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ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (called Shaoyao in China) is a common herb cultivated all over the world. In some Asian and European countries, such as China, Japan, South Korea and Britain, P. lactiflora has a long history of ethnomedical uses, which is widely used to relieve pain, treat gynecological diseases, anti-infection and so on. It is attributed to the extensive pharmacological activities of total glucosides of P. lactiflora. Up to now, it is still commonly used in clinical medicine. THE AIM OF THE REVIEW: The paper aims to make a comprehensive review on the botanical characterization and distribution, ethnopharmacology, phytochemistry, biosynthesis pathway, pharmacology, pharmacokinetics and quality control of P. lactiflora, so as to provide new insights and scientific evidence for the subsequent research. MATERIALS AND METHODS: The information of P. lactiflora was obtained from books related to traditional Chinese medicine and electronic databases, including Scifinder, PubMed, Web of Science, CNKI and Google Scholar. RESULTS: P. lactiflora is a kind of herb with a long history and it is used for medicine, food and ornamental, and shows high utilization value. There are 200 compounds have been identified from it, including terpenoids, flavonoids, polyphenols, organic acids and others, among those paeoniflorin, a monoterpenoid glycoside, has multiple activities and is currently the focus of pharmacological research. A great deal of pharmacological experiments supported the anti-inflammatory, anti-oxidant, hepatoprotective, neuroprotective, antibacterial, antitumor, dermatosis treating and other effects of P. lactiflora. In addition, evaluating the quality of P. lactiflora is essential to safe use of drug in humans. CONCLUSIONS: The chemical components of P. lactiflora are diverse and have a wide range of activities. Modern pharmacological studies have provided reliable evidence for the traditional efficacy, such as suppressing liver yang, regulating menstruation and relieving pain. However, there are still some problems to be solved, such as part of the pharmacological mechanism has not been clarified and the biosynthetic pathway of cage-like monoterpenoids remains poorly defined. In addition, further studies on compounds other than paeoniflorin are clearly warranted. It is hoped that P. lactiflora will serve the clinic better in the future.
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Etnofarmacología , Paeonia , Fitoquímicos , Control de Calidad , Paeonia/química , Humanos , Fitoquímicos/farmacología , Fitoquímicos/farmacocinética , Fitoquímicos/química , Fitoquímicos/uso terapéutico , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Fitoterapia , Medicina Tradicional ChinaRESUMEN
Paeonia lactiflora Pall. (PLP) is thought to promote blood circulation and remove blood stasis. This study used blood component analysis, network pharmacology, and molecular docking to predict the mechanism of PLP in the treatment of blood stasis syndrome (BSS). PLP was processed into Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA and PRR could significantly reduce whole blood viscosity (WBV) at 1/s shear rates and could increase the erythrocyte aggregation index (EAI), plasma viscosity (PV), and erythrocyte sedimentation rate (ESR) of rats with acute blood stasis. They prolonged the prothrombin time (PT), and PRR prolonged the activated partial thromboplastin time (APTT). PRA and PRR increased the thrombin time (TT) and decreased the fibrinogen (FBG) content. All the results were significant (p < 0.05). Ten components of Paeoniflorin, Albiflorin, Paeonin C, and others were identified in the plasma of rats using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A protein-protein interaction network (PPI) analysis showed that AKT1, EGFR, SRC, MAPK14, NOS3, and KDR were key targets of PLP in the treatment of BSS, and the molecular docking results further verified this. This study indicated that PLP improves BSS in multiple ways and that the potential pharmacological mechanisms may be related to angiogenesis, vasoconstriction and relaxation, coagulation, and the migration and proliferation of vascular cells.
