Essential oil extracted from Quzhou Aurantii Fructus prevents acute liver failure through inhibiting lipopolysaccharide-mediated inflammatory response

Quzhou Aurantii Fructus(QAF)has a long history as a folk medicine and food for the treatment of liver diseases.While our earlier study provided evidence of hepatoprotective properties contained within the flavonoids and limonins constituents in QAF,the potential preventative effects afforded by essential oil components present within QAF remains enigmatic.In this study,we prepared Quzhou Aurantii Fructus essential oil(QAFEO)and confirmed its anti-inflammatory effects on liver inflammation through experimentation on lipopolysaccharide and D-galactosamine(LPS/D-GalN)induced acute liver failure(ALF)mouse models.Using RNA-sequence(RNA-seq)analysis,we found that QAFEO prevented ALF by systematically blunting the pathways involved in response to LPS and toll-like receptor signaling pathways.QAFEO effectively suppressed the phosphorylation of tank-binding kinase 1(TBK1),TGF-beta activated kinase 1(TAK1),interferon regulatory factor 3(IRF3),and the activation of mitogen activated kinase-like protein(MAPK)and nuclear factor-kappa B(NF-κB)pathways in vivo and in vitro.Importantly,QAFEO substantially reduced myeloid differentiation primary response gene 88(MyD88)-toll-like receptor 4(TLR4)interaction levels.Moreover,8 compounds from QAFEO could directly bind to REAL,TAK1,MyD88,TBK1,and IRF3.Taken together,the results of our study support the notion that QAFEO exerts a hepatoprotective effect through inhibiting LPS-mediated inflammatory response.

GC-MS Analysis and Antibacterial Activity Study of Volatile Oil from 11 Kinds of Aurantii Fructus Immaturus Processed Products

[Objectives]To study the volatile components and antibacterial effects of 11 kinds of Aurantii Fructus Immaturus processed products.[Methods]11 kinds of Aurantii Fructus Immaturus processed products were obtained according to the traditional processing method,the volatile oil was extracted by steam distillation,and the composition of volatile oil in the 11 kinds of processed products was analyzed by gas chromatography-mass spectrometry(GC-MS).the relative percentage content of each component in these 11 kinds of processed products was determined using the peak area normalization.The drug sensitivity activity of the volatile oil of these 11 kinds of processed products was tested using the K-B paper diffusion method and the minimum inhibition volume fraction of volatile oil of these 11 kinds of processed products was tested using the microdilution method.[Results]The highest yield of volatile oil of 11 kinds of these processed products was baking(5.193%),and the lowest was stir-bake to scorch(1.998%).A total of 36 chemical components were identified from the volatile oils of these 11 kinds of processed products.The components with the most volatile oil were stir-bake to scorch(24 kinds),and the components with the least volatile oil were the method of processing with rice-washed water(15 kinds).They contain 8 kinds of common chemical components,such as limonene,linalool,myrcene,α-pinene.The highest content of limonene came from processing with honey(60.93%),the lowest came from processing with rice-washed water(55.25%);the highest content of linalool came from processing with rice-washed water(7.139%),the lowest came from processing with honey(5.436%);the highest content of myrcene came from processing with honey(1.899%),the lowest came from stir-bake to scorch(1.632%);the highest content ofα-pinene came from raw Aurantii Fructus Immaturus(2.355%),and the lowest came from stir-bake to scorch(1.618%).The volatile oil of these 11 kinds of Aurantii Fructus Immaturus processed products has good antibacterial effect on Escherichia coli and Staphylococcus aureus.[Conclusions]The oil yields of volatile oils of 11 kinds of Aurantii Fructus Immaturus processed products are different,the content of limonene is significantly different,and the changes of other chemical components and their contents are not significantly different.The volatile oil of 11 kinds of Aurantii Fructus Immaturus processed products has certain antibacterial effect.

