Background/Objectives: The extraction and encapsulation of Tanacetum parthenium L. (feverfew) represent highly relevant approaches for maximizing the recovery and protection of its bioactive phytocomplexes, particularly the main active compound, parthenolide (PAR). The present study aimed to develop and optimize a cyclodextrin-based extraction and encapsulation method for T. parthenium to improve the chemical and physicochemical properties and biological activity of bioactive-rich phytocomplexes. Methods: The extraction process was optimized by comparing conventional maceration (ME) and ultrasound-assisted extraction (UE), using different ethanol-water mixtures as extractants, with and without hydroxypropyl-β-cyclodextrin (CD) as an extraction enhancer. The highest PAR yield (approximately 6.3 mg/g dried biomass), combined with enhanced total polyphenol and flavonoid contents, was achieved using 50% (v/v) ethanol with 0.5% CD under UE. The optimized extract was spray-dried to produce powder formulations, with or without carrier material, which have been characterized for their technological, chemical, physicochemical, structural, and biological properties. Results: The inclusion of CD significantly improved process yield (approximately 65% compared to 47% for the non-encapsulated extract) and reduced residual moisture content, indicating enhanced drying efficiency and improved powder stability. Furthermore, the encapsulated formulation demonstrated preserved antioxidant and anti-inflammatory activity in cell-based assays. Conclusions: The developed CD-based encapsulation method represents a promising strategy for stabilizing feverfew bioactives and enhancing their potential applicability in pharmaceutical and dermo-cosmetic formulations.

The genus Plenodomus remains relatively understudied, with limited reports regarding its specialized metabolites. In this study, the endophytic strain Plenodomus sp. IQ-2000, isolated from Tanacetum parthenium (L.) Schultz-Bip, was investigated following preliminary screenings that revealed a promising capacity to produce chemically diverse entities and inhibit human protein tyrosine phosphatase 1B (hPTP1B1-400). Using a strategy based on Feature-Based Molecular Networking (FBMN) integrated with the bioactivity of active fractions, five secondary metabolites (1-5) were prioritized and isolated. Their structures were elucidated through extensive NMR spectroscopy and high-resolution mass spectrometry (HRESIMS). Among the isolates, two undescribed phomanolide-type meroterpenoids, 7,8-epoxy-prephomanolide (1) and prephomanolide (2), are reported, whose absolute configuration were assigned via electronic circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) calculations. The isolation of 2 provides crucial experimental evidence for the previously hypothesized biosynthesis of this class of compounds. Compounds 2 and 3 exhibited moderate inhibitory potential against the evaluated target, with inhibition rates of 73.0 ± 3.5% and 51.5 ± 4.5% at 20 μg/mL, respectively. Notably, all isolated compounds are reported from the genus Plenodomus for the first time, expanding the known chemical space of this fungal genus.

The aim of this study was to investigate the therapeutic effects of parthenolide (PTL), the active constituent of Tanacetum parthenium, on paclitaxel (PTX)-induced cardiotoxicity at both gene and protein expression levels. 48 male Sprague-Dawley rats were divided into 6 groups. While no intervention was performed in the control group, the second group received 8 mg/kg PTX. The third group was administered dimethyl sulfoxide (DMSO) as the vehicle control, whereas the fourth, fifth, and sixth groups were treated with 1, 2, and 4 mg/kg PTL, respectively, following PTX administration. The results demonstrated that oxidative stress biomarkers, including glutathione (GSH) and malondialdehyde (MDA), were significantly altered following PTX treatment, indicating oxidative damage; however, PTL administration restored these levels to physiological ranges. Histopathological analyses revealed that PTX caused pathological alterations in cardiac tissue, such as hemorrhage and mononuclear cell infiltration, whereas PTL treatment substantially ameliorated these histopathological lesions. Additionally, 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, indicative of DNA damage, as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels, markers of inflammation, were significantly elevated following PTX treatment. PTL administration mitigated these changes, bringing biomarker levels closer to normal. Furthermore, antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were assessed at gene expression, enzymatic activity, and protein expression levels. The findings indicate that PTL exerts a potent therapeutic effect against PTX-induced cardiotoxicity. These results support the cardioprotective potential of PTL, suggesting that it mitigates PTX-induced oxidative stress and inflammatory responses.

