RESUMEN
In this study, eight lindenane-type sesquiterpene dimers, including five previously undescribed sesquiterpene dimers (1-5), were isolated from the roots of Chloranthus fortunei, and their structures were elucidated using 1D/2D NMR, HRESIMS, and ECD calculations. Compound 1 presents the second example of a type of novel 8,9-seco lindenane-type sesquiterpene dimer, considered a product of 8/9-diketone oxidation. Compounds 2 and 3 represent the third and fourth examples, respectively, of this kind of C-11 methine dimer. Furthermore, compound 4 was considered as an artifact generated from the radical reaction of a known compound chlojaponilide F (6), which was explained by the density functional theory quantum calculation. All isolates were evaluated for their protective activity against the LPS-induced pulmonary epithelial cell line with compound 7 exhibiting the most potent bioactivity. Further in vitro biological evaluation demonstrated that 7 reduced the production of reactive oxygen species and interleukin-1ß, further regulated by the expression of the NLRP3. These results show that compound 7 exhibits therapeutic potential for lung inflammatory diseases.
RESUMEN
Background: Previous research has suggested that dyslipidemia may be a risk factor for rotator cuff syndrome (RCS), and lipid-lowering drugs may aid in its treatment, though conclusions have not been definitive. Mendelian randomization is a statistical method that explores the causal relationships between exposure factors and diseases. It overcomes the confounding issues inherent in traditional observational studies, thereby providing more reliable causal inferences. We employed this method to investigate whether hyperlipidemia is a risk factor for rotator cuff syndrome and whether lipid-lowering drugs can effectively treat this condition. Methods: Genetic variations linked to lipid traits low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) were acquired from the UK Biobank and the Global Lipids Genetics Consortium (GLGC). Data on genetic variation in rotator cuff syndrome were obtained from FinnGen, including 24,061 patients and 275,212 controls. In the next step, we carried out two-sample Mendelian randomization analyses to determine whether lipid traits correlate with rotator cuff syndrome risk. Additionally, we performed drug-target Mendelian randomization (MR) analyses on 10 drug targets related to rotator cuff syndrome. For the drug targets that showed significant results, further analysis was done using Summary-data-based Mendelian Randomization (SMR) and colocalization techniques. We performed a mediation analysis to identify potential mediators between HMG-CoA reductase (HMGCR) and RCS. Results: No causative link was established between these lipid traits and rotator cuff syndrome. However, a significant association has been identified where HMGCR inhibition corresponds to a reduced risk of rotator cuff disease (OR = 0.68, [95% CI, 0.56-0.83], p = 1.510 × 10-4). Additionally, enhanced expression of HMGCR in muscle tissues is also linked to a decreased risk of rotator cuff syndrome (OR = 0.88, [95% CI, 0.76-0.99], p = 0.03). Body mass index (BMI) mediated 22.97% of the total effect of HMGCR on RCS. Conclusion: This study does not support low-density LDL-C, TG, and TC as risk factors for rotator cuff syndrome. HMGCR represents a potential pharmaceutical target for preventing and treating rotator cuff syndrome. The protective action of statins on the rotator cuff syndrome might not be associated with their lipid-lowering properties.
