Frontiers in Pharmacology最新文献

Background: Oxidative stress and lipid peroxidation play crucial roles in the pathogenesis of atopic dermatitis (AD). Among the by-products of lipid peroxidation, 4-hydroxynonenal (4-HNE) is known to exacerbate inflammatory responses.

Methods: This study investigated the potential of Cinnamomum verum J. Presl. [Lauraceae] extract (CVE) in mitigating oxidative stress and suppressing 4-HNE-mediated inflammatory pathways in an AD model. The antioxidant properties of CVE were evaluated through lipid peroxidation assays, reactive oxygen species (ROS) measurement, and cytokine profiling.

Results: CVE treatment significantly reduced 4-HNE levels, decreased pro-inflammatory cytokine expression, and restored antioxidant enzyme activity.

Conclusion: These findings suggest that CVE may serve as a natural therapeutic agent for managing oxidative stress and inflammation in AD.

Objective: Diabetic kidney disease (DKD) is characterized by dysregulation of the renin-angiotensin system (RAS) and renal tubular injury. We investigated whether insulin treatment preserves renal homeostasis by modulating neprilysin (NEP), arginase-2 (Arg-2), and kidney injury molecule-1 (KIM-1) regulation in type 1 diabetic Akita mice.

Methods: Diabetic Akita mice received three subcutaneous sustained-release insulin implants (0.1 U/day) for 16 weeks. Blood measurements and urine collections were performed weekly. Western blot, enzymatic activity assays, and ELISA were used to analyze renal and urinary NEP, KIM-1, and Arg-2.

Results: Full-length immunoreactive NEP (95 kDa) expression and activity were significantly reduced in Akita mice (p < 0.05 vs. wild type [WT] non-diabetic controls) in both kidney and urine. This decrease was found in both young (9-week-old) and older (27-week-old). Novel urinary immunoreactive NEP smaller fragments (70, 50, and 37 kDa) were detected in 27-week-old diabetic Akita mice but absent in non-diabetic controls mice (WT). Insulin treatment normalized hyperglycemia, reduced albuminuria, and decreased glomerular fibrosis. Furthermore, it restored renal and urinary full-length NEP expression (p < 0.05) and increased NEP activity, while reducing NEP fragment shedding. Notably, while Western blot and activity assays demonstrated reduced full-length NEP expression and activity in Akita mice, ELISA revealed a paradoxical increase in urinary NEP concentration, suggesting the detection of inactive smaller urinary NEP fragments in addition to the full-length. Urinary KIM-1 and renal Arg-2 were significantly increased in 27- weeks old diabetic Akita mice, effects that were significantly attenuated by insulin treatment (p < 0.05).

Conclusion: Insulin therapy protects against diabetic nephropathy by: (i) augmenting renal NEP activity, (ii) reducing Arg-2-mediated injury, and (iii) attenuating tubular damage as evidenced by decreased urinary KIM-1 and NEP fragment shedding. The presence of low-molecular-weight NEP fragments in urine does warrant further investigation into their potential use as biomarkers for tracking the progression of DKD and monitoring the effectiveness of treatments.

Objective: The aim of this study is to investigate the effect of recombinant human thrombopoietin (rhTPO) on liver regeneration in rats with acute liver failure (ALF) induced by D-galactosamine (D-GalN).

Methods: Sixty-six rats were divided into a control group and a TPO group. The control group received daily injections of normal saline, while the TPO group received daily injections of rhTPO. After five consecutive days of treatment, an ALF model was established in all rats via D-GalN administration. Survival status of the two groups was observed. Platelet count (PLT), liver function indicators, hepatocyte growth factor (HGF), and liver regeneration-related indicators were measured at different time points. Additionally, transcriptomic and proteomic analyses were performed on liver tissues.

Results: Compared with the control group, the TPO group showed significantly higher levels of PLT, serum TPO, and HGF, milder liver tissue necrosis, a higher liver weight index, lower levels of alanine aminotransferase (ALT) and total bilirubin (TBil), and stronger liver regeneration capacity (as indicated by Ki67 and BrdU indices). Combined transcriptomic and proteomic analyses revealed that the expression of genes related to cell proliferation signaling pathways, such as Mapk1 and Map2k1, was significantly increased, while the expression of genes related to inflammatory pathways was significantly decreased.

Conclusion: rhTPO can promote the recovery of liver function and enhance liver regeneration in ALF rats by increasing PLT, stimulating cell proliferation, and inhibiting inflammation.

Background: Burnout incidents among community pharmacists continue to increase globally, resulting in impaired job performance and patient care as well as mental health deterioration. Research studies on pharmacist burnout and its connected risk factors remain insufficient for Saudi Arabian pharmacists.

Objectives: This research aimed to investigate burnout frequency alongside related risk elements for Saudi Arabian community pharmacists in the Aseer region of Saudi Arabia.

