Search Results (136)

Background: Standardised Ashwagandha root extract (SARE), characterised by its content of bioactive withanolides, is widely used for its antioxidant and adaptogenic properties; however, recent case reports have raised safety concerns, primarily involving non-standardised or multi-ingredient formulations. This systematic review evaluated the safety and tolerability of SARE in healthy adults, with a focus on clinical biomarkers and adverse event reporting. Methods: Randomised trials were identified through searches of PubMed, Web of Science and Google Scholar, published from 2010 to April 2026. Studies administering single-ingredient, standardised root-only extracts to generally healthy populations were included. Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Twenty-three studies with a total of 2317 participants met the inclusion criteria, with doses ranging from 125 to 600 mg/day and intervention durations from a single dose to 180 days. Across studies, hepatic, renal, haematological, endocrine, and cardiovascular biomarkers remained within normal clinical ranges, with no clinically meaningful adverse alterations reported. Reductions in cortisol were consistently observed, while increases in testosterone remained within physiological ranges. No serious adverse events attributable to SARE were reported. Mild adverse events, including gastrointestinal discomfort, headache, and transient drowsiness, were infrequently reported and occurred in both intervention and comparator groups. Conclusions: SARE was well tolerated in healthy adults at the studied doses and durations. However, limited long-term data (>180 days) and heterogeneity in study design and reporting warrant further large-scale, standardised trials to confirm safety across extended use and diverse populations. The review is registered in the PROSPERO database with ID CRD420261337116. Full article

Nowadays, it is central to generate innovations that convert agricultural by-products and food waste into valuable animal products while promoting the long-term resilience and sustainability of vulnerable animal production systems. Nutraceuticals (i.e., ‘nutrition + pharmaceutical’) are derived from foods that offer health benefits. In animal production, nutraceutical supplementation with Withania somnifera and Lepidium meyenii has shown positive effects on the endocrine, cardiopulmonary, and central nervous systems. We aimed to evaluate the possible impact of nutraceutical supplementation on rams fed a diet based on surplus feed from a highly industrialized Holstein cow production system, on corporal (live weight [LW], kg; body condition score [BCS], units), metabolic (blood glucose [GLU], mg dL⁻¹; serum protein [PRO], g 100 mL⁻¹), and sexual–testicular variables [sexual odor (ODOR, units); scrotal circumference (SC, cm); testicular volumes (TVOL, cm³); and estimated daily sperm production (EDSP, millions)]. Black Belly rams (n = 12; LW = 70.36 ± 1.2 kg; BCS = 2.96 ± 0.03 units; age = 3.8 ± 0.2 years; 25° N) were divided into 3 experimental groups: (1) WITH, supplemented with Withania somnifera (400 mg kg⁻¹ LW d⁻¹); (2) LEPI, supplemented with Lepidium meyenii (400 mg kg⁻¹ LW d⁻¹); and (3) CONT, not supplemented. The variables LW, BCS, GLU, PRO, and SC, as well as some components of TVOL, did not differ (p > 0.05) among the main effects of treatment or time; only ODOR, right transverse testicular diameter, and total testicular volume differed among treatments, generally favoring the WITH group. Furthermore, the TRT × T interaction demonstrated superior performance (p < 0.05) in the WITH group, with the largest values for LW, GLU, PRO, ODOR, SC, width of the right testicle, volume of the right testicle, total testicular volume, and EDSP. From a productive–reproductive perspective, the Robin Hood Effect—through the use of rejected dairy cattle rations as the base diet for rams—and supplemented with nutraceuticals (WITH and LEPI), emerges as a viable alternative to improve not only the productive–reproductive performance of Black Belly rams, but also other productive and socioeconomic outcomes; the latter contributing to the strengthening of producer and family well-being. Full article