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Simulación del Acoplamiento Molecular , Farmacología en Red , Paeonia , Paeonia/química , Animales , Ratas , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Viscosidad Sanguínea/efectos de los fármacos , Ratas Sprague-Dawley , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: In vitro single-cell experiments may yield inconsistent results compared to clinical trials. To enhance the reliability of cosmetic active ingredient screening, a coculture model of B16F10-HaCaT cells was established in vitro based on the structural characteristics of human skin, thereby improving the credibility of experimental outcomes. Currently, most cosmetic whitening additives primarily target simple efficacy goals such as inhibiting tyrosinase activity or melanin transfer. Therefore, investigating novel and efficient whitening additives has become a prominent research focus. OBJECTIVES: The aim is to establish an in vitro cell coculture model for more reliable experimental results and investigate the mechanism by which Paeonia lactiflora Pall seeds oil inhibits melanin production and transfer. METHODS: The impact of different concentrations of Paeonia lactiflora Pall seeds oil on cocultured cell proliferation rate was assessed using cck8 assay. Tyrosinase inhibition ability in cocultured cells was tested using levodopa as a substrate. Melanin production inhibition ability in coculture cells was evaluated by lysing cells with sodium hydroxide. The effect of Paeonia lactiflora Pall seeds oil on dendrite-related gene expression levels was examined through qPCR analysis. Additionally, Western blotting was employed to study the effect of Paeonia lactiflora Pall seeds oil on dendrite-related protein expression levels. RESULTS: Different concentrations of Paeonia lactiflora Pall seeds oil did not affect the proliferation activity of cocultured cells. A specific concentration of α-MSH increased cell tyrosinase activity, cellular melanin content, as well as Rac1, Cdc42, and PAR-2 gene and protein expression related to dendritic formation. Treatment with a certain concentration of Paeonia lactiflora Pall seeds oil resulted in decreased tyrosinase activity and melanin content in cells along with downregulated expression levels of Rac1, Cdc42, and PAR-2 genes and proteins associated with dendritic formation. CONCLUSIONS: Paeonia lactiflora Pall seeds oil at specific concentrations exhibits the ability to inhibit tyrosinase activity, decrease melanin content, and possesses the potential to impede melanin transfer.
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Proliferación Celular , Técnicas de Cocultivo , Melaninas , Monofenol Monooxigenasa , Paeonia , Aceites de Plantas , Semillas , Preparaciones para Aclaramiento de la Piel , Paeonia/química , Humanos , Melaninas/biosíntesis , Semillas/química , Aceites de Plantas/farmacología , Monofenol Monooxigenasa/metabolismo , Proliferación Celular/efectos de los fármacos , Preparaciones para Aclaramiento de la Piel/farmacología , Ratones , Animales , Células HaCaTRESUMEN
The plant of Paeonia lactiflora Pall. belongs to Ranunculaceae, and its root can be divided into two categories according to different processing methods, which included that one was directly dried without peeling the root of the P. lactiflora (PR), and the other was peeled the root of the P. lactiflora (PPR) after boiled and dried. To evaluate the difference of chemical components, UPLC-ESI-Q-Exactive Focus-MS/MS and UPLC-QQQ-MS were applied. The distribution of chemical components in different tissues was located by laser microdissection (LMD), especially the different ingredients. A total of 86 compounds were identified from PR and PPR. Four kind of tissues were isolated from the fresh root of the P. lactiflora (FPR), and 54 compounds were identified. Especially the content of gallic acid, albiflorin, and paeoniflorin with high biological activities were the highest in the cork, but they were lower in PR than that in PPR, which probably related to the process. To illustrate the difference in pharmacological effects of PR and PPR, the tonifying blood and analgesic effects on mice were investigated, and it was found that the tonifying blood and analgesic effects of PPR was superior to that of PR, even though PR had more constituents. The material basis for tonifying blood and analgesic effect of the root of P. lactiflora is likely to be associated with an increase in constituents such as paeoniflorin and paeoniflorin lactone after boiled and peeled. The study was likely to provide some theoretical support for the standard and clinical application.
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Glucósidos , Monoterpenos , Paeonia , Raíces de Plantas , Animales , Masculino , Ratones , Analgésicos/farmacología , Analgésicos/química , Analgésicos/análisis , Hidrocarburos Aromáticos con Puentes , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Ácido Gálico/análisis , Ácido Gálico/química , Glucósidos/análisis , Glucósidos/química , Rayos Láser , Cromatografía Líquida con Espectrometría de Masas , Microdisección/métodos , Monoterpenos/farmacología , Monoterpenos/análisis , Monoterpenos/química , Paeonia/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 µM, respectively.