Materials and methods: A cross-sectional survey was conducted among community pharmacists in the Aseer region of Saudi Arabia between March and July 2025. A structured questionnaire collected data on demographics, occupational factors, and burnout using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Statistical analyses were performed using SPSS (version 25.0), applying chi-square tests, t-tests, Pearson correlations, and logistic regression at a significance level of p < 0.05.

Result: The analysis revealed widespread burnout symptoms among study participants, including emotional exhaustion in 78.2% of respondents. In comparison, depersonalization affected 65.4% of participants, and a decline in personal accomplishment was experienced by 72.6%. Overall, a high proportion of participants demonstrated moderate-to-high burnout based on MBI-HSS cutoffs. Significant positive correlations were observed between burnout and heavy workload (p = 0.002), extended working hours (p = 0.004), and insufficient financial compensation (p = 0.006). Female pharmacists showed higher emotional exhaustion scores than their male counterparts, with 29.8 ± 6.4 and 25.6 ± 5.9, respectively (p = 0.03). Pharmacists who exceeded 48 h per week showed higher levels of professional burnout (p = 0.01), while those younger than 35 years demonstrated increased emotional exhaustion compared to their older counterparts (p = 0.02).

Conclusion: The findings indicate a high prevalence of burnout among community pharmacists in the Aseer region of Saudi Arabia, influenced by workload, long working hours, insufficient compensation, and demographic factors. Implementation of workload management systems, mental health support, and career development resources is recommended to decrease burnout and enhance pharmacist well-being and patient care quality.

Background: Intervertebral disc degeneration (IVDD) refers to the structural degeneration of intervertebral discs that occurs with aging or overuse, including annulus fibrosus rupture, nucleus pulposus dehydration, reduced proteoglycan content, and decreased elasticity. The bioactive metabolites of botanical drugs (BMBDs) refer to the chemical substances derived from plants that can exert specific physiological effects on living organisms, including the human body. Various types of the BMBDs regulate key protein targets and signaling pathways, demonstrating effects such as alleviating nucleus pulposus cell inflammation and oxidative stress levels, inhibiting extracellular matrix degradation, and regulating nucleus pulposus cell autophagy and apoptosis.

Methods: All experimental information and summaries used in this review were acquired from peer-reviewed articles in the relevant fields. The PubMed, Web of Science (WOS), Google Scholar, and China National Knowledge Infrastructure (CNKI) databases were searched for relevant articles. Information on the manual classification and selection of BMBDs that protect against IVDD is included in this review.

Results: The literature review identified multiple studies on the characteristics of BMBDs, which delay IVDD from various aspects through a wide range of key targets and signaling pathways.

Conclusion: This review summarizes the pharmacological effects and mechanisms of different types of BMBDs in the treatment of IVDD, providing a theoretical foundation for further pharmacological research and the development of new drugs for treating IVDD, as well as strong theoretical support for future clinical applications.

Background: Gastric ulcers affect approximately 10% of the global population, while current acid-suppressive therapies have notable limitations including impaired digestion and long-term safety concerns. Naeso-san (NSS), a traditional botanical formulation, has shown promising gastroprotective effects, yet its precise molecular mechanisms remain incompletely understood. This study investigated the molecular pathways underlying its gastroprotective effects versus conventional therapies.

Methods: We evaluated the gastroprotective effects of NSS (75, 300, 1200 mg/kg) in 7-week-old male ICR mice using a hydrochloric acid/ethanol (HCl/EtOH)-induced gastric injury model, with ranitidine (40 mg/kg) as positive control. Macroscopic damage scores were assessed, and molecular mechanisms including pro-inflammatory cytokines and mitogen-activated protein kinase (MAPK), protein kinase B (AKT), and nuclear factor-κB (NF-κB) signaling pathways were analyzed. In vitro studies using TNF-α-stimulated human gastric adenocarcinoma cell line (MKN45) gastric epithelial cells assessed inflammatory gene expression and cell viability.

Results: NSS demonstrated dose-dependent gastroprotection with superior efficacy compared to ranitidine. While ranitidine effectively reduced macroscopic damage and TNF-α mRNA expression, it showed no significant effects on IL-1β expression or JNK, p38, AKT, and NF-κB signaling pathways. In contrast, NSS significantly suppressed pro-inflammatory cytokines and comprehensively inhibited multiple molecular pathways including MAPK, AKT, and NF-κB activation across all doses. In vitro studies confirmed dose-dependent suppression of TNF-α-induced inflammatory gene expression (IL-6, IL-8, IL-1β, COX-2) without cytotoxicity.

Conclusion: NSS exhibits gastroprotective effects through multi-target anti-inflammatory mechanisms. These mechanistic advantages over conventional acid-suppressive therapies suggest NSS as a promising candidate for preclinical and translational studies evaluating its clinical applicability in inflammatory gastric conditions.

