Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29.406
Filtrar
1.
Pharm Biol ; 61(1): 135-143, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36617895

RESUMO

CONTEXT: Alkaloid-enriched extract of Huperzia serrata (Thunb.) Trevis (Lycopodiaceae) (HsAE) can potentially be used to manage neuronal disorders. OBJECTIVE: This study determines the anti-neuroinflammatory effects of HsAE on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and the underlying mechanisms. MATERIALS AND METHODS: BV-2 cells were pre- or post-treated with different concentrations of HsAE (25-150 µg/mL) for 30 min before or after LPS induction. Cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and no cytotoxicity was found. Nitric oxide (NO) concentration was determined using Griess reagent. The levels of prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were determined using enzyme-linked immunosorbent assay. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and the phosphorylation of mitogen-activated protein kinase (MAPK) were analyzed using western blotting. RESULTS: HsAE reduced LPS-induced NO production with half-maximal inhibitory concentration values of 99.79 and 92.40 µg/mL at pre- and post-treatment, respectively. Pre-treatment with HsAE at concentrations of 50, 100, and 150 µg/mL completely inhibited the secretion of PGE2, TNF-α, IL-6, and IL-1ß compared to post-treatment with HsAE. This suggests that prophylactic treatment is better than post-inflammation treatment. HsAE decreased the expression levels of iNOS and COX-2 and attenuated the secretion of pro-inflammatory factors by downregulating the phosphorylation of p38 and extracellular signal-regulated protein kinase in the MAPK signaling pathway. DISCUSSION AND CONCLUSIONS: HsAE exerts anti-neuroinflammatory effects on LPS-stimulated BV-2 cells, suggesting that it may be a potential candidate for the treatment of neuroinflammation in neurodegenerative diseases.


Assuntos
Alcaloides , Huperzia , Lipopolissacarídeos/farmacologia , Huperzia/metabolismo , Interleucina-6/metabolismo , Doenças Neuroinflamatórias , Dinoprostona/metabolismo , Microglia , Fator de Necrose Tumoral alfa/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Alcaloides/farmacologia , Alcaloides/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo
2.
BMC Vet Res ; 19(1): 4, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624444

RESUMO

Post-weaning diarrhea in piglets is a major problem, resulting in a significant loss in pig production. This study aimed to investigate the effects of piperine, an alkaloid abundantly found in black peppers, on biological activities related to the pathogenesis of post-weaning diarrhea using a porcine duodenal enteroid model, a newly established intestinal stem cell-derived in vitro model recapitulating physiology of porcine small intestinal epithelia. Porcine duodenal enteroid models were treated with disease-relevant pathological inducers with or without piperine (8 µg/mL and/or 20 µg/mL) before measurements of oxidative stress, mRNA, and protein expression of proinflammatory cytokines, nuclear factor-kappa B (NF-κB) nuclear translocation, barrier leakage, and fluid secretion. We found that piperine (20 µg/mL) inhibited H2O2-induced oxidative stress, TNF-α-induced mRNA, and protein expression of proinflammatory cytokines without affecting NF-κB nuclear translocation, and prevented TNF-α-induced barrier leakage in porcine duodenal enteroid monolayers. Importantly, piperine inhibited fluid secretion induced by both forskolin and heat-stable toxins (STa) in a three-dimensional model of porcine duodenal enteroids. Collectively, piperine possesses both anti-inflammatory and anti-secretory effects in porcine enteroid models. Further research and development of piperine may provide novel interventions for the treatment of post-weaning porcine diarrhea.


