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Metabolomics and genomics: revealing the mechanism of corydalis alkaloid on anti-inflammation in vivo and in vitro

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Abstract

As one of the major active components of Qizhiweitong (QZWT) prescription, corydalis alkaloid (CA) has been reported to have noticeable effect of anti-inflammation in pharmacological studies. However, the anti-inflammatory function and potential mechanism of CA in anti-inflammation remain to be clarified. Hence, the aim of this study was to investigate the anti-inflammation efficacy and potential mechanism of CA in anti-inflammation by metabonomic approach coupled with related gene analyzes in vivo and in vitro. Mice acute inflammation was induced by subcutaneous injection of formalin in hind paws, and evaluated the anti-inflammatory effect of CA via detecting the index of paw edema. The results indicated that CA has an anti-inflammatory effect on mice through alleviating the paw edema significantly. Moreover, metabolic profiling was performed by high performance liquid chromatography quadrupole-time-of-flight mass spectrometer (HPLC-QTOF-MS) combined with multivariate data analysis, such as principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). Thirteen metabolic targets (including lysophosphatidylcholine (LysoPC), choline, arachidonic acid, phosphodimethylethanolamine) and related pathways of the cholinergic anti-inflammatory and arachidonic acid (AA) metabolism were identified, Meanwhile, the relevant target genes, like iNOS, NF-κB, TNF-α, were detected and verified in vitro. The results indicated that CA has a good pharmacological effect of anti-inflammation through regulating multiple disordered targets and metabolic networks, which provides a theoretical basis for further research on CA. Furthermore, there is a great potential for the development of CA to be a new anti-inflammatory drug with high effective activities, little side effects and weak drug resistance.

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References

  • Aubin N, Curet O, Deffois A, Carter C (1998) Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. J Neurochem 71:1635–1642

    Article  CAS  PubMed  Google Scholar 

  • Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmüller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R (2016) Metabolomics enables precision medicine: “a white paper, community perspective”. Metabolomics 12:149

    Article  PubMed  PubMed Central  Google Scholar 

  • Calder PC, Ahluwalia N, Albers R, Bosco N, Bourdet-Sicard R, Haller D, Holgate ST, Jönsson LS, Latulippe ME, Marcos A, Moreines J, M’Rini C, Müller M, Pawelec G, van Neerven RJ, Watzl B, Zhao J (2013) A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br J Nutr 109:S1–S34

    Article  PubMed  Google Scholar 

  • Caligiuri SP, Aukema HM, Ravandi A, Pierce GN (2014) Elevated levels of pro-inflammatory oxylipins in older subjects are normalized by flaxseed consumption. Exp Gerontol 59:51–57

    Article  CAS  PubMed  Google Scholar 

  • Cao FL, Shang GW, Wang Y, Yang F, Li CL, Chen J (2011) Antinociceptive effects of intragastric DL-tetrahydropalmatine on visceral and somatic persistent nociception and pain hypersensitivity in rats. Pharmacol Biochem Behav 100:199–204

    Article  CAS  PubMed  Google Scholar 

  • Chang X, Wang S, Bao YR, Li TJ, Yu XM, Meng XS (2016) Multicomponent, multitarget integrated adjustment-Metabolomics study of Qizhiweitong particles curing gastrointestinal motility disorders in mice induced by atropine. J Ethnopharmacol 189:14–21

    Article  CAS  PubMed  Google Scholar 

  • Choi JG, Kang SY, Kim JM, Roh DH, Yoon SY, Park JB, Lee JH, Kim HW (2012) Antinociceptive effect of cyperi rhizoma and corydalis tuber extracts on neuropathic pain in rats. Korean J Physiol Pharmacol 16:387–392

    Article  PubMed  PubMed Central  Google Scholar 

  • Chueh FY, Hsieh MT, Chen CF, Lin MT (1995) DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms. Pharmacology 51:237–244

    Article  CAS  PubMed  Google Scholar 

  • Enot DP, Haas B, Weinberger KM (2011) Bioinformatics for mass spectrometry-based metabolomics. Methods Mol Biol 719:351–375

    Article  CAS  PubMed  Google Scholar 

  • Fang Z, Lu BX, Liu MY, Zhang MX, Yi ZH, Wen CP, Shi TL (2013) Evaluating the pharmacological mechanism of Chinese medicine Si-Wu-Tang through multi-level data integration. PLoS One 8:e72334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fiehn O, Kopka J, Dörmann P, Altmann T, Trethewey RN, Willmitzer L (2000) Metabolite profiling for plant functional genomics. Nat Biotechnol 18:1157–1161

    Article  CAS  PubMed  Google Scholar 

  • Gao JL, He TC, Li YB, Wang YT (2009) A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exertssynergistic anti-tumor activity. Oncol Rep 22:1077–1083