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Óxido Nítrico , Ácido Oleanólico , Paeonia , Fitoquímicos , Raíces de Plantas , Raíces de Plantas/química , Paeonia/química , Ratones , Animales , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/química , Células RAW 264.7 , Estructura Molecular , Óxido Nítrico/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Triterpenos/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/química , China , Macrófagos/efectos de los fármacosRESUMEN
BACKGROUND: Paeonia lactiflora Pall. (PLP) is a plant with excellent ornamental and therapeutic value that can be utilized in traditional Chinese medicine as Paeoniae Radix Alba (PRA) and Paeoniae Radix Rubra (PRR). PRA must undergo the "peeling" process, which involves removing the cork and a portion of the phloem. PLP's biological function is strongly linked to its secondary metabolites, and the distribution of metabolites in different regions of the PLP rhizome causes changes in efficacy when PLP is processed into various therapeutic compounds. METHODS: The metabolites of the cork (cor), phloem (phl), and xylem (xyl) were examined in the roots of PLP using a metabolomics approach based on UPLC-Q-Exactive-Orbitrap-MS/MS (UPLC-MS/MS), and the differential metabolites were evaluated using multivariate analysis. RESULTS: Significant changes were observed among the cor, phl, and xyl samples. In both positive and negative ion modes, a total of 15,429 peaks were detected and 7366 metabolites were identified. A total of 525 cor-phl differential metabolites, 452 cor-xyl differential metabolites, and 328 phl-xyl differential metabolites were evaluated. Flavonoids, monoterpene glycosides, fatty acids, sugar derivatives, and carbohydrates were among the top 50 dissimilar chemicals. The key divergent metabolic pathways include linoleic acid metabolism, galactose metabolism, ABC transporters, arginine biosynthesis, and flavonoid biosynthesis. CONCLUSION: The cor, phl, and xyl of PLP roots exhibit significantly different metabolite types and metabolic pathways; therefore, "peeling" may impact the pharmaceutical effect of PLP. This study represents the first metabolomics analysis of the PLP rhizome, laying the groundwork for the isolation and identification of PLP pharmacological activity, as well as the quality evaluation and efficacy exploration of PLP.
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Medicamentos Herbarios Chinos , Paeonia , Cromatografía Liquida , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem , Paeonia/química , Medicamentos Herbarios Chinos/química , Medicina Tradicional China , MetabolómicaRESUMEN
BACKGROUND: As a traditional Chinese herbal medicine, Paeonia lactiflora Pall is rich in various active ingredients such as polysaccharides and total flavonoids while having ornamental value. It has potential application value in the development of food and cosmetics. OBJECTIVE: To study the in vitro efficacy of Paeonia lactiflora Pall seeds oil. METHODS: Firstly, the levels of linolenic acid and linoleic acid in Paeonia lactiflora Pall seeds oil were quantified using gas chromatography. The impact of Paeonia lactiflora Pall seeds oil on the proliferation rate of B16F10 cells was assessed through the CCK-8 method, while the melanin content of B16F10 cells was determined using the sodium hydroxide lysis method. The inhibitory effects of Paeonia lactiflora Pall seeds oil on elastase, collagenase and hyaluronidase were evaluated by biochemical techniques in vitro. Lastly, the hen's egg chorioallantoic membrane test (HET-CAM) was conducted to confirm the absence of eye irritation caused by Paeonia lactiflora Pall seeds oil. RESULTS: Paeonia lactiflora Pall seeds oil within a certain volume concentration range (0.5%-4%) had no effect on the proliferation of B16F10 cells. Paeonia lactiflora Pall seeds oil showed significant inhibition of elastase, collagenase and hyaluronidase. Notably, the highest concentration tested, 4% Paeonia lactiflora Pall seed oil, yielded the most pronounced outcomes without causing any irritation. CONCLUSION: A certain concentration of Paeonia lactiflora Pall seeds oil has a significant effect on decreasing the melanin content in B16F10 cells and inhibiting the activities of elastase, collagenase, and hyaluronidase, which can provide a reference for the development of pure natural cosmetics raw materials.
