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1.
Phytochemistry ; 225: 114188, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38878943

RESUMEN

Phytochemical investigation on the fruits of Cydonia oblonga Mill., a traditional Uighur medicine, led to the isolation of seven undescribed and nine known megastigmane glycosides. Their structures including absolute configurations were characterized by an extensive analysis of spectroscopic data including HRESIMS and NMR, combined with ECD calculations. Additionally, compounds 1, 2, 4, and 6-16 exhibited anti-inflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharides (LPS) with inhibitory rates of 10.79%-44.58% at 20 µM.

2.
Phytochemistry ; 225: 114173, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38851474

RESUMEN

Saponins are bioactive components of many medicinal plants, possessing complicated chemical structures and extensive pharmacological activities, but the production of high-value saponins remains challenging. In this study, a 6'-O-glucosyltransferase PpUGT7 (PpUGT91AH7) was functionally characterized from Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz., which can transfer a glucosyl group to the C-6' position of diosgenin-3-O-rhamnosyl-(1 â†’ 2)-glucoside (1), pennogenin-3-O-rhamnosyl-(1 â†’ 2)-glucoside (2), and diosgenin-3-O-glucoside (5). The KM and Kcat values of PpUGT7 towards the substrate 2 were 8.4 µM and 2 × 10-3 s-1, respectively. Through molecular docking and site-directed mutagenesis, eight residues were identified to interact with the sugar acceptor 2 and be crucial for enzyme activity. Moreover, four rare ophiopogonins and ginsenosides were obtained by combinatorial biosynthesis, including an undescribed compound ruscogenin-3-O-glucosyl-(1 â†’ 6)-glucoside (10). Firstly, two monoglycosides 9 and 11 were generated using a known sterol 3-O-ß-glucosyltransferase PpUGT80A40 with ruscogenin (7) and 20(S)-protopanaxadiol (8) as substrates, which were further glycosylated to the corresponding diglycosides 10 and 12 under the catalysis of PpUGT7. In addition, compounds 7-11 were found to show inhibitory effects on the secretion of TNF-α and IL-6 in macrophages RAW264.7. The findings provide valuable insights into the enzymatic glycosylation processes in the biosynthesis of bioactive saponins in P. polyphylla var. yunnanensis, and also serve as a reference for utilizing UDP-glycosyltransferases to construct high-value or rare saponins for development of new therapeutic agents.

3.
Phytochemistry ; 225: 114185, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38876164

RESUMEN

Five undescribed leucosesterterpane sesterterpenoids, leucosceptrines A-E, two undescribed penta-nor-leucosesterterpane (C20) sesterterpenoids, nor-leucosceptrines A and B, and three known analogues, were obtained from the aerial parts of Leucosceptrum canum of Chinese origin. Leucosceptrines A-C are the first examples of leucosesterterpane-type sesterterpenoids with unclosed dihydropyran rings and reverse configurations at chiral centers C-4 and/or C-12. Nor-leucosceptrines A and B possesses an unusual penta-nor-leucosesterterpane skeleton. Their structures were unambiguously elucidated through comprehensive spectroscopic analyses and single-crystal X-ray diffraction. A plausible biogenetic pathway for these sesterterpenoids was proposed. The immunosuppressive effects of these isolates on the secretion of the cytokine IFN-γ by T cells stimulated with anti-CD3/CD28 monoclonal antibodies were observed with different potencies.

4.
Eur Radiol ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750169

RESUMEN

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

5.
Biomed Pharmacother ; 175: 116784, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38781865

RESUMEN

1,8-Cineole is a bicyclic monoterpene widely distributed in the essential oils of various medicinal plants, and it exhibits significant anti-inflammatory and antioxidant activities. We aimed to investigate the therapeutic effect of 1,8-cineole on anti-Alzheimer's disease by using transgenic Caenorhabditis elegans models. Our studies demonstrated that 1,8-cineole significantly relieved Aß1-42-induced paralysis and exhibited remarkable antioxidant and anti-Aß1-42 aggregation activities in transgenic nematodes CL4176, CL2006 and CL2355. We developed a 1,8-cineole/cyclodextrin inclusion complex, displaying enhanced anti-paralysis, anti-Aß aggregation and antioxidant activities compared to 1,8-cineole. In addition, we found 1,8-cineole treatment activated the SKN-1/Nrf-2 pathway and induced autophagy in nematodes. Our results demonstrated the antioxidant and anti-Alzheimer's disease activities of 1,8-cineole, which provide a potential therapeutic approach for Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Animales Modificados Genéticamente , Antioxidantes , Caenorhabditis elegans , Eucaliptol , Eucaliptol/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Caenorhabditis elegans/efectos de los fármacos , Antioxidantes/farmacología , Péptidos beta-Amiloides/metabolismo , Ciclodextrinas/farmacología , Ciclodextrinas/química , Fragmentos de Péptidos/farmacología , Autofagia/efectos de los fármacos , Modelos Animales de Enfermedad
6.
Orthop Surg ; 16(6): 1418-1433, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38658320

RESUMEN

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.


