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Depression is a multifactorial disorder shaped by genetic, psychosocial, and biological influences, with hypotheses ranging from monoamine deficiency and neuroplasticity deficits to inflammation and stress-induced dysregulation. St. John's wort ( L.) has long been used as an herbal antidepressant and is supported by clinical evidence for efficacy and safety in mild-to-moderate depression. While its multimodal mechanisms have been linked to neurotransmitter reuptake inhibition, neuroendocrine regulation, and modulation of neuroplasticity, recent findings suggest an additional role at the membrane level. Emerging lipidomic studies highlight that Ze 117, a low-hyperforin extract, counteracts stress- and glucocorticoid-induced increases in membrane fluidity by modulating lipid composition and cholesterol metabolism. These effects normalize receptor mobility and signal transduction, particularly of β1-adrenoceptors, and modulate glycerophospholipid metabolism in both cellular and animal models. Such membrane-stabilizing properties may represent a novel mechanistic pathway complementing classical neurochemical actions. This review revisits the mechanisms of St. John's wort with a special focus on its impact on membrane lipids, positioning lipidomics as a promising tool for elucidating antidepressant activity. These insights may open avenues toward personalized therapeutic strategies in depression.

Valerian root extracts are widely used as mild sedatives to promote sleep, with clinical studies confirming their efficacy. Their sleep-promoting effects are associated with the adenosine A1 receptor (A1AR), a key regulator of sleep through neural activity inhibition. Adenosine, a neuromodulator that accumulates during wakefulness, activates A1ARs to facilitate sleep transitions. Using advanced analytics, we detected adenosine at 0.05% in the valerian extract Ze 911, supporting direct A1AR activation in vitro. Additionally, we explored A1ARs’ allosteric sites for modulatory activity. Valerenic acid and pinoresinol, key constituents of Ze 911, were identified as positive allosteric modulators (PAMs) of A1ARs. Valerenic acid exhibited strong PAM activity, with high cooperativity (αβ = 4.79 for adenosine and αβ = 23.38 for CPA) and intrinsic efficacy (τB = 5.98 for adenosine and τB = 3.14 for CPA). Pinoresinol displayed weaker PAM activity, with moderate cooperativity (αβ = 3.42 for adenosine and αβ = 0.79 for CPA) and limited efficacy (τB = 0.93 for adenosine and τB = 1.66 for CPA). The allosteric modulation observed in valerian extract Ze 911 suggests a mechanism of action in which valerenic acid and pinoresinol enhance receptor activation through allosteric interactions, potentially amplifying the effects of endogenous adenosine. By targeting A1ARs’ allosteric sites, valerian extract Ze 911 offers increased therapeutic selectivity and reduced off-target effects, emphasizing its potential for managing sleep disorders.

Cimicifuga racemosa extracts, particularly the ethanolic extract Ze 450, are widely used to alleviate menopausal symptoms, such as hot flushes and excessive sweating. While their clinical efficacy is well established, the effects of these interventions on systemic energy metabolism remain unclear. This pilot study investigated the impact of Ze 450 on body composition, metabolic markers, and voluntary physical activity in non-ovariectomized female Wistar rats. Animals (N = 36) received Ze 450 at either 30 mg/kg or 130 mg/kg body weight, with or without access to voluntary wheel running over four weeks. Neither treatment influenced body weight gain or final body weight, indicating normal growth across all groups. Post-mortem analyses included visceral fat mass, serum cholesterol, and leptin levels. Both Ze 450 and running reduced visceral fat mass, adipocyte size, and circulating leptin levels, suggesting that they share overlapping mechanisms. Serum cholesterol was significantly lowered by running but remained unaffected by Ze 450, while liver weight and alanine aminotransferase activity were unchanged, confirming hepatic safety. Collectively, Ze 450 improved key metabolic parameters related to adiposity and appetite without affecting hepatic integrity, highlighting its potential as a safe, non-hormonal metabolic modulator complementary to physical activity.

The use of herbal medicines containing Petasites hybridus extracts has a long history in the treatment of various ailments. The observed effects are primarily due to pharmacologically active compounds such as petasin, isopetasin, and neopetasin. In evidence-based phytotherapy, extracts from leaves and rhizomes are applied for different indications. While leaf extracts are administered to treat allergic rhinitis symptoms, rhizome extracts are utilized among others in the management of gastrointestinal spasms and migraines. The quality and source of plants are critical for producing authorized herbal medicinal products. Although the preparation of P. hybridus leaf extracts from cultivated plant material is already established, the rhizomes used for preparing extracts are still derived from commercial wild collections. However, switching to cultivation is desirable to ensure consistent quality and availability. For regulatory purposes, comparative pharmacological studies are needed to assess the bioactivity of plant material from different sources. Therefore, this study analyzed rhizome extracts from wild harvesting and cultivation for their petasin composition (i.e., isopetasin, neopetasin, petasin) and spasmolytic effects on Ca2+-dependent precontracted guinea pig ileum ex vivo. The results confirm petasins as active compounds of P. hybridus rhizome extracts. Moreover, they demonstrate that the total content of petasins determines the spasmolytic effects, regardless of the individual composition of the different petasins. No significant differences in efficacy were found between cultivated and wild-collected rhizomes, demonstrating that cultivated material is a reliable, consistent, and sustainable alternative for P. hybridus rhizome extract production.

