Exploring the Mechanism of White Peony in the Treatment of Lupus Nephritis Based on Network Pharmacology and Molecular Docking.

INTRODUCTION: Lupus nephritis (LN) is still a great burden for patients with systemic lupus erythematosus, and also one of the most severe complications of SLE. Radix Paeoniae Alba (white peony, WP) is proved with potential efficacy in treating LN. This study was to explore the effective ingredients, potential targets, and pathways of WP in treating LN based on network pharmacology and molecular docking. METHODS: The active ingredients and potential protein targets of WP were gathered on Traditional Chinese Medicine Systematic Pharmacology Database and predicted by Swiss Target Prediction. LN-related therapeutic targets were acquired from multiple databases including Genecards, DisGeNET, OMIM, Drugbank, and PharmGKB. The intersection targets of WP and LN were acquired through Veeny 2.1.0. Protein-Protein Interaction (PPI) network was established by STRING. The results were then visualized by Cytoscape version 3.7.1. to study the mechanisms of WP on LN, gene ontology and functional enrichment analysis were carried out. Finally, molecular docking presented with the binding ability of key targets and major active components. RESULTS: We acquired a total of 13 active ingredients and 260 potential targets of WP. Among them, the intersection with targets of LN were 82 proteins. These targets were regarded as potential therapeutic targets. Through PPI network, we found that the top three proteins were RAC-alpha serine/threonine protein kinase (AKT1), vascular endothelial growth factor A (VEGFA), and transcription factor Jun (JUN), and their corresponding components were kaempferol, paeoniflorin, lactiflorin, paeoniflorgenone, etc. The results of enrichment analysis suggested that WP treatment for LN mainly involves in signaling pathways in cancer, lipid and atherosclerosis, advanced glycation end product (AGE)-receptor of AGE (RAGE) pathways, C-type lectin receptor and nuclear factor (NF)-kappa B signaling pathways. Molecular docking predicted that the above components have excellent affinity to AKT1, VEGFA, and JUN. CONCLUSIONS: This study gave an insight into the key target proteins and potential underlying pharmacological mechanism of WP in treating LN, which provided evidence for further researches on the mechanism of WP on LN.

Exploring the Mechanism of White Peony in the Treatment of Lupus Nephritis Based on Network Pharmacology and Molecular Docking

Introduction: Lupus nephritis (LN) is still a great burden for patients with systemic lupus erythematosus, and also one of the most severe complications of SLE. Radix Paeoniae Alba (white peony, WP) is proved with potential efficacy in treating LN. This study was to explore the effective ingredients, potential targets, and pathways of WP in treating LN based on network pharmacology and molecular docking. Methods: The active ingredients and potential protein targets of WP were gathered on Traditional Chinese Medicine Systematic Pharmacology Database and predicted by Swiss Target Prediction. LN-related therapeutic targets were acquired from multiple databases including Genecards, DisGeNET, OMIM, Drugbank, and PharmGKB. The intersection targets of WP and LN were acquired through Veeny 2.1.0. Protein-Protein Interaction (PPI) network was established by STRING. The results were then visualized by Cytoscape version 3.7.1. to study the mechanisms of WP on LN, gene ontology and functional enrichment analysis were carried out. Finally, molecular docking presented with the binding ability of key targets and major active components. Results: We acquired a total of 13 active ingredients and 260 potential targets of WP. Among them, the intersection with targets of LN were 82 proteins. These targets were regarded as potential therapeutic targets. Through PPI network, we found that the top three proteins were RAC-alpha serine/threonine protein kinase (AKT1), vascular endothelial growth factor A (VEGFA), and transcription factor Jun (JUN), and their corresponding components were kaempferol, paeoniflorin, lactiflorin, paeoniflorgenone, etc (AU)

To explore the mechanism of tripterygium wilfordii-white peony in rheumatoid arthritis based on network pharmacology and animal experiments / 中国现代医生

