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BACKGROUND: Echinacea purpurea is widely utilized in dietary supplements, nutraceuticals, and herbal medicine, yet its effectiveness and safety for children remain debated. OBJECTIVE: To evaluate the effectiveness and safety of E. purpurea in the treatment of upper respiratory tract infection (URTI) and otitis media (OM) in children. DATA SOURCES: Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, PubMed from January 2000 to December 2023. METHODS: This systematic review and meta-analysis were conducted and reported according to the PRISMA 2020 Checklist and Cochrane Training 2022 guidelines. RESULTS: 9 randomized controlled trials with 1518 participants in the treatment group, 1651 participants in the placebo control group, met the selection criteria. Products derived from E. purpurea are highly diverse, utilizing different plant parts such as roots, leaves, and flowers, available in various dosage forms like capsules and extracts, and manufactured in numerous countries worldwide. Risk of bias was assessed according to the PEDro scale with 3 studies of excellent quality, 5 studies of high quality and 1 study of moderate quality. The meta-analysis found that E. purpurea significantly benefits URTI, reducing treatment duration (SMD = -0.19, 95 % CI [-0.30; -0.09], p < 0.01), incidence (RR = 0.81, 95 % CI [0.75; 0.87]), and antibiotic use (RR = 0.18, 95 % CI [0.13; 0.25], p < 0.01). However, adverse events were moderately increased (RR = 1.38, 95 % CI [1.08; 1.78]), though generally mild. For OM, E. purpurea lowered episode incidence (RR = 0.56, 95 % CI [0.44; 0.73], p < 0.01) but did not shorten treatment duration (p = 0.10). Its effectiveness may be limited due to OM's bacterial etiology, often requiring antibiotics. While E. purpurea may help reduce recurrence, it is unlikely to speed recovery. Further research on optimal formulations and dosages is needed. The publication bias of pooled results as assessed by the funnel plot showed that the studies had certain bias, largely due to heterogeneity between studies. CONCLUSION: The meta-analysis of nine studies found that E. purpurea was effective in reducing the duration of treat

Athletes are increasingly relying on natural supplements to improve athletic performance. Echinacea, a common herbal supplement, has been studied for its potential erythropoietin-enhancing effects, with mixed results in the literature. The purpose of this meta-analysis is to determine whether echinacea supplementation has erythropoietic or ergogenic effects in athletes. A search strategy was developed to identify trials studying the impact of echinacea supplementation on erythropoiesis and maximal oxygen uptake. The database search yielded 502 studies, 496 of which were excluded in the two-reviewer screening process. Six studies with a total of 107 athletes were included in the analysis. For hemoglobin and hematocrit levels, there were small, positive effect sizes when comparing the difference in pre- and post-intervention levels between the echinacea and placebo groups, at 0.38 (p = 0.02, 95% CI -0.04-0.80, I2 = 70%) and 0.34 (p < 0.01, 95% CI -0.10-0.78, I2 = 86%), respectively, though they did not reach statistical significance. There was also no statistically significant change in erythropoietin (effect size -0.29, p = 0.05, 95% CI -0.75-0.17, I2 = 67%) or maximal oxygen uptake (effect size -0.20, p = 0.95, 95% CI -0.60-0.21, I2 = 0%). Echinacea supplementation did not influence erythropoietin, hemoglobin, hematocrit, or maximal oxygen uptake in athletes; however, the evidence base is limited.

Airline passengers experience a range of symptoms when travelling on long flights. This review evaluated the efficacy of functional foods, beverages, and supplements claiming to address the effects of air travel for healthy adults. Products were identified in a scoping review of electronic databases, search engines, and grey literature (March to August 2019). A systematic review of the efficacy of product ingredients was conducted using five electronic databases from inception to February 2021. Articles were screened, data extracted, and assessed for risk of bias by two researchers independently. Meta-analysis was performed. Of the 3842 studies identified, 23 met selection criteria: melatonin (n = 10), Pycnogenol (n = 4), various macronutrients (n = 2), caffeine (n = 2), Centella asiatica (n = 1), elderberry (n = 1), Echinacea (n = 1), fluid (n = 1), and Pinokinase (n = 1). Meta-analysis (random effects model) indicated melatonin reduced self-reported jetlag following eastbound (n = 5) and westbound (n = 4) flights: standard mean difference -0.76 (95% CI = -1.06 to -0.45, I2 0%, p < 0.00001) and -0.66 (95% CI = -1.07 to -0.26, I2 45%, p = 0.001), respectively. Pycnogenol also reduced edema scores (n = 3), standard mean -4.09 (95% CI = -6.44 to -1.74), I2 98%, p = 0.0006). Overall, 12 of 183 ingredients contained in 199 products had evidence to support claims.

