Anti-tumor withanolides as signal transducers and activators of transcription 3 (STAT3)-inhibition from Withania obtusifolia.

The Solanaceae family and the Withania genus specifically are rich sources of medicinal plants. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS/MS) revealed a predominance of withanolides from an organic extract of Withania obtusifolia. A constructed molecular network uncovered the presence of potentially novel withanolides. A series of withanolides were then isolated and structurally characterized from the extract including two new withanolides (withafolia A and withafolia B) and seven previously reported metabolites. Of the isolated compounds, cytotoxicity of withanolide J, physaperuvin G, and a commercial STAT3 inhibitor (S3I-201) were assessed against a human leukemia HL-60 cell line resulting in IC50 values of 26, 29, and 120 µM, respectively. In silico molecular docking simulations indicate that withanolide J and physaperuvin G can bind as an inhibitor in the active site of STAT3 with docking scores comparable to the selective STAT3 inhibitor, S3I-201.

Estrogen receptor alpha (ER-α) antagonistic activity of phytoconstituents from Potentilla atrosanguinea and Potentilla fulgens in breast cancer.

The Potentilla genus has long been used traditionally as food and a folklore medicine. In the present study, aerial parts of two Potentilla species, Potentilla fulgens and Potentilla atrosanguinea, of western Himalayan origin, were studied for their anti-breast cancer activity. Ethyl acetate (PAA-EA, PFA-EA), methanolic (PAA-ME, PFA-ME) and hydro-methanolic extract (PAA-HM, PFA-HM) of the plants were tested for their antiproliferative activities against MCF-7 and T-47D breast cancer cell lines. The extracts showed good antiproliferative activity against ER-α dominant breast cancer cell line T-47D, having IC50 values 6.19 ± 0.01 to 33.23 ± 0.04 µg/ml. Eight compounds were isolated, characterized, and quantified from ethyl acetate and methanolic extracts by column chromatography, 1D, 2D-NMR, HRMS and TLC densitometric analysis. Two compounds (4 and 6) have shown better antiproliferative activity than standard bazedoxifene and were further evaluated for their ER-α binding affinity via-fluorescence polarization-based competitive binding assay. The antiestrogenic properties of both compounds were assessed using western blotting. Compounds 4 and 6 were found to have significant affinity for the ER-α and managed to decrease its expression by 38 and 54% respectively. Compounds 4 and 6 also had good stability and reactivity as measured by minimal fluctuations in molecular dynamic simulation analysis, a good dock score in molecular docking, and a respectable HOMO-LUMO energy gap in DFT calculations. Compounds 4 and 6 have shown reliable results and can be used in the development of natural product-based anti-breast cancer agents.

Salvadora persica leaves: phytochemical profile and in vitro-inhibitory activity on inflammatory mediators implicated in periodontal disease.

CONTEXT: Virtually all parts of Salvadora persica L. (Salvadoraceae) are used in traditional medicine. The twigs and leaves are used for oral health, but leaves are far less investigated. OBJECTIVE: This study assesses the oral health-promoting potential of S. persica leaves with emphasis on anti-inflammatory and antiproliferative effects and provides an in depth-characterization of their metabolite profile. MATERIALS AND METHODS: Hot-water and methanolic S. persica leaf extracts (1, 10, and 100 µg/mL) and their major constituents (5, 10, and 50 µM), were subjected to cellular assays on IL-8 and TNFα release in LPS-stimulated human neutrophils, NO-release in LPS/IFNγ stimulated mouse macrophages, and proliferation of HNO97 human tongue carcinoma cells. Metabolite profiling was performed by UHPLC-HRMS analysis. Major constituents were isolated and structurally elucidated. RESULTS AND DISCUSSION: Both extracts showed pronounced anti-inflammatory activity in LPS-stimulated neutrophils. Major identified compound classes were flavonoid glycosides, the glucosinolate glucotropaeolin, phenyl- and benzylglycoside sulfates, and megastigmane glycosylsulfates, the latter ones identified for the first time in S. persica. Glucotropaeolin strongly inhibited the release of IL-8 and TNF-α (13.3 ± 2.0 and 22.7 ± 2.6% of the release of stimulated control cells at 50 µM), while some flavonoids and 3-(3'-O-sulfo-ß-d-glucopyranosyloxy)-7,8-dihydro-ß-ionone, a newly isolated megastigmane glycosylsulfate, were moderately active. Benzylisothiocyanate, which is likely formed from glucotropaeolin during traditional application of S. persica, showed considerable antiproliferative activity (IC50 in HNO97 cells: 10.19 ± 0.72 µM) besides strongly inhibiting IL-8 and TNFα release. CONCLUSIONS: Glucotropaeolin and benzylisothiocyanate are likely implicated in the oral health-promoting effects of S. persica leaves. The chemistry and pharmacology of the newly identified megastigmane glycosylsulfates should be further evaluated.

