Search Results (88)

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

Background/Objectives: There is a clear need for more options to control the progression of breast cancer and prevent the occurrence of breast cancer in minority populations that have a higher rate of mortality due to triple-negative breast cancer (TNBC) subtypes. Prevalent nutraceuticals such as Ashwagandha (also known as the Indian Winter Cherry) have anti-inflammatory and apoptotic capabilities, as well as the ability to inhibit cancer growth. The purpose of this study is to analyze the novel combination of withaferin A (derived from the Indian Winter Cherry and known to have histone deacetylase inhibition capabilities) and sodium butyrate (a short-chain fatty acid produced from the gut microbiome and known to have DNA methyltransferase inhibition capabilities) treatment on breast cancer-derived cell lines. There is a scientific gap of possible causality of decreasing breast cancer progression when treated with sodium butyrate and withaferin A. Methods: Two in vitro cell viability assays were utilized consisting of [MTT (4,5 Dimethylthiazol-2-yl)] and the neutral red assay to analyze the impact of treatment of compounds alone and in combination on breast cancer cells for 72 h. The Highest Single Agent (HSA) combination analysis was utilized to derive combination indexes for our breast cancer cell types. Protein and gene expression was investigated for Class 1 histone deacetylases, de novo DNA methyltransferase, the p65 subunit of NF-κB, and NFκB1. Lastly, DNA methyltransferase enzymatic activity was analyzed via the Epigentek DNMT Activity/Inhibition ELISA Easy Kit. Results: Through the cell viability assay [MTT (4,5 Dimethylthiazol-2-yl)], MCF−7, MDA−MB−231, and MDA−MB−157 cells were found to have a decrease in cell viability due to combinatorial treatment with withaferin A and sodium butyrate. Western blot results depicted a decrease in protein expression levels for DNA methyltransferases due to the administration of 2.5 mM sodium butyrate and 0.2 µM withaferin A alone and in combination for breast cancer cell lines MCF−7, MDA-MB-231, and MDA−MB−157. Additionally, the combination of these two components have successfully inhibited the progression of the NFκB1 gene within analysis through the quantitative polymerase chain reaction (qPCR). Conclusions: The novel combination of withaferin A and sodium butyrate have markedly reduced the progression of breast cancer-derived cell lines for cell viability, epigenetic DNMT gene expression, as well as inhibiting NFκB1 signaling on the gene expression level. 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

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly. Among the diverse pathological features of AD, amyloid beta (Aβ) aggregation and neuroinflammation are recognized as central and interlinked mechanisms driving disease progression. This review focuses specifically on these two processes and highlights current pharmacological limitations in modifying disease pathology. Natural products such as curcumin, resveratrol, Ginkgo biloba, epigallocatechin gallate (EGCG), crocin, ashwagandha, and cannabidiol (CBD) have shown promising activity in modulating Aβ aggregation and neuroinflammatory pathways, offering multi-target neuroprotective effects in preclinical studies. However, their therapeutic application remains hindered by poor solubility, instability, rapid metabolism, and limited blood–brain barrier (BBB) permeability. To overcome these barriers, nanotechnology-based drug delivery systems—including polymeric nanoparticles, niosomes, solid lipid nanoparticles, and chitosan-based carriers—have emerged as effective strategies to enhance brain targeting, bioavailability, and pharmacological efficacy. We summarize the mechanistic insights and nanomedicine approaches related to these bioactives and discuss their potential in developing future disease-modifying therapies. By focusing on Aβ aggregation and neuroinflammation, this review provides a targeted perspective on the evolving role of natural compounds and nanocarriers in AD treatment. 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

