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1.
Phytochemistry ; 193: 112987, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34768188

RESUMO

Picrasma quassioides, a member of the Simaroubaceae family, is the subject of research in numerous pharmacological and chemical studies. This plant mainly contains alkaloids, quassinoids and terpenoids. These molecules exhibit various pharmacological benefits, such as anti-inflammatory, anticancer, and anti-viral effects, on the cardiovascular system. Alkaloids make up the majority of these molecules. This review describes 127 alkaloid substances from P. quassioides. These alkaloids can be divided into the following classes: ß-carbolines, canthinones and alkaloid dimers. A compilation of their nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds and the pharmacological effects of P. quassioides are also included.


Assuntos
Alcaloides , Picrasma , Alcaloides/farmacologia , Vias Biossintéticas , Espectroscopia de Ressonância Magnética , Estrutura Molecular
2.
J Pharm Biomed Anal ; 208: 114467, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34775191

RESUMO

In this study, a supercritical fluid chromatography (SFC) method based on ion pair reagents was used to separate alkaloids. The chromatographic parameters, including the stationary phase, additive type, additive concentration, outlet pressure, temperature and flow rate, were optimized. Baseline separation was completed in 20 min on an Agilent Pursuit 5 PFP column (4.6 × 150 mm) using carbon dioxide as the mobile phase and 7.5 mM sodium 1-pentanesulfonate as an additive with gradient elution at 140 bar, 60 °C, and a flow rate of 1.5 mL/min. The retention rate and resolution of the analytes were satisfactory. The limits of detection were 27.04-298.03 ng/mL, and the limits of quantification were 90.15-993.42 ng/mL. The recoveries of low and high concentrations were 77.46-111.86% and 83.84-111.00%, respectively. This ion pair additive greatly improved the separation efficiency of alkaloids. Consequently, this SFC method was successfully applied to the separation of alkaloids from Rhizoma corydalis.


Assuntos
Alcaloides , Cromatografia com Fluido Supercrítico , Dióxido de Carbono , Temperatura
3.
J Pharm Biomed Anal ; 208: 114471, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34814080

RESUMO

Yunaconitine (YAC), crassicauline A (CCA), 8-deacetylyunaconitine (DYA), and 8-deacetylcrassicauline A (DCA), as hidden toxic Aconitum alkaloids, are detected in some products of processed Aconitum carmichaelii lateral root and poisoning cases. The distribution and toxicity of these four components in Aconitum herbs should be further systematically studied for medication safety. This study developed a new UHPLC-QQQ-MS/MS method to determine ten Aconitum alkaloids, including aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, YAC, CCA, DYA, and DCA, for Aconitum herbs simultaneously. YAC and CCA were founded in some samples of unprocessed A. carmichaelii lateral root (7.04%), A. carmichaelii root (9.43%), A. brachypodum root (6.00%), and A. ouvrardianum root (100%). Four hidden toxic Aconitum alkaloids were detected in processed A. carmichaelii lateral root (2.56%) and A. vilmorinianum root (100%). Four hidden toxic Aconitum alkaloids played significant roles in the classification of Aconitum herbs by OPLS-DA analysis. The acute toxicity test was performed by up-and-down procedure (UDP). The oral administration of the half lethal dose (LD50) of YAC, CCA, DYA, and DCA to female ICR mice was 2.37 mg/kg, 5.60 mg/kg, 60.0 mg/kg, and 753 mg/kg, respectively. The LD50 by intravenous injection was 0.200 mg/kg, 0.980 mg/kg, 7.60 mg/kg, and 34.0 mg/kg, respectively. The LD50 of unprocessed A. carmichaelii lateral root, A. vilmorinianum root, and A. brachypodum root to mice orally was 1.89 g/kg, 0.950 g/kg, and 0.380 g/kg, respectively. Symptoms of Aconitum alkaloid poisoning in mice were decreased activity, fur erect, palpebral edema, vomiting, polypnea, and convulsions. The main change of organs was flatulence. No poisoning or death occurred in mice at the maximum dosage (27.0 g/kg) of A. ouvrardianum root orally. To better control the quality and safety of Aconitum herbs, this study provides favorable support for improving the existing standards to strengthen the supervision of the four hidden toxic Aconitum alkaloids.


