Parthenolide is a natural compound that has shown highly promising anticancer activity. Even though its mode of action has been studied for decades, its antimitotic activity has been largely overlooked, limiting the understanding of its full anticancer potential. In this study, we combined click-chemistry with quantitative mass spectrometry and cell biology to elucidate the mechanism of action of parthenolide in mitosis. We show that parthenolide does not act as a microtubule-targeting agent in cells. Instead, it binds to the kinetochore protein ZNF207/BUGZ, preventing the establishment of proper kinetochore-microtubule attachment. Our results show that parthenolide covalently binds to Cys54 of BUGZ via Michael addition to its α-methylene-γ-lactone moiety. Since Cys54 is located within the second zinc-finger domain of the BUGZ microtubule-targeting region, we propose that parthenolide interferes with the microtubule-binding ability of BUGZ, consequently preventing kinetochore-microtubule attachments required for accurate chromosome congression to the spindle equator.

Covering: up to early 2025Privileged compound classes of anti-inflammatory natural products are those where there are many reported members that possess anti-inflammatory properties. The identification of these classes is of particular relevance to drug discovery, as they could serve as valuable starting points in developing effective and safe anti-inflammatory agents. The privileged compound classes of natural products include the polyphenols, coumarins, labdane diterpenoids, sesquiterpene lactones, isoquinoline and indole alkaloids, each offering a variety of molecular scaffolds and functional groups that enable diverse interactions with biological targets. From a medicinal chemistry point of view, natural products are both a boon and a bane. The multi-targeting nature of natural products is a boon in the treatment of multi-factorial diseases such as inflammation, but promiscuity, poor potency and pharmacokinetic properties are significant hurdles that must be addressed to ensure these compounds can be effectively used as therapeutics. In addition, there are continued controversies regarding the efficacies of some of these natural products that will continue to polarise their use. In this review, examples of natural products of six privileged compound classes will be discussed for their potential use and possible further development as anti-inflammatory drugs.

Tiryāq (Theriac) refers to a single or compound medication historically utilized as a general antidote against numerous poisons in several ethnomedical traditions, especially in traditional Persian medicine (PM). This study aims to summarize the traditional uses, phytochemistry, and pharmacological activities of medicinal plants with tiryāq properties, with a particular focus on their anti-hepatotoxic, hepatoprotective, neuroprotective, and cardioprotective activities.

Classical texts of traditional PM were broadly reviewed to extract information about tiryāq and its mechanisms. In addition, a detailed search of scientific databases was performed to validate the pharmacological properties of plants traditionally recognized for their antidotal effects.

Thirty-one medicinal plants with antidote properties were identified. The primary function of tiryāq, as described in PM, is to neutralize toxins and bolster the immune system. These plants have cardiotonic, hepatoprotective, and neuroprotective properties. In addition to their antidotal applications, tiryāq remedies were traditionally used to manage chronic cough, stomachache, asthma, colic, and other ailments. Modern pharmacological studies support these applications, highlighting the plants' antiviral, immunomodulatory, and antioxidant properties, especially against acute respiratory viral infections and other inflammatory circumstances.

Tiryāq plays a pivotal role in fortifying essential organs, including the heart, brain, and liver. Its prophylactic use during epidemics, along with its antioxidant and immune-stimulating properties, underscores its therapeutic potential. Further research is needed to conclusively determine the efficacy and broader therapeutic applications of medicinal plants with tiryāq properties.

Pulmonary fibrosis (PF) is a slow and irreparable damage of the lung caused by the accumulation of scar tissue, which eventually results in organ dysfunction and fatality from gas exchange failure. One of the extensively studied inflammatory pathways in PF is the NF-κB signalling pathway, which is reportedly involved in epithelial-mesenchymal transition, myofibroblast differentiation, and other cellular processes. Additionally, studies have evidence that NF-κB signalling pathways can be employed as a potential target for developing therapeutic agents against PF. In the current scenario, FDA-approved drugs, nintedanib and pirfenidone, have been used for the treatment of PF with potential side effects. Recently, the usage of bioactive compounds has attracted attention in the treatment of PF. This review focuses on the involvement of the NF-κB signalling pathway in PF and the significance of phytocompounds in regulating the NF-κB pathway. Both the in vitro and in vivo studies reveal that NF-κB-targeted plant-based bioactive compounds significantly ameliorate the PF condition as well as improve the health condition. Databases such as Scopus, PubMed, and Web of Science were used to conduct literature surveys and compile data on all the bioactive compounds. In conclusion, the plant-derived bioactive compounds are potent enough to target the NF-κB with its biological properties, and this could be a highly effective therapeutic strategy for PF in the future.

The popularity of herbal medicine continues to increase in modern health care practices; therefore, it is imperative to recognize and address potential risks associated with its everyday use. The Asteraceae family is one of the most extensively utilized medicinal plant families due to its abundance and diversity of bioactive secondary metabolites. The aim of this article is to review the current understanding of the allergic potential of the most significant medicinal plant species belonging to the Asteraceae family.

This review utilized various search engines, including PubMed Central, Cochrane Central, Google Scholar, and others, up to January 2024, considering only articles in English.

Asteraceae have long been acknowledged as important sensitizers within occupational environments, eliciting both immediate and delayed hypersensitivity reactions. Recent investigations have indicated the presence of panallergens in Asteraceae pollen, predominantly identified in Ambrosia artemisiifolia and Artemisia spp., which are pervasive across many species within the family. These panallergens contribute to cross-reactivity phenomena, serving as primary triggers for pollinosis and pollen-food or pollen-medicine allergy syndrome. In addition, the diverse array of secondary metabolites present in the Asteraceae family, particularly sesquiterpene lactones (SLs), possesses sensitizing properties capable of inducing skin irritation and inflammation. Moreover, SLs have the potential to incite systemic reactions, posing a risk to sensitized individuals upon ingestion. Although extensive cross-reactivity among SLs has been reported, further investigations are warranted to elucidate the underlying mechanisms and implications.

As numerous uncertainties persist regarding critical Asteraceae allergens and sensitizers further research is critical to augment our understanding of the potential risks posed by Asteraceae herbal medicine.

Background: Migraine, a complex neurological condition, poses significant challenges for both sufferers and healthcare providers. While prescription medications play a vital role in managing migraine attacks, the quest for natural, non-pharmacological alternatives has garnered increasing interest. This review explores the efficacy and safety of natural supplements as treatments for migraine relief, comparing them with conventional prescription medications. Methods: The review delves into herbal supplements, clinical studies on natural remedies, aromatherapy, dietary influences, and lifestyle modifications in the context of migraine management in several databases. Results: The findings shed light on the potential of natural supplements as complementary or alternative approaches to traditional migraine therapies, offering insights into a holistic and personalized treatment paradigm for migraine sufferers. Conclusions: Natural supplements have gained attention as potential treatments for migraine relief, often perceived as safer alternatives to conventional medications.

