Butterbur (Petasites)

INTRODUCTION: Seasonal allergic rhinitis (SAR) is a common health condition that is associated with an increased risk for bronchial asthma. Besides conventional medicine, treatments from traditional, complementary and integrative medicine are widely used by individuals with SAR. This review aims to systematically summarize evidence on the efficacy, effectiveness, and safety of European/Western phytotherapy (PT) and medications from anthroposophic medicine (AM) in individuals with SAR. METHODS: Four electronic databases were screened for clinical studies published between January 1990 and March 2023. The results were qualitatively synthesized and the study quality was assessed. RESULTS: In total, 14 studies were included, 11 from European/Western PT and three from AM. About half of the studies were rated as being of sufficient quality. The most frequently studied plant was Petasites hybridus (butterbur), showing beneficial effects on immunological parameters, subjective symptoms, and nasal airflow. Beneficial immunological and clinical effects were also shown for an herbal preparation combining Citrus limonis (lemon) and Cydonia oblonga (quince). The medications examined by studies of sufficient quality were judged to be safe. CONCLUSION: In summary, this systematic review highlights two herbal preparations, one from European/Western PT and one from AM, that appear to be promising options in the treatment of SAR. © 2024 S. Karger AG, Basel.

Herbal medicine is popularly used among patients who suffer from allergic rhinitis. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of single medicinal plants in the management of allergic rhinitis. We searched MEDLINE, CENTRAL, and Web of Science for randomised controlled trials which evaluated the use of single medicinal plant for allergic rhinitis among adults and children. Twenty-nine randomised controlled trials (n = 1879) were eligible while 27 (n = 1769) contributed data for meta-analyses. Most studies (studies = 20) compared medicinal plants against placebo and Petasites hybridus was most frequently investigated (studies = 5). Very-low-to-low-certainty evidence suggests that compared to placebo, single medicinal plants may improve overall total nasal symptoms (SMD -0.31, 95% CI -0.59 to -0.02; participants = 249; studies = 5; I2 = 21%) especially nasal congestion and sneezing; and rhinoconjunctivitis quality of life (RQLQ) scores (MD -0.46, 95% CI -0.84 to -0.07; participants = 148; studies = 3; I2 = 0%). Moderate-certainty evidence show no clear differences between single medicinal plants and antihistamine in overall symptoms (Total nasal symptoms: SMD -0.14, 95% CI -0.46 to 0.18; participants = 149; studies = 2; I2 = 0%). As adjunctive therapy, moderate-certainty evidence shows that medicinal plants improved SNOT-22 scores when given as intranasal treatment (MD -7.47, 95% CI -10.75 to -4.18; participants = 124; studies = 2; I2 = 21%). Risk of bias domains were low or not clearly reported in most studies while heterogeneity was substantial in most pooled outcomes. Route of administration and age were identified to be plausible source of heterogeneity for certain outcomes. Medicinal plants appear to be well tolerated up to 8 weeks of use. Clear beneficial evidence of medicinal plants for allergic rhinitis is still lacking. There is a need for improved reporting of herbal trials to allow for critical assessment of the effects of each individual medicinal plant preparation in well-designed future clinical studies. Copyright: © 2024 Lim et al. This is an open access article distributed under the terms of the Creat

OBJECTIVE: Although a wide range of acute and preventative medications are now available for the treatment of migraine headaches, many patients will not have a significant improvement in the frequency and severity of their headaches unless lifestyle modifications are made. Also, given the myriad side effects of traditional prescription medications, there is an increasing demand for "natural" treatment like vitamins and supplements for common ailments such as headaches. Here, we discuss the role of food triggers in the management of migraines, and review the evidence for supplements in migraine treatment. METHODS: A review of the English language literature on preclinical and clinical studies of any type on food triggers, vitamins, supplements, and migraine headaches was conducted. RESULTS: A detailed nutritional history is helpful in identifying food triggers. Although the data surrounding the role of certain foods and substances in triggering headaches is controversial, certain subsets of patients may be sensitive to phenylethylamine, tyramine, aspartame, monosodium glutamate, nitrates, nitrites, alcohol, and caffeine. The available evidence for the efficacy of certain vitamins and supplements in preventing migraines supports the use of these agents in the migraine treatment. CONCLUSIONS: The identification of food triggers, with the help of food diaries, is an inexpensive way to reduce migraine headaches. We also recommend the use of the following supplements in the preventative treatment of migraines, in decreasing order of preference: magnesium, Petasites hybridus, feverfew, coenzyme Q10, riboflavin, and alpha lipoic acid.

