Simultaneous determination of five compounds of fried Radix Paeoniae Alba extract in beagle dogs plasma by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry and its application in a pharmacokinetic study.

In this present study, we developed a reliable and simple ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin and isomaltopaeoniflorin in beagle dog plasma. We also analyzed the pharmacokinetics of those components after oral administration of fried Radix Paeoniae Alba (FRPA) in beagle dogs. Plasma samples were processed by protein precipitation with methanol. Chromatographic separation was performed with a Waters HSS-T3 C18 column (100 × 2.1 mm, 1.8 µm, kept at 40°C) using multiple reaction monitoring mode. A gradient elution procedure was used with solvent A (0.02% formic acid-water) and solvent B (0.02% formic acid-acetonitrile) as mobile phases. Method validation was performed as US Food and Drug Administration guidelines, and the results met the acceptance criteria. The method we establish in this experiment was successfully applied to the pharmacokinetic study after oral administration of FRPA extract to beagle dogs.

Covalent immobilization of tyrosinase on magnetic multi-walled carbon nanotubes for inhibitor screening.

The inhibition of tyrosinase is considered to be a common therapeutic strategy for some hyperpigmentation disorders. Screening of tyrosinase inhibitors is of great significance to the treatment of pigmentation diseases. In this study, tyrosinase was covalently immobilized on magnetic multi-walled carbon nanotubes for the first time, and the immobilized tyrosinase was applied for ligand fishing of tyrosinase inhibitors from complex medicinal plants. The immobilized tyrosinase was characterized by transmission electron microscopy, atomic force microscopy, Fourier-transform infrared spectroscopy, vibrating sample magnetometry, and thermo-gravimetric analyzer, which indicated that tyrosinase was immobilized onto magnetic multi-walled carbon nanotubes. The immobilized tyrosinase showed better thermal stability and reusability than the free one. The ligand was fished out from Radix Paeoniae Alba and identified as 1,2,3,4,6-pentagalloylglucose by ultra-performance liquid chromatography-quadrupole time-of-flight high-resolution mass spectrometry. 1,2,3,4,6-pentagalloylglucose was found to be a tyrosinase inhibitor with similar half maximal inhibitory concentration values of 57.13 ± 0.91 µM compared to kojic acid (41.96 ± 0.78 µM). This work not only established a new method for screening tyrosinase inhibitors but also holds considerable potential for exploring the new medicinal value of medicinal plants.

Identification of geographical origins of Radix Paeoniae Alba using hyperspectral imaging with deep learning-based fusion approaches.

The Radix Paeoniae Alba (Baishao) is a traditional Chinese medicine (TCM) with numerous clinical and nutritional benefits. Rapid and accurate identification of the geographical origins of Baishao is crucial for planters, traders and consumers. Hyperspectral imaging (HSI) was used in this study to acquire spectral images of Baishao samples from its two sides. Convolutional neural network (CNN) and attention mechanism was used to distinguish the origins of Baishao using spectra extracted from one side. The data-level and feature-level deep fusion models were proposed using information from both sides of the samples. CNN models outperformed the conventional machine learning methods in classifying Baishao origins. The generalized Gradient-weighted Class Activation Mapping (Grad-CAM++) was utilized to visualize and identify important wavelengths that significantly contribute to model performance. The overall results illustrated that HSI combined with deep learning strategies was effective in identifying the geographical origins of Baishao, having good prospects of real-world applications.

Rapid evaluation of Radix Paeoniae Alba and its processed products by near-infrared spectroscopy combined with multivariate algorithms.

