Search Results (5)

The use of herbal medicines containing Petasites hybridus extracts has a long history in the treatment of various ailments. The observed effects are primarily due to pharmacologically active compounds such as petasin, isopetasin, and neopetasin. In evidence-based phytotherapy, extracts from leaves and rhizomes are applied for different indications. While leaf extracts are administered to treat allergic rhinitis symptoms, rhizome extracts are utilized among others in the management of gastrointestinal spasms and migraines. The quality and source of plants are critical for producing authorized herbal medicinal products. Although the preparation of P. hybridus leaf extracts from cultivated plant material is already established, the rhizomes used for preparing extracts are still derived from commercial wild collections. However, switching to cultivation is desirable to ensure consistent quality and availability. For regulatory purposes, comparative pharmacological studies are needed to assess the bioactivity of plant material from different sources. Therefore, this study analyzed rhizome extracts from wild harvesting and cultivation for their petasin composition (i.e., isopetasin, neopetasin, petasin) and spasmolytic effects on Ca²⁺-dependent precontracted guinea pig ileum ex vivo. The results confirm petasins as active compounds of P. hybridus rhizome extracts. Moreover, they demonstrate that the total content of petasins determines the spasmolytic effects, regardless of the individual composition of the different petasins. No significant differences in efficacy were found between cultivated and wild-collected rhizomes, demonstrating that cultivated material is a reliable, consistent, and sustainable alternative for P. hybridus rhizome extract production. Full article

The retinal pigment epithelium (RPE) is a highly specialised monolayer epithelium subjected to constant oxidative stress, which, in the long term, favours the development of a complex pathological process that is the underlying cause of macular damage. Therefore, counteracting the overproduction of ROS is the best-researched approach to preserve the functional integrity of the RPE. S-Petasin, a secondary metabolite extracted from the plant Petasites hybridus, has numerous biological effects, which highlight its anti-inflammatory and antioxidative properties. The aim of our study is to investigate whether S-Petasin exerts cytoprotective effects by protecting the RPE from oxidative damage. The effects of pretreatment with S-Petasin were assessed by the determination of the cell viability, intracellular ROS levels, activation of the Nrf2 pathway and the resulting post-transcriptional antioxidant/antiapoptotic response. Our results show that S-Petasin pretreatment (1) reduces intracellular ROS levels, improving cell viability of RPE exposed to oxidative damage; (2) activates the Nrf2 signalling pathway, modulating the post-transcriptional response of its antioxidant chemical biomarkers; (3) reduces the Bax levels, and an increase in those of Bcl-2, with a concomitant downregulation of the Bax/Bc-2 ratio. Overall, our results provide the first evidence that S-Petasin is able to protect the RPE from oxidative damage. Full article

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO₂ extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC₅₀ values of 0.10 and 0.40 μg/mL, respectively. The IC₅₀ values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections. Full article

Petadolex^®, a defined butterbur extract has clinically proven efficacy against migraine attacks. However, spontaneous reports indicate cases of herbal induced liver injury (HILI). While most HILI patients presented mild serum biochemistry changes (<3 ULN, dose range 50 to 225 mg/day; treatment duration 4–730 days) nine developed severe HILI (average time-to-onset 103 days, ALT-range 3–153; AST 2–104-fold ULN). HILI cases resolved after medication withdrawal though two patients required liver transplantation. Liver biopsies revealed an inconsistent injury pattern, i.e. necrosis, macrovesicular steatosis, inflammation, cholestasis, and bile duct proliferation. Causality assessment rated 3 cases likely, 13 possible, 8 unlikely and 24 as unclassifiable/unclassified. Note, 22 patients reported hepatotoxic co-medications especially during periods of pain. A no-observable-adverse-effect-level at 15-fold of the maximal clinical dose (3 mg/kg/day MCD) was established for rats. At >45 and 90-fold MCD bile duct hyperplasia was observed but could not be confirmed in an explorative minipig study at 218-fold MCD. Human hepatocyte studies at 49-fold C_max serum petasins (=active ingredient) and therapeutic Ibuprofen, Paracetamol and Naratriptan concentrations evidenced liver transaminase and CYP-monooxygenase changes. Collectively, Petadolex^® HILI cases are rare, idiosyncratic and frequently confounded by co-medications. A physician-supervised self-medication plan with herbs and pain relief medication is needed to minimize risk for HILI. Full article

Calcitonin gene-related peptide (CGRP) is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine-related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL) and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL) extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 μM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S-petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further. Full article