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Objective To explore the possible mechanism of Radix Paeoniae Alba on hepatic fibrosis based on network pharmacology. Methods Tcmsp database was used to screen the active components of Paeonia alba. With the help of PubChem and Swiss target prediction database, the potential action targets of the effective components of Paeonia Alba were predicted. GeneCards and OMIM databases were used to screen the corresponding targets of liver fibrosis, and venn2.1.0 was used to obtain the common targets of white peony and liver fibrosis. Cytoscape 3.9.0 software was used to build the network diagram of “white peony - active ingredients - intersection target - liver fibrosis” and to predict the main active sites. String database was used to draw the PPI network. Go analysis of effective targets and enrichment analysis of KEGG in pathway were performed by David database. Results Six effective components, 213 targets of Paeonia Alba and 155 hepatic fibrosis targets were screened. There were 49 targets of Radix Paeoniae Alba in the treatment of liver fibrosis. The main active ingredients are kaempferol, paeoniflorin, mairin and β-Sitosterol. Go enrichment analysis showed 269 biological processes, 30 cell compositions, 64 molecular functions, and 67 pathways in KEGG pathway enrichment analysis. Conclusion The mechanism of anti-hepatic fibrosis of Radix Paeoniae Alba has been preliminarily studied through network pharmacology, which shows that Radix Paeoniae Alba has multi-component, multi-target, and multi-channel effects, and provides reference for further experimental research.
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Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.
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The goal of this work was to investigate the antidepressant fraction from Radix Paeoniae Alba and identify its major chemical constituents. Corticosterone injured rat phaeochromocytoma (PC12) cells and behavioral despair depression models of mice were used to evaluate the antidepressant effects of Radix Paeoniae Alba (Bai-Shao) ethanol extract (BS-E) and its three fractions (BS-10E, BS-60E, BS-95E) isolated by macroporous resin column chromatography. Animal experimental procedures were approved by the Animal Ethics Committee of the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: SLXD-20210618051). The results showed that BS-E, BS-10E and BS-60E had protective effects against PC12 cells injury induced by corticosterone, among which BS-60E had the strongest protective effect. BS-60E could significantly shorten the time of forced swimming and tail suspension in despair depression models of mice, and was identified as the antidepressant fraction of Radix Paeoniae Alba. The major chemical constituents in the antidepressant fraction were identified by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and their proposed fragmentation pathways in MS spectra were deduced. A total of 79 chemical constituents were identified from BS-60E, including 36 monoterpenes, 34 polyphenols, 6 oligosaccharides, and 3 other constituents, and monoterpenes and polyphenols may be major effective constituents of BS-60E.
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Elucidating the active components of traditional Chinese medicine(TCM)is essential for understanding the mechanisms of TCM and promote its rational use as well as TCM-derived drug development.Recent studies have shown that surface plasmon resonance(SPR)technology is promising in this field.In the present study,we propose an SPR-based integrated strategy to screen and analyze the major active components of TCM.We used Radix Paeoniae Alba(RPA)as an example to identify the compounds that can account for its anti-inflammatory mechanism via tumor necrosis factor receptor type 1(TNF-R1).First,RPA extraction was analyzed using an SPR-based screening system,and the potential active in-gredients were collected,enriched,and identified as paeoniflorin and paeonol.Next,the affinity con-stants of paeoniflorin and paeonol were determined as 4.9 and 11.8 μM,respectively.Then,SPR-based competition assays and molecular docking were performed to show that the two compounds could compete with tumor necrosis factor-α(TNF-α)while binding to the subdomain 1 site of TNF-R1.Finally,in biological assays,the two compounds suppressed cytotoxicity and apoptosis induced by TNF-α in the L929 cell line.These findings prove that SPR technology is a useful tool for determining the active in-gredients of TCM at the molecular level and can be used in various aspects of drug development.The SPR-based integrated strategy is reliable and feasible in TCM studies and will shed light on the eluci-dation of the pharmacological mechanism of TCM and facilitate its modernization.