It is well known that the processing method of herbal medicine has a complex impact on the active components and clinical efficacy, which is difficult to measure. As a representative herb medicine with diverse processing methods, Radix Paeoniae Alba (RPA) and its processed products differ greatly in clinical efficacy. However, in some cases, different processed products are confused for use in clinical practice. Therefore, it is necessary to strictly control the quality of RPA and its processed products. Giving that the time-consuming and laborious operation of traditional quality control methods, a comprehensive strategy of near-infrared (NIR) spectroscopy combined with multivariate algorithms was proposed. This strategy has the advantages of being rapid and non-destructive, not only qualitatively distinguishing RPA and various processed products but also enabling quantitative prediction of five bioactive components. Qualitatively, the subspace clustering algorithm successfully differentiated RPA and three processed products, with an accuracy rate of 97.1%; quantitatively, interval combination optimization (ICO), competitive adaptive reweighted sampling (CARS), and competitive adaptive reweighted sampling combined with successive projections algorithm (CARS-SPA) were used to optimize the PLS model, and satisfactory results were obtained in terms of wavelength selection. In conclusion, it is feasible to use NIR spectroscopy to rapidly evaluate the effect of processing methods on the quality of RPA, which provides a meaningful reference for quality control of other herbal medicines with numerous processing methods.

The most bioactive fraction of stir-fried Radix Paeoniae Alba regulating IL-6/STAT3 signaling pathway in allergic asthma mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Paeoniae Alba (RPA), a traditional Chinese medicine, has been used frequently in the treatment of asthma. Previous studies demonstrated the dichloromethane fraction of Stir-Frying RPA (FDCM) enhanced the effect of anti-allergic asthma compared with the dichloromethane fraction of RPA (DCM). AIM OF THE STUDY: The significant increasing of Paeoniflorin (PF), ethyl gallate (EG), 1,2,3,4,6-pentagalloylglucose (PGG) had been observed in FDCM. This study aimed to investigate the effects and mechanisms of these compounds from FDCM in ovalbumin (OVA)-induced allergic asthma mouse model. MATERIALS AND METHODS: The significant difference contents compounds fraction (FB-40) and other fractions in FDCM were enriched by Medium Pressure Liquid Chromatography (MPLC). The pharmacodynamics was verified among all fractions in OVA-induced allergic asthma mice. Moreover, the drug dose dependence of FB-40 (0.42 mg/kg, 0.21 mg/kg, and 0.07 mg/kg), which were the most active fraction from FDCM for anti-allergic asthma, was explored. The expression of IL-6, p-STAT3, and STAT3 was analyzed by Western blot analysis. In addition, the main components of FB-40 were identified by UPLC with standards. Finally, the anti-inflammatory effects of the main components from FB-40 were detected by LPS-stimulated BEAS-2B cells using an Elisa assay. RESULTS: The results showed that FB-40 was the most active fraction from FDCM, which could significantly improve the lung tissue pathological condition, and decrease the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). It had greater pharmacological activity than its main component PF. FB-40 also showed dose dependence and regulated the IL-6/STAT3 signaling pathway in allergic asthma mice. Besides, PF, Albiflorin (AF), PGG, EG, and 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) from FB-40 were identified by UPLC with the standard. At last, in the LPS-induced BEAS-2B cell experiments, EG, PGG, 1,2,3,6-Tetra-O-galloyl-ß-D-glucose (TGG) showed stronger inhibiting activities of cytokine than the monoterpenoid glycosides (PF and AF). CONCLUSION: The research proved that FB-40 was an active fraction in FDCM, which regulates IL-6/STAT3 Signaling Pathway to ameliorate allergic asthma. Gallic acids including TGG and PGG, and EG also play a role in the treatment of allergic asthma in FB-40.

Exploring the Target and Mechanism of Radix Paeoniae Alba on Sjogren's Syndrome.