Ashwagandha, a revered herb in Ayurvedic medicine for over 3000 years, is recognized for its potential benefits in regulating sleep and supporting overall vitality. This study evaluated the comparative effects of Ashwagandha root extract (ARE) and melatonin (MLT) on sleep quality in adults. In this prospective, randomized, double-blind, placebo-controlled trial, 200 men and women aged 18–50 years were randomized to receive ARE (300 mg twice daily; n = 50), MLT (3 mg/day; n = 50), a combination of ARE (600 mg/day) and MLT (3 mg/day; n = 50), or placebo (n = 50) for eight weeks. The primary outcome was the change in sleep onset latency (SOL) from baseline to week eight, measured by actigraphy. Secondary outcomes included actigraphy-based changes in total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE), as well as subjective measures such as the Pittsburgh Sleep Quality Index (PSQI) and the Hamilton Anxiety Scale (HAM-A). At week eight, SOL was significantly reduced across treatment groups, with the ARE–MLT (p < 0.0001) combination showing the greatest improvement. The combination group also demonstrated significant improvements in TST (p < 0.0001), WASO (p < 0.0001), and SE (p < 0.0001), whereas ARE and MLT monotherapy produced moderate but comparable benefits. Inferential analyses confirmed statistically significant improvements in objective and subjective sleep measures (p < 0.0001). Safety analyses indicated that mild adverse events occurred across all groups, with no clinically significant between-group differences. Overall, both Ashwagandha and melatonin improved sleep disturbances in adults, with combination therapy producing the most consistent and pronounced benefits. Full article

Ethnopharmacological relevance. Withania somnifera (L.) Dunal, widely used in traditional medical systems such as Ayurveda, Unani, and Middle Eastern folk medicine, is valued for its adaptogenic, anti-inflammatory, neuroprotective, antimicrobial, and anticancer properties. These activities are primarily attributed to withanolides, with Withaferin A recognized as one of the most bioactive constituents. Although traditional preparations often rely on the root, leaf use provides a more sustainable alternative and may yield significant quantities of active metabolites. Identifying efficient, modern extraction technologies that can enhance the recovery of bioactive compounds from leaves is essential for developing effective, standardized ethnopharmacological formulations. Materials and methods. Plants of W. somnifera grown from seeds were subjected to different environmental conditions (control, drought, cold, yeast extract treatment). Leaves were extracted using Pressurized Cyclic Solid–Liquid Extraction (PCSLE) with hydroalcoholic solvents and compared with conventional infusion of dried leaves. Extracts were fractionated with solvents of varying polarity and analyzed by TLC, HPLC, and NMR for quantification of Withaferin A. Expression levels of key withanolide-biosynthetic genes (CAS, SMT1, DWARF1, CYP71, CYP76) were assessed using qRT-PCR. Antimicrobial activity of pure Withaferin A, aqueous extract, and hydroalcoholic PCSLE extract was evaluated through MIC and MBC assays against Gram-positive and Gram-negative strains. Cytotoxic activity was measured via MTT assays in six human cancer cell lines after 3, 6, and 24 h of treatment. Results. PCSLE yielded substantially higher levels of Withaferin A than traditional infusion, especially in medium-polarity fractions (chloroform and ethyl acetate), with concentrations reaching 0.70% in fresh leaf mass (4.8% dry weight), compared to 0.11% obtained by infusion. Gene expression analysis revealed that 24-week-old plants exhibited the highest transcription of withanolide-biosynthetic genes, and drought stress significantly upregulated CAS, SMT1, DWARF1, CYP71, and CYP716, indicating enhanced metabolic flux toward withanolide production. Hydroalcoholic PCSLE extracts showed broad-spectrum antimicrobial activity, with MIC and MBC values comparable to pure Withaferin A and demonstrating bactericidal effects against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. The aqueous extract showed activity only against Gram-positive strains. Cytotoxicity assays demonstrated an optimistic, dose-dependent reduction in cell viability across all tumour cell lines treated with the hydroalcoholic PCSLE extract, closely mirroring the activity of pure Withaferin A and consistently exceeding the effect of the aqueous extract. IC50 values confirmed the high bioactive content of PCSLE extracts and suggested mechanisms like those known for Withaferin A. Conclusions. PCSLE proved to be a highly efficient extraction technology for obtaining leaf extracts rich in Withaferin A, outperforming conventional extraction methods while exploiting sustainable plant tissue. Developmental stage and drought stress significantly modulated the expression of genes involved in withanolide biosynthesis, highlighting agronomic strategies capable of enhancing metabolite production. Hydroalcoholic PCSLE extracts exhibited antimicrobial and cytotoxic activities comparable to pure Withaferin A, supporting their relevance as promising therapeutic candidates. These findings advocate for the use of W. somnifera leaves as a sustainable source of bioactive compounds and demonstrate that advanced extraction technologies can contribute to the development of innovative ethnopharmacological preparations for antimicrobial and anticancer applications. Full article

