Extensive targeted metabolomics analysis reveals the identification of major metabolites, antioxidants, and disease-resistant active pharmaceutical components in Camellia tuberculata (Camellia L.) seeds.

Sect. tuberculata plant belongs to the Camellia genus and is named for the "tuberculiform protuberance on the surface of the ovary and fruit". It is a species of great ornamental value and potential medicinal value. However, little has been reported on the metabolites of C. tuberculata seeds. Therefore, this study was conducted to investigate the metabolites of C. tuberculata seeds based on UPLC/ESI-Q TRAP-MS/MS with extensively targeted metabolomics. A total of 1611 metabolites were identified, including 107 alkaloids, 276 amino acids and derivatives, 283 flavonoids, 86 lignans and coumarins, 181 lipids, 68 nucleotides and derivatives, 101 organic acids, 190 phenolic acids, 10 quinones, 4 steroids, 17 tannins, 111 terpenoids, and 177 other metabolites. We compared the different metabolites in seeds between HKH, ZM, ZY, and LY. The 1311 identified different metabolites were classified into three categories. Sixty-three overlapping significant different metabolites were found, of which lignans and coumarins accounted for the largest proportion. The differentially accumulated metabolites were enriched in different metabolic pathways between HKH vs. LY, HKH vs. ZM, HKH vs. ZY, LY vs. ZY, ZM vs. LY and ZM vs. ZY, with the most abundant metabolic pathways being 4, 2, 4, 7, 7 and 5, respectively (p < 0.05). Moreover, among the top 20 metabolites in each subgroup comparison in terms of difference multiplicity 7, 8 and 13. ZM and ZY had the highest phenolic acid content. Ninety-six disease-resistant metabolites and 48 major traditional Chinese medicine agents were identified based on seven diseases. The results of this study will not only lead to a more comprehensive and in-depth understanding of the metabolic properties of C. tuberculata seeds, but also provide a scientific basis for the excavation and further development of its medicinal value.

Fraxetin pretreatment alleviates cisplatin-induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation.

Cisplatin-induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti-inflammatory, and anti-fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin-induced kidney injury in a time- and concentration-dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin-induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin-treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT-repeats binding site on mTORC1 protein. In  summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

[Pharmacokinetics of 11 active components of Psoraleae Fructus in normal and diabetic rats].

A total of 11 active ingredients including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, coryfolin, isobavachalcone, neobavaisoflavone, bakuchalcone, and corylifol A from Psoraleae Fructus in the plasma samples of diabetic and normal rats were simultaneously determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated to elucidate the pharmacokinetic profiles of coumarins, flavonoids, and monoterpene phenols in normal and diabetic rats. The rat model of type 2 diabetes mellitus(T2DM) was induced by a high-sugar and high-fat diet combined with injection of 1% streptozotocin every two days. The plasma samples were collected at different time points after the rats were administrated with Psoraleae Fructus. The proteins in the plasma samples were precipitated by ethyl acetate, and the plasma concentrations of the 11 components of Psoraleae Fructus were determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS 3.0. The results showed that the pharmacokinetic beha-viors of 8 components including psoralen, isopsoralen, bakuchiol, and bavachinin from Psoraleae Fructus in both female and male mo-del rats were significantly different from those in normal rats. Among them, the coumarins including psoralen, isopsoralen, and corylin showed lowered levels in the blood of both female and male model rats. The flavonoids(bavachinin, corylifol A, and bakuchalcone) and the monoterpene phenol bakuchiol showed decreased levels in the female model rats but elevated levels in the male model rats. It is suggested that the dosage of Psoraleae Fructus should be reasonably adjusted for the patients of different genders at the time of clinical administration.

Function-oriented mechanism discovery of coumarins from Psoralea corylifolia L. in the treatment of ovariectomy-induced osteoporosis based on multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood. AIM OF THE STUDY: To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites. MATERIALS AND METHODS: C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites. RESULTS: BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites. CONCLUSIONS: The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.