Ethnomedicinal Uses, Phytochemistry, Pharmacology, and Toxicology of Ruellia tuberosa L.: A Review.

Natural Products continue to be the purest source of physiologically active molecules employed in the identification of possible lead compounds in the drug discovery process. Acanthaceae is a big plant family with around 2500 species, found primarily in subtropical and tropical regions, as well as the Mediterranean, Australia, and the United States. Several species of the Acanthaceae family have been used traditionally to treat a variety of diseases, including gastrointestinal and cardiovascular ailments, etc. Ruellia tuberosa commonly known as "Mexican Bluebell" is a perennial herb that originated in Central America and has spread to some countries in the Southern tropics and Southeast Asia. It has been utilized as a traditional Rasayana plant from ancient times. R. tuberosa extracts and phytochemicals showed potent bioactivities, such as anticancer, anti-inflammatory, wound healing, antifungal, antimicrobial, anti-diabetic, hypoglycemic, hypolipidemic, gastro-protective, and anthelminthic activities. Chemical analyses have unveiled a range of bioactive constituents within the plant, including alkaloids, flavonoids, saponins, and phenolic compounds, suggestive of its therapeutic potential. Collectively, this review provides an overview of R. tuberosa, encompassing its traditional uses, ethnomedicinal importance, phytochemistry, pharmacological properties, and toxicity.

Picrasma quassioides leaves: Insights from chemical profiling and bioactivity comparison with stems.

BACKGROUND: In Chinese Pharmacopeia, Picrasma quassioides (PQ) stems and leaves are recorded as Kumu with antimicrobial, anti-cancer, anti-parasitic effects, etc. However, thick stems are predominantly utilized as medicine in many Asian countries, with leaves rarely used. By now, the phytochemistry and bioactivity of PQ leaves are not well investigated. METHODS: An Orbitrap Elite mass spectrometer was employed to comprehensively investigate PQ stems and leaves sourced from 7 different locations. Additionally, their bioactivities were evaluated against 5 fungi, 6 Gram-positive bacteria and 9 Gram-negative bacteria, a tumor cell line (A549), a non-tumor cell line (WI-26 VA4) and N2 wild-type Caenorhabditis elegans. RESULTS: Bioassay results demonstrated the efficacy of both leaves and stems against tumor cells, several bacteria and fungi, while only leaves exhibited anthelmintic activity against C. elegans. A total of 181 compounds were identified from PQ stems and leaves, including 43 ß-carbolines, 20 bis ß-carbolines, 8 canthinone alkaloids, 56 quassinoids, 12 triterpenoids, 13 terpenoid derivatives, 11 flavonoids, 7 coumarins, and 11 phenolic derivatives, from which 10 compounds were identified as indicator components for quality evaluation. Most alkaloids and triterpenoids were concentrated in PQ stems, while leaves exhibited higher levels of quassinoids and other carbohydrate (CHO) components. CONCLUSION: PQ leaves exhibit distinct chemical profiles and bioactivity with the stems, suggesting their suitability for medicinal purposes. So far, the antibacterial, antifungal, and anthelmintic activities of PQ leaves were first reported here, and considering PQ sustainability, the abundant leaves are recommended for increased utilization, particularly for their rich content of PQ quassinoids.