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OBJECTIVE: To investigate the absorption mechanism of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis and Siwu Decoction. METHODS: The circulatory perfusion technique was used in this study, the concentrations of paeoniflorin and phenol red in intestinal absorption circulation were respectively determined by HPLC and UV. The effects of pH value, drug concentration, absorption site and P-gp on the absorption of paeoniflorin were investigated separately. RESULTS: By comparing the absorption of paeoniflorin in Radix Paeoniae Alba, both of Radix Paeoniae Alba and Radix Angelica Sinensis, and Siwu Decoction, it was found that in the sample solution at the same absorption site, pH value and concentration (based on the concentration of paeoniflorin), the absorption, Ka and cumulative absorption of paeoniflorin in compound Siwu decoction group were significantly increased compared with the other groups (P<0.05), while t1/2 was significantly decreased (P<0.05). When combined with the inhibitor and inducer of P-gp, the absorption of paeoniflorin showed significant increase or decrease in the amount of absorption, Ka and cumulative absorption% compared with the control group (P<0.05), and t1/2 also showed significant decrease or increase (P<0.05). CONCLUSION: The absorption of paeoniflorin could be affected by P-gp, and under the same conditions, the absorption of paeoniflorin in complicated Chinese herbal formula is better than that in the single herb and herb-pair.
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Radix Paeoniae Alba, one of the common Chinese medicinal materials, comes from the dried root of Paeonia lactiflora Pall, and mainly contains monoterpene glycosides, triterpenoids, flavonoids, tannins and other chemical constituents. At present, 140 chemical constituents have been isolated from Radix Paeoniae Alba, including 55 volatile oils, 33 monoterpenes and their glycosides, 13 flavonoids, 10 tannins, 9 organic acids, 9 triterpenes, 4 mixed terpenoids, 4 steroids and 3 phenylethanol glycosides. Modern pharmacological research has showed that Radix Paeoniae Alba has anti-inflammatory, liver protecting, analgesic, blood nourishing and other pharmacological effects. This paper summarizes the research results of chemical composition and pharmacological action of Radix Paeoniae Alba, in order to provide reference for expanding the clinical application and further development of Radix Paeoniae Alba.
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This study analyzed the effect of the Radix Bupleuri-Radix Paeoniae Alba herb pair on endogenous metabolites in rats with chronic unpredictable mild stress (CUMS)-induced depression by using LC-MS liver metabolomics. Rats were randomly divided into 5 groups: a normal control group, a CUMS model group, a venlafaxine-positive group, and a high-low dose group for the Radix Bupleuri-Radix Paeoniae Alba herb pair, with continuous modeling and administration over 28 days. The efficacy of Radix Bupleuri-Radix Paeoniae Alba herb pair was evaluated by measuring traditional pharmacodynamic indicators of depression (body weight, open field test, sucrose preference test and forced swimming test). Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036). Liver metabolic profiles were obtained by the UHPLC-Q Exactive Orbitrap-MS metabolomics technique. The results show that the Radix Bupleuri-Radix Paeoniae Alba herb pair can significantly decrease depression-like behavior of rats in the CUMS model group. Increases in 25 depression-related metabolites were identified by LC-MS metabonomics, and the Radix Bupleuri-Radix Paeoniae Alba herb pair could significantly decrease 16 of them. Metabolic pathway analysis showed that D-glutamine and D-glutamate metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and glutathione metabolism were the main metabolic pathways altered by this herb pair in CUMS model rats.
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Objective: To establish the HPLC fingerprint of the chemical components of the decoction of Radix Paeoniae Alba(RPA)and determine the content of paeoniflorin, so as to provide a scientific method for the quality char- acterization and control of RPA and establish a correlation between the quality of standard granules in classical prescrip- tion and the quality of RPA. Methods: Thermo Syncronis C18(250 mm×4.6 mm, 5 μm)chromatographic column was used, the mobile phase was constituted by acetonitrile(A)and 0.05 % phosphate aqueous solution(B), the detection wavelength was 230 nm, the column temperature was 30℃, the flow rate was 1.0 ml/min, and the injection volume was 20 μl;the gradient eluting procedure was 0-15 min, 5% A-15% A;15-45 min, 15% A-25% A;45-65 min, 25% A-50% A. Results: The HPLC fingerprint of RPA was established, 11 common peaks were identified by HPLC-Q-TOFMS/ MS, and the similarity of 10 batches were evaluated. The content determination of paeoniflorin in 10 batches of RPA decoction-lyophilized powders was also completed. Conclusion: This study provides a scientific and reliable method for the quality characterization and control of RPA as well as a reference for the quality characterization and control of the standard decoction and granules.
