A Network Pharmacology Study on Active Components and Targets of Citri Reticulatae Pericarpium for Treating Keloids

[Objectives]To investigate the mechanisms and pharmacologic effects of Citri Reticulatae Pericarpium against keloids by network pharmacology systematically.[Methods]TCMSP,Uniprot and BATMAN-TCM databases were used to obtain the active constituents and targets of Citri Reticulatae Pericarpium."Keloid"was used as key word to search for related therapeutic targets from Drug Bank,OMIM,TTD,and GEO databases.The Chinese medicine compound-target network was constructed by Cytoscape software.Besides,gene ontology(GO)and Kyoto Encyclopedia of genes and genome enrichment analysis were also performed.Afterward,Discovery Studio software was used to assess the interaction of key components and genes.[Results]Five active components of Citri Reticulatae Pericarpium,773 compound targets and 676 keloid treatment targets were obtained in the databases.After the intersection,there are 47 targets of Citri Reticulatae Pericarpium for treating keloids.Hub genes were identified such as MMP9,IL6,TNF,TP53,and VEGFA,which were enriched in tumor necrosis factor-α,nuclear factor kappa-B,and other signaling pathways.The molecular docking stimulation confirmed the interaction between the MMP9 and three components of Citri Reticulatae Pericarpium.[Conclusions]Citri Reticulatae Pericarpium may play an important role in treating keloids through modulating genes and signaling pathways.The present study sheds light on the mechanisms of active compounds of Citri Reticulatae Pericarpium for the treatment of keloids.

Chemical Constituents from Pericarpium Citri Reticulatae

Objective To study the chemical constituents from Pericarpium Citri Reticulatae （Citrus reticulata）. Methods The chemical constituents were isolated and purified by silica gel column, Sephadex LH-20, and ODS column chromatography. The structures were identified by spectral data. Results Nineteen compounds were isolated and identified as 4＇,5,6,7-tetramethoxyflavone （1）, 3,3＇,4＇,5,6,7,8-heptmethoxyflavone （2）, sinensetin （3）, 5-O-demethylnobiletin （4）, tangeretin （5）, nobiletin （6）, apigenin （7）, 5-O- desmethyltangeretin （8）, 5,7-dihydroxy-3,3＇,4＇,6-tetramethoxyflavone （9）, pachypodol （10）, 4＇,5,6,7-tetramethoxyflavanone （11）, 3＇,4＇,5,7,8-pentamethoxyflavanone （12）, agestricin C （13）, scoparone （14）, isoscopoletin （15）, hesperidin （16）, didymin （17）, methylhesperidine （18）, and naringin （19）. Conclusion Compounds 9-15 are obtained from this plant for the first time.

Evaluation of bioactive flavonoids in Citri Reticulatae Pericarpium from different regions and its association with antioxidant andα-glucosidase inhibitory activities

Background:To explore the differences of 14 batches of Citri Reticulatae Pericarpium from different regions.Methods:The main aim of this study was to develop a high-performance liquid chromatography method-photodiode array detection for determining the contents of five flavonoids and the chromatographic fingerprints of Citri Reticulatae Pericarpium from different regions.Theα-glucosidase inhibitory activities and antioxidant properties of Citri Reticulatae Pericarpium,based on free-radical scavenging assays against 1,1-diphenyl-2-picrylhydrazyl,2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid),and hydroxyl radicals,were estimated and compared.Results:Among the tested compounds,the content of hesperidin(13.386-68.235 mg/g)was the highest and that of hesperitin(0.045-0.277 mg/g)was the lowest.In comparing different sources of Citri Reticulatae Pericarpium,the contents of narirutin in Citri Reticulatae Pericarpium from Guangdong(0.824-0.851 mg/g)and Sichuan(1.069-1.204 mg/g)provinces of China were lower than in other provinces.In contrast,nobiletin(8.429-12.237 mg/g)and tangeretin(3.947-4.613 mg/g)were most abundant in Guangdong sources of Citri Reticulatae Pericarpium,followed by samples from Sichuan Province(nobiletin:6.761-7.658 mg/g;tangeretin:3.422-3.933 mg/g).Correlation analysis showed that nobiletin and tangeretin were the main contributors to the antioxidant capacity,and narirutin was the main active component inhibiting theα-glucosidase activity of Citri Reticulatae Pericarpium.Conclusion:This work revealed that the intrinsic quality of Citri Reticulatae Pericarpium was affected by different growing regions,which provides a scientific basis for controlling the quality of Citri Reticulatae Pericarpium and rationally developing and utilizing Citri Reticulatae Pericarpium.