OBJECTIVE: To evaluate the efficacy of herbal medicines for the treatment of allergic rhinitis (AR). DATA SOURCES: Five electronic databases until November 8, 2005; bibliographies of located articles; manufacturers of commercially available preparations; and experts in the field. STUDY SELECTION: We only included double-blind randomized clinical trials (RCTs), which tested a herbal medicine against placebo or active comparator, in patients with AR, and evaluated clinically relevant outcomes. Study selection, data extraction, and evaluation of methodological quality were performed independently by 2 reviewers. Discrepancies were resolved by discussion and by seeking the opinion of the third reviewer. Meta-analysis was only performed if data were considered suitable for pooling. RESULTS: Sixteen eligible RCTs, testing 10 different herbal products against placebo or active comparator, were included. Six RCTs studied Petasites hybridus (butterbur) extract for AR and suggest that P hybridus is superior to placebo or similarly effective compared with nonsedative antihistamines for intermittent AR. Two RCTs studied an Indian herbal combination, Aller-7, in patients with AR and reported positive results. Single RCTs were identified for 8 other herbal products as treatments for AR, reporting positive outcomes, except for grape seed extract. The median methodological quality score was 4 of a possible maximum of 5. CONCLUSIONS: There is encouraging evidence suggesting that P hybridus may be an effective herbal treatment for seasonal (intermittent) AR. However, independent replication is required before a firm conclusion can be drawn because of the financial support from the manufacturer of P hybridus extract to the 3 large trials. There are also promising results generated for other herbal products, particularly Aller-7, Tinospora cordifolia, Perilla frutescens, and several Chinese herbal medicines. Although these results are confined to the paucity of data and the small sample size, confirmation in larger and more rigorously designed clinical trials is warranted.

The objective of this review was to evaluate the strength of evidence of effectiveness for Petasites hybridus in the prophylaxis of migraine. Several databases and other sources were searched to identify randomised-controlled trials investigating P. hybridus preparations. Two trials totalling 293 patients (60 and 233 patients) were included in this review. Both trials investigated the proprietary Petasites root extract Petadolex. The trials were described in narrative way, taking into consideration methodological quality scores. Pooling of data was not carried out due to the heterogeneity of the results. The extract at higher dose (150 mg) showed a greater decreased frequency of migraine attacks and a greater number of responders (improvement>50%) after treatment over 3-4 months than the extract at lower dose (100 mg) and placebo. Moderate evidence of effectiveness is, thus, available for a higher than the recommended dose of the proprietary Petasites root extract Petadolex in the prophylaxis of migraine. Further rigorous studies are required to confirm effectiveness and safety in long-term use before treatment with Petasites root extract can be recommended as an alternative option in the treatment schedule for the prophylaxis of migraine.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

BACKGROUND: Considering the negative effects of stress on health, there is a growing interest in stress-reducing interventions. The present study examines the effects of a fixed combination of valerian, passion flower, lemon balm, and butterbur extracts (Ze 185) on biological and affective responses to a standardized psychosocial stress paradigm. PURPOSE: The aim of the present study was to investigate the efficacy of Ze 185 on cortisol and anxiety stress responses to acute psychosocial stress in healthy subjects. STUDY DESIGN: This study was a randomized, placebo-controlled, double blind study with 3 parallel groups. METHODS: 72 healthy male participants were randomized to 3 groups (Ze 185, placebo or no treatment) during 4 days prior to a standardized psychosocial stress paradigm. Principle outcomes were salivary cortisol and self-reported anxiety responses to stress assessed at the fourth day. RESULTS: The stress paradigm induced significant and large cortisol and self-reported anxiety responses. Groups did not differ significantly in their salivary cortisol response to stress, but participants in the Ze 185 condition showed significantly attenuated responses in self-reported anxiety in comparison to placebo (F(3, 41) = 3.33, p = 0.03) and no treatment (F(3, 43) = 2.77, p = 0.05). CONCLUSION: The results show that Ze 185 significantly attenuated the subjective emotional stress response during an acute stress situation, without affecting biological stress responses. Given that a circumscribed biological stress response is to be considered as an adaptive mechanism, Ze 185 reduces self-reported anxiety response to stress without affecting assumingly adaptive biological stress responses.

Herbal drugs are often used in patients with somatoform disorders yet, the available evidence is limited. The aim of the present short-term study was to evaluate in a pharmaco-clinical trial the additional benefit of butterbur in a fixed herbal drug combination (Ze 185 = 4-combination versus 3-combination without butterbur and placebo) in patients with somatoform disorders.For a 2-week treatment in patients with somatization disorder (F45.0) and undifferentiated somatoform disorder (F45.1), 182 patients were randomized for a 3-arm trial (butterbur root, valerian root, passionflower herb, lemon balm leaf versus valerian root, passionflower herb, lemon balm leaf versus placebo). Anxiety (visual analogue scale - VAS) and depression (Beck's Depression Inventory - BDI) served as primary parameters, Clinical Global Impression (CGI) was a secondary parameter.The 4-combination was significantly superior to the 3-combination and placebo (4-combination > 3-combination > placebo) in all the primary and secondary parameters (PP-population). Analysis of the ITT population confirmed these results. As to safety, no serious adverse events occurred. In total 9 non-serious adverse events were documented but the distribution did not differ significantly between the treatment groups.This herbal preparation (Ze185) showed to be an efficacious and safe short-term treatment in patients with somatoform disorders.