Pharmacological properties of extracts and prenylated isoflavonoids from the fruits of Osage orange (Maclura pomifera (Raf.) C.K.Schneid.).

Osage orange trees (Maclura pomifera (Raf.) C.K.Schneid.) are distributed worldwide, particularly in south-east states of the USA. They produce large quantities of strong yellow fruits, bigger than oranges, but these fruits are inedible, with an acid milky juice which is little consumed by birds and insects. Extracts prepared from Osage orange fruits (hedge apple) have revealed a range of pharmacological properties of interest in human and veterinary medicine. In addition, Osage orange extracts can be used in agriculture and aquaculture, and as dyeing agent for the textile industry. Extracts contain potent antioxidant compounds, notably the isoflavonoids pomiferin and auriculasin, together with other terpenoids and flavonoids. The structural characteristics and pharmacological properties of the major prenylated isoflavones isolated from M. pomifera are discussed here, with a focus on the two phenolic compounds osajin and warangalone, and the two catechol analogues pomiferin and auriculasin. The mechanisms at the origin of their potent antioxidant and anti-inflammatory effects are presented, notably inhibition of xanthine oxidase, phosphodiesterase 5A and kinases such as RKS2 and kRAS. Osajin and auriculasin display marked anticancer properties, owing to their ability to inhibit tumor cell proliferation, migration and tumor angiogenesis. Different molecular mechanisms are discussed, including osajin­copper complexation and binding to quadruplex DNA. An overview of the mechanism of action of the prenylated isoflavones from Osage orange is presented, with the objective to promote their knowledge and to raise opportunities to better exploit the fruits of Osage orange, abundant but largely neglected at present.

Chemical profiling of Anthriscus cerefolium (L.) Hoffm., biological potential of the herbal extract, molecular modeling and KEGG pathway analysis.

This study was designed to investigate chemical composition and biological activities of the Anthriscus cerefolium methanolic extract. Chemical characterization of the extracts was performed by LC-HRMS/MS analysis. Antimicrobial activities of the extract were investigated on six bacteria and eight fungi while antioxidant activity was assessed by six different assays. Anti-enzymatic activity of the methanolic extract was tested on five enzymes associated with therapy of neurodegenerative diseases and diabetes mellitus type 2. Cytotoxic properties of the extract were tested on human immortalized keratinocytes (HaCaT) and tumor cell lines (SiHa, MCF7, HepG2). Anti-inflammatory activity of the extract was assessed on bacteria mediated inflammation model using HaCaT cell line. Molecular docking studies of enzymes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis were performed. The results showed that the obtained extract was rich in phenolic compounds (a total of seventy-two were identified), with malonyl-1,4-O-dicaffeoylquinic acid and 3,5-O-dicaffeoylquinic acid dominating in the sample. The extract expressed antimicrobial, antioxidant, anti-enzymatic, cytotoxic and anti-inflammatory properties. The identified compounds demonstrated strong binding to the acetylcholinesterase (AChE) and to a lesser extent, to the butyrylcholinesterase (BChE), glucosidase, amylase, and modestly, to tyrosinase. KEGG pathway analysis has shown that the certain phenolic compounds may be related to anti-tumor, anti-inflammatory and anti-microbial activities of the extract. The data obtained suggest that phenolic compounds of the extract and their mixtures should be considered for future research as ingredients in pharmaceutical and nutraceutical formulations.

Limonium brasiliense rhizomes extract against virulence factors of Porphyromonas gingivalis: Inhibition of gingipains, bacterial adhesion, and biofilm formation.