BACKGROUND: Radix Paeoniae Alba is a traditional Chinese herbal medicine. It can accelerate salivary secretion and alleviate the dry mouth of patients with Sjogren's syndrome (SS). Although it is widely used in clinical treatment, its target and mechanism remain unclear. OBJECTIVE: This study aims to analyze the main components of Radix Paeoniae Alba, explore the target genes, and propose the possible mechanism for Radix Paeoniae Alba's acceleration of salivary secretion. METHODS: The main active components and potential targets of Radix Paeoniae Alba were searched through the TCMSP database. Efforts were made to search for the related genes of Sjogren's syndrome in OMIM and GeneCards databases. Cytoscape v3.8.0 software was used to link target genes of active components and key genes of the disease. The software Autodock vina1.1.2. was adopted to simulate the interaction between active components and target genes. Human submandibular gland (HSG) cells were used in vitro experiments to verify the results of our analysis. RESULTS: ß-Sitosterol, the main component of Radix Paeoniae Alba, may intervene in the disease through CHRM3. Molecular docking shows ß-Sitosterol has a high affinity with CHRM3, and the interaction between CHRM3 and ß-Sitosterol is the basis of biological activity. The in vitro experiments showed that ß-Sitosterol could significantly up-regulate the mRNA and protein expression levels of both CHRM3 and secretion-related genes in HSG cells. CONCLUSION: Our study shows that the chemical components of Radix Paeoniae Alba have a positive effect on the related mechanism of salivary secretion. We found that ß-Sitosterol can promote the expression of CHRM3, stimulate salivary secretion, treat Sjogren's syndrome and potentially improve its prognosis.

Identification of the antidepressant fraction and its major chemical constituents of Radix Paeoniae Alba / 药学学报

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.

Mechanism of Radix Paeoniae Alba in the treatment of liver fibrosis based on network pharmacology / 药学实践与服务

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.

A strategy of screening and binding analysis of bioactive components from traditional Chinese medicine based on surface plasmon resonance biosensor.

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 ingredients were collected, enriched, and identified as paeoniflorin and paeonol. Next, the affinity constants 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 ingredients 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 elucidation of the pharmacological mechanism of TCM and facilitate its modernization.

Screening of Bioactive Fraction of Radix Paeoniae Alba and Enhancing Anti-Allergic Asthma by Stir-Frying Through Regulating PI3K/AKT Signaling Pathway.

Allergic asthma is a common respiratory inflammation disease. The crude Radix Paeoniae Alba (RPA) and its processed products have been used frequently as antipyretic and anti-inflammatory agents in traditional medicine. To evaluate the effect of honey and bran processing, different fractions of RPA were used for treating anti-allergic asthma in the ovalbumin (OVA)-induced mice model, and then, the most effective fraction of RPA and stir-frying Radix Paeoniae Alba with honey and bran (FRPA) for treating anti-allergic asthma were compared mutually for pharmacological effects. The results showed that the treatment of the dichloromethane fraction of RPA significantly improved the pathological condition of lung tissues, decreased the number of eosinophils and other cells in bronchoalveolar lavage fluid (BALF), and the increased the expression of various inflammatory factors. Furthermore, the study discovered that the lung pathological conditions, compared with the high dose of dichloromethane RPA fraction, could be ameliorated by high dose of dichloromethane FRPA fraction treatment. Moreover, the expression of inflammatory factors and the phosphorylation of the PI3K/AKT signaling pathway could be diminished by FRPA. Finally, the contents of compounds with a significant difference in the FRPA dichloromethane fraction were paeoniflorin, ethyl gallate, pentagalloylglucose, galloylpaeoniflorin, and others by UPLC/Q-TOF-MS analysis. These findings suggest that the dichloromethane fraction of FRPA has an enhancement effect on anti-allergic asthma and provide the experimental basis for exploring the processed mechanism of RPA.

A strategy of screening and binding analysis of bioactive components from traditional Chinese medicine based on surface plasmon resonance biosensor / 药物分析学报

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.

The Potential Effects of Dielectric Barrier Discharge Plasma on the Extraction Efficiency of Bioactive Compounds in Radix Paeoniae Alba.

