Chinensinaphthol methyl ether

Effective components and mechanism analysis of anti-platelet aggregation effect of Justicia procumbens L.[Pubmed:35589019]

J Ethnopharmacol. 2022 Aug 10;294:115392.

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 a(Ⅱb)beta(3), PKCalpha, PI3Kgamma, 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.

Development of a mesoporous silica based solid-phase extraction and ultra-performance liquid chromatography-MS/MS method for quantifying lignans in Justicia procumbens.[Pubmed:32040861]

Electrophoresis. 2020 Mar;41(5-6):379-385.

Justicia procumbens is a food and medicine homologous variety, popularly used for making vegetable soups. In this study, a novel mesoporous silica was synthesized and used as the sorbent of SPE for the purification of lignans from J. procumbens. A laboratory-made SPE cartridge was packed with 100 mg of mesoporous silica, which was washed with 10% methanol and eluted using 0.8 mL acetonitrile after sample loading. Afterward, the extract was analyzed by ultra-performance liquid chromatography (UPLC) and MS/MS. All the lignans were efficiently separated in 6 min with the noise level in the range of 50-150 cps. 6'-Hydroxy justicidin B, 6'-hydroxy justicidin A, justicidin B, Chinensinaphthol methyl ether, justicidin C, and neojusticdin A were identified to be the dominant molecular species in J. procumbens with contents of 0.065-0.37 mg/g in three tested sample batches from different geographic origins. In conclusion, the proposed mesoporous silica based SPE UPLC-MS/MS method is efficient in linearity (R(2) = 0.9989-0.9996), sensitivity (LOD

A novel anti-platelet aggregation target of chinensinaphthol methyl ether and neojusticin B obtained from Rostellularia procumbens (L.) Nees.[Pubmed:31072143]

J Enzyme Inhib Med Chem. 2019 Dec;34(1):999-1009.

This study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. The results of optical turbidimetry revealed that the ethyl acetate extraction obtained from R. procumbens (L.) Nees could inhibit platelet aggregation. Gene chip was used to investigate differentially expressed genes. According to the results of the gene chip, the targets of compounds isolated from the ethyl acetate extraction were predicted by network pharmacology. Computational studies revealed that Chinensinaphthol methyl ether and neojusticin B may target the integrin alpha(IIb)beta(3) protein. The results of Prometheus NT.48 and microscale thermophoresis suggested that the molecular interactions between the two compounds with purified integrin alpha(IIb)beta(3) protein in the optimal test conditions were coherent with the docking results. To our best knowledge, this is the first report to state that Chinensinaphthol methyl ether and neojusticin B target the integrin alpha(IIb)beta(3) protein.

Determination and pharmacokinetics of chinensinaphthol methyl ether in rat urine by a sensitive and specific UFLC-ESI-MS/MS method.[Pubmed:27595651]

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Oct 15;1033-1034:311-316.

A rapid, stable, and sensitive method based on ultra-fast liquid chromatography combined with electrospray ionization tandem mass spectrometry (UFLC-ESI-MS/MS) was established and optimized for quantification and pharmacokinetics analysis of Chinensinaphthol methyl ether (CME) in rat urine. Samples were prepared by liquid phase extraction with ethyl acetate, and chromatographic separation was performed on an ACQUITY UPLC((R)) BEH Phenyl column (2.1x50mm, 1.7mum). For gradient elution, we used a mobile phase consisting of water containing 0.1% formic acid and 5mmol/L ammonium formate and methanol with 0.1% formic acid. The quantification was executed under multiple reaction monitoring (MRM) in positive mode. The precursor/product transition (m/z) in the positive ion mode was [M+H](+)m/z=395.1-->346.1. This method was validated by evaluating specificity, linearity, matrix effects, recovery, accuracy, precision, and stability, which were all shown to be reasonable and reliable. The lower limit of quantification (LOQ) was 0.5ng/mL, and the linear range was 0.5-100ng/mL. The method was successfully applied to quantify and analyze the pharmacokinetics of CME in rat urine. After oral administration of a single dose of CME (5.0mg/kg), the accumulated amount of CME excreted in urine was 162.3+/-54.1ng, and the terminal elimination half-life was 53.4+/-5.3h, indicating low CME excretion in urine and significant CME metabolism in vivo.

