Effective components and mechanism analysis of anti-platelet aggregation effect of Justicia procumbens L.

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia procumbens L. is a traditional Chinese medicine, first recorded in "Shen Nong's Herbal Classic", for the treatment of lumbar pain and fever. As a widely distributed herb, it has also been documented in India, Nepal, and Malaysia. In "Tang Materia Medica", a famous medicinal book of Tang Dynasty in ancient China, it was first used to treat diseases associated with blood stasis. Blood stasis syndrome is closely related to thrombus formation and platelet aggregation. Although some compounds isolated from this plant have anti-platelet aggregation effects, the main chemical components and mechanism of J. procumbens in terms of these effects are little known. AIMS OF THE STUDY: Through in vivo and in vitro experiments, this studsy revealed the characteristic components and action mechanism of anti-platelet aggregation by J. procumbens from an overall perspective. MATERIALS AND METHODS: The effective crude extracts of the whole plant were screened via an in vitro anti-platelet aggregation test. After incubating these extracts with apheresis platelets, high affinity compounds were detected by HPLC-MS and regulatory genes were detected using gene chips. The effective components and potential target proteins were analyzed using computational docking technology. Furthermore, the compound with the strongest predicted activity was evaluated in vivo via an anti-thrombotic test. RESULTS: Integrin aⅡbß3, PKCα, PI3Kγ, and mitogen-activated protein kinase 14 were found to be potential targets. Justicidin B, tuberculatin, chinensinaphthol methyl ether, and neojusticin B were effective compounds that inhibited human platelet aggregation by suppressing Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways. Among the compounds that bind to platelets, justicidin B showed the strongest virtual binding force. The test of carotid artery thrombosis induced by ferric chloride in SD rats confirmed that justicidin B inhibited thrombus formation. CONCLUSION: Experimental investigation showed that arylnaphthalene lignan aglycones with one methylenedioxy group and two methoxy groups are effective components for anti-platelet aggregation by J. procumbens. These compounds inhibit Gq-PLC-PKC and Gi-PI3K-MAPK signaling pathways by suppressing the expression of genes such as ITGB3, PRKCA, PIK3CG, and MAPK14. These results reflected the characteristics of multi-component and multi-target synergistic treatment of Chinese medicine.

Reveals of candidate active ingredients in Justicia and its anti-thrombotic action of mechanism based on network pharmacology approach and experimental validation.

Thrombotic diseases seriously threaten human life. Justicia, as a common Chinese medicine, is usually used for anti-inflammatory treatment, and further studies have found that it has an inhibitory effect on platelet aggregation. Therefore, it can be inferred that Justicia can be used as a therapeutic drug for thrombosis. This work aims to reveal the pharmacological mechanism of the anti-thrombotic effect of Justicia through network pharmacology combined with wet experimental verification. During the analysis, 461 compound targets were predicted from various databases and 881 thrombus-related targets were collected. Then, herb-compound-target network and protein-protein interaction network of disease and prediction targets were constructed and cluster analysis was applied to further explore the connection between the targets. In addition, Gene Ontology (GO) and pathway (KEGG) enrichment were used to further determine the association between target proteins and diseases. Finally, the expression of hub target proteins of the core component and the anti-thrombotic effect of Justicia's core compounds were verified by experiments. In conclusion, the core bioactive components, especially justicidin D, can reduce thrombosis by regulating F2, MMP9, CXCL12, MET, RAC1, PDE5A, and ABCB1. The combination of network pharmacology and the experimental research strategies proposed in this paper provides a comprehensive method for systematically exploring the therapeutic mechanism of multi-component medicine.

Active Ingredients and Mechanism of Action of Rhizoma Coptidis against Type 2 Diabetes Based on Network-Pharmacology and Bioinformatics.

