This study aimed to validate the dermatological potential of Origanum dictamnus (dittany) infusion, traditionally recognized for its anti-inflammatory properties. To this end, 3D-printed hydrogel patches incorporating dittany were developed and evaluated for biocompatibility, wound-healing, anti-inflammatory activity, and effects on skin barrier. Hydrogel patches were fabricated via extrusion-based 3D printing using aloe vera gel, hydroxypropyl methylcellulose (HPMC), glycerol, and combinations of dittany infusion and panthenol. In vitro assays with HaCaT keratinocytes included cytotoxicity testing, scratch-wound healing, and qPCR-based analysis of inflammatory biomarkers. In vivo transepidermal water loss (TEWL) measurements were performed to assess skin barrier integrity and hydration after patch application. The traditional use of dittany infusion in skin ailments was confirmed, along with its relatively low cytotoxicity. Three 3D-printed gel types were evaluated in vitro, all showing superior performance to the raw plant extract. The optimal formulation contained 2% HPMC, 2% glycerol, 5% panthenol, and 0.06% dittany infusion (w/w% relative to aloe vera gel). At 3.25 mg/mL, this formulation achieved ~ 70% wound closure and significantly reduced IL-6 and TNF-α levels, indicating strong anti-inflammatory activity (p < 0.05). Both crude extract and patches show a trend toward reducing pro-inflammatory interleukins while simultaneously upregulating the anti-inflammatory cytokine IL-4. TEWL measurements indicated that none of the patches impaired the skin barrier function, confirming their compatibility with various skin types. This study provides the first scientific evidence that the incorporation of dittany infusion into 3D-printed hydrogels holds promise for safe, effective, plant-based topical therapies.

The efficacy of breast cancer chemotherapies is frequently limited by multidrug resistance (MDR), partly through efflux by ABC transporters, including ABCG2. This study evaluated whether phaeosphaeride A (PPA), a fungal metabolite isolated from a Paraphoma sp. endophyte of Ferula xylorhachis, can modulate ABCG2-mediated resistance to mitoxantrone (MTX). The endophyte was cultured and extracted with ethyl acetate, and the extract was purified by column chromatography and HPLC to yield PPA, whose structure was confirmed by NMR and MS analyses. Cytotoxicity of MTX, PPA, and their combination was assessed in MCF-7- and ABCG2-overexpressing MCF-7/MX cells. MTX showed marked differential cytotoxicity (IC50 = 1.6 µM, 95% CI: 1.4 - 1.9 in MCF-7 vs. > 25 µM in MCF-7/MX; p < 0.0001), whereas PPA exhibited comparable activity in both lines (23.2 µM, 95% CI: 18.0 - 30.1 vs. 36.1 µM, 95% CI: 28.7 - 46.0; p = 0.01). Co-treatment with PPA IC50 significantly reduced MTX IC50 to 0.4 µM (95% CI: 0.3 - 0.6) in MCF-7 and 1.9 µM (95% CI: 1.2 - 2.7) in MCF-7/MX, restoring MTX sensitivity in resistant cells to near MCF-7 levels. Flow cytometry showed that PPA (IC50) increased intracellular MTX accumulation with stronger effects in MCF-7/MX cells (p < 0.0001) than in MCF-7 (p < 0.05). In combination with MTX, PPA (IC50) increased Sub-G1 apoptotic populations in both lines.These findings demonstrate that PPA is unlikely to be a substrate of ABCG2 but functionally inhibits ABCG2-mediated efflux, contributing to the restoration of MTX sensitivity, although there may be additional mechanisms involved. PPA could be a promising MDR-reversal agent in ABCG2-driven chemotherapy resistance.

