Curcumin (Phytosome)

This systematic review evaluated a total of 31 included human intervention studies that have assessed methods to improve quercetin bioavailability from different formulations and food matrices using urine or blood samples up to July 2024. The bioavailability of quercetin in humans was affected by several factors. 1) Chemical structure: Quercetin-3-O-oligoglucosides exhibited 2-fold higher bioavailability than quercetin-3-O-glucoside, 10-fold higher than quercetin-3-O-rutinoside and ∼ 20-fold higher than quercetin aglycone. 2) Modification of physicochemical properties: In comparison to quercetin aglycone, the quercetin-3-O-glucoside-γ-cyclodextrin inclusion complex showed a 10.8-fold increase in bioavailability, while the self-emulsifying fenugreek galactomannans and lecithin encapsulation, and lecithin phytosome, showed a 62- and 20.1-fold increase, respectively. 3) Food matrix effects: the addition of dietary fats and fibre increased bioavailability by ∼2-fold. This review summarises key factors that enhance quercetin bioavailability, contributing to the development of more effective and practical quercetin supplements or functional foods for better bioactivity of quercetin in humans.

Currently approved therapies for COVID-19 are mostly limited by their low availability, high costs or the requirement of parenteral administration by trained medical personnel in an in-hospital setting. Quercetin is a cheap and easily accessible therapeutic option for COVID-19 patients. However, it has not been evaluated in a systematic review until now. We aimed to conduct a meta-analysis to assess the effect of quercetin on clinical outcomes in COVID-19 patients. Various databases including PubMed, the Cochrane Library and Embase were searched from inception until 5 October 2022 and results from six randomized controlled trials (RCTs) were pooled using a random-effects model. All analyses were conducted using RevMan 5.4 with odds ratio (OR) as the effect measure. Quercetin decreased the risk of intensive care unit admission (OR = 0.31; 95% confidence interval (CI) 0.10-0.99) and the incidence of hospitalisation (OR = 0.25; 95% CI 0.10-0.62) but did not decrease the risk of all-cause mortality and the rate of no recovery. Quercetin may be of benefit in COVID-19 patients, especially if administered in its phytosome formulation which greatly enhances its bioavailability but large-scale RCTs are needed to confirm these findings. © 2023 John Wiley & Sons Ltd.

Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome these limitations, nanocarrier-based drug delivery systems (NDS) are one of the most effective approaches being extensively explored over the last few decades to improve curcumin's physicochemical and pharmacological effects. Various NDS could provide productive platforms for addressing the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Among the 48 included studies, 3 studies were randomized controlled clinical trials, while 45 studies were animal models. To date, only five curcumin NDS have been studied in healthy volunteers: γ-cyclodextrin, phytosome, liposome, microemulsion and solid dispersion, while most curcumin NDS have been studied in animal models. Most included studies found that NDS could increase oral bioavailability of curcumin as compared to free curcumin. In conclusion, this systematic review showed evidence of the positive effect of NDS for enhancement of oral bioavailability of curcumin. EXECUTIVE SUMMARY: Curcumin is globally recognized for its health benefits, but its clinical application has been limited by its poor aqueous solubility and stability, which causes poor absorption in the gastrointestinal tract (GI tract) via oral administration. Nanocarrier-based drug delivery systems (NDS) are considered as a productive platform to solve the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Overall, most studies found that all studied NDS could increase the absorption of curcumin as compared to free curcumin. Curcumin was rapidly absorbed and exhibited a long residence time after oral administration of curcumin NDS. In summary, this systematic review showed pos

Aim of study is to analyze Bromelain' effects on the most common early complications after BCS (oedema and seroma). From January 2021 to December 2023 a double-blind randomized placebo-controlled trial was performed on 114 candidates for BCS at our Academic Unit. Group A received a supplement of Casperome™-Boswellia Phytosome® + Bromelain (CBB) in combination with alpha-lipoic acid + superoxide dismutase + B and D vitamins + centella asiatica. Group B received a supplement of CBB + placebo. Group C received placebo. The therapies were administrated for 30 days. On GEE logistic regression, drugs combination in A seems to be associated with statistical fewer oedema compared with C (P = 0.018 at 1 day and P = 0.002 after 1 month). Comparing B to C, B gained a significative value after 1 month (P = 0.007). On GEE logistic regression, the drugs combination in A has been associated with statistical fewer seroma compared with C (P = 0.009 at 15thpostoperative day and P < 0.001 after 1 month). B vs C reaches significant values 15 day and 1 month after surgery (P = 0.002 and P < 0.001, respectively). The current study is the first analyzing the employment of CBB association with/without neurotrophic agent on prevention of early complications after BCS. © 2025. The Author(s).

BACKGROUND: Melissa officinalis standardised extracts, characterised by the presence of hydroxycinnamic acids, have been experimentally demonstrated to be endowed with anti-anxiety and anti-insomnia pharmacological actions. These effects, probably attributable, at least in part, to the role played by rosmarinic acid on GABA-T, have not always been observed in a reproducible manner in humans, perhaps due to the poor bioavailability of these compounds. METHODS: as nutraceuticals and botanicals could be an alternative option to prescription medications for alleviating symptoms of mild anxiety and insomnia, we have verified in a prospective, double-blind, placebo-controlled, and cross-over study the supporting role on sleep quality played by a Melissa officinalis highly standardised extract, formulated as Phytosome™ (MOP) to improve the oral bioavailability of its active polyphenolic components. RESULTS: results showed a significant reduction in the ISI score in the treated group, with an average of 6.8 ± 4.1 compared to 9.7 ± 3.7 in the placebo group, indicating a significant reduction of 2.9 points (p = 0.003). The SWS phase duration increased by an average of 15%, while the REM phase decreased by 10%. Additionally, 87% of participants in the treated group reported improved sleep quality, compared to 30% in the placebo group, with significant differences measured by chi-square test (χ2(4) = 21.01, p = 0.0003), highlighting the effects due to Melissa officinalis L. No significant changes in physical activity or anxiety levels were observed. CONCLUSIONS: these findings suggest that MOP may represent a natural and safe alternative to traditional pharmacological treatments for insomnia.