An Herbal Formula (GPC) Suppresses the Releases of Pro-Inflammatory Effectors in Lipopolysaccharide/Peptidoglycan-Activated RAW264.7 Macrophages and Reduces the Extent of Chemical-Induced Acute/Chronic Inflammation in Rodents

Pharyngitis (an inflammation in the pharynx) is a commonly occurring symptom of upper respiratory tract infection in patients suffering from common cold. The high prevalence of upper respiratory tract infection necessitates a safe and effective antiinflammatory agent for pharyngitis. Chinese herbal medicine, which has been clinically prescribed for thousands of years, may offer a basis for the treatment of common cold as well as the amelioration of pharyngitis. In the present study, we investigated the in vitro and in vivo anti-inflammatory activities of a Chinese herbal formula, namely GPC, which is comprised of Glycyrrhiza Radix, Platycodonis Radix, Citri Reticulatae Pericarpium, Phyllanthi Fructus and Taraxaci Herba. Incubation with GPC (30, 100 and 300 μg/mL) suppressed the releases of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and nitric oxide in lipopolysaccharide/peptidoglycanactivated RAW264.7 macrophages. In addition to the cell-based study, long-term treatment with GPC (0.35, 1.05 and 2.10 mL/kg/day × 30 doses) was found to reduce the extent of inflammation in animal models of carrageenan-induced paw edema (acute inflammation) as well as cotton pellet-induced granuloma formation (chronic inflammation) in mice. The ability of GPC to enhance the tracheobronchial expectorant action suggested its immunomodulatory activity in the respiratory tract. This postulation was supported by the observation that GPC reduced the degree of pharyngitis and reversed the changes in plasma TNF-α and IL-6 levels in capsaicininduced pharyngitis in rats. The ensemble of results suggests that GPC may offer a promising prospect for alleviating the extent of pharyngitis by virtue of antiinflammatory activities.

Research on "Erchen" in Erchen decoction

Traditional Chinese Medicine has a long history of aging medicines,with the Erchen decoction(it is a traditional Chinese botanical formula),produced by Chenpi(Citri Reticulatae Pericarpium)(CRP)and Banxia(Pinelliae Rhizoma)(PR),as having the most research value.While modern pharmacological studies have found that the main active components of CRP are flavonoids and volatile oils.The relative contents of 30 CRP flavonoids increase with aging time.However,the expectorant effect of CRP is not proportional to its aging time,and its volatile oil composition is thought to be negatively correlated with its aging time,yet this correlation has not yet been established by research.In addition,different experimental measurement methods have found that aging has a reduced effect on the toxic components of different processing types of PR,such as calcium oxalate needle crystals and protein substances.These research also noted that different processing methods also resulted in differences in the efficacy of PR.For example,during the aging process of Jiangbanxia(Pinelliae Rhizoma Praeparatumcum Zingibere Et Alumine)and auxiliary materials,6-gingerol was produced,which enhanced the anti-vomiting effects of PR but weakened its expectorant and cough function.Using a method of Alum processed PR,increases the contents of Inosine,Guanosine,Adenosine and Succinate,which thus enhances its expectorant effect.Finally,the contents of 6-Gingerol,Glycyrrhizin,Ammonium Glycyrrhizate,and other substances produced in the aging process of PR,can be used as base compounds for producing additional products of PR.The research on the efficacy and uses of Erchen decoction,particularly compounds made with CRP and PR is voluminous,but no standards currently exist for effective and standardized application of these substances.This paper reviews the research with an aim to establish standardization of methods and of compound aging time.