Search Results (105)

The Turkistan Region of southern Kazakhstan lies within the Mountains of Central Asia biodiversity hotspot and harbors a flora of beneficial plants whose traditional use is well documented but whose chemistry and conservation status remain, for most species, formally unassessed. Following the PRISMA extension for Scoping Reviews (PRISMA-ScR), with accepted names verified against Plants of the World Online, this scoping review maps—for the first time as a single co-occurring assemblage rather than isolated single-taxon surveys—the evidence for nine regionally important species across the Nitrariaceae, Fabaceae, Apiaceae and Asteraceae. From 4362 records, 82 were charted by structured per-species extraction. The species span a broad chemical space: β-carboline alkaloids, furanocoumarins, sesquiterpene coumarins, sesquiterpene lactones and flavonoid-rich essential oils, sharing a recurring antioxidant and antimicrobial profile overlaid with species-specific effects such as the anthelmintic santonin of Artemisia cina. For most species the underlying data derive from non-Central Asian populations, limiting regional transferability, and safety evidence is sparse: no acute or repeated-dose toxicity study on regionally collected material was identified, although several species contain monoamine oxidase inhibitors, phototoxic furanocoumarins or thujone-rich oils. We propose a tiered, conservation-aware framework and a prioritized research agenda. Provenance was charted for all 82 records, and the country of origin could be established for 35. Full article

Bergapten is a plant-derived linear furanocoumarin widely distributed in Rutaceae and Apiaceae species and increasingly recognized for its multifunctional anticancer potential. This review critically synthesizes current evidence on bergapten’s biosynthesis, physicochemical and pharmacokinetic properties, anti-inflammatory and antioxidant pharmacodynamics, and mechanistic antitumor activity, highlighting its translational relevance within pharmaceutical development. Preclinical studies across diverse malignancies demonstrate pleiotropic anticancer effects. Mechanistically, bergapten activates mitochondrial apoptosis via Bax/Bcl-2 modulation and caspase cascades, induces cell cycle arrest through p53–p21 signaling, and suppresses PI3K/Akt/mTOR and NF-κB pathways. Additional effects include PTEN-mediated autophagy induction, interference with metabolic reprogramming, reversal of multidrug resistance through ABC transporter modulation, and context-dependent photoactivated cytotoxicity. Beyond direct tumor cell targeting, bergapten attenuates pro-inflammatory mediators and regulates redox homeostasis through downregulation of NOX4-derived ROS and activation of Nrf2-driven antioxidant defenses, addressing the redox–inflammatory axis implicated in carcinogenesis. Despite promising mechanistic depth, clinical translation is limited by incomplete human pharmacokinetic data and poor aqueous solubility. Nanotechnology-enabled delivery systems and structural derivatives offer strategies to enhance bioavailability and therapeutic index. Overall, bergapten emerges as a systems-level phytochemical candidate warranting further translational investigation in oncology. Full article

Finger lime (Citrus australasica) is an emerging high-value fruit species, yet the chemical profiles of Mediterranean-cultivated varieties remain underexplored. This study presents the first chemical characterization of two finger lime varieties, Pink Ice and Green Crystal, grown in Greece, providing the first report on the volatile and non-volatile composition of Green Crystal. Peel essential oils were extracted and analyzed through GC-MS across two harvesting periods (H1 and H2), while methanolic extracts were assessed for their total phenolic content (TPC) and DPPH radical scavenging activity. Non-volatile untargeted profiling was performed on stage H1 extracts using UHPLC-MS/MS. The results revealed a significant chemical divergence between the varieties. Green Crystal exhibited an unprecedented p-cymene/β-phellandrene/citronellal/citronellol volatile chemotype, while Pink Ice displayed a limonene/p-cymene/sabinene/terpinen-4-ol chemotype. Maturity of the fruit significantly influenced monoterpene distribution, with an increase in monoterpene hydrocarbons at the expense of oxygenated derivatives. TPC peaked at stage H1, showing a significant maturity-dependent decline in both varieties, whereas DPPH radical scavenging capacity remained stable across both harvests. UHPLC-MS/MS analysis annotated 58 metabolites, including several compounds reported for the first time in the species. Variety-specific tendencies were observed, with Pink Ice exhibiting greater diversity in flavanones, flavonols, and simple coumarins, whereas Green Crystal exhibited greater diversity in flavones, furanocoumarins, and HMG (hydroxy-3-methylglutaric acid)-flavonoid conjugates. These findings demonstrate that variety selection and harvesting timing are critical parameters for optimizing the commercial and bioactive value of Mediterranean-grown finger lime, highlighting the significant potential for expanded cultivation in the region. Full article