Urinary tract infections (UTIs) are the most common bacterial infections in postmenopausal women, and women with diabetes are possibly at a higher risk. The aim of this study is to evaluate the potential benefit on the prevention of UTI episodes, assessed by urinalysis and urine culture (primary outcome) after two, four and six months, of daily oral dietary supplement (120 mg highly standardized cranberry extract phytosome), compared to placebo, in diabetic postmenopausal women taking SGLT-2 inhibitors. Forty-six subjects (mean age 72.45 ± 1.76) completed the study (23 placebo/23 supplement). Considering UTI episodes, during the six-month supplementation period, an increase of 1.321 (95% CI: -0.322; 2.9650) was observed in the placebo group, while it remained at a steady value of 0.393 (95% CI: -4.230; 5.016) in the supplemented group. Regarding UTI episodes, in both groups, interaction between times for supplementation was statistically significant (p = 0.001). In particular, at follow-up 4, 9% of the placebo group showed infection versus only 3% with cranberry supplementation. Glycaemia and glycated hemoglobin values (secondary outcomes) were not modified at the end of six months with respect to the basal values in both groups, as expected. While in terms of quality of life per the SF-12 health questionnaire, there were no differences between the two groups, an improvement in SF-12 quality of life was observed in both groups (six months vs. basal). In conclusion, highly standardized cranberry extract phytosome supplementation reduced UTI recurrence.

BACKGROUND: Chronic fatigue (CF) is a complex phenomenon without clear etiology that may require long-term treatment, but to date, no specific therapy has been identified for it. Some botanicals might be helpful in the management of CF. Among these botanicals, quercetin demonstrates its capacity to modulate multiple biological pathways and acknowledged major properties in CF: antioxidant, anti-inflammatory, immunomodulating, improving exercise endurance, enhancing mitochondrial biogenesis, repairing mitochondrial dysfunction. PURPOSE: Given this background, the aim of this study was to evaluate if a 2-month period of daily Quercetin Phytosome™ 500 mg supplementation is of benefit for the relief of CF. METHODS: The primary end point has been the evaluation of fatigue, by Fatigue Impact Scale (FIS-40). The secondary end points have been the assessment of sleep, by Pittsburgh Sleep Quality Index (PSQI), evaluation of muscle performance, by short physical performance battery and by wearable armband-shaped sensor in order to evaluate the number of steps, body composition, by DXA and quality of life by Short-Form 12-Item Health Survey (SF-12). RESULTS: Seventy-eight subjects (42 F; 36 M) (mean age 56 ± 9) reporting CF symptoms, completed the study (placebo/supplement 38/40). The FIS-40 mean difference changes between groups (supplement minus placebo) was - 10.583 points (CI95% -11.985; -9.182) (p < 0.001). Also, statistically significant changes between groups have been recorded in Pittsburgh Sleep Quality Index - 2.040 points (CI95%: -2.770; -1.309), p < 0.01), number of steps 1443.152 (CI95%: 1199.556; 1686.749), and SPPB (score) 0.248 (CI95%: 0.105; 0.391) (p < 0.001). CONCLUSION: The quercetin supplementation counterbalances CF symptoms.

Menopause is characterized by weight gain and increased visceral fat, which acts as an endocrine organ secreting proinflammatory adipocytokines, with consequent increased risk of metabolic disorders. The aim of this double-blind, placebo-controlled randomized trial was to evaluate the effects of a 60-day dietary supplementation using Camellia sinensis leaf extract on adipose tissue dysfunction in overweight or class I obese post-menopausal, sedentary women. Primary endpoints were the respiratory quotient (RQ), the percentage of carbohydrates (%CHO), the percentage of fat oxidation (%FAT), and the resting energy expenditure (REE) measured by indirect calorimetry. Secondary endpoints included body composition, by dual x-ray absorptiometry (DXA), glucose profile, lipid profile, inflammatory state, liver and kidney function, hormonal status regarding satiety, and status of catecholamines. Twenty-eight women were randomized into two groups: 14 (BMI 31.1 ± 3.5) were supplemented and 14 (BMI 31.9 ± 2.2) received placebo. In regards to the between-group differences over time (β), a statistically significant difference between the supplemented and placebo group was observed for: RQ (β = -0.04, p = 0.009), % fat oxidation (β = 11.04, p = 0.0006), insulin (β = -1.74, p = 0.009), HOMA (β = -0.31, p = 0.02), waist circumference (β = -1.07, p = 0.007), REE (β = 83.21, p = 0.009), and CRP (β = -0.14, p = 0.02). These results demonstrate that a 60-day green tea extract supplementation counteracts the dysfunction of adipose tissue in overweight post-menopausal and class I obese women.