PURPOSE: Upper respiratory tract infection (URTI) is a common infection in children, generally caused by viral respiratory infection. Vitamin C is currently proposed as prophylaxis for URTI. The purpose of this study was to assess the effectiveness of vitamin C administration in children for the prevention and reduced duration of URTI through a systematic literature review. METHODS: Review of the literature conducted between October 2017 and January 2018 in the main medical databases (CENTRAL, Medline and Embase) and by a gray literature approach. The selection criteria were: double-blind randomized controlled trials (RCTs) comparing vitamin C use to placebo in children aged 3 months to 18 years without chronic infection. Efficacy was assessed in terms of incidence, duration and severity of symptoms of URTI. A meta-analysis was conducted where possible. RESULTS: Eight RCTs, including 3135 children aged 3 months to 18 years, were selected. Quantitative analysis showed no difference between vitamin C administration and placebo (odds ratio = 0.75, 95% CI [0.54-1.03], p = 0.07, I2 = 74%). Vitamin C administration was found to decrease the duration of URTI by 1.6 days (standardized mean differences = -0.30 [-0.53; -0.08], p = 0.009, I2 = 70%). Children under 6 years of age benefit from more effective vitamin C supplementation associated with echinacea. No serious adverse events were reported. CONCLUSIONS: Although no preventive effects were found, vitamin C intake reduced the duration of URTI. Considering the frequency of URTI, the inappropriate prescription of antibiotics, and the safe nature of vitamin C, its supplementation is justified, especially in children under 6 years of age and those who present a high frequency of URTI. There is a sound rationale for further trials with greater statistical power among children of this age.

Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd.

Erratum in Lancet Infect Dis. 2007 Sep;7(9):580. Comment in Lancet Infect Dis. 2008 Jun;8(6):346-7; author reply 347-8. doi: 10.1016/S1473-3099(08)70107-5. Echinacea is one of the most commonly used herbal products, but controversy exists about its benefit in the prevention and treatment of the common cold. Thus, we did a meta-analysis evaluating the effect of echinacea on the incidence and duration of the common cold. 14 unique studies were included in the meta-analysis. Incidence of the common cold was reported as an odds ratio (OR) with 95% CI, and duration of the common cold was reported as the weighted mean difference (WMD) with 95% CI. Weighted averages and mean differences were calculated by a random-effects model (DerSimonian-Laird methodology). Heterogeneity was assessed by the Q statistic and review of L'Abbé plots, and publication bias was assessed through the Egger weighted regression statistic and visual inspection of funnel plots. Echinacea decreased the odds of developing the common cold by 58% (OR 0.42; 95% CI 0.25-0.71; Q statistic p<0.001) and the duration of a cold by 1.4 days (WMD -1.44, -2.24 to -0.64; p=0.01). Similarly, significant reductions were maintained in subgroup analyses limited to Echinaguard/Echinacin use, concomitant supplement use, method of cold exposure, Jadad scores less than 3, or use of a fixed-effects model. Published evidence supports echinacea's benefit in decreasing the incidence and duration of the common cold.

Upper respiratory tract infections (URTIs) are a prevalent health issue, causing considerable morbidity. Despite the availability of conventional treatments, there is an increasing interest in natural products due to their potential antiviral and immunomodulatory benefits. This study aims to evaluate the efficacy of an ELA blend (E-Echinacea purpurea, L-Lonicera cerulea, A-Aronia melanocarpa) in preventing and alleviating the symptoms of URTIs. Additionally, the study examines the blend's antiviral and immunomodulatory effects both in vitro and through a clinical trial. A randomized, double-blind, placebo-controlled trial involved 61 participants prone to URTIs, with a 60-day treatment and follow-up period. A placebo group later received the ELA blend for 60 days. The ELA blend significantly reduced the incidence of URTIs during the observation period (2 vs. 8; p = 0.044) and, in particular, throat-related symptoms (8 vs. 16; p = 0.038). Analyses of PBMCs showed that baseline production of the cytokines IFN-γ (p = 0.020), IL-1β (p = 0.004), IL-2(p < 0.001), IL-6 (p < 0.001), and TNF-α (p < 0.001) increased after ELA blend treatment. Moreover, the ELA blend modulated cytokine production in response to PHA-L stimulation, decreasing IFN-γ (p = 0.008) and IL-2 (p = 0.012) while increasing IL-1β (p = 0.005). Following R848 stimulation, the ELA blend enhanced the production of INF-α (p = 0.012) and IL-2 (p = 0.025), and decreased IL-1β (p < 0.001), IL-6 (p < 0.001), and TNF-α (p = 0.049). The blend suppressed VSV replication and significantly increased cytokine levels, with IFN-γ increasing by 98 pg/mL (p = 0.002), IL-1β rising by 233.0 pg/mL (p = 0.004), and TNF-α showing an increase of 2905 pg/mL (p = 0.002). These findings highlight the ELA blend's potential to alleviate URTI symptoms, modulate inflammatory and antiviral immune responses, and inhibit viral replication. Further investigations should aim to validate these findings through large-scale studies, and explore the ELA blend's long-term safety and efficacy in diverse populations. Additionally, research should investigate optimal dosing strategies and explore potential synergistic effects with conventional t

INTRODUCTION: Many COVID-19 patients experience mild to severe symptoms, including respiratory system involvement. Different treatment instructions have been suggested for patients with COVID-19. Echinacea has known antiviral effects. However, there is still not enough evidence that it is effective in treating COVID-19. This study was conducted with the aim of determining the effect of Echinacea extract syrup on the outcomes of the lower respiratory tract in patients with COVID-19. METHODS: In this single-blind randomized controlled trial, 40 patients with COVID-19 who were inpatients in the hospitals of Mashhad University of Medical Sciences, Iran, were randomly selected and assigned to two equal control and experimental groups (n = 20). In addition to receiving routine care and treatment (oxygen supply, remdesivir, enoxaparin and heparin), the experimental group received 5 cubic centimeter (CC) of Imogen syrup three times a day for 5 days each. The control group only received routine care and treatment. The data were collected on the first, third and fifth days after hospitalization and were analyzed using descriptive and analytical tests in Statistical Package for the Social Sciences (SPSS). The significance level was set at p < 0.05. RESULTS: The mean white blood cell count in the experimental group after the intervention decreased significantly compared to that before the intervention (t = 0.434, p = 0.045, df = 19). Arterial oxygen pressure increased significantly in both the experimental group (t = 4.382, p = 0.000, df = 19) and control group (t = 3.239, p = 0.004, df = 19), however no statistical differences were observed between experimental and control groups after intervention. The level of lung involvement (p = 0.320) and cough symptoms (P = 0.347) were not significantly different between the experimental and control groups after the intervention. In addition, there were no significant differences between the experimental and control groups in terms of the mean oxygen saturation, temperature, and number of breaths per minute on the first, third, and fifth day (p > 0.05). DISCUSSION: The consumption of Echinacea extract syrup may not be able to improv