Assuntos
Aconitum , Alcaloides , Medicamentos de Ervas Chinesas , Aconitina/toxicidade , Alcaloides/toxicidade , Animais , Medicamentos de Ervas Chinesas/toxicidade , Camundongos , Camundongos Endogâmicos ICR , Raízes de Plantas , Espectrometria de Massas em Tandem
4.
J Hazard Mater ; 422: 126923, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34449334

RESUMO

Areca nut (AN) is a fundamental component of betel quid (BQ), an addictive and carcinogenic mixture chewed by hundreds of millions of people in India-Asia-Pacific. Chewing of BQ is associated with oral cancers due to specific carcinogenic alkaloids (arecaidine, guvacine, guvacoline, arecoline, N-Nitrosoguvacoline) in AN. To predict the hazardous health risks of short and long-term chewing of BQ, it is crucial to identify five toxic AN alkaloids in saliva and urine of BQ chewers. This study reports a green analytical methodology comprising in-syringe assisted vortex-induced salt-enhanced liquid-liquid microextraction coupled with ultra-HPLC-MS/MS for simultaneous biomonitoring of five AN alkaloids in saliva and urine. The analytical method validation results exhibited good linearities between 0.05 and 1000 ng mL-1 with r2 > 0.9930. The detection and quantification limits were between 0.01 and 1.5 and 0.05-5 ng mL-1. Relative recoveries ranged between 87.9% and 110.1% with RSD < 9.1% for saliva samples, 81.5-115.1% with RSD < 9.7% for urine samples. The results indicated the successful identification and real-time monitoring of concentrations of five target AN alkaloids in saliva and urine of BQ chewers and demonstrated the utility of this technique as an efficient analytical protocol for routine biomonitoring of levels of toxic AN alkaloids from BQ chewers and to predict the exposure level and its harmful health risk.


Assuntos
Alcaloides , Areca , Alcaloides/análise , Alcaloides/toxicidade , Monitoramento Biológico , Cromatografia Líquida de Alta Pressão , Humanos , Nozes/química , Espectrometria de Massas em Tandem
5.
Food Chem ; 368: 130832, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34474242

RESUMO

Piper nigrum L. is commonly used worldwide and its pericarp, stalks, leaves will be major wastes materials. 42 amide alkaloids were identified in black, white pepper and pericarp by UHPLC-LTQ-Orbitrap HRMS method, followed by 40 constituents in stalks and 36 constituents in leaves. 8 amide alkaloids were reported for the first time in P. nigrum. An ultra-high-performance supercritical fluid chromatography (UHPSFC)-MS method was firstly applied to simultaneously determine 9 characteristic constituents (piperine, piperlonguminine, piperanine, pipercallosine, dehydropipernonaline, pipernonatine, retrofractamide B, pellitorine and guineensine). The most abundant compound in each extract was piperine with a concentration from 0.10 to 12.37 mg/g of dry weight. The fruits, pericarp and leaves extracts could improve cell viability in 6-OHDA-induced SK-N-SH and SH-SY5Y cells. The results showed the characteristics of amide alkaloids of different parts of P. nigrum and evaluated their neuroprotective activities.


Assuntos
Alcaloides , Piper nigrum , Piper , Alcaloides/farmacologia , Benzodioxóis , Frutas , Extratos Vegetais/farmacologia , Folhas de Planta , Alcamidas Poli-Insaturadas/farmacologia
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120325, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34520895

RESUMO

This paper mainly focuses on the feasibility of rapidly identifying Fritillariae cirrhosae varieties, distinguishing its authenticity and detecting its components by using a portable near infrared (NIR) spectrometer. Five different varieties of Fritillariae cirrhosae, five common counterfeits and two main components (ethanol-soluble extractives and total alkaloids) were studied. The reference values of ethanol-soluble extractives were determined by hot dip method and the reference value of total alkaloid was determined by ultraviolet-visible spectrophotometry (UV-Vis). Linear discriminant analysis (LDA) algorithm was used to identify the sources of different varieties of Fritillariae cirrhosae and the common counterfeits of Fritillariae cirrhosae, respectively. As a result, the best models seemed to be effective, with accuracy of the two models' prediction sets reaches 83.33% and 90.91%, respectively. The partial least squares regression (PLSR) algorithm was used to relate the sample spectra with the reference values of ethanol-soluble extractives and total alkaloid content. Coefficient of determination of prediction (R2p) and root mean square errors of prediction (RMSEP) obtained were 0.8562 and 0.3911; 0.6917 and 0.0117, for ethanol-soluble extractives and total alkaloid content, respectively. The results showed that the portable NIR spectrometer could evaluate the quality of Fritillariae cirrhosae with high efficiency and practicability.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Análise dos Mínimos Quadrados , Refratometria
7.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34903659