Periodontitis is clinically characterized by destruction of the tooth support system and tooth loss. Porphyromonas gingivalis (Pg) plays a dominant role in periodontitis. Fractions and isolated compounds from an acetone-water extract of the roots of Limonium brasiliense (Lb) were tested in vitro for their anti-adhesive capacity against Pg on human KB buccal cells, influence on gingipains, the main virulence factors of Pg, and biofilm formation. Fractions EAF and FLB7 (50 µg/mL) reduced the bacterial adhesion of Pg to KB cells significantly (63 resp. 70%). The proanthocyanidin samarangenin A inhibited the adhesion (72%, 30 µM), samarangenin B (71%, 20 µM), and the flavan-3-ol epigallocatechin-3-O-gallate (79%, 30 µM). Fraction AQF, representing hydrophilic compounds, reduced the proteolytic activity of Arginin-specific gingipain (IC50 12.78 µg/mL). Fractions EAF and FLB7, characterized by lipohilic constituents, inhibited Arg-gingipain (IC50 3 µg/mL). On Lysine-specific gingipain, AQF has an IC50 15.89, EAF 14.15, and FLB7 6 µg/mL. The reduced bacterial adhesion is due to a strong interaction of proanthocyanidins with gingipains. AQF, EAF, and FLB7 significantly inhibited biofilm formation: IC50 11.34 (AQF), 11.66 (EAF), and 12.09 µg/mL (FLB7). In silico analysis indicated, that the polyphenols act against specific targets of Pg, not affecting mammalian cells. Therefore, Lb might be effective for prevention of periodontal disease by influencing virulence factors of Pg.

The genus Myrsine: A review of phytochemistry, pharmacology, and toxicology.

BACKGROUND: Myrsine (the family Primulaceae) contains flowering species. Pharmacologically, the plants of this genus belong to a list of medicinal plants that induce infectious and inflammatory treatments. There are no scientific publications that review phytochemistry and pharmacological activities. OBJECTIVE: The compilation and classification of phytochemicals, chromatographic information, essential oils, and pharmacological reviews are the ultimate aim. METHODS: References on phytochemical and pharmacological investigations of Myrsine species were collected from various sources, such as Google Scholar, PubMed, and Web of Science from the 1990s to present. The main keyword "Myrsine" was used alone or in combination with others to search for references. RESULTS: Chromatographic procedure of Myrsine extracts led to the purification of 134 compounds. Flavonoids, mono-phenols, saponins, quinones, megastigmanes, and lignans were the main phytochemical classes. Myrsine Volatile compounds are monoterpenoids, sesquiterpenoids, and aliphatic compounds. Myrsine constituents established a widespread panel of pharmacological activities, such as cytotoxicity, antioxidant, antimicrobial, anti-parasite, tyrosine inhibition, and hepatoprotection, especially anti-inflammation. Novel flavonoids myrsininones A-B are better than the standard triclosan against bacteria Staphylococcus warneri, S. mutan, S. sanguis, and Actinomyces naeslundii. M. seguinii aerial part ethanolic extract inhibited LPS (lipopolysaccharide)-stimulated inflammatory Raw 264.7 cells via Src/Syk/NF-κB (sarcoma kinase/spleen tyrosine kinase/ nuclear factor-kappa B) and IRAK-1/AP-1 (interleukin-1 receptor-associated kinase-1/activating protein-1) signaling inhibition. Generally, Myrsine plant extracts showed no toxicity. CONCLUSION: Myrsine constituents are good antimicrobial, antioxidative, and anti-inflammatory agents. However, the majority of earlier research focuses on the pharmacological analyses of M. africana. Thus, comprehensive findings for the remaining species are needed.

Ethnomedicinal, phytochemical, pharmacological and toxicological profile of Mondia whitei: A review.