A randomised open clinical/laboratory study was performed to evaluate the safety and cosmetic efficacy of facial cosmetics for females during the menopausal period. The cosmetics contain active ingredients of meristem cells derived from the medicinal plants Leontopodium alpinum, Buddeleja davidii, Centella asiatica, and Echinacea angustifolia. Recently, the major bioactive molecules of these medicinal plants (leontopodic acid, verbascoside, asiaticoside, and echinacoside, respectively) have been thoroughly evaluated in vitro for molecular pathways and cellular mechanisms and their preventive/curative effects on human skin cells exposed to factors promoting premature skin ageing and cellular senescence. Nevertheless, clinical data on their safety/efficacy to ageing human skin are scarce. This clinical study enrolled 104 Caucasian females in pre-menopause, menopause, or post-menopause periods. They applied cosmetic serums daily for 1 month. Questionnaires and instrumental and biochemical methods were used to assess dermatological/ophthalmological safety and cosmetic efficacy through changes of the skin physiology markers characteristic of ageing/menopause (elasticity, barrier functions, moisture, sebum, ultrasonic properties, and collagen content and structure). Quantitative microbiological tests were carried out for skin microbiota fluctuations. Data showed that the cosmetics were safe, and they shifted the skin physiology parameters to a younger biological age, enhanced collagen synthesis, inhibited lipid peroxidation, and favoured normal microbiota.

Echinacea purpurea (L.) Moench (EP), a medicinal plant native to North America, is now cultivated in various regions including Europe. With increasing popularity of Echinacea in Korea recently, a human clinical trial was conducted to evaluate immune-enhancing efficacy and safety of EP 60% ethanolic extract (EPE) in Koreans. Eighty volunteers were recruited for this randomized, double-blind, placebo-controlled clinical trial. They were randomly divided into two groups and given either a daily dose of 200 mg of EPE or a placebo. All participants underwent testing for Natural Killer (NK) cell cytotoxic activity, serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, TNF-α), Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), and Multidimensional Fatigue Scale (MFS) during this study to assess changes in outcomes. After 8 weeks of EPE consumption, a significant increase in NK cell cytotoxic activity compared to the placebo was observed. Additionally, serum cytokine levels of IL-2, IFN-γ, and TNF-α also significantly increased following EPE consumption. However, no significant changes were observed in WURSS-21 and MFS before and after EPE consumption. Throughout the 8-week study period, no adverse reactions were reported in relation to EPE consumption, and there were no clinically significant changes in diagnostic laboratory tests or vital signs in the EPE group. These results indicate that consumption of EPE could lead to immune improvement without any adverse effects. This clinical trial was the first to demonstrate beneficial effects of EPE consumption on immunity in Korean adults. © 2024 John Wiley & Sons Ltd.

Background and Objectives: Echinacea angustifolia and purpurea have known immunomodulatory effects which boost viral clearance, including HPV infection. However, evidence regarding the improvement due to Echinacea-based supplements of cervical HPV-related pathologies is still lacking. The aim of this study is to evaluate the efficacy of Echinacea supplementation on the remission of cervical low-grade squamous intraepithelial lesions (L-SIL). Materials and Methods: A single-blind 1:1:1 parallel randomized controlled trial was conducted at the Colposcopy Unit of a tertiary care referral center. Reproductive-aged women were allocated either to (a) an oral supplement based on Echinacea extracts plus vaginal hyaluronic acid-based soft gel capsules, (b) the Echinacea supplement alone, or (c) vaginal hyaluronic acid-based soft gel capsules alone for 3 months. The primary outcome was the regression of cervical intraepithelial neoplasia (CIN)-1 for each treatment arm at 3, 6 and 12 months after the diagnosis. Secondary outcomes included changes in the epithelialization, pap smear, colposcopic parameters, histological reports, and vaginal health indexes (VHI) in the study groups. Results: 153 women (52 for arm A, 50 for arm B and 51 for arm C) completed the follow-up and were included in the analysis. There were no significant differences in both primary and secondary outcomes for the three groups after 3 months. At the 6-month follow-up, the number of persistent CIN-1 diagnoses was significantly lower in arm A (15/51), rather than in arm B (23/48, p = 0.03) and C (27/49, p = 0.03). Similarly, the same effect was seen after 12 months for treatment A (5/51) relative to B (15/48, p = 0.03) and C (14/48, p = 0.03). Colposcopic, histological and vaginal parameters were all significantly improved at 6 and 12 months for arm A relative to B and C, while no beneficial effects were seen after 3 months. Conclusions: Echinacea extracts supplementation in women with L-SIL/CIN-1 significantly boosts HPV lesion clearance, reducing the overall amount of diagnosis, histological, colposcopic and vaginal parameters after 6 and 12 months. However, a limited sample size reduces the quality o