Congenital central hypoventilation syndrome (CCHS), a rare genetic disease caused by heterozygous PHOX2B mutations, is characterized by life-threatening breathing deficiencies. PHOX2B is a transcription factor required for the specification of the autonomic nervous system, which contains, in particular, brainstem respiratory centers. In CCHS, PHOX2B mutations lead to cytoplasmic PHOX2B protein aggregations, thus compromising its transcriptional capability. Currently, the only available treatment for CCHS is assisted mechanical ventilation. Therefore, identifying molecules with alleviating effects on CCHS-related breathing impairments is of primary importance. A transcriptomic analysis of cells transfected with different PHOX2B constructs was used to identify compounds of interest with the CMap tool. Using fluorescence microscopy and luciferase assay, the selected molecules were further tested in vitro for their ability to restore the nuclear location and function of PHOX2B. Finally, an electrophysiological approach was used to investigate ex vivo the effects of the most promising molecule on respiratory activities of PHOX2B-mutant mouse isolated brainstem. The histone deacetylase inhibitor SAHA was found to have low toxicity in vitro, to restore the proper location and function of PHOX2B protein, and to improve respiratory rhythm-related parameters ex vivo. Thus, our results identify SAHA as a promising agent to treat CCHS-associated breathing deficiencies.

Chronic migraine is recognized by the WHO as one of the most debilitating chronic conditions. It is primarily caused by central sensitization of the trigeminal nucleus caudalis. Key biomarkers associated with migraine include NFkB, IL-1β, CGRP, and iNOS. While CGRP antagonists have proven effective in treating migraines, Chrysanthemum indicum L., a traditional herbal remedy, has not been established as a treatment.

To address this, we investigated whether Fargesin, a lignan found in CI, could potentially reduce migraines by targeting these biomarkers. We conducted pharmacokinetic, toxicological, and in-silico studies. Molecular docking studies revealed a strong interaction between Fargesin and CGRP/iNOS.

The pharmacokinetic analysis indicated robust intestinal absorption and effective penetration of the blood-brain barrier. In-silico toxicity assessments showed favorable results. Promising interactions with drug targets were observed in bioactivity tests.

Fargesin from Chrysanthemum indicum may hold potential as a therapeutic agent for migraines.

Sesquiterpene lactones (STLs) are a prominent group of plant secondary metabolites predominantly found in the Asteraceae family and have multiple ecological roles and medicinal applications. This review describes the evolutionary and ecological significance of STLs, highlighting their roles in plant defence mechanisms against herbivory and as phytotoxins, alongside their function as environmental signalling molecules. We also cover the substantial role of STLs in medicine and their mode of action in health and disease. We discuss the biosynthetic pathways and the various modifications that make STLs one of the most diverse groups of metabolites. Finally, we discuss methods for identifying and predicting STL biosynthesis pathways. This article is part of the theme issue 'The evolution of plant metabolism'.

Tanacetum parthenium is a medicinal plant from the Asteraceae family that can be applied externally in the case of various skin diseases. The aim of the study was to perform a phytochemical analysis of hydroethanolic extracts from the aerial parts (herb), flower heads, and leaves of feverfew and to assess their biological properties. Hydrodistilled oils were analyzed using GC-MS. The chemical composition of the extracts was estimated using spectrophotometry and the HPLC method. Moreover, the extracts were evaluated to determine their antioxidant potential using DPPH and FRAP and measuring the intracellular level of ROS. The cytotoxicity of extracts toward keratinocytes and fibroblasts was also analyzed, as well as their antimicrobial properties against 12 microorganisms. The results of the research revealed that chrysanthenone and α-thujone were the dominant volatile compounds in the essential oil from the flowers, while camphor, trans-chrysanthenyl acetate, and camphene were predominant in the essential oil from the leaves and herb. The results of HPLC showed that the major polyphenol compounds present in the hydroethanolic extracts from various parts of T. parthenium were 3,5-dicaffeoyl-quinic acid, chlorogenic acid, and 3,4-dicaffeoyl-quinic acid. The extract from feverfew flowers was shown to have the highest content of total polyphenols, flavonoids, and phenolic acids, as well as the highest antioxidant potential. In turn, the herb extract had the highest content of condensed tannins and terpenoids and exhibited the most effective antimicrobial properties against the 12 bacterial and fungal strains. Moreover, the hydroethanolic extracts from different parts of T. parthenium plants were shown to have a potent protective effect on skin cells. The present study supports the potential applications of Tanacetum parthenium in the cosmetic and pharmaceutical industries.

ACT001 is a potent anti-inflammatory small-molecule drug. However, the single cell and spatial molecular basis of pyroptosis and whether ACT001 exerts a therapeutic effect by preventing pyroptosis on acute lung injury (ALI) remains unclear.

The bioinformatics approach was employed to identify single cell and spatial landscape of nucleotide-binding domains and leucine-rich repeat protein 3 (NLRP3)-dependent pyroptosis in lipopolysaccharide (LPS) and influenza virus-induced ALI. Molecular docking was performed to elucidate the relationship between ACT001 and NLRP3. LPS-induced ALI mice model was established. Histopathological analysis and bronchoalveolar lavage fluid collection were conducted to investigate the anti-inflammatory and protective effects. In vitro experiments were also performed on bone marrow-derived macrophages to explore the effect of ACT001 on the balance of mitochondrial fusion and fission protein.

Single cell transcriptomic and spatial transcriptomic analysis predicted that NLRP3-dependent pyroptosis significantly correlated with the development of ALI both in single cell and spatial distribution. Molecular docking provided a stable and reliable docking between ACT001 and NLRP3. ACT001 improved the 7-day survival of mice by approximately 50% over the loading dose of LPS-induced ALI. ACT001 (5 uM) attenuated the disruption of mitochondrial integrity and reactive oxygen species. Further, ACT001 reduced the overexpression of the mitochondrial fission protein DRP1 without affecting fusion protein Mitofusin2 levels. Moreover, ACT001 exerted a similar protective effect of suppressing pyroptosis as the DRP1-inhibitor Mdivi-1.

Our study revealed that pyroptosis genes were highly expressed in single-cell and spatial mapping along the first week of ALI occurrence. ACT001 attenuates ALI by reducing the NLRP3-dependent pyroptosis and balancing mitochondrial fission and fusion.