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Proliferación Celular , Colagenasas , Hialuronoglucosaminidasa , Melaninas , Paeonia , Elastasa Pancreática , Aceites de Plantas , Semillas , Paeonia/química , Semillas/química , Animales , Ratones , Melaninas/análisis , Elastasa Pancreática/metabolismo , Aceites de Plantas/farmacología , Proliferación Celular/efectos de los fármacos , Colagenasas/metabolismo , Ácido Linoleico/farmacología , Ácido Linoleico/análisis , Cosméticos/química , Cosméticos/farmacología , Melanoma Experimental/tratamiento farmacológico , Ácido alfa-Linolénico/farmacología , Ácido alfa-Linolénico/análisis , Membrana Corioalantoides/efectos de los fármacos , Línea Celular Tumoral , PollosRESUMEN
Skin health is a major concern across the world. The Paeonia lactiflora Pall. flower (PLPF) is well-known in China as an edible ornamental flower, that has been traditionally prescribed for the treatment of irregular menstruation and dysmenorrhea. However, its chemical constituents and bioactivities have not been systematically stuided. This study tentatively identified 27 compounds in aqueous and ethanol extracts of PLPF using ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry, including four monoterpene glycosides, six phenols, six tannins, ten flavonoids and a hydroxycinnamic acid amide. Online antioxidant and tyrosinase inhibitor screening assays based on post-column bioactivity tests were used to screen for bioactive compounds in the extracts. Online and offline bioactivity assays showed that both extracts exhibited notable antioxidant properties against DPPH, ABTS, and FRAP, potent antiglycation capacity, and significant inhibition of tyrosinase, cyclooxygenase-2, and collagenase. Gallic acid derivatives were the main contributors to the antioxidant and antityrosinase capacity and may also inhibit cyclooxygenase-2 and collagenase, but they exhibited weak antiglycation capacity. The antiglycation effects may be due to the synergistic action of gallic acid and specific flavonoids. PLPF is a promising source of bioactive compounds for the development of natural skin health products.
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Introduction: There has been a lack of treatments available to lower the frequency of recurrent aphthous ulcers (RAUs) until now. Total glucosides of paeony (TGP) is a botanical drug extracted from the dried roots of Paeonia lactiflora Pall. [Ranunculaceae; Paeoniae Radix Alba]. This study aims to evaluate the efficacy and safety of TGP in the treatment of RAU. Methods: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1900025623). Patients were randomly assigned to the TGP or placebo group and treated with 1.8 g/day for 24 weeks. Participants were observed for a total of 36 weeks and were asked to record ulcer severity, medication, and adverse reactions in the form of diaries or apps every day. The primary outcome was the monthly ulcer-free interval. Results: A total of 79 individuals were enrolled, with 40 assigned to the TGP group and 39 to the placebo group. The dropout rate was 18.18%. In the TGP group, the monthly ulcer-free interval was significantly longer than baseline (median, 9.6 days) since weeks 13-24 (median, 18.5 days) (p < 0.05), and after discontinuation, it was further prolonged (median, 24.7 days) than in weeks 13-24 (p < 0.05). In addition, the monthly ulcer-free interval was longer in the TGP group than in the placebo group (median, 15.9 days) at weeks 25-36 (p < 0.001). There were better improvements in the monthly number of ulcers and monthly area of ulcers, and visual analog scoring in the TGP group at weeks 25-36 (p < 0.001). Conclusion: TGP had a good long-term therapeutic effect on RAU with frequent occurrence. Systematic Review Registration: www.chictr.org.cn, identifier ChiCTR1900025623.
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ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PL) has been commonly used to de-stressing the liver and relieve depression in traditional Chinese medicine for over a thousand years. Recently, it has been widely used in studies on anti-depressant, anti-inflammatory and regulation of intestinal flora. However, the polysaccharide component has received less attention than the saponin component of PL. AIM OF THE STUDY: This study aimed to elucidate the effects of Paeonia lactiflora polysaccharide (PLP) on depressive behavior in mice in a chronic unpredictable mild stress (CUMS) model and its possible action mechanisms. MATERIALS AND METHODS: A model of chronic depression induced by the CUMS approach. Behavioral experiments were used to assess the success of the CUMS model and the therapeutic impact of PLP. Then the extent of damage to the colonic mucosa was assessed by H&E staining; the extent of neuronal damage was assessed by Nissler staining. Inflammatory factor expression was assessed at different sites in the mouse by enzyme-linked immunoassay (Elisa). The alterations of faecal microflora were detected by 16S rRNA gene sequencing. In the colonic tissues, NLRP3, ASC and Caspase-1 mRNA and protein levels detected by quantitative real-time PCR (qRT-PCR) and Western blot(WB). RUSULTS: PLP can improve depressive behavior in CUMS mice, and colonic mucosal and neuronal damage. Elisa assay showed that PLP could reduce interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) levels, and increase 5-Hydroxytryptamine(5-HT) levels in CUMS mice. 16S sequencing analysis showed that PLP could regulate the intestinal flora of CUMS mice and increase their species richness. In addition, PLP significantly inhibited NLRP3/ASC/Caspase-1 signalling pathways activation in the colonic tissues of CUMS mice. CONCLUSIONS: PLP modulates depression-related intestinal ecological dysregulation, increases species richness, and inhibits inflammatory factors levels and NLRP3 inflammasome activation to reduce colonic mucosal and neurons damage, thereby improving depression-like behavior and neurotransmitter release in CUMS mice.