OBJECTIVE: The present study aimed to investigate the effects of a 4-week repeated oral intake of a quercetin-containing supplement on allergen-induced reactions and relative subjective symptoms in Japanese adults who complained of discomfort in the eyes and nose. SUBJECTS AND METHODS: A randomized, placebo-controlled, double-blind parallel-group study was conducted on 66 subjects (22-78 years old) with allergic symptoms of pollinosis. The subjects were given the test product (200 mg quercetin) or the control product (vehicle) daily for 4 weeks. The Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) scores and other tests were examined in each subject before and after starting the product intake. A new food-grade bioavailable formulation of quercetin, Quercetin phytosome®, was used. RESULTS: At 1:4 weeks after the start of the supplement intake, several scores of JRQLQ, including allergic symptoms, such as eye itching, sneezing, nasal discharge, and sleep disorder, were significantly improved in the quercetin-containing supplement group compared with the placebo group. Furthermore, the quality of life of these subjects significantly improved based on the original questionnaire and visual analog scale. Minor notable adverse effects were noted throughout the study. CONCLUSIONS: The results indicated that oral intake of quercetin-containing supplements might effectively reduce some allergy symptoms derived from pollinosis.

We aimed to evaluate if dietary supplementation with a nutraceutical compound (Eufortyn® Colesterolo Plus) containing standardized bergamot polyphenolic fraction phytosome (Vazguard®), artichoke extract (Pycrinil®), artichoke dry extract. (Cynara scolymus L.), Q10 phytosome(Ubiqosome®) and zinc, could positively affect serum lipids concentration, systemic inflammation and indexes of non-alcoholic fatty liver disease (NAFLD) in 60 healthy subjects with polygenic hypercholesterolemia. Participants were adhering to a low-fat, low-sodium Mediterranean diet for a month before being randomly allocated to 8-week treatment with 1 pill each day of either Eufortyn® Colesterolo Plus or placebo. Dietary supplementation with Eufortyn® Colesterolo Plus was associated with significant improvement in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP) and endothelial reactivity (ER) in comparison with baseline, and with significant reductions in waist circumference, TC, LDL-C, LDL-C/HDL-C, lipid accumulation product and fatty liver index compared to placebo. The study shows that dietary supplementation with standardized bergamot polyphenolic fraction phytosome, artichoke extracts, Q10 phytosome and zinc safely exerts significant improvements in serum lipids, systemic inflammation, indexes of NAFLD and endothelial reactivity in healthy subjects with moderate hypercholesterolemia.

Acute diarrhea is a frequent problem worldwide, mostly due to gastrointestinal infections or food poisoning. Boswellia serrata could be active in the treatment of acute diarrhea due to its anti-inflammatory, antispasmodic, and antimicrobial activity. In this randomized, double-blind, placebo-controlled clinical study, 49 adults with acute diarrhea were randomly allocated to receive 250 mg of a lecithin-based delivery form of Boswellia serrata (CASP) or placebo for 5 days. The time it took to become healthy with stoppage of diarrhea (primary end point) was significantly shorter in the intervention group (3.08 vs. 4.44 days: p-value < 0.0001). The probability of subjects treated with CASP to recover sooner was equal to 80.2%. A significantly lower number of stools was observed in the CASP group over time (β = −0.17, p-value < 0.0001). A significant difference was observed between the two groups for abdominal pain, nausea, and GAE (global assessment of efficacy). In conclusion, the lecithin-based delivery form of Boswellia serrata extract could be a useful addition to the treatment of acute diarrhea in adults. CASP is safe and reduces the time it takes to become healthy, the frequency of stools, the abdominal pain and nausea of subjects with acute diarrhea. Further studies are needed to confirm these promising results.

Coenzyme Q10 (CoQ10 ) is a natural antioxidant compound that prevents the vascular damage induced by free radicals and the activation of inflammatory signaling pathways. Supplementation with CoQ10 is safe though its bioavailability is generally low, as far as variable depending on the pharmaceutical form of preparation. Recently, the development of phytosome technology has improved the bioavailability of CoQ10 and definitely facilitated its effective use in clinical practice. The present double-blind, randomized, placebo-controlled, crossover clinical study aimed to investigate the effect on endothelial reactivity and total antioxidant capacity (TAC) of either acute and chronic supplementation with CoQ10 phytosome in a sample of 20 healthy young nonsmoking subjects. CoQ10 phytosome supplementation acutely improved endothelial reactivity in comparison with baseline and placebo (+4.7% ± 0.9% vs. -0.1 %± 0.3% p < 0.05). Middle-term supplementation of the tested pharmaceutical formulation of CoQ10 significantly improved mean arterial pressure (-2.2 ± 1.1 mmHg vs. 0.2 ± 0.7 mmHg, p < 0.05 vs. placebo) and TAC (+29.6% ± 3.2% vs. +1.9% ± 0.8%, p < 0.05 vs. placebo). Endothelial reactivity improved compared with baseline following middle-term dietary supplementation with CoQ10 phytosome (+5.7% ± 1.1%, p < 0.05). © 2022 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.

Bloating is a symptom frequently reported by subjects with irritable bowel syndrome (IBS) and small bowel dysbiosis, and Low FODMAP’s diet (LFD) has been used to treat them. Extracts of Curcumalonga and Boswelliaserrata share anti-inflammatory and antimicrobial effects that could be useful in the management of these clinical conditions. The aim of this study was to evaluate the efficacy of curcumin and boswellia extracts (as Curcumin Boswellia Phytosome, CBP) and LFD on the relief of abdominal bloating in IBS subjects with small bowel dysbiosis, in comparison to LFD alone, in a 30-day supplementation, randomized trial. IBS participants were randomized to either the intervention (500 mg bid of CBP and LFD) or control arm (LFD). Small bowel dysbiosis has been defined by an increase of urinary indican with normal urinary skatole. A total of 67 subjects were recruited. The intervention group (33 subjects) showed a significant decrease (p < 0.0001) of bloating, abdominal pain, and indican values at the end of the study, when compared to the control group (34 subjects). Moreover, the subjects of the intervention group showed a significantly better (p < 0.0001) global assessment of efficacy (GAE) as compared to controls. In conclusion, in subjects with IBS and small bowel dysbiosis, abdominal bloating can be successfully reduced with a supplementation with CBP and LFD.