Background: Schistosomiasis remains a major neglected tropical disease, with praziquantel (PZQ) as the only widely used treatment, despite its limitations. Parthenolide (PTL), a sesquiterpene lactone, exhibits potent in vitro antischistosomal activity; however, its poor aqueous solubility, low oral bioavailability, and chemical instability may limit its in vivo efficacy. Objective: This study investigated whether nanoencapsulation in nanostructured lipid carriers (NLC) could enable the in vivo antischistosomal activity of PTL. Methods: PTL was isolated from Tanacetum parthenium and incorporated into NLC using hot emulsification followed by ultrasonication. The resulting formulation (NLC-PTL) was physicochemically characterized, and its in vivo antischistosomal efficacy was evaluated in a murine model of Schistosoma mansoni infection. Results: NLC-PTL exhibited nanoscale size, low polydispersity, high encapsulation efficiency, and sustained drug release. In vivo, free PTL showed no significant effect on worm burden, whereas NLC-PTL achieved a marked reduction (77.9%) in adult worms and significantly decreased egg output compared to controls (p < 0.001). Blank NLC had no antiparasitic effect. Conclusions: Nanoencapsulation was associated with in vivo antischistosomal activity of PTL compared to the free compound. These findings suggest that formulation strategies may influence the in vivo performance of lipophilic natural products in schistosomiasis.

Parthenolide (PTN), a sesquiterpene lactone derived from the medicinal plant feverfew (Tanacetum parthenium), and its derivatives such as dimethylamino parthenolide (DMAPT) and dimethylaminomicheliolide fumarate (ACT001) exhibit distinguished anti-inflammatory, anticancer, antioxidant, and epigenetic activities, with accumulating evidence demonstrating their therapeutic potential in respiratory diseases. This review systematically summarizes the antitumor, anti-inflammatory, antioxidative, and antifibrotic effects of PTN and its derivatives in relevant animal models, elucidates the underlying pharmacological mechanisms involving STAT3, NF-κB, MAPK/ERK, and PI3K signaling pathways, and highlights recent advances in clinical applications and drug delivery strategies. A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus up to February 2026. Results demonstrate that PTN and its derivatives exert significant therapeutic effects in lung cancer, pulmonary fibrosis, asthma, pneumonia, and acute lung injury. We summarize the clinical translation progress of ACT001, including its safety and pharmacokinetic profiles, discuss emerging delivery systems such as micelles, and review the patent landscape of PTN derivatives. By integrating mechanistic insights with progress in clinical applications and drug delivery, this review provides a foundation for further mechanistic studies and supports the translational development of PTN-based therapies for respiratory disorders.

Skeletal muscle atrophy is a complex condition associated with various diseases, including chronic inflammation, and significantly impairs quality of life. Parthenolide, a bioactive compound derived from Tanacetum parthenium (feverfew), is well known for its anti-inflammatory properties, but its potential therapeutic effects on muscle atrophy remain underexplored. In this study, we evaluated the protective effects of parthenolide against muscle atrophy in both in vitro and in vivo models. Using TNF-α-treated C2C12 myotubes and a lipopolysaccharide (LPS)-induced muscle atrophy in mice, we assessed the impact of parthenolide through histology, functional assays, and molecular analyses. Our results demonstrated that parthenolide promoted myoblast differentiation and alleviated TNF-α-induced myotube atrophy by restoring myosin heavy chain (MyHC) expression and inhibiting muscle-specific ubiquitin ligases MuRF1 and MAFbx. Mechanistically, parthenolide regulates protein homeostasis by activating the Akt-mTOR pathway, inhibiting FoxO transcription factors, and suppressing inflammation via NF-κB inhibition. In vivo, parthenolide effectively reduced LPS-induced muscle mass loss, muscle fiber atrophy, and grip strength decline, with improvements linked to the downregulation of atrophy markers and the preservation of MyHC levels in muscle tissue. These findings indicate that parthenolide mitigates skeletal muscle atrophy through dual regulation of protein homeostasis and inflammation, highlighting its potential as a novel therapeutic agent for muscle-wasting disorders such as sarcopenia.