The traditional use of Tanacetum parthenium (L.) Sch.Bip., commonly known as feverfew, extends across various medical conditions, notably those associated with pain and inflammation. In alignment with the growing trend towards developing medications that target specific signaling pathways for enhanced efficacy and reduced side effects, extensive research has been conducted to investigate and validate the pharmacological effects of feverfew. Among its bioactive compounds, parthenolide stands out as the most potent, categorized as a germacranolide-type sesquiterpene lactone, and has been extensively studied in multiple investigations. Significantly, the anti-inflammatory properties of feverfew have been primarily attributed to its capacity to inhibit nuclear factor-kappa B (NF-κB), resulting in a reduction in pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α). Furthermore, the anticancer properties of feverfew have been associated with the modulation of Mitogen-Activated Protein Kinase (MAPK) and NF-κB signaling pathways. This study further delves into the neuroprotective potential of feverfew, specifically in the management of conditions such as migraine headaches, epilepsy, and neuropathic pain through various mechanisms. The core objective of this study is to elucidate the phytochemical composition of feverfew, with a particular emphasis on understanding the molecular mechanisms and examining the signaling pathways that contribute to its pharmacological and therapeutic effects. Additionally, the safety, toxicity, and potential adverse effects of feverfew are comprehensively evaluated, with an overarching goal of providing valuable insights into the plant's potential for targeted and effective treatments.

Parthenolide (PTL) is a sesquiterpene lactone that occurs naturally. It demonstrates a variety of beneficial effects, such as antioxidant, anti-inflammatory, and antiapoptotic properties. The study investigated the potential protective impact of PTL on indomethacin (INDO) induced stomach ulcers in rats. The rats were classified into 5 distinct categories. Group 1 served as the "control" group. Rats in the second group received a single oral dosage of INDO (50 mg kg-1). Rats in Groups three and four received 20 and 40 mg kg-1 oral PTL 1 h before INDO. Omeprazole (30 mg kg-1) was given orally to Group 5 rats 1 h before INDO. Pretreatment with PTL increased stomach pH and decreased gastric volume as well as reduced the morphological and histological changes induced by INDO. Analysis of probable pathways showed that pre-treatment with PTL successfully reduced oxidative, inflammatory, and apoptotic consequences caused by INDO. The ingestion of PTL leads to a notable increase in the levels of glutathione reduced (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, PTL decreased the concentration of malondialdehyde (MDA). In contrast, it was shown that PTL increased both cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2). PTL shows a significant decrease in the expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). PTL therapy resulted in a decrease in Bcl-2-associated X protein (Bax) levels and an increase in B-cell lymphoma 2 (Bcl2) levels. In conclusion, PTL offers gastroprotection by its antioxidant, anti-inflammatory, and anti-apoptotic qualities.

Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (7), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (8), 1β-hydroxy-arbusculin A (9), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate (10) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (11); one lignan, pinoresinol (12); one norisoprenoid, loliolide (13); six flavonoids (four genins and two glycosides), hispidulin (14), nepetin (15), jaceosidin (16), eriodictyol (17), eriodictyol-3'-O-β-D-glucoside (18) and eriodictyol-7-O-β-D-glucuronide (19); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (20), arbutin (21) and nebrodenside A (22). From the isolated compounds, only nepetin (15) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound (18) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22, while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds' bioactivity ratings for potential therapeutic targets were very promising.

Huntington's disease (HD) is a progressive neurodegenerative disease that causes motor, cognitive, and psychiatric abnormalities, with no satisfying disease-modifying therapy so far. 3-nitropropionic acid (3NP) induces behavioural deficits, together with biochemical and histological alterations in animals' striata that mimic HD. The role of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in HD pathogenesis remains largely uncharacterized. Parthenolide (PTL), a naturally occurring nuclear factor kappa B (NF-κB) inhibitor, is also known to inhibit NLRP3 inflammasome. Whether PTL is beneficial in HD has not been established yet.

This study evaluated the possible neuroprotective effects of PTL against 3NP-induced behavioural abnormalities, striatal biochemical derangements, and histological aberrations.

Male Wistar rats received PTL (0.5 mg/kg/day, i.p) for 3 weeks and 3NP (10 mg/kg/day, i.p) was administered alongside for the latter 2 weeks to induce HD. Finally, animals were subjected to open-field, Morris water maze and rotarod tests. Rat striata were examined histologically, striatal protein expression levels of glial fibrillary acidic protein (GFAP), cluster of differentiation 45 (CD45) and neuron-specific enolase (NSE) were evaluated immunohistochemically, while those of interleukin (IL)-1β, IL-18, ionized calcium-binding adapter molecule-1 (Iba1) and glutamate were determined by ELISA. Striatal nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein (Keap1), NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, S100 calcium-binding protein A10 (S100A10) and complement-3 (C3) were assessed by gene expression analysis.

PTL improved motor, locomotor, cognitive and anxiety-like behaviours, restored neuronal integrity, upregulated Nrf2, and inhibited NLRP3 inflammasome, NF-κB and microglial activation. Additionally, PTL induced astrocyte shifting towards the neuroprotective A2 phenotype.

PTL exhibits neuroprotection against 3NP-induced HD, that might be ascribed, at least in part, to its modulatory effects on Keap1/Nrf2 and NF-κB/NLRP3 inflammasome signaling.

Parthenolide is a germacrane sesquiterpene lactone separated from the traditional medicinal plant feverfew. Previous studies have shown that parthenolide possesses many pharmacological activities, involving anti-inflammatory and anticancer activities. However, the antitumor mechanism of parthenolide has not been fully elucidated. Thus, we investigate the potential antitumor mechanisms of parthenolactone. We predicted through network pharmacology that parthenolide may target HIF-1α to interfere with the occurrence and development of cancer. We found that parthenolide inhibited PD-L1 protein synthesis through mTOR/p70S6K/4EBP1/eIF4E and RAS/RAF/MEK/MAPK signaling pathways and promoted PD-L1 protein degradation through the lysosomal pathway, thereby inhibiting PD-L1 expression. Immunoprecipitation and Western blotting results demonstrated that parthenolide inhibited PD-L1 expression by suppressing HIF-1α and RAS cooperatively. We further proved that parthenolide inhibited cell proliferation, migration, invasion, and tube formation via down-regulating PD-L1. Moreover, parthenolide increased the effect of T cells to kill tumor cells. In vivo xenograft assays further demonstrated that parthenolide suppressed the growth of tumor xenografts. Collectively, we report for the first time that parthenolide enhanced T cell tumor-killing activity and suppressed cell proliferation, migration, invasion, and tube formation by PD-L1. The current study provides new insight for the development of parthenolide as a novel anticancer drug targeting PD-L1.

