Search Results (29)

Ferns represent an evolutionarily distinct group of vascular plants and constitute an underexplored source of structurally diverse secondary metabolites with potential medicinal value. Several fern-derived compounds, including sesquiterpenes, triterpenes, flavonoids, phloroglucinol derivatives, lactones, and glycosides, have been associated with antibacterial, antidiabetic, analgesic, anticancer, hepatoprotective, neuroprotective, and other biological activities. However, despite their biochemical uniqueness and long-standing use in traditional medicine, ferns remain less extensively investigated than angiosperms as sources of bioactive compounds. In addition to their natural phytochemical diversity, the production of secondary metabolites in ferns may be influenced by abiotic stressors, such as light quality and intensity, temperature, salinity, drought, water availability, and mineral nutrition. Available studies indicate that selected abiotic stress conditions can enhance the accumulation of phenolic acids, flavonoids, polyphenols, carotenoids, and related compounds in several fern families, including Aspleniaceae, Athyriaceae, Dryopteridaceae, Onocleaceae, and Thelypteridaceae. Nevertheless, information on stress-induced modulation of metabolites that are unique or highly characteristic of ferns, particularly terpenes, terpene glycosides, and specific flavonoid derivatives, remains limited. This review summarizes the current knowledge on unique secondary metabolites in ferns, their reported medicinal properties, and the potential use of abiotic stress as an elicitation strategy to enhance their production. Overall, the review highlights ferns as promising but still insufficiently explored reservoirs of bioactive metabolites and identifies key directions for future phytochemical, pharmacological, and cultivation-based research. Full article

The Helianthus genus comprises more than 60 species distributed throughout North and Central America, with a few extending into South America. Among these, H. annuus and H. tuberosus represent the most widely utilized and extensively investigated species. The aim of this paper is to provide an overview of the current knowledge regarding the phytochemical composition and biological activities of Helianthus species. Phytochemical studies of Helianthus taxa have demonstrated that terpenoid constituents, including sesquiterpene lactones, diterpenes, and triterpenes, together with phenolic compounds, constitute the principal classes of secondary metabolites. Pharmacological investigations on Helianthus extracts have revealed a broad spectrum of biological activities. More than twenty distinct bioactivities have been reported for H. annuus, with the majority supported by in vitro assays (≈26 reports), reflecting multiple experimental evaluations per activity using different plant parts, extracts, and models; followed by a substantial number of in vivo studies in animal models (≈21 reports), and very limited clinical evidence. In comparison, five bioactivities have been described for H. tuberosus, mainly in vitro with a few in vivo reports, whereas only single in vitro bioactivities have been described for H. salicifolius and H. angustifolius. Among these, antidiabetic, antioxidant, antimicrobial, and anticancer properties are the most frequently documented. Full article

