYG alleviates hypertensive renal injury by regulating the Sestrin2 signaling pathway and improving local oxidative stress responses.

Objectives: Erectile dysfunction (ED), or impotence, means having trouble getting or keeping an erection. The National Institutes of Health (NIH) says ED can happen to men at any age, but it's more common as men get older. This review looks at PDE5 inhibitor drugs approved by health authorities to treat ED. We carefully studied available research and clinical data to understand these drugs, how they work, how well they help, their safety, and their role in managing ED.

Methods: A literature-based study was conducted using PubMed, ScienceDirect, and regulatory documents (FDA, EMA) from 2015-2025. Search terms included "PDE5 inhibitors," "erectile dysfunction," and "ED pharmacological interventions." Secondary data from peer-reviewed clinical trials, meta-analyses, and pharmacokinetic studies were synthesized and analyzed.

Key findings: PDE5 inhibitors significantly improve erectile function compared with placebo across diverse patient populations. While overall efficacy among approved agents is broadly comparable, differences in onset of action, duration, and pharmacokinetic characteristics allow treatment individualization. Adverse events are generally mild, transient, and dose-related, with a favourable benefit-risk profile when prescribed in accordance with contraindications and cardiovascular risk assessment. Alternative therapies are effective in PDE5 inhibitor non-responders. Formulation innovations, including chewable dosage forms, may enhance adherence.

Conclusion: In summary, this review helps doctors and researchers by providing clear information about PDE5 inhibitor drugs for ED and pointing out areas where more research can improve treatment and quality of life for men with this condition.

Objectives: Cardiac microvascular dysfunction contributes to the pathogenesis of cardiac hypertrophy (CH) and potentially progresses to cardiac failure. Dendrophenol (Den), a naturally derived compound isolated from Dendrobium moschatum, exhibits diverse biological properties, including anti-inflammatory, antioxidant, anti-angiogenic, anti-proliferative, and anti-metastatic effects. This investigation aimed to examine ferroptosis involvement in microvascular dysfunction and assess Den's capacity to suppress ferroptosis while ameliorating pressure overload-induced endothelial damage.

Methods: A rat CH model was established, and comprehensive experimental approaches were implemented, including network pharmacology (NP), molecular docking, Western blot analysis, hematoxylin and eosin staining, wheat germ agglutinin staining, Masson staining, Gel-ink staining, immunohistochemistry, Laser speckle contrast analysis, immunofluorescence, quantitative reverse transcription polymerase chain reaction, and luciferase reporter gene.

Key findings: NP methodologies were applied to predict Den's potential molecular targets. Echocardiographic assessments demonstrated that Den markedly enhanced cardiac function, while morphological staining analyses revealed that Den substantially suppressed CH development in rats. Additionally, Den ameliorated cardiac microvascular dysfunction in the abdominal aortic constriction-induced CH rat model. Mechanistic investigations revealed that Den suppresses C-Jun phosphorylation and decreases NCOA4 expression, consequently inhibiting ferroptosis in cardiac microvascular endothelial cells.

Conclusion: Den attenuated CH by suppressing ferroptosis in cardiac microvascular endothelial cells through the C-Jun/NCOA4 pathway.

Objectives: Artemisia scoparia is a perennial herb belonging to the Asteraceae family. Although research has shown that A. scoparia possesses antioxidant and anti-inflammatory properties, the anti-inflammatory activity and mechanisms of A. scoparia essential oil (ASEO) remain poorly understood.

Methods: Anti-inflammatory activities and mechanisms of ASEO were investigated using cellular experiments, gas chromatography-mass spectrometry (GC-MS), network pharmacology, and molecular docking.

Key findings: Cellular assays showed that ASEO ameliorated lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells by inhibiting nitric oxide (NO), myeloperoxidase (MPO), and tumor necrosis factor alpha (TNF-α) production and thereby suppressing inflammation in a dose-dependent manner. Notably, the effect of ASEO (6.25 μg/mL) was stronger than that of the positive control dexamethasone (7.85 μg/mL). The network pharmacology and molecular docking results indicated that the key components (methyleugenol, L-α-terpineol, α-bisabolol, and α-cadinol) exerted significant anti-inflammatory effects by acting on the key targets [peroxisome proliferative activated receptor gamma (PPARG), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), E1A Binding Protein P300 (EP300), peroxisome proliferator activated receptor alpha (PPARA), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)], and the main pathways involved were mainly the PPAR signaling pathway, neuroactive ligand-receptor interaction, cyclic adenosine monophosphate (cAMP) signaling pathway, and serotonergic synapse.

Conclusions: These findings suggest that ASEO has great potential as a natural anti-inflammatory agent, its key compositions and multiple anti-inflammatory mechanisms make it a promising candidate for further research and development for clinical applications.