Danggui Shaoyao San (DSS), a classical multi-herbal formulation of traditional Chinese medicine, demonstrates therapeutic potential for Type 2 Diabetes Mellitus (T2DM), Alzheimer's Disease (AD), and Polycystic Ovary Syndrome (PCOS). This review proposes a unified mechanism whereby DSS exerts its effects by modulating a network of shared pathological biomarkers across these disorders. We identify tryptophan (Trp) and phenylalanine (Phe) as host-derived metabolic biomarkers in plasma, and the gut bacterial phylum Bacteroidetes as a shared gut microbial biomarker. The therapeutic actions of DSS are mediated by its botanical constituents (e.g., ligustilides, paeoniflorin, ferulic acid), which help correct the dysregulated Trp-kynurenine and Phe metabolic pathways, while simultaneously enriching Bacteroidetes to alleviate gut dysbiosis and rebalance the gut-brain axis. This coordinated regulation of shared host metabolic and gut microbial biomarkers provides a scientific rationale for applying DSS as a multi-targeted agent, illustrating a molecular basis for a shared therapeutic approach.

Tribulus terrestris L. (T. terrestris L.), a traditional medicinal plant, has garnered increasing attention for its potential in treating skin disease. This review comprehensively summarizes current research on the protective effects of T. terrestris L. in skin diseases. T. terrestris L. contains various bioactive metabolites, including steroidal saponins, flavonoids and alkaloids. These metabolites exhibit anti-inflammatory, antioxidant, antibacterial properties, and tyrosinase-regulating effects, making T. terrestris L. a promising candidate for treating multiple skin disorders. Studies have shown its potential efficacy against conditions such as atopic dermatitis, acne, and vitiligo. However, several limitations remain: its precise mechanisms of action in skin diseases are not yet fully elucidated, its standalone efficacy for complex skin diseases may be limited, and there is a lack of high-quality, large-scale clinical trials to conclusively verify its efficacy and safety. In conclusion, current evidence suggests T. terrestris L. has significant promise for the treatment of skin diseases. Future research should focus on conducting rigorous clinical trials, exploring combination therapies with conventional treatments, and deepening the investigation into its active components and mechanisms to expand its application in skin diseases.

Chronic inflammation, driven by dysregulated immune responses and oxidative stress, underlies the pathogenesis of numerous diseases, from neurodegeneration to cancer. Cycloastragenol (CAG), a bioactive triterpenoid derived from Astragalus membranaceus, has emerged as a multifaceted therapeutic candidate due to its unique ability to simultaneously modulate inflammatory signaling networks, while exhibiting a favorable safety profile in preclinical models. This study aims to systematically evaluate the molecular mechanisms of CAG, including its coordinated anti-inflammatory, immune-regulatory, and tissue-protective effects. By integrating evidence from pharmacology, metabolomics, and clinical studies, our aim is to elucidate the therapeutic potential of CAG and identify strategies to overcome its pharmacokinetic limitations for clinical translation. A comprehensive literature review was conducted using databases such as PubMed, Web of Science, and Science Direct, employing target keywords related to cycloastragenol, inflammation, and disease treatment. Our analysis reveals that CAG exerts multidimensional and networked anti-inflammatory effects by synergistically regulating key inflammatory nodes such as NF-κB, Nrf2, and the NLRP3 inflammasome, as well as by alleviating oxidative stress. It has demonstrated therapeutic potential in diseases such as cancer, neurological disorders, asthma, and visceral fibrosis. CAG exerts significant anti-inflammatory effects by targeting the axis associated with inflammation, oxidative stress, and immune dysregulation. However, future efforts need to focus on improving its bioavailability and verifying its safety in human trials to develop a new generation of anti-inflammatory therapies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a highly infectious disease characterized by fever, acute respiratory illness, and pneumonia, known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects host cells through the interaction of its spike glycoprotein (S protein) with human angiotensin-converting enzyme 2 (hACE2). Structural studies have shown that hACE2 interacts exclusively with the receptor-binding domain (RBD) of the spike. A high binding affinity between spike and hACE2 has been linked to increased viral infection. Disrupting this interaction can reduce viral infectivity.

Methods: This study aimed to assess infection using Omicron variant pseudovirus in a stable HEK-293 cell line expressing hACE2 (HEK-293/ACE2), treated with bromhexine hydrochloride. First, immunofluorescence and Western blot confirmed the presence of hACE2 in the stable line. Then, bromhexine concentrations for treatment were determined by cytotoxicity assays. Next, infection was evaluated using Omicron pseudoviruses carrying GFP and luciferase reporter genes. Infection levels were measured through fluorescence or luciferase activity.

Results: Bromhexine reduced infection with an IC₅₀ of 17.3 ± 0.9 μM. About 40% inhibition was also observed against Alpha, Beta, and Delta variants at 40 μM. Computational docking followed by molecular dynamics simulations showed that bromhexine binds to the extracellular domain of hACE2, with recurrent contacts near Phe40, Phe390, and Asn394.

Conclusion: Consistent with this model, our findings support an entry-inhibition mechanism whereby bromhexine destabilizes the SARS-CoV-2 spike-ACE2 interface, preventing viral entry. Overall, these results suggest bromhexine as a potential repurposing candidate and support its inclusion in therapeutic strategies aimed at both current and emerging SARS-CoV-2 variants.