Objectives: This study investigates the effects of 600 mg/day Ashwagandha root extract on physiological stress biomarkers, perception of recovery, muscle strength and aerobic capacity in team sports athletes during pre-season training, a period associated with elevated cortisol and accumulated training stress. Methods: Fifty-six athletes (26.8 ± 4.4 years, 1.74 ± 0.10 m, 79.4 ± 17.3 kg, 11.0 ± 7.1 career years) across rugby, water polo and football were randomly assigned to an Ashwagandha (ASH; n = 28, 14 males and 14 females) or placebo (PLA; n = 28, 14 males and 14 females) group for 42 days. Salivary biomarkers were assessed after training, muscle strength and aerobic capacity were measured during training, and perception of recovery was evaluated with Hooper Index (HI) the following day. Mixed ANOVA was used to determine group × time interactions and Bonferroni post hoc analyses were conducted for multiple pairwise comparisons. Results: In female athletes, salivary cortisol increased significantly in PLA (p = 0.001), while recovery parameters such as the overall HI score (p = 0.001), Delayed Onset Muscle Soreness (DOMS) (p = 0.008) and perception of fatigue (p = 0.026) scores improved significantly in ASH. In males, salivary cortisone increased significantly in PLA (p = 0.022), while Countermovement Jump (CMJ) improved significantly in ASH (p = 0.018). Pull-up performance increased in both PLA (p = 0.004) and ASH (p < 0.0001) in males. Conclusions: Supplementation with 600 mg/day of Ashwagandha root extract for 42 days may stabilise stress biomarkers, improve perception of recovery and enhance muscle strength in team sports athletes during pre-season training. The trial is registered on ClinicalTrials.gov with the ID NCT07041853. 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

Ayurveda is the traditional medical system of India and has been in use for more than 5000 years. The focus of Ayurveda is to maintain harmony and balance of the three Doshas (Vata, Pitta, Kapha), or life forces, that govern the physiology and health of each individual. Ashwagandha is considered one of the most useful plants in the Ayurvedic system for various illnesses, including cancer. Ethnopharmacological and phytochemical analyses have been elucidating the bioactive compounds in ashwagandha that mediate the anti-cancer effects. The most bioactive compounds appear to be the withanolides, including withaferin-A (WFA), withanone, and other withanolide derivatives. The focus of this review will be to discuss the pre-clinical and translational anti-cancer properties of WFA, withanone, and selected withanolides in terms of their ability to inhibit the growth of systemic forms of cancer and gliomas. The mechanisms of action of how these compounds affect tumor cell growth will also be discussed in detail, and include the induction of apoptosis, the inhibition of signal transduction pathways, the arrest of the cell cycle, and the inhibition of receptor tyrosine kinases. The final part will review how ashwagandha and its bioactive compounds could be applied to glioblastoma and gliomas. Full article

Background/Objectives: High-intensity interval training (HIIT) is considered an effective way in improving aerobic capacity and selected health parameters. Ashwagandha is an herb with possible health-promoting properties that may affect metabolism and performance. The aim of this study was to evaluate the effects of ashwagandha supplementation (600 mg/day) during an 8-week HIIT on body composition, lipid profile and hormone levels related to energy homeostasis in healthy young men. Methods: The study was randomised, double-blind and placebo-controlled (Placebo group, PL, n = 20; ashwagandha, A, n = 18). HIIT was conducted on a rowing ergometer (3 times per week, 5–7 series of 1.5 min at 85–95% of maximum power, with intervals of 1.5 min at 70 W). Body composition (BIA, Tanita TBF 300P), serum lipid profile (tChol, HDL-cholesterol, LDL-cholesterol, TG) and serum levels of adiponectin, asprosin and irisin were analysed before (term 1) and after the8-week study (term 2). Both the lipid and hormonal profiles were measured in three time points: pre- and post-graded exercise test and after 24 h recovery period. Results: Analysis showed no effect of training or supplementation on body composition and lipid profile (p > 0.05). In turn, the 8-week HIIT decreased resting levels of adiponectin and increased irisin levels post-exercise and after 24 h (p < 0.05). Conclusions: In young, healthy men, an 8-week HIIT programme significantly affects selected hormones related to energy metabolism of adipose (adiponectin) and muscle (irisin) tissues, but ashwagandha supplementation did not significantly affect any of the hormonal parameters analysed. Full article