Hormonal imbalances, particularly involving the hypothalamic-pituitary-adrenal and gonadal axes, contribute to chronic conditions such as stress-related disorders, infertility, and metabolic dysregulation. Ashwagandha (Withania somnifera L.) has been proposed as a potential oral modulator of endocrine function due to its adaptogenic properties. This review aims to systematically evaluate the effects of oral ashwagandha supplementation on circulating hormone levels in adults. Our literature search included MEDLINE, Embase, and ClinicalTrials.gov. The protocol was registered in PROSPERO (CRD42024611576). We included randomized, placebo-controlled trials in adults assessing oral ashwagandha versus placebo that reported changes in hormone levels. Two reviewers independently screened studies, extracted summary data, and assessed risk of bias using the Cochrane tool. Meta-analyses were conducted using a random-effects model to calculate mean differences (MD) or standardized mean differences (SMD), with heterogeneity and publication bias assessed using I² and Egger's test, respectively. Twenty-three trials were included, encompassing 1706 patients. Ashwagandha significantly reduced cortisol (SMD =- 1.18, p < 0.04) and increased serotonin (MD = 31.75 ng/ml, p < 0.01). Subgroup analyses suggested possible dose-response effects based on withanolide content. No effect was found on TSH or T3, but T4 levels increased modestly (MD = 0.61 µg/dL, p = 0.02). Ashwagandha increased testosterone in men (MD = 57.43 ng/dl) but not in women (MD = 5.09 ng/dl), with a significant gender difference. This treatment did not influence E2 levels in either gender. Ashwagandha supplementation appears to modulate key hormonal pathways, particularly cortisol and sex hormones. However, heterogeneity and limited data on some endpoints warrant further standardized trials.

EA 575, the ivy leaf dry extract of the herbal medicine Prospan, has been widely used for the management of cough associated with various respiratory conditions. Over the past decade, new evidence has emerged from interventional and non-interventional studies offering a more comprehensive understanding of its efficacy, safety, and tolerability. This review provides an updated synthesis of clinical evidence of EA 575 in pediatric and adult patients with respiratory disease. A total of 27 publications were included, covering 13 interventional trials, 13 non-interventional studies, and 1 meta-analysis. These studies collectively enrolled 102 239 patients, of whom 84 022 received EA 575 treatment. The findings consistently demonstrate that EA 575 improves cough symptoms and lung function, as shown by improvements in the Bronchitis Severity Score, spirometry, and body plethysmography, depending on the parameters that have been assessed. Moreover, the tolerability of EA 575 has been increasingly confirmed through large real-world evidence studies that report a low number of non-serious adverse events. These results reinforce the well-established role of EA 575 in the effective and safe treatment of cough in clinical practice.

Cardiovascular diseases (CVDs) remain a major global health challenge, underscoring the need for novel, accessible, and effective therapeutic strategies. This review critically evaluates the phytochemical composition and cardioprotective potential of Passiflora species, summarizes the mechanisms of action of their principal bioactive compounds, and identifies key research gaps hindering clinical translation. With over 500 species distributed worldwide, many Passiflora plants are traditionally used in herbal medicine. Preclinical evidence suggests that compounds such as phenolics, alkaloids, and triterpenoid saponins exert cardioprotective effects through antioxidant and anti-inflammatory activities, vasodilation, blood pressure regulation, endothelial function improvement, and autonomic nervous system modulation. However, these findings are largely based on a limited number of species, often using non-standardized extracts, and lack comprehensive structure-activity relationship (SAR) analyses and clinical validation. Endemic Passiflora species remain underexplored, despite their potential to yield novel compounds with enhanced bioactivity. This review emphasizes the need for extract standardization, robust pharmacokinetic studies, and the integration of omics technologies and molecular modeling to accelerate compound discovery and development. Overall, Passiflora species contain promising bioactive molecules with significant in vitro and in vivo cardioprotective effects. Nonetheless, rigorous and standardized research, including clinical trials, is essential to fully assess their therapeutic value and support their integration into evidence-based cardiovascular care.

Dioscorea bulbifera (air potato), a climbing perennial of the Dioscoreaceae family, is widely distributed in tropical regions and valued in Ayurveda, Traditional Chinese Medicine, and African ethnomedicine for managing inflammatory, infectious, metabolic, and neoplastic disorders. This systematic review critically evaluates its phytochemistry, pharmacology, and toxicology. Primary metabolites contribute to its nutritional value, whereas secondary metabolites-predominantly steroidal saponins, flavonoids, and diterpenoids from bulbils and tubers-underlie its wide range of reported bioactivities. African accessions are rich in clerodane diterpenoids, while Asian ones are rich in saponins and flavonoids, underscoring the need for comparative metabolomic and chemotaxonomic studies.Preclinical studies confirm antiproliferative, antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and neuroprotective effects. However, furanoid diterpenoids, particularly diosbulbin B and 8-epidiosbulbin E acetate, have been shown to induce hepatotoxicity, with additional risks of nephrotoxicity, cardiotoxicity, gastrointestinal irritation, and thyroid dysfunction. Traditional processing methods, such as boiling and roasting, as well as co-administration with protective herbs, mitigate toxicity. Despite promising activity, clinical translation remains hindered by phytochemical variability, non-standardised preparations, and the complete absence of human trials. Future research should therefore focus on developing detoxified, standardised extracts supported by pharmacokinetic studies and well-designed randomised controlled trials to establish D. bulbifera as a safe and effective phytotherapeutic agent.