Radix paeoniae alba (RPA) is a kind of herbal medicine of traditional Chinese medicine (TCM) that is widely used for the treatment of liver diseases and rheumatoid arthritis in clinical practice. As a result of the low extraction efficiency of RPA by the conventional method, many patients are given high dosages. In this study, four exposure doses of dielectric barrier discharge (DBD) plasma (0, 60, 120, and 180 s) were applied to modify the extraction efficiency of paeoniflorin, benzoylpaeoniflorin, tannic acid, gallic acid, 2'-hydroxy-4'-methoxyacetophenone, and polysaccharide in RPA. Finally, the application of plasma for 180 s exhibited a 24.6% and 12.0% (p < 0.001) increase of tannic acid and polysaccharide contents, however, a 2.1% (p < 0.05) and 5.4% (p < 0.001) reduction of paeoniflorin and gallic acid composition, respectively, and no significant difference (p > 0.05) in results obtained from benzoylpaeoniflorin and 2'-hydroxy-4'-methoxyacetophenone contents. Our results of scanning electron microscopy (SEM), automatic specific surface area and pore analyzer, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermal gravimetric analysis (TGA) indicated that DBD plasma can etch the surface and undergo graft polymerization by reactive species thereby changing the water/oil holding capacity and eventually changing the extraction efficiency of bioactive compounds in RPA. Overall, our observations provide a scientific foundation for modifying the extraction efficiency of bioactive ingredients related to the pharmacological activities of RPA.

Investigation of the antidepressant mechanism of combined Radix Bupleuri and Radix Paeoniae Alba treatment using proteomics analysis of liver tissue.

Depression is a chronic, common mental illness characterized by depressed mood, anxiety, insomnia, cognitive impairment, and even suicidal tendency. In traditional Chinese medicine theory, the cause of depression is deemed to be "stagnation of liver qi". So relieving "stagnation of liver qi" is effective for depression. The combination of Radix Bupleuri and Radix Paeoniae Alba, which is used to soothe the liver and relieve depression, has antidepressant effects, but the mechanisms of the effects are still unclear. In this study, a rat model of chronic unpredictable mild stress was established as a model of depression, and proteomics analysis was used to explore the potential mechanisms of this combination in alleviating depression. Biological information analysis was performed on the selected differential proteins, and the enriched pathways mainly included the Jak-STAT signaling pathway, valine, leucine, and isoleucine degradation, and oxidative phosphorylation. The expression of key proteins included metallothionein-1, cyclin-dependent kinase, ubiquitin carboxyl-terminal hydrolase-1, and Cryab was further verified by western blotting, and the results which were consistent with the proteomics results, confirmed the reliability of the proteomic analysis. The antidepressant mechanism of combined Radix Bupleuri and Radix Paeoniae Alba treatment may be related to the oxidative stress response, neuroplasticity, the immune response, and neuroprotection.

Study on antidepressant mechanism of Radix Bupleuri-Radix Paeoniae Alba herb pair by metabonomics combined with 1H nuclear magnetic resonance and ultra-high-performance liquid chromatography-tandem mass spectrometry detection technology.

OBJECTIVES: Radix Bupleuri-Radix Paeoniae Alba (BP), a traditional Chinese medicine herb pair, has treated depression by coordinating the liver in Chinese classical medicine books and modern research. This study aims to verify the antidepressant effect of BP by behavioural examination, and reveal the underlying antidepressant mechanisms of BP. METHODS: The antidepressant effects in chronic unpredictable mild stress (CUMS) of BP were observed by behavioural indicators and 1H nuclear magnetic resonance (1H-NMR) and ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabonomics techniques combined with the related analysis platforms. KEY FINDINGS: BP could significantly improve the depressive behaviour of CUMS rats. Compared with the model group, body weight (P < 0.05), the number of crossing (P < 0.001) and rearing (P < 0.01) and sucrose preference rate (P < 0.01) were significantly enhanced, and the immobility time was shortened in the forced swimming test (P < 0.001) of the BP group. In metabonomics study, 35 depression-related metabolites were identified by 1H NMR and UHPLC-MS/MS metabonomics by comparing model and control groups. BP could significantly retrieve 17 depression-related metabolites. Thirteen depression-related metabolic pathways were found through Met-PA and BP could regulate seven metabolic pathways. CONCLUSIONS: BP herb pair had significantly antidepressant effect, which provides a basis for further finding drug targets.

Cleavage rules of mass spectrometry fragments and rapid identification of chemical components of Radix Paeoniae Alba using UHPLC-Q-TOF-MS.