Pharmacological and phytochemical insights on the pancreatic ß-cell modulation by Angelica L. roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica roots are a significant source of traditional medicines for various cultures around the northern hemisphere, from indigenous communities in North America to Japan. Among its many applications, the roots are used to treat type 2 diabetes mellitus; however, this application is not mentioned often. Ethnopharmacological studies have reported the use of A. japonica var. hirsutiflora, A. furcijuga, A. shikokiana, and A. keiskei to treat diabetes symptoms, and further reports have demonstrated the three angelica roots, i.e., A. japonica var. hirsutiflora, A. reflexa, and A. dahurica, exhibit insulin secretagogue activity. AIM OF THE STUDY: This study aimed to phytochemically characterize and compare angelica roots monographed in the European Pharmacopeia 11th, isolate major plant metabolites, and assess extracts and isolates' capability to modulate pancreatic ß-cell function. MATERIALS AND METHODS: Root extracts of Angelica archangelica, Angelica dahurica, Angelica biserrata, and Angelica sinensis were phytochemically profiled using liquid chromatography method coupled with mass spectrometry. Based on this analysis, simple and furanocoumarins were isolated using chromatography techniques. Extracts (1.6-50 µg/mL) and isolated compounds (5-40 µmol/L) were studied for their ability to modulate insulin secretion in the rat insulinoma INS-1 pancreatic ß-cell model. Insulin was quantified by the homogeneous time-resolved fluorescence method. RESULTS: Forty-one secondary metabolites, mostly coumarins, were identified in angelica root extracts. A. archangelica, A. dahurica, and A. biserrata root extracts at concentration of 12.5-50 µg/mL potentiated glucose-induced insulin secretion, which correlated with their high coumarin content. Subsequently, 23 coumarins were isolated from these roots and screened using the same protocol. Coumarins substituted with the isoprenyl group were found to be responsible for the extracts' insulinotropic effect. CONCLUSIONS: Insulinotropic effects of three pharmacopeial angelica roots were found, the metabolite profiles and pharmacological activities of the roots were correlated, and key structures responsible for the modulation of pancreatic ß-cell function were identified. These findings may have implications for the traditional use of angelica roots in treating diabetes. Active plant metabolites may also become lead structures in the search for new antidiabetic treatments.

Hydrangea paniculata coumarins alleviate adriamycin-induced renal lipotoxicity through activating AMPK and inhibiting C/EBPß.

ETHNOPHARMACOLOGICAL RELEVANCE: Throughout Chinese history, Hydrangea paniculata Siebold has been utilized as a traditional medicinal herb to treat a variety of ailments associated to inflammation. In a number of immune-mediated kidney disorders, total coumarins extracted from Hydrangea paniculata (HP) have demonstrated a renal protective effect. AIM OF THE STUDY: To investigate renal beneficial effect of HP on experimental Adriamycin nephropathy (AN), and further clarify whether reversing lipid metabolism abnormalities by HP contributes to its renoprotective effect and find out the underlying critical pathways. MATERIALS AND METHODS: After establishment of rat AN model, HP was orally administrated for 6 weeks. Biochemical indicators related to kidney injury were determined. mRNAs sequencing using kidney tissues were performed to clarify the underlying mechanism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, western blot, molecular docking, and drug affinity responsive target stability (DARTS) assay was carried out to further explore and confirm pivotal molecular pathways and possible target by which HP and 7-hydroxylcoumarin (7-HC) played their renal protection effect via modulating lipid metabolism. RESULTS: HP could significantly improve renal function, and restore renal tubular abnormal lipid metabolism and interstitial fibrosis in AN. In vitro study demonstrated that HP and its main metabolite 7-HC could reduce ADR-induced intracellular lipid deposition and fibrosis characteristics in renal tubular cells. Mechanically, HP and 7-HC can activate AMP-activated protein kinase (AMPK) via direct interaction, which contributes to its lipid metabolism modulation effect. Moreover, HP and 7-HC can inhibit fibrosis by inhibiting CCAAT/enhancer binding protein beta (C/EBPß) expression in renal tubular cells. Normalization of lipid metabolism by HP and 7-HC further provided protection of mitochondrial structure integrity and inhibited the nuclear factor kappa-B (NF-κB) pathway. Long-term toxicity using beagle dogs proved the safety of HP after one-month administration. CONCLUSION: Coumarin derivates from HP alleviate adriamycin-induced lipotoxicity and fibrosis in kidney through activating AMPK and inhibiting C/EBPß.

Plant-Derived Coumarins: A Narrative Review of Their Structural and Biomedical Diversity.

