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1.
J Biochem Mol Toxicol ; 38(4): e23691, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38500399

RESUMO

Sustained liver injuries predominantly promote oxidative stress and inflammation that lead to the progression of chronic liver disease (CLD), including fibrosis, cirrhosis, and hepatocellular carcinoma. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects. Currently, there is no definitive treatment option available for CLD. Therefore, we investigated the hepatoprotective effect of boldine against carbon tetrachloride (CCl4 )-induced chronic liver injury in rats. CCl4 (2 mL/kg., b.w., i.p.) was administered twice weekly for 5 weeks to induce chronic liver injury in rats. Separate groups of rats were given boldine (20 mg/kg b.w., and 40 mg/kg b.w.) and silymarin (100 mg/kg b.w.) orally, daily. Serum transaminases, lipid peroxidation, and antioxidant levels were measured, and nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (cox-2), interleukin-1 ß (IL-1ß), and α-smooth muscle actin (α-SMA) gene and protein expressions were evaluated. CCl4 administration increased liver marker enzymes of hepatotoxicity in serum and oxidative stress markers, inflammatory genes and α-smooth muscle actin expression in liver tissue. Boldine concurrent treatment suppressed CCl4 -induced elevation of transaminase levels in serum, restored enzymic and non-enzymic antioxidants, and downregulated NF-κB, TNF-α, Cox-2 and IL-1ß expressions, thereby suppressing hepatic inflammation. Boldine administration also repressed α-SMA expression. The results of this study demonstrate the antioxidant, anti-inflammatory, and antifibrotic properties of boldine, and it can be a potential therapeutic candidate in the treatment of CLD.


Assuntos
Aporfinas , Doença Hepática Induzida por Substâncias e Drogas , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Tetracloreto de Carbono/toxicidade , Actinas/metabolismo , Actinas/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Ciclo-Oxigenase 2/metabolismo , Fígado/metabolismo , Transdução de Sinais , Estresse Oxidativo , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo
2.
Sci Rep ; 14(1): 7086, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38528077

RESUMO

The destruction of the microvascular structure and function can seriously affect the survival and prognosis of patients with acute myocardial infarction (AMI). Nuciferine has a potentially beneficial effect in the treatment of cardiovascular disease, albeit its role in microvascular structure and function during AMI remains unclear. This study aimed to investigate the protective effect and the related mechanisms of nuciferine in microvascular injury during AMI. Cardiac functions and pathological examination were conducted in vivo to investigate the effect of nuciferine on AMI. The effect of nuciferine on permeability and adherens junctions in endothelial cells was evaluated in vitro, and the phosphorylation level of the PI3K/AKT pathway (in the presence or absence of PI3K inhibitors) was also analyzed. In vivo results indicated that nuciferine inhibited ischemia-induced cardiomyocyte damage and vascular leakage and improved cardiac function. In addition, the in vitro results revealed that nuciferine could effectively inhibit oxygen-glucose deprivation (OGD) stimulated breakdown of the structure and function of human coronary microvascular endothelial cells (HCMECs). Moreover, nuciferine could significantly increase the phosphorylation level of the PI3K/AKT pathway. Finally, the inhibitor wortmannin could reverse the protective effect of nuciferine on HCMECs. Nuciferine inhibited AMI-induced microvascular injury by regulating the PI3K/AKT pathway and protecting the endothelial barrier function in mice.


Assuntos
Aporfinas , Células Endoteliais , Infarto do Miocárdio , Humanos , Camundongos , Animais , Células Endoteliais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Infarto do Miocárdio/patologia , Apoptose
3.
Phytochemistry ; 220: 114020, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38364883

RESUMO

Three previously undescribed aporphine alkaloids, phaeanthuslucidines E-G, one previously undescribed naphthoquinone derivative, phaeanthusnaphthoquinone, and three known compounds were isolated from an EtOAc extract of the leaves of Phaeanthus lucidus Oliv. The structures of all previously undescribed compounds were established through extensive spectroscopic investigations and high-resolution mass spectroscopy. The 6aR configuration of phaeanthuslucidines E-G was assigned by comparing their ECD spectra and specific rotation values with the reported known compounds. Some isolated compounds were evaluated for their α-glucosidase inhibitory activity. Among these compounds, phaeanthuslucidine E showed the highest α-glucosidase inhibitory activity with an IC50 value of 17.9 ± 0.4 µM. The molecular docking of phaeanthuslucidine E was further studied.