RESUMO

Benzylisoquinoline alkaloids (BIAs) are a diverse class of medicinal plant natural products. Nearly 500 dimeric bisbenzylisoquinoline alkaloids (bisBIAs), produced by the coupling of two BIA monomers, have been characterized and display a range of pharmacological properties, including anti-inflammatory, antitumor, and antiarrhythmic activities. In recent years, microbial platforms have been engineered to produce several classes of BIAs, which are rare or difficult to obtain from natural plant hosts, including protoberberines, morphinans, and phthalideisoquinolines. However, the heterologous biosyntheses of bisBIAs have thus far been largely unexplored. Here, we describe the engineering of yeast strains that produce the Type I bisBIAs guattegaumerine and berbamunine de novo. Through strain engineering, protein engineering, and optimization of growth conditions, a 10,000-fold improvement in the production of guattegaumerine, the major bisBIA pathway product, was observed. By replacing the cytochrome P450 used in the final coupling reaction with a chimeric variant, the product profile was inverted to instead produce solely berbamunine. Our highest titer engineered yeast strains produced 108 and 25 mg/L of guattegaumerine and berbamunine, respectively. Finally, the inclusion of two additional putative BIA biosynthesis enzymes, SiCNMT2 and NnOMT5, into our bisBIA biosynthetic strains enabled the production of two derivatives of bisBIA pathway intermediates de novo: magnocurarine and armepavine. The de novo heterologous biosyntheses of bisBIAs presented here provide the foundation for the production of additional medicinal bisBIAs in yeast.


Assuntos
Benzilisoquinolinas/metabolismo , Isoquinolinas/metabolismo , Saccharomyces cerevisiae/metabolismo , Alcaloides/biossíntese , Vias Biossintéticas , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Fermentação , Engenharia Metabólica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Engenharia de Proteínas , Racemases e Epimerases/genética , Racemases e Epimerases/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/metabolismo
8.
Arch Microbiol ; 204(1): 59, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34940904

RESUMO

Staphylococcus aureus causes numerous community-acquired and nosocomial infections in humans by exploiting biofilm. In this context, this study aims to impede the formation of Staphylococcus aureus biofilm by exposing the cells to a plant-based alkaloid, piperine. Our study revealed that piperine exhibited considerable antimicrobial activity against the test organism. However, we had tested the lower concentrations (up to 32 µg/mL) of piperine to observe whether they could show any antibiofilm activity against the same organism. Several experiments, like crystal violet (CV) assay, estimation of total biofilm protein, and fluorescence microscopic observations, established that lower concentrations (up to 16 µg/mL) of piperine showed efficient antibiofilm activity against Staphylococcus aureus. In this connection, we also noticed that the lower concentrations (8 and 16 µg/mL) of piperine showed a considerable reduction in microbial metabolic activity. Besides, it was also observed that the mentioned concentrations of piperine did not compromise the microbial growth of the target organism while exhibiting antibiofilm activity. To understand the underlying mechanism of microbial biofilm inhibition under the influence of piperine, we observed that the compound was found to accumulate reactive oxygen species in the bacterial cells that could play an important role in the inhibition of biofilm formation. Furthermore, the tested concentrations (8 and 16 µg/mL) of piperine were able to inhibit the motility of the test organism that might compromise the development of biofilm. Thus, piperine could be considered as a potential agent for the effective management of biofilm threat caused by Staphylococcus aureus.


