Search Results (39)

Background/Objectives: Plant-based supplements are widely used for the management of anxiety, depression, and insomnia. Despite their over-the-counter availability and perceived safety, these products may pose relevant pharmacological and toxicological risks. This narrative review critically evaluates clinical evidence on commonly used herbal preparations, with particular emphasis on herb–drug interactions, adverse effects, and issues related to product adulteration. Methods: Major scientific databases (PubMed, Scopus, and Web of Science) were searched to identify clinical studies evaluating plant-based supplements for mental health and sleep disorders. Data on study design, dosage, efficacy, and adverse events were analyzed, together with regulatory information and reports of product adulteration and quality concerns. Results: Herbal supplements such as Hypericum perforatum, Passiflora incarnata, Valeriana officinalis, Piper methysticum, Withania somnifera, Crocus sativus, and Curcuma longa demonstrated anxiolytic, antidepressant, and sedative effects in clinical studies, with improvements in mood, stress levels, and sleep quality. Proposed mechanisms include modulation of monoaminergic and GABAergic pathways, serotonergic activity, regulation of the hypothalamic–pituitary–adrenal axis, and anti-inflammatory effects. However, clinically relevant risks were identified, including cytochrome P450–mediated drug interactions, excessive sedation, serotonin syndrome, and toxic effects associated with adulterated products, such as hepatotoxicity, cardiovascular events, and neurological disturbances. Conclusions: While plant-based supplements may provide clinically meaningful benefits for anxiety, depression, and insomnia, their use requires careful clinical monitoring due to potential pharmacokinetic and pharmacodynamic interactions and safety concerns. Increased awareness of herb–drug interactions and stricter quality control are essential to optimize therapeutic outcomes and minimize harm. Full article

Major Depressive Disorder (MDD) is a severe, chronic illness for which conventional treatments often show limited efficacy and side effects, driving a renewed interest in traditional medicinal plants. The therapeutic promise of these plants lies in their multi-targeted action, influencing neurotransmitter systems, modulating neuroinflammation and oxidative stress, impacting neuroplasticity, and regulating the Hypothalamic–Pituitary–Adrenal (HPA) axis. Despite their clinical potential, the use of medicinal plants is associated with challenges, including complex pharmacokinetics, significant adverse effects, and the risk of herb–drug interactions, alongside concerns regarding standardization and quality control. This manuscript aims to examine the therapeutic potential of key medicinal plants for managing MDD, including Hypericum perforatum, Rhodiola rosea, Melissa officinalis, Passiflora incarnata, Valeriana officinalis, and Cannabis sativa. Additionally, the review addresses emerging candidates such as Curcuma longa, Withania somnifera, Panax ginseng and Centella asiatica. By focusing on their mechanisms of action, pharmacokinetics, and associated risks, this review provides a more comprehensive understanding of their role in modern psychiatric care. Full article

Background/Objectives. Chronic benzodiazepine (BDZ) use is frequently maintained beyond recommended durations due to neuroadaptation, psychological dependence, and withdrawal-related issues. Passiflora incarnata L., herba (P. incarnata) has shown anxiolytic and GABAergic activity that may mitigate withdrawal symptoms, while cognitive-behavioural therapy (CBT) targets maladaptive beliefs and behaviours sustaining BDZ misuse. This study investigates the independent and interactive effects of P. incarnata and CBT on BDZ dose reduction during a three-month tapering program. Methods. This retrospective observational study included 186 outpatients with anxiety or depressive disorders in clinical remission undergoing BDZ tapering, of whom 93 received a dry extract of P. incarnata as adjunctive treatment and 93, matched for diagnosis, age and sex, followed a standard tapering protocol. BDZ doses were assessed at baseline and three months. CBT was recorded as a binary variable based on the information documented in the medical records. An ANCOVA was performed to assess the impact of CBT and P. incarnata on BDZ reduction (change in mg diazepam equivalents), adjusting for sex, age, education, baseline anxiety and depression scores, initial BDZ and antidepressant dosage. A subgroup analysis was conducted to investigate the role of P. incarnata dosage in BDZ reduction. Results. Both CBT and P. incarnata were associated with significantly greater reductions in BDZ dosage at three months (CBT: p = 0.005, effect size: 0.032; P. incarnata: p < 0.001, effect size: 0.128). A significant interaction between CBT and P. incarnata was also observed (p = 0.037, effect size: 0.018), indicating a synergistic effect when both interventions were combined. Baseline sociodemographic characteristics, BDZ and antidepressant dosage and symptom severity did not differ significantly between groups. Patients taking 400–600 mg of P. incarnata dry extract showed a higher BDZ reduction compared to those taking 200 mg. Conclusions. These findings suggest that P. incarnata and CBT exert independent yet complementary effects in supporting BDZ tapering. Their combination appears to enhance dose reduction beyond either intervention alone, supporting a multimodal approach that addresses both neurobiological and psychological components of BDZ addiction. Prospective controlled studies are needed to confirm these results and to clarify their impact on long-term discontinuation outcomes. Full article

