Abstract
Objective To investigate the pharmacological mechanism of the iridoid glycosides from Fructus Gardeniae in Jiangxi province by network pharmacology. To provide a valuable research strategy for the rational use and in-depth research and development of Fructus Gardeniae from Jiangxi. Method Previous research results of our group show that the contents of iridoid glycosides in Fructus Gardeniae from Jiangxi province have a significant difference compared with other regions (P < 0.05). Based on our previous experimental results, this study selected six characteristic high-content bioactive iridoid glycosides components of Fructus Gardeniae from Jiangxi province as candidate components. TCMSP database was used to obtain the process parameters of absorption, distribution, metabolism, and excretion (ADME) of candidate components. PubChem and SWISS online database were used to predict the related targets. Cytoscape software was used to the construct compound-target-disease (C-T-D) network of the Fructus Gardeniae iridoid glycosides ingredients. Furthermore, the GO biological process analysis and the pathway enrichment analysis were carried out using the CTD online analysis platform; then, an illustrated network that contains the main “chemicals-targets-pathway (C-T-P)” was constructed to analyze main biological pathways for obtaining the deep mechanism of Fructus Gardeniae in Jiangxi. Results 6 iridoid glycosides, namely geniposide, gardenoside, geniposidic acid, genipin 1-gentiobioside, gardoside, and shanzhiside, from Fructus Gardeniae in Jiangxi province were obtained as candidate components through previous work and network pharmacology screening. 36 corresponding targets were acted, such as BCL2, MAPT, F2, BCL2L1, PRKCD, PRKCB, HIF1A, and PRKCA. These targets could joint in pathways, such as signaling by GPCR, neuroactive ligand-receptor interaction, inflammatory mediator regulation of TRP channels, and ion channel transport. Interestingly, these pathways were highly associated with liver diseases, neurological diseases, hypertension, neoplasms, hyperalgesia, and inflammation. Remarkably, we boldly speculate that the Fructus Gardeniae from Jiangxi province can play a pharmacological role in hepatic encephalopathy through regulating multiple signaling pathways in an integrated manner. Conclusion The method based on system pharmacology could help to find the key targets of characteristic high-content chemical constituents of herb from different producing areas, the signaling pathway and disease network of TCM, and provide useful information and data support for giving a further study on traditional Chinese medicine resources in different regions of China.
Highlights
Gardenia jasminoides Ellis (Rubiaceae) is an evergreen shrub. e dried ripe fruits of Gardenia jasminoides have been recorded as Fructus Gardeniae (“zhi zi” in Chinese) in the Chinese Pharmacopoeia (2000–2015 edition) [1], and the fruits are used in traditional Chinese medicine because of their diuretic, antiphlogistic, anti-inflammatory, hemostatic, antipyretic, cholagogue, and laxative effects [2,3,4]
The yellow nodes (36) represent the potential targets related to the candidate compounds; the purple capsule-shaped nodes (6) represent the candidate compounds in Fructus Gardeniae from Jiangxi province; and the blue head-shaped nodes (32) represent the related diseases to the targets, while the edges represent the interactions between them. e node size varies according to degree, and edge thickness varies according to betweenness
Revised Materia Medica (Xin xiu ben cao), a materia medica commissioned by the government of the Tang Dynasty, stated: “if medicinal material is not produced from its native environment, the effect will be different.” at is to say, different geographical regions are suitable for growing different medicinal materials, and different medicinal materials have different adaptability to the ecological environment of different producing areas
Summary
Gardenia jasminoides Ellis (Rubiaceae) is an evergreen shrub. e dried ripe fruits of Gardenia jasminoides have been recorded as Fructus Gardeniae (“zhi zi” in Chinese) in the Chinese Pharmacopoeia (2000–2015 edition) [1], and the fruits are used in traditional Chinese medicine because of their diuretic, antiphlogistic, anti-inflammatory, hemostatic, antipyretic, cholagogue, and laxative effects [2,3,4]. E contents of chemical constituents in Fructus Gardeniae from different habitats are different, and the different chemical constituents can regulate the subjects through multiple targets and pathways, producing different pharmacological effects. Fructus Gardeniae cultivated in 10 different provinces in China has different high-content bioactive components and their different pharmacological activities. Preexperimental results demonstrated that the contents of geniposide, gardenoside, geniposidic acid, genipin 1-gentiobioside, gardoside, and shanzhiside in Fructus Gardeniae from Jiangxi province were significantly higher than those in other regions (P < 0.05) [16]; 6 iridoid glycosides were selected as the candidate components for the further pharmacological mechanism prediction. The key targets and signaling pathways of the characteristic highcontent bioactive components group of Fructus Gardeniae from Jiangxi province were searched by network pharmacology, and the related diseases were predicted, and the chemicals-target-disease network was constructed.
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