Background/Objectives: The flavonoid quercetin (Q) has recently been suggested as a natural anti-aging and senolytic agent. However, its low stability and poor oral bioavailability may limit its efficacy. To address this, we investigated whether a lecithin-based formulation of Q, Quercefit™ (QF), enhances stress resistance and delays aging in vivo. Methods: The nematode Caenorhabditis elegans was used as an animal model to evaluate the effects of QF under physiological and stress conditions. Unformulated Q was administered as a control. Worm survival, healthspan, resistance to thermal and oxidative stress, and expression of stress- and longevity-related genes were assessed. All the experiments were conducted at least in triplicate, each including a minimum of 15 worms. The data were analyzed using Student's t-test, one-way or two-way ANOVA, and Bonferroni's post hoc test. Results: One hundred micromolar Q administered in QF was more effective than equimolar unformulated Q in increasing the worms' ability to resist acute thermal stress at 35 °C (tested on 75 worms/group) and oxidative stress caused by 0.5 mM hydrogen peroxide (tested on 75 worms/group). In this last case, the protective effect of QF was similar to that of N-acetylcysteine and ascorbic acid. Under experimental conditions mimicking the long-term consequences of thermal stress, QF, like Q, increased the worms' lifespan and healthspan by approximately 50%, counteracting the age-related decline associated with stress (120 worms/group). These benefits are supported by QF's capacity to act as a reactive oxygen species scavenger; suppress heat-shock element gene transcription activated by thermal stress, such as hsp-16.2 and hsp-70, and stimulate the sod-3 and gst-4 genes that are involved in antioxidant and detoxification responses. Conclusions: These findings suggest that Q, when administered in the QF formulation, can act at the transcriptional level to protect against aging induced by stressful conditions.

BackgroundInterstitial cystitis (IC), a chronic inflammatory condition of the urinary bladder characterized by pain and difficulties with urination, has limited treatment options. Beta-caryophyllene (BCP) is a sesquiterpene with anti-inflammatory and analgesic properties, but has poor water solubility and limited intestinal absorption which may limit oral bioavailability. Indena Phytosome® is a proprietary food-grade lecithin-based delivery system that optimizes the bioavailability and pharmacokinetic profile of natural phytochemicals like BCP by producing a stable solid dispersion suitable for oral delivery.ObjectiveTo examine the therapeutic potential of an oral BCP Indena Phytosome® formulation (BCP Indena Phytosome®) for the treatment of IC.MethodsFemale BALB/c mice were pre-treated with BCP Indena Phytosome® or empty Indena Phytosome® vehicle, then IC was induced using lipopolysaccharide. 24 h later, inflammation was evaluated using intravital microscopy and histology. Pain was evaluated using behavior scoring and von Frey asethesiometry.ResultsPre-treatment with BCP Indena Phytosome® reduced leukocyte adhesion, histology scores, and behavior scores in IC mice, indicating a reduction in inflammation and pain. Lipopolysaccharide administration did not alter leukocyte rolling, capillary perfusion, or von Frey scores.ConclusionsOral BCP Indena Phytosome® effectively reduces pain and inflammation in experimental IC by decreasing leukocyte adhesion and extravasation in the bladder.

Terpenoids represent a large class of bioactive natural compounds with promising pharmacological properties, including anti-inflammatory, antimicrobial, and anticancer activities. However, their clinical application is often limited by poor aqueous solubility, low membrane permeability, and suboptimal bioavailability. Phytosomal delivery systems have emerged as a promising strategy to enhance the pharmacokinetic performance of plant-derived compounds by forming molecular complexes between bioactive molecules and phospholipids. This review critically examines the structural principles, preparation methods, physicochemical characterization, and biological performance of terpenoid phytosomes. Particular attention is given to the molecular interactions between terpenoids and phospholipids that govern complex formation and vesicular assembly. The review also summarizes current analytical techniques used to confirm phytosome formation and discusses the influence of formulation parameters, including phospholipid composition and molar ratios, on stability and biological activity. In addition, emerging insights from molecular modeling and membrane interaction studies are considered to better understand the mechanisms underlying improved drug delivery. Finally, challenges related to safety assessment, manufacturing scalability, and clinical translation of phytosomal systems are discussed. Overall, terpenoid phytosomes represent a promising nanodelivery platform capable of improving the pharmacokinetic profile and therapeutic potential of terpenoid compounds.