BACKGROUND: Migraine is very common in school-aged children, but despite a number of pharmacological and non-pharmacological options for prophylaxis, randomized controlled evidence in children is small. Evidence-based prophylactic drugs may have considerable side effects. OBJECTIVE: This study was to assess efficacy of a butterbur root extract (Petadolex) and music therapy in primary school children with migraine. DESIGN: Prospective, randomized, partly double-blind, placebo-controlled, parallel-group trial. METHODS: Following a 8-week baseline patients were randomized and received either butterbur root extract (n=19), music therapy (n=20) or placebo (n=19) over 12 weeks. All participants received additionally headache education ("treatment as usual") from the baseline onwards. Reduction of headache frequency after treatment (8-week post-treatment) as well as 6 months later (8-week follow-up) was the efficacy variable. RESULTS: Data analysis of subjects completing the respective study phase showed that during post-treatment, only music therapy was superior to placebo (p=0.005), whereas in the follow-up period both music therapy and butterbur root extract were superior to placebo (p=0.018 and p=0.044, respectively). All groups showed a substantial reduction of attack frequency already during baseline. CONCLUSION: Butterbur root extract and music therapy might be superior to placebo and may represent promising treatment approaches in the prophylaxis of paediatric migraine.

BACKGROUND: Petasin (Ze 339) was recently introduced on the market as a potent herbal antiallergic drug for treatment of respiratory allergies such as hay fever. Few clinical studies have been performed so far addressing the clinical effectiveness of Ze 339. OBJECTIVE: To evaluate the antiallergic properties of Ze 339 using skin prick tests with different stimuli, such as codeine, histamine, methacholine, and a relevant inhalant allergen. METHODS: A randomized, double-blind, placebo-controlled study was performed in which Ze 339 was compared to acrivastine, a short-acting antihistamine, in 8 patients with respiratory allergy and in 10 nonatopic, healthy volunteers. Antiallergic activity of Ze 339 was determined by analyzing inhibitory potency in skin prick tests with codeine, histamine, methacholine, and an inhalant allergen. Wheal-and-flare reactions were assessed 90 minutes after a double dose of Ze 339, acrivastine, or placebo. An interval of at least 3 days was left between the skin tests. RESULTS: Acrivastine was identified as the only substance that significantly inhibited skin test reactivity to all solutions analyzed in all study subjects. In contrast, no significant inhibition could be demonstrated for Ze 339 with any test solution. Moreover, the results of Ze 339 did not differ significantly from placebo. CONCLUSIONS: In this study we found no antiallergic, particularly antihistaminic, effect of Ze 339 in skin tests using a variety of stimuli often used to evaluate immediate skin test reactivity. The mechanism by which Ze 339 is effective in the treatment of seasonal allergic rhinitis still needs to be elucidated.

BACKGROUND: Intermittent allergic rhinitis (IAR) causes patients distress and impairs their work performance and quality of life. A variety of medicines are used by sufferers whose anguish frequently leads to trying new treatments, increasingly from herbal sources. METHODS: Prospective, randomized, double-blind, parallel group comparison study of Butterbur extract (Ze 339; 8 mg total petasine; one tablet thrice-daily), fexofenadine (Telfast 180, one tablet once-daily) and placebo in 330 patients. Protocol and analysis were according to the latest guidelines on new treatments for allergic rhinitis. The primary efficacy variable was a change in symptoms from baseline to endpoint during daytime. The secondary efficacy variables were: (a) as per primary variable (evening/night); (b) Physician's global assessment; (c) Responder rates. Safety was closely monitored. FINDINGS: Both active treatments were individually significantly superior to placebo (p<0.001) in improving symptoms of IAR, while there were no differences between the two active treatments (p=0.37). Superiority to placebo was similarly shown during the evening/night (p<0.001), by physicians' own assessment and by responder rates. Both treatments were well tolerated. INTERPRETATION: Butterbur Ze 339 and Fexofenadine are comparably efficacious relative to placebo. Despite being a herbal drug, Butterbur Ze 339 has now been subject to a series of well controlled trials and should be considered as an alternative treatment for IAR. Copyright (c) 2005 John Wiley & Sons, Ltd.

OBJECTIVE: To evaluate the clinical efficacy of a standardized special root extract from the plant Petasites hybridus as a preventive therapy for migraine. METHODS: This is a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome measure was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period. RESULTS: Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of patients with a > or =50% reduction in attack frequency after 4 months was 68% for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3 months based on this endpoint. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events, predominantly burping. CONCLUSIONS: Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasites 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.

OBJECTIVES: To investigate whether the efficacy and safety of Butterbur extract Ze339 are related to dosage when administered to patients with intermittent allergic rhinitis. DESIGN: Prospective, randomized, double-blind, placebo-controlled, parallel-group comparison. SETTING: Multicenter, including 6 outpatient general medicine and allergy clinics. PATIENTS: One hundred eighty-six patients were randomized (Butterbur Ze339 high dose, 60; low dose, 65; and placebo, 61 patients). Established diagnostic criteria for intermittent allergic rhinitis were confirmed by skin allergy tests in all patients. INTERVENTIONS: High-dose group, 1 tablet 3 times daily; low-dose group, 1 tablet twice daily; or matching placebo. All groups were treated for 2 consecutive weeks. MAIN OUTCOME MEASURES: The main efficacy variable was change in symptoms from baseline to end point during the daytime. The secondary efficacy variables were Clinical Global Impression score, change in symptoms from baseline to treatment day 7, and responder rates. Statistical analysis was prospective, on an intention-to-treat basis. RESULTS: Improvement in the main efficacy variable was significantly superior in the Butterbur Ze339 groups, relative to placebo, and a significant dose relationship was observed between the 2 Butterbur doses. The clinicians' assessment of efficacy and the overall responder rates were significantly superior for the active groups compared with placebo. The incidence and type of adverse events were indistinguishable across the herbal treatment and placebo groups. CONCLUSIONS: Butterbur Ze339 is an effective treatment for intermittent allergic rhinitis symptoms and is well tolerated. The effects of this herbal medicine are clear to patients and physicians in a double-blind evaluation against placebo.