Cucurbita pepo (CP) seeds are traditionally used to alleviate lower urinary tract symptoms associated with benign prostatic hyperplasia and overactive bladder. While these effects are often attributed to lipophilic constituents, recent studies have highlighted the therapeutic potential of oil-free hydroethanolic extracts. However, their composition remains insufficiently characterized, considering the species’ significant phenotypic and phytochemical variability. This study aimed to characterize the phytochemical profile of hydrophilic hydroethanolic seed extracts from ten CP cultivars originating from different European regions, with a focus on compositional variability. The elemental composition, along with primary and secondary metabolites, was analyzed using established spectroscopic and chromatographic methods. The extracts showed considerable variation in protein (45.39 to 114.58 mg/g dw) and free amino acid content (46.51 to 111.10 mg/g dw), as well as differences in elemental composition. Principal component analysis revealed distinct clustering patterns, with several samples displaying metabolite profiles comparable to the Cucurbita pepo var. styriaca variety currently recommended by the European Pharmacopoeia (Ph. Eur.) and the Committee on Herbal Medicinal Products (HMPC). These findings open the possibility of using other CP varieties as alternative sources for extract preparation and offer novel insights into the composition of less explored hydrophilic extracts derived from CP seeds.

Hydroethanolic Cucurbita pepo seed extracts are traditionally used for alleviating lower urinary tract symptoms (LUTS), yet their mechanisms remain unclear. Adenosine, a purine nucleoside involved in neuromodulation and smooth muscle relaxation, was recently identified in C. pepo seeds. Since A1 adenosine receptors (A1AR) suppress parasympathetic bladder overactivity by inhibiting acetylcholine (ACh) release, we investigated to which extent purines from pumpkin seed extracts contribute to A1AR activation. Complementary antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Three hydrophilic seed extracts containing different adenosine levels (0.60–1.18 mg/g dw) were evaluated for agonist activity using a cAMP inhibition assay. The most active extract showed an EC50 of 40.22 µg/mL. Selective removal of adenosine shifted the dose–response curve rightward, while further elimination of an adenosine derivative increased the EC50 to 212.10 µg/mL, confirming adenosine as the principal active compound. Guanosine and inosine did not exhibit A1AR agonist or allosteric effects. All samples exhibited measurable but weak antioxidant activity (IC50 = 1.02–4.19 mg/mL), consistent with their low total phenolic content. These findings underscore the importance of accounting for naturally occurring agonists in plant extracts to avoid overestimating receptor-mediated effects in vitro which are not translatable in vivo.

Background Membrane lipids have an important function in the brain as they not only provide a physical barrier segregating the inner and outer cellular environments, but are also involved in cell signaling. It has been shown that the lipid composition effects membrane fluidity which affects lateral mobility and activity of membrane-bound receptors. Methods Since changes in cellular membrane properties are considered to play an important role in the development of depression, the effect of St. John’s wort extract Ze 117 on plasma membrane fluidity in peripheral blood mononuclear cells (PBMC) was investigated using fluorescence anisotropy measurements. Changes in fatty acid residues in phospholipids after treatment of cortisol-stressed [1 μM] PBMCs with Ze 117 [10–50 µg/ml] were analyzed by mass spectrometry. Results Cortisol increased membrane fluidity significantly by 3%, co-treatment with Ze 117 [50 µg/ml] counteracted this by 4.6%. The increased membrane rigidity by Ze 117 in cortisol-stressed [1 μM] PBMC can be explained by a reduced average number of double bonds and shortened chain length of fatty acid residues in phospholipids, as shown by lipidomics experiments. Conclusion The increase in membrane rigidity after Ze 117 treatment and therefore the ability to normalize membrane structure points to a new mechanism of antidepressant action of the extract.

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2 extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, respectively. The IC50 values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

The indigenous yeasts associated with the spontaneous fermentation of phenolic-rich rose oil distillation wastewater (RODW) generated after the industrial distillation of rose oil were studied. The ITS-rDNA sequence analysis of the samples collected from RODW fermented at semi-sterile conditions, a waste deposition lagoon and endophytic yeasts isolated from industrially cultivated Rosa damascena suggests that the spontaneous RODW fermentation is caused by yeasts from the genus Cyberlindnera found also as endophytes in the rose flowers. Phylogenetic analysis based on the nucleotide sequences of the translation elongation factor (TEF1α) and 18S- and 26S- rRNA genes further confirmed the taxonomic affiliation of the RODW yeast isolates with the genus Cyberlindnera. The RODW fermentation capacity of a selected set of indigenous yeast isolates was studied and compared with those of common yeast strains. The indigenous yeast isolates demonstrated a superior growth rate, resulting in a nearly double reduction in the phenolic content in the fermented RODW. The indigenous yeasts’ fermentation changed the RODW phenolics’ composition. The levels of some particular phenolic glycosides decreased through the depletion and fermentation of their sugar moiety. Hence, the relative abundance of the corresponding aglycons and other phenolic compounds increased. The capacity for the biotransformation of RODW phenolics by indigenous yeasts is discussed.

The primary objective of this noninterventional, observational study was to assess the effectiveness of the Petasites hybridus leaf extract (Ze 339) on early allergic and late inflammatory symptoms of allergic rhinitis in Swiss outpatients. This study was conducted by general practitioners and allergologists. Data from 226 patients were collected during three documented visits. The intermediate visit was ideally made 2–4 weeks after the baseline visit, followed by the final visit approximately 2–4 months later. The mean study duration was 63 days, with 75% of patients being treated for at least 4 weeks. Of the patients, 58.5% started with Ze 339 monotherapy, and 41.5% received other antiallergic and/or sympathomimetic drugs. In both groups, the allergic total symptom score and the inflammatory total symptom scores were significantly (p < 0.001) reduced, and the scores for quality of life were improved. Both physicians and patients were very satisfied with the treatment and the concept of therapy, not only for short-term (seasonal) therapy but also for long-term therapy. The tolerability was good: only three mild gastrointestinal adverse events occurred. In summary, the effectiveness of P. hybridus leaf extract Ze 339 for the treatment of early allergic and late inflammatory symptoms of allergic rhinitis could be confirmed.