INTRODUCTION: Type 2 diabetes management remains challenging because of low bioavailability, side effects, and poor compliance with oral therapies. Transdermal delivery methods offer a non-invasive therapeutic approach with sustained delivery, which avoids first-pass metabolism. METHODS: A total of 207 different phytochemicals were virtually screened using i-dock against the diabetic target, PPAR-γ. Subsequently, three matrix-type transdermal patches were developed: a patch containing pure baicalin, a standard patch containing metformin, and a baicalin-loaded phytosomal patch. Phytosomes loaded with baicalin were optimized by using Central Composite Design and evaluated for their physicochemical properties, drug content, physical strength, in vitro, and ex vivo studies. In vivo antidiabetic efficacy was also studied in diabetic Wistar rats over 21 days, followed by a comparison of all formulations, including histopathological analysis of pancreatic tissue. RESULTS: Molecular docking studies showed promising results; baicalin has a high binding affinity for PPAR-γ (-9.8 kcal/mol). The optimized phytosomal patch confirmed a uniform drug content (91.4 ± 0.12 %) and showed sustained release over 12 hours. The ex vivo permeation study showed a significantly higher skin flux for the phytosomal patch (83.6%). In vivo studies confirmed that baicalin-loaded phytosomal patches showed significant blood glucose reductions (223 ± 0.32 to 96 ± 0.38 levels by Day 21), a comparable efficacy to standard metformin patches (224 ± 0.37mg/dL to 94 ± 0.34 mg/dL by Day 21). DISCUSSION: The enhanced skin permeation, penetration, and sustained-release exhibited by the phytosomal transdermal patch can be explained by the phospholipid-based shell structure, leading to better affinity with the skin, facilitating retention of the drug. The comparable glycemic control observed with metformin indicates that baicalin-loaded phytosomal transdermal patches can achieve effective therapeutic concentrations via transdermal delivery, which is corroborated across two studies. These observations are consistent with previous literature documenting improved solubility and bioavailability of plant-derive

Parkinson’s disease (PD) is an age-associated neurodegenerative disorder. While allopathic treatments offer symptomatic relief, they are often associated with side effects and reduced long-term efficacy. Hence, there is a need to bridge the gap between allopathic therapies, plant bioactives and optimized delivery systems for effective neurodegenerative disease Parkinsonism management. In contrast, plant-based therapies such as Premna integrifolia L. offer multifaceted mechanisms, enhanced bioavailability through nanophytosome delivery, blood-brain barrier permeability, and cost-effectiveness. This study aimed to evaluate, characterize, and optimize nanophytosome-loaded P. integrifolia in a haloperidol-induced PD model. Hydroalcoholic extract (HEPI, 250 mg/kg), phytosomal formulation (PHYPI, 250 mg/kg), and fraction (FPI, 100 mg/kg) were administered over 36 days. In silico molecular docking and simulations identified olivil as a potent constituent with high binding affinity to GRIA2 and ADRB2, surpassing Levodopa. Phytosomes were prepared using thin-film hydration and characterized via particle size, PDI, zeta potential, SEM, TEM, FTIR, and LC-MS. In vitro assays evaluated total phenolic/flavonoid content, oxidative stress markers (SOD, GSH, MDA), protein and dopamine levels, and inhibition of AChE, BChE, and MAO-B. In vivo assessments included behavioral tests (catalepsy, actophotometer, balance beam, rotarod) and histopathological analysis of the hippocampus and cortex. PHYPI250 significantly improved motor performance and elevated dopamine levels, while reducing oxidative stress. Olivil-GRIA2 complexes showed enhanced stability with up to five hydrogen bonds. Pro-inflammatory cytokines IL-6 and TNF-α were markedly suppressed. Enzymatic assays showed significant inhibition of AChE, BChE, and MAO-B. Histological evaluation showed preserved neuronal integrity in CA1 and CA3 regions with minimal degeneration. P. integrifolia phytosomes exhibit promising therapeutic potential in PD through antioxidant, anti-inflammatory, and neuroprotective mechanisms. Olivil demonstrates superior molecular binding and stability.

Anxiety disorders are among the most common mental health illnesses in the world, impacting millions of people from a wide range of backgrounds. Herbal anxiolytics have gained significant attention as natural therapeutic alternatives. However, many of these botanical extracts exhibit poor bioavailability, limiting their therapeutic efficacy. Phytosome technology has appeared as a cutting-edge method of drug delivery intended to improve the bioavailability and efficacy of herbal compounds. This review comprehensively explores the potential of phytosomes to improve the pharmacokinetics and bioavailability of anxiolytic herbs, focusing on their formulation strategies, delivery advantages, and the prospects for their application in anxiety management. While a substantial body of studies has examined the development and formulation of phytosomes for various therapeutic applications, few have specifically evaluated their anxiolytic properties. Additionally, this paper examines safety considerations, regulatory aspects, and future research directions essential for optimizing phytosome-based anxiolytic interventions. By bridging traditional herbal medicine with advanced drug delivery systems, phytosomes present a transformative strategy to enhance the therapeutic bioavailability and efficacy of herbal-based treatments for anxiety disorders.

BACKGROUND: Melissa officinalis L. (lemon balm) is a botanical support widely used for its calming and sleep-promoting properties. OBJECTIVE: To evaluate the impact of daily supplementation with Melissa phospholipids (MOP) at 200 or 400 mg for 3 weeks on sleep quality and psychological well-being in adults with emotional distress and poor sleep quality. DESIGN: This prospective, open-label, dose-comparison clinical study enrolled 32 adults with poor sleep quality and/or clinically significant emotional distress. Participants received daily supplementation with either 200 or 400 mg/day MOP for 3 weeks. Sleep quality (primary endpoint) was assessed using the Pittsburgh Sleep Quality Index (PSQI) at baseline (T0), and week 3 (T1). Secondary endpoints included depression, anxiety, and stress, positive and negative affect, mental well-being, and quality of life. Safety was also assessed through adherence monitoring, documentation of side effects or adverse events, and by routine blood biochemistry parameters of liver and renal functions. RESULTS: PSQI scores significantly improved over time (P < 0.0001), with greater and earlier benefits at 400 mg/day (-30% vs. -15%; P < 0.05). The 400 mg dose also produced significant reductions in depression (-26%), anxiety (-18%), and stress (-22%) scores (all P < 0.001), together with increased positive and negative affect together with Warwick-Edinburgh Mental Well-Being Scale (+15%). Quality of life improved across total score (33%) and its four domains, with significant results in physical well-being (P < 0.05). No statistically significant changes in safety parameters were detected and no adverse effects were reported. DISCUSSION: MOP, particularly at 400 mg/day, confirmed to significantly improve sleep and life quality, mood, and overall mental well-being. CONCLUSION: These findings support and extend the health benefits of MOP as a well-tolerated, safe natural approach in a dose-dependent frame to managing sleep quality and emotional distress. Future placebo-controlled trials are warranted to confirm these results and further elucidate the underlying mechanisms of action. © 2026 M. Rondanelli et al.