Assuntos
Alcaloides , Aporfinas , alfa-Glucosidases , Simulação de Acoplamento Molecular , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/química , Aporfinas/farmacologia , Aporfinas/química , Inibidores de Glicosídeo Hidrolases/farmacologia
4.
Fitoterapia ; 174: 105868, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38378133

RESUMO

In this study, the extract from Artabotrys hexapetalus showed strong antifungal activity against phytopathogenic fungi in vitro. Four unreported aporphine alkaloids, hexapetalusine A-D (1-4), were isolated from stems and roots of Artabotrys hexapetalus (L.f.) Bhandari, along with six known aporphine alkaloids (5-10). Their chemical structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1-3 were determined using single-crystal X-ray diffractions and ECD calculations. Hexapetalusine A-C (1-3) were special amidic isomers. Additionally, all isolated compounds were evaluated for their antifungal activity against four phytopathogenic fungi in vitro. Hexapetalusine D (4) exhibited weak antifungal activity against Curvularia lunata. Liriodenine (5) displayed significant antifungal activity against Fusarium proliferatum and Fusarium oxysporum f. sp. vasinfectum, which is obviously better than positive control nystatin, suggesting that it had great potential to be developed into an effective and eco-friendly fungicide.


Assuntos
Annonaceae , Aporfinas , Antifúngicos/farmacologia , Antifúngicos/química , Estrutura Molecular , Fungos , Aporfinas/farmacologia , Annonaceae/química
5.
Phytomedicine ; 125: 155312, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38232541

RESUMO

BACKGROUND: Cerebral ischemia has the characteristics of high incidence, mortality, and disability, which seriously damages people's health. Cerebral ischemia-reperfusion injury is the key pathological injury of this disease. However, there is a lack of drugs that can reduce cerebral ischemia-reperfusion injury in clinical practice. At present, a few studies have provided some evidence that nuciferine can reduce cerebral ischemia-reperfusion injury, but its specific mechanism of action is still unclear, and further research is still needed. OBJECTIVE: In this study, PC12 cells and SD rats were used to construct OGD/R and MCAO/R models, respectively. Combined with bioinformatics methods and experimental verification methods, the purpose of this study was to conduct a systematic and comprehensive study on the effect and mechanism of nuciferine on reducing inflammation induced by cerebral ischemia-reperfusion injury. RESULTS: Nuciferine can improve the cell viability of PC12 cells induced by OGD/R, reduce apoptosis, and reduce the expression of inflammation-related proteins; it can also improve the cognitive and motor dysfunction of MCAO/R-induced rats by behavioral tests, reduce the area of cerebral infarction, reduce the release of inflammatory factors TNF-α and IL-6 in serum and the expression of inflammation-related proteins in brain tissue. CONCLUSION: Nuciferine can reduce the inflammatory level of cerebral ischemia-reperfusion injury in vivo and in vitro models by acting on the PI3K/Akt/NF-κB signaling pathway, and has the potential to be developed as a drug for the treatment of cerebral ischemia-reperfusion injury.


Assuntos
Aporfinas , Isquemia Encefálica , Traumatismo por Reperfusão , Humanos , Ratos , Animais , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Sprague-Dawley , Infarto da Artéria Cerebral Média/patologia , Isquemia Encefálica/patologia , Inflamação/metabolismo , Traumatismo por Reperfusão/metabolismo
6.
Int J Mol Sci ; 25(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255776

RESUMO

Bisbenzylisoquinoline and aporphine alkaloids are the two main pharmacological compounds in the ancient sacred lotus (Nelumbo nucifera). The biosynthesis of bisbenzylisoquinoline and aporphine alkaloids has attracted extensive attention because bisbenzylisoquinoline alkaloids have been reported as potential therapeutic agents for COVID-19. Our study showed that NnCYP80A can catalyze C-O coupling in both (R)-N-methylcoclaurine and (S)-N-methylcoclaurine to produce bisbenzylisoquinoline alkaloids with three different linkages. In addition, NnCYP80G catalyzed C-C coupling in aporphine alkaloids with extensive substrate selectivity, specifically using (R)-N-methylcoclaurine, (S)-N-methylcoclaurine, coclaurine and reticuline as substrates, but the synthesis of C-ring alkaloids without hydroxyl groups in the lotus remains to be elucidated. The key residues of NnCYP80G were also studied using the 3D structure of the protein predicted using Alphafold 2, and six key amino acids (G39, G69, A211, P288, R425 and C427) were identified. The R425A mutation significantly decreased the catalysis of (R)-N-methylcoclaurine and coclaurine inactivation, which might play important role in the biosynthesis of alkaloids with new configurations.