The lack of protocols for breaking seed dormancy, inconsistent seed quality, and abiotic stress factors such as drought impede large-scale restoration efforts of pollinator-friendly native plant species. This research explores the germination response, dormancy-breaking techniques, and water stress tolerance in selected pollinator-friendly plant species with characteristics facilitating mechanized rehabilitation protocols and biodiversity enhancement. Forty-two commercial seed lots representing seven plant families with 28 species were evaluated under two alternating temperature regimes (15/25 °C and 20/30 °C) with and without gibberellic acid (GA₃) priming treatments. Six of the twenty-eight species were selected based on pollinator requirements for the monarch butterfly (Danaus plexippus L.) and further examined by priming seeds for 24 h in solutions containing GA₃, kinetin (KIN), and hydrogen peroxide (H₂O₂), or their combinations, to evaluate their dormancy-breaking responses. The effect of water stress on seed germination was assessed in controlled chambers at soil water potentials of −1.08, −0.75, −0.13, and 0 MPa. Initial seed quality of the 42 seed lots revealed that only 62% had greater than 50% germination, while of the same 42 lots, 98% had greater than 50% viability based on the commercial seed label. The difference was largely attributed to seed dormancy. In laboratory studies of the 42 seed lots, GA₃ significantly enhanced germination percentage, and reduced T₅₀ (time to 50% germination) across most seed lots. Overall, germination was higher and faster at 20/30 °C than 15/25 °C. Priming the six selected species with 1.0 mM GA₃ in 0.3% H₂O₂ consistently improved germination compared to the non-primed control after 14 days. Asclepias species (A. incarnata, A. syriaca, and A. tuberosa) exhibited consistently high germination across a broad moisture range of −0.75 to 0 MPa. In contrast, Echinacea purpurea required high moisture levels (−0.13 to 0 MPa) for optimal germination. Monarda fistulosa and Rudbeckia hirta showed their best performance under moderate moisture conditions (−0.13 MPa). Collectively, the use of GA₃ priming to break physiological seed dormancy offers a promising approach to enhance germination and improving the establishment potential of native pollinator species in restoration programs. Full article

Background/Objectives: Astrocytic redox-inflammatory signaling has been implicated in Parkinson’s disease (PD) pathology and may constrain hippocampal neurogenesis. We previously identified an astrocytic NOX4–MPO–OPN axis associated with impaired neurogenic capacity. Here, we tested whether a saffron-derived antioxidant (SDA; Crocus sativus extract) and Passiflora incarnata L. extract (PI) modulate this pathway in an MPTP-induced PD mouse model. Methods: Male C57BL/6J mice were randomized to Sham, MPTP, and treatment groups (n = 9/group for behavior; n = 4–5/group for histology/immunoblotting). SDA or PI (50 mg/kg/day, oral, 5 weeks) was administered, with resveratrol as a positive control. Behavioral, histological, and molecular analyses were performed by investigators blinded to group allocation where feasible. Results: SDA and PI were associated with reduced NOX4/MPO/OPN signals, mainly in GFAP-positive astrocytes, along with recovery of neurogenesis markers (Ki67, DCX, BrdU/NeuN) and synaptic markers (PSD95, synaptophysin), and improved motor performance. Mitochondrial and oxidative injury markers (TIM23, TOM20, OXPHOS subunits; 4-HNE) and apoptotic markers (Bax, cleaved caspase-3, Bcl-2) also shifted toward Sham levels. Given previous reports of Passiflora extracts’ sedative effects, we note that metabolic measures (body weight, food intake, and water intake) were similar across groups; however, specific tests for sedation or arousal were not conducted. Conclusions: These findings offer preclinical evidence that SDA and PI modulate redox-inflammatory and mitochondrial stress signatures and are associated with neurogenic, synaptic, and behavioral improvements in an acute MPTP model. Further validation in chronic/genetic PD models and pharmacokinetic/brain exposure studies will be necessary to confirm their translational potential. Full article