Multidrug resistance (MDR) is a central cause of chemotherapy failure and tumor recurrence and metastasis, and its mechanism involves enhanced drug efflux, target mutation, upregulation of DNA repair and remodeling of the tumor microenvironment. ABC transporter protein (P-gp, MRP, and BCRP)-mediated efflux of drugs is the most intensively researched aspect of the study, but the first three generations of small-molecule reversal agents were stopped in the clinic because of toxicity or pharmacokinetic defects. Natural products are considered as the fourth generation of MDR reversal agents due to their structural diversity, multi-targeting and low toxicity. In this paper, we systematically summarize the inhibitory activities of monoterpenes, sesquiterpenes, diterpenes and triterpenes against ABC transporter proteins in in vitro and in vivo models and focus on the new mechanism of reversing drug resistance by blocking efflux pumps, modulating signaling pathways such as PI3K-AKT, Nrf2, NF-κB and remodeling the tumor microenvironment. For example, Terpenoids possess irreplaceable core advantages over traditional multidrug resistance (MDR) reversers: Compared with the first three generations of synthetic reversers, natural/semisynthetic terpenoids integrate low toxicity (mostly derived from edible medicinal plants, half-maximal inhibitory concentration IC₅₀ > 50 μM), high target specificity (e.g., oleanolic acid specifically inhibits the ATP-binding cassette (ABC) transporter subtype ABCC1 without cross-reactivity with ABCB1), and multi-mechanistic synergistic effects (e.g., β-caryophyllene simultaneously mediates the dual effects of “ABCB1 efflux inhibition + apoptotic pathway activation”). These unique characteristics enable terpenoids to effectively circumvent key limitations of traditional synthetic reversers, such as high toxicity and severe drug–drug interactions. Among them, lupane-type derivative BBA and euphane-type sooneuphanone D (triterpenoids), as well as dihydro-β-agarofuran-type compounds and sesquiterpene lactone Conferone (sesquiterpenoids), have emerged as the core lead compounds with the greatest translational potential in current MDR reverser research, attributed to their potent in vitro and in vivo MDR reversal activity, low toxicity, and excellent druggable modifiability. At the same time, we point out bottlenecks, such as low bioavailability, insufficient in vivo evidence, and unclear structure–activity relationship and put forward a proposal to address these bottlenecks. At the same time, the bottlenecks of low bioavailability, insufficient vivo evidence and unclear structure–activity relationship have been pointed out, and future research directions such as nano-delivery, structural optimization and combination strategies have been proposed to provide theoretical foundations and potential practical pathways for the clinical translation research of terpenoid compounds, whose clinical application still requires further in vivo validation and translational research support. Full article

Terpenes, the largest class of plant specialized products, are built from C5 building blocks via terpene synthases and oxidized by cytochrome P450 enzymes (CYPs) for structural diversity. In some cases, CYPs do not simply oxidize the terpene backbone, but induce backbone rearrangements, methyl group shifts, and carbon–carbon (C–C) scissions. Some of these reactions were characterized over 25 years ago, but most of them were reported in recent years, indicating a highly dynamic research area. These reactions are involved in mono-, sesqui-, di- and triterpene metabolism and provide key catalytic steps in the biosynthesis of plant hormones, volatiles, and defense compounds. Many commercially relevant terpenoids require such reaction steps in their biosynthesis such as triptonide (rodent pest management), secoiridoids (flavor determinants), as well as ginkgolides, cardenolides, and sesquiterpene lactones with pharmaceutical potential. Here, we provide a comprehensive overview of the underlying mechanisms. Full article

Oleanolic acid derivatives, specifically lactones (2–8) and bromolactones (9–14), were synthesised and evaluated for their cytotoxic, antioxidant, and pharmacokinetic profiles. The compounds were characterised using molecular docking simulations targeting the 1M17 protein, representing the EGFR tyrosine kinase domain. Compound 6 emerged as the most promising candidate, demonstrating strong interactions with residues critical for EGFR activity, such as LYS 721 and ASP 831. Biological assays revealed that compounds 6, 2, and 10 exhibited IC₅₀ values across various cancer cell lines in the micromolar range, with a favourable Selectivity Index. Antioxidant activity assays (CUPRAC and DPPH) highlighted compound 7 as the most substantial electron donor and compound 10 as the most influential radical scavenger. ADMETox analysis confirmed the favourable pharmacokinetic and safety profiles of the derivatives. These findings underscore the potential of the selected oleanolic acid derivatives as drug candidates for targeted cancer therapies, offering cytotoxic and antioxidant benefits. Despite their promising cytotoxic and antioxidant activities, translating oleanolic acid derivatives to clinical applications remains challenging due to their bioavailability and metabolic stability. Our findings highlight compound 6 as a leading candidate with enhanced activity, providing a foundation for further optimising and developing EGFR-targeted anticancer therapies. Full article