Assuntos
Alcaloides , Staphylococcus aureus , Alcaloides/farmacologia , Antibacterianos/farmacologia , Benzodioxóis , Biofilmes , Humanos , Testes de Sensibilidade Microbiana , Piperidinas , Alcamidas Poli-Insaturadas , Espécies Reativas de Oxigênio
9.
J Agric Food Chem ; 69(51): 15562-15574, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34905918

RESUMO

Adipocyte-derived leptin activates multiple oncogenic signaling, leading to breast cancer cell progression and metastasis. Hence, finding effective strategies to inhibit the oncogenic effects of leptin would provide a novel approach for disrupting obesity-associated breast cancer. In the current study, we explored the role of piperine, a major plant alkaloid from Piper nigrum (black pepper), against leptin-induced breast cancer. Piperine treatment significantly inhibited leptin-induced breast cancer cell proliferation, colony formation, migration, and invasion. We found that piperine downregulated the expression of PPARα, a predicted target of miR-181c-3p. Mechanistically, piperine potentiates miR-181c-3p-mediated anticancer potential in leptin-induced breast cancer cells. Interestingly, the knockdown of PPARα reduced the proliferative potential of leptin-induced breast cancer cells. Further, oral administration of piperine inhibited breast tumor growth in diet-induced obese mice, accompanied by the upregulation of miR-181c-3p and downregulation of PPARα expression. Together, piperine represents a potential candidate for further development as an anticancer agent for treating obesity-associated breast cancer.


Assuntos
Alcaloides , Neoplasias da Mama , MicroRNAs , Animais , Benzodioxóis , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Dieta , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/genética , Obesidade/tratamento farmacológico , Obesidade/genética , PPAR alfa/genética , Piperidinas , Alcamidas Poli-Insaturadas
10.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5727-5735, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951160

RESUMO

Mecicinal plants boast abundant natural compounds with significant pharmacological activity, and such compounds, featuring diversified and complex structures, can be used for research and development of drugs. At present, these natural compounds are directly extracted from herbs which, however, suffer from damaged wild resources and shortage of planting resources attributing to the increasing demand. Moreover, the low content in medicinal plants and complex structures are another challenge to the research and development of drugs. Heterologous synthesis with synthetic biology methods is a solution that has attracted wide attention. Synthetic bio-logy for the production of natural active compounds in Chinese medicinal plants involves the exploration of key enzymes in compound bio-synthetic pathways from plants, analysis of enzyme functions and mechanisms, and reconstruction and optimization of biosynthetic pathways in microorganisms for efficient synthesis of compounds. This study briefed the development process of synthetic biology and the biosynthetic pathways of terpenoids, alkaloids, and flavonoids, and summarized the related strategies of synthetic biology such as the reconstruction and optimization of metabolic pathways, regulation of fermentation process, and strain improvement, and the latest applications of heterogeneous synthetic biology in the production of natural compounds from Chinese medicinals. This study is expected to serve as a reference for the efficient production of terpenoids, alkaloids, flavonoids, and other active compounds from Chinese medicinal plants with strategies of synthetic biology.


Assuntos
Alcaloides , Plantas Medicinais , Vias Biossintéticas , China , Biologia Sintética
11.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5895-5901, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951180

RESUMO

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.


Assuntos
Alcaloides , Artrite Experimental , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/genética , Bovinos , Citocinas , Camundongos , Camundongos Endogâmicos DBA , Quinolizinas
12.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6271-6277, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951254

RESUMO

The present study investigated the differences in pharmacokinetics and intestinal absorption of six alkaloids in Sanmiao Pills and Simiao Pills in rats and explored the different efficacies of the two formulae. After oral administration of Sanmiao Pills and Simiao Pills in rats, blood samples were collected at different time points. Samples were prepared for the determination of six alkaloids in plasma by UPLC-MS/MS. The chromatography was performed on an ACE Excel 3 C_(18 )column with acetonitrile-0.1% formic acid in water as the mobile phase for gradient elution. Analytes were detected in the positive ion mode. Plasma concentrations and pharmacokinetic parameters were calculated. Intestinal absorption of alkaloids was investigated by single-pass intestinal perfusion and absorption parameters of ingredients were calculated. The results showed that the UPLC-MS/MS method for simultaneous determination of concentrations of six alkaloids in plasma was developed and validated by methodological investigations, such as specificity, calibration curves, precision, accuracy, recovery, matrix effect, and stability. The results of the pharmacokinetic assay revealed that C_(max) and AUC values of phellodendrine, berberine, magnoflorine, berberrubine, and jatrorrhizine in Simiao Pills were significantly increased, and CL/F values were reduced as compared with those in Sanmiao Pills, which indicated the increase in plasma concentrations of alkaloids. The intestinal absorption parameters K_(a )and P_(eff) values of phellodendrine, berberine, and jatrorrhizine in Simiao Pills were higher than those in Sanmiao Pills. The intestinal absorption and plasma concentrations of alkaloids in Simiao Pills were significantly higher than those in Sanmiao Pills, suggesting that the composition of Simiao Pills was more conducive to the alkaloids into the blood to resist inflammation and lower uric acid.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Absorção Intestinal , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
13.
BMC Plant Biol ; 21(1): 591, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903180

