RESUMEN
Unsaturated fatty acids (UFAs) are fatty acids with one or more carbon-carbon double bonds (C=C). They are building blocks of structurally complex lipids. According to the position of C=C bond in the UFAs, there are multiple isomers with different physiological activities. Therefore, an accurate understanding of UFAs is essential. Combining Paternò-Büchi (PB) reaction with tandem mass spectrometry (MS/MS) analysis has been successfully used to identify unsaturated lipids in bio-samples. However, there are still some challenges, such as low reactive rate and low MS response of PB products. In this study, 3-pyridinecarboxaldehyde (3-PYA) was selected as an efficient PB reagent for the first time. According to the nitrogen rule, introduction of nitrogen did not only make the target MS and MS/MS ions to be easily identified but also increase the ionization efficiency significantly. The developed method in this study demonstrated greater efficiency and sensitivity for the identification of UFAs in total lipid extracts from bovine liver compared with other commonly used PB reagents.
Asunto(s)
Ácidos Grasos Insaturados , Espectrometría de Masas en Tándem , Animales , Carbono/química , Bovinos , Ácidos Grasos Insaturados/análisis , Hígado/química , Nitrógeno , Espectrometría de Masas en Tándem/métodosRESUMEN
Stilbenes are some of the important phenolic compounds originating from plant families like Vitaceae, Leguminaceae, Gnetaceae, and Dipterocarpaceae. Structurally, they have a C6-C2-C6 skeleton, usually with two isomeric forms. Stilbenes are biosynthesized due to biotic and abiotic stresses such as microbial infections, high temperatures, and oxidation. This review aims to provide a comprehensive overview of stilbenes' botanical sources, chemistry, biosynthetic pathways, pharmacology, and clinical applications and challenges based on up-to-date data. All included studies were collected from PubMed, ScienceDirect, Google Scholar, and CNKI, and the presented data from these indexed studies were analyzed and summarized. A total of 459 natural stilbene compounds from 45 plant families and 196 plant species were identified. Pharmacological studies also show that stilbenes have various activities such as anticancer, antimicrobial, antioxidant, anti-inflammatory, anti-degenerative diseases, anti-diabetic, neuroprotective, anti-aging, and cardioprotective effects. Stilbene synthase (STS) is the key enzyme involved in stilbene biosynthetic pathways. Studies on the therapeutic application of stilbenes pinpoint that challenges such as low bioavailability and isomerization are the major bottlenecks for their development as therapeutic drugs. Although the medicinal uses of several stilbenes have been demonstrated in vivo and in vitro, studies on the development of stilbenes deserve more attention in the future.
Asunto(s)
Estilbenos , Fitoquímicos/química , Plantas/metabolismo , Estilbenos/química , Estrés FisiológicoRESUMEN
The genus Uncaria belongs to the family of Rubiaceae, which contains approximately 34 species. It has been widely used as a traditional Chinese medicine (TCM) in China to treat hypertension, fevers, headaches, gastrointestinal illness, epilepsy, wounds, and ulcers. Uncaria rhynchophylla. (Miq.) Miq. ex Hvail.(URM) and Uncaria hirsuta Havil.(UHH) are mainly used as remedies for hypertension, which both belong to the resource of "Gou-teng" in the Chinese Pharmacopoeia. However, the authentic antihypertensive components of Uncaria still have not been fully elucidated until now. In this work, we firstly explored and compared the vasorelaxation effect of URM and UHH on the isolated rat mesenteric artery ring. Then, the variations of metabolite profiles between URM and UHH samples were investigated by UHPLC/Q-Orbitrap-MS, and 16 different metabolites have been found through multivariate statistical analysis. Further, the potential vasodilative compounds which include corynoxeine, isocorynoxeine, isorhynchophylline, rhynchophylline, hirsuteine and hirsutine were screened through the correlation analysis between metabolites and anti-hypertension activities. And the relaxation effects of the six compounds on the mesenteric artery have verified. The results indicated that metabolomics combined with correlation analysis could be effective strategies to rapid explore the active compounds from TCM.