Anemophilous weeds from the Asteraceae family are highly allergenic and represent a significant source of aeroallergens in late summer and autumn. Ragweed and mugwort pollen allergies have become a significant health burden in Europe. Some people with respiratory allergies to weed pollen may also suffer hypersensitivity reactions to herbal medicines obtained from certain cross-reactive plants in the Compositae family, such as chamomile, marigold, and purple coneflower. General physicians, ear, nose, and throat (ENT) specialists, and pulmonologists need to be familiar with the diagnostic tests used by allergists in clinical practice to support accurate diagnosis in such patients. Allergists must also be aware of the suggestions of the European Medicines Agency (EMA)'s Herbal Medicinal Products Committee and the broad spectrum of herbal therapies to educate their patients about potential risks.

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.

Parthenolide (PTL), a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium, exhibits various biological effects by targeting NF-kB, STAT3, and other pathways. It has emerged as a promising adjunct therapy for multiple malignancies.

To evaluate the in vitro and in vivo effect of PTL on cyclophosphamide (CTX) metronomic chemotherapy.

The cytotoxicity of PTL and CTX on Lewis lung cancer cells (LLC cells) was assessed by measuring cell activity and apoptosis. The anti-tumor efficiency was evaluated using a tumor xenograft mice model, and the survival of mice and tumor volume were monitored. Additionally, the collected tumor tissues were analyzed for tumor microenvironment indicators and inflammatory factors.

In vitro, PTL demonstrated a synergistic effect with CTX in inhibiting the growth of LLC cells and promoting apoptosis. In vivo, metronomic chemotherapy combined with PTL and CTX improved the survival rate of tumor-bearing mice and reduced tumor growth rate. Furthermore, metronomic chemotherapy combined with PTL and CTX reduced NF-κB activation and improved the tumor immune microenvironment by decreasing tumor angiogenesis, reducing Transforming growth factor β, and α-SMA positive cells.

PTL is an efficient compound that enhances the metronomic chemotherapy effects of CTX both in vitro and in vivo, suggesting its potential as a supplementary therapeutic strategy in metronomic chemotherapy to improve the chemotherapy effects.

Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the "omics" era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.

The microtubule (MT) network plays a major role in the transport of the cardiac sodium channel Nav1.5 to the membrane, where the latter associates with interacting proteins such as dystrophin. Alterations in MT dynamics are known to impact on ion channel trafficking. Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, is associated with an increase in MT detyrosination, decreased sodium current (INa), and arrhythmias. Parthenolide (PTL), a compound that decreases MT detyrosination, has shown beneficial effects on cardiac function in DMD. We here investigated its impact on INa and Nav1.5 subcellular distribution.

Ventricular cardiomyocytes (CMs) from wild-type (WT) and mdx (DMD) mice were incubated with either 10 µM PTL, 20 µM EpoY, or dimethylsulfoxide (DMSO) for 3-5 h, followed by patch-clamp analysis to assess INa and action potential (AP) characteristics in addition to immunofluorescence and stochastic optical reconstruction microscopy (STORM) to investigate MT detyrosination and Nav1.5 cluster size and density, respectively. In accordance with previous studies, we observed increased MT detyrosination, decreased INa and reduced AP upstroke velocity (Vmax) in mdx CMs compared to WT. PTL decreased MT detyrosination and significantly increased INa magnitude (without affecting INa gating properties) and AP Vmax in mdx CMs, but had no effect in WT CMs. Moreover, STORM analysis showed that in mdx CMs, Nav1.5 clusters were decreased not only in the grooves of the lateral membrane (LM; where dystrophin is localized) but also at the LM crests. PTL restored Nav1.5 clusters at the LM crests (but not at the grooves), indicating a dystrophin-independent trafficking route to this subcellular domain. Interestingly, Nav1.5 cluster density was also reduced at the intercalated disc (ID) region of mdx CMs, which was restored to WT levels by PTL. Treatment of mdx CMs with EpoY, a specific MT detyrosination inhibitor, also increased INa density, while decreasing the amount of detyrosinated MTs, confirming a direct mechanistic link.

Attenuating MT detyrosination in mdx CMs restored INa and enhanced Nav1.5 localization at the LM crest and ID. Hence, the reduced whole-cell INa density characteristic of mdx CMs is not only the consequence of the lack of dystrophin within the LM grooves but is also due to reduced Nav1.5 at the LM crest and ID secondary to increased baseline MT detyrosination. Overall, our findings identify MT detyrosination as a potential therapeutic target for modulating INa and subcellular Nav1.5 distribution in pathophysiological conditions.

Parkinson's disease (PD) is the most common progressive neurodegenerative disorder affecting more than 10 million people worldwide and is characterized by the progressive loss of Daergic (DA) neurons in the substantia nigra pars compacta. It has been reported that signaling pathways play a crucial role in the pathogenesis of PD, while the active ingredients of traditional Chinese medicine (TCM) have been found to possess a protective effect against PD. TCM has demonstrated significant potential in mitigating oxidative stress (OS), neuroinflammation, and apoptosis of DA neurons via the regulation of signaling pathways associated with PD.

This study discussed and analyzed the signaling pathways involved in the occurrence and development of PD and the mechanism of active ingredients of TCM regulating PD via signaling pathways, with the aim of providing a basis for the development and clinical application of therapeutic strategies for TCM in PD.

With "Parkinson's disease", "Idiopathic Parkinson's Disease", "Lewy Body Parkinson's Disease", "Parkinson's Disease, Idiopathic", "Parkinson Disease, Idiopathic", "Parkinson's disorders", "Parkinsonism syndrome", "Traditional Chinese medicine", "Chinese herbal medicine", "active ingredients", "medicinal plants" as the main keywords, PubMed, Web of Science and other online search engines were used for literature retrieval.

PD exhibits a close association with various signaling pathways, including but not limited to MAPKs, NF-κB, PI3K/Akt, Nrf2/ARE, Wnt/β-catenin, TLR/TRIF, NLRP3, Notch. The therapeutic potential of TCM lies in its ability to regulate these signaling pathways. In addition, the active ingredients of TCM have shown significant effects in improving OS, neuroinflammation, and DA neuron apoptosis in PD.

The active ingredients of TCM have unique advantages in regulating PD-related signaling pathways. It is suggested to combine network pharmacology and bioinformatics to study the specific targets of TCM. This not only provides a new way for the prevention and treatment of PD with the active ingredients of TCM, but also provides a scientific basis for the selection and development of TCM preparations.

Infection and inflammation are critical to global human health status and the goal of current pharmacological interventions intends formulating medications/preventives as a measure to deal with this situation. Chemokines and their cognate receptors are major regulatory molecules in many of these ailments. Natural products have been a keen source to the drug development industry, every year contributing significantly to the growing list of FDA approved drugs. A multiverse of natural resource is employed as a part of curative regimen in folk/traditional/ethnomedicine which can be employed to discover, repurpose, and design potent medications for the diseases of clinical concern.