This study examined the relationship between flavonoid content and the antiviral effects of plant extracts against the dengue virus (DENV). Fourteen extracts from medicinal plants cultivated in Colombia, which were prepared by ultrasonic-assisted solvent extraction (UAE) and supercritical fluid extraction (SFE) were included. UHPLC/ESI-Q-Orbitrap-MS analysis identified forty-six flavonoids. Antiviral effect on viral adsorption was evaluated using the DENV-CPE-based assay. UAE extracts of Scutellaria coccinea, Scutellaria incarnata, and Lippia alba contained higher amounts of flavonoid glycosides (from 97.0% to 87.9%) than aglycones, and showed antiviral effect (IC₅₀: 3.0 to 65 µg/mL; SI: 0.4 to 71). In contrast, UAE and SFE extracts from Lippia origanoides had higher content of flavonoid aglycones (41.7% to 93.4%) than glycosides (0.0 to 58.3%) and showed no antiviral effect. Cluster and one-way ANOVA analyses revealed a positive correlation between increased levels of flavone glycosides in the extract and a strong antiviral effect. Docking analyses (AutoDock Vina) revealed that the flavonoid glycosides exhibited a higher binding affinity for the target proteins (E, Gas6-Axl, clathrin, and dynamin) than the aglycones did. This study establishes a scientific basis for using extracts rich in flavonoid glycosides, particularly flavones, as starting points for developing plant-based therapies to treat dengue. Full article

Diabetic neuropathy (DN) is one of the most prevalent complications of diabetes mellitus, affecting a substantial proportion of patients and contributing to progressive sensorimotor dysfunction. Despite its clinical significance, available treatments are often insufficient and associated with undesirable effects. This study aims to evaluate the potential of Morus alba (MA), Angelica archangelica (AA), Valeriana officinalis (VO), and Passiflora incarnata (PI) extracts in ameliorating nociceptive alterations and inflammatory markers in the alloxan-induced diabetic rat model. Male Wistar rats with alloxan-induced DN received oral administration of the plant extracts (200 mg/kg/day) or gabapentin (100 mg/kg/day) for 15 days, the dosage regimen being established based on prior efficacy data in preclinical neuropathy models. Behavioral assessments of thermal and mechanical hypersensitivity were conducted using hot plate, tail withdrawal, von Frey, and Randall–Sellito tests. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were quantified in brain and liver homogenates to evaluate neuro-inflammatory responses. All plant extracts produced significant improvements in nociceptive thresholds compared to diabetic control, with the most marked effects observed for MA extract. Pro-inflammatory cytokine levels were significantly reduced in all treatment groups, with MA and AA extracts inducing the most significant reductions in TNF-α and IL-6 concentrations. Computational target prediction and molecular docking analyses revealed that key phytochemicals from the plant extracts may exert antihyperalgesic effects through multi-target modulation, notably via interactions with AAK1, a kinase involved in neuropathic pain signaling. The investigated plant extracts displayed significant antihyperalgesic and anti-inflammatory activities in a rat model of DN. Among them, MA extract revealed the most consistent therapeutic profile, supporting its potential role as a strategy for managing DN. Full article