Assuntos
Alcaloides , Aporfinas , Benzilisoquinolinas , Nelumbo , Nelumbo/genética , Aminoácidos
7.
J Ethnopharmacol ; 323: 117693, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38176669

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves. AIM OF THE STUDY: Using plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications. MATERIALS AND METHODS: UHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites. RESULTS: A total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers. CONCLUSION: Given the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Animais , Aconitum/toxicidade , Alcaloides/metabolismo , Aporfinas/metabolismo , Cardiotoxicidade , Doença Hepática Induzida por Substâncias e Drogas , Diterpenos/metabolismo , Medicamentos de Ervas Chinesas/toxicidade , Medicamentos de Ervas Chinesas/metabolismo , Folhas de Planta , Raízes de Plantas , Espectrometria de Massas em Tandem , Peixe-Zebra
8.
Food Funct ; 15(2): 967-976, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38175708

RESUMO

Increasing evidence suggests that brown adipose tissue (BAT) plays an important role in obesity and related diseases. Increasing the amount or activity of BAT could prevent obesity. Therefore, a safe and effective method of activating BAT is urgently required. Here, we evaluated the potential effects of lotus leaf extract (LLE) on BAT function. We found that LLE substantially increased UCP1 mRNA and protein levels as well as thermogenic protein expression in primary brown adipocytes. Additionally, LLE treatment reduced diet-induced obesity and improved glucose homeostasis owing to BAT activation and increased energy expenditure. We found that nuciferine, an active ingredient of LLE, could dose-dependently activate BAT in vitro and in vivo, alleviate diet-induced obesity, and improve glucose homeostasis by increasing energy expenditure. Mechanistically, we found that nuciferine induced PPARG coactivator 1 alpha (PGC1-α) expression, which is a key gene involved in mitochondrial biogenesis promoter activity, by directly binding to RXRA. Furthermore, RXRA knockdown abolished expression of the nuciferine-induced mitochondrial and thermogenesis-related gene in primary brown adipocytes. In summary, we found that LLE and nuciferine have a notable effect on BAT activation and highlight the potential applications of the main component of LLE in preventing obesity and treating metabolic disorders.


Assuntos
Tecido Adiposo Marrom , Aporfinas , Humanos , Tecido Adiposo Marrom/metabolismo , Obesidade/genética , Obesidade/prevenção & controle , Obesidade/metabolismo , Aporfinas/farmacologia , Metabolismo Energético , Glucose/metabolismo
9.
Mol Cell Biochem ; 479(2): 243-254, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37036633

RESUMO

Human urine-derived stem cells (hUSCs) process self-renewal and multilineage differentiation ability. Due to their non-invasive and easily available clinical source, hUSCs represent a promising alternative source of mesenchymal stem cells (MSCs) for application potential in cytotherapy. However, technical limitations, such as stemness property maintenance, have hindered hUSCs' clinical application. Certain some small molecules have been recognized with advantage in maintaining the stemness of stem cells. In this study, we identified stemness-regulated key targets of hUSCs based on the StemCellNet database, CMAP database and literature mining. Furthermore, we identified a small molecule compound, boldine, which may have the potential to promote the stemness of hUSCs. It promotes cell proliferation, multilineage differentiation and maintains stemness of hUSCs by cell viability assay, single-cell clone formation, osteogenic differentiation and stemness marker expression (OCT-4 and C-MYC). We identified that boldine may be a potential GSK-3ß inhibitor by molecular docking and confirmed that it can upregulate the level of ß-catenin and promote translocation of ß-catenin into nucleus of hUSCs using Western blotting and immunofluorescence analysis. Our study indicates boldine activates the Wnt/ß-catenin signaling pathway in hUSCs and provides an effective strategy for MSCs research and application of small molecules in maintaining the stemness of hUSCs.