Mondia whitei is an aromatic plant native to sub-Saharan Africa. This spice is commonly used in the treatment of various diseases, such as hypertension, diabetes, erectile dysfunction, and premature ejaculation. This review was undertaken to provide updated information on the botanical, phytochemical, pharmacological, and toxicological knowledge of this plant of high relevance to African populations. Moreover, its mechanism of action was described based on previous experimental studies. Data were compiled from various online databases such as PubMed, Google Scholar, Scopus, Science Direct, Web of Science, Springer link, Taylor and Francis, and SciFinder. Additionally, books, book chapters and proceedings were used as secondary sources. The chemical structures of phytocompounds were drawn using PubChem Sketcher program. M. whitei contains various phytocompounds, including reducing sugars, triterpenes, steroids, alkaloids, saponins, tannins, phenolics, hydrogen cyanide, carotenoid, oxalate and phytate. Moreover, para-pentylphenyl-benzoate, (-)-Loliolide, 5-chloropropacin, propacin, 2-hydroxy-4-methoxybenzaldehyde, isovanillin, 9-hexacosene, 2-hexen-1-ol, and heptacosane were isolated from this spice. M. whitei has several pharmacological benefits, including aphrodisiac, pro-fertile, pro-erectile, androgenic, antioxidant, antiparasitic, antimalarial, antibacterial, antiviral, antifungal, antiepileptic, anti-inflammatory, analgesic, antidepressant, antidiarrheal, hepatoprotective, antisickling, and anticancer activities. Toxicological studies showed an LD50 of above 5000 mg/Kg and no signs of toxicity after one week of oral treatment. The aphrodisiac effect of this spice is one of its main activities, supported by numerous experimental studies. Because M. whitei delays contractions of the bulbospongiosus muscles, its aphrodisiac effect could be mediated through the modulation of the spinal generator of ejaculation. This can justify its folkloric use in the treatment of premature ejaculation.

Cardiac glycosides with cytotoxic activity from the seeds of Thevetia peruviana.

Phytochemical investigation on the extract of the seeds of Thevetia peruviana resulted in the isolation of six new cardiac glycosides, namely theveperosides A-F (1-6), including a rare 19-nor-cardenolide (1), together with seven known analogues (7-13). The chemical structures of these compounds were determined based on detailed spectroscopic analysis. The cytotoxic activities of 1-13 were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cell lines, and their structure-activity relationships (SARs) were investigated. Compound 3 exhibited the significant cytotoxic effects with IC50 values ranging from 0.032 to 0.055 µΜ, which could induce HepG2 cells apoptosis in a dose-dependent manner.

Sesquiterpene dimers with a rare skeleton from Chloranthus holostegius exhibiting multidrug resistance reversal activity in vitro and in vivo.

Two previously unreported lindenane sesquiterpene dimers (1 and 2) with a rare skeleton containing an oxaspiro[4.5]decane moiety were isolated from the roots of Chloranthus holostegius var. trichoneurus. Their structures were elucidated by HRESIMS, NMR, ECD, and NMR quantum chemical calculations, along with DP4+ probability analysis. In bioassay, compound 1 exhibited significant activity to reverse the multidrug resistance (MDR)in MCF-7/ADR cells, with an IC50 value of 4.4 µM. Further mechanistic studies revealed that compound 1 combined with doxorubicin could induce apoptosis of MCF-7/ADR cells and block the cell cycle in the G2/M phase. Mechanistically, compound 1 could inhibit the efflux function of P-glycoprotein (P-gp) using the zebrafish model. Finally, the enhanced chemotherapeutic effects of doxorubicin were further confirmed by in vivo zebrafish xenograft experiments.

Chrysosaxillins A-E, cucurbitane triterpenoid derivatives from Chrysosplenium axillare Maxim. (Yajima) and their cytotoxic activities.