BACKGROUND: Butterbur (Petasites hybridus) contains the active ingredient petasin, which exhibits antileukotriene and antihistamine activity. Previous studies of intermittent allergic rhinitis (IAR) have demonstrated a comparable response to butterbur compared with a histamine H1-receptor antagonist on the 36-Item Short-Form Health Survey quality-of-life score. However, there has been no placebo-controlled study of the effects of butterbur use on objective and subjective outcomes in IAR. OBJECTIVE: To evaluate the effects of treatment with butterbur vs placebo on objective and subjective outcomes in IAR. METHODS: A double-blind, placebo-controlled, crossover study was carried out during the grass pollen season in Tayside, Scotland. Thirty-five patients (14 men and 21 women) with IAR received butterbur, 50 mg twice daily, or placebo for 2 weeks. Domiciliary measurements were taken in the morning and evening for peak nasal inspiratory flow (PNIF) (the primary outcome variable), nasal and eye symptoms, and rhinoconjunctivitis-specific quality-of-life score. RESULTS: Butterbur treatment had no significant effect on PNIF, total nasal symptom score, eye symptom score, or quality of life compared with placebo use. Mean (SEM) morning and evening PNIF values were 107 (6) and 114 (6) L/min, respectively, for butterbur vs 105 (6) and 117 (6) L/min for placebo. Mean (SEM) morning and evening total nasal symptom scores (maximum total score, 12) were 3.4 (0.4) and 3.5 (0.4), respectively, for butterbur vs 3.7 (0.3) and 3.8 (0.4) for placebo. CONCLUSIONS: There was no significant clinical efficacy of butterbur use vs placebo use on objective and subjective outcomes in IAR. Further studies are now indicated to investigate the use of butterbur in persistent allergic rhinitis.

BACKGROUND: There are presently no placebo-controlled data regarding the effects of butterbur (BB) on subjective and objective outcomes in patients with perennial allergic rhinitis. OBJECTIVE: We performed a placebo-controlled evaluation of the effects of BB and fexofenadine (FEX) on subjective and objective outcomes in patients with perennial allergic rhinitis. METHODS: Sixteen patients with perennial allergic rhinitis and house dust mite sensitization were randomized in double-blind cross-over fashion to receive for 1 week either BB 50 mg twice daily, FEX 180 mg once daily and placebo (PL) once daily, or PL twice daily. The peak nasal inspiratory flow (PNIF) response to adenosine monophosphate (AMP) challenge administered as a single 400 mg/mL dose was measured over a 60-min period after challenge, and domiciliary total nasal symptom score was recorded. RESULTS: Pre-challenge values for mean+/-SEM PNIF (L/min) were not significantly different comparing all groups; BB (138+/-8), FEX (140+/-9), and PL (138+/-8). The maximum % PNIF fall from baseline after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (46+/-3), with BB (34+/-3) and FEX (39+/-3). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (1734+/-156), with BB (1052+/-258) and FEX (1194+/-161). There was also a significant reduction (P<0.05) in total nasal symptom score with BB (1.8+/-0.4) and FEX (1.8+/-0.4), compared to PL (2.8+/-0.5). There were no significant differences between BB and FEX for any outcomes. CONCLUSION: BB and FEX, in comparison to PL, were equally effective in attenuating the nasal response to AMP and in improving nasal symptoms, highlighting a potential role for BB in the treatment of allergic rhinitis.

BACKGROUND: Butterbur or Petasites hybridus is an herbal remedy that exhibits antihistamine and antileukotriene activity and has been shown to attenuate the response to adenosine monophosphate challenge in patients with allergic rhinitis and asthma. However, no data are available regarding its effects on the histamine and allergen cutaneous response. OBJECTIVE: To evaluate the effects of butterbur compared with fexofenadine and montelukast on the histamine and allergen wheal and flare cutaneous responses. METHODS: Atopic patients were randomized into a double-blind, double-dummy, crossover study to receive for 1 week butterbur, 50 mg twice daily (8 AM and 10 PM); fexofenadine, 180 mg once daily (10 PM), and placebo once daily (8 AM); montelukast, 10 mg once daily (10 PM), and placebo once daily (8 AM); or placebo twice daily (8 AM and 10 PM). Patients attended the department at 10 AM and had measurements of the cutaneous wheal and flare responses to histamine, allergen, and saline control at 10-minute intervals for 60 minutes. RESULTS: Twenty patients completed the study. The mean +/- SE histamine wheal and flare responses, respectively, were significantly attenuated (P < .05) by fexofenadine (9.4 +/- 1.8 mm2 and 13.5 +/- 3.2 mm2) compared with placebo (15.5 +/- 3.3 mm2 and 179.8 +/- 74.3 mm2) but not by butterbur (16.4 +/- 2.1 mm2 and 297.7 +/- 121.2 mm2) or montelukast (19 +/- 1.9 mm2 and 240.2 +/- 66.6 mm2). The allergen wheal and flare responses, respectively, were also significantly attenuated (P < .05) by fexofenadine (31.1 +/- 6.3 mm2 and 256.9 +/- 86.5 mm2) compared with placebo (65.4 +/- 15.2 mm2 and 1,014.5 +/- 250.0 mm2) but not by butterbur (50.4 +/- 9.2 mm2 and 1,110.3 +/- 256.1 mm2) or montelukast (58.8 +/- 9.1 mm2 and 1,463.6 +/- 295.6 mm2). CONCLUSIONS: Butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared with placebo, whereas mediator antagonism with fexofenadine but not montelukast produced significant attenuation. This finding would suggest that butterbur may not be effective in allergic skin disease.