RESUMEN
The present study utilizes network pharmacology and molecular docking methodologies to investigate the mechanism of action behind the intervention of Polygonum capitatum Buch.-Ham.ex D. Don (THL) in treating pulmonary nodules (PN). This research aims to provide a theoretical foundation for broadening the clinical application of THL. Active components of THL were identified and screened through an extensive literature review and the PharmMapper database, followed by an analysis of their target interactions. Relevant targets associated with PN were selected using databases such as OMIM and GeneCards, with an intersection of the two sets being determined. STRING11.5 facilitated the acquisition of protein-protein interaction data, which was then imported into Cytoscape 3.7.2 to establish a protein interaction network topology. This enabled the identification of pivotal targets affected by THL intervention in PN. The study further employed the Metascape database to conduct GO and KEGG bioinformatics enrichment analyses, which illuminated core pathways involved in THL's therapeutic effects on PN. A comprehensive component-target-pathway diagram was constructed utilizing Cytoscape 3.7.2 software, with molecular docking validations carried out via Maestro software. A total of 49 active THL ingredients were discerned, implicating 67 PN-relevant targets. Subsequent software analysis pinpointed 10 key targets, including ALB, EGFR, and SRC. Molecular docking studies indicated strong binding affinities for most protein-compound pairs, with 44 out of 60 docking results exhibiting binding energies below -5 kcal/mol. Enrichment analysis highlights that key targets are mainly involved in pathways such as cancer, lipid metabolism and atherosclerosis, estrogen signaling, IL-17 signaling, complement and coagulation cascades, and chemical carcinogenesis through receptor activation. Through comprehensive network pharmacological approaches, this research delineates the synergy of THL's multiple components, targets, and pathways in mitigating PN. It posits that primary active ingredients of THL - quercetin, salidroside, and oleanolic acid - may exert effects on targets like ALB, EGFR, SRC, potentially modulating pathways associated with cancer, lipid and atherosclerosis, and IL-17 signaling in the context of PN intervention.
Asunto(s)
Simulación del Acoplamiento Molecular , Farmacología en Red , Polygonum , Polygonum/química , Humanos , Farmacología en Red/métodos , Mapas de Interacción de Proteínas , Nódulo Pulmonar Solitario/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/químicaRESUMEN
This study aims to analyze the effective components of Polygonum capitatum (PC) inhibiting Escherichia coli based on network pharmacology methods and predict its molecular mechanism of action. PC compounds and targets were collected from the TCMSP database, Swiss Target Prediction, and the literature. E coli targets were searched using the GeneCards database. The targets of E coli and the targets of the active ingredients of PC were taken as intersections to obtain the intersecting targets. The resulting overlapping targets were uploaded to the STRING database to construct the protein interaction network diagram of E coli target inhibition. The key targets for the inhibitory effect of PC on E coli were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by uploading key targets into the DAVID database. The results showed that there were 50 targets for PC to inhibit E coli. Among them, there are 5 core targets, mainly including AKT1, TNF, EGFR, JUN, and ESR1. A total of 196 gene ontology functional analysis results and 126 Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results were obtained. These include cellular response to cadmium-ion, cellular response to reactive oxygen species, pathways in cancer, prostate cancer, and PI3K-Akt signaling pathway. Molecular docking results indicate that Lutedin, Hirsutin, Flazin, and Ellagic acid in PC have high affinity for the target genes AKT1, TNF, MAPK3 and EGFR. PC exerts its inhibitory effect on E coli through multi-targets and multi-pathways, which provides a new basis for the new use of PC as an old medicine.
Asunto(s)
Escherichia coli , Simulación del Acoplamiento Molecular , Farmacología en Red , Polygonum , Polygonum/química , Escherichia coli/efectos de los fármacos , Humanos , Mapas de Interacción de Proteínas/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/químicaRESUMEN
The biosynthetic route for flavonol in Camptotheca acuminata has been recently elucidated from a chemical point of view. However, the genes involved in flavonol methylation remain unclear. It is a critical step for fully uncovering the flavonol metabolism in this ancient plant. In this study, the multi-omics resource of this plant was utilized to perform flavonol O-methyltransferase-oriented mining and screening. Two genes, CaFOMT1 and CaFOMT2 are identified, and their recombinant CaFOMT proteins are purified to homogeneity. CaFOMT1 exhibits strict substrate and catalytic position specificity for quercetin, and selectively methylates only the 4'-OH group. CaFOMT2 possesses sequential O-methyltransferase activity for the 4'-OH and 7-OH of quercetin. These CaFOMT genes are enriched in the leaf and root tissues. The catalytic dyad and critical substrate-binding sites of the CaFOMTs are determined by molecular docking and further verified through site-mutation experiments. PHE181 and MET185 are designated as the critical sites for flavonol substrate selectivity. Genomic environment analysis indicates that CaFOMTs evolved independently and that their ancestral genes are different from that of the known Ca10OMT. This study provides molecular insights into the substrate-binding pockets of two new CaFOMTs responsible for flavonol metabolism in C. acuminata.