Furanocoumarins and their derivatives are found in various plant species and have attracted considerable attention due to their diverse biological activities. By analyzing the genomes of Apium Graveolens L. and Peucedanum praeruptorum Dunn, we characterized a set of candidate genes encoding key enzymes involved in furanocoumarin biosynthesis, including one prenyltransferase (AgPT1), cyclases (AgCOC1, PpCOC1 and PpCOC2), and methyltransferases (AgOMT1 and AgOMT2). Functional validation in Saccharomyces cerevisiae demonstrated that AgCOC1 and PpCOC2 accept both linear and angular substrates, whereas PpCOC1 accepts only linear substrates. Depending on the reaction conditions, these cyclases can produce compounds with either furan or pyran scaffolds. These findings reveal a previously unappreciated catalytic versatility of cyclases involved in furanocoumarin biosynthesis. Notably, the genes encoding the prenyltransferase and cyclases were found to be co-localized in the genome, which may significantly enhance the efficiency of furanocoumarin biosynthesis. This mechanism may account for the pronounced accumulation of furanocoumarins in Apiaceae plants. Finally, we provide the first evidence that AgOMT1 functions as a multifunctional methyltransferase capable of catalyzing the O-methylation modifications observed in furanocoumarins in A. graveolens. In conclusion, this study fills a research gap in our understanding of furanocoumarin biosynthesis and reveals that genes encoding cyclases and prenyltransferases are clustered in the genome, a pattern that arose during evolution. Full article

Xanthotoxin (8-methoxypsoralen) belongs to the group of naturally occurring furanocoumarin (furocoumarin) compounds and is a product of plant secondary metabolism. Analysis of the available literature indicates that xanthotoxin exhibits a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, immunomodulatory, and antibacterial effects. Xanthotoxin has been shown to stimulate autophagy via inhibition of the AKT/mTOR pathway, as well as to block cell migration by modulating RIG-1 and NF-κB signaling. Moreover, its effects on JNK/MAPK, PI3K/AKT, Calcium–CaMYK/PYK2, and other signaling cascades have been confirmed. Among its most promising properties is the ability to inhibit ABC transporters, thereby preventing the reduction of chemotherapeutic agent concentrations within tumor cells and enhancing their intracellular accumulation. Thus, the aim of this study was to evaluate xanthotoxin as a potential anticancer agent. The literature review was based on publications indexed in Google Scholar, Scopus, Web of Science, and PubMed and published between 2010 and 2026. Studies describing the biological properties of xanthotoxin, its toxicity, anticancer mechanisms of action, and modulation of ABC transporters were included. This literature review summarizes the pharmacological profile of xanthotoxin, and its biological activities and therapeutic potential, as well as its antitumor effects in various cancer cell lines. The available evidence may provide a foundation for the future development of xanthotoxin as a lead compound for anticancer drug discovery. Full article