    CAS  PubMed  Google Scholar 

  • Han JR, Xie Y, Sui FY, Liu CH, Du XW, Liu CG, Feng XL, Jiang DY (2016) Zisheng shenqi decoction ameliorates monosodium urate crystal-induced gouty arthritis in rats through anti-inflammatory and anti-oxidative effects. Mol Med Rep 14:2589–2597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang KC, Huang TW, Yang TY, Lee MS (2015) Chronic NSAIDs use increases the risk of a second hip fracture in patients after hip fracture surgery: evidence from a STROBE-compliant population-based study. Medicine 94:e1566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang KH, Kong CS, Seo Y, Kim MM, Kim SK (2009) Anti-inflammatory effect of coumarins isolated from Corydalis heterocarpa in HT29 human colon carcinoma cells. Food Chem Toxicol 47:2129–2134

    Article  CAS  PubMed  Google Scholar 

  • Kim YA, Kong CS, Yea SS, Seo Y (2010) Constituents of Corydalis heterocarpa and their anti-proliferative effects on human cancer cells. Food Chem Toxicol 48:722–728

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Ryu YB, Lee WS, Kim YH (2014) Neuraminidase inhibitory activities of quaternary isoquinoline alkaloids from corydalis turtschaninovii rhizome. Bioorg Med Chem 22:6047–6052

    Article  CAS  PubMed  Google Scholar 

  • Kiraly O, Gong GY, Muthupalani S, Engelward BP (2015) Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genet 11:e1004901

    Article  PubMed  PubMed Central  Google Scholar 

  • Koek MM, Jellema RH, van der Greef J, Tas AC, Hankemeier T (2011) Quantitative metabolomics based on gas chromatography mass spectrometry: status and perspectives. Metabolomics 7:307–328

    Article  CAS  PubMed  Google Scholar 

  • Li L, Zhang L, Yang CC (2016) Multi-target strategy and experimental studies of traditional chinese medicine for alzheimer’s disease therapy. Curr Top Med Chem 16:537–548

    Article  CAS  PubMed  Google Scholar 

  • Li TJ, Wang S, Meng XS, Bao YR, Guan SS, Liu B, Lu C, Wang L, Ran XR (2014) Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of corydalis yanhusuo alkaloid. PLoS One 9:e82499

    Article  Google Scholar 

  • Lin G, Liu C, Feng CP, Fan ZY, Dai ZL, Lai CH, Li Z, Wu GY, Wang JJ (2012) Metabolomic analysis reveals differences in umbilical vein plasma metabolites between normal and growth-restricted fetal pigs during late gestation. J Nutr 142:990–998

    Article  CAS  PubMed  Google Scholar 

  • Ling HY, Wu LM, Li LD (2006) Corydalis yanhusuo rhizoma extract reduces infarct size and improves heart function during myocardial ischemia/reperfusion by inhibiting apoptosis in rats. Phytother Res 20:448–453

    Article  CAS  PubMed  Google Scholar 

  • Liu ZY, Guo FF, Wang Y, Li C, Zhang XL, Li HL, Diao LH, Gu JY, Wang W, Li D, He FC (2016) BATMAN-TCM: a bioinformatics analysis tool for molecular mechanism of traditional chinese medicine. Sci Rep 6:21146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martin KR, Ohayon D, Witko-Sarsat V (2015) Promoting apoptosis of neutrophils and phagocytosis by macrophages: novel strategies in the resolution of inflammation. Swiss Med Wkly 145:w14056

    PubMed  Google Scholar 

  • Nicholson JK, Lindon JC, Holmes E (1999) ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29:1181–1189

    Article  CAS  PubMed  Google Scholar 

  • Nording ML, Yang J, Hegedus CM, Bhushan A, Kenyon NJ, Davis CE, Hammock BD (2010) Endogenous levels of five fatty acid metabolites in exhaled breath condensate to monitor asthma by high-performance liquid chromatography: Electrospray tandem mass spectrometry. IEEE Sens J 10:123–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oestvang J, Anthonsen MW, Johansen B (2003) Role of secretory and cytosolic phospholipase A enzymes in lysophosphatidylcholine-stimulated monocyte arachidonic acid release. FEBS Lett 555:257–262

    Article  CAS  PubMed  Google Scholar 

  • Oestvang J, Anthonsen MW, Johansen B (2011) LysoPC and PAF trigger arachidonic acid release by divergent signaling mechanisms in monocytes. J Lipids 2011:532145

    Article  PubMed  PubMed Central  Google Scholar 

  • Pak W, Takayama F, Mine M, Nakamoto K, Kodo Y, Mankura M, Egashira T, Kawasaki H, Mori A (2012) Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis. J Clin Biochem Nutr 51:227–234

    CAS  PubMed  PubMed Central  Google Scholar 

  • Papke RL, Bencherif M, Lippiello P (1996) An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the alpha 7 subtype. Neurosci Lett 213:201–204