Chrysosplenium axillare Maxim. is used in traditional Tibetan medicine for the treatment of various human diseases, such as fever, headache, cholecystitis, acute icterohepatitis and acute liver necrosis. In this study, five new cucurbitane triterpenoid derivatives, chrysosaxillins A-E (1-5), along with three known structurally related compounds (6-8) have been isolated from whole herb of C. axillare. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR, HRESIMS, UV, IR, ECD and single-crystal X-ray diffraction. All isolates were evaluated for cytotoxic activities against four tumor cell lines including PC-3, A549, MCF-7, and HepG2. The results discovered that compound 1 possessed the most potent cytotoxicity against A549 cells with IC50 value of 0.05 µM, while compounds 2 and 4 have mild cytotoxicities against cells tested with IC50 values ranging from 8.78 to 41.72 µM. Our study suggests that C. axillare might serve as a valuable source of cucurbitane triterpenoids potentially useful for the development of new anti-tumor agents and support its use as a crop benefits to local economic.

Evaluating the anticancer potential of Polygonum multiflorum root-derived stilbenes against H2452 malignant pleural mesothelioma cells.

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.

Botany, phytochemistry, pharmacology, and applications of Pandanus amaryllifolius Roxb.: A review.

Pandan (Pandanus amaryllifolius Roxb.), a member of the Pandanaceae family, has been consumed as food and medicine since ancient times. The current paper provides an overview of the botanical profile, phytochemistry, pharmacology, and applications of P. amaryllifolius. Information regarding P. amaryllifolius was collected from online sources (using PubMed, Science Direct, Google Scholar, Web of Science, ACS, and CNKI) as well as traditional textbooks. Over 100 compounds have been identified, including its characteristic components 2-Acetyl-1-pyrroline and Pandanus alkaloids. Several therapeutic uses of P. amaryllifolius, such as antioxidant, hypoglycemic, antimicrobial, and antitumor activities, have been demonstrated in modern pharmacological studies. Additionally, it could be applied in various fields, including food, energy, material, and the environment. Continued research on P. amaryllifolius can contribute to the development of new drugs and therapies for various diseases. And further studies are needed to improve its utilization.

Rosin: A comprehensive review on traditional uses, phytochemistry, and pharmacology.

Rosin, a natural resin obtained from conifer trees, has a long history of use in traditional folk medicine for treating abscesses, wounds, carbuncles, and burns, etc. It has been employed in ancient Egypt, China, Nordic countries, and Turkey as a therapeutic remedy. This comprehensive review examines the traditional uses, phytochemistry, and pharmacology of rosin, and it provides a critical update on current knowledge of rosin and identifies potential therapeutic opportunities. The chemical composition of rosin is known to vary depending on factors such as botanical sources, geographical locations, and processing methods. Rosin acids, which account for over 90% of its primary chemical constituents, have been identified as the predominant compounds in rosin. Researchers have isolated approximately 50 compounds from rosin, with terpenoid rosin acids being the most prevalent. Furthermore, the review highlights the potential pharmacological activities of rosin and its constituents. Crude extracts and isolated rosin acids have demonstrated promising properties, including antimicrobial, anti-inflammatory, anti-tumor, insecticidal, wound healing, and anti-obesity effects. However, the review emphasizes that further research is needed, as existing studies are predominantly preliminary. Many of the reported bioactivities require further verification, and the underlying mechanisms of action remain largely unexplored. In conclusion, rosin has been extensively used in traditional medicine across different cultures, and its chemical composition has been confirmed to a significant extent. The pharmacological activities observed in crude extracts and isolated rosin acids support its traditional uses. Nevertheless, additional research is necessary to deepen our understanding of the pharmacological mechanisms underlying its effects.

Differential distribution of characteristic constituents in peel and pulp of Aurantii Fructus Immaturus (Citrus aurantium L.) using MALDI mass spectrometry imaging.