Asunto(s)
Camptotheca , Metiltransferasas , Simulación del Acoplamiento Molecular , Especificidad por Sustrato , Camptotheca/enzimología , Camptotheca/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , Metiltransferasas/química , Flavonoles/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Filogenia , Metilación , Secuencia de AminoácidosRESUMEN
We report two practical and step-economical methodologies for the chemodivergent synthesis of tri-substituted pyrroles and 3-oxazolines from the domino reactions of 2H-azirines and acetone. For instance, acetone served as a nucleophile to react with 2H-azirines under the basic conditions to furnish pyrroles. Upon changing the catalyst to TfOH, acetone served as an electrophile to synthesize 3-oxazolines. Moreover, the products could be synthesized on a gram scale, and the possible catalytic cycles were proposed.
RESUMEN
BACKGROUND: Persicaria capitata (Buch.-Ham. ex D.Don) H.Gross (P. capitata, PCB), a traditional drug of the Miao people in China, is potential traditional drug used for the treatment of diabetic nephropathy (DN). PURPOSE: The purpose of this study is to investigate the function of P. capitata and clarify its protective mechanism against DN. METHODS: We induced DN in the Guizhou miniature pig with injections of streptozotocin, and P. capitata was added to the pigs' diet to treat DN. In week 16, all the animals were slaughtered, samples were collected, and the relative DN indices were measured. 16S rRNA sequencing, metagenomics, metabolomics, RNA sequencing, and proteomics were used to explore the protective mechanism of P. capitata against DN. RESULTS: Dietary supplementation with P. capitata significantly reduced the extent of the disease, not only in term of the relative disease indices but also in hematoxylin-eosin-stained tissues. A multiomic analysis showed that two microbes (Clostridium baratii and Escherichia coli), five metabolites (oleic acid, linoleic acid, 4-phenylbutyric acid, 18-ß-glycyrrhetinic acid, and ergosterol peroxide), four proteins (ENTPD5, EPHX1, ARVCF and TREH), four important mRNAs (encoding ENTPD5, EPHX1, ARVCF, and TREH), six lncRNAs (TCONS_00024194, TCONS_00085825, TCONS_00006937, TCONS_00070981, TCONS_00074099, and TCONS_00097913), and two circRNAs (novel_circ_0001514 and novel_circ_0017507) are all involved in the protective mechanism of P. capitata against DN. CONCLUSIONS: Our results provide multidimensional theoretical support for the study and application of P. capitata.
Asunto(s)
Nefropatías Diabéticas , Porcinos Enanos , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Porcinos , Diabetes Mellitus Experimental , Estreptozocina , Medicamentos Herbarios Chinos/farmacología , Suplementos Dietéticos , Masculino , ProteómicaRESUMEN
In our research on naturally occurring sesquiterpenes, eight shizukaol-type dimers, one chlorahololide-type dimer, and one sarcanolide-type dimer were isolated from the roots of Chloranthus fortunei. As the project was implemented, we accidentally discovered that shizukaol-type dimers can be converted into peroxidized chlorahololide-type dimers. This potential change was discovered after simulations of the changes in corresponding shizukaols showed that three peroxide products were generated (1-3), indicating that peroxidation reactions occurred. HPLC-HR-MS analysis results obtained for the shizukaol derivatives further demonstrate that the reaction occurred, and the type of substituent of small organic ester moieties at positions C-15' and C-13' of unit B were not decisively related to the reaction. Quantum chemical calculations of the mode dimer further demonstrated this phenomenon. The highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy of the precursor and production revealed the advantageous yield of 4ß-hydroperoxyl production. Additionally, the potential reaction mechanism was speculated and validated using the free energy in the reaction which successfully explained the feasibility of the reaction. Finally, the anti-inflammatory activity of the precursors and products was evaluated, and the products of peroxidation showed better anti-inflammatory activity.