Objective Using network pharmacology to explore the mechanism of action of tripterygium wilfordii-white peony in the treatment of rheumatoid arthritis(RA)and validating it using an adjuvant arthritis rat model.Methods Obtain the effective ingredients of tripterygium wilfordii and white peony through TCMSP database and predict the action targets;Obtain the disease targets of RA using DisGeNET and GeneCards online database;Draw the network of"tripterygium wilfordii-white peony-active ingredient-RA"and screen the core effective components using the software Cytoscape 3.9.1;Construct the protein-protein interaction(PPI)network using String database and screen the core targets using the CytoNCA plug-in,using the Metascape database for gene enrichment analysis of common targets,and using Auto Dock Tools and Pymol software for molecular docking of core active ingredients and targets.Enzyme linked immunosorbent assay(ELISA)detection of serum tumor necrosis factor-α(TNF-α),interleukin(IL)-4,IL-6,and IL-17 levels in adjuvant arthritis rats,Western blot was used to detect the expression of phosphorylated phosphatidylinositol 3-hydroxy kinase(p-PI3K)and phosphorylated AKT protein(p-AKT),validate the results of network pharmacology analysis.Results There were a total of 61 effective ingredients in the treatment of RA with tripterygium wilfordii-white peony,with 116 targets and 191 signaling pathways involved.Animal experiments have shown that compared with the model group rats,the serum cytokine TNF-α,IL-6 and IL-17 of rats in tripterygium wilfordii-white peony group and tripterygium wilfordii extract group were significantly decreased(P<0.05),IL-4 significantly increased(P<0.05);The expression of p-PI3K and p-AKT in synovial tissue was significantly reduced(P<0.05);Compared with rats in tripterygium wilfordii extract group,the TNF-α,IL-6,IL-17,p-PI3K and p-AKT of rats in tripterygium wilfordii-white peony group were significantly reduced(P<0.05),while IL-4 was significantly increased(P<0.05).Conclusion Tripterygium wilfordii-white peony can inhibit the overexpression of phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)signaling pathway,regulate cytokine release,exert anti-inflammatory effects,and ultimately treat RA through multiple active ingredients and targets.

A botanical dietary supplement from white peony and licorice attenuates nonalcoholic fatty liver disease by modulating gut microbiota and reducing inflammation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related metabolic disease that is highly associated with gut dysbiosis and inflammation. A botanical dietary supplement, mainly containing an herbal pair of white peony root and licorice as well as grape seeds and broccoli extracts (WLT), exerts auxiliary protection against chemical liver injury. However, it is unclear whether WLT protects against the development of NAFLD induced by a high energy diet. PURPOSE: To investigate the protective role of WLT against NAFLD development induced by a high-fat and high-sucrose (HFHS) diet and its mechanism of action. METHODS: We investigated the anti-NAFLD effects of WLT on a HFHS diet-induced NAFLD C57BL/6J mouse model by detecting the hepatic triglyceride (TG) level, performing histological examination of the liver tissue, and evaluating glucose tolerance and systemic inflammation. Then, we analyzed the impact of WLT on gut microbiota by 16S rRNA gene sequencing, followed by fecal microbiota transplantation. Furthermore, we performed hepatic transcriptomic analysis of mice with or without WLT treatment using the RNA sequencing approach. RESULTS: Our results showed that WLT supplement attenuated body weight gain, hepatic steatosis, glucose tolerance, and systemic inflammation in HFHS-fed mice. Moreover, WLT supplement altered the composition of gut microbiota, which contributed at least in part, to the anti-NAFLD effect. Meanwhile, WLT improved the intestinal integrity and comprehensively modulated the expression of hepatic genes in HFHS mice, particularly reducing the expression of genes in the toll-like receptor-mediated inflammatory pathway. CONCLUSION: WLT is protective against NAFLD formation induced by an HFHS diet, and its effect is associated with the modulation of gut microbiota and inflammation, highlighting the potential of WLT to reduce the risk of metabolic disorders as a functional dietary supplement.

Widely targeted metabolomics analysis of white peony teas with different storage time and association with sensory attributes.

The sensory features of white peony teas (WPTs) significantly change with storage age; however, their comprehensive associations with composition are still unclear. This study aimed to clarify the sensory quality-related chemical changes in WPTs during storage. Liquid chromatography-tandem mass spectrometry based on widely targeted metabolomics analysis was performed on WPTs of 1-13 years storage ages. Weighted gene co-expression network analysis (WGCNA) was used to correlate metabolites with sensory traits including color difference values and taste attributes. 323 sensory trait-related metabolites were obtained from six key modules via WGCNA, verified by multiple factor analysis. The decline and transformation of abundant flavonoids, tannins and amino acids were related to the reduced astringency, umami and increased browning of tea infusions. In contrast, the total contents of phenolic acids and organic acids increased with storage. This study provides a high-throughput method for the association of chemical compounds with various sensory traits of foods.