Plant-derived coumarin (PDC) is a naturally occurring heterocyclic backbone that belongs to the benzopyrone family. PDC and its based products are characterized by low toxicity and high distribution in a variety of herbal treatments that have numerous therapeutic potentials. These include anticoagulants, antibacterials, anti-inflammatory agents, anticancer agents, antioxidants, and others. So, it may be appropriate to investigate the qualities and potential bioactivities of PDCs. This article provides an overview of the biomedical potentials, availability, and clinical use possibilities of PDCs, with a focus on their important modes of action, using information on various pharmacological qualities discovered. The data used in this study came from published research between 2015 and 2023. We reviewed a selection of databases, including PubMed, Scopus, Web of Science, and Google Scholar, during that period. In conclusion, because of their abundance in medicinal plants, the clinical biochemistry attributes of PDCs are currently of interest. In a variety of medical specialties, PDCs serve a useful role as therapeutic agents.

Dietary supplementation of osthole and icariin improves the production performance of laying hens by promoting follicular development.

Osthole (Ost) and icariin (Ica) are extracted from traditional Chinese medicine Cnidium monnieri and Epimedii Folium, respectively, and both exhibit estrogen-like biological activity. This study aimed to determine the efficacy and safety of combining Ost with Ica on the production performance of laying hens and to explore their possible mechanisms. The production performance, egg quality, residues of Ost and Ica in eggs, serum reproductive hormone levels, expression of ovarian reproductive hormone receptor, proliferation of granulosa cells in small yellow follicles (SYF), and progesterone secretion in large yellow follicles (LYF) related genes and proteins expression were detected. The results showed that adding 2 mg/kg Ost + 2 mg/kg Ica to the feed increased the laying rate, average egg weight, Haugh unit, and protein height of laying hens. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (P4) levels increased, and the expression of ovarian estrogen receptor (ER), follicle-stimulating hormone receptor (FSHR), and progesterone receptor (PGR) mRNA was up-regulated. Additionally, the mRNA and protein levels of steroidogenesis acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) increased in LYF. Furthermore, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin E1, and cyclin A2 were up-regulated in SYF. The residues of Ost and Ica in egg samples were not detected by high-performance liquid chromatography (HPLC). In conclusion, dietary supplementation of Ost and Ica increased granulosa cells proliferation in SYF and increased P4 secretion in granulosa cells of LYF, ultimately improving the production performance of laying hens.

A comprehensive review of Pfaffia glomerata botany, ethnopharmacology, phytochemistry, biological activities, and biotechnology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia glomerata (Spreng.) Pedersen, Amaranthaceae, is found in South America, mainly in Brazil, where it is considered a species of great medicinal interest owing to its popular use as a tonic, aphrodisiac, anti-inflammatory, and analgesic. These properties can be attributed to the presence of the phytosteroid, 20-Hydroxyecdysone (ß-ecdysone), the main compound found in its roots. AIM OF THE REVIEW: This review aims to provide information about the botanical characteristics, ethnomedicinal uses, the phytochemistry, the biological activities, and the biotechnology of P. glomerata, an important species to local communities and groups researching medicinal plants of South America. MATERIALS AND METHODS: The information available on P. glomerata was collected from scientific databases (ScienceDirect, PubMed/MEDLINE, SciELO, and Scopus) until June 7, 2023, using the search terms "Pfaffia glomerata", "Pfaffia glomerata (Spreng.) Pedersen", and "Brazilian ginseng". The review includes studies that evaluated the botanical, ethnopharmacological, and phytochemical aspects, biological properties, nutraceutical uses, and the application of biotechnology for improving the biosynthesis of metabolites of interest. RESULTS: A total of 207 studies were identified, with 81 articles read in full. Seventy-six studies were included for qualitative synthesis. Overall, 40 compounds belonging to different classes are presented in this review, including ecdysteroids, triterpenes, saponins, flavonoids, anthraquinones, tannins, coumarins, alkaloids, and polysaccharides. Among them, flavonoids, anthraquinones, tannins, coumarins, and alkaloids were only putatively identified. ß-Ecdysone, triterpenes, saponins, and polysaccharides are the chemical components most frequently identified and isolated from P. glomerata and possibly responsible for ethnopharmacological use and the biological activities of this species, with important in vitro and in vivo activities, such as anti-inflammatory, antidepressant, aphrodisiac, analgesic, gastroprotective, antioxidant, and prebiotic. CONCLUSIONS: This review summarizes discussions about the P. glomerata species, highlighting its ethnopharmacological, chemical, biotechnological, and nutraceutical importance. New scientific studies on this species are encouraged in the search for new therapeutic molecules with pharmaceutical potential and nutraceutical applications.