Memory impairment associated with cholinergic dysfunction is a key feature of cognitive decline. Natural products with neuroprotective properties have attracted increasing interest as potential interventions for memory dysfunction. This study investigated the protective effects of a propolis-Petasites japonicus mixture (PPJM) against scopolamine-induced memory impairment in mice and explored its underlying mechanisms. Male C57BL/6 mice were pretreated with PPJM prior to scopolamine administration. Spatial learning and memory were evaluated using the Morris water maze. Hippocampal cholinergic function was assessed by measuring acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities. Molecular mechanisms were examined by Western blot analysis of neuroplasticity-related signaling (BDNF-TrkB-AKT-CREB), phosphorylated Tau (p-Tau), MAPK activation, and neuroinflammatory markers. Immunohistochemical staining for TrkB and p-Tau, along with histological analysis, was performed to assess hippocampal alterations. PPJM pretreatment significantly ameliorated scopolamine-induced deficits in spatial learning and memory, as indicated by reduced escape latency and increased time spent in the target quadrant. PPJM partially restored cholinergic function by reducing AChE activity and increasing ChAT activity in the hippocampus. In addition, PPJM was associated with increased BDNF-TrkB-AKT-CREB signaling, along with reduced p-Tau and attenuation of JNK/p38 MAPK activation. Neuroinflammatory responses, including NF-κB activation and the expression of COX-2, TNF-α, and IL-6, were also reduced following PPJM pretreatment. Histological analyses further indicated preservation of neuronal architecture and modulation of TrkB and p-Tau expression in the hippocampus. These findings suggest that PPJM exerts protective effects against scopolamine-induced memory impairment, accompanied by modulation of cholinergic function, neuroplasticity-related signaling, and neuroinflammatory responses. However, further studies are required to validate these effects in chronic and translational models.

Dianthus superbus var. superbus (D. superbus) and Petasites paradoxus (Retz.) Baumg. (P. paradoxus) are traditionally used medicinal plants from the Italian flora. This study presents the first investigation into the cytotoxic and genotoxic potential of methanolic leaf extracts from both species. Genotoxicity was assessed using the automated cytokinesis-block micronucleus (CBMN) assay in Chinese Hamster Ovary (CHO-K1) cells. Both extracts exhibited dose-dependent cytotoxic effects, with IC50 values of 27 µg/mL for D. superbus and 56 µg/mL for P. paradoxus. At the lowest tested concentration (6.3 µg/mL), D. superbus extract did not significantly affect micronucleus frequency in the presence or absence of mitomycin C (MMC). However, at the highest concentration (25 µg/mL), D. superbus extract significantly increased micronucleus frequency under both conditions compared to control cells. For P. paradoxus, the lowest concentration tested (12.5 µg/mL) did not alter micronucleus frequency in the absence of MMC, but notably reduced micronucleus formation when co-administered with MMC, suggesting potential antigenotoxic activity. Conversely, the highest concentration of P. paradoxus extract (50 µg/mL) induced a significant increase in micronucleus frequency compared to MMC treatment alone. These results indicate that both extracts possess cytotoxic and genotoxic properties. Future research should focus on elucidating the mechanisms underlying these genotoxic effects and identifying the specific phytochemicals responsible.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites japonicus leaves (EPJ) on dextran sulfate sodium (DSS)-induced colitis and depression-like behaviors. The physiological compounds identified in the EPJ were citric acid, chlorogenic acid, caffeic acid, fukinolic acid, 3,5-dicaffeoylquinic acid, quercetin 3-O-β-D-glucose-6″-acetate, 4,5-dicaffeoylquinic acid, kaempferol-3-O-(6″-acetyl)-β-glucopyranoside, and pedunculoside. EPJ significantly alleviated DSS-induced colitis, as evidenced by improvements in body weight loss (87.41% vs. 76.02% in the DSS group), colon length (5.75 vs. 4.34 cm), intestinal permeability (52.80 vs. 163.01 μg/mL), and myeloperoxidase (MPO) activity (0.24 vs. 0.67 U/mg) (p < 0.05). Histological analysis further confirmed recovery of goblet cells and attenuation of muscle layer thickening. EPJ also reversed DSS-induced gut microbiota dysbiosis and contributed to the restoration of microbial homeostasis. Behavioral assessments showed that EPJ effectively ameliorated depression-like behaviors. EPJ improved antioxidant systems in colon and brain tissues by modulating malondialdehyde (MDA) levels and reduced glutathione (GSH) and superoxide dismutase (SOD) activity. EPJ further upregulated tight junction protein expression and suppressed TLR4/NF-κB inflammatory pathway activation in both colon and brain tissues. Moreover, EPJ modulated serum stress-related hormones, normalized hypothalamic-pituitary-adrenal (HPA) axis dysregulation, regulated the BDNF/TrkB signaling pathway, and modulated tryptophan-kynurenine metabolism. Collectively, these findings suggest that EPJ exerts protective effects against DSS-induced colitis and depression-like behaviors.