Asunto(s)
Biología Computacional , Células Madre Mesenquimatosas , Osteogénesis , Osteoporosis Posmenopáusica , Humanos , Osteoporosis Posmenopáusica/genética , Animales , Femenino , Células Madre Mesenquimatosas/metabolismo , Ratones , Biología Computacional/métodos , Osteogénesis/fisiología , Osteogénesis/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Aprendizaje Automático , Diferenciación Celular , Adenosina/metabolismo , Adenosina/genética , Adenosina/análogos & derivados
7.
J Nat Prod ; 87(4): 1103-1115, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38600744

RESUMEN

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.


Asunto(s)
Alcaloides , Animales Ponzoñosos , Quilópodos , Animales , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Estructura Molecular , Artrópodos/química , Fibrosis/tratamiento farmacológico , Riñón/efectos de los fármacos , Quinolinas/farmacología , Quinolinas/química , Antiinflamatorios/farmacología , Antiinflamatorios/química , Humanos
8.
J Agric Food Chem ; 72(17): 9746-9754, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38602331

RESUMEN

The latex of Euphorbia peplus and its major component 20-deoxyingenol-3-angelate (DI3A) displayed significant nematicidal activity against Caenorhabditis elegans and Panagrellus redivivus. DI3A treatment inhibited the growth and development of nematodes and caused significantly negative effects on locomotion behavior, reproduction, and accumulation of reactive oxygen species. Transcriptome analysis indicated that differential expression genes in DI3A-treated C. elegans were mainly associated with the metabolism, growth, and development process, which were further confirmed by RT-qPCR experiments. The expression level of TPA-1 gene encoding a protein kinase C isotype was obviously upregulated by DI3A treatment, and knockdown of TPA-1 by RNAi technology in the nematode could relieve the growth-inhibitory effect of DI3A. Metabolic analysis indicated that DI3A was hardly metabolized by C. elegans, but a glycosylated indole derivative was specifically accumulated likely due to the activation of detoxification. Overall, our findings suggested that DI3A from E. peplus latex exerted a potent nematicidal effect through the gene TPA-1, which provides a potential target for the control of nematodes and also suggests the potential application value of E. peplus latex and DI3A as botanical nematicides.


Asunto(s)
Antinematodos , Caenorhabditis elegans , Euphorbia , Látex , Proteína Quinasa C , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/enzimología , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/crecimiento & desarrollo , Látex/química , Látex/metabolismo , Antinematodos/farmacología , Antinematodos/química , Antinematodos/metabolismo , Euphorbia/química , Proteína Quinasa C/metabolismo , Proteína Quinasa C/genética , Extractos Vegetales/farmacología , Extractos Vegetales/química
10.
Med ; 5(6): 570-582.e4, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38554711

RESUMEN

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).


Asunto(s)
Análisis Costo-Beneficio , Cirrosis Hepática , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/economía , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Transversales , Diabetes Mellitus/mortalidad , Diabetes Mellitus/epidemiología , Diabetes Mellitus/economía , Anciano , Medición de Riesgo , Diagnóstico por Imagen de Elasticidad/economía , Valor Predictivo de las Pruebas , Encuestas Nutricionales , Curva ROC
11.
Org Biomol Chem ; 22(15): 3019-3024, 2024 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-38530279

RESUMEN

An unusual pyridine-containing sesterterpenoid, leucosceptrodine (1), and five new nor-leucosceptrane sesterterpenoids, including bisnor- (C23, 2), tetranor- (C21, 3) and pentanor- (C20, 4-6) skeletons, were isolated from the leaves of Tibetan Leucosceptrum canum. Their structures including their absolute configurations were determined by extensive spectroscopic analyses and quantum chemical calculations. A single crystal of one epimer (5) was crystallized from a pair of inseparable epimers, and its structure including its absolute configuration was determined by X-ray crystallographic analysis. The immunosuppressive activities of compounds 1-4 with different potencies were evaluated by inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.