Background/Objectives: Adaptogens are plant-derived substances that enhance the body’s nonspecific resistance to physical, chemical, biological, and psychological stressors by normalizing physiological functions. This article discusses the molecular mechanisms of action of seven key plant adaptogens—Rhodiola rosea, Schisandra chinensis, Withania somnifera, Eleutherococcus senticosus, Panax ginseng, Ocimum tenuiflorum, and Bacopa monnieri—in the context of chronic stress and lifestyle-related diseases. Methods: A review of the scientific literature is performed, including preclinical in vitro and in vivo studies, randomized placebo-controlled clinical trials, and studies employing network pharmacology analyses, molecular docking, and genomic techniques such as gene expression profiling. The interactions of active constituents with signaling pathways, molecular targets, and synergistic mechanisms were analyzed based on publications from the years 2010–2025. Results: Adaptogens exhibit pleiotropic activity: they regulate the HPA axis (Hypothalamic–Pituitary–Adrenal axis); induce Hsp70/Hsp16 expression; modulate SAPK/JNK, FOXO, and NF-κB pathways; and demonstrate antioxidant and mitoprotective effects. Specific mechanisms include: salidroside from R. rosea activating PI3K/Akt; schizandrin B from S. chinensis stimulating Hsp70; withanolides from W. somnifera inhibiting PDE4D; ginsenosides from P. ginseng suppressing FKBP51; and bacosides from B. monnieri enhancing acetylcholine synthesis. Clinical studies confirm reductions in cortisol levels (14–30%), decreased fatigue, and improved cognitive function without adverse effects. Conclusions: Understanding the molecular mechanisms of adaptogens supports their application in integrative medicine for the treatment of stress-related disorders, depression, anxiety, and neurodegenerative diseases. Further clinical studies are needed to optimize dosages and standardize extracts. Full article

Ashwagandha (Withania somnifera L.) root powder and extracts have long been used in Ayurvedic medicine to improve sleep and anxiety. Recent scientific investigations into its efficacy have shown promise for relief from anxiety, insomnia and stress and for improving the immune system. It has also been suggested that oxygen uptake in the cardiovascular system, muscle strength, cognitive function, the reproductive system and the aging process significantly benefit from ashwagandha treatment. Since the herbal remedy is taken daily by millions of people in India, China and parts of the West, it is interesting that there are very few case reports of side effects directly attributed to the treatment, suggesting that the administration of ashwagandha preparations may be safe. Currently, neither the European Medicines Agency nor the FDA considers ashwagandha as a drug or general health supplement. Therefore, ashwagandha products are marketed in the West as dietary supplements so that users may be exposed to unscrupulous vendors. In this narrative/literature review, scientific findings from basic research and human clinical trials on herbal remedies, spanning the period from 1994 to date, were critically evaluated for the purpose of highlighting knowledge gaps to provide context for new research. Such investigations will provide evidence for the efficacy and safety of ashwagandha treatment, thus making the herbal preparations more accessible to a wider audience. Full article

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: Interest in the use of nutraceuticals and phytotherapy for the management of andrological diseases has increased markedly in recent years. In particular, growing attention has been directed toward the treatment of patients affected by erectile dysfunction (ED), male infertility, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and induratio penis plastica (IPP). However, several areas of uncertainty remain. This narrative review aims to examine the role of nutraceuticals and phytotherapeutic agents in the management of andrological disorders. Methods: A narrative review was conducted using PubMed, Scopus, Cochrane CENTRAL, and EMBASE to identify relevant studies published over the past 25 years. Only articles published in English and involving adult populations were included in the analysis. Results: Nutraceuticals and phytotherapeutic compounds have been extensively investigated in the current literature, and certain formulations—particularly specific combinations—have been evaluated in high-quality studies. Conversely, other compounds lack sufficient scientific evidence and therefore should not be recommended in routine clinical practice. In the management of ED, the following compounds, administered either alone or in combination, have demonstrated clinically significant effects: Panax ginseng, Tribulus terrestris, L-arginine, and Withania somnifera. L-carnitine, combined with micronutrients, antioxidants, and various traditional herbal supplements, appears to be an effective therapeutic option for male infertility and subfertility. Pollen extracts play an important role in the management of CP/CPPS, while carnitine, coenzyme Q10, silymarin, bromelain, and curcumin show promising potential in the treatment of IPP. Conclusions: Nutraceuticals and phytotherapeutic agents may provide favorable outcomes in the management of andrological diseases. Although current evidence is encouraging, larger prospective studies employing standardized protocols and treatment schedules are required to confirm long-term efficacy and to optimize therapeutic strategies. Full article