Throughout history, Cannabis sativa has been linked to the therapeutic management of epilepsy and Tilia × viridis has a tradition of use as a sedative.This study aimed to evaluate the protective effect of an ethanolic extract of C. sativa (CSRD), an aqueous extract of T. × viridis (TE), and their combination against oxidative stress induced by glutamate in a murine hippocampal neuronal (HT-22) cell line, as well as their anti-inflammatory activity in male Wistar rats' microglial cells stimulated with LPS. A phytochemical analysis was also conducted. Glutamate-induced reactive oxygen species (ROS) were quantified using 2',7'-dichlorodihydrofluorescein diacetate via fluorescence microscopy. Cell viability was assessed using the MTT assay. Distinct microglial cell phenotypes were identified via immunofluorescence.Extracts partially reversed glutamate-induced loss of cell viability (52% to 200% for CSRD; 22% to 82% for TE). Their combination produced a greater effect, reversing glutamate-induced toxicity by 133% to 284% and fully restoring cell viability to control levels. Moreover, the combined treatment reduced intracellular ROS levels (52% to 58%). Notably, the combination also exhibited the most pronounced anti-inflammatory effects, significantly reducing the proportion of reactive phenotype 1 cells, while increasing the population of anti-inflammatory phenotype 2 cells and preserving the trophic phenotype 3 subpopulation. In conclusion, this study not only validates the ethnobotanical uses of C. sativa and T. × viridis but also reveals a potent synergy when combined. This provides a strong foundation for the development of phytomedicines with translational potential for managing complex pathologies like epilepsy or neuroinflammation associated with neurodegenerative diseases.

Diabetic retinopathy (DR) is a leading cause of blindness, and its pathogenesis is strongly linked to the activation of aldose reductase (AR) under hyperglycemic conditions. Developing effective AR inhibitors (ARIs), particularly from natural sources, remains a critical therapeutic goal. This study investigated the AR inhibitory potential of an 80% ethanol extract from the leaves of Aster tataricus. Using UPLC-Q-Orbitrap-MS, we identified 11 major compounds, with caffeoylquinic acids (CQAs) being predominant. In vitro assays on rat lens aldose reductase (RLAR) revealed that di-caffeoylquinic acids (di-CQAs), particularly 3,5-di-O-caffeoylquinic acid (3,5-DCQA; IC50 = 0.31 µM), were potent noncompetitive inhibitors. Molecular docking simulations provided insights into their binding modes within the enzyme. The therapeutic relevance of these findings was confirmed in vivo using a larval zebrafish model of hyperglycemia, where both the A.tataricus extract and its constituent CQAs significantly suppressed hyaloid-retinal vessel dilation without inducing toxicity. Quantitative HPLC analysis confirmed that 3,5-DCQA was the most abundant di-CQA in the extract. These findings establish the CQA constituents of A.tataricus leaves as promising natural product leads for developing therapeutics to manage early-stage diabetic retinopathy.

Ugonins are distinctive chemotaxonomic bioactive metabolites identified in Helminthostachys zeylanica. This uncommon fern species generates a diverse array of flavonoids, including ugonins, which facilitate various biological processes such as anti-inflammatory, neuroprotective, melanogenesis-inhibiting, antioxidant, anti-osteoporotic, and immunomodulatory functions. Our objective in this comprehensive literature review is to deliver a clear and visually engaging analysis of the therapeutic potential inherent in each of the compounds found in H. zeylanica. This review covers the isolation of ugonins A - Y and other metabolites from this plant. These compounds demonstrate a diverse range of biological properties, which are thoroughly discussed in this review. The binding scores of all ugonins A - Y against PTP1B were also presented, indicating their potential activities for future consideration. Ultimately, a thorough understanding of the diverse therapeutic properties inherent in this unique fern can be achieved through a meticulous examination of the existing literature.