BACKGROUND: The acute anxiolytic effects of the echinacea angustifolia extract (EP107TM) have been demonstrated in two previous human trials. The goals of this study were to examine the anxiolytic and mood-enhancing effects of echinacea angustifolia over a longer duration with a larger sample size. METHODS: In this 6-week, 3-arm, parallel-group, double-blind, randomised controlled trial, 108 adults with mild-to-moderately severe anxiety were recruited and randomised to receive either a placebo, 20 mg, or 40 mg of echinacea angustifolia, twice daily. Outcome measures included the Clinically Useful Anxiety Outcome Scale (CUXOS), Positive and Negative Affect Scale (PANAS), Short Form-36 (SF-36), and Bergen Insomnia Scale (BIS). RESULTS: Based on data collected from 104 participants, both doses of echinacea were associated with overall reductions in anxiety, although improvements were not different from the placebo. However, both doses of echinacea were associated with greater improvements in the PANAS positive and negative affect scores, and SF-36 emotional wellbeing score compared to the placebo. LIMITATIONS: The positive improvements associated with echinacea were only identified via the secondary outcome measures and, therefore, require validation in future trials. CONCLUSIONS: The echinacea angustifolia extract (EP107TM) administered for 6 weeks at a dose of 40 and 80 mg daily was not associated with greater improvements in anxiety in adults with mild-to-moderately severe anxiety compared to the placebo. However, there were greater improvements in positive and negative affect, and emotional wellbeing, suggesting antidepressant effects. Further studies using clearly-defined populations and validated outcome measures will be useful in future trials.

The objective of this study was to reveal the synergistic antibacterial activity and mechanism of Echinacea purpurea (L.) Moench crude extract (EE) and citric acid (CA) against Cronobacter sakazakii isolated from powdered infant formula (PIF). The minimum inhibitory concentration (MIC) of EE against C. sakazakii was determined, and then growth curve and time-kill analysis were used to screen the optimal antibacterial combination of 1 MIC of EE and CA. Changes in cell membrane potential, cell integrity, cell permeability, bacterial protein, DNA, and intracellular reactive oxygen species (ROS) levels, and cell morphology of C. sakazakii were used to reveal the synergistic inhibitory mechanism of EE and CA. The inactivation effect of EE in combination with CA against C. sakazakii on common contact surfaces was used to evaluate its efficacy as a natural disinfectant. The results showed that the MIC value of EE against C. sakazakii was 60 mg/mL, and the growth curve of C. sakazakii treated by 1 MIC of EE combined with CA (pH 3.0) was significantly inhibited compared with the control groups. The results of time-kill analysis showed that after combined treatment with 1 MIC of EE and CA (pH 3.0) for 30 min, approximately 8 log cfu/mL of C. sakazakii were inactivated. Cell membrane hyperpolarization, damaged cell membrane integrity, improved cell membrane permeability, decreased bacterial protein and DNA levels, increased and then decreased intracellular ROS contents, and deformed and ruptured cell morphology were found in C. sakazakii treated by EE combined with CA, and these phenomena were more pronounced than in C. sakazakii treated by EE or CA alone. When inoculated stainless steel, glass, ceramic, polystyrene, bamboo, and wood were sprayed with 1 MIC of EE combined with CA (pH 3.0) and after 15 min of treatment, approximately 5 log cfu/mL of C. sakazakii were inactivated. These findings suggest that EE combined with CA can effectively inactivate C. sakazakii isolated from PIF and can be used as a natural disinfectant to reduce the contamination of C. sakazakii in PIF production environments or households. The Authors. Published by Elsevier Inc. on behalf of the Ame

Comment in J Clin Anesth. 2024 Oct;97:111544. doi: 10.1016/j.jclinane.2024.111544. Use of herbal medications and supplements has experienced immense growth over the last two decades, with retail sales in the USA exceeding $13 billion in 2021. Since the Dietary Supplement Health and Education Act (DSHEA) of 1994 reduced FDA oversight, these products have become less regulated. Data from 2012 shows 18% of U.S. adults used non-vitamin, non-mineral natural products. Prevalence varies regionally, with higher use in Western states. Among preoperative patients, the most commonly used herbal medications included garlic, ginseng, ginkgo, St. John's wort, and echinacea. However, 50-70% of surgical patients fail to disclose their use of herbal medications to their physicians, and most fail to discontinue them preoperatively. Since herbal medications can interact with anesthetic medications administered during surgery, the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA) recommend stopping herbal medications 1-2 weeks before elective surgical procedures. Potential adverse drug effects related to preoperative use of herbal medications involve the coagulation system (e.g., increasing the risk of perioperative bleeding), the cardiovascular system (e.g., arrhythmias, hypotension, hypertension), the central nervous system (e.g., sedation, confusion, seizures), pulmonary (e.g., coughing, bronchospasm), renal (e.g., diuresis) and endocrine-metabolic (e.g., hepatic dysfunction, altered metabolism of anesthetic drugs). During the preoperative evaluation, anesthesiologists should inquire about the use of herbal medications to anticipate potential adverse drug interactions during the perioperative period.

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John's wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care. © 2022. The Author(s).