Asunto(s)
Lamiaceae , Sesterterpenos , Sesterterpenos/química , Tibet , Lamiaceae/química , Cristalografía por Rayos X , Piridinas/farmacología , Estructura Molecular
12.
J Org Chem ; 89(5): 3652-3656, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38353480

RESUMEN

An efficient synthetic approach was developed and applied to the syntheses of four linear biosynthetic C25-precursors of leucosceptroids. The synthesis features a Julia-Kocienski olefination and a late-stage bioinspired photo-oxidation as key steps. The immunosuppressive effects of all synthetic compounds on mouse T cells and macrophage RAW264.7 were determined.


Asunto(s)
Estructura Molecular , Animales , Ratones , Oxidación-Reducción
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(1): 62-66, 2024 Jan 15.
Artículo en Chino | MEDLINE | ID: mdl-38269461

RESUMEN

OBJECTIVES: To investigate the risk factors for diabetic ketoacidosis (DKA) in children/adolescents with type 1 diabetes mellitus (T1DM) and to establish a model for predicting the risk of DKA. METHODS: A retrospective analysis was performed on 217 children/adolescents with T1DM who were admitted to General Hospital of Ningxia Medical University from January 2018 to December 2021. Among the 217 children/adolescents,169 cases with DKA were included as the DKA group and 48 cases without DKA were included as the non-DKA group. The risk factors for DKA in the children/adolescents with T1DM were analyzed, and a nomogram model was established for predicting the risk of DKA in children/adolescents with T1DM. RESULTS: For the 217 children/adolescents with T1DM, the incidence rate of DKA was 77.9% (169/217). The multivariate logistic regression analysis showed that high levels of random blood glucose, hemoglobin A1c (HbA1c), blood ketone body, and triglyceride on admission were closely associated with the development of DKA in the children/adolescents with T1DM (OR=1.156, 3.2031015, 20.131, and 9.519 respectively; P<0.05). The nomogram prediction model had a C-statistic of 0.95, with a mean absolute error of 0.004 between the risk of DKA predicted by the nomogram model and the actual risk of DKA, indicating that the model had a good overall prediction ability. CONCLUSIONS: High levels of random blood glucose, HbA1c, blood ketone body, and triglyceride on admission are closely associated with the development of DKA in children/adolescents with T1DM, and targeted intervention measures should be developed to reduce the risk of DKA.


Asunto(s)
Diabetes Mellitus Tipo 1 , Cetosis , Niño , Adolescente , Humanos , Diabetes Mellitus Tipo 1/complicaciones , Glucemia , Hemoglobina Glucada , Estudios Retrospectivos , Factores de Riesgo , Cuerpos Cetónicos , Triglicéridos
14.
Phytochem Anal ; 35(4): 621-633, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38191170

RESUMEN

INTRODUCTION: Steroidal saponins characterised by intricate chemical structures are the main active components of a well-known traditional Chinese medicine (TCM) Rhizoma Paridis. The metabolic profiles of steroidal saponins in vivo remain largely unexplored, despite their renowned antitumor, immunostimulating, and haemostatic activity. OBJECTIVE: To perform a comprehensive analysis of the chemical constituents of Rhizoma Paridis total saponins (RPTS) and their metabolites in rats after oral administration. METHOD: The chemical constituents of RPTS and their metabolites were analysed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). RESULTS: A reliable UPLC-Q-TOF-MS/MS method was established, and a total of 142 compounds were identified in RPTS. Specifically, diosgenin-type saponins showed the diagnostic ions at m/z 415.32, 397.31, 283.25, 271.21, and 253.20, whereas pennogenin-type saponins exhibited the diagnostic ions at m/z 413.31, 395.30, and 251.20. Based on the characteristic fragments and standard substances, 15 specific metabolites were further identified in the faeces, urine, plasma, and bile of rats. The metabolic pathways of RPTS, including phase I reactions (de-glycosylation and oxidation) and phase II reactions (glucuronidation), were explored and summarised, and the enrichment of metabolites was characterised by multivariate statistical analysis. CONCLUSION: The intricate RPTS could be transformed into relatively simple metabolites in rats through de-glycosylation, which provides a reference for further metabolic studies and screening of active ingredients for TCM.