INTRODUCTION: Triple-negative breast cancer (TNBC) is the most aggressive malignancy in women, with limited treatment options and significant adverse effects. Natural products have emerged as promising anticancer agents, either alone or in combination with standard therapies. Within the National Biodiversity Future Center, this study aims to valorize Italy's plant biodiversity, as a source of novel bioactive compounds with therapeutic and nutraceutical potential. METHODS: Leaf extracts of Petasites paradoxus, Salvia pratensis, and Typha laxmannii were profiled by UPLC-ESI-HRMS. TNBC MDA-MB-231 and non-tumorigenic MCF 10A mammary epithelial cells were exposed to 5 μg/mL of each DMSO-resuspended extract. Viability, proliferation, migration, cell-cycle, and ROS were assessed. Genes and miRNA expression were quantified by RT-qPCR, supported by immunofluorescence, bioinformatic functional enrichment, and patients' survival analyses. RESULTS: Each species showed a specific phytochemical fingerprint. Notably, S. pratensis, enriched in rosmarinic acid, caffeic acid esters, and luteolin derivatives, selectively reduced TNBC cell viability after 24 h. The treatment also impaired proliferation, migration, and cell cycle, increasing mitochondrial reactive oxygen species, and inducing apoptosis. Underlying the molecular mechanisms, S. pratensis stimulation modulated genes associated with tumor aggressiveness. Importantly, over-representation analysis on the differentially expressed genes pool identified miR-34a-5p as a potential regulator, its low expression being linked to poor TNBC prognosis. MiR-34a-5p in treated MDA-MB-231 was significantly up-regulated compared to controls. DISCUSSION: These findings position S. pratensis as a promising source of naturally derived bioactive compounds with selective anticancer activity, mediated in part via miR-34a-5p signaling. This study highlights the potential of plant-based bioactives for preventive and complementary strategies in TNBC, supporting further exploration of their integration into dietary or therapeutic interventions.

BACKGROUND: Petasites hybridus is a plant from the Asteraceae family used in migraine prophylaxis. Petasins and isopetasins, one of its constituents, act through antinociceptive, anti-CGRP, anti-inflammatory mechanisms and on calcium channels. OBJECTIVE: This study aimed to evaluate the therapeutic efficacy of Petasites hybridus in the prophylaxis of episodic migraine (EM) and chronic migraine (CM). METHODS: This was a single-center, retrospective, observational, uncontrolled, descriptive, and real-world study with 120 consecutive patients with EM or CM treated with Petasites hybridus. RESULTS: One hundred and twenty patients (72 with EM and 48 with CM) were treated with Petasites hybridus, whose mean age was 35.4 ± 12.4 years, ranging from 18 to 60 years. Before treatment, the average frequency of headache for EM and CM was 6.0 ± 2.7 and 26.3 ± 5.1 days per month, respectively. After 12 weeks, there was a reduction in the number of days with headache, both in the EM and CM, respectively, to 2.6 ± 2.9 and 12.7 ± 8.6 (p < 0.0001). The reduction in headache attacks was greater than 50% in 59.2% of patients. There was a reduction in disability in both groups. Adverse events occurred in 28.3% of patients, including a bitter sensation in the mouth and/or eructation, lasting 6.4 ± 2.7 days and ranging from 2 to 14 days. CONCLUSION: Petasites hybridus was well tolerated and reduced the number of headache days per month by ≥50% in 60% of migraine patients within the first 12 weeks, providing a reduction in the degree of disability. Furthermore, Petasites hybridus (Petamig®) is free of pyrrolizidine alkaloids, making it appropriate and safe for prescription to patients.

BACKGROUND: Oral melanoma is one of the most devastating cancers in dogs. We previously developed a novel agent extracted from Japanese butterbur shoots and its petasin derivatives demonstrated anti-proliferative activity in canine oral melanoma cells. The aim of this study was to evaluate the safety and clinical efficacy of the butterbur shoot extract (BSE) in dogs with oral melanoma as a combined phase 1 and 2 study. RESULTS: All enrolled dogs underwent radiation therapy or surgery as local therapy before BSE administration. We enrolled nine dogs in the phase 1 study, and BSE was orally administered at doses escalating from 50 to 200 mg/kg. Grade 1 alanine aminotransferase elevation and diarrhoea were observed in each dog. We determined that 200 mg/kg BSE was safe to administer. We subsequently administered it to sixteen dogs with stage 3 oral melanoma in the phase 2 study. Their progression-free survival and overall survival were compared with those of the historical controls, and adverse events were assessed. BSE administration significantly extended overall survival but did not prolong progression-free survival. No dose-limiting toxicities were observed. CONCLUSIONS: These results indicate that 200 mg/kg of BSE is safe to administer and may improve the outcome of canine oral melanoma.