Evaluation and structure-activity relationship analysis of a new series of arylnaphthalene lignans as potential anti-tumor agents.[Pubmed:24675875]

PLoS One. 2014 Mar 27;9(3):e93516.

Arylnaphthalene lignan lactones have attracted considerable interest because of their anti-tumor and anti-hyperlipidimic activities. However, to our knowledge, few studies have explored the effects of these compounds on human leukemia cell lines. In this study, five arylnaphthalene lignans including 6'-hydroxy justicidin A (HJA), 6'-hydroxy justicidin B (HJB), justicidin B (JB), Chinensinaphthol methyl ether (CME) and Taiwanin E methyl ether (TEME) were isolated from Justicia procumbens and their effects on the proliferation and apoptosis of the human leukemia K562 cell line were investigated then used to assess structure-activity relationships. To achieve these aims, cytotoxicity was assayed using the MTT assay, while intracellular SOD activity was detected using the SOD Activity Assay kit. Apoptosis was measured by both the using a cycle TEST PLUS DNA reagent kit as well as the FITC Annexin V apoptosis detection kit in combination with flow cytometry. Activation of caspase-mediated apoptosis was evaluated using a FITC active Caspase-3 apoptosis kit and flow cytometry. The results indicated that HJB, HJA and JB significantly inhibited the growth of K562 cells by decreasing both proliferation and SOD activity and inducing apoptosis. The sequence of anti-proliferative activity induced by the five tested arylnaphthalenes by decreasing strength was HJB > HJA > JB > CME > TEME. HJB, HJA and JB also decreased SOD activity and induced apoptosis in a dose-dependent manner. Activation of caspase-3 further indicated that HJB, HJA and JB induced caspase-dependent intrinsic and/or extrinsic apoptosis pathways. Together, these assays suggest that arylnaphthalene lignans derived from Justicia procumbens induce apoptosis to varying degrees, through a caspase-dependent pathway in human leukemia K562 cells. Furthermore, analysis of structure-activity relationships suggest that hydroxyl substitution at C-1 and C-6' significantly increased the antiproliferative activity of arylnaphthalene lignans while a methoxyl at C-1 significantly decreased the effect.

Simultaneous determination of seven lignans in Justicia procumbens by high performance liquid chromatography-photodiode array detection using relative response factors.[Pubmed:23355351]

J Sep Sci. 2013 Feb;36(4):699-705.

A simple and sensitive HPLC coupled with photodiode array (HPLC-PDA) method was developed for simultaneous determination of seven lignans in Justicia procumbens using relative response factors (RRFs). The chromatographic separation was performed on a Shiseido Capcell Pak C(18) column (250 x 4.6 mm id, 5 mum), a gradient elution of acetonitrile/water, and a photodiode array detector. The column temperature was maintained at 35 degrees C and the detection wavelength was set at 256 nm. Chinensinaphthol methyl ether was selected as the reference compound for calculating the relative response factors of the lignans. It has shown that the RRFs for lignans are quite similar at 256 nm of detection under different analytical conditions (different columns and HPLC instruments). Using RRFs, not every lignan is needed as a reference standard, making the method ideal for rapid, routine analysis, especially for those laboratories where lignans standards are not readily available. An economic and practicable HPLC method using RRFs was established for the determination of seven lignans in J. procumbens. This method not only can determine multiple indexes in traditional Chinese medicines (TCMs) simultaneously, but also resolve the problem of lacking of chemical standards. It will be a good quality evaluation method and pattern for TCMs.

Application of a sensitive and specific LC-MS/MS method for determination of chinensinaphthol methyl ether in rat plasma for a bioavailability study.[Pubmed:22831883]

J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Aug 15;903:75-80.