BACKGROUND: Dietary supplement use has continued to rise. In addition to supplement-drug interactions, it is prudent to consider how dietary supplements may interact with a patient's specific pharmacogenetics. Variations in genes associated with CYP 450 enzymes have evidence of impacting drug metabolism and adverse effects. AIMS: This research was performed to evaluate CYP P450 enzyme activity of the top 15 dietary supplements used in the USA in order to initiate pharmacogenetic considerations specific to commonly used dietary supplements. METHODS: The most common dietary supplements used in the USA were obtained from the National Health and Nutrition Examination Survey (NHANES). Primary literature detailing supplement CYP P450 activity was compiled from PubMed using MeSH search terms: supplement name(s), cytochrome P450 enzymes, metabolism, and pharmacokinetics. Additional resources utilized for documented CYP enzyme genotypes were the pharmacogenetic databases from Clinical Pharmacogenetics Implementation Consortium and The Pharmacogenomic Variation Consortium. RESULTS: Of the 15 most common dietary supplements used in the USA, 53% (cranberry, echinacea, garlic, ginkgo biloba, ginseng, melatonin, milk thistle, and valerian) exhibit CYP P450 metabolism, with some having possible induction activity as well. Melatonin and garlic are substrates of CYP1A2 and CYP2C19, respectively. Additionally, there is evidence of echinacea having possible CYP3A4 induction activity. CONCLUSION: CYP P450 activity is an important consideration for any patient but becomes increasingly critical if patients have certain CYP P450 phenotypes that impact metabolism. These popular supplements have the potential for changes in supplement exposure, and adverse effects based on pharmacogenetic profiles. Furthermore, these sites of metabolism are shared with many medications, setting the stage for possibly more profound interactions between medications and supplements. This paper highlights the mechanisms in which dietary supplements may constitute a risk for patients with certain CYP P450 phenotypes. Further research is needed in the area of dietary supplements and their pharmacogenomic impl

The management of neuropsychiatric disorders relies heavily on pharmacotherapy. The use of herbal products as complimentary medicine, often concomitantly, is common among patients taking prescription neuropsychiatric drugs. Herb-drug interaction, a clinical consequence of this practice, may jeopardize the success of pharmacotherapy in neuropsychiatry. Besides the wellknown ability of phytochemicals to inhibit and/or induce drug-metabolizing enzymes and transport proteins, several phytoconstituents are capable of exerting pharmacological effects on the central nervous system. This study reviewed the relevant literature and identified 13 commonly used herbal products - celery, echinacea, ginkgo, ginseng, hydroxycut, kava, kratom, moringa, piperine, rhodiola, St. John's wort, terminalia/commiphora ayurvedic mixture and valerian - which have shown clinically relevant interactions with prescription drugs used in the management of neuropsychiatric disorders. The consequent pharmacokinetic and pharmacodynamic interactions with orthodox medications often result in deleterious clinical consequences. This underscores the importance of caution in herb-drug co-medication.

Preparations of Echinacea purpurea (E. purpurea) are widely used for the management of upper respiratory infections, influenza, and common cold, often in combination with other conventional drugs. However, the potential of phytochemical constituents of E. purpurea to cause herb-drug interactions via ABCB1 and ABCG2 efflux transporters remains elusive. The purpose of this study was to investigate the impact of E. purpurea-derived caffeic acid derivatives (cichoric acid and echinacoside) and tetraenes on the mRNA and protein expression levels as well as on transport activity of ABCB1 and ABCG2 in intestinal (Caco-2) and liver (HepG2) cell line models. The safety of these compounds was investigated by estimating EC20 values of cell viability assays in both cell lines. Regulation of ABCB1 and ABCG2 protein in these cell lines were analyzed after 24 h exposure to the compounds at 1, 10, and 50 μg/mL. Bidirectional transport of 0.5 μg/mL Hoechst 33342 and 5 μM rhodamine across Caco-2 monolayer and profiling for intracellular concentrations of the fluorophores in both cell lines were conducted to ascertain inhibition effects of the compounds. Cichoric acid showed no cytotoxic effect, while the EC20 values of tetraenes and echinacoside were 45.0 ± 3.0 and 52.0 ± 4.0 μg/mL in Caco-2 cells and 28.0 ± 4.3 and 62.0 ± 9.9 μg/mL in HepG2 cells, respectively. In general, the compounds showed heterogeneous induction of ABCB1 with the strongest 3.6 ± 1.2-fold increase observed for 10 μg/mL tetraenes in Caco-2 cells (p < 0.001). However, the compounds did not induce ABCG2. None of the phytocompounds inhibited significantly net flux of the fluorophores across Caco-2 monolayers. Overall, tetraenes moderately induced ABCB1 but not ABCG2 in Caco-2 and HepG2 cells while no compound significantly inhibited activity of these transporters at clinically relevant concentration to cause herb-drug interactions.