Asunto(s)
Uncaria , Animales , China , Cromatografía Líquida de Alta Presión , Metabolómica , Ratas , VasodilataciónRESUMEN
The efficacy of raw and processed products of Polygonum multiflorum (PM) varies greatly. "Nine cycles of steaming and sunning" (NCSS) is recognized as an effective technology in enhancing efficacy and reducing toxicity for PM. In this paper, PM was prepared differently into three groups (including group R, M, and "9"), which represent raw PM, PM processed using the method of Chinese Pharmacopoeia (ChP) and PM processed using traditional NCSS, respectively. The purpose is to establish an effective method to distinguish raw PM from different processed products and highlight the rationality of processing technology. The main organic compounds that could distinguish these three groups of samples were identified by in-depth mining of mass spectral information and various chemometric methods. Level of related metal cations have been quantified and used as another important distinguishing markers. The electronic tongue was utilized to determine the taste traits of aqueous extract from PM. Furthermore, the material basis that caused the difference in taste was discovered according to correlation analysis. In detail, saltiness has the most important contribution associated with the concentrations of K+ and Na+, however, bitterness and astringency were mainly associated with the contents of epicatechin gallate, catechin, procyanidin B1, procyanidin B2 and epicatechin. This study proposed a novel and effective strategy for identification of processing technology of PM. It lays the foundation for clarifying the modern scientific recommendations of processing technology to PM. On the other hand, it also provides a reference for related researches on other traditional Chinese medicine (TCM).
Asunto(s)
Fallopia multiflora , Polygonum , Cromatografía Liquida , Nariz Electrónica , Espectrometría de Masas en Tándem , GustoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb.(PM), (known as Heshouwu () in China) is one of the most important and well mentioned Chinese medicinal herbs in the literature for its use in blackening hair, nourishing liver and kidney, anti-aging, anti-hyperlipidemia, antioxidant, anti-inflammatory, anticancer, hepatoprotection, cardio-protection and improving age-related cognitive dysfunction. The purpose of this review is to give a comprehensive and recent update on PM: new compounds or isolated for the first time, potential hepatotoxic compounds and their mechanisms. Moreover, future perspectives and challenges in the future study of this plant are conversed which will make a new base for further study on PM. MATERIALS AND METHODS: A comprehensive review of relevant published literature on PM using the scientific databases SCOPUS, PubMed, and Science Direct was done. RESULTS: PM is broadly produced in many provinces of China and well known in other Eastern Asian Countries for its ethno-medical uses. Previous phytochemical investigation of PM had led to the isolation of more than 175 compounds including recently isolated 70 new compounds. Most of the new compounds isolated after 2015 are majorly dianthrone glycosides and stilbene glycosides. Processing has also a significant effect on chemical composition, pharmacological activities, and toxicity of PM. PM-induced liver injury is increasing after the first report in Hong Kong in 1996. Hepatotoxicity of PM was constantly reported in Japan, Korea, China, Australia, Britain, Italy, and other countries although its toxicity is related to idiosyncratic hepatotoxicity. More interestingly, although there is indispensable interest to predict idiosyncratic hepatotoxicity of PM and understand its mechanisms, the responsible hepatotoxic compounds and mechanisms of liver damage induced by PM are still not clear. There is a big controversy on the identification of the most responsible constituent. Anthraquinone and stilbene compounds in PM, mainly emodine and TSG are mentioned in the literature to be the main responsible hepatotoxic compounds. However, comparing the two compounds, which one is the more critical toxic agent for PM-induced hepatotoxicity is not well answered. Affecting different physiological and metabolic pathways such as oxidative phosphorylation and TCA cycle pathway, metabolic pathways, bile acid excretion pathway and genetic polymorphisms are among the mechanisms of hepatotoxicity of PM. CONCLUSION: Deeper and effective high throughput experimental studies are still research hotspots to know the most responsible constituent and the mechanism of PM-induced hepatotoxicity.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/química , Fallopia multiflora/química , Animales , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Medicina Tradicional China , Fitoquímicos/efectos adversos , Fitoquímicos/análisis , Fitoquímicos/química , Fitoquímicos/farmacologíaRESUMEN
RELEVANCE: Bisbenzylisoquinoline (BBIQ) alkaloids are generally present in plants of Berberidaceae, Monimiaceae and Ranunculaceae families in tropical and subtropical regions. Some species of these families are used in traditional Chinese medicine, with the effects of clearing away heat and detoxification, promoting dampness and defecation, and eliminating sores and swelling. This article offers essential data focusing on 13 representative BBIQ compounds, which are mainly extracted from five plants. The respective botany, traditional uses, phytochemistry, pharmacokinetics, and toxicity are summarized comprehensively. In addition, the ADME prediction of the 13 BBIQ alkaloids is compared and analyzed with the data obtained. MATERIALS AND METHODS: We have conducted a systematic review of the botanical characteristics, traditional uses, phytochemistry, pharmacokinetics and toxicity of BBIQ alkaloids based on literatures collected from PubMed, Web of Science and Elsevier during 1999-2020. ACD/Percepta software was utilized to predict the pharmacokinetic parameters of BBIQ alkaloids and their affinity with enzymes and transporters. RESULTS: Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity of 13 alkaloids, namely, tetrandrine, dauricine, curine, trilobine, isotrilobine, cepharanthine, daurisoline, thalicarpine, thalidasine, isotetrandrine, liensinine, neferine and isoliensinine, have been summarized in this paper. It can't be denied that these alkaloids are important material basis of pharmacological effects of family Menispermaceae and others, and for traditional and local uses which has been basically reproduced in the current studies. The 13 BBIQ alkaloids in this paper showed strong affinity and inhibitory effect on P-glycoprotein (P-gp), with poor oral absorption and potent binding ability with plasma protein. BBIQ alkaloids represented by tetrandrine play a key role in regulating P-gp or reversing multidrug resistance (MDR) in a variety of tumors. The irrationality of their usage could pose a risk of poisoning in vivo, including renal and liver toxicity, which are related to the formation of quinone methide during metabolism. CONCLUSION: Although there is no further clinical evaluation of BBIQ alkaloids as MDR reversal agents, their effects on P-gp should not be ignored. Considering their diverse distribution, pharmacokinetic characteristics and toxicity reported during clinical therapy, the quality standards in different plant species and the drug dosage remain unresolved problems.