Asunto(s)
Artefactos , Sesquiterpenos , Antiinflamatorios/farmacología , Sesquiterpenos/químicaRESUMEN
As our ongoing searching for the bioactive natural terpenoids, nine ent-kauranoids (1-9), including three previously undescribed ones (1, 2, and 9), were isolated from the aerial parts of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic data analysis, including NMR, MS, and ECD. Compounds 1 and 2 were a pair of tautomeric compounds, which was confirmed by the HPLC analysis and low temperature NMR testing. The underlying mechanism of the tautomer was proposed as an intramolecular SN2 reaction, which was explained by quantum chemical calculation. The HOMO-LUMO gap and the free energy revealed the spontaneous of the tautomeric of the 1 and 2. Additionally, the similar phenomena were also found in the two groups of known compounds 3 and 4 and 6 and 7, respectively. Apart from the tautomer, compounds 3 and 4 can be hydrolyzed into 5 through ester hydrolysis in CDCl3, while compounds 6, 7 can be hydrolyzed into 8 through ester hydrolysis. These phenomena were also confirmed through HPLC analysis and low temperature nuclear magnetic resonance tests and the mechanism was studied using quantum chemical calculation.
Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Isodon , Estructura Molecular , Isodon/química , Componentes Aéreos de las Plantas/química , Ésteres , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
An increasing number of peripheral pulmonary lesions (PPLs) requiring tissue verification to establish a definite diagnosis for further individualized management are detected due to the growing adoption of lung cancer screening by chest computed tomography (CT), especially low-dose CT. However, the morphological diagnosis of PPLs remains challenging. Transbronchial lung cryobiopsy (TBLC) that can retrieve larger specimens with more preserved cellular architecture and fewer crush artifacts in comparison with conventional transbronchial forceps biopsy (TBFB), as an emerging technology for diagnosing PPLs, has been demonstrated to have the potential to resolve the clinical dilemma pertaining to currently available sampling devices (e.g., forceps, needle and brush) and become a diagnostic cornerstone for PPLs. Of note, with the introduction of the 1.1 mm cryoprobe that will be more compatible with advanced bronchoscopic navigation techniques, such as radial endobronchial ultrasound (r-EBUS), virtual bronchoscopic navigation (VBN) and electromagnetic navigation bronchoscopy (ENB), the use of TBLC is expected to gain more popularity in the diagnosis of PPLs. While much remains for exploration using the TBLC technique for diagnosing PPLs, it can be envisaged that the emergence of additional studies with larger data accrual will hopefully add to the body of evidence in this field.
RESUMEN
Escherichia coli, a well-known prokaryotic organism, has been widely employed as a versatile host for heterologous overexpression of proteins/biocatalysts and the production of pharmaceutically important intermediates/small molecules. However, some E. coli endogenous enzymes showing substrate promiscuity may disturb the heterologous metabolic flux, which will result in the reduction of substrates, intermediates, and target products. Here we reported an unexpected E. coli-catalyzed regioselective O-acetylation of various glucosides. The regioselectively O-acetylated products, 6'-O-acetyl-loganin and 6'-O-acetyl-loganic acid, were obtained and characterized from the enzymatic reaction in which the supernatants of E. coli expressing either CaCYP72A565 and CaCPR, the key enzymes involved in camptothecin biosynthesis, or empty vector were used as catalyst and loganin and loganic acid as independent substrate. An alkaloidal glucoside strictosamide was converted into the regioselectively O-acetylated product 6'-O-acetyl-strictosamide, implying substrate promiscuity of the E. coli-catalyzed O-acetylation reaction. Furthermore, 8 glucosides, including 5 iridoid glucosides and 3 flavonoid glucosides, were successfully converted into the regioselectively O-acetylated products by E. coli, indicating the wide substrate range for the unexpected E. coli-catalyzed O-acetylation. E. coli maltose O-acetyltransferase was demonstrated to be responsible for the mentioned regioselective O-acetylation at the 6-OH of the glucopyranosyl group of multiple classes of natural product glucosides through candidate acetyltransferase-encoding gene analysis, gene knock-out, gene complementation, and the relevant enzymatic reaction activity assays. The present study not only provides an efficient biocatalyst for regioselective O-acetylation but also notifies cautions for metabolic engineering and synthetic biology applications in E. coli. KEY POINTS: ⢠6-OH of glucosyl of multiple glucosides was regioselectively O-acetylated by E. coli. ⢠Endogenous EcMAT is responsible for the regioselective O-acetylation reaction.