Assuntos
Aporfinas , Via de Sinalização Wnt , beta Catenina , Humanos , Glicogênio Sintase Quinase 3 beta , Simulação de Acoplamento Molecular , Osteogênese , Células-Tronco , Diferenciação Celular , Proliferação de Células
10.
Infect Disord Drug Targets ; 24(1): e201023222495, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37881077

RESUMO

Plant material and their derived byproducts have been used in medicine for the treatment of human disorders and complications. Plants give us a distinct class of natural compounds, commonly called secondary metabolites and better examples are the flavonoids, phenols, terpenoids, alkaloids, tannins, and carotenoids. Plant derived phytoproducts have been used for the treatment of human disorders in both traditional as well as modern medicine. Naturally occurring aporphines and their synthetic derivatives are well known in medicine for their pharmacological activities, including an affinity for dopaminergic, adrenergic and serotonergic receptors. (+)-nantenine is an aporphine alkaloid isolated from Nandina domestica and other plants. The aim of the present study is to analyze the biological potential and therapeutic effectiveness of nantenine in medicine. In the present work scientific information of nantenine for their medicinal uses and pharmacological activities have been collected from scientific databases such as Google, Google Scholar, PubMed, Scopus, and Science Direct . Scientific information of nantenine was further analyzed to know their health beneficial aspects in medicine. However, the detail pharmacological activity of nantenine has been discussed in the present work with its analytical aspects. Scientific data analysis described the medicinal importance and pharmacological activities of nantenine. Nantenine revealed adrenergic response, behavioral response, cardiovascular effect, vasorelaxant effect, acetylcholinesterase inhibitory potential, cytotoxicity, and biphasic tracheal relaxation. Present work also signified the biological potential of nantenine for their anti-inflammatory activity, anticonvulsant effect, antiserotonergic activities, anti-MDMA effect, antileishmanial activity, effect on histamine and serotonin, human 5-hydroxytryptamine (5-HT(2A)) and h5-HT(2B) receptors and isolated tissues. Further, the analytical techniques used for the separation, isolation and identification of nantenine have also been described in this work. The present scientific data describes the therapeutic potential and pharmacological activities of (+)-nantenine in medicine.


Assuntos
Acetilcolinesterase , Aporfinas , Humanos , Aporfinas/farmacologia , Serotonina , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Adrenérgicos
11.
Fitoterapia ; 172: 105737, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37939737

RESUMO

Three undescribed alkaloids (+)-9-hydroxy-N-acetylnordicentrine (1), illigeparvinine (2), and deca-(2E,4Z)-2,4-dienoic acid 4-hydroxy-2-phenethyl amide (3), along with 19 known analogues (4-22), were isolated from the ethnic medicinal plant Illigera parviflora. Their structures were established using NMR, MS, and other spectroscopic analyses as well as X-ray diffraction. Moderate inhibition of human gastric carcinoma (MGC-803) and breast adenocarcinoma (T-47D) cell lines proliferation was observed for actinodaphnine (4) with IC50 values of 28.74 and 11.65 µM, respectively. These findings contribute new anticancer potential compounds and expand the chemical diversity known from the valuable traditional medicinal plant I. parviflora.


Assuntos
Alcaloides , Aporfinas , Hernandiaceae , Plantas Medicinais , Humanos , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/metabolismo , Aporfinas/farmacologia , Plantas Medicinais/química , Espectroscopia de Ressonância Magnética , Hernandiaceae/química , Hernandiaceae/metabolismo
12.
J Dairy Sci ; 107(1): 625-640, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37709032