Ostericum palustre (Besser) Besser (synonym Angelica pancicii Vandas ex. Velen.) is a Eurasian species from the Apiaceae family, previously related to the Balkan endemic species A. pancicii. The study aims to provide a thorough profiling of methanol-aqueous extracts from O. palustre leaves, roots, and inflorescences integrated with an evaluation of antioxidant potential and enzyme inhibitory activity towards some therapeutic targets. For the first time, a series of simple coumarins and furanocoumarins alongside phenolic and acylquinic acids, and flavonoids were annotated/dereplicated in the O. palustre of Bulgarian origin by liquid chromatography coupled with quadrupole—Orbitrap high resolution mass spectrometry acquisition platform. According to the discriminant analysis (sPLS-DA) of the biological potential, radical scavenging activity (47.9 mg TE/g in DPPH and 61.8 mg TE/g in ABTS), reducing power (102.2 mg TE/g in CUPRAC and 57.4 mg TE/g in FRAP), and metal-chelating capacity (20.1 mg EDTAE/g) accounted mainly for the stronger antioxidant activity of inflorescences extract than roots and leaves. Root extracts exhibited anti-collagenase, anti-elastase, and anti-hyaluronidase effects with lower IC₅₀ values (IC₅₀ 37.22, 42.47 and 32.09 μg/mL, respectively). Pearson relationship analysis revealed potent antioxidants including furanocoumarins (oxypeucedanin hydrate, xanthotoxol/bergaptol, byakangelicin/isobyakangelicin, ostruthol) and phenolic acids, while a series of angelols alongside feruloylquinic and dicaffeoylquinic acids, and flavonol glycosides hold significance for the neuroprotective activity of the leaves extract. The enzyme inhibitory activity of the root extracts towards collagenase, elastase and hyaluronidase, related to the anti-aging activity, was ascribed to simple hydroxylated/methoxylated coumarins. The study suggests the potential health benefits of O. palustre extracts as antioxidant, anti-aging, and neuroprotective agents. Full article

Imperatorin, a naturally occurring furanocoumarin found in several medicinal plants, has attracted considerable scientific interest due to its broad spectrum of pharmacological activities and emerging relevance in oncology. In recent years, an increasing number of experimental studies have investigated its biological effects and molecular mechanisms across different tumor models. Due to this, the review synthesizes the current preclinical and pharmacological evidence on imperatorin in cancer, with the aim of consolidating the main mechanistic pathways involved in its antitumor activity, identifying its therapeutic opportunities, and highlighting existing challenges and future research perspectives. Available in vitro and in vivo studies demonstrate that imperatorin exerts multi-targeted antitumor effects, including the induction of apoptosis, inhibition of proliferation, suppression of angiogenesis, modulation of oxidative stress, attenuation of inflammation, and disruption of oncogenic signaling pathways such as PI3K/Akt, MAPK, mTOR, and NF-κB. Imperatorin also influences the tumor microenvironment by reducing pro-inflammatory mediators, impairing stromal–tumor cross-talk, and enhancing immune-cell-mediated cytotoxicity. In addition, we also summarize pharmacokinetic and safety limitations that hinder clinical translation, including low oral bioavailability, extensive plasma protein binding, cytochrome P450 interactions, and insufficient toxicological data. In parallel, we highlight recent advances in the genetics and biosynthesis of imperatorin, which support perspectives for sustainable production and structural optimization of imperatorin derivatives. Finally, we outline key knowledge gaps and future directions, including improved delivery strategies, investigation of additional regulatory pathways, and more robust in vivo and translational studies, emphasizing that imperatorin remains a promising yet still incompletely characterized anticancer candidate. The review highlights the need for more comprehensive pharmacokinetic and safety assessments, as well as the development of improved delivery systems to address absorption and stability challenges. Further research into imperatorin’s effects on autophagy, ferroptosis, metabolic reprogramming, and the immune microenvironment is essential to deepen mechanistic understanding. Additionally, fully elucidating the biosynthetic enzymes responsible for imperatorin formation may facilitate sustainable production and the design of structurally optimized analogs. Full article