Assuntos
Alcaloides , NF-kappa B , Suínos , Animais , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa , Desmame , Peróxido de Hidrogênio , Diarreia/tratamento farmacológico , Diarreia/veterinária , Alcaloides/farmacologia , Citocinas , RNA Mensageiro
3.
Forensic Toxicol ; 41(1): 25-46, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36652065

RESUMO

PURPOSE: The emergence of novel psychoactive substances (NPS) has been being a continuous and evolving problem for more than a decade. Every year, dozens of new, previously unknown drugs appear on the illegal market, posing a significant threat to the health and lives of their users. Synthetic cathinones are one of the most numerous and widespread groups among NPS. The purpose of this work was to identify and summarize available data on newly emerging cathinones in very recent years. METHODS: Various online databases such as PubMed, Google Scholar, but also databases of government agencies including those involved in early warning systems, were used in search of reports on the identification of newly emerging synthetic cathinones. In addition, threads on various forums created by users of these drugs were searched for reports on the effects of these new substances. RESULTS: We have identified 29 synthetic cathinones that have been detected for the first time from early 2019 to mid-2022. We described their structures, known intoxication symptoms, detected concentrations in biological material in poisoning cases, as well as the countries and dates of their first appearance. Due to the lack of studies on the properties of the novel compounds, we compared data on the pharmacological profiles of the better-known synthetic cathinones with available information on the newly emerged ones. Some of these new agents already posed a threat, as the first cases of poisonings, including fatal ones, have been reported. CONCLUSIONS: Most of the newly developed synthetic cathinones can be seen as analogs and replacements for once-popular compounds that have been declining in popularity as a result of legislative efforts. Although it appears that some of the newly emerging cathinones are not widely used, they may become more popular in the future and could become a significant threat to health and life. Therefore, it is important to continue developing early warning systems and identifying new compounds so that their widespread can be prevented.


Assuntos
Alcaloides , Drogas Ilícitas , Drogas Ilícitas/efeitos adversos , Psicotrópicos/efeitos adversos , Gerenciamento de Dados
4.
Genes (Basel) ; 14(1)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36672960

RESUMO

Fritillaria cirrhosa D. Don (known as Chuan-Bei-Mu in Chinese) can synthesize isosteroidal alkaloids (ISA) with excellent medicinal value, and its bulb has become an indispensable ingredient in many patented drugs. Members of the cytochrome P450 (CYP450) gene superfamily have been shown to play essential roles in regulating steroidal alkaloids biosynthesis. However, little information is available on the P450s in F. cirrhosa. Here, we performed full-length transcriptome analysis and discovered 48 CYP450 genes belonging to 10 clans, 25 families, and 46 subfamilies. By combining phylogenetic trees, gene expression, and key F. cirrhosa ISA content analysis, we presumably identify seven FcCYP candidate genes, which may be hydroxylases active at the C-22, C-23, or C-26 positions in the late stages of ISA biosynthesis. The transcript expression levels of seven FcCYP candidate genes were positively correlated with the accumulation of three major alkaloids in bulbs of different ages. These data suggest that the candidate genes are most likely to be associated with ISA biosynthesis. Finally, the subcellular localization prediction of FcCYPs and transient expression analysis within Nicotiana benthamiana showed that the FcCYPs were mainly localized in the chloroplast. This study presents a systematic analysis of the CYP450 gene family in F. cirrhosa and provides a foundation for further functional characterization of the CYPs involved in ISA biosynthesis.


Assuntos
Alcaloides , Fritillaria , Fritillaria/genética , Fritillaria/metabolismo , Filogenia , Perfilação da Expressão Gênica , Sistema Enzimático do Citocromo P-450/genética
5.
ACS Chem Biol ; 18(1): 123-133, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36608315

RESUMO

Lavanduquinocin (LDQ) is a potent neuroprotective carbazole alkaloid from Streptomyces species that features a rare cyclic monoterpene/cyclolavandulyl moiety attached to the tricyclic carbazole nucleus. We elucidated the biosynthetic logic of LDQ by enzymatically reconstituting the total biosynthetic pathway and identified the genes required for generating the cyclolavandulyl moiety in LDQ based on mutagenetic analysis, including a cyclolavandulyl diphosphate synthase gene ldqA and a squalene synthase-like aromatic prenyltransferase gene ldqG. LdqG is homologous to carbazole prenyltransferases, NzsG and CqsB4, discovered from the biosynthetic pathways of two bacterial carbazoles, neocarazostatin and carquinostatin. Based on analysis of the sequences and modeled protein structures, further in vitro and in vivo site-directed mutagenetic analyses led to identification of two residue sites, F53 and C57 in NzsG vs I54 and A58 in LdqG, which play crucial roles in governing the prenyl donor specificities toward cyclolavandulyl, dimethylallyl, and geranyl diphosphates. By applying this knowledge in strain engineering, prenyl donor delivery was rationally switched to produce the desired prenylated carbazoles. The study provides an opportunity to rationally manipulate the prenylation modification to carbazole alkaloids, which could influence the biological activities by increasing the affinity for membranes as well as the interactions with cellular targets.


