Cultivated lichen mycobionts represent a valuable resource for obtaining unique natural compounds. Mycobionts of Astrothelium straminicolor and Nigrovothelium inspersotropicum, collected in Vietnam, were isolated, cultivated, and subjected to chemical investigation. Consequently, three new compounds, straminones A - B (A1: and A2: ) and chlorosemivioxanthin (N1: ), along with five known compounds, 3S,4R-(+)-4-hydroxymellein (A3: ), 6-methoxymellein (A4: ), vioxanthin (N2: ), pigmentosin A (N3: ), and semivioxanthin (N4: ), were isolated and structurally elucidated. Straminones A and B represent the first examples of 3-methylhexahydrocyclopenta[c]pyran-1(3H)-one skeletons found in nature. The relative configuration of A1: was confirmed by DFT calculation. Compounds A3: and N4: demonstrated weak alpha-glucosidase inhibitory activity, with IC50 values of 314 and 366 µM, respectively. The other compounds showed no inhibition in the tested assay. Notably, compounds N1: -N3: showed significant inhibitory effects on NO production, with IC50 values ranging from 14 to 25 µM, compared with the positive control L-NMMA (IC50 = 49 µM). Further molecular docking clarified the inhibitory mechanism of the active compounds.

Curcumin is a versatile natural compound that has been extensively studied for its potential activity in cancer models. However, its clinical development faces challenges, including poor water solubility, chemical instability under physiological conditions, rapid metabolism, and limited systemic bioavailability. These issues have driven efforts to modify the curcumin structure to enhance stability, pharmacokinetics, and target interaction, while preserving or improving its antiproliferative effects. This review highlights key medicinal chemistry strategies for creating analogs beyond curcumin, including (i) monocarbonyl variants that replace the β-diketone group to improve stability, (ii) aromatic ring modifications that adjust electronic properties, lipophilicity, and cellular entry, (iii) prodrug designs that conceal phenolic groups to increase solubility or permeability, and (iv) hybrid molecules and conjugates for dual targeting or better delivery. Additionally, we discuss metal-curcumin(oid) complexes as promising options to modify stability, redox activity, and biological effects in cancer models. We also propose a basic evaluation toolkit to support more consistent comparisons among analogs, emphasizing the need to report chemical stability, microsomal metabolism, selectivity, and in vivo exposure, alongside in vitro viability/proliferation readouts and, where available, orthogonal cytotoxicity endpoints. Rather than treating beyond-curcumin chemistry as a catalog of potency-improving modifications, this review frames the major scaffold classes in terms of developability, evidentiary burden, and translational pragmatism. Overall, successful translation will depend less on isolated IC50 gains and more on standardized profiling and alignment of mechanism claims with achievable exposure.

Hydroxychloroquine (HCQ), a commonly used drug for Sjögren's syndrome (SS), is ineffective, highlighting the need for better treatments for salivary gland damage in SS. The study evaluated the effects of Polygonatum sibiricum (HJ) on SS using non-obese diabetic (NOD) mice treated with HJ, HCQ, or both for six weeks. Body weight, saliva levels, and submandibular gland histology were assessed. Various techniques were used to analyze apoptosis and oxidative stress. Network pharmacology identified therapeutic targets, and lentivirus technology was used to suppress CHRM3 gene expression to understand HJ's mechanisms against SS. HJ treatment significantly mitigates salivary gland damage, resulting in increased body weight, reduced water intake, and improved saliva flow rates. Histological evaluations revealed HJ reduced lymphocytic infiltration, restored glandular architecture, and alleviated oxidative stress. In addition, the study has the following key mechanistic finding: HJ upregulated the expression of the target proteins CHRM3 and AQP5 in submandibular glands. Additionally, HJ can significantly enhance the expression of CHRM3 and AQP5 in human salivary gland (HSG) cells after silencing CHRM3. This study revealed that HJ may act as a novel SS treatment by activating the CHRM3/AQP5 axis, promoting water channel transport, alleviating salivary gland damage, and enhancing saliva secretion. Moreover, the combination of HJ and HCQ could significantly improve the therapeutic benefit. These findings provide a new therapeutic strategy for SS.

Herbal medicinal products (HMPs) are widely used in European paediatric practice, but formal authorisations for their use in children remain limited. Following the 2024 workshop in Krakow, the Foundation Plants for Health (FPfH) organised a further workshop in Naples on 31 August 2025 as part of the 73rd International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA) to present updates of recent activities in the field of real-world data (RWD) and real-world evidence (RWE) for rationalising the usage of herbal medicines in children. Speakers presented concrete new data sources - private health insurance claims, patient reported outcome cohorts, and a social-media-based user survey - as well as modern methods in epidemiology. The workshop concluded that decision-relevant paediatric data on the use of HMPs can be generated efficiently by establishing new RWD data sources. For the subsequent next steps, it is necessary to engage with regulators to open usage of these data pools in regulatory practice.