Aurantii Fructus Immaturus (AFI) was structurally divided into two parts named "peel" and "pulp". The exocarp and mesocarp of materials named "peel". The endocarp separated into multiple compartments and the cystic hair attached to it named "pulp". In order to explore the distribution and content of constituents in AFI, an efficient method to explore the distribution of constituents was developed based on matrix assisted laser desorption/ionization fourier transform ion cyclotron resonance mass spectrometry imaging (MALDI-FTICR-MSI). After simple processing, thirty-two constituents with distinct localization in the mass range of 101-1200 Da were identified by MALDI-FTICR-MSI. In addition, the identified four flavnoids (poncirin, sinensetin, 3,5,6,7,8,3',4'-heptemthoxyflavone, and tangeritin) were analyzed for differences between using LC-MS. Quantitative analysis results supported the quantitative results from MALDI-FT-ICR-MSI. The results implied that different parts had different constituents in AFI, and demonstrated MALDI-MSI have high potential in the direct analysis of constituents.

Biological and metabolomics-guided isolation of tetrahydrofurofuran lignan from Croton spp. with antiproliferative activity against human melanoma cell line.

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 µg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 µg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.

An anti-mitotic compound, (+)-6-tuliposide A, isolated from the Canadian glacier lily, Erythronium grandiflorum.

The Canadian prairie ecosystem is subjected to abiotic and biotic conditions that induce plants to produce secondary metabolites that affect mammalian physiology. Extracts prepared from certain plant species native to Canadian prairie and montane cordillera ecosystems have previously been shown to have anti-mitotic activity on human cancer cell lines. In this study, we investigated the glacier lily, Erythronium grandiflorum (Liliaceae), in which the species was the most phylogenetically distant from Asteraceae and had anti-mitotic activity. When added to cell lines, E. grandiflorum extracts induced rounded cell morphology and arrested cells in the G2/M phase of the cell cycle. Of the cells that displayed a rounded phenotype, all were positive for phospho-histone H3 and contained a distorted mitotic spindle. This anti-mitotic activity was distinct from that of the compound colchicine, which has been previously isolated from the Liliaceae family. By biology-guided fractionation, we isolated the natural product (+)-6-tuliposide A and are the first to report its anti-mitotic activity. These results reveal a chemical motif in secondary metabolites and expand the range of Canadian prairie plants with anti-mitotic activity that can become new scientific tools or used in the development of anti-proliferative medicines.

Antibacterial, antibiofilm, and chemical profiles of Ammi visnaga L. and Foeniculum vulgare mill. Essential oils, and ADMET, molecular docking investigation of essential oils major components.

This study determined chemical profiles, antibacterial and antibiofilm activities of the essential oils (EOs) obtained by A. visnaga aerial parts and F. vulgare fruits. Butanoic acid, 2-methyl-, 3-methylbutyl ester (38.8%), linalyl propionate (34.7%) and limonene (8.5%) resulted as main constituents of A. visnaga EO. In F. vulgare EO trans-anethole (76.9%) and fenchone (14.1%) resulted as main components. The two EOs were active against five bacterial strains (Acinetobacter baumannii, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus) at different degrees. The MIC values ranged from 5 ± 2 to 10 ± 2 µL/mL except for S. aureus (MIC >20 µL/mL). EOs exhibited inhibitory effect on the formation of biofilm up to 53.56 and 48.04% against E. coli and A. baumannii, respectively and activity against bacterial metabolism against A. baumannii and E. coli, with biofilm-inhibition ranging from 61.73 to 73.55%. The binding affinity of the identified components was estimated by docking them into the binding site of S. aureus gyrase (PDB code 2XCT) and S. aureus tyrosyl-tRNA synthetase (PDB code 1JIJ). trans-Anethole and butanoic acid, 2-methyl-, 3-methylbutyl ester showed relatively moderate binding interactions with the amino acid residues of S. aureus tyrosyl-tRNA synthetase. In addition, almost all predicted compounds possess good pharmacokinetic properties with no toxicity, being inactive for cytotoxicity, carcinogenicity, hepatotoxicity, mutagenicity and immunotoxicity parameters. The results encourage the use of these EOs as natural antibacterial agents in food and pharmaceutical industries.