A pharmacological network of "component/target/pathway" for Rhizoma coptidis against type 2 diabetes (T2D) was established by network-pharmacology, and the active components of Rhizoma coptidis and its mechanism were explored. A literature-based and database study of the components of Rhizoma coptidis was carried out and screened by ADME parameters. The targets of Rhizoma coptidis were predicted by the ligand similarity method. Related pathways were analyzed with databases, and software was used to construct a "component/target/path" network. The mechanism was further confirmed by GEO database with R software. A total of 12 active components were screened from Rhizoma coptidis, involving 57 targets including MAPK1, STAT3, INSR, and 38 signaling pathways were associated with T2D. Related signaling pathways included essential pathways for T2D such as insulin resistance, and pathways that had indirect effect on T2D. It was suggested that Rhizoma coptidis may exert its effects against T2D through multi-component, multi-target, and multi-pathway forms.

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect.

Albiziae Flos (AF) has been experimentally proven to have an antidepressant effect. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of action of AF in depression has not been completely deciphered. This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF. The methods included collection and screening of chemical components, prediction of depression-associated targets of the active components, gene enrichment, and network construction and analysis. Quercetin and 4 other active components were found to exert antidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand-receptor interaction pathways. DRD2, HTR1A, and SLC6A4 were identified as important targets of the studied bioactive components of AF. This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.

Screening for cytotoxic chemical constituents from Justicia procumbens by HPLC-DAD-ESI-MS and NMR.

BACKGROUND: The Acanthaceae family is an important source of therapeutic drugs and ethno medicines. There are many famous medicinal plants from this family, such as Andrographis paniculata, Baphicacanthus cusia, and Dicliptera chinensis. Justicia procumbens (J. procumbens) is widely distributed in tropical and sub-tropical of the world. It has long been used in traditional Chinese medicine for cancer. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed the ethyl acetate extract of J. procumbens had a cytotoxic activity. Therefore, qualitative and quantitative analysis of the chemical constituents in the ethyl acetate extract was important for understanding its pharmacological mechanism. RESULTS: A high-performance liquid chromatography with diode array detection coupled to electrospray ionisation quadrupole time-of-flight tandem mass spectrometry procedure was established. Eleven dibenzylbutanes and four arylnaphthalenes were confirmed by HPLC-DAD-ESI-QTOF-MS analysis. A novel dibenzylbutane (5-methoxy-4,4'-di-O-methylsecolariciresinol-9'-monoacetate) and seven isomers of arylnaphthalene were isolated and characterized by NMR and QTOF-MS. Compounds 1, 2, and 13 were detected for the first time. The content of six lignans were determinated in the ethyl acetate extract. CONCLUSIONS: This study showed that the cytotoxic activity assay of J. procumbens could be mainly attributed to the constituents of lignans. The bioactivity of the ethyl acetate extract and determined compounds support the traditional use of this plant in cancer. These chemical constituents may be developed as novel therapeutics.

[Studies on the chemical constituents in ethyl acetate extraction from the fruit of Polygonum orientale].

OBJECTIVE: To study on the chemical constituents in ethyl acetate extraction from Polygonum orientale. METHODS: By repeated silica gel chromatographic seperation and spectral analysis the structures were determined. RESULTS: Seven compounds were isolated and identified from Polygonum orientale. They were 3,5,7-trihydrochromone (I), kaempferol (II), 5,7,4'-trihydroxydihydroflavonol (III), dihydroquercetin (IV), quercetin (V), p-hydroxyphenylethanol ferulate (VI), p-hydroxyphenylethanol-p-coumaric (VII). CONCLUSION: Compounds II, III are isolated from this plant for the first time.

[HPLC fingerprint of flavonoids in fruits of Polygonum orientale].

OBJECTIVE: To compare HPLC fingerprint of flavonoids in fruits of Polygonnm orientale from different regions. METHODS: Diamonsil C18 (250 mm x 4.6 mm, 5 microm) had been used, the mobile phase consisted of methanol and 0.2% phosphoric acid as fradient eluent. The flow rate was 1 ml/min, and the detection wavelength was 310 nm. RESULTS: The finerprint of flaxonoids in fruits of Poligonum orientale with 11 common peaks was eatablished. The realative retention time and the range of relative area of the common peaks were determined. CONCLUSION: The established fingerprint can be used for the identification and quality control of flavonoids of Poligonum orientale from different regions.