    Article  CAS  PubMed  Google Scholar 

  • Parrish WR, Rosas-Ballina M, Gallowitsch-Puerta M, Ochani M, Ochani K, Ochani M, Yang LH, Hudson L, Lin X, Patel N, Johnson SM, Chavan S, Goldstein RS, Czura CJ, Miller EJ, Al-Abed Y, Tracey KJ, Pavlov VA (2008) Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling. Mol Med 14:567–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pereira RR, Amladi ST, Varthakavi PK (2011) A study of the prevalence of diabetes, insulin resistance, lipid abnormalities, and cardiovascular risk factors in patients with chronic plaque psoriasis. Indian J Dermatol 56:520–526

    Article  PubMed  PubMed Central  Google Scholar 

  • Pharmacopoeia Commission of PRC (2015) Pharmacopoeia of the People’s Republic of China, vol. I. Chemical Industry Press, Beijing, 139

  • Riedel W, Lang U, Oetjen U, Schlapp U, Shibata M (2003) Inhibition of oxygen radical formation by methylene blue, aspirin, or α-lipoic acid, prevents bacterial-lipopolysaccharide-induced fever. Mol Cell Biochem 247:83–94

    Article  CAS  PubMed  Google Scholar 

  • Smani Y, Domínguez-Herrera J, Ibáñez-Martínez J, Pachón J (2015) Therapeutic efficacy of lysophosphatidylcholine in severe infections caused by Acinetobacter baumannii. Antimicrob Agents Chemother 59:3920–3924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun H, Zhang AH, Wang XJ (2012) Potential role of metabolomic approaches for chinese medicine syndromes and herbal medicine. Phytother Res 26:1466–1471

    Article  CAS  PubMed  Google Scholar 

  • Wallace JL (1997) Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 112:1000–1016

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Sun NL, Zhang WD, Li HL, Lu GC, Yuan BJ, Jiang H, She JH, Zhang C (2008) Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats. J Ethnopharmacol 117:300–308

    Article  CAS  PubMed  Google Scholar 

  • Wen CP, Wu LM, Ling HY, Li LD (2007) Salutary effects of Corydalis yanhusuo extract on cardiac hypertrophy due to pressure overload in rats. J Pharm Pharmacol 59:1159–1165

    Article  CAS  PubMed  Google Scholar 

  • Wessler I, Kilbinger H, Bittinger F, Unger R, Kirkpatrick CJ (2003) The non-neuronal cholinergic system in humans: expression, function and pathophysiology. Life Sci 72:2055–2061

    Article  CAS  PubMed  Google Scholar 

  • Wolfe MM, Lichtenstein DR, Singh G (1999) Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 340:1888–1899

    Article  CAS  PubMed  Google Scholar 

  • Wu LM, Ling HY, Li LD, Jiang LX, He ML (2007) Beneficial effects of the extract from Corydalis yanhusuo in rats with heart failure following myocardial infarction. J Pharm Pharmacol 59:695–701

    Article  CAS  PubMed  Google Scholar 

  • Yoo SR, Kim Y, Lee MY, Kim OS, Seo CS, Shin HK, Jeong SJ (2016) Gyeji-tang water extract anti-inflammatory activity through inhibition of ERK and NF-κB pathways inlipopolysaccharide-stimulated RAW 264.7 cells. BMC Complement Altern Med 16:390

    Article  PubMed  PubMed Central  Google Scholar 

  • Yun KJ, Shin JS, Choi JH, Back NI, Chung HG, Lee KT (2009) Quaternary alkaloid, pseudocoptisine isolated from tubers of Corydalis turtschaninovi inhibits LPS-induced nitric oxide, PGE(2), and pro-inflammatory cytokines production via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells. Int Immunopharmacol 9:1323–1331

    Article  CAS  PubMed  Google Scholar 

  • Zhang AH, Sun H, Yan GL, Wang P, Wang XJ (2016) Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research. Biomed Chromatogr 30:7–12

    Article  PubMed  Google Scholar 

  • Zhu ZJ, Schultz AW, Wang J, Johnson CH, Yannone SM, Patti GJ, Siuzdak G (2013) Liquid chromatography quadrupole time-of-flight mass spectrometry characterization of metabolites guided by the METLIN database. Nat Protoc 8:451–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (No. 81241111) and the project of institutions of higher learning talents to support in Liaoning province (No. LR2013044).

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Correspondence to Xiansheng Meng.

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The authors declare that they have no competing interests.

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Yan Wang and Tianjiao Li contributed equally to this work.

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Wang, Y., Li, T., Meng, X. et al. Metabolomics and genomics: revealing the mechanism of corydalis alkaloid on anti-inflammation in vivo and in vitro. Med Chem Res 27, 669–678 (2018). https://doi.org/10.1007/s00044-017-2092-6

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