Background/Objectives: Osteoporosis is a metabolic bone disease characterized by reduced bone mass and impaired bone microarchitecture. It has become a major clinical challenge due to the limitations of current therapeutic approaches. Isoimperatorin (ISO), a naturally occurring and biologically active furanocoumarin extracted from various traditional herbals, exhibits therapeutic potential in combating osteoporosis. However, toxicity limits its application. Methods: In vivo, compound B15 was evaluated in an Ovariectomy (OVX) mice model, where treatment was associated with changes in bone microarchitecture parameters, modulation of serum bone metabolism markers, and alterations in the histopathological features of bone tissue. Results: In this study, a new series of furanocoumarin derivatives was designed and synthesized for the treatment of osteoporosis. Compared with ISO, compound B15 has less toxicity and better ability to inhibit osteoclast formation in vitro. Compound B15 could decelerate the progression of osteoporosis in ovariectomized mice. It is worth mentioning that the expression of estradiol in the serum of mice with excised ovaries was significantly increased by compound B15. Conclusions: These results imply that the novel furanocoumarin derivative B15 is a promising therapeutic option for osteoporosis. Full article

Peucedanum praeruptorum is increasingly cultivated as wild resources are depleted. However, cultivated plants often contain lower levels of coumarins than wild individuals and may not meet the standards of the Chinese Pharmacopoeia. To clarify whether growth year could influence coumarin accumulation, we analyzed P. praeruptorum populations cultivated for 1–3 years using a newly developed 17-coumarin quantification method and conducted transcriptomics to characterize gene expression across growth years. The results suggest that total coumarins and major pyranocoumarins (notably praeruptorin B) increased steadily with growth years, while furanocoumarins and simple coumarins increased initially then declined. Notably, despite substantial intra-population variation in coumarin content, cultivated plants could be classified into two distinct chemotypes: chemotype A (higher praeruptorin A and praeruptorin E, lower praeruptorin B) and chemotype B (lower praeruptorin A and praeruptorin E, higher praeruptorin B, pteryxin, and qianhucoumarin D than chemotype A). Both chemotypes coexisted across all examined populations, with the proportion of chemotype B increasing with growth years. Transcriptomic profiling revealed that 3-year-old plants showed higher expression of pyranocoumarin biosynthetic genes and lower expression of genes associated with simple coumarin and furanocoumarin biosynthesis compared with 1-year-old plants. Differential expression analysis further identified key candidate genes associated with growth years and chemotypes. Together, these results demonstrate that growth year and chemotype synergistically regulate coumarin accumulation in cultivated P. praeruptorum, providing a two-dimensional framework for improving the quality of cultivated medicinal materials. Full article

Sosnovsky’s hogweed (Heracleum sosnowskyi Manden.) is an invasive plant species widely distributed across Eastern Europe and Russia that poses a serious threat to human health due to its pronounced phototoxic properties. Contact with the plant sap followed by exposure to solar ultraviolet (UV) radiation frequently results in phytophotodermatitis, which is characterized by erythema, blistering, ulceration, and persistent hyperpigmentation. The development of these photochemical injuries—most notably furanocoumarins—act as potent photosensitizers and induce cellular and DNA damage upon UV activation. This review provides an integrated overview of the geographical spread and invasiveness of H. sosnowskyi, the chemical composition of its biologically active metabolites, and the molecular mechanisms underlying hogweed-induced skin injury. Particular emphasis is placed on the photochemical transformations of furanocoumarins, including psoralens and their photooxidation products, such as 1,2-dioxetanes, which generate reactive oxygen species and DNA crosslinks. In addition, the review examines other compounds derived from hogweed biomass—including furan derivatives, aromatic compounds, fatty acids, sterols, and their oxidative products—that may contribute to phototoxic and cytotoxic effects. Clinical manifestations of hogweed-induced burns, their classification, symptomatology, and current therapeutic approaches are critically discussed, highlighting the absence of standardized treatment guidelines. Rather than serving as a purely clinical or botanical survey, this review frames Sosnovsky’s hogweed injury as a solar-light-activated photochemical hazard, tracing the sequence from environmental sunlight exposure through molecular photochemistry to biological tissue damage. By integrating chemical, biological, and dermatological perspectives, the review aims to clarify injury mechanisms and support the development of more effective preventive and mitigation strategies under real-world exposure conditions. Full article