Asunto(s)
Alcaloides/farmacocinética , Bencilisoquinolinas/farmacocinética , Medicamentos Herbarios Chinos/farmacocinética , Medicina Tradicional China/métodos , Fitoquímicos/farmacocinética , Plantas Medicinales , Alcaloides/uso terapéutico , Alcaloides/toxicidad , Animales , Bencilisoquinolinas/uso terapéutico , Bencilisoquinolinas/toxicidad , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/toxicidad , Etnobotánica/métodos , Etnofarmacología/métodos , Humanos , Fitoquímicos/uso terapéutico , Fitoquímicos/toxicidadRESUMEN
Hyperuricemia seriously jeopardizes human health by increasing the risk of several diseases, such as gout and stroke. Nuciferine is able to alleviate hyperuricemia significantly. However, the underlying metabolic regulation mechanism remains unknown. To understand the metabolic effects of nuciferine on hyperuricemia by establishing a rat model of rapid hyperuricemia, 1H NMR and liquid chromatography-mass spectrometry were used to conduct nontargeted metabolomics studies. A total of 21 metabolites were authenticated in plasma and urine to be closely related with hyperuricemia, which were mainly correlated to the six metabolic pathways. Moreover, 16S rRNA analysis indicated that diversified intestinal microorganisms are closely related to changes in differential metabolites, especially bacteria from Firmicutes and Bacteroidetes. We propose that indoxyl sulfate and N-acetylglutamate in urine may be the potential biomarkers besides uric acid for early diagnosis and prevention of hyperuricemia. Gut microbiological analysis found that changes in the gut microbiota are closely related to these metabolites.
Asunto(s)
Microbioma Gastrointestinal , Hiperuricemia , Animales , Aporfinas , Cromatografía Líquida de Alta Presión , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/genética , Metabolómica , Espectroscopía de Protones por Resonancia Magnética , ARN Ribosómico 16S/genética , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Emergence of drug resistance and lack of therapeutic efficacy of modern antimalarial drugs are the most triggering factors for the searching of new lead compounds with different mechanisms of action. Medicinal plants with documented traditional uses are a viable option for treatment of malaria. Traditionally, the leaf latex of Aloe weloensis has been used in the treatment of malaria in Ethiopia. Hence, this study was undertaken to investigate the antimalarial activity of the leaf latex of Aloe weloensis in Plasmodium berghei-infected mice. METHODS: A four-day suppressive test was employed to evaluate the antimalarial effect of the leaf latex of the plant against P. berghei in Swiss albino mice. Mice were randomly assigned in five groups of five animals in each and given 100, 200, and 400 mg/kg of the leaf latex, chloroquine 25 mg/kg, and distilled water. The level of parasitemia, packed cell volume, survival time, temperature, and body weight was used to determine the antimalarial activity. RESULTS: The acute toxicity study indicated that the leaf latex of A. weloensis caused neither mortality nor signs and symptoms of toxicity at a dose of 2000 mg/kg. Furthermore, the 4-day suppressive test indicated that the latex of the plant exhibited a significant parasitemia reduction in a dose-dependent manner as compared to negative control. The leaf latex of the plant exhibited a percent inhibition of 13.05%, 41.87%, and 66.84% at doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively. The chemosuppression of the antimalarial activity was statistically significant at 100 mg/kg (p < 0.05), 200 mg/kg (p < 0.01), and 400 mg/kg (p < 0.01) as compared to negative control. All doses of the leaf latex prevented weight loss and reduction in temperature and packed cell volume and increased the survival time of infected mice. CONCLUSION: The results of this study demonstrated that the leaf latex of Aloe weloensis possessed antiplasmodial activity confirming the genuine traditional use of the plant as an antimalarial agent.