Commercial formulations of 29 commonly used herbal supplements (HSs) and grapefruit juice were evaluated for drug interaction potential via quantification of their CYP3A inhibitory potential in two in vitro experimental models of human small intestine, cryopreserved human intestinal mucosa (CHIM), and cryopreserved human enterocytes (CHEs). Two CYP3A substrates were used-in the studies with CHIM, CYP3A activity was quantified via liquid chromatography tandem mass spectrometry quantification of midazolam 1'-hydroxylation, whereas in CHE, luciferin-IPA metabolism to luciferin was quantified by luminescence. Upon treatment of CHIM with the estimated lumen concentration of the HS upon each oral administration (manufacturers' recommended dosage dissolved in 200 ml of culture medium), >80% CYP3A inhibition was observed for green tea extract, St. John's wort, valerian root, horehound, and grapefruit juice. Less than 50% inhibition was observed for fenugreek, aloe vera, guarana, soy isoflavone, maca, echinacea, spirulina, evening primrose, milk thistle, cranberry, red yeast rice, rhodiola, ginkgo biloba, turmeric, curcumin, white kidney bean, garlic, cinnamon, saw palmetto berries, panax ginseng, black elderberry, wheat grass juice, flaxseed oil, black cohosh, and ginger root. The results were confirmed in a a dose-response study with HSs obtained from three suppliers for the four inhibitory HSs (green tea extract, horehound, St. John's wort, valerian root) and three representative noninhibitory HSs (black cohosh, black elderberry, echinacea). Similar results were obtained with the inhibitory HSs in CHE. The results illustrate that CHIM and CHE represent physiologically relevant in vitro experimental models for the evaluation of drug interaction potential of herbal supplements. Based on the results, green tea extract, horehound, St. John's wort, and valerian root may cause drug interactions with orally administered drugs that are CYP3A substrates, as was observed for grapefruit juice. SIGNIFICANCE STATEMENT: In vitro evaluation of 29 popular herbal supplements in cryopreserved human intestinal mucosa identified green tea extract, horehound, St. John's wort, and valerian

Covering: 2000 to 2019 According to a 2012 survey from the Centers for Disease Control and Prevention, approximately 18% of the U.S. population uses natural products (including plant-based or botanical preparations) for treatment or prevention of disease. The use of plant-based medicines is even more prevalent in developing countries, where for many they constitute the primary health care modality. Proponents of the medicinal use of natural product mixtures often claim that they are more effective than purified compounds due to beneficial "synergistic" interactions. A less-discussed phenomenon, antagonism, in which effects of active constituents are masked by other compounds in a complex mixture, also occurs in natural product mixtures. Synergy and antagonism are notoriously difficult to study in a rigorous fashion, particularly given that natural products chemistry research methodology is typically devoted to reducing complexity and identifying single active constituents for drug development. This report represents a critical review with commentary about the current state of the scientific literature as it relates to studying combination effects (including both synergy and antagonism) in natural product extracts. We provide particular emphasis on analytical and Big Data approaches for identifying synergistic or antagonistic combinations and elucidating the mechanisms that underlie their interactions. Specific case studies of botanicals in which synergistic interactions have been documented are also discussed. The topic of synergy is important given that consumer use of botanical natural products and associated safety concerns continue to garner attention by the public and the media. Guidance by the natural products community is needed to provide strategies for effective evaluation of safety and toxicity of botanical mixtures and to drive discovery in botanical natural product research.

OBJECTIVE: Assessing adverse drug reactions (ADRs) is a proven method to estimate the safety of medicines. The ADRs to herbal medicines in Australia (and by inference, the safety of herbal medicines in Australia) remain unknown. This study examines spontaneous ADR cases to four of the most popular herbs in Australia from 2000 to 2015: echinacea (Echinacea purpurea), valerian (Valeriana officinalis), black cohosh (Actaea racemosa) and ginkgo (Ginkgo biloba). METHODS: ADRs of echinacea, valerian, black cohosh and ginkgo reported to the Australian Therapeutic Goods Administration (TGA) between 2000 and 2015 were obtained from the TGA database. Data were collated and analysed according to age, sex, severity, type of ADR and body system affected. Statistics were calculated using GraphPad Prism software. RESULTS: Most ADRs were mild or moderate. However, every herbal medicine was associated with life-threatening ADRs. In each life-threatening case, the herbal medicine was taken concomitantly with prescription medications. Black cohosh was associated with a significant number of severe ADRs (30.3% of the total), with 39.4% of these ADRs being associated with abnormal hepatic function, hepatitis or hepatotoxicity. CONCLUSION: This study highlights the lack of public awareness with regard to herb-drug interactions, since most of the severe ADRs involved a herb-drug interaction.

OBJECTIVE: The aim of this study was to assess the potential risks of interactions between biologically based complementary and alternative medication (BB-CAM) and conventional drugs during systemic therapy in breast and gynecological cancer patients by analyzing the actual CAM-drug combinations from individual patients' records. METHODS: From September 2014 to December 2014 and from February 2017 to May 2017, all patients (n = 717) undergoing systemic therapy at the Gynecologic Oncology Day Care Unit in the Gynecology and Obstetrics Department of the Technical University of Munich, Germany, were asked to participate in a questionnaire about all their medications. To assess the potential risk of CAM-drug interactions (CDIs), we initially utilized the Lexicomp drug interaction database. This assessment was then expanded with a systematic search of other digital databases, such as the National Center for Complementary and Integrative Health, Memorial Sloan Kettering Cancer Center, PubMed, and MEDLINE as well as the Cochrane Library. RESULTS: Among 448 respondents, 74.1% reported using BB-CAM simultaneously with their systemic therapy. The assessment showed 1 patient with a potentially clinically relevant CDI, where the interaction was based on a self-medicated combination of Echinacea and cyclophosphamide. Furthermore, 81 patients (18.1%) were thought to have interactions because of a combination of BB-CAMs and cytochrome P450 3A4-metabolized anticancer drugs. CONCLUSIONS: Our data demonstrated high overall use of BB-CAMs by cancer patients undergoing systemic therapy. The analyses showed only 1 clinically relevant CDI.