RESUMO

Excessive free fatty acid (FFA) oxidation and related metabolism are the major cause of oxidative stress and liver injury in dairy cows during the early postpartum period. In nonruminants, activation of transcription factor EB (TFEB) can improve cell damage and reduce the overproduction of mitochondrial reactive oxygen species. As a downstream target of TFEB, peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α, gene name PPARGC1A) is a critical regulator of oxidative metabolism. Nuciferine (Nuc), a major bioactive compound isolated from the lotus leaf, has been reported to possess hepatoprotective activity. Therefore, the objective of this study was to investigate whether Nuc could protect bovine hepatocytes from FFA-induced lipotoxicity and the underlying mechanisms. A mixture of FFA was diluted in RPMI-1640 basic medium containing 2% low fatty acid bovine serum albumin to treat hepatocytes. Bovine hepatocytes were isolated from newborn calves and treated with various concentrations of FFA mixture (0, 0.3, 0.6, or 1.2 mM) or Nuc (0, 25, 50, or 100 µM), as well as co-treated with 1.2 mM FFA and different concentrations of Nuc. For the experiments of gene silencing, bovine hepatocytes were transfected with small interfering RNA targeted against TFEB or PPARGC1A for 36 h followed by treatment with 1.2 mM FFA for 12 h in presence or absence of 100 µΜ Nuc. The results revealed that FFA treatment decreased protein abundance of nuclear TFEB, cytosolic TFEB, total (t)-TFEB, lysosome-associated membrane protein 1 (LAMP1) and PGC-1α and mRNA abundance of LAMP1, but increased phosphorylated (p)-TFEB. In addition, FFA treatment increased the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and decreased the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in bovine hepatocytes. Moreover, FFA administration enhanced the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactose dehydrogenase (LDH) in the medium of FFA-treated hepatocytes, but reduced the content of urea. In FFA-treated bovine hepatocytes, Nuc administration increased TFEB nuclear localization and the protein abundance of t-TFEB, LAMP1, and PGC-1α and mRNA abundance of LAMP1, decreased the contents of MDA and H2O2 and the protein abundance of p-TFEB, and enhanced the activities of CAT and GSH-Px in a dose-dependent manner. Consistently, Nuc administration reduced the activities of ALT, AST, and LDH and increased the content of urea in the medium of FFA-treated hepatocytes. Importantly, knockdown of TFEB reduced the protein abundance of p-TFEB, t-TFEB, LAMP1, and PGC-1α and mRNA abundance of LAMP1, and impeded the beneficial effects of Nuc on FFA-induced oxidative damage in bovine hepatocytes. In addition, PPARGC1A silencing did not alter Nuc-induced nuclear translocation of TFEB, increase of the protein abundance of t-TFEB, LAMP1, and PGC-1α and mRNA abundance of LAMP1, or decrease of the protein abundance of p-TFEB, whereas it partially reduced the beneficial effects of Nuc on FFA-caused oxidative injury. Taken together, Nuc exerts protective effects against FFA-induced oxidative damage in bovine hepatocytes through activation of the TFEB/PGC-1α signaling pathway.


Assuntos
Aporfinas , Ácidos Graxos não Esterificados , PPAR gama , Feminino , Bovinos , Animais , Ácidos Graxos não Esterificados/farmacologia , PPAR gama/metabolismo , Peróxido de Hidrogênio , Hepatócitos/metabolismo , Estresse Oxidativo , Fatores de Transcrição/genética , Glutationa Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Ureia
13.
Chem Biol Drug Des ; 103(1): e14356, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37731180

RESUMO

Both luteolin and magnoflorine have been reported to regulate the development of breast cancer, which makes them easier to co-administrate. Luteolin was co-administrated with magnoflorine to evaluate their potential interaction. The pharmacokinetic study was performed on male Sprague-Dawley rats randomly grouped as the single administration of luteolin and the co-administration of luteolin and magnoflorine with six rats of each. CaCO-2 cell transwell assay was employed for transport evaluation, and the metabolic stability of luteolin and CYP3A activity were assessed in rat liver microsomes. The effect of luteolin on MDA-MB-231 cells was assessed with CCK8 assay. Magnoflorine significantly changed the pharmacokinetic profile of luteolin with increased area under the curve (AUC), prolonged t1/2 , and reduced clearance rate. Magnoflorine also suppressed the efflux ratio and improved the in vitro metabolic stability of luteolin. Magnoflorine also enhanced the inhibitory effect of luteolin on MDA-MB-231 cells. Magnoflorine significantly inhibited CYP3A activity with the IC50 of 18.99 µM. Magnoflorine prolonged the system exposure, enhanced the metabolic stability, and enhanced the anti-tumor effect of luteolin through inactivating CYP3A.


Assuntos
Aporfinas , Citocromo P-450 CYP3A , Luteolina , Humanos , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Luteolina/farmacologia , Luteolina/metabolismo , Citocromo P-450 CYP3A/metabolismo , Células CACO-2 , Microssomos Hepáticos/metabolismo , Interações Medicamentosas
14.
Drug Res (Stuttg) ; 73(9): 513-519, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37935203

RESUMO

BACKGROUND: Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied. METHODS: Wistar rats were used and the urine volume was noted for 8 h and further studied. RESULTS: The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ​​remained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization. CONCLUSIONS: This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.