Biosynthesis of squalene in the plant chassis has broad application prospects, and identifying efficient enzymes is of great importance. Here, we analyzed the function of squalene synthase genes WsSQS and WsSQS2 from Withania somnifera for squalene biosynthesis in tobacco. WsSQS and WsSQS2 shared 93.7% amino acid (aa) similarity, with divergent residues related to catalysis, NADPH binding, and membrane anchoring. Heterologous expression of WsSQS and WsSQS2 in tobacco increased squalene content by 2.05-fold and 1.68-fold, respectively, with the OE-WsSQS lines reaching 3.19 μg/g DW and the OE-WsSQS2 lines reaching 2.58 μg/g DW, compared to the control plants. Further transcriptomic assays revealed that overexpression of WsSQS induced broader transcriptional changes in the squalene metabolic pathway than WsSQS2. Specifically, the overexpression of WsSQS up-regulated AACT, HMGS, MVD, IspE, FPPS1, FPPS2, and SQS upstream of squalene biosynthesis and down-regulated GGPPS3 downstream of FPP biosynthesis, which is the direct precursor of squalene biosynthesis, while WsSQS2 exerted a more targeted impact, primarily up-regulating HMGS and the key rate-limiting enzyme gene HMGR in the squalene biosynthesis pathway. These findings are consistent with the high efficiency of WsSQS in squalene biosynthesis in tobacco. In summary, this study provides fundamental molecular and biochemical insights into the utilization of heterologous SQSs for squalene production based on the tobacco chassis. Full article

Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by progressive neuronal loss, amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, cholinergic dysfunction, and gut–brain axis dysregulation. Despite advances in anti-amyloid therapeutics, current interventions provide only modest symptomatic relief and face limitations in accessibility, cost, and long-term efficacy. Plant-derived bioactive compounds, rooted in traditional medicine systems such as Ayurveda and Traditional Chinese Medicine, have gained increasing attention as multi-target therapeutic agents due to their pleiotropic actions, relative safety, and ability to cross the blood–brain barrier. This review synthesizes mechanistic and translational evidence on major phytochemicals, including withanolides (Withania somnifera), curcumin (Curcuma longa), ginkgolides and bilobalide (Ginkgo biloba), bacosides (Bacopa monnieri), ginsenosides (Panax ginseng), crocin/safranal (Crocus sativus), epigallocatechin-3-gallate (Camellia sinensis), rosmarinic acid (Salvia officinalis, Melissa officinalis), and asiaticosides (Centella asiatica). These compounds exert neuroprotective effects by inhibiting Aβ aggregation, reducing tau phosphorylation, scavenging reactive oxygen species, attenuating NF-κB-mediated inflammation, modulating cholinergic signaling, enhancing synaptic plasticity via brain-derived neurotrophic factor/cAMP response element-binding protein (BDNF/CREB) activation, and regulating gut microbiota. Multi-target approach analyses underscore their synergistic potential in targeting interconnected AD pathways. However, translation remains hindered by poor oral bioavailability, rapid metabolism, and variability in clinical outcomes. Advances in delivery platforms, including liposomes, bilosomes, solid lipid nanoparticles, and nanostructured lipid carriers, are improving stability, blood–brain penetration, and therapeutic efficacy in preclinical models. Collectively, plant-derived phytochemicals serve as promising, affordable, and multi-modal candidates for reshaping AD management, bridging traditional knowledge with modern therapeutic innovation. Full article

Concurrent consumption of ethanol (EtOH) and herbal preparations containing Withania somnifera (WS, ashwagandha) is increasingly common, but the neurobehavioral and molecular consequences of such interactions remain poorly characterized. This study investigated how three purified withanolides—withanolide A (WITA), withanone (WIN), and withaferin A (WTFA)—modulate the effects of acute EtOH exposure in zebrafish (Danio rerio) larvae. Locomotor behavior was quantified under EtOH concentrations ranging from 0 to 4.0%, and the expression of four GABAA receptor subunit genes (gabra1, gabra2, gabrd, gabrg2) was analyzed by qPCR. EtOH alone induced a biphasic locomotor response, with stimulation at low-to-moderate doses and suppression at higher doses. WITA and WIN modulated this pattern in a dose-dependent manner, preserving or enhancing hyperactivity, while WTFA consistently potentiated locomotor suppression. mRNA profile analysis revealed subunit-specific changes, including downregulation of gabra1 and gabra2, compound-dependent regulation of gabrd, and complex gabrg2 responses. These results demonstrate that individual withanolides distinctly shape behavioral and molecular outcomes of EtOH exposure, suggesting specific interactions at the level of inhibitory neurotransmission. The findings provide mechanistic insight into the combined effects of WS-derived compounds and EtOH and highlight the importance of considering such interactions in both experimental and applied contexts. Full article