Asunto(s)
Escherichia coli , Glucósidos , Escherichia coli/metabolismo , Glucósidos/metabolismo , Maltosa/metabolismo , Acetilación , Acetiltransferasas/genética , CatálisisRESUMEN
Pulmonary fibrosis (PF) is a serious interstitial disease that includes diffuse collagen deposition of lung tissue. Polygonum capitatum Buch.-Ham. ex D. Don (THL) is a traditional vaccine that has antibacterial and anti-inflammatory effects. In this research, to investigate the mechanism of action of THL in the intervention of pulmonary fibrosis by network pharmacology and molecular docking related research methods, in order to provide a theoretical basis for expanding the scope of THL medication. A total of 49 active ingredients were analyzed and screened in Cephalus cephalusis, including 35 pulmonary fibrosis targets, and 10 key targets such as ALB, EGFR were screened after software analysis. The molecular docking results showed that there were 44 binding energies less than -3 kcal·mol-1 in the 60 docking results, indicating that most proteins had strong binding energies with compounds. The key targets of KEGG enrichment analysis were mainly enriched in 20 core action pathways, such as hemostasis-related pathway, regulation of kinase activity. This study shows that based on network pharmacology, the multicomponent-multitarget-multipathway effect of THL intervention in pulmonary fibrosis is discussed.
Asunto(s)
Polygonum , Fibrosis Pulmonar , Humanos , Fibrosis Pulmonar/tratamiento farmacológico , Farmacología en Red , Simulación del Acoplamiento Molecular , AntibacterianosRESUMEN
Eleven previously unreported compounds (1-11), including five diterpenoids (1-5) and six sesquiterpenoids (6-11), together with two known diterpenoids (12-13), have been isolated from the roots of Salvia prattii. Their structures were comprehensively elucidated through spectroscopic methods, and their configurations were established using computational 13C nuclear magnetic resonance and electronic circular dichroism. Compound 1 was found to be an abietane-type diterpenoid with a novel rearrangement generated from the cleavage of the C-4/5 chemical bond, 20-methyl shift, and the rearrangement of the C-10 side chain. Compounds 2-3 were the third and fourth examples of arrangement seco-norabietanes with a spiro-lactone ring. We evaluated all compounds for their protective effects against alcoholic liver diseases (ALD). Compound 2 exhibited potential protective activity and hence can be used as a novel anti-ALD candidate.