Assuntos
Aporfinas , Diuréticos , Ratos , Animais , Diuréticos/farmacologia , Cálcio , Ratos Wistar , Aporfinas/farmacologia , Sódio , Receptores Muscarínicos
15.
Int J Mol Sci ; 24(19)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37833979

RESUMO

Oral squamous cell carcinoma (OSCC) poses a significant obstacle to the worldwide healthcare system. Discovering efficient and non-toxic medications is crucial for managing OSCC. Nuciferine, an alkaloid with an aromatic ring, is present in the leaves of Nelumbo nucifera. It has been proven to play a role in multiple biological processes, including the inhibition of inflammation, regulation of the immune system, formation of osteoclasts, and suppression of tumors. Despite the demonstrated inhibitory effects of nuciferine on different types of cancer, there is still a need for further investigation into the therapeutic effects and potential mechanisms of nuciferine in OSCC. Through a series of in vitro experiments, it was confirmed that nuciferine hindered the growth, movement, and infiltration, while enhancing the programmed cell death of OSCC cells. Furthermore, the administration of nuciferine significantly suppressed the signal transducer and activator of transcription 3 (STAT3) signaling pathway in comparison to other signaling pathways. Moreover, the activation of the STAT3 signaling pathway by colivelin resulted in the reversal of nuciferine-suppressed OSCC behaviors. In vivo, we also showed the anti-OSCC impact of nuciferine using the cell-based xenograft (CDX) model in nude mice. Nonetheless, colivelin diminished the tumor-inhibiting impact of nuciferine, suggesting that nuciferine might partially impede the advancement of OSCC by suppressing the STAT3 signaling pathway. Overall, this research could offer a fresh alternative for the pharmaceutical management of OSCC.


Assuntos
Aporfinas , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Camundongos Nus , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Aporfinas/uso terapêutico
16.
Alkaloids Chem Biol ; 90: 1-96, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37716795

RESUMO

Morphinan alkaloids have attracted constant attention since the isolation of morphine by Sertürner in 1805. However, a group of 45 compounds possessing a complete ent-morphinan backbone can also be found in the literature. These compounds are related to the morphinandienone subgroup and display a substitution pattern which is different from the morphinans. In particular, these alkaloids could be substituted at position C-2 and C-8 either by a hydroxy function or a methoxy moiety. Four groups of ent-morphinan alkaloids can be proposed, the salutaridine, pallidine, cephasugine and erromangine series. Interestingly, the botanical distribution of the ent-morphinans is more widespread than for the morphinans and includes the Annonaceae, Berberidaceae, Euphorbiaceae, Fumariaceae, Hernandiaceae, Lauraceae, Menispermaceae, Monimiaceae, Papaveraceae, and Ranunculaceae families. To date, their exact mode of production remains elusive and their interplay with the biosynthetic pathway of other classes of benzyltetrahydroisoquinoline alkaloids, in particular aporphines, should be confirmed. Exploration of the biological and therapeutic potential of these compounds is limited to some areas, namely central nervous system (CNS), inflammation, cancer, malaria and viruses. Further studies should be conducted to identify the cellular/molecular targets in view of promoting these compounds as new scaffolds in medicinal chemistry.


Assuntos
Annonaceae , Aporfinas , Morfinanos , Humanos , Morfina , Biologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-37623175

RESUMO

Traumatic spinal cord injury (SCI) results in wide-ranging cellular and systemic dysfunction in the acute and chronic time frames after the injury. Chronic SCI has well-described secondary medical consequences while acute SCI has unique metabolic challenges as a result of physical trauma, in-patient recovery and other post-operative outcomes. Here, we used high resolution mass spectrometry approaches to describe the circulating lipidomic and metabolomic signatures using blood serum from mice 7 d after a complete SCI. Additionally, we probed whether the aporphine alkaloid, boldine, was able to prevent SCI-induced changes observed using these 'omics platforms'. We found that SCI resulted in large-scale changes to the circulating lipidome but minimal changes in the metabolome, with boldine able to reverse or attenuate SCI-induced changes in the abundance of 50 lipids. Multiomic integration using xMWAS demonstrated unique network structures and community memberships across the groups.