Assuntos
Alcaloides , Dimetilaliltranstransferase , Dimetilaliltranstransferase/metabolismo , Farnesil-Difosfato Farnesiltransferase/genética , Farnesil-Difosfato Farnesiltransferase/metabolismo , Carbazóis/química , Prenilação
6.
Anal Chim Acta ; 1241: 340777, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36657870

RESUMO

Ligand-induced assembly of disordered DNAs attracts much attention due to its potential action in transcription regulation and molecular switches-based sensors. Among natural isoquinoline alkaloids (NIAs), we screened out nitidine (NIT) as polyvalent-binding assembler to program poly(dA) into a parallel duplex assembly at neutral pH. The molecule planarity of NIAs was believed to be a determinant factor in programming the parallel poly(dA) assembly. Poly(dA) with more than six adenines can initiate the synergistic binding of NIT to generate the parallel assembly. It is expected that one A-A pair in duplex can bind one NIT molecule provided that poly(dA) is long enough, suggesting the pivotal role of the polyvalent synergy of NIT in programming the parallel poly(dA) assembly. A gold nanoparticles-based colorimetric method was also developed to screen NIT out of NIAs having the potential to construct the poly(dA) assembly. Our work will inspire more interest in developing polyadenine-based switches and sensors by concentrating NIT within the polyadenine parallel assembly.


Assuntos
Alcaloides , Nanopartículas Metálicas , Ouro , Isoquinolinas
7.
Prog Chem Org Nat Prod ; 119: 1-335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587292

RESUMO

This book describes a unique class of secondary metabolites, the mono- and dimeric naphthylisoquinoline alkaloids. They occur in lianas of the paleotropical Ancistrocladaceae and Dioncophyllaceae families, exclusively. Their unprecedented structures include stereogenic centers and rotationally hindered, and thus likewise stereogenic, axes. Extended recent investigations on six Ancistrocladus species from Asia, as reported in this review, shed light on their fascinating phytochemical productivity, with over 100 such intriguing natural products. This high chemodiversity arises from a likewise unique biosynthesis from acetate-malonate units, following a novel polyketidic pathway to plant-derived isoquinoline alkaloids. Some of the compounds show most promising antiparasitic activities. Likewise presented are strategies for the regio- and stereoselective total synthesis of the alkaloids, including the directed construction of the chiral axis.


Assuntos
Alcaloides , Antimaláricos , Caryophyllales , Humanos , Antimaláricos/química , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/química , Antiparasitários , Caryophyllales/química
8.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36601753