This review aims to systematically document the ethnopharmacologically active agents targeting the infectious-inflammatory diseases through the chemokine-receptor nexus.

Articles related to chemokine/receptor modulating ethnopharmacological anti-inflammatory, anti-infectious natural sources, bioactive compounds, and formulations have been examined with special emphasis on women related diseases. The available literature has been thoroughly scrutinized for the application of traditional medicines in chemokine associated experimental methods, their regulatory outcomes, and pertinence to women's health wherever applicable. Moreover, the potential traditional regimens under clinical trials have been critically assessed.

A systematic and comprehensive review on the chemokine-receptor targeting ethnopharmaceutics from the available literature has been provided. The article discusses the implication of traditional medicine in the chemokine system dynamics in diverse infectious-inflammatory disorders such as cardiovascular diseases, allergic diseases, inflammatory diseases, neuroinflammation, and cancer. On this note, critical evaluation of the available data surfaced multiple diseases prevalent in women such as osteoporosis, rheumatoid arthritis, breast cancer, cervical cancer and urinary tract infection. Currently there is no available literature highlighting chemokine-receptor targeting using traditional medicinal approach from women's health perspective. Moreover, despite being potent in vitro and in vivo setups there remains a gap in clinical translation of these formulations, which needs to be strategically and scientifically addressed to pave the way for their successful industrial translation.

The review provides an optimistic global perspective towards the applicability of ethnopharmacology in chemokine-receptor regulated infectious and inflammatory diseases with special emphasis on ailments prevalent in women, consecutively addressing their current status of clinical translation and future directions.

Tanacetum parthenium L. (Asteraceae) is a perennial herbaceous plant with a long-standing historical use in traditional medicine. Recently Tanacetum parthenium L. essential oil has been associated with a promising potential for future applications in the pharmaceutical industry, in the cosmetics industry, and in agriculture. Investigations on the essential oil (EO) have indicated antimicrobial, antioxidant, and repellent activity. The present study aimed to evaluate the chemical composition of Bulgarian T. parthenium essential oil from two different regions, to compare the results to those reported previously in the literature, and to point out some of its future applications. The essential oils of the air-dried flowering aerial parts were obtained by hydrodistillation using a Clevenger-type apparatus. The chemical composition was evaluated using gas chromatography with mass spectrometry (GC-MS). It was established that the oxygenated monoterpenes were the predominant terpene class, followed by the monoterpene hydrocarbons. Significant qualitative and quantitative differences between both samples were revealed. Camphor (50.90%), camphene (16.12%), and bornyl acetate (6.05%) were the major constituents in the feverfew EO from the western Rhodope Mountains, while in the EO from the central Balkan mountains camphor (45.54%), trans-chrysanthenyl acetate (13.87%), and camphene (13.03%) were the most abundant components.

The medicinal plants of the Asteraceae family are a valuable source of bioactive secondary metabolites, including polyphenols, phenolic acids, flavonoids, acetylenes, sesquiterpene lactones, triterpenes, etc. Under stressful conditions, the plants develop these secondary substances to carry out physiological tasks in plant cells. Secondary Asteraceae metabolites that are of the greatest interest to consumers are artemisinin (an anti-malarial drug from Artemisia annua L.-sweet wormwood), steviol glycosides (an intense sweetener from Stevia rebaudiana Bert.-stevia), caffeic acid derivatives (with a broad spectrum of biological activities synthesized from Echinacea purpurea (L.) Moench-echinacea and Cichorium intybus L.-chicory), helenalin and dihydrohelenalin (anti-inflammatory drug from Arnica montana L.-mountain arnica), parthenolide ("medieval aspirin" from Tanacetum parthenium (L.) Sch.Bip.-feverfew), and silymarin (liver-protective medicine from Silybum marianum (L.) Gaertn.-milk thistle). The necessity to enhance secondary metabolite synthesis has arisen due to the widespread use of these metabolites in numerous industrial sectors. Elicitation is an effective strategy to enhance the production of secondary metabolites in in vitro cultures. Suitable technological platforms for the production of phytochemicals are cell suspension, shoots, and hairy root cultures. Numerous reports describe an enhanced accumulation of desired metabolites after the application of various abiotic and biotic elicitors. Elicitors induce transcriptional changes in biosynthetic genes, leading to the metabolic reprogramming of secondary metabolism and clarifying the mechanism of the synthesis of bioactive compounds. This review summarizes biotechnological investigations concerning the biosynthesis of medicinally essential metabolites in plants of the Asteraceae family after various elicitor treatments.

Some of the vernacular or scientific names are related to possible medicinal and/or toxic properties that can reveal the presence of potential bioactive agents, contributing to the discovery of new drugs and/or knowledge of the risks associated with their use. This study sought to list the scientific and vernacular names of plants whose lexicons are related to those possible properties of plants and to compare them with the "ethno" (ethnobotanical and ethnopharmacological) and pharmacological data available in the scientific literature. A floating reading of the two classical and reference works on Brazilian medicinal plants was performed, and plants with vernacular and/or scientific names related to the possible medicinal and/or toxic properties were listed. Correlations between the meanings of the species' names (lexicon) and their possible biological properties were made from their translation from Latin by consulting dictionaries. A bibliographic survey was conducted on the "ethno" and pharmacological data for each species. Finally, data from these three dimensions (lexicon, "ethno," and pharmacology) were classified and compared using a bioprospection classification. It resulted in a list of 90 plant species belonging to 47 families. 66 of the 90 species presented "ethno" data from the scientific literature, while 46 species presented pharmacological data. Of these, 46 (69.7%) and 27 (58.7%), respectively, showed equivalence with the possible medicinal and/or toxic properties of plants according to their lexicons. According to this study, half of the plants investigated demonstrate equivalence in the three dimensions analyzed (lexicons, "ethno," and pharmacological data from the scientific literature). Gastrointestinal and nervous system categories are among the most common in all three dimensions. Plant lexicons may be closely linked to the possible medicinal and/or toxic properties and the study of plant lexicons may represent one more approach for the search for new drugs, mainly considering the gastrointestinal, nervous, and parasites categories.