Insight into the Efficacy and Potential Mechanism of Fructus Aurantii on Skin Based on Network Pharmacology

[Objectives]This study was conducted to explore the mechanism and pharmacological activity of Fructus Aurantii on human skin through network pharmacology.[Methods]The active components and targets of Fructus Aurantii were screened byTCMSPand SymMap data-bases,and the targets were humanized after de-duplication by UniProt database.Relevant therapeutic targets were searched in Gencards data-base with"skin"as the key word,and those with higher weights were retained.An effective component-human skin action target network of Fructus Aurantii was established by Cytoscape software.Then,the topological analysis of protein-protein interaction(PPI)network was made by using String database and Cytoscape software.Gene Ontology(GO)funetional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out by david database,and the analysis results were visualized by Hiplot soft-ware.[Results]Thirteen active compounds of Fructus Aurantii were obtained by screening,and 99 gene targets of Fructus Aurantii which might have pharmacological activity on human skin were obtained by intersection analysis.PTGS2,PTGS1,HSP90AB1,HSP90AAI,NCOA2 and PIK3CG might be core action targets of Fructus Aurantii on human skin according to the topological analysis of the active component-target network.The analysis of PPI network showed that IL-1β,INS,TNF,TP53 and ESR1 might be core action proteins of Fructus Auranti.GO enrichment analysis showed that Fructus Aurantii might balance the imbalance of skin microenvironment caused by various in-vitro stimuli by participating in biological processes such as response to xenobiotic stimulus and regulation of small molecule metabolic process.KEGG pathway enrichment analysis showed that the targets of Fructus Aurantii acting on human skin were enriched in pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,pathways in measles,AGE-RAGE signaling pathway in diabetic complications,IL.-17 signaling pathway,etc.[Conclusions]Fructus Aurantii may act on human skin targets through a variety of active components,and play a regulatory role in skin-related diseases.

Concentration Prediction of Total Flavonoids in Aurantii Fructus Extraction Process:Locally Weighted Regression versus Kinetic Model Equation Based on Fick's Law

Objective To predict the total flavonoids concentration of Aurantii Fructus fried with bran in its extraction process. Methods Ultraviolet spectrophotometry was used to determine the concentration of total flavonoids in different extraction time （t） and solvent load （M）. Then the predicted procedure was carried out using the following data： 1 ） based on Ficks second law, the parameters of the kinetic model could be deduced and the equation was established; 2） Locally weighted regression （LWR） code was developed in the WEKA software environment to predict the concentration. And then we used both methods to predict the concentration of total flavonoids in new experiments. Results After comparing the predicted results with the experimental data, the LWR model had better accuracy and performance in the prediction. Conclusion LWR is applied to analyze the extraction process of Chinese herb for the first time, and it is totally fit for the extraction. LWR-based system is a more simple and accurate way to predict than the established equation. It is a good choice especially for a process which exists no clear rules, and can be used in the real-time control during the process.

Chromatographic fingerprint analysis of Fructus Aurantii Immaturus by HPLC-DAD and chemometric methods

An efficient method for quality control of Fructus Aurantii Immaturus (FAI),a famous traditional Chinese medicine (TCM) was established. A simple and reliable high-performance liquid chromatography-photodiode array detector (HPLC-DAD) procedure coupled with chemometric methods was developed for fingerprint analysis,qualitative analysis and quantitative determination of this herb. In qualitative and quantitative analyses,heuristic evolving latent projection (HELP) method was employed to resolve the overlapping peaks of the tested samples. Two bioactive components,namely hesperidin and naringin,are confirmed and determined,together with four flavonoids compounds tentatively identified including two new ones. From fingerprint analysis,the fingerprint data were processed with correlation coefficients for quantitative expression of their similarity and dissimilarity. The developed method based on an integration of chromatographic fingerprint and quantitative analysis is scientific,and the obtained results can be applied to the quality control of herb medicine.

Two new phenolic glycosides isolated from the fruits of Citrus aurantium

The present study was designed to investigate the chemical constituents of the fruit of Citrus aurantium L.. The compounds were isolated and purified by various chromatographic techniques, and their structures were elucidated on the basis of physicochemical properties and spectral data. Two new phenolic glycosides(compounds 1 and 2) were obtained and identified as 1-O-3, 5-dihydroxyphenyl-(6-O-4-hydroxybenzoyl)-β-D-glucopyranoside(1) and 1-O-3, 5-dihydroxyphenyl-(6-O-3-methoxy-4-hydroxy benzoyl)-β-D-glucopyranoside(2), respectively.