RESUMO

Oxysophoridine (OSR) is an alkaloid extracted from Sophora alopecuroides L. and exerts beneficial effects in cerebral ischemia/reperfusion (I/R) injury. However, the molecular mechanism underlying the regulatory effects of OSR in cerebral I/R injury remains unclear. In the present study, a cerebral I/R injury rat model was established by occlusion of the right middle cerebral artery. Hematoxylin and eosin and triphenyltetrazolium chloride staining were performed to assess histopathological changes and the extent of cerebral injury to the brain. A Cell Counting Kit­8 and TUNEL assay and western blotting were performed to assess cell viability and apoptosis. Ferroptosis and oxidative stress were evaluated based on ATP and Fe2+ levels and DCFH­DA staining. The protein expression levels of inflammatory factors were assessed using ELISA. The protein expression levels of members of the toll­like receptor (TLR)4/p38MAPK signaling pathway were evaluated using immunofluorescence staining and western blotting. The results demonstrated that OSR decreased brain injury and neuronal apoptosis in the hippocampus in I/R­induced rats. OSR inhibited reactive oxygen species (ROS) production, decreased levels of ATP, Fe2+ and acyl­CoA synthetase long­chain family member 4 (ACSL4) and transferrin 1 protein and increased the protein expression levels of ferritin 1 and glutathione peroxidase 4. Furthermore, OSR blocked TLR4/p38MAPK signaling in brain tissue in the I/R­induced rat. In vitro experiments demonstrated that TLR4 overexpression induced generation of ROS, ATP and Fe2+, which promoted the expression of ferroptosis­associated proteins in hippocampal HT22 neuronal cells. The ferroptosis inducer erastin decreased the effects of OSR on oxygen­glucose deprivation/reoxygenation (OGD/R)­induced cell viability, oxidative stress and inflammatory response. Together, the results demonstrated that OSR alleviated cerebral I/R injury via inhibition of TLR4/p38MAPK­mediated ferroptosis.


Assuntos
Alcaloides , Isquemia Encefálica , Ferroptose , Traumatismo por Reperfusão , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like , Traumatismo por Reperfusão/metabolismo , Alcaloides/farmacologia , Apoptose , Isquemia Encefálica/metabolismo , Trifosfato de Adenosina/farmacologia
9.
Food Res Int ; 163: 112172, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596118

RESUMO

Lotus seed plumule (LP) is rich in a variety of antioxidant and anti-inflammatory secondary metabolites, making it a traditional food and medicine widely used in China. Physiological and histological evidences indicated that LP mainly accumulated metabolites in 15-24 days after pollination (DAP) during their development. To systematically investigate the dynamic accumulation of major secondary metabolites, the UPLC-HRMS-based widely targeted metabolomics analyses were performed on maturing LP at 15, 18, 21, and 24 DAP. In total, 767 metabolites were identified, including many secondary metabolites, e.g., 27 % flavonoids and 8 % alkaloids. Among them, 591 were identified as differentially accumulated metabolites (DAMs). The majority of secondary metabolites showed great accumulation after 18 DAP even at the late stage of LP maturation, such as hesperidin, neohesperidin, orobol, serotonin, and lotus special O-nornuciferine, endowing mature LP with effective pharmaceutical properties. The paralleled transcriptomic analysis identified 11,019 differentially expressed genes (DEGs). Based on the comprehensive data, several systematical metabolic regulation maps were established for different secondary metabolites, and 18 DAP was found as a switching point for LP maturing from active primary metabolism to massive secondary metabolites deposition. This study provides valuable information for understanding the mechanism of secondary metabolite accumulation in maturing LP and facilitates its pharmaceutical application.


Assuntos
Alcaloides , Nelumbo , Nelumbo/genética , Nelumbo/metabolismo , Transcriptoma , Sementes/genética , Preparações Farmacêuticas
10.
Acc Chem Res ; 56(2): 140-156, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36594722