The coumarin component isofraxidin targets the G-protein-coupled receptor S1PR1 to modulate IL-17 signaling and alleviate ulcerative colitis.

OBJECTIVE: The increasing global prevalence of ulcerative colitis (UC) underscores the imperative to explore novel therapeutic approaches. Traditional Chinese medicine has historically shown potential in addressing this ailment. The current study aimed to elucidate the functional attributes and underlying mechanisms of isofraxidin, a coumarin derivative from Acanthopanax, in the context of UC. METHODS: A murine model of dextran sodium sulfate (DSS)-induced UC was established, and we conducted a comprehensive assessment of the influence of isofraxidin on UC symptomatology, colonic histopathological manifestations, the inflammatory response, and apoptosis. The potential receptor of isofraxidin was initially identified through the Target database and molecular docking analysis. Subsequent in vivo and in vitro experiments were conducted to determine the effects of isofraxidin on the identified receptor and associated signaling pathways. Transfection was used to examine the receptor's role in the regulatory mechanism of isofraxidin. RESULTS: Isofraxidin reduced UC symptoms and colonic histopathological impairments. Furthermore, isofraxidin ameliorated the DSS-induced inflammatory response and apoptosis in tissues. S1PR1 was identified as a target of isofraxidin and effectively suppressed activation of the IL-17 signaling pathway. Intriguingly, cellular experiments indicated that overexpression of S1PR1 counteracted the protective effect of isofraxidin. DISCUSSION: In summary, our investigation revealed that isofraxidin could modulate S1PR1 and regulate the IL-17 signaling pathway, thus ameliorating DSS-induced UC. These findings establish a robust foundation for considering isofraxidin as a prospective therapeutic intervention to treat UC.

Natural linear coumarin-heterocyclic conjugates: A review of their roles in phytotherapy.

Heterocycle conjugates provide a fresh investigative scope to find novel molecules with enhanced phytotherapeutic characteristics. Coumarin-based products are widely used in the synthesis of several compounds with biological and medicinal properties since they are naturally occurring heterocycles with a broad dispersion. The investigation of coumarin-based phytochemicals with annulated heterocyclic rings is a promising approach to discovering novel conjugates with significant phytotherapeutic attributes. Due to the applicable coumarin extraction processes, a range of linear coumarin-heterocyclic conjugates were isolated from different natural resources and exhibited remarkable therapeutic efficacy. This review highlights the phytotherapeutic potential and origins of various natural linear coumarin-heterocyclic conjugates. We searched several databases, including Science Direct, Web of Science, Springer, Google Scholar, and PubMed. After sieving, we ultimately identified and included 118 pertinent studies published between 2000 and the middle of 2023. This will inspire medicinal chemists with extremely insightful ideas for designing and synthesizing therapeutically active lead compounds in the future that are built on the pharmacophores of coumarin-heterocyclic conjugates and have significant therapeutic attributes.

Cnidii Fructus: A traditional Chinese medicine herb and source of antiosteoporotic drugs.

BACKGROUND: Osteoporosis (OP) is a prevalent chronic metabolic bone disease for which limited countermeasures are available. Cnidii Fructus (CF), primarily derived from Cnidium monnieri (L.) Cusson., has been tested in clinical trials of traditional Chinese medicine for the management of OP. Accumulating preclinical studies indicate that CF may be used against OP. MATERIALS AND METHODS: Comprehensive documentation and analysis were conducted to retrieve CF studies related to its main phytochemical components as well as its pharmacokinetics, safety and pharmacological properties. We also retrieved information on the mode of action of CF and, in particular, preclinical and clinical studies related to bone remodeling. This search was performed from the inception of databases up to the end of 2022 and included PubMed, China National Knowledge Infrastructure, the National Science and Technology Library, the China Science and Technology Journal Database, Weipu, Wanfang, the Web of Science and the China National Patent Database. RESULTS: CF contains a wide range of natural active compounds, including osthole, bergapten, imperatorin and xanthotoxin, which may underlie its beneficial effects on improving bone metabolism and quality. CF action appears to be mediated via multiple processes, including the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK), Wnt/ß-catenin and bone morphogenetic protein (BMP)/Smad signaling pathways. CONCLUSION: CF and its ingredients may provide novel compounds for developing anti-OP drugs.

