RESUMO
Prunella vulgaris L. (P. vulgaris) has great application value and development prospects in improving sleep. In this study, we continued to evaluate the sleep-improvement function and mechanism of P. vulgaris from both chemical characterization and function based on sleep-improvement functional ingredients, rosmarinic acid and salviaflaside, screened out in the previous stage as the index components. The chemical constituents of P. vulgaris and its phenolic acid fraction were characterized by the UPLC-MSn technology. The quality of the sleep-improvement phenolic acid fraction of P. vulgaris was scientifically evaluated by fingerprints combined with quantitative analysis of rosmarinic acid and salviaflaside. The function of phenolic acid parts of P. vulgaris in improving sleep was verified by different insomnia models including the PCPA-induced insomnia model and surface platform sleep deprivation model. HE staining was used to observe the effect of P. vulgaris on the morphology of nerve cells in different brain regions. In vivo experiments and molecular docking explored the sedative-hypnotic effects of functional ingredients of P. vulgaris. All these results investigated the material basis and mechanism of P. vulgaris to improve sleep from multiple perspectives, which contribute to providing a basis for the development of functional food to improve sleep.
Assuntos
Depsídeos , Extratos Vegetais , Prunella , Ácido Rosmarínico , Sono , Prunella/química , Animais , Sono/efeitos dos fármacos , Depsídeos/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Masculino , Cinamatos/análise , Simulação de Acoplamento Molecular , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Hidroxibenzoatos/análise , Camundongos , Hipnóticos e Sedativos/farmacologiaRESUMO
Metabolites identification is crucial to develop functional foods or perform quality control. Prunella vulgaris (Xia-Ku-Cao) is a medicinal and edible plant used as the herbal medicine or main additive in functional beverage. However, current analytical strategies can only on-line characterize tens of compounds, restricted by insufficient chromatographic resolution and low coverage of the mass spectrometric scan methods. This work was designed to characterize the wide-polarity components from the ear of P. vulgaris. The total extract was fractionated by semi-preparative high-performance liquid chromatography into the retained medium-polarity fraction and unretained polar fraction, which were further analyzed by offline two-dimensional liquid chromatography (2D-LC) and hydrophilic interaction chromatography, respectively. Data-independent high-definition MSE of the Vion™ ion mobility time-of-flight mass spectrometer was utilized enabling the high-coverage acquisition of collision-induced dissociation-MS2 data. The offline 2D-LC, configuring the XBridge Amide and HSS T3 columns, gave high orthogonality (0.81) and effective peak capacity (1555). Automatic peak annotation facilitated by the UNIFI™ bioinformatics platform and comparison with 62 reference compounds achieved the efficient and more reliable structural elucidation. We could characterize 255 compounds from P. vulgaris, with numerous phenylpropanoid phenolic acids and triterpenoid O-glycosides newly reported. Especially, collision cross section (CCS) prediction and targeted isolation of three compounds assisted in the identification of 39 groups of isomers. Additionally, 17 hydrophilic compounds, involving oligosaccharides and organic acids, were characterized from the unretained polar fraction. Conclusively, the in-depth metabolites identification of P. vulgaris was accomplished, and the results can benefit the development and better quality control of this valuable plant.
Assuntos
Interações Hidrofóbicas e Hidrofílicas , Extratos Vegetais , Prunella , Prunella/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Espectrometria de Mobilidade Iônica/métodosRESUMO
BACKGROUND: The pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. PURPOSE: This study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). METHODS: High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. RESULTS: A total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. CONCLUSION: XKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS.