Five new non-holostane di- and trisulfated triterpene pentaosides, conicospermiumosides A₃-1 (1), A₃-2 (2), A₃-3 (3), A₇-1 (4), and A₇-2 (5) were isolated from the Far Eastern sea cucumber Cucumaria conicospermium Levin et Stepanov (Cucumariidae, Dendrochirotida). Twelve known glycosides found earlier in other Cucumaria species were also obtained and identified. The structures of new compounds were established on the basis of extensive analysis of the 1D and 2D NMR spectra, as well as by the HR-ESI-MS data. The aglycones of 1–5 differed by side chains structures. Additionally, conicospermiumoside A₇-1 (4) had a 9(11)-double bond in the aglycone, while the remaining glycosides contained a 7(8)-intranuclear double bond. Eight types of carbohydrate chains known earlier from the glycosides of the sea cucumbers of the Cucumaria genus were found as part of the glycosides of C. conicospermium. The set of sugar chains of the glycosides from C. conicospermium was similar to that from C. okhotensis. The raw biogenetic series of aglycones, leading to the formation of hexa-nor-lanostane derivatives in the process of biosynthesis and a sort of functionally-structural division that was realized due to separation of biosynthetic pathways of holostane and lanostane derivatives, can be traced when the structures of the glycosides isolated from C. conicospermium are compared. The cytotoxic action against three human breast cancer cell lines (MCF-7, T-47D, MDA-MB-231), and non-tumor MCF-10A and hemolytic activity of compounds 1–5, as well as seven known glycosides were tested. Conicospermiumosides A₃-3 (3) and A₇-1 (4), having a 22-oxo-23(24)-en fragment, were strongly hemolytic despite lacking a lactone in their aglycones. Moreover, both compounds demonstrated a promising suppressing action against triple negative breast cancer cells. The cells of the MDA-MB-231 line were most sensitive to the cytotoxic action of the glycosides, while the MCF-7 cell line was most sustainable. Six glycosides were selected for further study of some aspects of anticancer action against MDA-MB-231. The selective action of the compounds 4 and 8 on the MDA-MB-231 cells without significant toxicity against the MCF-10A cells was noticeable. More importantly, the selectivity of the compounds was changed over time and maximal selectivity to cancer cells was demonstrated by glycoside 1 at 48 h of exposition. The glycosides 1, 3 and the desulfated derivative 7a strongly inhibited colony formation and growth of the TNBC cells until the process stops completely. Okhotoside B₁ (8), DS-okhotoside A₁-1 (7a), and conicospermiumoside A₃-3 (3) showed a potent cell migration-inhibiting capacity. Quantitative structure–activity relationships (QSARs) calculated on the basis of a correlational analysis of the physicochemical properties and structural features of the glycosides and their cytotoxic activity against different cell lines showed some structural features influenced differently, sometimes even in opposite ways, on the activity of glycosides toward diverse cells (erythrocytes, MCF-10A, and TNBC MDA-MB-231 cells). This observation indicated that glycosides obviously target different membrane components, such as lipids of erythrocytes and some receptors on the surface of mammary normal or tumor cells. Full article

In this work, the leaves of K. tomentosa were macerated with hexane, chloroform, and methanol, respectively. The phytochemical profiles of hexane and chloroform extracts were unveiled using GC/MS, whereas the chemical composition of the methanol extract was analyzed using UPLC/MS/MS. The antibacterial activity of extracts was determined against gram-positive and gram-negative strains through the minimal inhibitory concentration assay, and in silico studies were implemented to analyze the interaction of phytoconstituents with bacterial peptides. The antioxidant property of extracts was assessed by evaluating their capacity to scavenge DPPH, ABTS, and H₂O₂ radicals. The toxicity of the extracts was recorded against Artemia salina nauplii and Caenorhabditis elegans nematodes. Results demonstrate that the hexane and chloroform extracts contain phytosterols, triterpenes, and fatty acids, whereas the methanol extract possesses glycosidic derivatives of quercetin and kaempferol together with sesquiterpene lactones. The antibacterial performance of extracts against the cultured strains was appraised as weak due to their MIC₉₀ values (>500 μg/mL). As antioxidants, treatment with extracts executed high and moderate antioxidant activities within the range of 50–300 μg/mL. Extracts did not decrease the viability of A. salina, but they exerted a high toxic effect against C. elegans during exposure to treatment. Through in silico modeling, it was recorded that the flavonoids contained in the methanol extract can hamper the interaction of the NAM/NAG peptide, which is of great interest since it determines the formation of the peptide wall of gram-positive bacteria. This study reports for the first time the biological activities and phytochemical content of extracts from K. tomentosa and proposes a possible antibacterial mechanism of glycosidic derivatives of flavonoids against gram-positive bacteria. Full article