Migraine is a prevalent neurovascular disorder strongly associated with neuroinflammation, altered neurotransmitter release, and sensory hypersensitivity. Extracts of Petasites hybridus (butterbur) rootstocks, standardized with eremophilane-type sesquiterpenoids (petasins), have clinically demonstrated efficacy in migraine. However, the pharmacological properties of purified petasins remain insufficiently explored. This study aimed to evaluate their antimigraine and anti-neuroinflammatory potential both in vivo and in vitro. Six sesquiterpenoids were isolated via centrifugal partition chromatography and preparative high-performance liquid chromatography. Male C57BL/6 J mice were subjected to a nitroglycerin model of migraine-like pain, followed by administration of the isolated sesquiterpenoids and mechanical hypersensitivity was evaluated via von Frey filaments. The sesquiterpenoid and neurotransmitter levels in the brain tissues were analyzed via LC‒MS/MS, and the cytokine levels were measured via ELISA. In LPS-stimulated BV-2 microglial cells, anti-inflammatory effects were assessed via Griess assay and a cytokine bead array, and cell viability was measured via MTT assay. Isopetasin significantly attenuated nitroglycerin‒induced mechanical allodynia in both the paw and periorbital regions. These effects may be associated with reduced brain levels of the chemokine CCL2, while LC‒MS/MS confirmed the central bioavailability of isopetasin. In vitro, sesquiterpenoids suppressed LPS‒induced nitric oxide and proinflammatory cytokine release, with isopetasin showing the broadest anti-inflammatory activity. Neurochemical profiling revealed modulation of glutamic acid and GABA associated with the excitatory/inhibitory balance. Purified petasins from butterbur rootstocks, particularly isopetasin, display significant antinociceptive and anti-inflammatory activity in preclinical migraine model. These findings support the importance of well-chemically defined butterbur constituents and provide a foundation for their further investigation as anti-neuroinflammatory agents. © 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Background: Ultraviolet B (UVB) radiation accelerates skin aging by inducing oxidative stress, collagen degradation, and cellular senescence. Although Petasites japonicus is known for its antioxidant properties, its anti-photoaging potential remains underexplored. This research explored the protective properties of a hot water extract from P. japonicus leaves (KP-1) against photoaging caused by UVB exposure. Methods: Hairless mice were exposed to UVB three times per week and orally administered KP-1 for 13 weeks. Wrinkle formation, epidermal thickness, skin hydration, and collagen content were assessed. Protein expression related to MAPK/AP-1, TGF-β/Smad2/3, and p53/p21 pathways was analyzed by Western blotting. Results: KP-1 significantly reduced UVB-induced wrinkle area, epidermal and dermal thickening, and transepidermal water loss while restoring collagen density and skin hydration. KP-1 inhibited MMP-1 expression, enhanced COL1A1 levels, suppressed MAPK/AP-1 activation, and activated TGF-β/Smad2/3 signaling. It also balanced p53/p21 expression and restored cyclin D1 and CDK4 levels, thereby preventing UVB-induced senescence. Conclusions: The findings of this research revealed that KP-1 can serve as a promising natural substance for safeguarding the skin from damage and aging caused by UVB exposure.

Airway inflammation driven by particulate matter (PM) exposure underlies diseases such as asthma and allergic rhinitis. Although conventional anti-inflammatory therapies exist, they often cause significant side effects. Natural plant extracts offer non-toxic alternatives with comparable efficacy. The present study evaluated the effects of Petasites japonicus-propolis (PJP) mixture in a mouse model co-exposed to PM (intranasal) and ovalbumin (OVA; intraperitoneal) over 30 days. PJP was administered orally at 50, 100 or 200 mg/kg daily for 9 days. PJP reduced sneezing and nasal rubbing. Serum levels of total IgE and OVA-specific IgG1 were decreased by PJP. In addition, bronchoalveolar lavage fluid and nasal lavage fluid showed lower histamine and IL-4 concentrations. In lung tissue, PJP reduced the epithelial thickness and inflammatory cell infiltration (goblet cells, eosinophils and mast cells). At the molecular level, PJP downregulated suppression of tumorigenicity 2, IL-33, TNF-α and IL-4 expression, and inhibited NF-κB phosphorylation. PJP attenuated PM/OVA-induced airway inflammation by suppressing NF-κB signaling and associated cytokine responses, highlighting its potential as a therapeutic candidate for inflammatory respiratory diseases. Copyright: © 2025 Park et al.

Allergic rhinitis (AR) is a global health problem on the rise. More and more people are affected, and climate change is exacerbating this health problem in the long term. The quality of life of those affected is often severely compromised, and the financial burden on healthcare systems cannot be disregarded. Therefore, effective and safe medicines are needed to counteract this trend. P. hybridus (butterbur) leaf extract (Ze 339) displays a promising alternative to antihistamines in the treatment of AR symptoms. More than two decades after the first market launch it is now possible to draw a meaningful conclusion on its safety and efficacy. This review summarizes the available preclinical and clinical data, real-world data (RWD) as well as data from post-marketing pharmacovigilance monitoring about the herbal medicinal drug Ze 339. It focusses on the current knowledge about the mode of action as well as the evaluation of its efficacy and safety in the treatment of AR. Given its favourable safety profile and lack of sedative side effects, Ze 339 offers a valuable alternative to antihistamines and should therefore continue to be considered by medical practitioners for the treatment of allergic rhinitis symptoms.

We investigated the effect of the butanol fraction from the methanol extract of butterbur (Petasites japonicus Max.) (BMP) on the plasma lipid profiles and oxidative damage of liver in mice challenged with monosodium l-glutamate (MSG). ICR mice (6-8 weeks old, male) were fed BMP (0.1% or 0.3%) for 1 week, and on day 7, MSG (4 mg/g) was administered intraperitoneally to the mice. Administration of MSG resulted in a significant decrease of antioxidant biomarkers such as total glutathione level and antioxidant enzyme activities such as glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S-transferase (GST), and quinone reductase (NQO1), whereas the thiobarbituric acid-reactive substances (TBARS) value was increased in liver tissue. However, BMP supplementation markedly enhanced the hepatic antioxidant enzyme activities, including GPx, GR, GST, and NQO1, whereas it lowered TBARS, compared to the MSG-treated group. Moreover, BMP supplementation decreased total cholesterol, atherogenic index, and low-density lipoprotein-cholesterol, compared to the MSG-treated group. Based on these results, it was proposed that BMP improve the plasma lipid profiles and decrease the oxidative stress by up-regulating the hepatic antioxidant enzymes in mice challenged with MSG.

AIMS AND OBJECTIVE: In this research, multicomponent reactions of cefixime, isothiocyanates, and alkyl bromides were carried out for the synthesis of new iminothiazole derivatives with high yields in water as the solvent at room temperature in the presence of catalytic amounts of Cu@KF/CP NPs as catalysts. Also, the ability of Cu@KF/Clinoptilolite nanoparticles (NPs) to adsorb and remove 4-NP and cefixime from water was investigated. The Cu@KF/Clinoptilolite nanoparticles were synthesized by employing a water extract of Petasites hybridus rhizomes. MATERIALS AND METHODS: For this experiment, all of the components obtained from Fluka and Merck were subjected to further purification. The antibiotic used in this investigation, cefixime, was obtained from a pharmaceutical facility situated in Sari, Mazandaran, Iran. The antibiotic factory is located in Sari City, Iran. All solutions were prepared using distilled water. The shape of Cu@KF/CP nanoparticles was analyzed using images obtained from a Holland Philips XL30 scanning electron microscope. An analysis was performed on the crystalline structure of Cu@KF/CP nanoparticles (NPs), and a room temperature X-ray diffraction (XRD) examination was carried out utilizing a Holland Philips Xpert X-ray powder diffractometer. The X-ray diffraction (XRD) examination was conducted using CuK radiation, which has a wavelength of 0.15406 nm. The analysis covered a 2ε angle range from 20 to 80°. The nanostructures that were produced were chemically analyzed using X-ray energy dispersive spectroscopy (EDS) with an S3700N equipment. The morphology and dimensions of Cu@KF/CP nanoparticles were characterized using a Philips EM208 transmission electron microscope operated at an acceleration voltage of 90 kV. RESULTS: The primary objective of this study was to develop a sustainable approach for producing new iminothiazole derivatives 4. This was achieved using a highly efficient three-component reaction combining cefixime 1, isothiocyanates 2, and alkyl bromides 3. The reaction was carried out in water at ambient temperature, using Cu@KF/CP NPs as a highly effective catalyst, leading to excellent yields. Moreover, the study findings sho

BACKGROUND: The intensified search for low-threshold herbal anti-viral drugs would be of great advantage in prevention of early stages of infection. Since the SARS-CoV-2 Omicron variant has prevailed in western countries, the course has only been mild, but there are still no widely available drugs that can alleviate or shorten disease progression and counteract the development of Long-COVID. This study aimed to investigate the antiviral effects of a CO2-extract from Petasites hybridus (Ze 339). METHODS: We analyzed the infection and replication rate of SARS-CoV-2 in primary normal human bronchial epithelial cells (NHBEs) using a GFP-expressing version of the wild-type SARS-CoV-2 virus and live cell imaging. Upon infection with a clinical isolate of the Omicron variant, viral RNA content was quantified, and plaque assays were performed. In addition, the human transcriptome was analyzed after 4- and 24-hours post infection using whole genome microarrays. RESULTS: Ze 339 had a protective effect on primary airway epithelial cells during SARS-CoV-2 infection and impeded SARS-CoV-2 infection and replication in NHBE. Notably, Ze 339 inhibited the expression of infection-induced IFNA10 by 8.6-fold (p < 0.05) and additionally reduced a wide range of other interferons (IFNA6, IFNA7, IFNA8, IFNA21, IFNE, IFNW1). CONCLUSION: Thereby, Ze 339 attenuated epithelial infection by SARS-CoV-2 and modeled the IFN response. In conclusion, this study highlights Ze 339 as a potential treatment option for COVID-19 that limits infection-associated cell intrinsic immune responses.