Assuntos
Modelos Animais de Doenças , Doença de Graves , Luteolina , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Prunella , Linfócitos T Reguladores , Animais , Luteolina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Doença de Graves/tratamento farmacológico , Feminino , Linfócitos T Reguladores/efeitos dos fármacos , Prunella/química , Camundongos , Células T Auxiliares Foliculares/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Glândula Tireoide/efeitos dos fármacos , Antioxidantes/farmacologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacosRESUMO
Prunella vulgaris (PV) is one of the most commonly used nutraceuticals as it has been proven to have anti-inflammatory and antioxidant properties. The aim of this study was to evaluate the phytochemical composition of PV and its in vivo antioxidant properties. A phytochemical analysis measuring the total phenolic content (TPC), the identification of phenolic compounds by HPLC-DAD-ESI, and the evaluation of the in vitro antioxidant activity by the DPPH assay of the extract were performed. The antioxidant effects on inflammation induced by turpentine oil were experimentally tested in rats. Seven groups with six animals each were used: a control group, the experimental inflammation treatment group, the experimental inflammation and diclofenac sodium (DS) treatment group, and four groups with their inflammation treated using different dilutions of the extract. Serum redox balance was assessed based on total oxidative status (TOS), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), total thiols, and an oxidative stress index (OSI) contents. The TPC was 0.28 mg gallic acid equivalents (GAE)/mL extract, while specific representatives were represented by caffeic acid, p-coumaric acid, dihydroxybenzoic acid, gentisic acid, protocatechuic acid, rosmarinic acid, vanillic acid, apigenin-glucuronide, hesperidin, kaempferol-glucuronide. The highest amount (370.45 µg/mL) was reported for hesperidin, which is a phenolic compound belonging to the flavanone subclass. The antioxidant activity of the extracts, determined using the DPPH assay, was 27.52 mmol Trolox/mL extract. The PV treatment reduced the oxidative stress by lowering the TOS, OSI, NO, and MDA and by increasing the TAC and thiols. In acute inflammation, treatment with the PV extract reduced oxidative stress, with lower concentrations being more efficient and having a better effect than DS.
Assuntos
Antioxidantes , Inflamação , Estresse Oxidativo , Compostos Fitoquímicos , Extratos Vegetais , Prunella , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Ratos , Prunella/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Masculino , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Fenóis/farmacologia , Fenóis/análise , Ratos WistarRESUMO
Prunella vulgaris, aptly named for its withering at the summer solstice, displays significant variation in quality arising from differing harvest time. However, research on the chemical composition changes of its spikes at various stages is limited, and the specific metabolites remain unclear. In order to elucidate the metabolites and metabolic pathways of the spikes of P. vulgaris, the current study deployed ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) and targeted metabolomics to characterize the compound variability in the spikes of P. vulgaris across different periods. Multivariate statistical techniques such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to identify the differences in metabolites, and relevant metabolic pathways were analyzed. A total of 602 metabolites were identified by metabolomics, of which organic acids and their derivatives were the most abundant, followed by flavonoids. Multiple differential metabolites, including p-hydroxybenzoic acids and gallic acids were identified based on variable importance in projection(VIP)>1 and P<0.05. The results of enrichment analysis suggested that isoflavonoids biosynthesis, aminobenzoate degradation, benzoate degradation, anthocyanins biosynthesis, metabolic pathways, microbial metabolism in different environments, secondary plant metabolite biosynthesis, tryptophan metabolism, and phenylpropanoid synthesis were the main metabolic pathways. These results intend to elucidate the dynamic changes of differential metabolites of P. vulgaris and provide a theoretical basis for further study of the harvesting mechanism of spikes of P. vulgaris.
Assuntos
Metabolômica , Prunella , Espectrometria de Massas em Tandem , Prunella/química , Prunella/metabolismo , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão , Metabolômica/métodos , Espectrometria de Massa com Cromatografia LíquidaRESUMO
Artificial nanozymes (enzyme-mimics), specifically metallic nanomaterials, have garnered significant attention recently due to their reduced preparation cost and enhanced stability in a wide range of environments. The present investigation highlights, for the first time, a straightforward green synthesis of biogenic platinum nanoparticles (PtNPs) from a natural resource, namely Prunella vulgaris (Pr). To demonstrate the effectiveness of the phytochemical extract as an effective reducing agent, the PtNPs were characterized by various techniques such as UV-vis spectroscopy, High-resolution Transmission electron microscopy (HR-TEM), zeta-potential analysis, Fourier-transform infrared spectroscopy (FTIR), and Energy dispersive spectroscopy (EDS). The formation of PtNPs with narrow size distribution was verified. Surface decoration of PtNPs was demonstrated with multitudinous functional groups springing from the herbal extract. To demonstrate their use as viable nanozymes, the peroxidase-like activity of Pr/PtNPs was evaluated through a colorimetric assay. Highly sensitive visual detection of H2O2 with discrete linear ranges and a low detection limit of 3.43 µM was demonstrated. Additionally, peroxidase-like catalytic activity was leveraged to develop a colorimetric platform to quantify glutamate biomarker levels with a high degree of selectivity, the limit of detection (LOD) being 7.00 µM. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) test was used to explore the scavenging nature of the PtNPs via the degradation of DPPH. Overall, the colorimetric assay developed using the Pr/PtNP nanozymes in this work could be used in a broad spectrum of applications, ranging from biomedicine and food science to environmental monitoring.