Plants of the Meliaceae family have long attracted researchers’ interest due to their various insecticidal activities, with triterpenes being the main active ingredients. In this paper, we discuss 93 triterpenoids with insecticidal activity from 37 insecticidal plant species of 15 genera (Munronia, Neobeguea, Pseudocedrela, Nymania, Quivisia, Ruagea, Dysoxylum, Soymida, Lansium, Sandoricum, Walsura, Trichilia, Swietenia, Turraea, and Xylocarpus) in the family Meliaceae. Among these genera, Trichilia deserves further research, with twelve species possessing insecticidal activity. The 93 insecticidal molecules included 27 ring-seco limonoids (comprising 1 ring A-seco group chemical, 1 ring B-seco group chemical, 5 ring D-seco group chemicals, 14 rings A,B-seco group chemicals, 5 rings B,D-seco group chemicals, and 1 rings A,B,D-seco group chemical), 22 ring-intact limonoids (comprising 5 cedrelone-class chemicals, 6 trichilin-class chemicals, 7 havanensin-class chemicals, 2 azadirone-class chemicals, 1 vilasinin-class chemical, and 1 other chemical), 33 2,30-linkage chemicals (comprising 25 mexicanolide-class chemicals and 8 phragmalin-class chemicals), 3 1,n-linkage-group chemicals, 3 onoceranoid-type triterpenoids, 2 apotirucallane-type terpenoids, 2 kokosanolide-type tetranortriterpenoids, and 1 cycloartane triterpene. In particular, 59 molecules showed antifeedant activity, 30 molecules exhibited poisonous effects, and 9 molecules possessed growth regulatory activity. Particularly, khayasin, beddomei lactone, 3β,24,25-trihydroxycycloartane, humilinolides A–E and methyl-2-hydroxy-3β-isobutyroxy-1-oxomeliac-8(30)-enate showed excellent insecticidal activities, which were comparable to that of azadirachtin and thus deserved more attention. Moreover, it was noteworthy that various chemicals (such as 12α-diacetoxywalsuranolide, 11β,12α-diacetoxycedrelone, 1α,7α,12α-triacetoxy-4α-carbomethoxy-11β-hydroxy-14β,15β-epoxyhavanensin, and 11-epi-21-hydroxytoonacilide, etc.) from Turraea showed excellent insecticidal activity. Specially, the insecticidal activity of khayasin from Neobeguea against the coconut leaf beetle were similar to that of rotenone. Therefore, it was a promising candidate insecticide for the control of the coconut leaf beetle. Full article

Vernonia cinerea (L.) Less. is a perennial herbaceous plant found mainly in tropical areas, particularly in Southeast Asia, South America, and India. Various parts of V. cinerea have traditionally been used in folk medicine to treat several diseases, such as malaria, fever, and liver diseases. V. cinerea has so far yielded about 92 secondary metabolites. The majority of these are sesquiterpene lactones, but triterpenes, flavonoids, steroids, phenolics, and other compounds are present as well. V. cinerea crude extracts reportedly exhibit anti-inflammatory, antiprotozoal, antidiabetic, anticancer, antimicrobial, antioxidant, and renoprotective activities. This study aims to provide the latest up-to-date information on the botanical characterization, distribution, traditional uses, phytochemistry, and pharmacological activity of V. cinerea. Information on V. cinerea was thoroughly reviewed. The literature published between 1950 and 2024 was compiled through online bibliographic databases, including SciFinder, Web of Science, Google Scholar, PubMed, ScienceDirect, Springer Link, Wiley, and the MDPI online library. The keywords used for the literature search included Vernonia cinerea (L.) Less. and the synonyms Cyanthillium cinereum (L.) H.Rob., Conyza cinerea L., and various others. Full article