This study provides a unique translational research opportunity to help both humans and dogs diagnosed with diseases that carry dismal prognoses in both species: histiocytic sarcoma (HS), hemangiosarcoma (HSA), and disseminated mastocytosis/mast cell tumor (MCT). Although exceedingly rare in humans, these so called "orphan diseases" are relatively more common in dogs. For these and other more commonplace cancers like lymphoma (Lym), dogs are an excellent translational model for human disease due to remarkably similar disease biology. In this study, assays were performed to assess the therapeutic potential of parthenolide (PTL), a known canonical nuclear factor kappa B (NF-κB) signaling inhibitor with additional mechanisms of antineoplastic activity, including alteration of cellular reduction-oxidation balance. Canine cell lines and primary cells are sensitive to PTL and undergo dose-dependent apoptosis after exposure to drug. PTL exposure also leads to glutathione depletion, reactive oxygen species generation, and NF-κB inhibition in canine cells. Standard-of-care therapeutics broadly synergize with PTL. In two canine HS cell lines, expression of NF-κB pathway signaling partners is downregulated with PTL therapy. Preliminary data suggest that PTL inhibits NF-κB activity of cells and extends survival time in a mouse model of disseminated canine HS. These data support further investigation of compounds that can antagonize canonical NF-κB pathway signaling in these cancers and pave the way for clinical trials of PTL in affected dogs. As dogs are an excellent natural disease model for these cancers, these data will ultimately improve our understanding of their human disease counterparts and hopefully improve care for both species. SIGNIFICANCE STATEMENT: Disseminated neoplasms in human and canine cancers are challenging to treat, and novel therapeutic approaches are needed to improve outcomes. Parthenolide is a promising treatment for histiocytic sarcoma, hemangiosarcoma, and mast cell neoplasia.

Rosacea is a chronic skin disorder that affects more than 5% of the world's population, with the number increasing every year. Moreover, studies show that one-third of those suffering from rosacea report a degree of depression and are less compliant with treatment. Despite being the subject of prolonged studies, the pathogenesis of rosacea remains controversial and elusive. Since most medications used for the management of this pathology have side effects or simply do not yield the necessary results, many patients lose trust in the treatment and drop it altogether. Thus, dermato-cosmetic products with natural ingredients are gaining more and more notoriety in front of synthetic ones, due to the multiple benefits and the reduced number and intensity of side effects. This review is a comprehensive up-to-date report of studies that managed to prove the beneficial effects of different botanicals that may be useful in the short and long-term management of rosacea-affected skin. Based on recent preclinical and clinical studies, this review describes the mechanisms of action of a large array of phytochemicals responsible for alleviating the clinical symptomatology of the disease. This is useful in further aiding and better comprehending the way plant-based products may help in managing this complex condition, paving the way for research in this area of study.

Five new sesquiterpenoids, including a campherenane-type (1), a bergamotane-type (2), a drimane-type (3), and two bisabolane-type (5-6) sesquiterpenoids have been isolated from Biscogniauxia sp. 71-10-1-1. Their structures were determined by spectroscopic analyses, quantum chemical ECD calculations,13C chemical shifts calculations, and X-ray crystallography. This is the first report of campherenane-type and drimane-type sesquiterpenoids from Biscogniauxia. Furthermore, the anti-inflammatory assays of all compounds are evaluated, and the results showed that compounds 3 and 7 exhibited the effects against the production of the pro-inflammatory cytokine TNF-α.

The Vitamin D receptor (VDR) is a crucial nuclear receptor that plays a vital role in various physiological functions. To a larger extent, the genomic effects of VDR maintain general wellbeing, and its modulation holds implications for multiple diseases. Current evidence regarding using vitamin D or its synthetic analogs to treat non-communicable diseases is insufficient, though observational studies suggest potential benefits. Traditional Chinese medicines (TCMs) and bioactive compounds derived from natural sources have garnered increasing attention. Interestingly, TCM formulae and TCM-derived bioactive compounds have shown promise in modulating VDR activities. This review explores the intriguing potential of TCM and bioactive compounds in modulating VDR activity. We first emphasize the latest information on the genetic expression, function, and structure of VDR, providing a comprehensive understanding of this crucial receptor. Following this, we review several TCM formulae and herbs known to influence VDR alongside the mechanisms underpinning their action. Similarly, we also discuss TCM-based bioactive compounds that target VDR, offering insights into their roles and modes of action.

In this work, we studied Tanacetum vulgare, Tanacetum parthenium, and Tanacetum corymbosum (Asteraceae) cultivated at the Ghirardi Botanic Garden (Toscolano Maderno, Brescia, Northern Italy) of the University of Milan. An integrative research approach was adopted: microscopic and histochemical, with special focus on the secretory structures responsible for the productivity of secondary metabolites; phytochemical, with the analysis of the essential oil (EO) profiles from the air-dried, flowered aerial parts collected in June 2021; bio-ecological, with emphasis, based on literature data, on the ecology and biological activity of the main EO components. In all three species, two basic trichome morphotypes (flagellar non-glandular and biseriate glandular) occurred with different distribution patterns. The glandular ones produced terpenes, along with flavonoids. A high level of chemical variability in the EO compositions emerged, specifically for qualitative data. T. vulgare profile was more complex and heterogeneous than those obtained from T. parthenium and T. corymbosum, with camphor as the predominant compound, followed by farnesol and α-santalone, respectively. Finally, the obtained scientific findings were made available to the visitors of the botanic garden through new dissemination labeling that highlights the "invisible", microscopic features of the plants, from an Open Science perspective ("Botanic Garden, factories of molecules…work in progress"-Lombardy Region Project Lr. 25/2016, year 2021).

The chemotherapeutic agent paclitaxel (PTX) causes testicular toxicity due to oxidative stress. Parthenolide (PTL), the active ingredient of the Tanacetum parthenium plant, is used to treat inflammation, dizziness, and spasms. In the present study, we evaluated the therapeutic effect of PTL on PTX-induced testicular toxicity in rats and its role in reproductive function. To this end, 6 groups were formed: control, PTX, sham, T1, T2, and T3. After testicular toxicity was induced in rats with 8 mg/kg PTX, the rats were treated with 1 mg/kg, 2 mg/kg, and 4 mg/kg PTL for 14 days. GSH and MDA levels were measured in rat testicular tissue after the last dose of PTL was administered. To determine the damage caused by PTX to testicular tissue by detecting 8-OHdG and iNOS, sections were prepared and examined histopathologically and immunohistochemically. Furthermore, the gene expressions and enzymatic activities of SOD, CAT, GPx, GST, and GR were investigated in all groups. After PTL treatment, MDA, 8-OHdG, and iNOS levels decreased while GSH levels increased in testicular tissue. Increased levels of antioxidant genes and enzymes also reduced oxidative stress. Additionally, the expression levels of the Dazl, Ddx4, and Amh genes, which are involved in gametogenesis and sperm production, decreased in case of toxicity and increased with PTL treatment. The data from this study show that PTL may have a therapeutic effect in the treatment of testicular damage by eliminating the oxidative stress-induced damage caused by PTX in testicular tissue, providing an effective approach to alleviating testicular toxicity, and playing an important role in reproduction/sperm production, especially at a dose of 4 mg/kg.