The Japanese pearl tree (Styphnolobium japonicum), an ornamental species native to East Asia, has long been valued in traditional Chinese medicine and is now gaining renewed attention for its multifaceted pharmacological potential. This review synthesizes the current knowledge of its bioactive compounds, particularly flavonoids such as genistein, rutoside, quercetin, and sophoricoside, and their broad-spectrum biological activities, including antioxidant, anti-inflammatory, antimicrobial, neuroprotective, and wound-healing effects. These phytochemicals contribute to protective mechanisms against oxidative stress, skin photoaging, osteoporosis, cardiovascular dysfunction, and metabolic disorders such as diabetes and obesity. Emerging evidence also supports their role in managing neurodegenerative and inflammatory diseases, alopecia, and postmenopausal symptoms. Despite its promise, the clinical translation of S. japonicum remains limited by gaps in safety, pharmacokinetic characterization, and standardized extraction protocols. Looking ahead, integrative approaches combining phytochemistry, pharmacogenomics, and advanced biotechnology are expected to unlock its full therapeutic potential. By bridging traditional use with precision medicine and sustainable bioprocessing, S. japonicum stands as a prospective source of next-generation plant-based therapeutics for modern healthcare.

Flavonoids are a large group of polyphenolic secondary metabolites of plants with high biologically active properties. Their determination in plant extracts (medicinal, edible, and other plants, as well as products made from them) with a complex chemical composition is a difficult task and requires effective separation of the components. In this study, a new approach to the determination of 18 flavonoids in plant extracts using reversed-phase comprehensive two-dimensional liquid chromatography with UV detection (LC×LC-UV) is proposed. The approach has been successfully tested on various plant raw materials: above-ground parts of bog rosemary, bog bilberry, bilberry, lingonberry, and cranberry, as well as aspen and apricot knots. It was found that aspen knots are a rich source of aromadendrin and naringenin and their derivatives, while apricot knots are a rich source of catechin and epicatechin, and bog rosemary is a rich source of quercetin glycosides-hyperoside, reinoutrin, and avicularin. The approach for isolation of pure hyperoside, reinoutrin, and avicularin from bog rosemary extract by preparative HPLC was proposed. Other phenolic compounds of the studied plant extracts were classified (by LC×LC-MS/MS) as hydroxycinnamic acid derivatives, iridoids, and flavonoids. The developed approaches are promising for bioprospecting of flavonoids and phenolic compounds in various plant materials. It can also be used for quality control of medicinal, edible, and other plants, as well as products made from them.

Angiogenesis plays a key role in tissue regeneration by delivering oxygen and nutrients to the injury site. In diabetes mellitus, various factors, including hyperglycemia, neuropathy, increased reactive oxygen species, and proinflammatory cytokines, decrease the levels of proangiogenic factors and increase levels of antiangiogenic factors, hamper angiogenesis, and hinder wound healing. Reconstruction of the vasculature of the wound bed is crucial for promoting diabetic wound healing and improving the quality of life of patients. Given the urgent need for innovative therapies to promote angiogenesis and accelerate the repair of diabetic wounds, researchers have increasingly focused on identifying herbal products and their active constituents with promising proangiogenic activity.The aim of this review is to present verified data on the current knowledge on the effect of herbal products and their active constituents on angiogenesis processes in diabetic wounds.The electronic databases were searched for articles published from 2014 to the present. The 38 articles comparing topically used herbal products/active constituents on angiogenesis in diabetic wound healing treatment versus control treatments (placebo or active therapy) were selected.Herbal products and their active constituents are rich sources of novel angio-modulators that may affect the angiogenesis process in diabetic wound healing via different mechanisms of action, including stimulation of VEGF and HRMs and activation of the Nrf2, PI3K/AKT, and HIF-1α signaling pathways. Topical applications of herbal products and their active constituents, especially when incorporated into wound dressings, show promising proangiogenic activity and represent a potential alternative for the treatment of diabetic wounds.