Asunto(s)
Ratas Sprague-Dawley , Saponinas , Espectrometría de Masas en Tándem , Animales , Saponinas/análisis , Saponinas/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Masculino , Ratas , Rizoma/química , Medicamentos Herbarios Chinos/química , Esteroides/análisis
15.
Cell Signal ; 115: 111038, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38195035

RESUMEN

N6-methyladenosine (m6A), the most prevalent internal modification in mRNA, is related to the pathogenesis of osteoporosis (OP). Although methyltransferase Like-3 (METTL3), an m6A transferase, has been shown to mitigate OP progression, the mechanisms of METTL3-mediated m6A modification in osteoblast function remain unclear. Here, fluid shear stress (FSS) induced osteoblast proliferation and differentiation, resulting in elevated levels of METTL3 expression and m6A modification. Through Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) and Transcriptomic RNA Sequencing (RNA-seq), SRY (Sex Determining Region Y)-box 4 (SOX4) was screened as a target of METTL3, whose m6A-modified coding sequence (CDS) regions exhibited binding affinity towards METTL3. Further functional experiments demonstrated that knockdown of METTL3 and SOX4 hampered osteogenesis, and METTL3 knockdown compromised SOX4 mRNA stability. Via RNA immunoprecipitation (RIP) assays, we further confirmed the direct interaction between METTL3 and SOX4. YTH N6-Methyladenosine RNA Binding Protein 3 (YTHDF3) was identified as the m6A reader responsible for modulating SOX4 mRNA and protein levels by affecting its degradation. Furthermore, in vivo experiments demonstrated that bone loss in an ovariectomized (OVX) mouse model was reversed through the overexpression of SOX4 mediated by adeno-associated virus serotype 2 (AAV2). In conclusion, our research demonstrates that METTL3-mediated m6A modification of SOX4 plays a crucial role in regulating osteoblast proliferation and differentiation through its recognition by YTHDF3. Our research confirms METTL3-m6A-SOX4-YTHDF3 as an essential axis and potential mechanism in OP.


Asunto(s)
Metiltransferasas , Osteoblastos , Animales , Ratones , Proliferación Celular , Metiltransferasas/metabolismo , Osteoblastos/metabolismo , ARN , ARN Mensajero/metabolismo
16.
J Asian Nat Prod Res ; 26(1): 78-90, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38069835

RESUMEN

Phytochemical investigation on the aerial parts of Salvia deserta led to the isolation of eight new pentacyclic triterpenoids including three oleanane- (1 - 3) and five ursane-type (4 - 8) triterpenoids, whose structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculation. Weak immunosuppressive potency was observed for compounds 1, 2, and 4 - 8 via inhibiting the secretion of cytokines TNF-α and IL-6 in LPS-induced macrophages RAW264.7 at 20 µM. In addition, compounds 1, 2, and 4 - 6 exhibited moderate protective activity on t-BHP-induced oxidative injury in HepG2 cells.


Asunto(s)
Salvia , Triterpenos , Triterpenos/farmacología , Triterpenos/química , Salvia/química , Estructura Molecular , Citocinas , Componentes Aéreos de las Plantas/química
17.
J Med Chem ; 67(1): 513-528, 2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-38150591

RESUMEN

Intragastric administration of the total sesterterpenoid extract (TSE) of medicinal plant Leucosceptrum canum at 2.5 g/kg dose protected mice from LPS-induced sepsis. Phytochemical investigation led to the isolation and identification of 47 leucosceptrane sesterterpenoids (1-47) including 30 new compounds (1-30) with complicated oxygenation patterns. Biological screening indicated their immunosuppressive activity via inhibiting IFN-γ secretion and/or proliferation of T cells with different potencies. Mechanism study of compounds 9, 25, and 32 revealed that they inhibited the activations of AKT-mTOR, JNK, p38 MAPK or ERK pathway in T cells and macrophages. In addition, compounds 9 and 25 induced G0/G1 cell arrest of T cells. The major component, leucosceptroid N (32), significantly lowered the levels of IL-6 and TNF-α in peripheral blood serum, and ameliorated the multiorgan damages of LPS-induced sepsis mice at 25 mg/kg dose. These findings suggest that leucosceptrane sesterterpenoids are a new type of potential immunosuppressive agents for sepsis treatment.