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Objective To evaluate the clinical efficacy and adverse reaction of acitretin combined with total glucosides of peony for patients with psoriasis.Methods Clinical controlled trials that compared acitretin with combination therapy of acitretin and total glucosides of peony for patients with psoriasis were searched in the Cochrane Library,PubMed,Embase and so on(from establishment to October 2016).All extractive data analysis was performed by Review Manage version 5.3 after the data was extracted and the quality was assessed according to the inclusion criteria.Results A total of 8 articles were included.The results of meta-analysis showed that the total effective rate[OR=3.15,95％CI(2.04,4.86),P0.05).Conclusion Acitretin combined with total glucosides of peony for patients with psoriasis can improve the clinical efficacy and reduce the incidence of adverse reaction.
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Objective To explore the medication rules of State Medical MasterYan Zhenghua. Methods The prescriptions containing Radix Paeoniae Alba that prescribed by Pro. Yan were collected to build a database based on traditional Chinese Medicine(TCM)inheritance assist system. After analyzed by the statistical reports module and the data analysis module which were from TCM inheritance assist system, and the methods of data-mining that including association rules and apriori algorithm, the frequency of single medicine, the frequency of drug combination, the association rules between drugs and core drug combinations which all were including Radix Paeoniae Alba can be get from the database.Results The prescriptions including Radix Paeoniae Alba were commonly used to treat megrim, stomach-ache, acid regurgitation and other syndromes. The highest frequency used drugs were Radix PaeoniaeRubra, PericarpiumCitriReticulatae, Radix SalviaeMiltiorrhizae, Radix AngelicaeSinensis, Poria, and so on. The most frequency drug combinations were “RadxPaeoniae Alba, Radix PaeoniaeRubra”, “Radix SalviaeMiltiorrhizae, Radix Paeoniae Alba”, and “Radix Paeoniae Alba, PericarpiumCitriReticulatae”. The drug association rules that the confidence was more than once were “Radix PaeoniaeRubra - Radix Paeoniae Alba”, “OsDraconis - Concha Ostreae”, “Radix AngelicaeSinensis,RadixPaeoniaeRubra - Radix Paeoniae Alba”, and “Radix PaeoniaeRubra, HerbaTaxilli - Radix Paeoniae Alba”, and so on.Conclusions The drugs in the prescriptions containing Radix Paeoniae Alba that built by Pro. Yan mostly had the effects of enriching the blood and invigorating the circulation of blood, relieve uneasiness of mind and body tranquilization, which reflected the clearly thought when constructing prescriptions.
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Objective To investigate the HPLC fingerprint of the EtOAc extract, the major bioactive extract of Radix Paeoniae Alba (RPA), a traditional Chinese medicine from Paeonia lactiflora Pall., quantitatively determine main components in the EtOAc extract and perform fast RPA quality evaluation by the HPLC method using RPA samples from different areas of China to afford a useful method for the RPA quality control. Methods A Waters HPLC equipment with a 2996 photodiode array detector(PDA) was used for HPLC, and the PDA detector was set to scan a range from 200-400 μm. HPLC was carried out on a Scincehome C18 column (4. 6 mm × 250 mm, 5 μm)using acetonitrile-aqueous phosphoric acid solution (pH 2.7) in a linear gradient at 1. 0 ml/min of the flow rate as mobile phase, and each 10 μl of sample solutions was injected to the column. HPLC chromatograms for fingerprint analysis were taken at 230 nm, and the fingerprint analysis was performed both by the similarity analysis and the hierarchical cluster analysis(HCA) methods. Results A standard fingerprint of RPA was obtained, where 11 peaks have been assigned using reference compounds. The similarity analysis and HCA upon the fingerprints from 33 batches of RPA samples gave grossly consistent results to divide these RPA into two categories. Moreover, an HPLC method to simultaneously determine 6 main components in RPA was established and applied to quantitatively determine the 6 components in 11 RPA samples purchased from different areas of China. Conclusion The quality evaluation of RPA by fingerprinting coupled with simultaneous determination of multi-components showed higher specificity and provided a useful HPLC method for quality control of RPA.