Insomnia is repeated difficulty in falling asleep, maintaining sleep, or experiencing lowquality sleep, resulting in some form of daytime disturbance. Sleeping disorders cause daytime fatigue, mental confusion, and over-sensitivity due to insufficient recovery from a sound sleep. There are some drugs, such as benzodiazepines and anti-histaminic agents, which help to sleep induction and insomnia cure. However, the prolonged administration is unsuitable because of tolerance and dependence. Therefore, the researchers attempt to find new medicines with lesser adverse effects. Natural products have always been good sources for developing new therapeutics for managing diseases such as cancer, cardiovascular disease, diabetes, insomnia, and liver and renal problems. Ample research has justified the acceptable reason and relevance of the use of these herbs in the treatment of insomnia. It is worth noting that in this study, we looked into various Persian herbs in a clinical trial and in vivo to treat insomnia, such as Artemisia annua, Salvia reuterana, Viola tricolor, Passiflora incarnata, lettuce, and Capparis spinose. According to research, herb extracts and fractions, particularly n-butanol fractions with non-polar agents, impact the benzodiazepine receptors and have hypnotic properties. Also, alkaloids, glycosides, flavonoids, saponins, and tannins in practically every plant are mentioned making them the popular natural compounds to help with sleep disorders and promote calmness.

Humans are constantly at high risk of emerging pandemics caused by viral and bacterial infections. The emergence of new pandemics is mainly caused by evolved viruses and bacteria that are highly resistant to existing medications. The rapid evolution of infectious agents demands the urgent investigation of new therapeutic strategies to prevent and treat these infections at an early stage. One of these therapeutic strategies includes the use of medicinal herbs for their antibacterial and antiviral properties. The use of herbal medicines as remedies is very ancient and has been employed for centuries. Many studies have confirmed the antimicrobial activities of herbs against various pathogens in vitro and in vivo. The therapeutic effect of medicinal herbs is mainly attributed to the natural bioactive molecules present in these plants such as alkaloids, flavonoids, and terpenoids. Different mechanisms have been proposed for how medicinal herbs enhance the immune system and combat pathogens. Such mechanisms include the disruption of bacterial cell membranes, suppression of protein synthesis, and limitation of pathogen replication through the inhibition of nucleic acid synthesis. Medicinal herbs have been shown to treat a number of infectious diseases by modulating the immune system's components. For instance, many medicinal herbs alleviate inflammation by reducing pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha (TNF-α), interleukin-1, IL-6) while promoting the production of anti-inflammatory cytokines (e.g., IL-10). Medicinal herbs also play a role in defense against viral and intracellular infections by enhancing the proliferation and functions of natural killer cells, T-helper-1 cells, and macrophages. In this review, we will explore the use of the most common herbs in preventing and treating infectious and non-infectious diseases. Using current and recently published studies, we focus on the immunomodulatory and therapeutic effects induced by medicinal herbs to enhance immune responses during diseases.

Headache disorders are a significant global health burden, leading to reduced quality of life. While vast pharmacological treatments are available, they may be associated with adverse effects or inadequate efficacy for some patients, therefore there is a need for exploring alternate treatment strategies. This review gives a brief explanation and evaluation of some established and emerging non-pharmacological approaches for headache management, focusing on nutraceuticals and diet, acupuncture, cognitive behavioral therapy (CBT), biofeedback, relaxation techniques, autogenic training, and neuromodulation. Special consideration is given to psychological interventions as they increase patient self-efficacy and provide strategies for managing chronic pain. Future research should focus on optimizing these therapies, identifying patient-specific factors influencing their effectiveness, and integrating them into holistic headache management strategies.

Tuberculosis is a disease of poverty, discrimination, and socioeconomic burden. Epidemiological studies suggest that the mortality and incidence of tuberculosis are unacceptably higher worldwide. Genomic mutations in embCAB, embR, katG, inhA, ahpC, rpoB, pncA, rrs, rpsL, gyrA, gyrB, and ethR contribute to drug resistance reducing the susceptibility of Mycobacterium tuberculosis to many antibiotics. Additionally, treating tuberculosis with antibiotics also poses a serious risk of hepatotoxicity in the patient's body. Emerging data on drug-induced liver injury showed that anti-tuberculosis drugs remarkably altered levels of hepatotoxicity biomarkers. The review is an attempt to explore the anti-mycobacterial potential of selected, commonly available, and well-known phytocompounds and extracts of medicinal plants against strains of Mycobacterium tuberculosis. Many studies have demonstrated that phytocompounds such as flavonoids, alkaloids, terpenoids, and phenolic compounds have antibacterial action against Mycobacterium species, inhibiting the bacteria's growth and replication, and sometimes, causing cell death. Phytocompounds act by disrupting bacterial cell walls and membranes, reducing enzyme activity, and interfering with essential metabolic processes. The combination of these processes reduces the overall survivability of the bacteria. Moreover, several phytochemicals have synergistic effects with antibiotics routinely used to treat TB, improving their efficacy and decreasing the risk of resistance development. Interestingly, phytocompounds have been presented to reduce isoniazid- and ethambutol-induced hepatotoxicity by reversing serum levels of AST, ALP, ALT, bilirubin, MDA, urea, creatinine, and albumin to their normal range, leading to attenuation of inflammation and hepatic necrosis. As a result, phytochemicals represent a promising field of research for the development of new TB medicines.

Tanacetum parthenium, also known as feverfew, is rich in bioactive compounds, namely sesquiterpene lactones, flavonoids, and volatile oils. Sesquiterpene lactones possess anti-migraine activity, while phenolic compounds possess anti-inflammatory and antioxidant action. Phytochemical composition determines the pharmacological activity and so profiling is essential in quality assessment. The study aimed to evaluate cultivated feverfew plants' phenolic profiles and antioxidant activity. Eleven phenolic compounds were identified in the samples of feverfew in Ukraine. Hydroxycinnamic acids predominate in the quantitative content of all the samples, namely chlorogenic acid, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid. The total content of flavonoids ranged from 0.8 to 2.6%; the content of hydroxycinnamic acids varied from 3.3 to 6.5%. The obtained data testify to the prospects of using Ukrainian feverfew as a raw material with a significant content of phenolic substances to develop new herbal medicines.