Characterization, multivariate analysis and bioactivity evaluation of coumarins in the bark of Fraxinus mandshurica.

The bark of Fraxinus mandshurica is a traditional folk herb used to clear heat and dry dampness. To investigate the differences in coumarins content in the bark of F. mandshurica, 24 batches of samples from four origins were collected and analyzed. Eight coumarins were obtained by traditional natural product extraction, isolation and identification techniques and quantified by high performance liquid chromatography-photodiode array (HPLC-DAD). The quantitative results showed that the overall content of compound 30 (Fraxinol) was higher at 100.23 mg/g, while the overall content of compound 23 (Cichoriin) was lower, which may be related to environmental factors in different regions. The method validation showed that the linear range of the eight standards was between 10 and 2500 µg/mL with correlation coefficient (R2) values >0.9991; the relative standard deviation (RSD, %) values of intra-day precision were between 0.35 and 1.38, while the RSD values of inter-day precision were between 0. 29-1.78; the RSD (%) values for the reproducibility experiments ranged from 0.29 to 1.87, while the RSD (%) values for the stability experiments ranged from 0.22 to 2.33; the spiked recovery of the samples ranged from 98.65 to 101.34%, and the RSD (%) values ranged from 0.22 to 1.96. The method validation results showed that the instrument used for the analysis had good precision, the reproducibility and stability of the samples were good, and the accuracy of the experimental method was high. In addition, a total of 54 chemical components were identified from F. mandshurica bark by ultra performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS). Based on this, fingerprinting, heatmap and multivariate analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were established for 24 batches of samples, and four marker compounds that could be used to distinguish different origins of F. mandshurica were screened. To further investigate the bioactivities of the eight coumarins, in vitro enzyme activity inhibition studies were performed, and the results showed that they all exhibited different degrees of inhibition of acetylcholinesterase, tyrosinase and α-glucosidase, thus having potential applications in the treatment of Alzheimer's disease, blemish whitening and anti-diabetes, and becoming a new source of natural enzyme activity inhibitors. This study established an identification and evaluation method applicable to plants of different origins, which provides a strong reference for quality control, origin evaluation and clinical application of traditional medicinal plants.

Optimization of ultrasonic-assisted supramolecular solvent microextraction of coumarins from Cortex fraxini using response surface methodology combined with artificial neural network-genetic algorithm.

A simple, fast, and efficient ultrasonic-assisted supramolecular solvent microextraction combined with high performance liquid chromatography method was developed for the determination of coumarins in Cortex fraxini, including esculin, esculetin and fraxetin. In this study, a novel supramolecular solvent was prepared with 1-octanol, tetrahydrofuran and water for the first time, and its composition, viscosity, density, structure, and micromorphology were characterized. The prepared supramolecular solvent exhibited vesicular structures and had the characteristics of low viscosity. Through single-factor experiments, response surface methodology and artificial neural network-genetic algorithm, the optimal extraction conditions were obtained as follows: NaCl concentration of 1 mol mL-1, pH value of 10, solid-liquid ratio of 10:1, vortex time of 30 s, ultrasonic power of 100 W, ultrasonic temperature of 60 °C, ultrasonic time of 15 min, centrifugation speed of 5000 rpm, and centrifugation time of 1 min. The results demonstrated that the artificial neural network model exhibited maximum R-values of 0.98703, 0.97440, 0.99836, and 0.95447 for training, testing, validation, and all dataset, respectively. The minimum mean square errors were 0.75, 10.15, 1.99, and 2.63, respectively. This indicated that the predicted values were almost consistent with the actual values. Under the optimal conditions, the total extraction yields of target analytes reached 2.80 %. The calibration curves for each analyte exhibited excellent linearity within the linear range (r > 0.9993). The limits of detection and quantification ranged from 4.87 to 6.55 ng mL-1 and 16.24 to 21.84 ng mL-1, respectively. The recoveries ranged from 98.71 % to 111.01 % with relative standard deviations of less than 3.6 %. The present method had the advantages of short extraction time (15 min) and less solvent consumption (0.5 mL). The prepared supramolecular solvent was proved to have great potential in extracting coumarins from medicinal plants.