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Objective To evaluate the effect of total glucosides of paeony (TGP) on the expression of interleukin-18 (IL-18) in human HaCaT keratinocytes,and to explore the roles of extracelluar signal-regulated protein kinase1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) signaling pathways in the effect.Methods Some cultured human HaCaT keratinocytes were classified into three groups:control group treated with dimethyl sulfoxide (0.031％),TGP groups treated with 6 different concentrations (0.5,2.5,12.5,62.5,125.0 and 312.5 mg/L) of TGP respectively,inhibitor groups treated with TGP of 125 mg/L after 2-hour pretreatment with PD98059 (an ERK1/2 inhibitor) and SP600125 (a JNK1/2 inhibitor) of 10 μmol/L respectively.After additional culture for 48 hours,reverse transcription (RT)-PCR was performed to measure the mRNA expression level of IL-18,and enzymelinked immunosorbent assay (ELISA) to determine the level of IL-18 protein in the culture supematant of HaCaT cells.Some HaCaT keratinocytes were classified into two groups to be treated with TGP of 125 mg/L for 15,30 and 60 minutes with or without the pretreatment with PD98059 and SP600125 of 10 μmol/L; then,Western blot was carried out to determine the phosphorylation levels of ERK1/2 and JNK1/2 in HaCaT cells.Results The levels of IL-18 mRNA and protein in culture supernatant were significantly increased by TGP of 0.5 and 2.5 mg/L,but decreased by TGP of 62.5 and 125.0 mg/L,and TGP of 125.0 mg/L showed the strongest inhibitory effect.After treatment with TGP of 125.0 mg/L,the level of phosphorylated ERK1/2 in HaCaT cells peaked at 15 minutes (0.448 ± 0.018),decreased to 0.213 ± 0.005 at 30 minutes and 0.217 ± 0.005 at 60 minutes,with significant differences between TGP-treated and untreated cells at 15 minutes (0.448 ± 0.018 vs.0.204 ± 0.005,P＜ 0.05) but not at 30 or 60 minutes (both P ＞ 0.05).The phosphorylation level of ERK1/2 was 0.237 ± 0.010 in HaCaT cells pretreated with PD98059 prior to the treatment with TGP,significantly different from that in HaCaT cells treated with TGP only (P ＜0.01).TGP of 125.0 mg/L had no obvious effect on JNK phosphorylation,and there was no significant difference in the level of phosphorylated JNK1/2 between HaCaT cells untreated and those treated with TGP of 125.0 mg/L for different durations (all P ＞ 0.05).Conclusions TGP can inhibit the expression of IL-18 mRNA and protein in HaCaT cells,likely through the ERK1/2 signaling pathway.
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Objective To optimize the extraction process of Radix Paeoniae Alba in Baijin Capsule by orthogonal experiment.Methods The study employed the extraction rate of paeoniflorin and total glucosides of paeony as evaluation indexes. The orthogonal design was used to investigate effects of solvent volume, extraction time and extraction frequency on extraction results.Results The optimal extracting condition was extracted 3 times, with 14 fold 70% alcohol, 1.5 h for each time. Conclusion The method is simple and steady, which will provide instruction and reference to the production of Baijin Capsule.
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Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract (RPAE). A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS combined with MetaboLynx? software and mass defect filtering (MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.
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In present paper, research achievements of post-harvest handling concerning decorticating, boiling, sul-fur-fumigation, drying and sterilizing as well as quality control of Radix Paeoniae Alba were reviewed. Major prob-lems in the post-harvest handling and quality evaluation of Radix Paeoniae Alba were discussed. Strategies for im-provement in post-harvest handling and quality control were proposed, so that the safety and quality consistency can be assured in the medicinal application of Radix Paeoniae Alba.
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Objective To observe the influence of total glucosides of peony (TGP) combined with leflunomide on serum level of TNF-α,IL-8 in the patients with psoriatic arthritis(PsA) ,to evaluate its efficacy and safety and to preliminarily study its action mechanism .Methods The open clinical study was adopted .36 patients with PsA were treated by TGP combined with leflunomide for 12 weeks .at the same time 20 healthy control were selected .The double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was adopted to detect the level of serum TNF-α and IL-8 before treatment and in 12 weeks after treatmention the two groups .The Psoriasis Area And Severity Index (PASI) was adopted as the main effective index and the Health Assessment Ques-tionaire(HAQ) was taken as the secondary effective index .The level of CRP ,ESR ,TNF-α,IL-8 before and after treatment were an-alysed .Results The serum TNF-α,IL-8 levels before therapy in the poriatic arthritis group were significantly higher than those in the normal control group(P0 .05) .Conclusion TGP combined leflunomide for treating PsA has better effect and better safety ,which could play the role by influencing serum TNF-α,IL-8 levels .