RESUMO

ConspectusSecurinega alkaloids, composed of more than 100 members characterized by the compact tetracyclic scaffold, have fascinated the synthetic community with their structural diversity and notable bioactivities. On the basis of the structural phenotype, oligomerizations and oxidations are major biosynthetic diversification modes of the basic Securinega framework. Despite the rich history of synthesis of basic monomeric Securinega alkaloids, the synthesis of oligomeric Securinega alkaloids, as well as oxidized derivatives, has remained relatively unexplored because of their extra structural complexity. In the first half of this Account, our synthetic studies toward high-order Securinega alkaloids are described. We aimed to establish a reliable synthetic method to form C14-C15' and C12-C15' bonds, which are prevalent connection modes between monomers. During our total synthesis of flueggenine C (9), we have invented an accelerated Rauhut-Currier reaction capable of forming the C14-C15' bond stereoselectively. Installation of the nucleophilic functionality to the Michael acceptor, which ushers the C-C bond forming conjugate addition to follow the intramolecular pathway, was the key to success. The C12-C15' linkage, which was inaccessible via an accelerated Rauhut-Currier reaction, was established by devising a complementary cross-coupling/conjugate reduction-based dimerization strategy that enabled the total synthesis of flueggenines D (11) and I (14). In this approach, the C12-C15' linkage was established via a Stille cross-coupling, and the stereochemistry of the C15' position was controlled during the following conjugate reduction step. In the later half of this Account, our achievements in the field of high-oxidation state Securinega alkaloids synthesis are depicted. We have developed oxidative transformations at the N1 and C2-C4 positions, where the biosynthetic oxidation event occurs most frequently. The discovery of a VO(acac)2-mediated regioselective Polonovski reaction allowed us to access the key 2,3-dehydroallosecurinine (112). Divergent synthesis of secu'amamine A (62) and fluvirosaones A (60) and B (61) was accomplished by exploiting the versatile reactivities of the C2/C3 enamine moiety in 112. We have also employed a fragment-coupling strategy between menisdaurilide and piperidine units, which allowed the installation of various oxygen-containing functionality on the piperidine ring. Combined with the late-stage, light-mediated epimerization and well-orchestrated oxidative modifications, collective total synthesis of seven C4-oxygenated securinine-type natural products was achieved. Lastly, the synthesis of flueggeacosine B (70) via two synthetic routes from allosecurinine (103) was illustrated. The first-generation synthesis (seven overall steps) employing Pd-catalyzed cross-coupling between stannane and thioester to form the key C3-C15' bond enabled the structural revision of the natural product. In the second-generation synthesis, we have invented visible-light-mediated, Cu-catalyzed cross-dehydrogenative coupling (CDC) between an aldehyde and electron-deficient olefin, which streamlined the synthetic pathway into four overall steps. Organisms frequently utilize dimerization (oligomerization) and oxidations during the biosynthesis as a means to expand the chemical space of their secondary metabolites. Therefore, methods and strategies for dimerizations and oxidations that we have developed using the Securinega alkaloids as a platform would be broadly applicable to other alkaloids. It is our sincere hope that lessons we have learned during our synthetic journey would benefit other chemists working on organic synthesis.


Assuntos
Alcaloides , Securinega , Estereoisomerismo , Piperidinas
11.
Funct Integr Genomics ; 23(1): 35, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36629976

RESUMO

Rohitukine is a chromone alkaloid and precursor of potent anticancer drugs flavopiridol, P-276-00, and 2,6-dichloro-styryl derivative (11d) (IIIM-290). The metabolite is reported to possess anticancer, anti-inflammatory, antiadipogenic, immunomodulatory, gastroprotective, anti-implantation, antidyslipidemic, anti-arthritic, and anti-fertility properties. However, the physiological role of rohitukine in plant system is yet to be explored. Here, we studied the effect of rohitukine isolated from Dysoxylum gotadhora on Arabidopsis thaliana. The A. thaliana plants grown on a medium fortified with different rohitukine concentrations showed a significant effect on the growth and development. The root growth of A. thaliana seedlings showed considerable inhibition when grown on medium containing 1.0 mM of rohitukine. Transcriptomic analysis indicated the expression of 895 and 932 genes in control and treated samples respectively at a cut-off of FPKM ≥ 1 and P-value < 0.05. Gene ontology (GO) analysis revealed the upregulation of genes related to photosynthesis, membrane transport, antioxidation, xenobiotic degradation, and some transcription factors (TFs) in response to rohitukine. Conversely, rohitukine downregulated several genes including RNA helicases and those involved in nitrogen compound metabolism. The RNA-seq result was also validated by real-time qRT-PCR analysis. In light of these results, we discuss (i) likely ecological importance of rohitukine in parent plant as well as (ii) comparison between responses to rohitukine treatment in plants and mammals.