Parthenolide (PTL) and salicin (SA), the main active components in Feverfew (Tanacetum parthenium) and White Willow (Salix alba), respectively, have been traditionally used as a remedy for various types of pain, including headaches. Because PTL and SA have different mechanisms of action, we hypothesize that a combination of these drugs would result in an additive effect. We investigated the effects of local and/or systemic administration of PTL, SA, or their combination on cephalic mechanical hypersensitivity (MH) in acute and chronic model of migraine induced by dural application of inflammatory soup (IS) in rats of both sexes. We also studied the effect of combination of PTL and SA on the sensitization of the trigeminocervical complex (TCC) induced by IS application using immunohistochemical (calcitonin gene-related peptide [CGRP] expression) and electrophysiological approaches. When combining low doses of PTL (2.5 mg/kg) and SA (5 mg/kg), we found that single systemic administration of combination prevented acute cephalic MH only in females. However, when administered daily, the combination prevented both chronic ictal and interictal cephalic MH as well as the IS-induced increase in CGRP-immunoreactivity within the TCC, in both sexes. Notably, a single dural application of the combination also prevented acute sensitization of TCC wide dynamic range neurons. Combining PTL and SA have an antimigraine effect in both male and female rats. The combination exerts its preventive effect, at least in part, by blocking the afferent inputs from the dura during the induction phase, preventing thus the establishment of central sensitization.

Feverfew (Tanacetum parthenium) has been evaluated in multiple clinical studies for migraine management, with earlier meta-analyses suggesting therapeutic potential. Given recent randomised controlled trials (RCTs), this updated systematic review and meta-analysis aimed to assess feverfew's efficacy in reducing migraine frequency, severity, and associated symptoms. A comprehensive search of PubMed, EMBASE, and Google Scholar up to August 2025 identified nine double-masked, placebo-controlled RCTs involving 899 participants. Feverfew significantly reduced migraine attack frequency (IV: -1.11 [-1.23 to -0.99], p < 0.00001; I[2] = 28%), migraine duration (IV: -4.43 [-7.63, -1.23] at 95% CI, p = 0.007; I[2] = 98% and showed a non-significant trend towards reduced pain severity (IV: -0.63 [-1.48 to 0.21], p = 0.14; I[2] = 85%). No significant effects were observed on migraine associated symptoms such as nausea, vomiting, photophobia, and phonophobia. Moderate heterogeneity, risks of selection, and attrition bias limited the overall quality of the evidence. Feverfew may offer modest benefits in migraine prevention, warranting further high-quality, large-scale RCTs with standardised protocols.

Tanacetum parthenium (Asteraceae) has been traditionally used worldwide for medicinal purposes, and some of its therapeutic uses have been attributed to the pharmacological effects of its secondary metabolites. The root culture of this species might represent a sustainable source of several pharmacologically active compounds. The biomass of a root T. parthenium culture was extracted with methanol and fractionated using column chromatography. Three selected fractions (4TP, 5TP, and 8TP) were analyzed via spectrophotometric, chromatographic, and mass spectrometry techniques and in vitro pharmacological assays. The greatest values for total phenolic and phenolic acid contents and antibacterial activity against Escherichia coli were determined for 4TP. The highest values for total flavonoid and sesquiterpene lactone contents, antioxidant potential, and α-amylase inhibitory effect were determined for 8TP. The antibacterial effect against Staphylococcus aureus was not significantly different among the three fractions. The root culture of T. parthenium is a potential source of several metabolites, such as phenolic acids, fatty acids, coumarins, sesquiterpenoids, and triterpenoids, which are capable of exerting α-amylase inhibition and antioxidant, antibacterial, and cytotoxic effects. Among eight phenolic compounds detected and quantified in the fractions, chlorogenic acid was the most abundant.

Pyrethrum parthenium, a perennial herb from the genus Pyrethrum within the Asteraceae family, is known for its potent fragrance and significant economic value. Nevertheless, the mechanisms involved in the synthesis and regulation of its floral fragrance compounds remain unclear. This study used gas chromatography-mass spectrometry (GC-MS) to analyze the volatile compounds in five parts of P. parthenium: tubular flowers, ligulate flowers, sepals, receptacles, and leaves. The results showed that the volatile aromatic components include terpenes such as camphor, α-pinene, camphene, d-limonene, β-caryophyllene, and β-farnesene, with camphor being the main volatile compound. Based on the transcriptome data of tubular flowers of P. parthenium, a terpene synthase gene, PpTPS5, was identified. The results of both in vitro and in vivo enzymatic assays demonstrated that PpTPS5 functions as a bifunctional terpene synthase gene. The qRT-PCR results showed that the gene expression pattern of PpTPS5 is correlated with the release pattern of the corresponding terpene aromatic compounds in P. parthenium. Subcellular localization and inhibitor experiments indicated that PpTPS5 functions in the cytosol. Additionally, dual-luciferase and electrophoretic mobility shift assay (EMSA) assays revealed that PpMYB9 can bind to the promoter of PpTPS5 to regulate the biosynthesis of terpenoids. In conclusion, the results of this study provide a theoretical basis for further exploration of the transcriptional regulation of terpene floral fragrance compounds in P. parthenium.