Assuntos
Antioxidantes , Ácido Glutâmico , Peróxido de Hidrogênio , Nanopartículas Metálicas , Platina , Prunella , Platina/química , Nanopartículas Metálicas/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análise , Antioxidantes/química , Antioxidantes/análise , Antioxidantes/farmacologia , Prunella/química , Ácido Glutâmico/análise , Ácido Glutâmico/química , Extratos Vegetais/químicaRESUMO
PURPOSE: To investigate and systematically describe the mechanism of action of Prunella vulgaris (P. vulgaris) against digestive system tumors and related toxicity reduction. METHODS: This study briefly describes the history of medicinal food and the pharmacological effects of P. vulgaris, focusing on the review of the anti-digestive tumor effects of the active ingredients of P. vulgaris and the mechanism of its toxicity reduction. RESULTS: The active ingredients of P. vulgaris may exert anti-tumor effects by inducing the apoptosis of cancer cells, inhibiting angiogenesis, inhibiting the migration and invasion of tumor cells, and inhibiting autophagy. In addition, P. vulgaris active ingredients inhibit the release of inflammatory factors and macrophages and increase the level of indicators of oxidative stress through the modulation of target genes in the pathway to achieve the effect of toxicity reduction. CONCLUSION: The active ingredients in the medicine food homology plant P. vulgaris not only treat digestive system tumors through different mechanisms but also reduce the toxic effects. P. vulgaris is worthy of being explored more deeply.
Assuntos
Prunella , Prunella/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Animais , Estresse Oxidativo/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/químicaRESUMO
Prunella vulgaris (PV) is a medicine and food homologous plant, but its quality evaluation seldom relies on the polysaccharides (PVPs). In this work, we established the multi-level fingerprinting and in vitro anti-inflammatory evaluation approaches to characterize and compare the polysaccharides of P. vulgaris collected from the major production regions in China. PVPs prepared from 22 batches of samples gave the content variation of 5.76-24.524 mg/g, but displayed high similarity in the molecular weight distribution. Hydrolyzed oligosaccharides with degrees of polymerization 2-14 were characterized with different numbers of pentose and hexose by HILIC-MS. The tested 22 batches of oligosaccharides exhibited visible differences in peak abundance, which failed to corelate to their production regions. All the PVPs contained Gal, Xyl, and Ara, as the main monosaccharides. Eleven batches among the tested PVPs showed the significant inhibitory effects on NO production on LPS-induced RAW264.7 cells at 10 µg/mL, but the exerted efficacy did not exhibit correlation with the production regions. Conclusively, we, for the first time, investigated the chemical features of PVPs at three levels, and assessed the chemical and anti-inflammatory variations among the different regions of P. vulgaris samples.
Assuntos
Prunella , Prunella/química , Estrutura Molecular , Polissacarídeos/farmacologia , Polissacarídeos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , OligossacarídeosRESUMO
Prunellae Spica is the dried spica of Prunella vulgaris belonging to Labiatae and it is widely used in pharmaceutical and general health fields. As a traditional Chinese medicine cultivated on a large scale, it produces a large amount of non-medicinal parts, which are discarded because they are not effectively used. To analyze the chemical constituents in the different samples from spica, seed, stem, and leaf of P. vulgaris, and explore the application value and development prospect of these parts, this study used ultrahigh performance liquid chromatography-tandem quadrupoles time of flight mass spectrometry(UPLC-Q-TOF-MS/MS) to detect chemical constituents in different parts of P. vulgaris. As a result, 117 compounds were detected. Among them, 87 compounds were identified, including 32 phenolic acids, 8 flavonoids, and 45 triterpenoid saponins. Some new triterpenoid saponins containing the sugar chain with 4-6 sugar units were found. Further, multivariate statistical analysis was conducted on BPI chromatographic peaks of multiple batches of different parts, and the results showed that spica had the most abundant chemical constituents, including salviaflaside and linolenic acid highly contained in the seed and phenolic acids, flavonoids, and triterpenoid saponins in the stem and leaf. In general, the constituents in the spica were composed of those in the seed, stem, and leaf. UPLC was used to determine the content of 6 phenolic acids(danshensu, protocatechuic acid, protocatechuic aldehyde, caffeic acid, salviaflaside, and rosmarinic acid) in different parts. The content of other phenolic acids in the seed was generally lower than that in the spica except that of salviaflaside. The content of salviaflaside in the spica was higher than that in the stem and leaf, but the content of other phenolic acids in the spica was not significantly different from that in the stem. The content of protocatechuic aldehyde and caffeic acid in the spica was lower than that in the leaf. DPPH free radical scavenging method was used to detect the antioxidant activity of four parts, and there was no significant difference in the antioxidant activity between the spica and the stem and leaf, but that was significantly higher than the seed. Moreover, the antioxidant activity of these parts was correlated with the content of total phenolic acids. Based on the above findings, the stem and leaf of P. vulgaris have potential application value. Considering the traditional medication rule, it is feasible to use the whole plant as a medicine. Alternatively, salviaflaside, occurring in the seed, can be used as a marker compound for the quality evaluation of Prunellae Spica, if only using spica as the medicinal part of P. vulgaris, as described in the Chinese Pharmacopoeia(2020 edition).