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Microbioma Gastrointestinal , Paeonia , Ratones , Animales , Depresión/tratamiento farmacológico , Depresión/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Caspasa 1/metabolismo , ARN Ribosómico 16S , Transducción de Señal , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Intersubgeneric hybrids of Paeonia lactiflora (Paeonia lactiflora pall., P. lactiflora.) cover a huge variety of systems in the genus Paeonia. In recent years, many studies have confirmed that the intersubgeneric hybrids of P. lactiflora. are rich in paeoniflorin and other medicinal ingredients, however, it has always proved difficult to clarify the medicinal value of the hybrids and whether they can be used for medicinal purposes. In this study, the consistency of the plant population was evaluated through DUS evaluation, in order to clarify whether the selected research materials had stability and consistency within the population and specificity between populations. The differences between the paeoniflorin contents in the roots of the nine intersubgeneric hybrids of the P. lactiflora. varieties and two medicinal varieties were critically compared. The differences in the chemical components of the roots of nine intersubgeneric hybrids of P. lactiflora. and reference medicine substances of P. lactiflora. and Paeonia anomala subsp. veitchii (Lynch) D. Y. Hong and K. Y. Pan (Paeonia veitchii Lynch., P. veitchii.) were explored via stoichiometric and chemical fingerprint high performance liquid chromatography analyses. The results showed that there were significant differences in the chemical compositions between the intersubgeneric hybrids of P. lactiflora. and the medicinal reference materials, and the contents of paeoniflorin were elevated such that the hybrids could be used as the raw material for extraction of paeoniflorin, thus providing an opportunity to explore the medicinal value of the hybrids. This study explored the key differential components among the varieties and provides a reference and basis for the study of the medicinal value and the identification of the intersubgeneric hybrids of the P. lactiflora. varieties.
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ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao-Gancao Tang (SGT) is a traditional Chinese medicine formulation. It has been used to treat kinds of pain and to alleviate asthma in clinic. However, the mechanism of action is not known. AIM OF THE STUDY: To investigate the anti-asthma effect of SGT involving modulation of the T-helper type 1 (Th1) Th1/Th2 ratio in the gut-lung axis and alteration of the gut microbiota (GM) in rats with ovalbumin (OVA)-induced asthma. MATERIALS AND METHODS: The main constituents of SGT were analyzed by high-performance liquid chromatography (HPLC). A model of asthma was established in rats by OVA-induced allergen challenge. Rats suffering from asthma (RSAs) were treated with SGT (2.5, 5.0 and 10.0 g/kg), dexamethasone (1 mg/kg) or physiologic saline for 4 weeks. The level of immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF) and serum was determined by enzyme-linked immunosorbent assay. Histology of lung and colon tissues was investigated using staining (hematoxylin and eosin and periodic acid-Schiff). The Th1/Th2 ratio and levels of cytokines (interferon (IFN)-γ and interleukin (IL)-4) in the lung and colon were detected by immunohistochemistry. The GM in fresh feces was analyzed by 16 S rRNA gene sequencing. RESULTS: Twelve main constituents (gallic acid, albiflorin, paeoniflorin, liquiritin apioside, liquiritin, benzoic acid, isoliquiritin apioside, isoliquiritin, liquiritigenin, glycyrrhizic acid, isoliquiritigenin and glycyrrhetinic acid) of SGT were simultaneously determined by HPLC. SGT treatment (5.0 and 10.0 g/kg) was found to reduce the IgE level (a vital marker of hyper-responsiveness) in BALF and serum, improve typical morphological changes (inflammatory-cell infiltration and goblet cell metaplasia) in the lung and colon, alleviate airway remodeling (including bronchiostenosis and basement membrane-thickening) in the lung, significantly decrease the IL-4 level and increase the IFN-γ level in the lung and colon, which led to restoration of the IFN-γ/IL-4 ratio. The dysbiosis and dysfunction of GM in RSAs were modulated by SGT. The abundance of bacteria of the genera Ethanoligenens and Harryflintia was increased in RSAs and was decreased upon SGT treatment. The abundance of Family_XIII_AD3011_group was decreased in RSAs and increased upon SGT treatment. Moreover, SGT therapy increased the abundance of bacteria of the genera Ruminococcaceae_UCG-005 and Candidatus_Sacchrimonas, and decreased that of Ruminococcus_2 and Alistipes. CONCLUSIONS: SGT ameliorated rats with OVA-induced asthma via regulation of the Th1/Th2 ratio in the lung and gut, and modulated the GM.