Background: Chronic neuropathic low back pain (LBP) is a prevalent health condition and difficult to treat. Conventional therapies often provide limited relief and raise safety concerns. Supplemental palmitoylethanolamide (PEA), an endogenous fatty acid amide with analgesic and anti-inflammatory properties, has shown benefits in neuropathic pain, but its application as a supportive strategy has been limited by poor oral bioavailability. Objectives: This study aimed to investigate a phospholipid-based palmitoylethanolamide formulation (PEA-PL, Cronilief™), developed using Phytosome™ delivery technology, with respect to solubility optimization, systemic exposure, and associated clinical effects in individuals with chronic neuropathic LBP. Methods: PEA-PL solubility was assessed in fasted-state simulated intestinal fluid and compared with unformulated PEA. Plasma PEA concentrations were evaluated in healthy volunteers after 2 weeks of supplementation with unformulated PEA (300 mg/day) or PEA-PL (300 or 600 mg/day). Clinical efficacy was assessed in a double-blind, placebo-controlled randomized, trial in which 120 adults with neuropathic LBP received PEA-PL 600 → 300 mg (n = 40), PEA-PL 450 mg (n = 40), or placebo (n = 40), daily for 8 weeks in addition to Standard of Care. Primary outcomes were effects on neuropathic pain (Douleur Neuropathique 4, DN4) and its intensity (Numeric Pain Rating Scale, NPRS). Secondary outcomes included effect on functional disability (Oswestry Disability Index, ODI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), quality of life (QoL) (SF-12), and concomitant analgesic use. Safety was monitored throughout the 8-week supplementation period. Results: PEA-PL increased PEA solubility approximately eight-fold and resulted in higher plasma PEA concentrations than unformulated PEA. Both PEA-PL regimens significantly improved pain, functional disability, sleep, and QoL outcomes versus placebo (all p < 0.0001), with greater effects for the 600 → 300 mg regimen. Analgesic discontinuation occurred more frequently in PEA-PL groups (65-70%). Supplementation was well tolerated. Conclusions: A phospholipid-based (Phytosome™) PEA formulation (C

145. Oxid Med Cell Longev. 2025 Nov 21;2025:9871678. doi: 10.1155/omcl/9871678. eCollection 2025. Correction to "Antimetabolic Syndrome Effect of Phytosome Containing the Combined Extracts of Mulberry and Ginger in an Animal Model of Metabolic Syndrome". [No authors listed] Erratum for Oxid Med Cell Longev. 2019 Nov 11;2019:5972575. doi: 10.1155/2019/5972575. [This corrects the article DOI: 10.1155/2019/5972575.].

This study, for the first time, evaluated the therapeutic potential of resveratrol-loaded phytosome nanoparticles (RES-PNPs) against Ehrlich ascites carcinoma (EAC) and associated testicular dysfunction, compared with free resveratrol (RES). Ninety male Swiss albino mice were divided into six groups, (1) control; (2) RES (10 mg/kg/day, orally); (3) RES-PNPs (10 mg/kg/day, orally); (4) EAC, induced by intraperitoneal injection of 2.5 × 106 cells; (5) EAC + RES; and (6) EAC + RES-PNPs, treated for 20 days post-tumor inoculation. Tumor growth parameters, reproductive function, antioxidant enzyme activities, inflammatory mediators, apoptotic markers, and histopathological features were assessed. Additionally, in silico docking was performed to identify molecular targets mediating RES effects. RES-PNPs markedly reduced tumor volume, ascitic cell viability, and body weight gain while significantly prolonging survival compared with free RES. Molecular assays revealed enhanced pro-apoptotic signaling (increased Bax and Caspase-3, decreased Bcl-2), suppression of vascular endothelial growth factor (VEGF), and inhibition of COX-2 with reduced TNF-α, IFN-γ, and IL-1β levels. RES-PNPs also restored semen quality, normalized reproductive hormones, elevated antioxidant enzyme activities, and reduced lipid and protein oxidation, corroborated by notable testicular histological protection. In conclusion, Resveratrol-loaded phytosome nanoparticles provide superior anti-tumor, antioxidant, anti-inflammatory, and pro-apoptotic benefits compared with free RES. These findings highlight RES-PNPs as a potent and stable nanoformulation for effective EAC suppression and preservation of male reproductive integrity.