OBJECTIVES: To elucidate the benefits, pitfalls and risks of phytotherapy in the clinical practice of otorhinolaryngology. MATERIAL AND METHODS: The PubMed and Cochrane databases were searched using the following keywords: phytotherapy, phytomedicine, herbs, otology, rhinology, laryngology, otitis, rhinitis, laryngitis and otorhinolaryngology. Seventy-two articles (18 prospective randomized studies, 4 Cochrane analyses, 4 meta-analysis and 15 reviews of the literature) devoted to clinical studies were analyzed. Articles devoted to in vitro or animal studies, biochemical analyses or case reports (including fewer than 10 patients) and articles dealing with honey, aromatherapy or minerals were excluded. RESULTS: Per os ginkgo biloba has no indications in tinnitus, presbycusis or anosmia following viral rhinitis. Traditional Asian medicine has no proven benefit in sudden deafness or laryngeal papillomatosis. Per os mistletoe extracts associated to conventional treatment for head and neck squamous cell carcinoma does not increase 5-year survival. Extracts of various herbs, notably echinacea, eucalyptus, petasites hybridus, pelargonium sidoides, rosemary, spirulina and thyme, show superiority over placebo for rhinosinusitis and allergic rhinitis, as does gingko biloba for selected vertigo. There have been encouraging preliminary results for intratumoral injection of mistletoe in head and neck carcinoma and acupoint herbal patching for allergic rhinitis. Herb intake should be screened for in case of certain unexplained symptoms such as epistaxis, headache or dizziness, or signs suggesting allergy. Phytotherapy should be interrupted ahead of surgery and/or chemotherapy. CONCLUSION: Scientific proof of the benefit of phytotherapy in otorhinolaryngology remains to be established but, given its widespread use and the reported data, knowledge of this form of treatment needs to be developed.

OBJECTIVE: To systematically identify herbal supplements with immunostimulatory properties that may trigger or exacerbate autoimmune skin diseases. METHODS: We conducted a systematic scoping review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. PubMed was searched for studies published before 3 August 2025 using predefined immune, herbal supplement, autoimmune, skin and interferon terms. Articles in English that described immunostimulatory effects of herbal supplements in vitro, in model organisms or in human/clinical studies were included. Data were extracted by four reviewers and synthesised qualitatively, with herbs categorised according to levels of supporting evidence for their immunostimulatory properties. A subgroup of herbs with the strongest evidence was identified based on predefined criteria. RESULTS: From 11 819 unique articles screened, 469 studies met inclusion criteria. Across these, 227 distinct immunostimulatory herbal supplements were identified: 79 supported by human studies, 145 by model organism studies and 148 by in vitro studies. 15 herbs demonstrated the most robust evidence across all three evidence types, supported by more than five single-ingredient studies or more than 25 references overall. These included alfalfa, ashwagandha, astragalus, chlorella, echinacea, garlic, ginseng, green tea extract, Indian mulberry, liquorice, mistletoe, reishi mushroom, skullcap, spirulina and tinospora. These herbs were widely marketed for 'immune support' and shared proinflammatory mechanisms, including toll-like receptor activation, NF-κB/MAPK signalling and increased production of inflammatory cytokines including IL-1β, IL-6, TNF-α, IL-12 and IFN-γ. CONCLUSIONS: We identified 227 herbal supplements with immunostimulatory properties, of which 15 were most strongly supported by the evidence. This article may serve as a reference to help clinicians counsel patients with autoimmune skin diseases on the risks associated with use of specific herbal supplements. © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and perm

Echinacoside (ECH), a naturally occurring water-soluble phenylethanoid glycoside, is one of the primary bioactive compounds present in several plant species, such as Echinacea, Cistanche, Plantago, Rosa, Buddleja, and Rehmannia. Research has revealed that these plants, rich in ECH, have diverse traditional uses and pharmacological activities, like anti-diabetic, anti-inflammatory, anti-fatigue, anti-allergic, anti-ageing, anti-skin glycation, analgesic, wound healing, and aphrodisiac properties. Among other activities, ophthalmic, haematopoiesis, pulmonary, anti-bacterial, anti-protozoal, anti-fungal, and anti-viral effects of ECH have been reported. Chemically, the compound comprises caffeic acid glycoside containing a trisaccharide that includes two glucose and one rhamnose unit. These units are linked through glycosidic bonds to a caffeic acid and a dihydroxyphenylethanol (hydroxytyrosol) residue, which are connected to the central rhamnose. The biosynthesis of ECH has been reported to start with forming L-phenylalanine and tyrosine precursors via the shikimic acid pathway. The structure-activity relationship of ECH has shown that various functional groups in the structure, particularly phenolic hydroxyl groups, are crucial for antioxidant activities. Similarly, in silico studies have revealed that ECH binds to different receptors, like Kelch-like ECH-associated protein 1 (Keap1), receptor for advanced glycation end products (RAGE), etc., to affect various pharmacological activities. The ECH contents in the reported plants often own these multifaceted properties, highlighting their importance in clinical research. Evident from its therapeutic efficacy, there is a huge potential for a comprehensive understanding of the mechanisms of actions of ECH, which underscores the need for more research in this area. Thus, this review is a compendium of the latest literature to analyse the existing knowledge on ECH, encompassing its distribution, traditional uses, extraction, chemical constituents, biosynthesis, pharmacological activities, structure-activity relationship, and in silico studies, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Immune health products represent approximately 10% of all US dietary supplement sales. Claims made on products to support or boost the immune system are attractive to the otherwise healthy consumer who may or may not be experiencing certain life stressors. The purpose of this systematic review is to critically evaluate the purported benefits and/or potential harms of select dietary supplement ingredients frequently listed on the labels of products having immune health or related market claims. With a focus on resilience, research questions were related to whether dietary supplement ingredients are efficacious in preserving and protecting immune health in healthy individuals; and when faced with a stressor, whether taking a supplement prophylactically can assist in maintaining health and resisting or bouncing back more quickly. Thirty-nine randomized controlled studies involving populations including children, adults and seniors exposed to stressors, such as air travel, intense exercise, academic stress, and/or exposure to winter weather, met eligibility criteria. The studies included eight of the 27 supplement ingredients identified through a market-driven scoping review. Those ingredients used in single ingredient products were echinacea, elderberry, garlic, vitamin A, vitamin C, vitamin D, vitamin E, and zinc. Whereas some studies may point to evidence for benefit, specific gaps preclude the authors from making firm statements with regard to the overall evidence-base for these products and ingredients and in answering the research questions. As we move toward a vision of health promotion and resilience rather than a sole focus on disease prevention and treatment, further work in this area of dietary supplements is of utmost importance.