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Asma , Microbioma Gastrointestinal , Ratas , Animales , Ratones , Ovalbúmina/farmacología , Interleucina-4 , Asma/inducido químicamente , Asma/tratamiento farmacológico , Asma/patología , Pulmón , Líquido del Lavado Bronquioalveolar , Citocinas/farmacología , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad , Células Th2/patologíaRESUMEN
The roots of Paeonia lactiflora Pall., (Paeoniae Radix, PL) are a well-known herbal remedy used to treat fever, rheumatoid arthritis, systemic lupus erythematosus, hepatitis, and gynecological disorders in East Asia. Here we evaluated the genetic toxicity of PL extracts (as a powder [PL-P] and hot-water extract [PL-W]) in accordance with the Organization for Economic Co-operation and Development guidelines. The Ames test revealed that PL-W was not toxic to S. typhimurium strains and E. coli in absence and presence of the S9 metabolic activation system at concentrations up to 5000 µg/plate, but PL-P produced a mutagenic response to TA100 in the absence of S9 mix. PL-P was cytotoxic in in vitro chromosomal aberrations (more than a 50 % decrease in cell population doubling time), and it increased the frequency of structural and numerical aberrations in absence and presence of S9 mix in a concentration-dependent manner. PL-W was cytotoxic in the in vitro chromosomal aberration tests (more than a 50 % decrease in cell population doubling time) only in the absence of S9 mix, and it induced structural aberrations only in the presence of S9 mix. PL-P and PL-W did not produce toxic response during the in vivo micronucleus test after oral administration to ICR mice and did not induce positive results in the in vivo Pig-a gene mutation and comet assays after oral administration to SD rats. Although PL-P showed genotoxic in two in vitro tests, the results from physiologically relevant in vivo Pig-a gene mutation and comet assays illustrated that PL-P and PL-W does not cause genotoxic effects in rodents.
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Aberraciones Cromosómicas , Paeonia , Extractos Vegetales , Animales , Ratones , Ratas , Daño del ADN , Escherichia coli , Ratones Endogámicos ICR , Paeonia/toxicidad , Ratas Sprague-Dawley , Extractos Vegetales/toxicidad , Raíces de Plantas/toxicidad , Salmonella typhimuriumRESUMEN
Abscisic acid (ABA) is a major phytohormone affecting seed dormancy and germination in plants. ABA is synthesized mainly through the C40 carotenoid pathway. In the ABA biosynthesis pathway, 9-cis-epoxycarotenoid dioxygenase (NCED) is a key rate-limiting enzyme that regulates the accumulation and content of ABA. However, the role of the NCED gene in perennial plants with complex seed dormancy remains largely unknown. Here, we cloned two differentially expressed paralogs of herbaceous peony NCED genes, named PlNCED1 and PlNCED2, and further identified their involvement in seed dormancy from perennial herbaceous peony experiencing complex double seed dormancy. The deduced PlNCED amino acid sequences had high sequence homology with NCED sequences from other plants and contained the typical conserved RPE65 domain of the NCED family. Phylogenetic analysis showed that PlNCED1 and PlNCED2 have a close relationship with PoNCED in Paeonia ostii and VvNCED6 in Vitis vinifera, respectively. A subcellular localization assay demonstrated that the PlNCED1 protein resided within the nucleus, while the PlNCED2 protein was located in the cytoplasm, indicating their different roles in the biosynthesis of ABA. Furthermore, the content of endogenous ABA in transgenic calluses showed that PlNCEDs were positively correlated with ABA content. Both PlNCED transgenic Arabidopsis lines and the functional complementation of Arabidopsis NCED mutants found that PlNCEDs promoted seed dormancy and delayed seed germination. These results reveal that PlNCEDs participate in the seed dormancy of herbaceous peony by regulating the accumulation of endogenous ABA.