INTRODUCTION: Radix Paeoniae Alba (RPA) presents several pharmacological effects, including analgesia, liver protection, and toxicity reduction. RPA consists mostly of monoterpenes and their glycosides, tannins, flavonoids, and organic acids, with monoterpenes being the main active pharmaceutical ingredients. OBJECTIVE: To establish an effective method for rapid classification and identification of the main monoterpenes, flavonoids, and organic acids in RPA. METHODS: We used ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and data post-processing technology to rapidly classify and identify the monoterpenoids, flavonoids, and organic acids in RPA. We also summarised the diagnostic product ions and neutral losses of monoterpenoids, flavonoids, and organic acids in RPA reported in the literature. RESULTS: We identified 24 components, namely 18 monoterpenoids, one flavonoid, and five organic acids. CONCLUSION: In this study, we analysed the chemically active pharmaceutical ingredients and assessed the quality of RPA. In addition, we demonstrated that UHPLC-Q-TOF-MS can be used to qualitatively classify and identify the variety of chemical components of traditional Chinese medicines (TCMs) to a certain extent. Moreover, we confirmed that mass spectrometry can be used to identify the components of TCMs.

Efficacy, Chemical Constituents, and Pharmacological Actions of Radix Paeoniae Rubra and Radix Paeoniae Alba.

Radix Paeoniae Rubra and Radix Paeoniae Alba are the different characteristic forms of Paeonia lactiflora Pall. They are widely used as traditional Chinese medicines in clinical practices. This study analyzes the development history, efficacy, chemical compositions, and pharmacological effects of Radix Paeoniae Rubra and Radix Paeoniae Alba, and explores the causes of the similarities and differences of these two amalgams. It provides a basis for the clinical application of these two Chinese medicinal materials, and lays a foundation for further study of the pharmacological effects and the quality identification of Paeonia lactiflora Pall as it applies to traditional Chinese medicine.

An integrative metabolomics and network pharmacology method for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba on anti-depression.

Depression is a common mental illness, which is caused by 'liver qi stagnationin in traditional Chinese medicine (TCM) theory. Thus, relieving "liver qi stagnation" is considered to be effective at treating depression. The Radix Bupleuri and Radix Paeoniae Alba drug pair is the most classic compatible drug pair for mitigating a great variety of depression symptoms. However, its mechanisms remain largely unclear. In this study, metabolomics and network pharmacology methods were used to explore the potential mechanism of antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair. Analysis of metabolomics results showed that the drug pair can significantly improve CUMS-induced depression. The underlying mechanism of its antidepressant effect involves regulating the expression of brain-derived neurotrophic factors, inhibiting neurotoxicity, and regulating the HPA axis. Network pharmacology showed that drug pairs screened a total of 23 active ingredients and 63 targets, participated in the regulation of protein metabolism, Metabolism, Energy pathways, Cell growth and / or maintenance and other biological processes (BP), and mainly involved multiple signaling pathways and metabolic pathways to jointly exert antidepressant effects. Four related metabolic pathways regulated by the Radix Bupleuri and Radix Paeoniae Alba drug pair were input into the KEGG database to obtain the key genes of the related metabolic pathways. The predicted target of the network pharmacology was compared with the key genes of the metabolic pathway, and the common genes were screened: CYP1A1, CYP1A2; Western blot results showed that the drug pair up-regulated the protein expression of CYP1A1, CYP1A2. The medicine has an antidepressant effect by regulating the action of key enzymes. Metabolomics combined with network pharmacology research strategy revealed that antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair are characterized by multi-component, multi-target and multi-path mechanism of action.

Transcriptomics- and metabolomics-based integration analyses revealed the potential pharmacological effects and functional pattern of in vivo Radix Paeoniae Alba administration.

