Background/Objectives: Inflammation is a vital response of the immune system, frequently linked to the development and progression of numerous chronic and autoimmune diseases. Targeting inflammation represents an attractive strategy to prevent and treat these pathologies. In this context, many pathways, including pro-inflammatory cytokines secretion, NFκB activation, reactive oxygen species (ROS) production, inflammasome activation and arachidonic acid metabolism could be highlighted and addressed. Several plant materials have traditionally been used as effective and non-harmful anti-inflammatory agents. However, well-established scientific evidence is lacking, and their mechanisms of action remain unclear. The current article compares the effects of seven plant extracts, including Quercus robur L. (Oak), Plantago lanceolata L. (narrowleaf plantain), Plantago major L. (broadleaf plantain), Helichrysum stoechas L. (immortelle or helichrysum), Leontopodium nivale alpinum Cass. (edelweiss), Medicago sativa L. (alfafa) and Capsella bursa-pastoris Moench (shepherd’s purse) on different inflammatory pathways. Results: All of the plant extracts significantly affected ROS production, but their action on cytokine production was more variable. As the Quercus robur extract showed the highest efficacy in our models, it was subsequently assessed on several inflammatory signaling pathways. Quercus robur significantly decreased the secretion of IFNγ, IL-17a, IL-12, IL-2, IL-1β and IL-23 in stimulated human leucocytes, and the expression of TNFα, IL-6, IL-8, IL-1β and CXCL10 in M1-like macrophages. Additionally, a significant reduction in PGE2 secretion, COX2, NLRP3, caspase1 and STAT3 expression and NFκB p65 phosphorylation was observed. Conclusions: Our results clearly indicate that Quercus robur has a potent anti-inflammatory effect, making it a promising candidate for both the treatment and prevention of inflammation and related diseases, thereby promoting overall well-being.

The methanolic extract of the leaves of Macaranga hurifolia Beille showed arginase inhibitory activity (40% at 100 µg/mL) and was then fractionated to obtain nine polyphenolic compounds. Their structures were elucidated on the basis of NMR spectroscopic data, and by comparison with data previously reported in the literature, as gallic acid (1), 3,4-dihydroxybenzoic acid (2), chlorogenic acid, (3), corilagin (4), cynaroside (5), cosmosiin (6), hyperoside (7) isoquercitrin (8) and guajaverin (9). These compounds have been evaluated as arginase inhibitors. Compounds 4, 7, 8 and 9 showed varying arginase inhibitory activities with IC₅₀ values ranging from 102 to 302 μM. All the isolated compounds were previously identified in this species but their activities on arginase are reported here for the first time.

High arginase activity is associated with several pathological conditions, including TGF-β-induced fibrosis, by increasing levels of the proline precursor l-ornithine, thereby promoting collagen biosynthesis and increasing oxidative stress due to nitric oxide synthase (NOS) uncoupling. The natural piceatannol has been shown to have beneficial effects on collagen deposition, fibrosis and oxidative stress. In this study, we present an in-depth structure-activity relationship study on arginase I, which resulted in the thioamide derivative 12a with dual catechol rings that displays potent inhibitory activity with IC₅₀ values of 9 μM and 55 μM for bovine and human arginase I, respectively. Quantum chemical modelling suggested that the sulphur atom in the thioamide group plays a crucial role in binding affinity by forming a stable hydrogen bond within the active site of the enzyme. In addition, compound 12a demonstrated high radical scavenging activity and effectively normalised collagen and procollagen levels at 5 μM in an in vitro cell model of a dermal fibrosis.

The imbalance of phosphodiesterase 5 (PDE5) enzyme in the male body, or excessive PDE5 enzyme levels, can occur due to factors such as aging, diseases (e.g., cardiovascular disease, diabetes, depressive disorder), and physical behaviors (e.g., alcoholism, smoking, stress). PDE5 is directly associated with erectile dysfunction disease. Currently, many studies aim to find natural PDE5 inhibitors as an alternative to commercial drugs. This study is the first to demonstrate that the ethanolic leaf extract of D. cochinchinensis exhibits potent PDE5-inhibitory activity. The PDE5-inhibitory activity of five plant parts was evaluated: leaf (IC₅₀ = 1.53 ± 0.12 µg/mL), twig (3.37 ± 0.54), fruit (14.92 ± 2.85), heartwood (19.05 ± 5.60), and bark (16.03 ± 2.92). However, there is still uncertainty about which compounds in leaf extract are responsible for the PDE5 inhibition. Therefore, the purpose of this study is to identify the chemical constituents in the leaf of D. cochinchinensis, including determining which of these compounds may act as PDE5 inhibitors. This study was achieved using at-line LC-QTOF-MS².

The inhibition of steroid 5-alpha reductase (S5AR), a key mechanism for managing dihydrotestosterone-dependent conditions, has been demonstrated in teak (Tectona grandis L.f.) leaf extracts. Our recent clinical study confirmed the effectiveness of a hair growth formulation containing teak leaf extract in males with androgenic alopecia. However, significant variability in S5AR inhibitory activity among teak leaf samples from different regions underscores the need for quality control of raw materials. This study applied a metabolomics approach to investigate the influence of leaf age, harvesting period, and geographic origin on chemical composition and S5AR inhibitory activity, as well as to identify active S5AR inhibitors. Geographic origin emerged as the primary determinant of variations in chemical profiles and S5AR inhibitory activity. Using orthogonal partial least squares analysis, six diterpenoid S5AR inhibitors were identified, including four compounds reported for the first time as S5AR inhibitors: rhinocerotinoic acid, 7-oxo-8-labden-15-oic acid, 8-hydroxy-labd-13-en-15-oic acid, and a novel diterpene, 7-hydroxy-labd-8,13-dien-15-oic acid. These findings highlight the potential of metabolomics as a powerful tool for discovering bioactive compounds and optimizing raw material selection. By prioritizing proven geographic sources, consistent bioactivity can be achieved, supporting the therapeutic potential of teak leaves in managing S5AR-related conditions.

Acrolein is a highly reactive α,β-unsaturated aldehyde implicated in numerous diseases and pathological conditions. Developing strategies to alleviate its harmful effects is thus of key importance, with scavengers that trap acrolein emerging as a promising approach. Recent efforts have focused on identifying effective phytoconstituents, but detecting active components in complex plant matrices remains a challenging and time-consuming task. This study introduces a new application of HPLC-DAD for the instantaneous detection of acrolein scavengers in such complex extracts. To mimic this chemical diversity and test the method's efficiency, a multicomponent mixture of ten phytochemical standards was employed. The procedure involved pre-column incubation of the mixture with varying concentrations of acrolein, allowing for the selective identification of active components through signal reduction. The results were further validated through conventional evaluation of individual constituents, confirming the method's reliability.•Development of a novel application of HPLC-DAD for the instantaneous detection of acrolein-trapping constituents in complex plant matrices•Application of the method to a ten-phytoconstituent mixture designed to simulate the chemical complexity of a plant extract•Validation of method efficiency through comparison with conventional scavenging evaluations of individual compounds.