This study evaluated the effect of a nutraceutical supplementation (NS) and Mediterranean hypocaloric diet (MHD) on hepatic steatosis indices (HSIs), γ-glutamyl transferase (γGT), and lipid profile in adults with hyperlipidemia and nonalcoholic fatty liver disease (NAFLD). In vitro study on HepG2 cells explored potential molecular mechanisms. A retrospective study was conducted on 45 overweight/obese subjects (19 M) prescribed MHD with/without NS. Anthropometric data, biochemical parameters, HSIs, and γGT were collected at baseline and after 3 months. In vitro, cells were pretreated with single and mixed NS components and then with tumor necrosis factor α (TNFα) or fatty acids (FAs). Antioxidant and antiinflammatory activities were evaluated by fluorescence assays and quantitative polymerase chain reaction or enzyme-linked immunosorbent assay; antiapoptotic effects by Western blot. After 3 months, all subjects improved anthropometric and biochemical parameters but only the combined MHD and NS treatment significantly reduced insulin resistance, HSIs, low-density lipoprotein cholesterol, and γGT. In vitro, treatment with mixed NS components decreased TNFα-/FAs-induced reactive oxygen species. Combined treatment also modulated the inflammatory response by lowering interleukin-6 and interleukin-1β, increasing interleukin-10 and pro-caspase 8 expression. These findings suggest that NS, due to its antiinflammatory properties, represents a promising strategy for NAFLD management. © 2025 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.

Phyllanthus amarus has been a cornerstone of traditional medicine in Africa, renowned for its hepatoprotective, antiviral, and antidiabetic properties. However, its therapeutic applications in modern medicine are limited by poor bioavailability due to challenges such as low solubility, rapid metabolism, and instability of its bioactive compounds. Addressing these limitations is essential for optimizing its pharmacological potential and enabling its broader integration into evidence-based healthcare systems. This review highlights various strategies to enhance the bioavailability of Phyllanthus amarus, including nanotechnology, phytosome technology, biopiperine supplementation, fermentation, and sustained-release formulations. These approaches not only improve solubility and absorption but also stabilize the herb's phytochemicals, ensuring better therapeutic outcomes. Moreover, the review explores how bioavailability enhancement can transform Phyllanthus amarus into a standardized therapeutic agent, bridging the gap between traditional and modern medicine. Enhancing the bioavailability of Phyllanthus amarus has profound implications for healthcare in Africa. Improved formulations can amplify its therapeutic efficacy in traditional practices, while enabling its adoption in modern pharmacology through clinical validation and pharmaceutical-grade products. By addressing cost, accessibility, and regulatory challenges, these advancements can ensure that Phyllanthus amarus continues to be a vital, sustainable resource in addressing pressing health issues across the continent.

BACKGROUND: Hyperuricemia is associated with several metabolic and cardiovascular disorders, and traditional treatments, such as xanthine oxidase (XO) inhibitors, often have limitations, such as severe hypersensitivity reactions or ineffectiveness in achieving target serum urate levels in some patients. Quercetin, a naturally occurring flavonoid, has shown potential as a hypouricemic agent through XO inhibition. OBJECTIVE: This study aims to evaluate the potential hypouricemic effect of Quercetin Phytosome™ (QP) supplementation across three cohort studies involving healthy adults with various metabolic health profiles, exploring its potential as a safe, effective intervention for hyperuricemia. METHODS: Clinical data collected in various clinics in Italy between September 2021 and April 2024 under real-life clinical settings from three distinct cohort studies, were analyzed. Cohort 1 consisted of 164 healthy participants (87 QP-treated, 77 probiotic Streptococcus salivarius (S. salivarius) K12-treated) who were monitored for 90 days. Cohort 2 included 22 mildly hyperuricemic adults with metabolic disorders receiving QP, while Cohort 3 comprised 64 obese adults with hypercholesterolemia, further divided into moderately hyperuricemic QP-treated group (n = 20), a moderately hyperuricemic Berberine Phytosome™ and monacolins (BM)-treated group (n = 22), and a normouricemic BM-treated group (n = 22). QP was administered at 400 mg of quercetin daily in all cohorts. Primary endpoints were reductions in serum uric acid levels, while secondary outcomes included effects on lipid profile, glycemia, liver enzymes, and treatment tolerability. RESULTS: In Cohort 1, QP significantly reduced uric acid levels by 15.2% in males and 13.8% in females, with no significant changes observed in the probiotic group. Cohort 2 showed a significant 13.1% reduction in uric acid (p < 0.01) and a concurrent 10.2% reduction in triglycerides (p < 0.05). In Cohort 3, QP led to a 13.7% decrease in uric acid and a 20.8% reduction in triglycerides (p < 0.01), with no significant uric acid changes in the BM-treated group. QP was well tolerated across all cohorts, with minimal, transient side effects.

BACKGROUND: Small bowel dysbiosis (SBD) is a frequent finding in subjects with irritable bowel syndrome (IBS). The sunflower lecithin (phytosome) formulation of Curcuma longa and Boswellia serrata demonstrated beneficial effects on intestinal microbiota. This study aimed to evaluate the impact of a lecithin-based delivery formulation of Curcuma longa and Boswellia serrata extracts (CUBO) on SBD in IBS subjects. SUBJECTS: Forty-nine adult subjects with IBS and SBD were randomly supplemented for 30 days with CUBO and a low-FODMAP diet (LFD) (intervention) or with LFD and placebo (control group). RESULTS: The intervention group showed a significant reduction in urinary indican (p < 0.001), which was the marker of SBD, and of abdominal bloating (p < 0.001) and abdominal pain (p < 0.001). The pre-post control group analysis did not evidence significant differences. The comparison between the two groups (net effect in intervention minus control subjects) showed that the changes differ significantly for urinary indican p < 0.001 (-42.88; 95% CI: -62.04 to -23.72), abdominal bloating p < 0.001 (-1.50; 95% CI: -1.93 to -1.07), and abdominal pain p < 0.001 (-2.37; 95% CI: -3.61 to -1.13) and for the global assessment of efficacy (p < 0.001). The efficacy was 20% greater in males than in females. CONCLUSIONS: In IBS subjects, the intervention with CUBO and LFD shows a significantly higher reduction in SBD, abdominal pain, and bloating compared to LFD and placebo. Additional research is needed to confirm these data.