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The aims of this work were to obtain total glucosides of paeony (TGP) with high content of paeoniflorin and evaluate the hepo-protective properties of TGP. After optimization by response surface methodology, optimized conditions were as follows: extraction time 33.0 min, extraction temperature 48 °C, ethanol content 44%, and the yield of TGP was 47.68 mg/g. Moreover, under established macroporous resin purification, paeoniflorin content of TGP achieved 67.6% in 1.5 L scale-up verification experiment. Purified TGP (p-TGP) was further analyzed by UHPLC-Q-Orbitrap-MS/MS, and 35 compouds including paeoniflorin were identified. The obtained p-TGP effectively reduced biochemical indexes and inflammatory cytokines in liver tissue of acute alcoholic liver injury mice model. Depending on this work, TGP with definitive compound composition exhibited great protective effect against acute alcoholic liver injury in vivo. Furthermore, the finding of this work will be helpful to understand the relationship between compound composition and functional properties of Chinese herb extracts.
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Glicósidos , Paeonia , Ratones , Animales , Glicósidos/farmacología , Paeonia/química , Espectrometría de Masas en Tándem , Glucósidos/farmacologíaRESUMEN
Paeonia lactiflora Pall. (P. lactiflora) is a famous ornamental plant with showy and colorful flowers that has been domesticated in China for 4,000 years. However, the genetic basis of phenotypic variation and genealogical relationships in P. lactiflora population is poorly understood due to limited genetic information, which brings about bottlenecks in the application of effective and efficient breeding strategies. Understanding the genetic basis of color-related traits is essential for improving flower color by marker-assisted selection (MAS). In this study, a high throughput sequencing of 99 diploid P. lactiflora accessions via specific-locus amplified fragment sequencing (SLAF-seq) technology was performed. In total, 4,383,645 SLAF tags were developed from 99 P. lactiflora accessions with an average sequencing depth of 20.81 for each SLAF tag. A total of 2,954,574 single nucleotide polymorphisms (SNPs) were identified from all SLAF tags. The population structure and phylogenetic analysis showed that P. lactiflora population used in this study could be divided into six divergent groups. Through association study using Mixed linear model (MLM), we further identified 40 SNPs that were significantly positively associated with petal color. Moreover, a derived cleaved amplified polymorphism (dCAPS) marker that was designed based on the SLAF tag 270512F co-segregated with flower colors in P. lactiflora population. Taken together, our results provide valuable insights into the application of MAS in P. lactiflora breeding programs.
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Paeonia lactiflora Pall. is known as the king of herbaceous flowers with high ornamental and precious medicinal value. However, the lack of a stable genetic transformation system has greatly affected the research of gene function in P. lactiflora. The Agrobacterium-mediated transient gene expression is a powerful tool for the characterization of gene function in plants. In this study, the seedlings of P. lactiflora were used as the transformation receptor materials, and the efficient transient transformation system with a GUS reporter gene was successfully established by Agrobacterium harboring pCAMBIA1301. To optimize the system, we investigated the effects of germination time, Agrobacterium cell density, infection time, acetosyringone (AS) concentration, co-culture time, negative pressure intensity, Tween-20 concentration and different receptor materials on the transient transformation efficiency of P. lactiflora. The results showed that the highest transient transformation efficiency (93.3%) could be obtained when seedlings in 2-3 cm bud length were subjected to 12 h infection of resuspension solution comprising 1.2 OD600 Agrobacterium, 200 µM AS and 0.01% Tween-20 under 10 of negative pressure intensity followed by 3 days of co-culture in darkness condition. This method is more suitable for the study of gene function in P. lactiflora. Subsequently, stress resistance genes PlGPAT, PlDHN2 and PlHD-Zip were used to verify the effectiveness of this transformation system. These results can provide critical information for identification of key genes in non-model plants, such as P. lactiflora, and promote the development of molecular biology research for P. lactiflora.