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. Full article

Ecuador is one of the major cocoa producers worldwide, but its productivity has lately been affected by diseases. Endophytic biocontrol agents have been used to minimize pathogenic effects; however, compounds produced by endophytes are minimally understood. This work presents the chemical characterization of the Trichoderma species extracts that proved inhibition against cocoa pathogens. Solid–liquid extraction was performed as a partitioning method using medium with the fungal mycelia of Trichoderma reesei (C2A), Trichoderma sp. (C3A), Trichoderma harzianum (C4A), and Trichoderma spirale (C10) in ethyl acetate individually. The extract of T. spirale (C10) exhibited the growth inhibition (32.97–47.02%) of Moniliophthora perniciosa at 10 µg/mL, while a slight stimulation of Moniliophthora roreri was shown by the extracts of T. reesei (C2A) and T. harzianum (C4A) at higher concentrations. The inhibitory activity could be related to alkaloids, lactones, quinones, flavonoids, triterpenes, and sterols, as indicated by chemical screening and antifungal compounds, such as widdrol, β-caryophyllene, tyrosol, butyl isobutyrate, sorbic acid, palmitic acid, palmitelaidic acid, linoleic acid, and oleic acid, which were identified by gas chromatography–mass spectrometry (GC-MS). The results showed that the extracts, particularly T. spirale (C10), have the potential as biocontrol agents against witches’ broom disease; however, further studies are needed to confirm their effectiveness. Full article

Fruiting bodies, mycelia, or spores in the form of extracts or powder of various medicinal mushrooms are used to prevent, treat, or cure a range of ailments and balance a healthy diet. Medicinal mushrooms are found in several genera of fungi and their fruit bodies, cultured mycelia, and cultured broth contains phytochemical constituents such as triterpenes, lectins, steroids, phenols, polyphenols, lactones, statins, alkaloids, and antibiotics. Edible mushrooms are considered functional foods that can be used as supplements for complementary and alternative medicines where the markets are growing rapidly. Several species of edible mushrooms possess therapeutic potential and functional characteristics. The psilocybin-containing types, sometimes known as magic mushrooms, have been utilized for generations by indigenous communities due to their hallucinogenic, medicinal, and mind-manifestation properties. Recent clinical research also convinces that these psychedelics have the potential to treat addiction, depression, anxiety, and other mental health concerns. This has escalated the demand for the natural products derived from the mushrooms of these sources, yet the agronomic aspect and biotechnology approaches to produce the active ingredients are not collectively documented. The objectives of this review article are to examine the general type and variation of therapeutic mushrooms, especially those belonging to the Psilocybe. The biotechnology approach for cultivation and the production of secondary metabolites is also appraised. The ultimate purposes are to provide guidance for farmers and companies to pursue sustainable ways to produce natural products for the development of functional food and pharmaceuticals and to support the alteration of the stigmatic drug concerns around psychedelic mushrooms. Full article

The transcription factor MYB is expressed predominantly in hematopoietic progenitor cells, where it plays an essential role in the development of most lineages of the hematopoietic system. In the myeloid lineage, MYB is known to cooperate with members of the CCAAT box/enhancer binding protein (C/EBP) family of transcription factors. MYB and C/EBPs interact with the co-activator p300 or its paralog CREB-binding protein (CBP), to form a transcriptional module involved in myeloid-specific gene expression. Recent work has demonstrated that MYB is involved in the development of human leukemia, especially in acute T-cell leukemia (T-ALL) and acute myeloid leukemia (AML). Chemical entities that inhibit the transcriptional activity of the MYB-C/EBPβ-p300 transcription module may therefore be of use as potential anti-tumour drugs. In searching for small molecule inhibitors, studies from our group over the last 10 years have identified natural products belonging to different structural classes, including various sesquiterpene lactones, a steroid lactone, quinone methide triterpenes and naphthoquinones that interfere with the activity of this transcriptional module in different ways. This review gives a comprehensive overview on the various classes of inhibitors and the inhibitory mechanisms by which they affect the MYB-C/EBPβ-p300 transcriptional module as a potential anti-tumor target. We also focus on the current knowledge on structure-activity relationships underlying these biological effects and on the potential of these compounds for further development. Full article