Background/Objectives: Anxiety, agitation, and mood disturbances are increasingly common among children and adolescents. Given the limitations of conventional pharmacological treatments in the pediatric population, particularly for subthreshold or mild conditions, interest in complementary approaches such as phytotherapy is growing. This review aims to critically evaluate the clinical evidence supporting the use of herbal medicines and botanical food supplements for mental health symptoms in youths and to explore the pharmacological basis of their activity. Methods: A systematic search was conducted across main databases for clinical trials involving herbal products for psychologically related symptoms in children and adolescents. Eligible studies included those using registered herbal medicines, as well as authorized food supplements, that evaluated behavioral or cognitive outcomes. In addition, bioinformatic analyses were performed on selected phytocompounds to predict their molecular targets. Results: Twenty-nine clinical trials were identified, including eighteen targeting pathological conditions (notably attention deficit/hyperactivity disorder (ADHD), anxiety, and depression) and eleven addressing borderline symptoms such as nervous agitation, restlessness, or sleep disturbances. Herbal products showing clinical promise include Bacopa monnieri (L.) Wettst., Crocus sativus L., Ginkgo biloba L., Hypericum perforatum L., Lavandula angustifolia Mill., Melissa officinalis L., Panax ginseng C.A. Meyer, Passiflora incarnata L., Pinus pinaster Aiton, Valeriana officinalis L., and Withania somnifera (L.) Dunal. Bioinformatic predictions revealed polypharmacological activity profiles involving neuroinflammatory, neuroprotective, and neurotransmitter-related pathways. Conclusions: This review highlights both the potential and the current limitations of herbal products in pediatric mental health care. Evidence supports their use for selected indications, provided that standardized preparations and clinical oversight are ensured. Further research is essential, particularly to inform dosing, safety, and integrative care strategies. Full article

Background: Chronic pain poses a major global health burden, often inadequately managed by conventional analgesics due to limited efficacy and side effects. In this context, plant-based therapies offer a promising alternative. This study aimed to evaluate the antioxidant and analgesic potential of four medicinal plants traditionally used for pain relief: Morus alba, Angelica archangelica, Valeriana officinalis, and Passiflora incarnata. Methods: Phytochemical analyses quantified total phenolic acid, flavonoid, and polyphenolic acid contents in the extracts. Antioxidant activity was assessed using the ABTS radical scavenging assay. Analgesic effects were evaluated in vivo using the hot-plate and tail-flick tests in mice treated for 14 days with plant extracts or paracetamol. Results: Morus alba showed the highest polyphenolic content and strongest antioxidant activity (IC₅₀ = 0.0695 mg/mL). In analgesic tests, Angelica archangelica demonstrated the most significant effect in the hot-plate test (72.2% increase in latency), while Valeriana officinalis had the highest efficacy in the tail-flick test (41.81%), exceeding paracetamol’s performance in that model. Conclusions: While antioxidant activity correlated with polyphenol content, analgesic effects appeared to involve additional mechanisms. These findings support the potential of Angelica archangelica and Valeriana officinalis as effective natural alternatives for pain relief. Full article

Background/Objectives: Passiflora (passionflower), traditionally used for anxiety and insomnia, is primarily known for GABAergic modulation. However, evidence suggests broader neuropharmacological actions. This review aimed to systematically explore non-GABAergic mechanisms of Passiflora. Methods: We performed a systematic review following PRISMA Guidelines (PROSPERO: CRD420251028681). PubMed/Medline, PsycINFO, Embase, Web of Science, and Scopus were searched for original research on non-GABA neurobiological mechanisms of Passiflora species (P. incarnata, P. edulis, P. caerulea, P. actinia, P. foetida). Studies were screened and assessed for eligibility, and data on design, Passiflora preparation, mechanisms, and main findings were extracted. Results: Thirteen studies revealed diverse non-GABAergic actions. Passiflora modulates opioidergic and nicotinic cholinergic systems (relevant to analgesia), monoaminergic pathways (affecting dopamine, norepinephrine, serotonin), and the glutamatergic system (offering neuroprotection via NMDA receptor inhibition). It also exhibits significant anti-inflammatory and antioxidant effects (reducing cytokines, activating Nrf2) and modulates the HPA axis (reducing stress hormones). Other mechanisms include gut microbiota modulation and metabolic effects. Conclusions: Passiflora’s therapeutic potential extends beyond GABA, involving multiple neurotransmitter systems and neuroprotective, anti-inflammatory, antioxidant, and HPA axis-regulating activities. This multi-target profile likely contributes to its clinical efficacy in conditions like anxiety, pain, and stress, potentially with a favorable side-effect profile. Further research, including mechanistic studies and clinical trials with relevant biomarkers, is needed to fully elucidate its complex pharmacology. Full article