RESUMEN
Therapeutic agents can be transformed into reactive metabolites under the action of various metabolic enzymes in vivo and then covalently combine with biological macromolecules (such as protein or DNA), resulting in increasing toxicity. The screening of reactive metabolites in drug discovery and development stages and monitoring of biotransformation in post-market drugs has become an important research field. Generally, reactive metabolites are electrophilic and can be captured by small nucleophiles. Glutathione (GSH) is a small peptide composed of three amino acids (i.e., glutamic acid, cysteine, and glycine). It has a thiol group which can react with electrophilic groups of reactive metabolic intermediates (such as benzoquinone, N-acetyl-p-benzoquinoneimine, and Michael acceptor) to form a stable binding conjugate. This paper aims to provide a review on structure-based reactivity profiles of reactive metabolites with GSH. Furthermore, this review also reveals the relationship between drugs' molecular structures and reactive metabolic toxicity from the perspective of metabolism, giving a reference for drug design and development.
Asunto(s)
Glutatión/metabolismo , Compuestos Orgánicos/metabolismo , Animales , Glutatión/química , Humanos , Estructura Molecular , Compuestos Orgánicos/química , Relación Estructura-ActividadRESUMEN
BACKGROUND: The role of free radical reactions in disease pathology is well known to be involved in many acute and chronic disorders in human beings, such as diabetes, atherosclerosis, aging, immunosuppression and neurodegeneration. The search for new drugs of plant origin becomes increasingly urgent due to drug resistance. Aloe schelpei is an endemic Aloe species traditionally used for the treatment of infectious and chronic diseases. AIM: This study was conducted to evaluate free radical scavenging activities of leaf latex of Aloe schelpei and its isolated compounds. METHODS: The leaf latex of A. schelpei was subjected to preparative thin-layer chromatography to afford three compounds. Free radical scavenging activities of the leaf latex and its constituents was carried out using a 2, 2-diphenyl-1-picrylhydrazyl method. RESULTS: Phytochemical investigation of the leaf latex Aloe schelpei by prepartive thin layer chromatography led to the isolation of three compounds, identified as microdontin A/B (1), aloin A/B (2) and aloinoside A/B (3). The results showed that the leaf latex had a strong free radical scavenging activity reaching a maximum of 84.3% at a concentration of 100 µg/mL, and with an IC50 value of 25.3 ± 2.45 µg/mL (p < 0.05). Among the isolated compounds, microdontin A/B (1) was found to have the strongest free radical scavenging activity with an IC50 value of 0.07 ± 0.005 mµ, followed by aloinoside A/B (IC50 = 0.13 ± 0.01 mM) and aloin A/B (IC50 = 0.15 ± 0.02 mM). CONCLUSION: The traditional medicinal practice of the leaf latex may be due to the antioxidant activities of the leaf latex of A. schelpei and the isolated compounds.
Asunto(s)
Aloe/química , Antioxidantes/farmacología , Compuestos de Bifenilo/antagonistas & inhibidores , Látex/farmacología , Fitoquímicos/farmacología , Picratos/antagonistas & inhibidores , Extractos Vegetales/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Látex/química , Látex/aislamiento & purificación , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Relación Estructura-ActividadRESUMEN
Malaria is one of the three major global public health threats due to a wide spread resistance of the parasites to the standard antimalarial drugs. Considering this growing problem, the ethnomedicinal approach in the search for new antimalarial drugs from plant sources has proven to be more effective and inexpensive. The leaves of Aloe pulcherrima Gilbert and Sebsebe, an endemic Ethiopian plant, are locally used for the treatment of malaria and other infectious diseases. Application of the leaf latex of A. pulcherrima on preparative silica gel TLC led to the isolation of two C-glycosylated anthrones, identified as nataloin (1) and 7-hydroxyaloin (2) by spectroscopic techniques (UV, IR, ¹H- and 13C-NMR, HR-ESIMS). Both the latex and isolated compounds displayed antimalarial activity in a dose-independent manner using a four-day suppressive test, with the highest percent suppression of 56.2% achieved at 200 mg/kg/day for 2. The results indicate that both the leaf latex of A. pulcherrima and its two major constituents are endowed with antiplasmodial activities, which support the traditional use of the leaves of the plant for the treatment of malaria.