RESUMEN
Bupleurum chinense DC (Chaihu)-Paeonia lactiflora Pall (Baishao) is among the most accepted herb pairs in many classic antidepressant prescriptions. Our previous study has shown that the Chaihu-Baishao herb pair (CBHP) had a better antidepressant effect than Chaihu or Baishao. Nevertheless, the synergistic antidepressant mechanism of this herb pair was not clearly understood. This study aimed to investigate the compatibility mechanism of Chaihu and Baishao for treating depression through a strategy of non-targeted metabolomics combined with targeted quantitative analysis and molecular biology techniques. First, the compatibility effects of CBHP were assessed by the chronic unpredictable mild stress (CUMS) rat model. Next, cortex metabolomics based on ultra-high-performance liquid chromatography combined with quadrupole orbitrap mass spectrometry (UPLC-Q-Orbitrap/MS) was used to discover the metabolic pathway that was synergistically regulated by CBHP. Based on the results of metabolomics analysis, metabolites were quantitatively validated by UPLC-MS/MS combined with the MRM mode in the crucial metabolic pathway. In addition, the signaling pathway associated with this metabolic pathway was detected by molecular biology techniques to further identify the biological meaning of the crucial metabolite on the synergistic antidepressant effect of CBHP. The antidepressant effect of CBHP was significantly better than that of Chaihu or Baishao single administrated in the behavioral test. According to cortex metabolomics, a total of 21 differential metabolites were screened out, and purine metabolism was selected as the crucial metabolic pathway by the enrichment analysis of differential metabolites. Subsequently, purine metabolism was confirmed as disorder in the CUMS group by targeted quantitative analysis, CBHP regulated more purine metabolites (six) than individual administration (two and two). The results showed that purine metabolism was modulated by CBHP through synergistically decreasing xanthine levels and inhibiting the conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XOD). Finally, the synergistic regulation effect of CBHP on xanthine synthesis was found to be related to inhibition of malondialdehyde (MDA) production, Nod-like receptor protein 3 (NLRP3) inflammasome expression, and interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α secretion. The present study demonstrated that the regulation of purine metabolism, the suppression of oxidative stress, and inflammatory responses in the cortex were involved in the synergistic antidepressant effect of CBHP.
RESUMEN
Paeonia lactiflora Pall., one of the most famous classical herbal medicine, has been used to treat diseases for over 1200 years. In this research, the functional ingredients were purified by online-switch two-dimensional high-speed counter-current chromatography combined with inner-recycling and continuous injection mode. The antioxidant activity was evaluated by investigating the 2,2'-azobis (2-amidinopropane) dihydrochloride-induced oxidant damage in vitro and confirmed through molecular docking. n-Butanol/ethyl acetate/water (2:3:5, v/v) solvent system was used for the first-dimensional separation and optimized the sample loading. Two pure compounds and a polyphenol-enriched fraction were separated. The polyphenol-enriched fraction was separated with a solvent system n-hexane/ethyl acetate/methanol/water (2:8:4:6, v/v) with continuous injection mode. Five compounds were successfully separated, including gallic acid (1), methyl gallate (2), albiflorin (3), paeoniflorin (4), and ethyl gallate (5). Their structures were identified by mass spectrometry and NMR spectroscopy. The results from the antioxidant effect showed that albiflorin had stronger antioxidant activity. Molecular docking results indicated that the affinity energy of the identified compounds ranged from -3.79 to -8.22 kcal/mol and albiflorin showed the lowest affinity energy. Overall, all those findings suggested that the strong antioxidant capacity of albiflorin can be potentially used for the treatment of diseases caused by oxidation.
Asunto(s)
Paeonia , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión/métodos , Distribución en Contracorriente/métodos , Simulación del Acoplamiento Molecular , Paeonia/química , Polifenoles , Solventes , AguaRESUMEN
Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17ß-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-ß2, ß-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3ß in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings.