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Extracts obtained from common butterbur ( ), standardized to petasins, are existing pharmaceutical options for the treatment and/or prevention of allergic rhinitis (leaves) and migraine (rhizomes). In this study, the total phenolic content, flavonoid content, and antioxidant potential of ten samples of Croatian species (four , four , one , and one ) obtained by ultrasound-assisted extraction of leaves were compared. The total phenolic content (Folin-Ciocalteu assay) of methanolic leaf extracts ranged from 4.43 ± 0.09 to 10.76 ± 0.60 mg gallic acid equivalent g dry mass (mg GAE g DM) for and from 6.66 ± 0.43 to 19.92 ± 2.90 mg GAE g DM for samples, while those of and were equal to 7.56 ± 0.17 mg GAE g DM and 10.22 ± 0.46 mg GAE g DM, respectively. Flavonoid content (AlCl assay) varied between 2.51 ± 0.10 and 4.03 ± 0.08 mg quercetin equivalent g dry mass (mg QE g DM) for and between 2.21 ± 0.09 and 5.22 ± 0.02 mg QE g DM for samples, while those of and were equal to 5.59 ± 0.05 mg QE g DM and 5.50 ± 0.09 mg QE g DM, respectively. Antioxidant potential was in high correlation with total phenolic content ( = 0.93, < 0.001). Due to the expected contribution of plant polyphenols and flavonoids to the activity of butterbur extracts and their observed great variabilities, determining the content of these compounds may be of interest to the pharmaceutical industry.

During the last decades, the research on the biological activities of extracts from Cimicifuga / Actaea species and Petasites japonicus as well as their active ingredients has been intensified. Besides terpenoids as dominant natural product group, hydroxycinnamic acid esters such as fukinolic acid and several cimicifugic acids have been isolated from Actaea and Petasites species and their chemical structures have been elucidated. Investigations on the biological properties of these hydroxycinnamic acid esters are currently undertaken and some compounds might be promising therapeutic tools. In this review, we have gathered information on the genera Actaea and Petasites , the occurrence of cimicifugic and fukinolic acids and some aspects of their biosynthesis. Furthermore, we have summarized the medicinal aspects of fukinolic acid and cimicifugic acids. In connection with the biological activities of these compounds, structural features of the hydroxycinnamic acid derivatives move into the focus. The position of the hydroxyl group at the aromatic rings and the introduction of an electron-donating moiety may be important for anti-inflammatory, antiviral, cytotoxic and vasoactive effects of these compounds.

Extracellular vesicles (EVs) have recently been isolated from different plants. Plant-derived EVs have been proposed as potent therapeutics and drug-delivery nanoplatforms for delivering biomolecules, including proteins, RNAs, DNAs, and lipids. Herein, Petasites japonicus-derived EVs (PJ-EVs) were isolated through a series of centrifugation steps and characterized using dynamic light scattering and transmission electron microscopy. Immunomodulatory effects of PJ-EVs were assessed using dendritic cells (DCs). PJ-EVs exhibited a spherical morphology with an average size of 122.6 nm. They induced the maturation of DCs via an increase in the expression of surface molecules (CD80, CD86, MHC-I, and MHC-II), production of Th1-polarizing cytokines (TNF-α and IL-12p70), and antigen-presenting ability; however, they reduced the antigen-uptake ability. Furthermore, maturation of DCs induced by PJ-EVs was dependent on the activation and phosphorylation of MAPK and NF-κB signal pathways. Notably, PJ-EV-treated DCs strongly induced the proliferation and differentiation of naïve T cells toward Th1-type T cells and cytotoxic CD8+ T cells along with robust secretion of IFN-γ and IL-2. In conclusion, our study indicates that PJ-EVs can be potent immunostimulatory candidates with an ability of strongly inducing the maturation of DCs.

Inhibition of inflammatory responses from the spike glycoprotein of SARS-CoV-2 (Spike) by targeting NLRP3 inflammasome has recently been developed as an alternative form of supportive therapy besides the traditional anti-viral approaches. Clerodendrum petasites S. Moore (C. petasites) is a Thai traditional medicinal plant possessing antipyretic and anti-inflammatory activities. In this study, C. petasites ethanolic root extract (CpEE) underwent solvent-partitioned extraction to obtain the ethyl acetate fraction of C. petasites (CpEA). Subsequently, C. petasites extracts were determined for the flavonoid contents and anti-inflammatory properties against spike induction in the A549 lung cells. According to the HPLC results, CpEA significantly contained higher amounts of hesperidin and hesperetin flavonoids than CpEE (p < 0.05). A549 cells were then pre-treated with either C. petasites extracts or its active flavonoids and were primed with 100 ng/mL of spike S1 subunit (Spike S1) and determined for the anti-inflammatory properties. The results indicate that CpEA (compared with CpEE) and hesperetin (compared with hesperidin) exhibited greater anti-inflammatory properties upon Spike S1 induction through a significant reduction in IL-6, IL-1β, and IL-18 cytokine releases in A549 cells culture supernatant (p < 0.05). Additionally, CpEA and hesperetin significantly inhibited the Spike S1-induced inflammatory gene expressions (NLRP3, IL-1β, and IL-18, p < 0.05). Mechanistically, CpEA and hesperetin attenuated inflammasome machinery protein expressions (NLRP3, ASC, and Caspase-1), as well as inactivated the Akt/MAPK/AP-1 pathway. Overall, our findings could provide scientific-based evidence to support the use of C. petasites and hesperetin in the development of supportive therapies for the prevention of COVID-19-related chronic inflammation.

The primary objective of this noninterventional, observational study was to assess the effectiveness of the Petasites hybridus leaf extract (Ze 339) on early allergic and late inflammatory symptoms of allergic rhinitis in Swiss outpatients. This study was conducted by general practitioners and allergologists. Data from 226 patients were collected during three documented visits. The intermediate visit was ideally made 2–4 weeks after the baseline visit, followed by the final visit approximately 2–4 months later. The mean study duration was 63 days, with 75% of patients being treated for at least 4 weeks. Of the patients, 58.5% started with Ze 339 monotherapy, and 41.5% received other antiallergic and/or sympathomimetic drugs. In both groups, the allergic total symptom score and the inflammatory total symptom scores were significantly (p < 0.001) reduced, and the scores for quality of life were improved. Both physicians and patients were very satisfied with the treatment and the concept of therapy, not only for short-term (seasonal) therapy but also for long-term therapy. The tolerability was good: only three mild gastrointestinal adverse events occurred. In summary, the effectiveness of P. hybridus leaf extract Ze 339 for the treatment of early allergic and late inflammatory symptoms of allergic rhinitis could be confirmed.

Migraine is a disabling neurovascular disorder with few targeted, tolerable and effective treatments. Phytomedicines, or plant-based medicinal formulations, hold great promise in the identification of novel therapeutic targets in migraine. Many patients also turn toward herbal and plant-based therapies for the treatment of their migraines as clinical and preclinical evidence of efficacy increases. Patients seek effective and tolerable treatments instead of or in addition to current conventional pharmacologic therapies. We review some phytomedicines potentially useful for migraine treatment—feverfew ( Tanacetum parthenium ), butterbur ( Petasites hybridus ), marijuana ( Cannabis spp.), Saint John’s Wort ( Hypericum perforatum ) and the Damask rose ( Rosa × damascena )—with respect to their mechanisms of action and evidence for treatment of migraine. The evidence for feverfew is mixed; butterbur is effective with potential risks of hepatotoxicity related to preparation; marijuana has not been shown to be effective in migraine treatment, and data are scant; Saint John’s Wort shows relevant physiological activity but is a hepatic enzyme inducer and lacks clinical studies for this purpose; the Damask rose when used in topical preparations did not show efficacy in one clinical trial. Other plant preparations have been considered for migraine treatment but most without blinded randomized, placebo-controlled trial evidence.