Four new triterpene disulfated glycosides, chitonoidosides E₁ (1), F (2), G (3), and H (4), were isolated from the Far-Eastern sea cucumber Psolus chitonoides and collected near Bering Island (Commander Islands) at depths of 100–150 m. Among them there are two hexaosides (1 and 3), differing from each other by the terminal (sixth) sugar residue, one pentaoside (4) and one tetraoside (2), characterized by a glycoside architecture of oligosaccharide chains with shortened bottom semi-chains, which is uncommon for sea cucumbers. Some additional distinctive structural features inherent in 1–4 were also found: the aglycone of a recently discovered new type, with 18(20)-ether bond and lacking a lactone in chitonoidoside G (3), glycoside 3-O-methylxylose residue in chitonoidoside E₁ (1), which is rarely detected in sea cucumbers, and sulfated by uncommon position 4 terminal 3-O-methylglucose in chitonoidosides F (2) and H (4). The hemolytic activities of compounds 1–4 and chitonoidoside E against human erythrocytes and their cytotoxic action against the human cancer cell lines, adenocarcinoma HeLa, colorectal adenocarcinoma DLD-1, and monocytes THP-1, were studied. The glycoside with hexasaccharide chains (1, 3 and chitonoidoside E) were the most active against erythrocytes. A similar tendency was observed for the cytotoxicity against adenocarcinoma HeLa cells, but the demonstrated effects were moderate. The monocyte THP-1 cell line and erythrocytes were comparably sensitive to the action of the glycosides, but the activity of chitonoidosides E and E₁ (1) significantly differed from that of 3 in relation to THP-1 cells. A tetraoside with a shortened bottom semi-chain, chitonoidoside F (2), displayed the weakest membranolytic effect in the series. Full article

Six new triterpene tetra-, penta- and hexaosides, chitonoidosides A (1), A₁ (2), B (3), C (4), D (5), and E (6), containing one or two sulfate groups, have been isolated from the Far-Eastern sea cucumber Psolus chitonoides, collected near Bering Island (Commander Islands) from the depth of 100–150 m. Three of the isolated compounds (1, 3 and 6) are characterized by the unusual aglycone of new type having 18(20)-ether bond and lacking a lactone in contrast with wide spread holostane derivatives. Another unexpected finding is 3-O-methylxylose residue as a terminal unit in the carbohydrate chains of chitonoidosides B (3), C (4), and E (6), which has never been found before in the glycosides from holothurians belonging to the Psolidae family. Moreover, this monosaccharide is sulfated in the compound 4 into unprecedented 3-O-methylxylose 4-O-sulfate residue. Chitonoidoside C (4) is characterized by tetrasaccharide moiety lacking a part of the bottom semi-chain, but having disaccharide fragment attached to C-4 of Xyl1. Such architecture is not common in sea cucumber glycosides. Cytotoxic activities of the compounds 1–5 against mouse and human erythrocytes and human cancer cell lines: adenocarcinoma HeLa, colorectal adenocarcinoma DLD-1, and leukemia promyeloblast HL-60 cells were studied. The cytotoxic effect of chitonoidoside d (5) was the most significant in this series due to the presence of pentasaccharide disulfated sugar chain in combination with holostane aglycone. Surprisingly, the glycosides 1 and 3, comprising the new aglycone without γ-lactone, demonstrated similar activity to the known compounds with holostane aglycones. Chitonoidoside C (4) was less cytotoxic due to the different architecture of the carbohydrate chain compared to the other glycosides and probably due to the presence of a sulfate group at C-4 in 3-O-MeXyl4. Full article