Assuntos
Prunella , Saponinas , Triterpenos , Antioxidantes/química , Espectrometria de Massas em Tandem/métodos , Prunella/química , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Cafeicos , Flavonoides/análise , Triterpenos/análise , AçúcaresRESUMO
Five new triterpenoids, including four ursane types (1-4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6-20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1-20). The results indicated that (7-9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73-71.41 µM (cisplatin as positive control, IC50 14.49 ± 0.97 µM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.
Assuntos
Citostáticos , Prunella , Neoplasias da Glândula Tireoide , Triterpenos , Humanos , Prunella/química , Simulação de Acoplamento Molecular , Triterpenos Pentacíclicos/química , Triterpenos/farmacologia , Estrutura MolecularRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The genus Prunella L. (Lamiaceae) is represented by nine species in the world and four species in Turkey. The infusion prepared from the aerial parts of Prunella vulgaris L. is used internally for abdominal pain and as an expectorant, the decoction prepared from all parts is used internally or externally as a wound healing. AIM OF THE STUDY: This study aims to investigate the wound healing potential of Prunella vulgaris L. on the scientific platform. MATERIAL AND METHODS: The aerial parts of the plant were extracted with 80% methanol. The resulting aqueous methanol extract was partitioned with n-hexane and ethyl acetate, and sub-extracts were obtained. The wound healing effects of the methanol extract and sub-extracts were studied in mice and rats using linear incision and circular excision wound models, and the anti-inflammatory effect was investigated using acetic acid-induced capillary permeability test. Isolation studies were performed using the ethyl acetate sub-extract, which exhibited the highest activity. RESULTS: Using various chromatographic methods, 6 compounds were isolated from the ethyl acetate sub-extract. The structures of the compounds were identified as methyl arginolate, ursolic acid, chlorogenic acid, rosmarinic acid, methyl 3-epimaclinate, and ethyl rosmarinate by spectroscopic techniques (UV, IR, 13C-NMR, 1H-NMR, 2D-NMR, MS). The wound healing mechanisms of the pure compounds were investigated by performing assays to inhibit the enzymes hyaluronidase, collagenase, and elastase. Ursolic acid, chlorogenic acid, and rosmarinic acid were found to be responsible for the anti-inflammatory and wound healing effects. CONCLUSION: The experimental study revealed that Prunella vulgaris showed significant wound healing and anti-inflammatory activities.
Assuntos
Anti-Inflamatórios , Extratos Vegetais , Prunella , Cicatrização , Animais , Anti-Inflamatórios/farmacologia , Ácido Clorogênico/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Metanol , Camundongos , Extratos Vegetais/farmacologia , Prunella/química , Ratos , Triterpenos/farmacologia , Cicatrização/efeitos dos fármacos , Ácido Rosmarínico , Ácido UrsólicoRESUMO
BACKGROUND: Prunella vulgaris , family Lamiaceae also known as self-heal, has been traditionally used as an expectorant, anti-inflammatory, anti-pyretic, and anti-rheumatic. Due to the widespread distribution of the plant, Vulgaris is also called 'vulgar' in Latin adjective meaning common. OBJECTIVE: The objective of this review was to describe the relevant aspects of phytochemistry and therapeutic uses of different fractions as well as isolated compounds from Prunella vulgaris . An attempt was also made to enumerate the possible leads, e.g . betulinic acid, oleanolic acid, ursolic acid, umbelliferone, scopoletin, esculetin, luteolin, homoorientin, Rosmarinic acid and cinaroside, for further development. METHOD: For peer-reviewed research literature, we undertook a structured search of bibliographic databases using a focused review question. Scientific databases such as PubMed, Scopus, Science Direct, and Google Scholar were searched. RESULTS: Phytochemistry of Prunella vulgaris (PV) after a thorough literature survey revealed varied and copious metabolites, such as triterpenoids, phenolic acid, sterols, carbohydrates, coumarins, fatty acids, and volatile oils. Many of these compounds have been found to possess a wide range of biological activities per se, including anti-microbial, immunosuppressive, anti-cancer, cardio- protective, anti-allergic and anti-inflammatory activities. CONCLUSION: Prunella vulgaris is a medicinal plant of immense medicinal importance having a variety of compounds, such as triterpenoids, phenolic acid, sterols, carbohydrates, coumarins, fatty acids, and volatile oils, and diversity in the pharmacological spectrum. The plant could be further exploited to isolate the various biologically active constituents responsible for its activity.