BACKGROUND: Radix Paeoniae Alba (RPA) and other natural medicines have remarkable curative effects and are widely used in traditional Chinese Medicine (TCM). However, due to their multi-component and multi-target characteristics, it is difficult to study the detailed pharmacological mechanisms for those natural medicines in vivo. Therefore, their real effects on organisms is still uncertain. METHODS: RPA was selected as research object, the present study was designed to study the complex mechanisms of RPA in vivo by integrating and interpreting the transcriptomic based RNA-seq and metabolomic based NMR spectrum after RPA administration in mice. A variety of dimension-reduction algorithms and classifier models were applied to the processing of high-throughput data. RESULTS: Among serum metabolites, the contents of PC and glucose were significantly increased, while the contents of various amino acids, lipids and their metabolites were significantly decreased in mice after RPA administration. Based on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, differential analysis showed that the liver was the site where RPA exerted a significant effect, which confirmed the rationality of "meridian tropism" in the theory in TCM. In addition, RPA played a role in lipid metabolism by regulating genes encoding enzymes of the glycerolipid metabolism pathway, such as 1-acyl-sn-glycerol-3-phosphate acyltransferase (Agpat), phosphatidate phosphatase (Lpin), phospholipid phosphatase (Plpp) and endothelial lipase (Lipg). We also found that RPA regulates several substance addiction pathways in the brain, such as the cocaine addiction pathway, and the related targets were predicted based on the sequencing data from pathological model in the GEO database. The overall effective pattern of RPA was intuitively presented with a multidimensional radar map through a self-designed model which found that liver and brain were mainly regulated by RPA compared with the traditional meridian tropism theory. CONCLUSIONS: Overall this study expanded the potential application of RPA and provided possible targets and directions for further mechanism study, meanwhile, it also established a multi-dimensional evaluation model to represent the overall effective pattern of TCM for the first time. In the future, such study based on the high-throughput data sets can be used to interpret the theory of TCM and to provide a valuable research model and clinical medication reference for the TCM researchers and doctors.

A comparative analysis of raw and processed Radix Paeoniae Alba samples using HPLC, chemometrics, and antioxidant activity.

Radix Paeoniae Alba (RPA) and its processed products are commonly used in traditional Chinese medicine, but the chaos phenomenon among processed products often occurs. In this study, we used multiple chemometric methods to analyze raw and six different processed products of RPA based on HPLC fingerprinting. Heat map analysis was used to assess the changes in chemical composition. Principal component analysis was used for classification, and the samples were divided into four classes: class 1 (raw, wine-processed, and vinegar-processed products), class 2 (bran-processed and soil-processed products), class 3 (stir-fried products), and class 4 (coke products). Further, the orthogonal partial least squares discriminant analysis model was used to obtain chemical markers among different classes. The antioxidant property of RPA is an important factor responsible for its pharmacological effects, and so the antioxidant activity of RPA was also investigated. We measured 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and hydroxyl radical scavenging ability, and ferric reducing antioxidant power. The total antioxidant activity follows the order: coke > stir-fried > soil-processed > bran-processed > wine-processed > raw > vinegar-processed products. These results suggest that different processing methods affect the chemical composition and antioxidant power of RPA, and thus, different products of RPA should not be mixed.

Immunoregulation and antioxidant activities of a novel acidic polysaccharide from Radix Paeoniae Alba.

Radix Paeoniae Alba is widely used in Chinese traditional medicine to treat various diseases such as gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In this paper, a novel acidic polysaccharide RPAPS purified from Radix Paeoniae Alba was evaluated for its structural features and potential of immunomodulatory and antioxidant activities. RPAPS (molecular weight: 1.0× 105 Da) was mainly composed of α-(1 → 4)-Glcp, α-Arap, α-Galp, α-Rhap, ß-D-Glcp, α-(1 → 6)-linked Glcp and GalA. Immunological tests indicated that RPAPS could improve RAW264.7 phagocytic activity and LPS-induced splenocyte proliferation. For antioxidant activities, RPAPS showed reducing power and DPPH scavenging activity in dose dependent. Moreover, RPAPS could significantly protect the PC12 cells from H2O2 damage. These data implied polysaccharides RPAPS had the potential to be novel natural antioxidative and immunopotentiating agents for using in functional foods or medicine.