Herbal medicinal products are increasingly used alongside conventional medicines, raising the risk of potential interactions such as pharmacodynamic drug–herb interactions (PD-DHIs) that can cause serious adverse drug reactions (ADRs). This review aims to present available pharmacological, clinical and pharmacoepidemiological literature regarding potential DHIs associated with serotonin syndrome or cardiac arrhythmias. Furthermore, it assesses the current evidence using the Oxford Centre for Evidence-Based Medicine (CEBM) 2009 framework. Serotonin syndrome most often results from combining serotonergic herbs (e.g., St. John’s wort) with antidepressants like serotonin reuptake inhibitors (SSRIs), as supported by repeated case reports and mechanistic plausibility (CEBM Level 3, Grade C). Other herbs such as black cohosh, ginseng, Syrian rue, turmeric, rhodiola, ashwagandha, and L-tryptophan/5-HTP have been linked to serotonin syndrome when used with SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), but evidence is limited (Levels 4–5, Grade D). For cardiac arrhythmias, PD-DHIs arise when herbs interact with drugs that alter cardiac electrophysiology—such as QT-prolonging agents, psychotropics, antiarrhythmics or digoxin—thereby amplifying arrhythmogenic risk. Ephedra with sympathomimetics is strongly associated with arrhythmias (Level 2–3, Grade B). Licorice may potentiate digoxin and QT-prolonging drugs via hypokalemia (Level 4, Grade C). Other related PD-DHIs include aconite with antiarrhythmics, bitter orange or caffeine with QT-prolonging psychotropics, yohimbine with cardiovascular agents, and aloe or senna with digoxin. Overall, the evidence for PD-DHIs varies from moderate to weak but large-scale pharmacoepidemiological data is scarce. Future approaches, including artificial intelligence with explainable machine learning and network pharmacology, may integrate mechanistic, clinical, and real-world data to improve early detection or prediction of PD-DHIs. However, several specific challenges must be addressed. Therefore, it is crucial for healthcare providers in both clinical and community settings to increase their awareness of these interactions and ADRs to ensure the safe use of herbal remedies alongside conventional therapies. 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

Background: Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative disorders and the most common form of dementia. Although current treatments examine disease progression, many have side effects and primarily target symptomatic relief as opposed to halting further neurodegeneration. Objective: The current study aims to determine the neuroprotective effects of water-soluble coenzyme Q10 (Ubisol-Q10) and an ethanolic Ashwagandha extract (E-ASH) on a transgenic mouse model of AD. Methods: A variety of immunofluorescence staining of biomarkers was conducted to assess mechanisms commonly implicated in the disease. Additionally, spatial and non-spatial memory tests evaluated cognitive functions at two timepoints throughout the progression of the disease. Results: A substantial reduction in microglial activation and amyloid-β (Aβ) plaques when treated with a combination of natural health products (NHPs), Ubisol-Q10 and E-ASH. Moreover, activation of autophagy was upregulated in both the Ubisol-Q10 and combination (Ubisol-Q10+E-ASH given as a combined “Tonic” solution) groups. Oxidative stress was decreased across treated groups, while astrocyte activation was elevated in both the E-ASH and Tonic group. The Tonic group expressed an elevation in the fluorescent intensity of neuronal nuclei (NeuN) and brain-derived neurotrophic factor (BDNF) levels. Interestingly, treatment with E-ASH and Ubisol-Q10 enhanced synaptic vesicle formation compared to controls. Pre-mortem memory tests revealed the treatments to be effective at preserving cognitive abilities. Conclusions: Based on these findings, the combination of E-ASH and Ubisol-Q10 may effectively mitigate the various mechanisms implicated in AD and ultimately prevent further disease progression. Full article

Stress is a major factor that threatens the body’s homeostasis or well-being. Excessive stress causes psychological anxiety and tension, which disrupts the balance of the autonomic nervous system that maintains the body’s balance, resulting in hormonal imbalance and brain changes. In this study, we investigated the effects of Withania somnifera (Ashwagandha) extract on depression, neurobehavior, and hippocampal changes in model mice exposed to stress. Using an excessive restraint stress-induced depression model, we measured the behavioral changes and the levels of brain-derived neurotrophic factor (BDNF) and antioxidant genes in five groups: control, stress, low-dose W. somniferous extract (20 mg/kg/day), high-dose W. somniferous extract (40 mg/kg/day), and L-theanine (50 mg/kg/day, positive control). Stressed mice showed poorer performance in the open field and elevated plus maze tests compared with the control group. The impaired performance was restored following W. somniferous extract administration. In addition, W. somniferous extract restored the decreased expression of BDNF in the hippocampus caused by restraint stress, improved the balance of stress hormones (i.e., cortisol, dopamine, and norepinephrine), and also regulated BDNF, inflammatory genes, and antioxidant genes in brain tissue. Therefore, W. somniferous extract can induce antidepressant and anti-stress effects by maintaining brain BDNF expression and preventing hippocampal tissue alterations caused by restraint stress. Full article