Assuntos
Óleos Voláteis , Prunella , Triterpenos , Cumarínicos , Ácidos Graxos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Prunella/química , EsteróisRESUMO
BACKGROUND: Prunella vulgaris L. (PV) has been used to treat autoimmune thyroiditis (AIT), but the underlying mechanism remains unknown. The present study was designed to evaluate the effect of PV on AIT and explore the role of high-mobility group box-1 (HMGB1) signaling in PV-mediated effects in vivo and in vitro. METHODS: In the present study, bioactive components of PV were identified using UPLC-ESI-MS. The protective effects and potential mechanisms critical for the anti-inflammatory and immunomodulatory effects of PV in AIT were investigated in a rat model of thyroglobulin-induced experimental autoimmune thyroiditis (EAT) and in lipopolysaccharide (LPS)-induced thyroid follicular cells (TFCs). RESULTS: The main bioactive compound identified in PV was rosmarinic acid. The thyroid volume, thyroiditis inflammation score and serum thyroglobulin antibody levels of EAT rats were attenuated by PV treatment (P<0.01). In addition, PV significantly reduced the elevated levels of the proinflammatory cytokines TNF-α, IL-6, IL-1ß and monocyte chemoattractant protein-1 (MCP-1) both in vivo (P<0.01) and in vitro (P<0.05). PV downregulated HMGB1 mRNA and protein expression, reduced HMGB1 secretion, and inhibited TLR9 signaling pathways (TLR9 and MyD88) in PV-treated EAT rats and TFCs. Moreover, PV reversed the increases in the numbers of splenic Th1, Th2, and Th17 cells. Finally, our results acquired following administration of ethyl pyruvate, an HMGB1 inhibitor, to splenocytes cultured in vitro supported the hypothesis that the HMGB1/TLR9 pathway is involved in the PV-mediated reductions in Th1, Th2 and Th17 cells. CONCLUSION: PV decreased the activity of the TLR9/MyD88 pathway and proinflammatory cytokines through HMGB1. In addition, we are the first to show that PV attenuated the HMGB1-induced increases in Th1, Th2 and Th17 cells in AIT models. These findings provide new evidence for the potential therapeutic value of PV as a treatment for AIT and other autoimmune diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia , Prunella/química , Tireoidite Autoimune/tratamento farmacológico , Animais , Anti-Inflamatórios/isolamento & purificação , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Proteína HMGB1/metabolismo , Lipopolissacarídeos , Ratos , Ratos Endogâmicos Lew , Transdução de Sinais/efeitos dos fármacos , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Tireoidite Autoimune/imunologia , Receptor Toll-Like 9/metabolismoRESUMO
BACKGROUND: Prunella vulgaris (PV), a traditional Chinese medical herb, is considered beneficial for some thyroid diseases. However, the effectiveness is not consistent in different studies. This review compiles the evidence from randomized controlled trials (RCTs) and quantifies the effects of PV preparation on thyroid nodules. METHODS: Eight databases were searched up to April 2021 to identify eligible studies. Only RCTs were included. Meta-analysis of homogeneous studies was performed by RevMan5.3 software. Cochrane risk of bias assessment tool version 2.0 was used to assess the risk of bias of each trial. The research screening, data extraction, and risk of bias assessment were employed by 2 reviewers independently, and disagreement will be decided by a third senior reviewer. The risk ratio (RR), mean difference (MD) and corresponding 95% confidence interval (CI) of each study are summarized. RESULTS: Thirteen RCTs with 1468 patients were included in this study. A meta-analysis showed that the RR of the clinical efficacy of PV combined with levothyroxine sodium tablets was 1.22 (95% CI [1.11, 1.33]). The MD of thyroid nodule diameter was -0.43 (95% CI [-0.63, -0.22]). The MD of free triiodothyronine and free tetraiodothyronine levels was -1.99 (95% CI [-3.14, -0.86]) and -3.20 (95% CI [-5.50, -0.89]), respectively. The RR of the adverse reaction rate was 0.67 (95% CI [0.36, 1.22]), and the RR of the clinical efficacy of PV preparation combined with thyroxin tablets was 1.29 (95% CI [1.03, 1.62]). CONCLUSIONS: PV combined with levothyroxine sodium tablets or thyroxin tablets has more benefits for thyroid nodules, further improving the clinical efficiency, reducing the diameter of nodules and reducing the occurrence of adverse reactions. However, the quality of these studies is uncertain, and higher quality and more RCTs are needed to provide comprehensive evidence-based medical evidence in the future.