Hydrogen peroxide (H₂O₂) functions as a signaling molecule that triggers physiological and biochemical adjustments that help plants cope with environmental stress. This study evaluated the effects of foliar application of 1.5 mM H₂O₂ on the physiological and biochemical responses of Passiflora incarnata subjected to 14 days of drought stress followed by 5 days of rehydration. Drought reduced Fv/Fm and photochemical efficiency, as well as stomatal conductance and transpiration rates. H₂O₂ treatment under drought further reduced stomatal conductance and transpiration, suggesting enhanced water conservation. Drought-stressed plants treated with H₂O₂ exhibited increased concentrations of glucose, fructose, and mannose along with reduced sucrose levels, indicating osmotic adjustment and energy mobilization. Enzymatic antioxidant activity, particularly that of superoxide dismutase and catalase, increased with H₂O₂ treatment, while peroxidase activity remained low. The content of vitexin, arabinose, and trehalose decreased under drought, likely due to their roles in membrane protection, as MDA levels remained stable. After rehydration, Fv/Fm and ΦPSII recovered, and H₂O₂-treated plants showed higher carbon assimilation and carboxylation efficiency. These results indicate that H₂O₂ promotes drought acclimation and enhances post-stress recovery in P. incarnata. We conclude that H₂O₂ induces signaling pathways, with trehalose, arabinose, and vitexin contributing to the regeneration of the photochemical apparatus, as well as defense and acclimation under drought conditions. Full article

The current study evaluated the anticonvulsant properties of ethanolic extracts from Morus alba, Angelica archangelica, Passiflora incarnata, and Valeriana officinalis using integrated phytochemical, in vivo, biochemical, and computational approaches. Phytochemical analysis by UHPLC-HRMS/MS revealed the presence of various bioactive compounds, notably flavonoids such as isorhamnetin, quercetin, and kaempferol. In an electroshock-induced seizure model, Morus alba extract (MAE, 100 mg/kg) demonstrated significant anticonvulsant effects, reducing both seizure duration and incidence, likely mediated by flavonoid interactions with GABA-A and 5-HT3A receptors, as suggested by target prediction and molecular docking analyses. The extracts of Angelica archangelica (AAE, 100 mg/kg) and Passiflora incarnata (PIE, 50 mg/kg) exhibited moderate, non-significant anticonvulsant activities. At the same time, Valeriana officinalis (VOE, 50 mg/kg) displayed considerable antioxidant and anti-inflammatory properties but limited seizure protection. All extracts significantly reduced brain inflammation markers (TNF-α) and enhanced antioxidant defenses, as indicated by total thiols. Molecular docking further supported the interaction of key phytochemicals, including naringenin and chlorogenic acid, with human and mouse 5-HT3A receptors. Overall, Morus alba extract exhibited promising therapeutic potential for epilepsy management, warranting further investigation into chronic seizure models and optimized dosing strategies. Full article