RESUMO

BACKGROUND: Agarwood is a highly sought-after resinous wood for uses in medicine, incense, and perfume production. To overcome challenges associated with agarwood production in Aquilaria sinensis, several artificial agarwood-induction treatments have been developed. However, the effects of these techniques on the metabolome of the treated wood samples are unknown. Therefore, the present study was conducted to evaluate the effects of four treatments: fire drill treatment (F), fire drill + brine treatment (FS), cold drill treatment (D) and cold drill + brine treatment (DS)) on ethanol-extracted oil content and metabolome profiles of treated wood samples from A. sinensis. RESULTS: The ethanol-extracted oil content obtained from the four treatments differed significantly (F < D < DS < FS). A total of 712 metabolites composed mostly of alkaloids, amino acids and derivatives, flavonoids, lipids, phenolic acids, organic acids, nucleotides and derivatives, and terpenoids were detected. In pairwise comparisons, 302, 155, 271 and 363 differentially accumulated metabolites (DAM) were detected in F_vs_FS, D_vs_DS, F_vs_D and FS_vs_DS, respectively. The DAMs were enriched in flavonoid/flavone and flavonol biosynthesis, sesquiterpenoid and triterpenoid biosynthesis. Generally, addition of brine to either fire or cold drill treatments reduced the abundance of most of the metabolites. CONCLUSION: The results from this study offer valuable insights into synthetically-induced agarwood production in A. sinensis.


Assuntos
Metaboloma , Óleos Vegetais/química , Thymelaeaceae/metabolismo , Madeira/metabolismo , Alcaloides/metabolismo , Aminoácidos/metabolismo , Ácidos Carboxílicos/metabolismo , Temperatura Baixa , Etanol , Incêndios , Flavonas/metabolismo , Flavonoides/metabolismo , Hidroxibenzoatos/metabolismo , Metabolismo dos Lipídeos , Nucleotídeos/metabolismo , Sais/farmacologia , Terpenos/metabolismo , Thymelaeaceae/química , Thymelaeaceae/efeitos dos fármacos , Madeira/química , Madeira/efeitos dos fármacos
14.
Planta ; 254(6): 122, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786595

RESUMO

MAIN CONCLUSION: An ABCB-type transporter for sanguinarine, a benzophenanthridine alkaloid, was isolated from Argemone mexicana seeds. An ABCB-type transporter, AmABCB1, was identified in a transcriptome from unfolding seedlings of A. mexicana by its amino acid sequence identity to previously characterized alkaloid transporters from Coptis japonica and Thalictrum minus. Expression analysis revealed mature seeds as its main location; meanwhile, in vitro assays in yeast cells showed that AmABCB1 had uptake and efflux activities for sanguinarine and berberine, respectively.


Assuntos
Alcaloides , Argemone , Berberina , Papaveraceae , Sementes
15.
An Acad Bras Cienc ; 93(suppl 4): e20200944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34817035

RESUMO

Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 µg/mL and MFC 62.5 µg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 µg/mL), and C. tropicalis (MIC 31.2 µg/mL and MFC 125 µg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained.


Assuntos
Alcaloides , Poríferos , Alcaloides/farmacologia , Animais , Antifúngicos/farmacologia , Candida , Testes de Sensibilidade Microbiana
16.
Appl Microbiol Biotechnol ; 105(23): 8869-8880, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34748037