Heracleum sosnowskyi is considered to be a dangerous invasive plant species that has successfully naturalized within a variety of plant communities across numerous countries. As a result of its superior competitiveness, the alien species is able to displace the indigenous species from their native habitats, thus changing the ecosystems and decreasing biodiversity. The phytochemicals present in the H. sosnowskyi aqueous extracts were revealed using GC/MS and HPLC/DAD/TOF techniques. Isopsoralen, methoxsalen, (iso)pimpinellin and/or bergapten were determined to be major compounds in the leaf, inflorescence and root extracts. Glutaric, quinic, linolenic, (iso)chlorogenic and other polyphenolic acids were identified in the extracts. Furthermore, a number of furanocoumarins, including hermandiol, bakuchicin, candinols (A and C) and candibirin F, and coumarins, umbelliferone and yunngnins (A and B), were identified in the roots. Additionally, the presence of flavonoids, including astragalin, quercetin 7,3,4-trimethyl ether, nicotiflorin and rutin, has been detected in the flower and leaf extracts. Allelopathic effects of H. sosnowskyi aqueous extracts were tested on four model plants, lettuce (Lactuca sativa L.) and three native Lithuanian meadow herbs, perennial ryegrass (Lolium perenne L.), timothy (Phleum pratense L.) and white clover (Trifolium repens L.), using the Petri dish method. H. sosnowskyi flower and leaf extracts demonstrated the strongest inhibitory effects on the germination and growth of the tested plant seeds. At the highest relative concentrations, 0.5 and 1.0, extracts of Sosnowsky’s hogweed inflorescences inhibited timothy seedling growth by 95.47% (from 19.64 ± 2.57 mm to 0.89 ± 0.73 mm) and 100%, respectively. The leaf extracts exhibited the strongest inhibitory effects on white clover seedlings. The highest relative concentrations tested (0.5 and 1.0) suppressed clover seedling growth by 94.66% (from 41.22 ± 2.53 mm to 2.20 ± 0.63 mm) and 100%, respectively. Additionally, the germination rate and vigor index of model plants were assessed. The research is of significance for the regulation and monitoring of the spreading of aggressive H. sosnowskyi plants. Moreover, it is important for the development of natural herbicides based on active phytotoxic compounds from these plants. Full article

Heracleum sosnowskyi Manden., or H. sosnowskyi, of the Apiaceae was first cultivated in the USSR in 1947 as a potential fodder plant. Due to the development of cold-resistant cultivars and the characteristics of H. sosnowskyi, it quickly became feral. As a result, H. sosnowskyi began to spread as an aggressive invasive species in the 1970s and 1980s. By the 90s it had become an ecological disaster. As well as forming monocultures and displacing native species, H. sosnowskyi contains furanocoumarins, photosensitizing compounds that increase skin sensitivity to ultraviolet rays and cause severe burns. In addition, furanocoumarins have cytotoxic, genotoxic, mutagenic and estrogenic effects. H. sosnowskyi also contains essential oils, which are particularly active during flowering and can irritate the mucous membranes of the eyes and respiratory tract, as well as cause allergic reactions in the form of bronchospasm in people with asthma and hypersensitivity. When released in high concentrations, these biologically active compounds have an allelopathic effect on native plant species, displacing them and reducing biodiversity. As H. sosnowskyi is not native; the biologically active compounds it secretes have a xenobiotic effect, causing serious damage to the ecosystems it occupies. However, in parallel with these negative properties, furanocoumarins have been found to be effective in the treatment of cancer and skin diseases. Furanocoumarins possess antimicrobial antioxidant osteo- and neuroprotective properties. Essential oils containing octyl acetate, carboxylic acid esters, and terpenes can be used in the pharmaceutical industry as antiseptic and anti-inflammatory agents. Additionally, essential oils can be used as biofumigants and natural herbicides. A comprehensive approach allows H. sosnowskyi to be viewed in two ways. On the one hand, it is an aggressive alien species that causes significant damage to ecosystems and poses a threat to human health. On the other hand, it is a potentially valuable natural resource whose biomass can be used within the principles of the circular economy. It is hoped that the use of H. sosnowskyi for economic interests can be a partial compensation for the problem of its aggressive invasion, which is of anthropogenic origin. Full article