Chinensinaphthol methyl ether (CME) is a potential pharmacologically active ingredient isolated from the dried plants of Justicia procumbens L. (Acanthaceae). A sensitive and specific LC-MS/MS method was developed and validated for the analysis of CME in rat plasma using buspirone as the internal standard (IS). The analyte was extracted with ethyl acetate and chromatographed on a reverse-phase Agilent Zorbax-C18 110 A column (50 mm x 2.1mm, 3.5 mum). Elution was achieved with a gradient mobile phase consisting of water and acetonitrile both containing 0.1% formic acid at a flow rate of 0.40 mL/min. The analytes were monitored by tandem-mass spectrometry with positive electrospray ionization. The precursor/product transitions (m/z) in the positive ion mode were 394.5-->346.0 and 386.1-->122.0 for CME and IS, respectively. The assay was shown to be linear over the range of 0.50-500 ng/mL, with a lower limit of quantification of 0.50 ng/mL. The method was shown to be reproducible and reliable with the inter- and intra-day accuracy and precision were within +/-15%. The assay has been successfully used for pharmacokinetic evaluation of CME after intravenous and oral administration of 1.80 mg/kg CME in rats. The oral absolute bioavailability (F) of CME was estimated to be 3.2+/-0.2% with an elimination half-life (t(1/2)) value of 2.4+/-0.8h, suggesting its poor absorption and/or strong metabolism in vivo.

Chromatographic fingerprint analysis and simultaneous determination of eight lignans in Justicia procumbens and its compound preparation by HPLC-DAD.[Pubmed:21328534]

J Sep Sci. 2011 Mar;34(6):667-74.

HPLC fingerprints were developed for the quality evaluation of Justicia procumbens and its compound preparation, Jian-er syrup, together with the simultaneous quantification of eight arylnaphthalide lignans (6'-hydroxy justicidin B, 6'-hydroxy justicidin A, 6'-hydroxy justicidin C, justicidin B, Chinensinaphthol methyl ether, justicidin C, taiwanin C, and neojusticin A). Samples were separated with a Shiseido Capcell Pak C(18) reversed-phase column (250x4.6 mm id, 5 mum) using acetonitrile and water as the mobile phase. The column temperature was maintained at 35 degrees C and the wavelength of detector was set at 256 nm. For fingerprint analysis, 17 peaks were selected as the characteristic peaks for the evaluation of the similarities among different J. procumbens samples collected in different places. The structures of lignans were confirmed by diagnostic fragments in the positive ESI-MS(n) . The new method was successfully applied for the chromatographic fingerprint analysis and simultaneous determination of eight lignans in its compound preparation, Jian-er syrup. All the results indicated that HPLC fingerprint assay in combination with multi-marker determination afforded a useful method for the quality control of J. procumbens and its compound preparation, Jian-er syrup.

[Research on quality specification of Herba Justiciae].[Pubmed:20209906]

Zhongguo Zhong Yao Za Zhi. 2009 Nov;34(21):2748-50.

OBJECTIVE: To provide scientific basis for the utilization and development of Herba Justiciae by setting up the quality control specification of Herba Justiciae. METHOD: Moisture and ash were determined by aquametry and method of ash determination. And the bioactive constituents were analyzed by HPLC. RESULT: The contents of total ash, acid-insoluble ash, and moisture of 28 samples from different origins were determined. The quantitative analysis of Chinensinaphthol methyl ether by HPLC were preformed, respectively. CONCLUSION: The established method can be used for the quality control of Herba Justiciae.

Antiplatelet arylnaphthalide lignans from Justicia procumbens.[Pubmed:8988600]

J Nat Prod. 1996 Dec;59(12):1149-50.

Fractionation of the EtOH extract of Justicia procumbens, guided by antiplatelet bioassay, led to the isolation of nine known arylnaphthalide lignans, neojusticin A (1), justicidin B (2), justicidin A (3), taiwanin E methyl ether (4), neojusticin B (5), Chinensinaphthol methyl ether (6), taiwanin E (8), chinensinaphthol (9), and diphyllin (10), and a new arylnaphthalide lignan that was characterized by spectral means as 4'-demethylChinensinaphthol methyl ether (7). Compounds 1, 2, 4, and 8 significantly inhibited platelet aggregation.