Assuntos
Lamiaceae/efeitos adversos , Prunella/efeitos adversos , Nódulo da Glândula Tireoide/tratamento farmacológico , Estudos de Casos e Controles , Composição de Medicamentos/métodos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Iodeto Peroxidase/sangue , Lamiaceae/química , Masculino , Medicina Tradicional Chinesa/métodos , Prunella/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Nódulo da Glândula Tireoide/patologia , Tiroxina/administração & dosagem , Tiroxina/uso terapêutico , Resultado do Tratamento , Tri-Iodotironina/sangueRESUMO
Vulgarisins are members of diterpenoids with rare 5/6/4/5 ring skeleton from Prunella vulgaris Linn. (P. vulgaris). Their molecular scaffolds comprise different hydroxylation and degree of esterification. Vulgarisins have attracted many attentions in the fields of food and medicine for their potent bioactivities. Firstly, four reference compounds were analyzed by higher-energy collisional dissociation mass spectrometry (HCD MS/MS) and the fragmentation patterns for molecular scaffold were summarized. And then, a high-performance liquid chromatography/electrospray ionization/high-resolution mass spectrometry (HPLC-ESI-HR-MS) method was adopted to investigate the P. vulgaris extracts. Finally, the proposed analysis results were successfully applied to facilitate the discovery of the vulgarisins analogues from P. vulgaris. For the four reference compounds, the sodium adduct was the predominate ion in full scan. A specific fragmentation pathway of [M+Na]+ ions leads to produce diagnostic ions of vulgarisins at m/z 325 under HCD, which was formed through consecutive-side chains lost. Twenty-three diterpenoids, including 18 vulgarisins analogues, were identified or tentatively characterized in the botanical extracts of P. vulgaris based on their elemental constituents and characteristic fragment ion profiles. Two new vulgarisins analogues in the plant were isolated and their structures were illustrated based on extensive spectroscopic analysis using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy. The HCD MS/MS method, including the profiles of the diagnostic ions induced by characteristic fragmentation, is an effective technique for the discovery of vulgarisins analogues in P. vulgaris. The expected fragmentation pattern knowledge will also facilitate the analysis of other natural products.
Assuntos
Extratos Vegetais/química , Prunella/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
Prunella vulgaris is a widely used edible Chinese medicinal plant. In the present study, two new abietane-type diterpenoids, abietoquinones A (1) and B (2), were isolated from this plant by an immunosuppressive bioassay-guided isolation procedure. Their structures were elucidated unambiguously by NMR spectroscopic analysis, single-crystal X-ray crystallography, and electronic circular dichroism calculations. Compounds 1 and 2 bear a cyclohex-2-ene-1,4-dione moiety, which is uncommon among abietane diterpenes. Also, abietoquinone A (1) suppressed murine splenocyte proliferation and decreased the production of proinflammatory cytokines induced by concanavalin A (Con A) in vitro. In Con A-challenged mice, preinjection with 1 significantly ameliorated liver injury. Additionally, abietoquinone A (1) exhibited inhibitory activities against the proliferation of murine splenocytes and human T cells induced by anti-CD3/anti-CD28 monoclonal antibodies (mAbs).