Assuntos
Aporfinas , Traumatismos da Medula Espinal , Masculino , Animais , Camundongos , Lipidômica , Soro , Aporfinas/farmacologia , Aporfinas/uso terapêutico
18.
J Cosmet Dermatol ; 22(10): 2765-2768, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37584260

RESUMO

BACKGROUND: Neck skin is thinner and has a more delicate dermal layer than facial skin. The studied product was specifically formulated for the neck combining a hydrating delivery system with a trifunctional corrective technology composed of 0.2% pure retinol, 2.5% tripeptide concentrate, and 5.0% glaucine complex to help improvement in signs of aging. OBJECTIVES: To evaluate cosmetic and histologic changes 3 months after treatment using immunostains for Type I collagen, Type III collagen, and glycosaminoglycan (GAGS). In addition, overall clinical improvement in photoaged skin was measured by both Griffith's photonumeric photoaging scale, photographic improvement, and questionnaires. METHODS: This study was an open-label, blinded clinical trial evaluating a combined retinol, tripeptide, and glaucine containing cream in the treatment of photo-aged skin. The study enrolled a total of 20 healthy male or female subjects, who applied the product for 3 months to their face and neck. RESULTS: Clinical as well histologic changes were consistent with improvement in all 20 subjects. CONCLUSION: Use of a combined retinol, tripeptide, and glaucine containing cream led to both clinical and histologic improvement of phototoaging.


Assuntos
Aporfinas , Envelhecimento da Pele , Feminino , Humanos , Masculino , Pele/diagnóstico por imagem , Creme para a Pele , Resultado do Tratamento , Vitamina A/uso terapêutico
19.
Neurochem Res ; 48(11): 3283-3295, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37462836

RESUMO

Boldine is an alkaloid obtained from the medicinal herb Peumus boldus (Mol.) (Chilean boldo tree; boldo) and belongs to the family Monimiaceae. It exhibits a wide range of pharmacological effects such as antioxidant, anticancer, hepatoprotective, neuroprotective, and anti-diabetic properties. There is a dearth of information regarding its pharmacokinetics and toxicity in addition to its potential pharmacological activity. Boldine belongs to the aporphine alkaloid class and possesses lipophilic properties which enable its efficient absorption and distribution throughout the body, including the central nervous system. It exhibits potent free radical scavenging activity, thereby reducing oxidative stress and preventing neuronal damage. Through a variety of neuroprotective mechanisms, including suppression of AChE and BuChE activity, blocking of connexin-43 hemichannels, pannexin 1 channel, reduction of NF-κß mediated interleukin release, and glutamate excitotoxicity which successfully reduces neuronal damage. These results point to its probable application in reducing neuroinflammation and oxidative stress in epilepsy, Alzheimer's disease (AD), and Parkinson's disease (PD). Moreover, its effects on serotonergic, dopaminergic, opioid, and cholinergic receptors were further investigated in order to determine its applicability for neurobehavioral dysfunctions. The article investigates the pharmacokinetics of boldine and reveals that it has a low oral bioavailability and a short half-life, requiring regular dosage to maintain therapeutic levels. The review studies boldine's potential therapeutic uses and mode of action while summarizing its neuroprotective benefits.  Given the favorable results for boldine as a potential neurotherapeutic drug in laboratory animals, more research is required. However, in order to optimise its therapeutic potential, it must be more bioavailable with fewer detrimental side effects.


Assuntos
Aporfinas , Doenças do Sistema Nervoso , Peumus , Animais , Cinética , Antioxidantes/farmacologia , Aporfinas/farmacologia , Aporfinas/uso terapêutico , Aporfinas/química , Peumus/química
20.
Pharmacol Res ; 193: 106820, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37315822

RESUMO

Nuciferine aporphine alkaloid mainly exists in Nelumbo nucifera Gaertn and is a beneficial to human health, such as anti-obesity, lowering blood lipid, prevention of diabetes and cancer, closely associated with inflammation. Importantly, nuciferine may contribute to its bioactivities by exerting intense anti-inflammatory activities in multiple models. However, no review has summarized the anti-inflammatory effect of nuciferine. This review critically summarized the information regarding the structure-activity relationships of dietary nuciferine. Moreover, biological activities and clinical application on inflammation-related diseases, such as obesity, diabetes, liver, cardiovascular diseases, and cancer, as well as their potential mechanisms, involving oxidative stress, metabolic signaling, and gut microbiota has been reviewed. The current work provides a better understanding of the anti-inflammation properties of nuciferine against multiple diseases, thereby improving the utilization and application of nuciferine-containing plants across functional food and medicine.


Assuntos
Aporfinas , Fígado , Humanos , Fígado/metabolismo , Aporfinas/farmacologia , Aporfinas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Relação Estrutura-Atividade
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