RESUMO

Huperzine-A (HupA) is an emerging, powerful, and promising natural acetylcholinesterase inhibitor. Despite that, the achieved yields of HupA from microbial sources are still far from the industrial applications. Accordingly, this paper was conducted to valorize solid-state fermentation (SSF) as an efficient production platform of HupA. Four agro-industrial wastes, namely rice bran, potato peel, sugarcane bagasse, and wheat bran, were tested and screened as cultural substrates for the production of HupA by the endophytic Alternaria brassica under SSF. Maximum HupA production was attained on using rice bran moistened by Czapex's dox mineral broth. In the effort to increase the HupA titer, supplementation of the best moistening agent by different carbon and nitrogen sources was successfully investigated. Additionally, factors affecting HupA production under SSF including substrate concentration, moistening level, and inoculum concentration were optimized using response surface methodology. A Box-Behnken design was applied for generating a predictive model of the interactions between these factors. Under the optimum conditions of 15 g rice bran, inoculum concentration of 5 × 106 spores mL-1, and 60% moisture level, HupA concentration was intensified to 518.93 µg g-1. Besides, HupA production by the fungal strain was further enhanced using gamma-irradiation mutagenesis. The final HupA production was significantly intensified following exposure to 0.5 KGy gamma radiation to 1327 µg g-1, which represents a 12.85-fold increase. This is the first report on the successful production of the natural fungal metabolite HupA under SSF. Moreover, the achieved yield in this study using agro-industrial wastes may contribute to reducing the cost of HupA manufacture.Key points• Different agro-industrial by-products were tried as cultural substrates for the production of the acetylcholinesterase inhibitor HupA under SSF for the first time.• Factors affecting HupA production under SSF were optimized using response surface methodology.• The final HupA production was intensified following exposure to gamma radiation recording 1327 µg g-1, which represents a 12.85-fold increase.


Assuntos
Alternaria , Inibidores da Colinesterase , Acetilcolinesterase , Alcaloides , Fermentação , Raios gama , Sesquiterpenos
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(10): 1519-1526, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34755667

RESUMO

OBJECTIVE: To explore the role of cell cycle checkpoint kinase 1/2 (CHK1/2) in mediating the inhibitory effect of oxymatrine (OMT) against renal inflammation and fibrosis in diabetic rats. METHODS: SD rats were randomly divided into normal control group, diabetes model group (DM) and OMT treatment group (n=6). HE and Masson staining were used to observe histopathological changes of the renal tissue, and the expressions of CHK1, CHK2, p-CHK1 and p-CHK2 were localized by immunohistochemical staining. The contents of interleukin-6 (IL-6) and IL-1ß in the renal tissue were detected using ELISA, and the expression levels of CHK1, CHK2, p-CHK1, p-CHK2, type Ⅲ collagen (Col-Ⅲ), type Ⅳ collagen (Col-Ⅳ), and fibronectin (FN) were determined using Western blotting. The changes in the expressions of CHK1, CHK2, p-CHK1, p-CHK2, Col-Ⅲ, Col-Ⅳ and FN proteins were also examined with Western blotting in NRK-52E cells in response to high glucose exposure, OMT treatment and siRNA-mediated CHK1/2 knockdown. RESULTS: In diabetic rats, OMT treatment significantly decreased the levels of blood glucose, serum creatinine and 24 h urinary protein (P < 0.05) and obviously improved inflammatory cell infiltration and fibrosis phenotype in the renal tissue (P < 0.05). CHK1 and CHK2 were mainly expressed in the cytoplasm and nuclei of renal tubule cells, and their phosphorylation levels were significantly higher in DM group than in the control group and OMT group. OMT treatment significantly decreased the protein expression levels of p-CHK1, p-CHK2, Col-Ⅲ, Col-Ⅳ and FN in the renal tissue of diabetic rats and in NRK-52E cells exposed to high glucose (P < 0.05). In NRK-52E cells, CHK1/2 knockdown resulted in significant reduction of the protein expressions of p-CHK1/2, Col-Ⅲ, Col-Ⅳ and FN (P < 0.05). CONCLUSION: The inhibitory effects of OMT against renal inflammation and fibrosis in diabetic rats are mediated probably by lowered phosphorylation levels of CHK1 and CHK2, which result in reduced release of the downstream inflammatory mediators and decreased secretion and deposition of extracellular matrix.