White Peony (Fermented Camellia sinensis) Polyphenols Help Prevent Alcoholic Liver Injury via Antioxidation.

White peony is a type of white tea (Camellia sinensis) rich in polyphenols. In this study, polyphenols were extracted from white peony. In vitro experiments showed that white peony polyphenols (WPPs) possess strong free radical scavenging capabilities toward 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Long-term alcohol gavage was used to induce alcoholic liver injury in mice, and relevant indices of liver injury were examined. WPPs effectively reduced the liver indices of mice with liver injury. The serum levels of aspartate aminotransferase (ATS), alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglycerides (TG), total cholesterol (TC), blood urea nitrogen (BUN), nitric oxide (NO), and malondialdehyde (MDA) were downregulated, while those of albumin (ALB), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were upregulated. WPPs also reduced the serum levels of interluekin-6 (IL-6), interluekin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) in mice with liver injury. Pathology results showed that WPPs reduced alcohol-induced liver cell damage. Quantitative polymerase chain reaction (qPCR) and western blot results revealed that WPPs upregulated the mRNA and protein expressions of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), manganese superoxide dismutase (Mn-SOD), cupro-zinc superoxide dismutase (Cu/Zn-SOD), and CAT and downregulated iNOS expression in the liver of mice with liver injury. WPPs protected against alcoholic liver injury, and this effect was equivalent to that of silymarin. High-performance liquid chromatography revealed that WPPs mainly contained the polyphenols gallic acid, catechinic acid, and hyperoside, which are critical for exerting preventive effects against alcoholic liver injury. Thus, WPPs are high-quality natural products with liver protective effects.

Study on Drug Pair of Cassia Twig and White Peony Root by HPLC/MS Analysis Based on Theory of“Xin-Gan Hua-Yang and Suan-Gan Hua-Yin” / 世界科学技术-中医药现代化

This article was aimed to study the different clinical characteristics using drug pair of Cassia twig and white peony root with the contents ratio of 1:1 and 1:2. Based on the different clinical treatment of drug pair of Cas-sia twig and white peony root, different compositional ingredients in ratio of 1:1 and 1:2 were illuminated by HPLC/MS method. The drug pair of Cassia twig and white peony roots in ratio of 1:1 and 1:2 and single herbs were ex-tracted for HPLC/MS analysis. A protocol was followed, including acetonitrile - 0.1% acetic acid with gradient elution, positive mode, 350℃ capillary temperature and 300℃ vaporization temperature. The results showed that Procyanidol B2 and 2-Hydroxy cinnamal dehyde can be extracted from single Cassia twig, but 2-Hydroxy cinna-mal dehyde cannot be detected in drug pair. It showed the contents of Procyanidol B2 in 1:1 ratio was more than 1:2 ratio. Simultaneously, Palbinone, paeoniflorin sulfonate, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Pae-oniflorin isomers, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers can also be dissolved in white peony root. In addition, the contents of 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Palbinone, paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It was concluded that Procyanidol B2, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Pal-binone, Paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It provided a scientific basis for traditional Chinese medicine treatment using rational drug pair.

Immunostimulatory effect of a composition isolated from white peony root oral liquid in the treatment of radiation-induced esophagitis.

The aim of this study was to explore the immune repairing effect of a composition isolated from white peony root oral liquid (cWPROL), a traditional Chinese herbal composition, in the treatment of experimental radiation-induced esophagitis in rats. A total of 128 Wistar rats were randomly divided into eight groups, irradiated with 43 Gy 60Co γ-rays to induce esophagitis and treated by different methods. Flow cytometry, hematological analysis and immune nephelometry were used to detect the absolute numbers and percentages of CD3+, CD4+ and CD8+ T lymphocytes, numbers and classification of leukocytes, and the levels of IgG and complement C3 in the peripheral blood of the rats at each experimental time point. Following irradiation, the total number of leukocytes, absolute numbers and percentages of CD3+, CD4+ and CD8+ T lymphocytes, and levels of IgG and complement C3 in the peripheral blood of the rats were decreased. Furthermore, the total numbers of leukocytes, absolute numbers and percentages of CD3+, CD4+ and CD8+ T lymphocytes, and levels of IgG and complement C3 in the peripheral blood were higher in the administered with cWPROL by intra-esophageal perfusion compared with those in the untreated irradiated groups, but lower in the groups treated with a mixture of lidocaine hydrochloride, dexamethasone sodium phosphate and gentamicin sulfate. This study suggested that cWPROL is able to repair the impaired cellular and humoral immunity of rats with radiation-induced esophagitis.