Assuntos
Abietanos/farmacologia , Hepatite Autoimune/tratamento farmacológico , Substâncias Protetoras/farmacologia , Prunella/química , Abietanos/isolamento & purificação , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Concanavalina A , Citocinas , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Substâncias Protetoras/isolamento & purificação , Baço/citologia , Linfócitos T/efeitos dos fármacosRESUMO
Until now, antiviral therapeutic agents are still urgently required for treatment or prevention of SARS-coronavirus 2 (SCoV-2) virus infection. In this study, we established a sensitive SCoV-2 Spike glycoprotein (SP), including an SP mutant D614G, pseudotyped HIV-1-based vector system and tested their ability to infect ACE2-expressing cells. Based on this system, we have demonstrated that an aqueous extract from the Natural herb Prunella vulgaris (NhPV) displayed potent inhibitory effects on SCoV-2 SP (including SPG614 mutant) pseudotyped virus (SCoV-2-SP-PVs) mediated infections. Moreover, we have compared NhPV with another compound, Suramin, for their anti-SARS-CoV-2 activities and the mode of their actions, and found that both NhPV and Suramin are able to directly interrupt SCoV-2-SP binding to its receptor ACE2 and block the viral entry step. Importantly, the inhibitory effects of NhPV and Suramin were confirmed by the wild type SARS-CoV-2 (hCoV-19/Canada/ON-VIDO-01/2020) virus infection in Vero cells. Furthermore, our results also demonstrated that the combination of NhPV/Suramin with an anti-SARS-CoV-2 neutralizing antibody mediated a more potent blocking effect against SCoV2-SP-PVs. Overall, by using SARS-CoV-2 SP-pseudotyped HIV-1-based entry system, we provide strong evidence that NhPV and Suramin have anti-SARS-CoV-2 activity and may be developed as a novel antiviral approach against SARS-CoV-2 infection.
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Tratamento Farmacológico da COVID-19 , COVID-19/virologia , Extratos Vegetais/farmacologia , Prunella/química , SARS-CoV-2/efeitos dos fármacos , Suramina/farmacologia , Internalização do Vírus/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Neutralizantes/farmacologia , COVID-19/genética , COVID-19/metabolismo , Linhagem Celular , Chlorocebus aethiops , Quimioterapia Combinada , Humanos , Mutação , Ligação Proteica , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Prunella vulgaris L. (P. vulgaris) is a medicinal plant belonging to the Labiatae family, and its dried spikes is called as Xiakucao in China, which is a common traditional Chinese medicine with the activities of clearing the liver and expelling fire, improving eyesight, dispersing nodules and detumescence. Modern pharmacological studies have proved that P. vulgaris has various pharmacological activities such as immunomodulatory, antiviral, antibacterial and anti-insomnia activities. AIMS OF THIS REVIEW: P. vulgaris have been reported to have anti-insomnia effects. Nevertheless, the pharmacodynamic substance basis of this anti-insomnia effect is still unclear. The aim of this study was to identify the active components responsible for evoking the anti-insomnia effect of P. vulgaris and to evaluate its anti-insomnia effect. MATERIALS AND METHODS: In this study, we proposed a method combined with pharmacodynamic experiments, extraction and enrichment of chemical components, and the plasma pharmacochemistry to screen out the anti-insomnia components of P. vulgaris. Firstly, the active eluted fraction of the ethanol extract was screened out based on pharmacodynamic tracing method, and then the chemical composition was analyzed systematically by UPLC-MS/MS. Thirdly, pharmacodynamic tracing method and silica gel column chromatography were employed to screen out the active fraction of 70% ethanol eluted fraction, and its bioactive components in vitro and in vivo were identified by UPLC-MS/MS. Finally, screening out the anti-insomnia components of P. vulgaris by comparing the difference between in vivo and in vitro components, and three potentially bioactive ingredients were validated experimentally. RESULTS: It was confirmed that the fraction eluted with 70% ethanol from macroporous adsorption resin column was responsible for the anti-insomnia efficacy, and 55 compounds were identified or preliminarily identified. Then totally 9 compounds in vitro and 12 compounds in vivo from the active fraction of 70% ethanol eluted fraction were tentatively identified. Among them, mangiferin, rosmarinic acid and salviaflaside were the prototype components of P. vulgaris, which indicated that the three compounds might play the key role in the anti-insomnia activities. In vivo, compared to blank control group, the three compounds significantly shortened the sleeping latency and prolonged the sleeping time produced by pentobarbital sodium. CONCLUSIONS: This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris. This is the first study on screening out the active ingredients responsible for evoking the anti-insomnia effect of P. vulgaris. The three compounds of P. vulgaris may help develop one or more drugs to prevent or treat insomnia. Further investigations are recommended to define the mechanism of the anti-insomnia activity of P. vulgaris.