Assuntos
Diabetes Mellitus Experimental , Alcaloides , Animais , Diabetes Mellitus Experimental/complicações , Fibrose , Inflamação/tratamento farmacológico , Fosforilação , Quinolizinas , Ratos , Ratos Sprague-Dawley
18.
BMC Genomics ; 22(1): 838, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34794378

RESUMO

BACKGROUND: Black pepper (Piper nigrum L.), an important and long-cultivated spice crop, is native to South India and grown in the tropics. Piperine is the main pungent and bioactive alkaloid in the berries of black pepper, but the molecular mechanism for piperine biosynthesis has not been determined. MicroRNAs (miRNAs), which are classical endogenous noncoding small RNAs, play important roles in regulating secondary metabolism in many species, but less is known regarding black pepper or piperine biosynthesis. RESULTS: To dissect the functions of miRNAs in secondary metabolism especially in piperine biosynthesis, 110 known miRNAs, 18 novel miRNAs and 1007 individual targets were identified from different tissues of black pepper by small RNA sequencing. qRT-PCR and 5'-RLM-RACE experiments were conducted to validate the reliability of the sequencing data and predicted targets. We found 3 miRNAs along with their targets including miR166-4CL, miR396-PER and miR397-CCR modules that are involved in piperine biosynthesis. CONCLUSION: MiRNA regulation of secondary metabolism is a common phenomenon in plants. Our study revealed new miRNAs that regulate piperine biosynthesis, which are special alkaloids in the piper genus, and they might be useful for future piperine genetic improvement of black pepper.


Assuntos
Alcaloides , MicroRNAs , Piper nigrum , Benzodioxóis , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Piperidinas , Plantas Geneticamente Modificadas , Alcamidas Poli-Insaturadas , Reprodutibilidade dos Testes , Análise de Sequência de RNA
19.
Pan Afr Med J ; 40: 58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795837

RESUMO

Introduction: Marsdenia macrantha is a crucial source of traditional medicine in Northern Namibia. Its roots are used to treat various health conditions ranging from mouth infections to urinary retention. Despite its medicinal application, there is no known knowledge of its therapeutic properties. Thus, we investigated the phytochemical content and antibacterial activity of M. macrantha. Methods: M. macrantha root extracts were obtained using three different solvents (distilled water, methanol and acetone) - in the soxhlet and maceration extraction methods. Total phytochemical (terpenoid, alkaloid and/or flavonoid) content was determined by spectrophotometry. Antibacterial activity against common foodborne pathogens (Staphylococcus aureus, Escherichia coli and Salmonella typhi) was determined by both well and disc diffusion method. Results: we detected the presence of all the tested phytochemicals. Methanol gave the highest percentage yield of extraction (mean: 13.95 ± standard deviation: 0.41%) followed by water (10.92 ± 0.11%) and acetone (6.85 ± 0.23%), F-ratio=326.71 and p<0.0003. The total content determined showed that M. macrantha root extract contained more flavonoids than alkaloids (mg of standard per grams of the dry material). Antibacterial analyses showed inhibitory activity against all the selected pathogens, with the highest inhibition zone against S. typhi (19.7 ± 0.3 mm) - for the acetone-prepared root extract. There were variations in minimum inhibitory concentrations of the extracts prepared by the different solvents. Conclusion: this is the first study demonstrating the presence of phytochemicals and antibacterial properties of M. macrantha roots. Further studies are needed to isolate and characterize the phytochemicals for antibacterial application.


Assuntos
Antibacterianos/farmacologia , Marsdenia/química , Extratos Vegetais/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antibacterianos/isolamento & purificação , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Escherichia coli/efeitos dos fármacos , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Raízes de Plantas , Salmonella typhi/efeitos dos fármacos , Solventes/química , Staphylococcus aureus/efeitos dos fármacos , Terpenos/isolamento & purificação , Terpenos/farmacologia
20.
Fa Yi Xue Za Zhi ; 37(4): 561-568, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34726012

RESUMO

Abstract: Synthetic cathinones are a class of new psychoactive substances with a structure similar to amphetamine drugs, which can produce excitatory effects similar to drugs such as amphetamine and cocaine after being taken. In recent years, the abuse of synthetic cathinones worldwide has become increasingly serious, posing a serious threat to social security and public health. This article focuses on several common synthetic cathinones, collects their research results in animal autonomous activity experiments and drug dependence model experiments and summarizes their relevant experimental conclusions in animal body temperature regulation, learning and memory, and anxiety, in order to provide data reference and method guidance for the domestic development of related drug research.


Assuntos
Alcaloides , Drogas Ilícitas , Alcaloides/farmacologia , Anfetamina , Animais , Comportamento Animal
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