BACKGROUND: Echinacea preparations are commonly used to prevent and treat upper respiratory tract infection. OBJECTIVES: To assess current evidence for the safety and efficacy of echinacea containing preparations in preventing and treating upper respiratory tract infection. DATA SOURCES: MEDLINE, EMBASE, CAB extracts, Web of Science, Cochrane DARE, clinicaltrials.gov and the WHO ICTRP - 1980 to present day. ELIGIBILITY CRITERIA: Randomised double-blind placebo-controlled trials using an echinacea preparation to prevent or treat upper respiratory tract infections. PARTICIPANTS AND INTERVENTIONS: Participants who are otherwise healthy of any age and sex. We considered any echinacea containing preparation. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the Cochrane collaborations tool for quality assessment of included studies and performed three meta-analyses; on the prevention, duration and safety of echinacea. RESULTS: For the prevention of upper respiratory tract infection using echinacea we found a risk ratio of 0.78 [95% CI 0.68-0.88], for the treatment of upper respiratory tract infection using echinacea we found a mean difference in average duration of -0.45 [95% 1.85-0.94] days, finally for the safety meta-analyses we found a risk ratio of 1.09 [95% CI 0.95-1.25]. LIMITATIONS: The limitations of our review include the clinical heterogeneity - for example many different preparations were tested, the risk of selective reporting, deviations from our protocol and lack of contact with study authors. CONCLUSIONS: Our review presents evidence that echinacea might have a preventative effect on the incidence of upper respiratory tract infections but whether this effect is clinically meaningful is debatable. We did not find any evidence for an effect on the duration of upper respiratory tract infections. Regarding the safety of echinacea no risk is apparent in the short term at least. The strength of these conclusions is limited by the risk of selective reporting and methodological heterogeneity. IMPLICATIONS OF KEY FINDINGS: Based on the results of this review users of echinacea can be assured that echinacea preparations are safe to consume in the short term howeve

Comment in Pharmacol Res. 2019 Mar;141:609-610. doi: 10.1016/j.phrs.2019.01.033. Although several studies on pharmacokinetic and/or pharmacodynamic herb-drug interactions (HDI) have been conducted in healthy volunteers, there is large uncertainty on the validity of these studies. A qualitative review and a meta-analysis were performed to establish the clinical evidence of these interaction studies. Out of 4026 screened abstracts, 32 studies were included into the qualitative analysis. The meta-analysis was performed on eleven additional studies. St. John's wort (SJW) significantly decreased the AUC (p < 0.0001) and clearance (p = 0.007) of midazolam. Further subgroup analysis identified age to affect Cmax of midazolam (p < 0.01) in the presence of SJW. Echinacea purpurea (EP) significantly increased the clearance of midazolam (p = 0.01). Evidence of publication bias (p > 0.001) was shown on the effect of the herbal products o half-life of midazolam. Green tea (GT) showed significant 85% decrease in plasma concentration of nadolol. The study findings suggest that GT, SJW and EP perpetuate significant interactions with prescribed medications via CYP3A4 or OATP1A2. Our studies show that meta-analyses are important in the area of natural products to provide necessary information on their use in overall medication plans in order to avoid unintended interactions.

The use of alternative medicine in chronic rhinosinusitis (CRS) continues to increase in popularity, for the most part without meeting the burden of being based on sound clinical evidence. New and emerging treatments, both natural and developed, are numerous, and it remains a challenge for otolaryngologists as well as general practitioners to keep up to date with these therapies and their efficacy. In this systematic review, we discuss a number of alternative therapies for CRS, their proposed physiologic mechanisms, and evidence supporting their use. This analysis is based on our review of the English-language literature on alternative therapies for CRS (we did not include any therapies that are already recommended by accepted professional bodies). Data collection was performed using the PubMed database (not restricted to MEDLINE due to the nature of the subject matter), the Cochrane databases, and bibliography searches. We found that while many of the alternative therapies we reviewed might have a firm basis in science, they lack any clinical evidence to support their use specifically for CRS. Some emerging therapies, such as therapeutic ultrasonography and phonophoresis, show some promise, based on a growing body of positive evidence. In addition, the use of baby shampoo, thyme honey, and bromelain additives to saline lavage in CRS are all supported by clinical evidence, as is Sinupret, an oral preparation that contains echinacea. However, higher levels of evidence gleaned from large, well-designed, prospective, randomized, controlled trials are needed before any of these therapies can be recommended.