Natural products are a valuable source of bioactive compounds with established roles in oncology. Their structural diversity and ability to target multiple cancer-related pathways make them promising candidates for anticancer drug development. Increasing preclinical and clinical data highlight their potential not only to exert direct antitumor effects but also to enhance patient tolerance to conventional therapies by reducing side effects and improving treatment adherence. The Mediterranean region, known for its biodiversity and traditional dietary habits, provides a rich array of natural compounds with documented health benefits. Key Mediterranean natural plant products (MNPPs), including bioactives from olive oil, onion, citrus fruits, chili pepper and grapes, exhibit antioxidant, anti-inflammatory, and anti-proliferative properties. This review focuses on the molecular mechanisms of selected MNPPs, such as polyphenols, flavonoids, alkaloids, terpenes, organosulfur and furanocoumarin compounds, which modulate oxidative stress, inflammation, apoptosis, and tumor progression. Evidence from in vitro and in vivo studies supports their role in cancer prevention and as adjuvants in therapy. While further clinical research is needed, these findings suggest that incorporating MNPPs into therapeutic regimens could offer low-toxicity, multi-targeted support in oncology, improving both outcomes and quality of life in cancer patients. Full article

The invasive plant Heracleum sosnowskyi Manden. is a valuable source of a number of bioactive metabolites that can be used in the pharmaceutical industry and medicine and may have some other applications as well. Today, there is a need to summarize data on these substances as well as analyze the toxicological profile of the metabolites of H. sosnowskyi. In this study, we collected a dataset of 225 metabolites of H. sosnowskyi from different literature sources and performed cluster analysis of their chemical structures; we revealed five main clusters of compounds: terpenoids, aromatic compounds, polyaromatic compounds, fatty acids, and furanocoumarins. In order to fill the gaps in the experimental data on the toxicity of the studied substances, we used machine learning (ML) algorithms previously designed for high-accuracy prediction of toxicity end-points. The ML-based approach allowed us to fill in up to 90% of the missing median lethal dose $L{D}_{50}$ (mouse) data for the studied molecules. The validity of each predicted value was confirmed by analyzing the applicability domain of the used ML models. For the calculations and ML modeling, we used the Syntelly chemoinformatics platform. For the most toxic compounds—hydroxycoumarins and furanocoumarins of H. sosnowskyi—the values for hepatotoxicity, drug-induced liver injury (DILI), cardiotoxicity, and carcinogenicity were predicted. Based on the analysis of $L{D}_{50}$ values for the mouse animal model, the greatest toxicity for furanocoumarins is expected with the intravenous route of administration (62–450 mg/kg), which can cause drug-induced liver injury. At the same time, the data do not show high cardiotoxicity risks for the studied furanocoumarins. Based on the presented results, we discuss prospects of using some of the compounds as pharmaceutical agents. Full article

For thousands of years, medicinal plants and their constituents have been used, mostly empirically/ethnopharmacologically, to cure patients with central nervous system (CNS) disorders. Anxiolytics derived from natural products (NPs) often share similar mechanisms of action to synthetic ones (e.g., benzodiazepines, BDZs). Although typically as effective as synthetic anxiolytics, NPs are considered to be devoid of the serious side effects linked to the use of BDZs. 8-Methoxypeucedanin (8-MP) is a rare furanocoumarin present in the fruits of Peucedanum luxurians Tamamsch. (Apiaceae). The primary objective of the presented study was to assess the anxiolytic activity of 8-MP using a zebrafish (Danio rerio) model of anxiety. Danio rerio larvae at 5 days post-fertilization (dpf) were used, with reversed thigmotaxis considered as an index of the anxiolytic activity. In addition to the behavioral study, qPCR analyses were performed to assess the role of 8-MP in modulating the expression of c-fos and bdnf, two key genes involved in neural activity. As evidenced by the behavioral study, 8-MP (1.5–15 µM) exhibited a significant influence on anxiety, with a U-shape dose–response effect. Moreover, the expression of c-fos and bdnf genes was significantly downregulated, providing novel insights into the mechanisms of action of the tested furanocoumarin. Full article