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Extratos Vegetais/farmacologia , Prunella/química , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Animais , Cromatografia Líquida de Alta Pressão , Cinamatos/isolamento & purificação , Cinamatos/farmacologia , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fenilpropionatos/isolamento & purificação , Fenilpropionatos/farmacologia , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Xantonas/isolamento & purificação , Xantonas/farmacologia , Ácido RosmarínicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional use of Prunella vulgaris is for the treatment of liver cancer in a few areas of China. At present, it is used primarily for the treatment of thyroid cancer, throat cancer, and lymphosarcoma among others. However, there are few current scientific reports regarding its use for the treatment of liver cancer. In this paper, the effective treatment for liver cancer is studied to provide an experimental basis for the application of Prunella vulgaris, which is related to preparations in the treatment of liver cancer. AIM OF THE STUDY: To study the anti-hepatocarcinoma effect of Prunella vulgaris total flavonoids and explores the possible molecular mechanism. METHODS: The effects of Prunella vulgaris total flavonoids on the proliferation of SMMC-7721 cells were respected by RTCA analysis system. The tumor volume and weight were found in H22 tumor bearing mice. ELISA was used to observe the apoptosis and autophagy protein expressions in tumor tissue homogenate, along with the immune serum factor. Tumor tissue apoptosis was respected by the TUNEL method. And Bax, Bcl2, PI3K, Akt, mTOR, Beclin-1 and LC3-I/LC3-II expression were observed through Western blot. We also observed the expression of Beclin-1 and LC3-I/LC3-II through immunohistochemistry. RESULTS: The total flavonoids of Prunella vulgaris inhibited the activity of SMMC-7721 cells, and reduced the tumor volume and weight in H22 tumor bearing mice. HE staining showed that the Prunella vulgaris total flavonoids inhibited liver metastasis of H22 tumor. The Prunella vulgaris total flavonoids significantly made the expressions of IL-6, TNF-α and IFN-γ immune factors increasing in the serum of tumor bearing mice, and the contents of caspase-3 and caspase-9 increase as well in tumor tissue homogenate. TUNEL showed that the mean density in the intervention group was significantly higher than that in the control group. P62 content in tumor tissue homogenate increased and ATG5 decreased after intervention. Immunohistochemistry showed Beclin-1 expression decreased and LC3-I/LC3-II increased in the tumor tissue. Western blot showed Bcl2, Beclin-1 expression decreased and Bax, PI3K, Akt, mTOR, LC3-I/LC3-II increased in the tumor tissue. CONCLUSION: Prunella vulgaris total flavonoids have an obvious anti-hepatocarcinoma effect, and the mechanism may be linked to the inhibition of autophagy and promotion of apoptosis in liver cancer cells. The inhibition of autophagy may be related to activation of the PI3K/Akt/mTOR pathway.
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Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Prunella/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/análise , Flavonoides/uso terapêutico , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Metástase Neoplásica , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: As a well-known herb used in the treatment of colon adenocarcinoma (COAD), Spica Prunellae (SP) shows favorable clinical effect and safety in China for many years, but its active ingredients and therapeutic mechanisms against COAD remain poorly understood. Therefore, this study aims to uncover active ingredients and mechanisms of SP in the treatment of COAD using a combined approach of network pharmacology and bioinformatics. METHODS: A comprehensive approach mainly comprised of target prediction, network construction, pathway and functional enrichment analysis, and hub genes verification was adopted in the current study. RESULTS: We collected 102 compounds-related genes and 3549 differently expressed genes (DEGs) following treatment with SP, and 64 disease-drug target genes between them were recognized. In addition, a total of 25 active ingredients in SP were identified. Pathway and functional enrichment analyses suggested that the mechanisms of SP against COAD might be to induce apoptosis of colon cancer cells by regulating PI3K-Akt and TNF signaling pathways. Recognition of hub genes and core functional modules was performed by constructing protein-protein interaction (PPI) network, from which TP53, MYC, MAPK8 and CASP3 were found as the hub target genes that might play an important part in therapy for COAD. Subsequently we further compared the differential expression level and assessed the prognostic value of these four hub genes. These result of verification suggested that SP exerted therapeutic effects against COAD via a PPI network involving TP53, MYC, MAPK8 and CASP3. CONCLUSION: In this study, active ingredients and mechanisms of SP in the treatment of COAD were systematically discussed, which provided the foundation for further experimental studies and might act to promote its appropriate clinical application.