Medicinal plants and herbal products sit at the intersection of a complex matrix of national laws and European regulations governing the medicinal, food, cosmetic, medical device, and narcotic sectors. Within this regulatory framework and pursuant to the 11 th edition of the European Pharmacopoeia, the term "herbal drug" serves as a synonym for "herbal substance", as applied in European legislation on herbal medicinal products. Comparative analysis indicates that while medical devices and cosmetics are subject to restrictive pre-control and verification mechanisms, the food and food supplement sector exhibits certain regulatory gaps. A critical focus of this study highlights the absence of a statutory definition of "poisonous medicinal plants" (PMPs) in Bulgarian legislation, which induces regulatory inconsistencies regarding their collection, storage, and accessibility. Examination of Ordinance No. 28 on pharmacy operations reveals that its Annex No. 9 lacks specific poisonous herbal substances containing potent compounds equivalent to conventional medicines. Furthermore, modest qualification requirements and a lack of advanced identification methods at herbal collection points present additional risk factors during primary control. The current regulatory framework remains fragmented, necessitating an update of Bulgarian legislation through the introduction of precise definitions, a medically supervised dispensing regime for PMPs, and innovative digital approaches for the inbound monitoring of herbal raw materials.
Background: Primary ovarian insufficiency (POI) is characterized by depletion of ovarian follicles and impaired ovarian function. Oxidative stress, inflammation, and dysregulation of intracellular signaling pathways play important roles in POI progression. Pterostilbene (PTS) is a natural stilbene compound with potent antioxidant and anti-inflammatory properties, demonstrating protective effects in several experimental models. The present study investigated the effects of PTS on oxidative stress and inflammation, as well as sirtuin 1 (SIRT1) and forkhead box O3a (FOXO3a) gene expression in a rat model of 4-vinylcyclohexene diepoxide (VCD)-induced POI. Methods: Female Sprague-Dawley rats were randomly divided into five experimental groups (six animals per group). Intraperitoneal (i.p.) administration of VCD (160 mg/kg) was used to induce POI. The rats were then treated with 17β-estradiol, PTS (50 mg/kg) orally by gavage, or their combination according to the study design, while the control group received the appropriate vehicle only. The serum levels of total antioxidant capacity (T-AOC) and nuclear factor-kappa B (NF-κB) were determined using an enzyme-linked immunosorbent assay (ELISA). Ovarian expression of SIRT1 and FOXO3a was assessed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Immunohistochemical (IHC) staining for cleaved caspase-3 (CASP3) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was used to evaluate apoptosis and oxidative deoxyribonucleic acid (DNA) damage in ovarian tissue, respectively. The combination effect was assessed using the Bliss equation. Results: Treatment with PTS significantly reduced NF-κB (P = 0.0496) and upregulated SIRT1 and FOXO3a gene expression (P = 0.0001), with maximum fold changes of 11.04 and 8.83, respectively. It also significantly reduced CASP3 and 8-OHdG (P = 0.0001), whereas the increase in T-AOC did not reach statistical significance (P = 0.3260). Overall, compared with 17β-estradiol, treatment with PTS produced greater effects on SIRT1 and FOXO3a gene expression. The combination treatment showed synergistic or near-additive effects for several evaluated parameters, whereas antagonistic interactions were observed for SIRT1 and FOXO3a gene expression. Combination index values for all measured parameters were as follows: T-AOC, 0.942; NF-κB, 0.690; SIRT1, 11.688; FOXO3a, 11.942; CASP3 percentage score (P-score), 1.0; CASP3 immunoreactive score (IRS), 0.997; 8-OHdG P-score, 0.943; and 8-OHdG IRS, 0.962. Conclusion: Treatment with PTS attenuated VCD-induced ovarian injury through antioxidant and anti-inflammatory mechanisms, with modulation of SIRT1/FOXO3a gene expression and reduced NF-κB-mediated inflammation and CASP3-associated apoptosis.
Background : Benign prostatic hyperplasia (BPH) is a popular age-linked ailment featured by prostatic enlargement and urinary obstruction. Dinoprostone (DINO) is prostaglandin E 2 having anti-proliferative and anti-inflammatory actions. Objective : This research attempted to assess the effect of DINO vs. finasteride (FINA) on testosterone (TEST)-induced BPH in rats. Methods : 40 adult male rats were haphazardly separated into 4 groups (n = 10); namely control, TEST, TEST + FINA, and TEST + DINO. BPH was induced with subcutaneous TEST (3 mg per kg per day) for 4 weeks. FINA (5 mg per kg) and DINO (7 mg per kg) were delivered orally. Results : TEST administration led to marked prostatic enlargement and hyperplasia, paralleled by remarkable elevations in PCNA, DHT, 5α-reductase, β-catenin, ERβ, pro-inflammatory IL-6, and pro-fibrotic TGF-β and VEGF mediators. FINA and DINO effectively attenuated these alterations, restoring prostate weight and histoarchitecture, downregulating β-catenin and ERβ, ameliorating PCNA expression, and suppressing DHT and 5α-reductase activity. Both drugs modified inflammatory and angiogenic mechanisms and corrected PPAR-γ expression and regulated BCL-2 levels, indicating diminished apoptosis. While FINA surpassed DINO in inhibiting DHT, IL-6, and β-catenin expression, both treatments were equally effective in terms of anti-hypertrophic, anti-inflammatory, and anti-angiogenic actions. Conclusions : DINO demonstrated promising anti-BPH effects comparable to FINA, acting via EP receptor-mediated modulation of prostatic growth and inflammation. These findings are viewed as preliminary and warrant further investigations of DINO for BPH treatment.
A structured narrative review examined how vesicle composition, size, charge, surface modification, and aerosolization affect pulmonary delivery and used the findings to construct an operational formulation decision framework. PubMed was searched for English-language publications from 2021 to September 2026, with targeted searches of publisher and regulatory sources. Selection was non-systematic and relevance-based, without a formal risk-of-bias assessment; 62 sources were graded according to a four-level hierarchy. Several framework elements—aerosol stability, PEG-lipid effects, and nucleic acid delivery—rely partly on non-liposomal comparators, requiring confirmation in conventional liposomes. The framework is an eight-step decision matrix linking therapeutic objective, deposition region, dominant barrier, formulation variables, aerosol platform, and verification readouts, applied to four disease contexts. Smaller or PEGylated vesicles may improve mucus transport, but PEGylation can reduce cellular uptake and alter surfactant interactions; nebulization and drying may compromise vesicle integrity. Amikacin liposome inhalation suspension remains the principal clinical precedent. The approach supports hypothesis-driven selection but requires prospective validation.
A total of 277 female students from 11 specialties participated in an online cross-sectional survey at the Medical University of Sofia. Differences between specialties were observed in knowledge of human papillomavirus transmission, understanding of Pap smear results, testing practices, and vaccination. Despite generally satisfactory awareness, gaps in preventive knowledge and practices remained among some student groups. Lack of time, insufficient information, fear, and embarrassment were identified as the main barriers to screening. Regression analysis identified specialty, age, year of study, parental education, place of residence, and understanding of Pap smear results as factors associated with variations in knowledge and preventive practices. The findings indicate that health-related education alone does not ensure consistent preventive behavior. More targeted and comprehensive educational interventions addressing human papillomavirus, screening, and vaccination may strengthen preventive practices among future healthcare professionals.