Parthenolide is confirmed to be an important component of the anticancer drug-ACT001. However, parthenolide biosynthesis in Saccharomyces cerevisiae (S. cerevisiae) was greatly hindered by the low conversion rate of its precursor, costunolide. In this study, the Position Specific Scoring Matrix (PSSM) was used to analyze the sequence evolutionary information of parthenolide synthase from Tanacetum parthenium (TpPTS), and a series of mutants were designed and validated. Notably, when the mutant of TpPTS-Y22G was introduced in S. cerevisiae, the parthenolide titer increased by 110 % compared to that of the TpPTS wild-type. Considering TpPTS as an endoplasmic reticulum-localized cytochrome P450 and the importance of heme supply, endoplasmic-associated molecular chaperone HRD1 (hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1) and heme biosynthesis gene HEM2 (aminolevulinate dehydratase) were overexpressed in S. cerevisiae to improve TpPTS expression and catalytic activity. As a result, a titer of 27.08 mg/L parthenolide was achieved in a shake flask, which was further increased by 209 %. Additionally, the conversion rate of costunolide to parthenolide increased from 20.4 % to 51.8 % compared to the initial strain yYTQ001. Eventually, a parthenolide titer of 99.71 mg/L was achieved in a 5-L bioreactor. Our research provides effective strategies and valuable references for engineering rate-limiting cytochrome P450 enzymes to improve sesquiterpenes production in S. cerevisiae.

The cytokine storm, a hyperinflammatory response characterized by the excessive release of pro-inflammatory mediators such as TNFα, INFγ, IL-1β, IL-6, and GM-CSF, has been identified as a critical factor in the progression and severity of acute inflammatory conditions. Regulating these pathways is essential for mitigating systemic damage and improving outcomes. Natural products from tropical American plants have shown significant potential in modulating these hyperinflammatory responses. Key polyphenols, like quercetin and luteolin, found in plants such as Achyrocline satureioides and Mangifera indica demonstrate the downregulation of NF-κB and inhibition of pro-inflammatory cytokines. Alkaloids, such as berberine and mitraphylline, isolated from Berberis species and Uncaria tomentosa, respectively, have shown potent effects in suppressing nitric oxide production and regulating inflammasomes. Terpenoids, including parthenolide from Tanacetum parthenium and curcumol from Curcuma longa, exhibit multitarget activity, reducing cytokine levels and inhibiting key inflammatory enzymes like COX-2 and iNOS. These findings highlight the immense potential of bioactive compounds from tropical American plants as modulators of immune-inflammatory pathways, providing a foundation for developing effective therapeutic agents to counteract the severe effects of cytokine storms.

Over the last twenty years, the role of microgliosis and astrocytosis in the pathophysiology of neurodegenerative diseases has increasingly been recognized. Dysregulation of microglial and astrocyte properties and function has been described also in the fatal degenerative motor neuron disease amyotrophic lateral sclerosis (ALS). Microglia cells, the immune cells of the nervous system, can either have an immunonegative neurotoxic or immunopositive neuroprotective phenotype. The feverfew plant (Tanacetum parthenium) derived compound parthenolide has been found to be capable of interfering with microglial phenotype and properties. Positive treatment effects were shown in animal models of neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. Now we were able to show that PTL has a modulating effect on primary mouse microglia cells, both wild type and SOD1, causing them to adopt a more neuroprotective potential. Furthermore, we were able to show that PTL, through its positive effect on microglia, also has an indirect positive impact on motor neurons, although PTL itself has no direct effect on these primary motor neurons. The results of our study give reason to consider PTL as a drug candidate for ALS.