Assuntos
Alcaloides , Antineoplásicos , Arabidopsis , Animais , Arabidopsis/genética , Antineoplásicos/farmacologia , Cromonas/farmacologia , Cromonas/uso terapêutico , Alcaloides/farmacologia , Perfilação da Expressão Gênica , Transcriptoma , Regulação da Expressão Gênica de Plantas , Mamíferos
12.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675181

RESUMO

Despite their advantages, biotechnological and omic techniques have not been applied often to characterize phytotoxicity in depth. Here, we show the distribution of phytotoxicity and glycoalkaloid content in a diploid potato population and try to clarify the source of variability of phytotoxicity among plants whose leaf extracts have a high glycoalkaloid content against the test plant species, mustard. Six glycoalkaloids were recognized in the potato leaf extracts: solasonine, solamargine, α-solanine, α-chaconine, leptinine I, and leptine II. The glycoalkaloid profiles of the progeny of the group with high phytotoxicity differed from those of the progeny of the group with low phytotoxicity, which stimulated mustard growth. RNA sequencing analysis revealed that the upregulated flavonol synthase/flavonone 3-hydroxylase-like gene was expressed in the progeny of the low phytotoxicity group, stimulating plant growth. We concluded that the metabolic shift among potato progeny may be a source of different physiological responses in mustard. The composition of glycoalkaloids, rather than the total glycoalkaloid content itself, in potato leaf extracts, may be a driving force of phytotoxicity. We suggest that, in addition to glycoalkaloids, other metabolites may shape phytotoxicity, and we assume that these metabolites may be flavonoids.


Assuntos
Flavonoides , Extratos Vegetais , Solanum tuberosum , Alcaloides/análise , Alcaloides/toxicidade , Diploide , Flavonoides/análise , Flavonoides/toxicidade , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Extratos Vegetais/toxicidade , Folhas de Planta/química
13.
Curr Microbiol ; 80(2): 67, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607432

RESUMO

Weeds cause destructive agricultural losses, so weed control is an urgent challenge facing agriculture. The extensive use of synthetic chemical herbicides has detrimental environmental impacts and promotes the emergence of resistant species. Therefore, in this study we tried to find a new natural weed control that can ensure biosafety and eco-sustainability. The phytotoxic potential of culture filtrates of the endophytes Bacillus inaquosorum NL1 and Bacillus safensis NL2 isolated from Nerium oleander leaf against the invasive harmful weed species Cenchrus echinatus was evaluated. Culture filtrates of both bacterial species exhibited potent phytotoxic activity, which resulted in 100% germination inhibition of C. echinatus. The chemical analysis of culture filtrates revealed high contents of total phenolics and n-alkanes that have phytotoxic effects against seed germination. According to the findings of this study the endophytic bacteria associated with N. oleander leaf can be used in the future to develop a sustainable bio-herbicide formulation.


Assuntos
Alcaloides , Cenchrus , Herbicidas , Nerium , Plantas Daninhas , Germinação , Sementes , Herbicidas/farmacologia , Folhas de Planta , Bactérias
14.
J Pharm Biomed Anal ; 225: 115224, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36603394

RESUMO

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.


Assuntos
Alcaloides , Berberina , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Ratos , Animais , Xenobióticos , Alcaloides/química , Medicamentos de Ervas Chinesas/química
15.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675133

RESUMO

Corydalis saxicola Bunting (CSB), whose common name in Chinese is Yanhuanglian, is a herb in the family Papaveraceae. When applied in traditional Chinese medicine, it is used to treat various diseases including hepatitis, abdominal pain, and bleeding haemorrhoids. In addition, Corydalis saxicola Bunting injection (CSBI) is widely used against acute and chronic hepatitis. This review aims to provide up-to-date information on the botanical distribution, description, traditional uses, phytochemistry, pharmacology, and clinical applications of CSB. A comprehensive review was implemented on studies about CSB from several scientific databases, such as SciFinder, Elsevier, Springer, ACS Publications, Baidu Scholar, CNKI, and Wanfang Data. Phytochemical studies showed that 81 chemical constituents have been isolated and identified from CSB, most of which are alkaloids. This situation indicates that these alkaloids would be the main bioactive substances and that they have antitumour, liver protective, antiviral, and antibacterial pharmacological activities. CSBI can not only treat hepatitis and liver cancer but can also be used in combination with other drugs. However, the relationships between the traditional uses and modern pharmacological actions, the action mechanisms, quality standards, and the material basis need to be implemented in the future. Moreover, the pharmacokinetics of CSBI in vivo and the toxicology should be further investigated.