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Objective To evaluate the effects of total glucosides of paeony (TCP) on cell proliferation of and expression of VECF and IL-23 in human HaCaT keratinocytes and their potential mechanisms. Methods MTT assay was performed to detect the cell proliferation of HaCaT cells incubated with various concentrations (0.5 to 312.5 mg/L) of TGP. HaCaT cells were classified into 8 groups, control group without any treatment, TGP groups treated with 6 different concentrations of TGP, SB203580 group treated with TGP of 125 mg/L after 2-hour pretreatment with SB203580 of 10 μmol/L After additional culture, reverse transcription (RT)- PCR and enzyme linked immunosorbent assay (ELISA) were conducted to determine the expression levels of VEGF and IL-23 mRNA and protein, Western blot to test the phosphorylation of p38 mitogen-activated protein kinase (MAPK) in these cells. Results The proliferation of HaCaT cells was promoted by TGP of low concentrations (0.5 and 2.5 mg/L), but inhibited by TGP of equal to or more than 12.5 mg/L, and peaked at the concentration of 125 mg/L. TGP of 0.5 and 2.5 mg/L enhanced the mRNA and protein expressions of VEGF and IL-23, while TGP of 12.5 to 125 mg/L suppressed the expression of VEGF mRNA and protein, and TGP of 62.5 to 125 mg/L downregulated the expression of IL-23 mRNA and protein. The phosphorylation of p38 protein kinase in HaCaT cells was induced by TGP of 125 mg/L in a time-dependant manner. Concretely, the level of phosphorylated p38 kinase in HaCaT cells was 0.3314 ± 0.0245 (peak) at 5 minutes, decreased to 0.2173 ± 0.0189 at 10 minutes (still statistically higher than untreated HaCaT cells) and 0.1664 ± 0.0201 at 30 minutes after treatment with TGP of 125 mg/L. SB203580 attenuated the effect of TGP on p38 phosphorylation, and the level of phosphorylated p38 kinase was 0.1529 ±0.0147 in HaCaT cells pretreated with SB203580 prior to the treatment with TGP. Conclusion TGP can inhibit the cell proliferation of and expressions of VEGF and IL-23 mRNA and protein in HaCaT cells, likely mediated by the p38 MAPK signaling pathway.
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Aim: To establish the HPLC and LC-MC methods for the quality analysis of the different species of Radix Paeoniae Alba cultivated in Bozhou. Methods: The LC-MS method was applied to analyze the chemical composition of the cultivated species, the HPLC method was applied to determine the contents of paeoniforin, ben-zoic acid and paeonivayin in crude drugs and processing products. Results: 10 characteristic peaks were identified by LC-MS with reference standards. The significant difference was observed in the chemical compositions of 3 cultivated species. The significant difference was observed in the chemical compositions of 3 cultivated species. The content of paeoniflorin was increased significantly after traditional processing. The results indicated the 4-year-old pubang and 5-year-old xiantiao are the best cultivated species. Conclusion: The methods are simple, rapid and precise to assess and control the quality of different species of Radix Paeoniae Alba cultivated in Bozhou.
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Objective To determine the content of paeoniflorin with different medicinal parts in Radix Paeoniae Alba and offer a reference for collection and processing. Methods The content of paeoniflorin was measured by HPLC method. Combining air drying with weight relief condition, the content of paeoniflorin was calculated in fresh Radix Paeoniae Alba. Results There was the highest content of paeoniflorin in Radix Paeoniae Alba in 24～48 hours after collection, and the another increasing of the content was founded 120 hours after collection. Conclusion Radix Paeoniae Alba should be processed in 48 hours after collection.
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Objective To study the protective effects of total glycosides of Pacony(TGP) on acute myocardial infarction in dogs.Methods Thirty domestic dogs were randomly divided into 5 groups(6 in each group): model control group,positive control group(ISM),and TGP groups with doses of 2.0,4.0,and 8.0 mg?kg~(-1),respectively.The descending branch of left coronary artery was ligated to construct the model of myocardial infarction in the anesthetic thoraco-opened dogs.The effect of TGP on epicardium electrocardiogram(EECG),myocardial infarction size(MIS) and serum myocardial enzymes were observed.Results Compared with controls,the ischemia degree(∑-ST,P