Therapeutic effect of compound of White Peony Root Oral Liquids on radiation-induced esophageal toxicity via the expression of EGF and TGF-ß1.

The predominant pathological processes of radiation-induced esophageal toxicity include inflammatory reactions in the early stage and the fibrotic process in the late stage. An increased expression of the epidermal growth factor (EGF) and transforming growth factor ß1 (TGF-ß1) is capable of reducing inflammatory reactions and TGF-ß1 is considered responsible for the initiation, development and persistence of fibrosis. In the present study, we investigated in vivo the therapeutic effect of the compound of white peony root oral liquids (cWPROL) on reducing the toxicity via modulating the expression levels of EGF and TGF-ß1. Adult male Wistar rats were treated and tissue sections were obtained. The tissue sections were stained using histological, Masson and immunohistochemical staining. The results revealed that cWPROL had a higher rate of repairing damaged structures compared with the control group. In addition, immunohistochemistry showed that although cWPROL and the mixture of lidocaine, dexamethasone and gentamycin (mLDG) induced levels of EGF and TGF-ß1 expression, there were differences between the two types of intervention. These results are significant for understanding that the mechanism of therapeutic effect of cWPROL varied to some extent from that of mLDG.

Compositional differences in different processing technology of radix paeoniae alba and different origin of red peony / 中国基层医药

Objective To determine and compare the contents of oxypaeoniflorin and paeoniflorin of Paeoniae Radix,and to improve the quality standard of Radix Paeonia.Methods The contents of oxypaeoniflorin and paeoniflorin in different kind of White and Red Peony Root were successfully analyzed by HPLC.Results The content of oxypaeoniflorin in Red Peony Root is more than White Peony Root at 0.8361％ ;The content of paeoniflorin in White Peony Root is more than Red Peony Root at 0.2157％.The proportion of paeoniflorin and oxypaeoniflorin in White Peony Root is more than Red Peony Root.Conclusion With HPLC technology,quantitative analysis of active constituents in Paeoniae Radix was performed accurately.

Herbological Study of Red Peony and White Peony Used in Chinese Medicine / 日本東洋医学雑誌

In China, the roots of several species of Paeonia plants in the Paeoniaceae family have been used as crude drugs under the names of Ji-shao-yao, or the red peony, and Bai-shao-yao, or the white peony, since olden times. While in Japan, the simply dried root of Paeonia lactiflora Pallas has been used as the Chinese crude drug Shao-yao, or Shakuyaku in Japanese. As for the origins of the modern “red” and “white” peony names, there have been a variety of theories, e.g. the names were perhaps derived from differences in their root or flower colors, or whether they were wild or cultivated. Based on our herbological study, we have concluded that the dried root with a cork surface was named the red peony, and those peeled cork layers, the white peony. During the Ming Dynasty, in China, the root of wild peonies such as Paeonia veiitchii and P. obovata, whose flowers are reddish, were processed into the red peony, while cultivated peony root of the white flowered variety, P. lactiflora, was processed into the white peony drug. Because of this coincidence in flower color and name of the processed product, red flowered varieties or wild plants came to be called the plant origin of the red peony, while the white flowered varieties or cultivated plants came to be called the white peony.

Effect of Different Processing Methods on Paeoniflorin Content in White Peony Root / 中国中医药信息杂志

Objective To study the effect of different processing methods on paeoniflorin content and to provide a basis for stabilizing the processing technology of white peony root.Methods RP-HPLC method was used to determine the content of paeoniflorin on Agilent Eclipse XDB-C18(150 mm?4.6 mm,5 ?m),with mobile phase of acetonitrile-0.1% phosphoric acid(14∶86),flow rate of 1.0 mL/min,column temperature of 25 ℃,and detective wavelength of 230 nm.Results The average recovery rate was 99.195%,RSD=0.8%(n=6).The content of paeoniflorin was 0.55%,2.70%,3.40%,3.25%,respectively.Conclusion In the processing of white peony root,heating,water immersion and sulfur smoked have greater effect of paeoniflorin content in white peony root.