Assuntos
Alcaloides , Corydalis , Medicamentos de Ervas Chinesas , Hepatite , Humanos , Corydalis/química , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Hepatite/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
16.
Molecules ; 28(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36677539

RESUMO

Isoquinoline alkaloids constitute one of the most common classes of alkaloids that have shown a pronounced role in curing various diseases. Finding ways to reduce the toxicity of these molecules and to increase their therapeutic margin is an urgent matter. Here, a one-step method for the synthesis of a series of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines was performed in 85-98% yield by the Pictet-Spengler reaction. This was accomplished using the reaction between 3,4-dimethoxyphenylethylamine and substituted benzaldehydes boiling in trifluoroacetic acid. Furthermore, 1-(3'-amino-, 4'-aminophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were obtained in 94% and 97% yield by reduction in 1-(3'-nitro-, 4'-nitrophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines with SnCl2 × 2H2O. The structures of the substances obtained were confirmed by infrared (IR) and nuclear magnetic resonance (1H and 13C NMR) spectra. ADMET/TOPKAT in silico study concluded that the synthesized compounds exhibited acceptable pharmacodynamic and pharmacokinetic properties without carcinogenic or mutagenic potential but with variable hepatotoxicity. The acute toxicity and structure-toxicity relationship (STR) in the series of 20 derivatives of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines (3a-r, 4a, b) was studied via determination of acute toxicity and resorptive action in white mice employing intragastric step-by-step administration. The first compound, 1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3a), showed the highest toxicity with LD50 of 280 mg/kg in contrast to 1-(3'-bromo -4'-hydroxyphenyl)-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (3e) which proved to be the safest of the compounds studied. Its toxicity was 13.75 times lower than that of the parent compound 3a. All compounds investigated showed high local anesthetic activity on rabbit eyes in the concentrations studied. Only 3r, 3n, and 4a caused eye irritation and redness. All investigated derivatives (except 4b) in 1% concentration were more active than lidocaine, providing longer duration of complete anesthesia. Therefore, based on the obtained results of in silico tests, local anesthesia, and acute toxicity, a conclusion can be drawn that the experimental compounds need further extensive future investigations and possible modifications so that they can act as promising drug candidates.


Assuntos
Alcaloides , Tetra-Hidroisoquinolinas , Camundongos , Animais , Coelhos , Anestésicos Locais , Anestesia Local , Tetra-Hidroisoquinolinas/toxicidade , Tetra-Hidroisoquinolinas/química , Alcaloides/toxicidade , Dose Letal Mediana
17.
Molecules ; 28(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677613

RESUMO

These days an extensive amount of the attention of researchers is focused towards exploring bioactive compounds of natural or herbal origin for therapeutic intervention in different ailments of significant importance. One such novel bioactive compound that has a variety of biological properties, including anti-inflammatory and antioxidant activities, is piperine. However, until today, piperine has not been explored for its potential to improve inflammation and enhance healing in acute and chronic wounds. Therefore, the present study aimed to investigate the wound healing potential of piperine hydrogel formulation after topical application. Hydrogels fit the need for a depot system at the wound bed, where they ensure a consistent supply of therapeutic agents enclosed in their cross-linked network matrices. In the present study, piperine-containing carbopol 934 hydrogels mixed with Aloe vera gels of different gel strengths were prepared and characterized for rheological behavior, spreadability, extrudability, and percent (%) content uniformity. Furthermore, the wound healing potential of the developed formulation system was explored utilizing the excision wound healing model. The results of an in vivo study and histopathological examination revealed early and intrinsic healing of wounds with the piperine-containing bioactive hydrogel system compared to the bioactive hydrogel system without piperine. Therefore, the study's findings establish that the piperine-containing bioactive hydrogel system is a promising therapeutic approach for wound healing application that should be diligently considered for clinical transferability.