Background: Feeding and Eating Disorders (FEDs) are severe mental health conditions often emerging during childhood or adolescence, with rising prevalence. They are frequently associated with psychiatric and organic comorbidities, including anxiety symptoms and insomnia. Phytotherapy, particularly Passiflora incarnata L. Herba, has been suggested as a potential treatment option for anxiety and insomnia in youth. Methods: this is an observational and retrospective study that includes patients assessed in a third-level Italian Regional Centre for Feeding and Eating Disorders in Children and Adolescents between 1 January 2020 and 31 December 2023. Eligible patients had a confirmed diagnosis of a FED, along with either an anxiety or a sleep disorder. During follow-up, the clinical efficacy of Passiflora incarnata L. Herba was assessed using the Clinical Global Impression–Improvement scale (CGI-I). Comparative analyses were conducted by stratifying the sample based on the target symptoms (sleep disorders/insomnia and anxiety), FED subtype, and whether polytherapy was used. Results: this study includes 94 patients, with most diagnosed with anorexia nervosa (71.3%). Passiflora incarnata L. Herba was administered at a dosage of 200 mg (1–2 tablets for day). It was often combined with selective serotonin reuptake inhibitors (SSRIs) (56.5%), atypical antipsychotics (27.7%), or benzodiazepines (7.4%). Treatment was initiated for anxiety symptoms (75.5%) or insomnia (28.7%). No side effects were reported. Among patients with specific outcome data, 53.3% reported improvements in anxiety symptoms, and 45.4% reported improvements in insomnia. Conclusions: this is the first study to evaluate the use of Passiflora incarnata L. Herba for anxiety and insomnia in children and adolescents with FEDs. Our findings suggest that Passiflora incarnata L. Herba may serve as a well-tolerated adjunctive treatment, showing symptomatic improvement in up to 53% of the patients with data on treatment outcomes. Notably, 53.3% and 45.4% of participants, with specific outcome data, reported reduced anxiety and insomnia symptoms, respectively. Given its excellent safety profile and preliminary efficacy, Passiflora incarnata L. Herba may represent a promising alternative for patients with mild symptoms or for caregivers hesitant about conventional pharmacotherapy. Full article

The diversity in anthocyanin flower pigmentation is vital in the ornamental plant market. To understand the regulation of the corona filament pigmentation of the Passiflora flower, we investigated the anthocyanin profiles of five distinct species (P. violacea, P. caerulea, P. edulis, P. incarnata, and P. coccinea) using HPLC-MS. A total of 14 anthocyanins, differentially distributed in the analyzed species, were identified as responsible for the differences in corona color, which can be attributed to different ratios of pelargonidin, cyanidin, and delphinidin. Additionally, we evaluated the expression of some biosynthetic genes, including dehydroflavonol reductase (DFR), flavonoid 3′-hydroxylase (F3′H), and flavonoid 3′,5′-hydroxylase (F3′5′H). F3′H seems to regulate the accumulation of cyanidins, F3′5′H determines blue pigmentation, and DFR enhances the biosynthesis of pelargonidins. Furthermore, three genes coding for key transcription factors, Myeloblastosis (MYB), basic helix-loop-helix (bHLH), and WD repeat protein (WD40), were examined using qPCR. The results confirm that such genes regulate anthocyanin biosynthesis and provide insight into the molecular mechanisms that underlie pigment biosynthesis for application in biotechnologies. Full article

Background/Objectives: This study explored the antitumor effect of Passiflora incarnata leaves’ nanoformulation (N-EEP) in fibroblasts, A375 cell lines, and in vivo using Dalton’s lymphoma ascites (DLA)-bearing mice. Methods: N-EEP treatment could significantly slow scratch closing in A375 cells compared to in the extract itself (EEP). Results: The hemolytic assay showed that N-EEP had less than 2% hemolysis, making the formulation highly biocompatible. In vivo N-EEP administration delayed the tumor growth rate, reduced weight gain, and increased the tumor-bearing mice’s life span. Furthermore, the ascitic cells were aspirated from the tumor and investigated for various gene expressions. The tumor suppressor gene p53, which plays a significant role in the mitochondrial-mediated apoptosis pathway, was found to be elevated in animals treated with N-EEP. We assessed the cytotoxicity of isolated DLA cells from induced mice using both the trypan blue and MTT assays, while apoptotic studies were conducted using Hoechst staining. Results from the trypan blue and MTT assays indicated that nearly 80% of the cells were killed by N-EEP treatment (200 μg/mL). Additionally, apoptosis, characterized by condensed nuclei, was observed after N-EEP treatment, confirming that one of the modes of cell death was caspase-dependent apoptosis. Conclusions: Our study suggests that N-EEP delayed the growth of DLA by upregulating p53 gene expression and inducing apoptosis. Full article