While adaptogens are popular in dietary supplements for their health-promoting properties, their safety is compromised by the risk of heavy metal contamination, a threat amplified by inconsistent regulatory standards. This study aimed to assess the extent of heavy metal contamination in adaptogenic supplements on the Polish market and evaluate their compliance with international safety limits. Eleven commercially available supplements (tablets, powders, dried materials) containing Withania somnifera, Rhodiola rosea, Panax ginseng, and Schisandra chinensis were analyzed for lead (Pb), cadmium (Cd), mercury (Hg), nickel (Ni), and other elements using flame atomic absorption spectroscopy (FAAS) and mercury analysis (AMA 254). Results demonstrated widespread contamination, primarily with Pb and Ni. In processed forms (tablets and dried fruits), Pb concentrations exceeded permissible limits by up to 235%, while Ni levels were exceeded by up to 321%. Schisandra chinensis preparations showed the highest contamination levels. Furthermore, raw materials from India contained significantly higher Ni concentrations than those from China (p < 0.01). These findings reveal that a majority of the tested supplements fail to meet toxicological safety criteria, posing a significant health risk to consumers. This underscores a critical regulatory gap and highlights the urgent need for harmonized standards and stringent quality control for dietary supplements. Full article

The protective effects of the herbal feed supplements Silybum marianum, Silymarin, Withania somnifera, and Centella asiatica against ochratoxin A (OTA) toxicity were studied in 48 New Zealand White rabbits (37-day-old) during an 80-day experiment. OTA was given at 2 ppm, whereas Silybum marianum, Silymarin, Withania somnifera, and Centella asiatica were given at feed levels of 5000 ppm, 25,000 ppm, 4000 ppm, and 4600 ppm, respectively. All rabbits were immunized against Rabbit Hemorrhagic Disease Virus (RHDV). OTA was found to induce an immunosuppressive effect on the humoral immune response. Reliable protection against OTA-provoked immunosuppression by Silimarin and Withania somnifera was found. The OTA-induced immunosuppression was responsible for secondary bacterial infection (pasteurellosis) and the death of two rabbits from the OTA-exposed group and one rabbit each from the groups protected with Silybum marianum and Centella asiatica. A decreased body weight was found in rabbits exposed to OTA, but the decrease was slighter in the rabbits protected with herbal supplements. The target organs damaged by OTA exposure were the liver, kidneys, and spleen, while weaker lesions were found in other internal organs, except in the cases of secondary pasteurellosis, in which the strongest damage was found in the lung. All investigated herbal supplements appeared to have stronger protective effects against OTA-induced damage to the kidneys and liver, with slightly protective effects observed in the lungs, myocardium, spleen, brain, intestine, testicles, and ovaries. Full article

Fibromyalgia syndrome (FMS) is a chronic disorder marked by widespread musculoskeletal pain, fatigue, mood disturbances, and cognitive impairments. Current treatments primarily focus on symptom management. Ashwagandha (Withania somnifera), a traditional Ayurvedic herb, is known for its adaptogenic and neuroprotective properties. This study evaluated the protective effects of the methanolic root extract of Ashwagandha (ARE) in a reserpine-induced fibromyalgia model in male Swiss albino mice. Mice received oral ARE (100 mg/kg) for 17 days and reserpine (0.5 mg/kg, subcutaneously) for three consecutive days to induce fibromyalgia-like symptoms. Behavioral assessments included Von Frey, tail suspension, rotarod, and Y-maze tests. Histological analysis was conducted on the hippocampus and thalamus; however, neurochemical analysis focused on markers such as serotonin, norepinephrine, IL-1β, TNFα, MDA, and NO. Results indicated that ARE significantly reduced pain and depressive-like behavior and improved motor function (p < 0.0001); however, no significant changes were observed in open-field locomotion. Histological examination revealed protection of Ashwagandha against neurodegeneration and improved hippocampal integrity, accompanied by increased serotonin and norepinephrine levels and decreased pro-inflammatory cytokines. These findings suggest that Ashwagandha root extract may offer therapeutic benefits for managing fibromyalgia symptoms. Full article