Asunto(s)
Diterpenos , Salvia , Terpenos/farmacología , Estructura Molecular , Salvia/química , Diterpenos/farmacología , Diterpenos/química , Abietanos/farmacología , Abietanos/químicaRESUMEN
Dozens of triterpenes have been isolated from Camptotheca acuminata, however, triterpene metabolism in this plant remains poorly understood. The common C28 carboxy located in the oleanane-type and ursane-type triterpenes indicates the existence of a functionally active triterpene, C28 oxidase, in this plant. Thorough mining and screening of the CYP716 genes were initiated using the multi-omics database for C. acuminata. Two CYP716A (CYP716A394 and CYP716A395) and three CYP716C (CYP716C80-CYP716C82) were identified based on conserved domain analyses and hierarchical cluster analyses. CYP716 microsomal proteins were prepared and their enzymatic activities were evaluated in vitro. The CYP716 classified into the CYP716C subfamily displays ß-amyrin oxidation activity, and CYP716A displays α-amyrin and lupeol oxidation activity, based on gas chromatography-mass spectrometry analyses. The oxidation products were determined based on their mass and nuclear magnetic resonance spectrums. The optimum reaction conditions and kinetic parameters for CYP716C were determined, and functions were verified in Nicotiana benthaminana. Relative quantitative analyses revealed that these CYP716C genes were enriched in the leaves of C. acuminata plantlets after 60 d. These results indicate that CYP716C plays a dominant role in oleanane-type triterpene metabolism in the leaves of C. acuminata via a substrate-specific manner, and CYP716A is responsible for ursane- and lupane-type triterpene metabolism in fruit. This study provides valuable insights into the unique CYP716C-mediated oxidation step of pentacyclic triterpene biosynthesis in C. acuminata.
Asunto(s)
Camptotheca , Triterpenos , Camptotheca/metabolismo , Oxidorreductasas , Triterpenos Pentacíclicos , Triterpenos/metabolismoRESUMEN
The detailed metabolic map for camptothecin (CPT) biosynthesis in Camptotheca acuminata has been proposed according to our combined omics results. However, the CYP450-mediated epoxidation step in CPT biosynthesis remains unexplored. A proteomics-guided approach was used to identify and annotate the proteins enriched during the vigorous CPT metabolism period in mature C. acuminata and seedlings. Comparative analyses revealed that the CPT and flavonoid biosyntheses were vigorous in stems and all of the samples except the leaves, respectively. The CYP71BE genes were screened based on their enrichment patterns at the transcriptomic-proteomic level and biochemically characterized in Saccharomyces cerevisiae WAT11. Four CYP71BE proteins exhibited in vitro isoliquiritigenin epoxidase activity. Additionally, CYP71BE206 showed epoxidase activity toward strictosamide, the critical precursor for CPT biosynthesis, both in vitro and in Nicotiana benthamiana. In planta functional verification suggested that CYP71BE206 is involved in CPT biosynthesis. Their catalytic conditions were optimized, and the enzymatic parameters were determined. This study provides valuable insight into the CYP71BE-mediated epoxidation step for CPT biosynthesis and offers evidence to verify that the newly characterized epoxidase (CYP71BE206) is simultaneously responsible for the biosynthesis of CPT and the flavonoid in this plant. An evolution event probably happened on ancestral CYP71BE, resulting in the neofunctionalization of CYP71BE206.
Asunto(s)
Camptotheca , Camptotecina , Proteómica , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismoRESUMEN
Salvia miltiorrhiza Bunge is an important traditional herb. Salvia miltiorrhiza is distributed in the Sichuan province of China (here called SC). Under natural conditions, it does not bear seeds and its sterility mechanism is still unclear. Through artificial cross, there was defective pistil and partial pollen abortion in these plants. Electron microscopy results showed that the defective pollen wall was caused by delayed degradation of the tapetum. Due to the lack of starch and organelle, the abortive pollen grains showed shrinkage. RNA-seq was performed to explore the molecular mechanisms of pollen abortion. KEGG enrichment analysis suggested that the pathways of phytohormone, starch, lipid, pectin, and phenylpropanoid affected the fertility of S. miltiorrhiza. Moreover, some differentially expressed genes involved in starch synthesis and plant hormone signaling were identified. These results contribute to the molecular mechanism of pollen sterility and provide a more theoretical foundation for molecular-assisted breeding.