Periodontitis is a chronic inflammatory disease driven by dysbiosis of the subgingival microbiota, leading to immune dysregulation and progressive alveolar bone loss. In recent years, immunotherapeutic approaches, particularly those involving natural products, have gained attention as potential adjuvants to conventional therapy. This study evaluated the effects of four alkaloids, boldine, laurolitsine, laurotetanine, and N-methyl-laurotetanine, on alveolar bone loss and local immune regulation in experimental periodontitis.Male and female C57BL/6 mice with ligature-induced periodontitis received daily oral administration of each alkaloid (20 mg/kg) for 10 days. Alveolar bone loss was quantified by micro-computed tomography (micro-CT). Periodontal immune responses were assessed by RT-qPCR analysis of pro-inflammatory cytokines, T-cell-related transcription factors, and bone metabolism mediators (RANKL and OPG). In addition, regulatory T (Treg) cells in cervical lymph nodes were analyzed by flow cytometry.Boldine and laurolitsine significantly reduced alveolar bone loss compared with untreated periodontitis, in parallel with decreased RANKL expression. All four alkaloids significantly reduced IL-6 expression, with laurolitsine additionally suppressing IL-17A expression in periodontal tissues, whereas N-methyl-laurotetanine reduced IL-10 expression. No significant changes were observed in CD4+, CD4+FoxP3+, and CD4+FoxP3+CD25+ T-cell frequencies between treated and untreated groups.Oral administration of boldine and laurolitsine attenuates periodontitis-associated alveolar bone loss, likely through differential modulation of cytokine networks and osteoclastogenic signaling. These findings support their potential as host-modulating agents in the management of periodontitis.

Previous studies have highlighted the effects of lemongrass essential oil (Cymbopogon citratus) on the cardiovascular system, particularly its hypotensive and vasodilatory properties. Given the heart's crucial role in blood pressure regulation, this study aimed to investigate the impact of lemongrass essential oil (EOCC) on cardiac excitation-contraction coupling and voltage-gated ion channel currents. Chemical analysis of EOCC, conducted through gas chromatography-mass spectrometry, identified geranial (39.9%) and neral (27.4%) as the primary components. The effect of EOCC on cardiac contractility was assessed using isolated guinea pig atria. The results showed that EOCC decreased both the contraction amplitude and the frequency of spontaneous atrial contraction in a concentration-dependent manner (IC50 values of 106.8 µg/mL, 95% CI=78.9 to 133 µg/mL and 258.4 µg/mL, 95% CI=202.7 to 443.2 µg/mL n = 5 - 8, respectively). Notably, EOCC exhibited arrhythmogenic activity, since it induced spontaneous contractions in isolated atrial preparations. Additionally, in an arrhythmia model induced by ouabain, EOCC significantly reduced the time to arrhythmia onset by 67.8% (n = 4). To further explore the mechanisms of the essential oil in atrial excitability, we employed the patch-clamp technique on isolated ventricular cardiomyocytes to examine EOCC's effects on the L-type calcium current (ICa-L). The human embryonic kidney cell line (HEK293) transiently expressing human NaV 1.5 was used to study the effects on cardiac sodium currents (INa). EOCC reduced the peak amplitude of both INa and ICa-L in a concentration- and voltage-dependent manner, with IC50 values of 299.7 µg/mL (95% CI=241.5 to 358 µg/mL, n = 6 - 7) for INa and 132.8 µg/mL (95% CI=71 to 173.8, n = 9) for ICa-L. In conclusion, the negative inotropic of EOCC may significantly contribute to its hypotensive effects. However, the association of relatively low concentrations of EOCC with cardiac arrhythmias raises concerns about its medicinal use.

Herbal preparations of Senna leaves or fruits are commonly used as laxatives. The European Medicines Agency (EMA) sets a daily dose of 10 - 30 mg for the hydroxyanthracene glycosides (HAG) determined by spectrophotometry. A recent revision of the European Pharmacopoeia monographs on Senna replaced the photometric assay with HPLC. The new method offers improved reproducibility and specificity but results in lower content, while the dose recommendation in the EMA monograph still refers to the photometric determination.The systematic difference between the photometric and the HPLC method has been studied in a collaborative inter-laboratory trial by seven participating quality control laboratories. The goal was to compare precision and reproducibility and ideally to derive a conversion factor. The HAG determination by spectrophotometry according to the method from Ph. Eur. Edition 8.3. was compared to the HPLC assay according to the new method for Senna leaves or pods (Ph. Eur. Ed. 10.1).The photometric method showed a low inter-laboratory reproducibility of about ± 28% (RSD) but an intra-laboratory precision of around 2%, while the HPLC method showed an inter-laboratory precision of around ± 10% and an intra-laboratory precision of 1.5%.Assay values obtained by HPLC were about 90% of the values of the photometric method, but this relation seems to be sample dependent. Because of its dependency on the raw material, a simple conversion factor between the two methods is not yet satisfying, but an additional method-specific dose recommendation for the EMA monographs is proposed by the authors.