Asunto(s)
Inmunosupresores , Sepsis , Animales , Ratones , Inmunosupresores/farmacología , Inmunosupresores/uso terapéutico , Inmunosupresores/metabolismo , Lipopolisacáridos/metabolismo , Macrófagos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Sepsis/inducido químicamente , Sepsis/tratamiento farmacológico
18.
J Nat Prod ; 86(11): 2468-2473, 2023 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-37939268

RESUMEN

Three unusual sesterterpenoids featuring unprecedented rearranged colquhounane (C25) and tetranorcolquhounane (C21) frameworks, colquhounoids E (1) and F (3) and norcolquhounoid F (2), were isolated from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. Their structures were elucidated by spectroscopic analysis and quantum chemical calculations. A biomimetic inspired regioselective cyclopropane cleavage was achieved under acidic conditions. The immunosuppressive activities of these new sesterterpenoids were also evaluated.


Asunto(s)
Lamiaceae , Plantas Medicinales , Análisis Espectral , Lamiaceae/química , Estructura Molecular
19.
Quant Imaging Med Surg ; 13(10): 7294-7303, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37869348

RESUMEN

Background: The combination of computed tomography angiography (CTA) and computed tomography perfusion (CTP) evaluation of cerebral perfusion status and vascular conditions can improve the diagnostic accuracy of infarction, ischemia, and vascular occlusion in stroke patients, as well as a comprehensive assessment of cerebral edema, collateral circulation, and blood perfusion in the lesion area. However, the consequent radiation safety and contrast agent nephropathy have aroused increasing concern. The purpose of this study was to assess the image quality and diagnostic accuracy of CTA images derived from CTP data, and to explore the feasibility of replacing conventional CTA. Methods: A total of 31 consecutive patients with suspected acute ischemic stroke were retrospectively analyzed. All patients underwent head and neck CTA and brain CTP examinations. All the CTP images were transmitted to the ShuKun artificial intelligence system, which reconstructs CTA derived from CTP (CTA-DF-CTP). The images were divided into 2 groups, including CTA-DF-CTP (Group A) and conventional CTA (Group B). The CT attenuation values, subjective image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), image quality, CT volume dose index (CTDIvol), dose length product (DLP), and effective radiation dose (ED) were compared between the 2 groups. Moreover, the consistency of vascular stenosis and stenosis degree between the 2 groups were measured and evaluated. Results: There were no significant differences in image noise, SNR, or CNR between Groups A and B (P>0.05). The CT attenuation values of the arteries were higher in Group A than in B [internal carotid artery (ICA) =548±112 vs. 454±85 Hounsfield units (HU), middle cerebral artery (MCA) =453±118 vs. 388±70 HU, and basilar artery (BA) =431±99 vs. 360±83 HU] (P<0.01). The image quality of the 2 groups met the requirement of clinical diagnosis (4.97±0.18 vs. 4.94±0.25). No significant difference was found in subjective evaluation (P>0.05). In Group A compared with Group B, the following reductions were observed: CTDIvol (10.7%; 100.8 vs. 112.9 mGy), DLP (23.0%; 1,613±0 vs. 2,093±88 mGy·cm), and ED (23.0%; 5.00±0.00 vs. 6.49±0.27 mSv). Conclusions: CTA-DF-CTP data provide diagnostic accuracy and image quality similar to those of conventional CTA of head and neck CTA.

20.
Phytochemistry ; 215: 113852, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37690698

RESUMEN

Neocinnamomum delavayi (Lauraceae) leaves with abundant oil cells are seldom attacked by insects, but their chemical constituent and biological function remain obscure. Three furofuran lignans, including (+)-eudesmin (3), (+)-magnolin (4), and demethoxyaschantin (5), were identified to be the major specialized metabolites in the oil cells of N. delavayi leaves through laser microdissection coupled with NMR analysis. Compounds 3 and 4 exhibited obvious antifeedant activity against a generalist insect Spodoptera exigua, and their natural contents in the leaves could effectively defend against generalist insects. Intriguingly, three specific metabolites 9-11, the O-demethylation derivates of compounds 3-5, were identified from a native specialist insect Dindica polyphaenaria feeding with N. delavayi leaves, implying an adaptation mechanism of specialist insects to plant defensive compounds. The results revealed a chemical connection between plants and insects, which would contribute to our understanding of plant-insect interaction and insect management.


Asunto(s)
Lauraceae , Lignanos , Animales , Insectos , Lignanos/farmacología , Lignanos/química , Spodoptera
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