A short review of our recent research on the essential oil phytochemical composition of (L.) Gaertn. and (L.) G. Gaertn., B. Mey. & Scherb. (Asteraceae) as well as on the oils of L., (Podp.) O. Schwarz and Lapeyr. (Plantaginaceae) is presented. All essential oils contained a variety of oxygenated sesquiterpenes among their major constituents, including a bakkane type sesquiterpene fukinanolid (bakkenolide A). The paper is focused on: ) a short overview of the abundance of major terpenes in the essential oils of and species from Croatia; ) possible biosynthetic pathways of major identified sesquiterpenes; and ) biological activities (literature data) of major sesquiterpenes from and species.

The study investigated the effects of Petasites japonicus (Siebold & Zucc.) Maxim. extract (PJE) and fenofibrate on diet-induced obesity (DIO) in mice. PJE was found to contain various bio-active polyphenolic compounds, including kaempferol, p-hydroxybenzoic acid, ferulic acid, gallic acid, chlorogenic acid, 3,4-dicaffeoylquinic acid, caffeic acid, quercetin, rutin, protocatechuic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, p-coumaric acid, apigenin, and 1,3-dicaffeoylquinic acid. The results showed that PJE treatment up to 1000 μg/mL did not affect the viability of 3T3-L1 cell line, and it reduced the feed efficiency ratio in DIO mice. PJE administration also resulted in a significant reduction in body weight gain and fat accumulation in the liver compared to the DIO control group. Additionally, PJE administration improved the levels of lipid and related parameters, including total cholesterol, triacylglycerol, low-density lipoprotein, very low-density lipoprotein, glucose, insulin, insulin resistance, leptin, and atherogenic or cardiac indexes compared to the DIO control group. The study suggested that PJE may have a beneficial effect on insulin resistance, lipid profiles, atherogenesis, adipokines, and cardiac risk associated with diet-induced obesity.

Winter Heliotrope ( Petasites pyrenaicus , previously P. fragrans ), is a persistent, rhizome-forming species found throughout the Mediterranean region and North Africa and is an Invasive Alien Plant (IAP) in the UK and Ireland. P. pyrenaicus excludes native flora by forming a dense, compact canopy that persists for much of the growing season, and is often found growing in rough ground, riparian areas and along communication routes, incurring significant management costs at sites of conservation interest. Our study describes the first field-based assessment of P. pyrenaicus control treatments, testing 12 physical and/or chemical treatments in replicated 1 m 2 plots over four years and one chemical treatment over three years. Treatments focused on understanding phenology and resource allocation to exploit rhizome source-sink relationships in P. pyrenaicus . Multiple-stage glyphosate- and picloram-based treatments reduced leaf canopy cover to zero (%) over time, though no treatment completely eradicated P. pyrenaicus . When designing management strategies, effective P. pyrenaicus control may be achieved by a single annual soil and/or foliar application of picloram at 1.34 kg AE ha -1 in spring, or by a single annual foliar application of glyphosate in spring at 2.16 kg AE ha -1 . Control is not improved by the addition of other herbicides or physical treatment methods, underlining the importance of these herbicides for perennial invasive plant management. This work confirms the importance of considering plant phenology, resource allocation and rhizome source-sink relationships, to increase treatment efficacy and reduce the environmental impacts associated with the management of P. pyrenaicus and other invasive, rhizome forming species.

Oriental natural plants have been used as medical herbs for the treatment of various diseases for over 2,000 years. In this study, we evaluated the effect of several natural plants on the preservation of male fertility by assessing the ability of plant extracts to stimulate spermatogonial stem cell (SSC) proliferation by using a serum-free culture method. In vitro assays showed that Petasites japonicus extracts, especially the butanol fraction, have a significant effect on germ cells proliferation including SSCs. The activity of SSCs cultured in the presence of the Petasites japonicus butanol fraction was confirmed by normal colony formation and spermatogenesis following germ cell transplantation of the treated SSCs. Our findings could lead to the discovery of novel factors that activate SSCs and could be useful for the development of technologies for the prevention of male infertility.