Asunto(s)
Infertilidad Masculina , Salvia miltiorrhiza , Masculino , Humanos , Transcriptoma , Perfilación de la Expresión Génica/métodos , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Infertilidad Vegetal/genéticaRESUMEN
Tetracycline pollution in soil irreversibly damages the biosafety of plants by inhibiting the mitochondrial function. Some traditional Chinese medicine (TCM) plants, such as Salvia miltiorrhiza Bunge, have a strong tolerance to mitochondrial damage. We comprehensively compared the doxycycline (DOX) tolerances of two ecotypes of S. miltiorrhiza in the Sichuan and Shandong provinces and found that the Sichuan ecotype had a lower yield reduction, more stable accumulation of medicinal ingredients, higher mitochondrial integrity, and a more robust antioxidant system. The synergetic response networks under DOX pollution of both ecotypes were constructed using RNA sequencing and ultrahigh-performance liquid chromatography-tandem mass spectrometry. The differentiation of the downstream pathways of aromatic amino acids (AAAs) produced variations in the DOX tolerance of S. miltiorrhiza in different regions. The Sichuan ecotype maintained redox homeostasis and xylem development by activating salvianolic acid and indole biosynthesis, while the Shandong ecotype balanced chemical and mechanical defenses by regulating the flavonoid biosynthesis. Rosmarinic acid, a downstream AAA molecule, maintains the mitochondrial homeostasis of plant seedlings under DOX pollution by targeting the ABCG28 transporter. We also highlight the significance of downstream AAA small molecules in guiding the development of bio-based environmental pollution remediation agents.
Asunto(s)
Salvia miltiorrhiza , Salvia miltiorrhiza/química , Salvia miltiorrhiza/genética , Salvia miltiorrhiza/metabolismo , Doxiciclina/farmacología , Doxiciclina/análisis , Doxiciclina/metabolismo , Ecotipo , Multiómica , Contaminación Ambiental , Raíces de Plantas/química , Raíces de Plantas/metabolismoRESUMEN
Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1-2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM.
Asunto(s)
Antineoplásicos , Gelsemium , Alcaloides de Triptamina Secologanina , Estructura Molecular , Gelsemium/química , Indoles , Alcaloides de Triptamina Secologanina/farmacología , Alcaloides de Triptamina Secologanina/química , Antineoplásicos/farmacología , Extractos Vegetales/farmacología , Alcaloides Indólicos/químicaRESUMEN
The etiology of premature ovarian failure (POF) is mainly related to inflammatory diseases, autoimmune diseases, and tumor radiotherapy and chemotherapy; however, its specific pathogenesis has not been clarified. Vitamin D (VD), a fat-soluble vitamin, is an essential steroid hormone in the human body. Neutrophil extracellular traps (NETs) are meshwork structures that are formed when neutrophils are stimulated by inflammation and other factors and are closely associated with autoimmune and inflammatory diseases. Notably, VD inhibits NET formation and intervenes in the development of POF in terms of inflammatory and immune responses, oxidative stress, and tissue fibrosis. Therefore, this study aimed to theorize the relationship between NETs, VD, and POF and provide new ideas and targets for the pathogenesis and clinical treatment of POF.
Asunto(s)
Trampas Extracelulares , Menopausia Prematura , Insuficiencia Ovárica Primaria , Femenino , Humanos , Vitamina D/farmacología , Vitamina D/uso terapéutico , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Neutrófilos/patología , Vitaminas/farmacología , Vitaminas/uso terapéuticoRESUMEN
The amino alcohol meglumine solubilizes organic compounds in water and enforces the formation of electron donor acceptor (EDA) complexes of haloarenes with indoles, anilines, anisoles or thiols, which are not observed in organic solvents. UV-A photoinduced electron transfer within the EDA complexes induces the mesolytic cleavage of the halide ion and radical recombination of the arenes leading, after rearomatization and proton loss to C-C or C-S coupling products. Depending on the substitution pattern selective and unique cross-couplings are observed. UV and NMR measurements reveal the importance of the assembly for the photoinduced reaction. Enforced EDA aggregate formation in water allows new activation modes for organic photochemical synthesis.