Parthenolide (PTL) is a new compound extracted from traditional Chinese medicine. In recent years, it has been proven to play an undeniable role in tumors, autoimmune diseases, and inflammatory diseases. Similarly, an increasing number of experiments have also confirmed the biological mechanism of PTL in these diseases. In order to better understand the development trend and potential hot spots of PTL in cancer and other diseases, we conducted a detailed bibliometric analysis. The purpose of presenting this bibliometric analysis was to highlight and inform researchers of the important research directions, co-occurrence relationships and research status in this field. Publications related to PTL research from 2002 to 2022 were extracted on the web of science core collection (WoSCC) platform. CiteSpace, VOSviewers and R package "bibliometrix" were applied to build relevant network diagrams. The bibliometric analysis was presented in terms of performance analysis (including publication statistics, top publishing countries, top publishing institutions, publishing journals and co-cited journals, authors and co-cited authors, co-cited references statistics, citation bursts statistics, keyword statistics and trend topic statistics) and science mapping (including citations by country, citations by institution, citations by journal, citations by author, co-citation analysis, and keyword co-occurrence). The detailed discussion of the results explained the focus and latest trends from the bibliometric analysis. Finally, the current status and shortcomings of the research field on PTLwere clearly pointed out for reference by scholars.

The present study was designed to conduct a comprehensive systematic review and meta-analysis to assess the efficacy of herbal medicines as add-on therapy on lung function in asthmatic patients.

A comprehensive search of online databases was performed up to December 2021 to identify randomized controlled trials that used orally herbal preparations for asthma as add-on therapy. Studies were assessed for methodological quality using the Cochrane Collaboration's Risk of Bias tool. The main outcome was percent predicted value of forced expiratory volume (% predicted FEV1). Pooled weighted mean difference (WMD) estimate with corresponding 95% confidence interval (CI) was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account clinical and conceptual heterogeneity.

As a result, 1,525 studies were identified. 169 studies were reviewed in-depth and 23 studies met our systematic review inclusion criteria. Finally, nine randomized controlled trials were included in the meta-analysis. Findings indicated that use of herbal medicines in patients with asthma significantly improved % predicted FEV1 (WMD 3.73, 95% CI 1.76-5.70), with no evidence for significant heterogeneity (p = 0.56 [Q statistic], I² = 0.0%). In subgroup analysis by age, improvement in % predicted FEV1 was higher and significant in adults (WMD 5.16; 95% CI 2.68-7.63) compared to children (WMD = 1.27; 95% CI -1.98-4.51). Sensitivity analysis showed the significant effect of herbal medicine consumption on improving FEV1 was consistently (range of summary WMDs 3.27-4.59), indicating that the meta-analysis model was robust. There was no evidence of publication bias both visually and statistically.

Findings support, the complementary use of herbal medicines resulted in significant improvement in the lung function compared to standard treatment in asthmatic patients with no considerable adverse events. This improvement is more likely to be observed amongst adults.

Tanacetum parthenium (L.) Sch.Bip. (T. parthenium) is an aromatic perennial plant belonging to the Asteraceae family, also known as feverfew. It is widely distributed in various regions of Europe and other parts of the world. The plant has a rich background in the traditional medicine of many nations and has been used as a remedy for fever, pain, inflammation, asthma, rheumatism, menstrual disorders, etc. Methods: GC-MS analysis was conducted to determine the chemical composition of the isolated essential oil (EO). Using the method proposed by Litchfield and Wilcoxon, the average lethal dose (LD₅₀) of the EO on Wistar rats was determined for two routes of administration: oral (p.o.) and intraperitoneal (i.p.). The subacute toxicity of the EO was also tested by oral administration of a daily dose of 1.0 g/kg body weight (BW) for 28 days. The toxicity of the EO was evaluated by observing and evaluating changes in behavior, body weight, basic hematological and serum biochemical parameters, and histopathological changes of the internal organs.

Thirty-seven volatile organic compounds representing 94.58% of the total oil composition were tentatively detected in the obtained T. parthenium EO. The dominant compounds were camphor (45.47%), trans-chrisantenyl acetate (21.65%), camphene (9.48%), and cis-isogeraniol (5.42%). The results showed that the EO was not toxic when administered in acute oral doses. The acute mean lethal dose for intraperitoneal administration was LD₅₀ i.p. = 2.13 g/kg BW. In the subacute study involving administration of an oral dose of EO for 28 days, there were a number of changes in the hematological and serum biochemical parameters of the blood compared with the control group of animals. However, no symptoms of toxicity, changes in the body weight of the rats, death, or pathological changes in the histological indicators of the examined organs-brain, heart, stomach, liver, spleen and kidney-were found. Extrapolating the results obtained from the rat experiments, we can state that the EO is safe for use in doses below 1 g/kgBW for a period not exceeding one month.

Natural products have attracted extensive attention from researchers in medical fields due to their abundant biological activities. Parthenolide (PTL) is a sesquiterpene lactone originally purified from herb Feverfew (Tanacetum parthenium), recent studies have showed its potential activities of anti-cancer and anti-inflammatory. Acting as the most studied inflammasome, NLRP3 inflammasome played an important role in human diseases including type-2 diabetes (T2D), Alzheimer's disease (AD) and cryopyrin-associated periodic syndromes (CAPS). In this article, we show that PTL specially inhibits the activation of NLRP3 inflammation by block the upstream signal and prevent the assembly of NLRP3 inflammasome complex. Furthermore, we showed the treatment of PTL significantly attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation and dextran sulfate sodium (DSS)-induced colitis in mice models. Thus, our results demonstrate that PTL alleviates inflammation by targeting NLRP3 inflammasome, which indicate that PTL acting as a promising natural product for the treatment of NLRP3 inflammasome-related diseases.

Despite an increase in the incidence of breast cancer worldwide, overall prognosis has been consistently improving owing to the development of multiple targeted therapies and novel combination regimens including endocrine therapies, aromatase inhibitors, Her2-targeted therapies, and cdk4/6 inhibitors. Immunotherapy is also being actively examined for some breast cancer subtypes. This overall positive outlook is marred by the development of resistance or reduced efficacy of the drug combinations, but the underlying mechanisms are somewhat unclear. It is interesting to note that cancer cells quickly adapt and evade most therapies by activating autophagy, a catabolic process designed to recycle damaged cellular components and provide energy. In this review, we discuss the role of autophagy and autophagy-associated proteins in breast cancer growth, drug sensitivity, tumor dormancy, stemness, and recurrence. We further explore how autophagy intersects and reduces the efficacy of endocrine therapies, targeted therapies, radiotherapy, chemotherapies as well as immunotherapy via modulating various intermediate proteins, miRs, and lncRNAs. Lastly, the potential application of autophagy inhibitors and bioactive molecules to improve the anticancer effects of drugs by circumventing the cytoprotective autophagy is discussed.