Asiaticasics A-O, structurally intriguing coumarins from Toddalia asiatica with potential inflammatory inhibitory activity.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.

Structurally Diverse Coumarins from Peucedanum praeruptorum and their Anti-Inflammatory Activities via NF-κB Signaling Pathway.

The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66 µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.

Cytotoxic and antiviral activities of Jatropha variegata and Jatropha spinosa in relation to their metabolite profile.

Jatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin conditions such as wound healing, as antibacterial and hemostatic. In this study, we evaluated the cytotoxicity and the antiviral activities of the methanolic J. variegata (leaves: Ext-1, stems: Ext-2, and roots: Ext-3), and J. spinosa extracts (aerial parts: Ext-4 and roots: Ext-5), in addition to their methylene chloride fractions of roots extracts (F-6 and F-7, respectively). All samples were tested against three human cancer cell lines in vitro (MCF-7, HepG2, and A549) and two viruses (HSV-2 and H1N1). Both plants showed significant cytotoxicity, among them, the methylene chloride fractions of roots of J. variegata (F-6) and J. spinosa roots (F-7) showed the highest activity on MCF-7 (IC50 = 1.4 and 1 µg/mL), HepG2 (IC50 = 0.64 and 0.24 µg/mL), and A549 (IC50 = 0.7 and 0.5 µg/mL), respectively, whereas the IC50 values of the standard doxorubicin were (3.83, 4.73, and 4.57 µg/mL) against MCF-7, HepG2, and A549, respectively. These results revealed that the roots of both plants are potential targets for cytotoxic activities. The in vitro results revealed potential antiviral activity for each of Ext-3, Ext-5, F-6, and F-7 against HVS-2 with IC50 of 101.23, 68.83, 4.88, 3.24 µg/mL and against H1N1 with IC50 of 51.29, 27.92, 4.24, and 3.06 µg/mL respectively, whereas the IC50 value of the standard acyclovir against HVS-2 was 83.19 µg/mL and IC50 value of the standard ribavirin against H1N1 was 52.40 µg/mL .The methanol extracts of the roots (Ext-3 and Ext-5) of both plants were characterized using UPLC/MS. A total of 73 metabolites were annotated, including fourteen diterpenoids, eleven flavonoids, ten phenolic acid conjugates, twelve fatty acids and their conjugates, five triterpenes and steroids, two sesquiterpenes, and six coumarins. The cytotoxicity and antiviral activities determined in the present work are explained by the existence of flavonoids, coumarins and diterpenes with commonly known cytotoxicity and antiviral activities.

Quality assessment and Q-markers discovery in Citri Sarcodactylis Fructus by integrating serum pharmacochemistry and network pharmacology.

INTRODUCTION: Citri Sarcodactylis Fructus (CSF), a common fruit and traditional Chinese medicine (TCM), has been hindered in its further development and research owing to the lack of comprehensive and specific quality evaluation standards. OBJECTIVE: This study aimed to establish clear TCM quality standards related to the therapeutic mechanisms of CSF and to provide a basis for subsequent research and development. METHODS: Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-orbitrap HRMS) technology was used to comprehensively identify CSF components and explore their absorbance levels in rat serum. Network pharmacology research methods were employed to investigate the potential mechanisms of action of the identified components in the treatment of major clinical diseases. Subsequently, a combination of HPLC chromatographic fingerprinting for qualitative analysis and multi-index content determination was used to evaluate the detectability of the identified quality markers (Q-markers). RESULTS: Twenty-six prototype components were tentatively characterized in rat serum. Network pharmacology analysis showed six effective components, namely 7-hydroxycoumarin, isoscopoletin, diosmin, hesperidin, 5,7-dimethoxycoumarin, and bergapten, which played important roles in the treatment of chronic gastritis, functional dyspepsia, peptic ulcer, and depression and were preliminarily identified as Q-markers. The results of content determination in 15 batches of CSF indicated significant differences in the content of medicinal materials from different origins. However, compared with the preliminarily determined Q-markers, all six components could be measured and were determined as Q-markers of CSF. CONCLUSION: The chemical Q-markers obtained in this study could be used for effective quality control of CSF.

Fraxini cortex: Progresses in phytochemistry, pharmacology and ethnomedicinal uses.