Assuntos
Alcaloides , Hidrogéis , Ratos , Animais , Hidrogéis/farmacologia , Pele/patologia , Cicatrização , Alcaloides/farmacologia , Alcaloides/uso terapêutico
18.
Molecules ; 28(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36677722

RESUMO

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.


Assuntos
Alcaloides , Antineoplásicos , COVID-19 , Medicamentos de Ervas Chinesas , Ephedra , Humanos , Medicamentos de Ervas Chinesas/química , Alcaloides/farmacologia , Ephedra/química , Efedrina/farmacologia
19.
Molecules ; 28(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677781

RESUMO

This study aimed to examine the influence of the addition of a precursor (phenylalanine) on the accumulation of secondary metabolites in agitated shoot cultures of Ruta graveolens. Cultures were grown on Linsmaier and Skoog (LS) medium, with plant growth regulators (0.1 mg/L α-naphthaleneacetic acid-NAA-and 0.1 mg/L 6-benzylaminopurine-BAP). Phenylalanine was added to the cultures at a concentration of 1.25 g/L after 4 and 5 weeks of growth cycles. Biomass was collected after 2, 4, and 7 days of precursor addition. Both control and experimental cultures had the same secondary metabolites accumulated. Using the HPLC method, linear furanocoumarins (bergapten, isoimperatorin, isopimpinellin, psoralen, and xanthotoxin), furoquinoline alkaloids (γ-fagarine, 7-isopentenyloxy-γ-fagarine, and skimmianine), and catechin were detected and quantified in the methanolic extracts. In turn, phenolic acids, such as gallic acid, protocatechuic acid, p-hydroxybenzoic acid, syringic acid, p-coumaric acid, and ferulic acid were detected in hydrolysates. The production of phenolic acids and catechin (1.5-fold) was significantly increased by the addition of precursor, while there was no significant effect on the production of coumarins and alkaloids. The highest total content of phenolic acids (109 mg/100 g DW) was obtained on the second day of phenylalanine addition (the fourth week of growth cycles). The dominant phenolic compounds were p-coumaric acid (maximum content 64.3 mg/100 g DW) and ferulic acid (maximum content 35.6 mg/100 g DW). In the case of catechins, the highest total content (66 mg/100 g DW) was obtained on the third day of precursor addition (the fourth week of growth cycles). This study is the first to document the effect of feeding the culture medium with phenylalanine on the accumulation of bioactive metabolites in in vitro cultures of R. graveolens.


Assuntos
Alcaloides , Catequina , Ruta , Fenilalanina/metabolismo , Catequina/metabolismo , Alcaloides/metabolismo
20.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677886

RESUMO

Benzoxazole alkaloids exhibit a diverse array of structures and interesting biological activities. Herein we report the identification of a benzoxazole alkaloid-encoding biosynthetic gene cluster (mich BGC) in the marine-derived actinomycete Micromonospora sp. SCSIO 07395 and the heterologous expression of this BGC in Streptomyces albus. This approach led to the discovery of five new benzoxazole alkaloids microechmycin A-E (1-5), and a previously synthesized compound 6. Their structures were elucidated by HRESIMS and 1D and 2D NMR data. Microechmycin A (1) showed moderate antibacterial activity against Micrococcus luteus SCSIO ML01 with the minimal inhibitory concentration (MIC) value of 8 µg mL-1.


Assuntos
Alcaloides , Micromonospora , Micromonospora/genética , Micromonospora/química , Antibacterianos/farmacologia , Antibacterianos/química , Alcaloides/farmacologia , Alcaloides/química , Espectroscopia de Ressonância Magnética , Genômica , Estrutura Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...