Background: Available evidence from randomized clinical trials is contrasting and definitely inconclusive in determining whether or not CoQ10 dietary supplementation is advisable in patients with statin intolerance or poor statin tolerability. Methods: This randomized, double-blind, placebo-controlled clinical study aimed at investigating the effect of chronic dietary supplementation with coenzyme Q10 (CoQ10) phytosome on physical performance in older adults with a ≥3-month history of statin-associated asthenia. The study's participants were randomized to either a placebo or 300 mg daily CoQ10 phytosome (equivalent to 60 mg CoQ10; Ubiqsome®, Indena SpA, Milan, Italy). Asthenia, handgrip strength (HGs), 2-min step test (2MST), and 1-min sit-to-stand (STS) repetitions were assessed at baseline and at 8-week follow-up. Results: After the first 4 weeks of dietary supplementation, individuals taking CoQ10 phytosome showed a greater improvement in asthenia compared to the placebo group (p < 0.05). Even more significantly, at 8-week follow-up, participants receiving CoQ10 showed substantial improvements in asthenia (-30.0 ± 20.0%), HGS (+29.8 ± 3.6%), 2MST (+11.1 ± 1.8%), and 1-min STS repetitions (+36.4 ± 3.9%) compared to both baseline and placebo (p < 0.05). Conclusions: According to our findings, chronic dietary supplementation with CoQ10 phytosome significantly enhances physical performance in older adults with statin-associated asthenia. This could have relevant implications for improving the compliance of older adults with statin treatment.

Background: Melissa officinalis L. (MO), commonly known as lemon balm, a member of the mint family, is considered a calming herb. In various traditional medicines, it has been utilized to reduce stress and anxiety and promote sleep. A growing body of clinical evidence suggests that MO leaf extract supplementation possesses considerable neuropharmacological properties. However, its possible mechanism of action largely remains unknown. Objective: In the present in vitro studies, we comparatively investigated the central nervous system (CNS)-calming and antioxidative stress properties of an innovative standardized phospholipid carrier-based (Phytosome™) MO extract (Relissa™) vs. an unformulated dry MO extract. Methods: The neuropharmacological effect of the extract was studied in the anti-depressant enzymes γ-aminobutyrate transaminase (GABA-T) and monoamine oxidase A (MAO-A) assays and SH-SY5Y cells brain-derived neurotrophic factor (BDNF) expression assay. The neuroprotective effect of the extract against oxidative stress was assessed in SH-SY5Y cell-based (H2O2-exposed) Total Antioxidant Status (TAS) and Total Reactive Oxygen Species (ROS) assays. The cytotoxic effect of the extract was evaluated using MTT and LDH assays. The extract antioxidant effect was also evaluated in cell-free chemical tests, including TEAC-ABTS, DPPH, Ferric Reducing Antioxidant Power (FRAP), Oxygen Radical Antioxidant Capacity (ORAC), and Hydroxyl Radical Antioxidant Capacity (HORAC) assays. Results: Relissa™ exhibited high GABA-T inhibitory activity, IC50 (mg/mL) = 0.064 vs. unformulated dry MO extract, IC50 (mg/mL) = 0.27. Similar inhibitory effects were also observed for MAO-A. Relissa™ demonstrated an improved neuroprotective antioxidant effect on SH-SY5Y cells against H2O2-induced oxidative stress. Compared to unformulated dry MO extract, Relissa™ exerted high protective effect on H2O2-exposed SH-SY5Y cells, leading to higher cells BDNF expression levels. Moreover, cell-free chemical tests, including TEAC-ABTS, DPPH radical scavenging, FRAP, ORAC, and HORAC assays, validated the improved antioxidant effect of Relissa™ vs. unformulated dry MO extract. Conclusion: The results of the

Background: Berberine is a poorly absorbed natural alkaloid widely used as nutraceutical to counteract diarrhoea and to lower cholesterol and hyperglycaemia. It has also been reported to reduce signs and symptoms of polycystic ovary syndrome (PCOS). Objective: To explore, through a multi-centric, randomized, controlled and prospective study, the possible role played by a form berberine that is more easily absorbed (Berberine Phytosome®, BP) in 130 Pakistani women with a diagnosis of PCOS and fertility problems due to menstrual and ovary abnormalities. Results: Ninety days of supplementation with BP, administered at 550 mg x2/die, determined (i) resumption of regular menstruation in about 70% of women (versus 16% in the control group; p < 0.0001), (ii) normalization of the ovaries anatomy in more than 60% of women (versus 13% in the control group; p < 0.0001), (iii) acne improvement in 50% of women (versus 16% in the control group; p = 0.0409) and (iv) hirsutism reduction in 14% of women (versus 0% in the control group; p = 0.0152). The metabolic and the hormonal profiles of the women in the two groups did not significantly differentiate at the end of the study. BP was well-tolerated and no specific side-effects were registered. Respectively after one, two and 8 years of trying, three women supplemented with BP became and are currently pregnant. Conclusion: Our study showed the positive effects of BP supplementation in women with PCOS and confirmed the high safety profile of this nutraceutical. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05480670.