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxini cortex, which has been widely used as a traditional Chinese medicine for 2000 years, is made from the dried bark of four plant species: Fraxinus chinensis subsp. rhynchophylla (Hance) A.E.Murray, Fraxinus chinensis Roxb., Fraxinus chinensis subsp. chinensis and Fraxinus stylosa Lingelsh.. In Chinese traditional medicine, it possesses the properties of heat-clearing and dampness-drying, asthma relief and cough suppression, as well as vision improvement. It is utilized for treating bacterial disorders, enteritis, leukorrhea, chronic bronitis, painful red eyes with swelling, lacrimation due to windward exposure, psoriasis, and other diseases or related symptoms. AIM OF THE STUDY: Fraxini cortex is abundant in chemical constituents and has garnered significant attention from plant chemists, particularly regarding coumarins, as evidenced by the recently identified three coumarin compounds. Considering the current dearth of systematic reporting on studies pertaining to Fraxini cortex, herein we provide a comprehensive summary of the advancements in phytochemistry, pharmacology, detection methods, and ethnomedicinal applications of Fraxini cortex. MATERIALS AND METHODS: We conducted a comprehensive search across online data sources (Web of Science, Public Medicine (PubMed), China National Knowledge Infrastructure (CNKI), as well as Chinese dissertations) and traditional Chinese medicine classics to gather the necessary literature resources for this review. RESULTS: Briefly, The Fraxini cortex yielded a total of 132 phytochemicals, including coumarins, lignans, secoiridoids, phenylethanol glycosides, flavonoids, triterpenoids, and other compounds. Among them, the main active ingredients are coumarins which possess a diverse range of pharmacological activities such as anti-inflammatory effects, anti-tumor properties, prevention of tissue fibrosis and oxidation damage as well as cardioprotective effects. CONCLUSIONS: All types of research conducted on Fraxini cortex, particularly in the field of ethnopharmacology, phytochemistry, and pharmacology, have been thoroughly reviewed. However, certain traditional applications and pharmacological activities of Fraxini cortex lack scientific evaluation or convincing evidence due to incomplete methodologies and ambiguous results, as well as a lack of clinical data. To validate its pharmacological activity, clinical efficacy, and safety profile, a systematic and comprehensive research evaluation is imperative. As an important traditional Chinese medicine, Fraxini cortex should be further explored to facilitate the development of novel drugs and therapeutics for various diseases. Greater attention should be given to how it can be better utilized.

Osthole impairs mitochondrial metabolism and the autophagic flux in colorectal cancer.

BACKGROUND: Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the regulatory activity of osthole in colorectal cancer development, focusing on mitochondrial metabolism, is not well known. HYPOTHESIS/PURPOSE: We hypothesized that osthole may suppress progression of colorectal cancer and aimed to determine the underlying mitochondrial metabolism and the autophagic flux. STUDY DESIGN: In this study, we elucidated the mechanism of action of osthole in colorectal cancer using an in vivo azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model and an in vitro cell culture system. METHODS: AOM/DSS mouse model was established and analyzed the effects of osthole on survival rate, diseases activity index, number of tumor and histopathology. Then, cell based assays including viability, cell cycle, reactive oxygen species (ROS), apoptosis, calcium efflux, and mitochondrial function were analyzed. Moreover, osthole-mediated signaling was demonstrated by western blot analyses. RESULTS: Osthole effectively suppressed the growth of colorectal tumors and alleviated AOM/DSS-induced intestinal injury. Osthole restored the function of goblet cells and impaired the expression of Claudin1 and Axin1 impaired by AOM/DSS. In addition, osthole specifically showed cytotoxicity in colorectal carcinoma cells, but not in normal colon cells. Osthole decreased the ASC/caspase-1/IL-1ß inflammasome pathway and induced mitochondrial dysfunction in redox homeostasis, calcium homeostasis. Furthermore, osthole inhibited both oxidative phosphorylation (OXPHOS) and glycolysis, leading to the suppression of ATP production. Moreover, via combination treatment with chloroquine (CQ), we demonstrated that osthole impaired autophagic flux, leading to apoptosis of HCT116 and HT29 cells. Finally, we elucidated that the functional role of tiRNAHisGTG regulated by osthole directly affects the cellular fate of colon cancer cells. CONCLUSION: These results suggest that osthole has the potential to manage progression of colorectal cancer by regulating autophagy- and mitochondria-mediated signal transduction.