Pharmacologic Overview of Chlorogenic Acid and its Metabolites in Chronic Pain and Inflammation

Author(s): Deniz Bagdas*, Zulfiye Gul, Julie A. Meade, Betul Cam, Nilufer Cinkilic, Mine Sibel Gurun.

Journal Name: Current Neuropharmacology

Volume 18 , Issue 3 , 2020

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Become Reviewer

Graphical Abstract:


Abstract:

Background: Natural phenolic compounds in medicinal herbs and dietary plants are antioxidants which play therapeutic or preventive roles in different pathological situations, such as oxidative stress and inflammation. One of the most studied phenolic compounds in the last decade is chlorogenic acid (CGA), which is a potent antioxidant found in certain foods and drinks.

Objective: This review focuses on the anti-inflammatory and antinociceptive bioactivities of CGA, and the putative mechanisms of action are described. Ethnopharmacological reports related to these bioactivities are also reviewed.

Materials and Methods: An electronic literature search was conducted by authors up to October 2019. Original articles were selected.

Results: CGA has been shown to reduce inflammation and modulate inflammatory and neuropathic pain in animal models.

Conclusion: The consensus of the literature search was that systemic CGA may facilitate pain management via bolstering antioxidant defenses against inflammatory insults.

Keywords: Chlorogenic acid, inflammation, pain, inflammatory, neuropathic, antihyperalgesic, antiallodynic.

[1]
Merskey, H.; Bogduk, N. Classification of chronic pain, descriptions of chronic pain syndromes and definitions of pain terms, 2nd ed; Iasp Press: Seattle, 1994.
[2]
Stannard, C.F.; Booth, S. Churchill’s Pocketbook of Pain 2nd ed. Churchill; Livingstone, 1998.
[3]
Interagency Pain Research Coordinating Committee. National pain strategy: a comprehensive population health-level strategy for pain. https://iprcc.nih.gov/sites/default/files/HHSNational_Pain_Strategy_508C.pdf201 (Accessed May 5, 2019)
[4]
Woolf, A.D.; Pfleger, B. Burden of major musculoskeletal conditions. Bull. World Health Organ, 2003, 81, 646-656. [pii]
[http://dx.doi.org/S004296862003000900007]
[5]
Smith, B.H.; Elliott, M.; Chambers, W.; Smith, W.C.; Hannaford, P.C.; Penny, K. The impact of chronic pain in the community. Fam. Pract., 2001, 18, 292-299.
[http://dx.doi.org/10.1093/fampra/18.3.292]
[6]
Bouhassira, D.; Lantéri-Minet, M.; Attal, N.; Laurent, B.; Touboul, C. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain, 2008, 136(3), 380-387.
[http://dx.doi.org/10.1016/j.pain.2007.08.013f]
[7]
Millan, M.J. The induction of pain: An integrative review. Prog. Neurobiol., 1999, 57, 1-164.
[http://dx.doi.org/10.1016/S0301-0082(98)00048-3]
[8]
Huang, W.Y.; Cai, Y.Z.; Zhang, Y. Natural phenolic compounds from medicinal herbs and dietary plants: Potential Use for cancer Prevention. Nutr. Cancer, 2009, 62, 1-20.
[http://dx.doi.org/10.1080/ 01635580903191585]
[9]
Kim, Y.C. Neuroprotective phenolics in medicinal plants. Arch. Pharm. Res., 2010, 33, 1611-1632.
[http://dx.doi.org/10.1007/s12272-010-1011-x]
[10]
Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr., 2004, 79, 727-747.
[http://dx.doi.org/10.1093/ajcn/79.5.727]
[11]
Scalbert, A.; Manach, C.; Morand, C.; Rémésy, C.; Jiménez, L. Dietary polyphenols and the prevention of diseases. Crit. Rev. Food Sci. Nutr., 2005, 45, 287-306.
[http://dx.doi.org/10.1080/1040869059096]
[12]
El-Seedi, H.R.; El-Said, A.M.; Khalifa, S.; Göransson, U.; Bohlin, L.; Borg-Karlson, A.K.; Verpoorte, R. Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids. J. Agric. Food Chem., 2012, 60, 10877-10895.
[http://dx.doi.org/10.1021/jf301807g]
[13]
Clifford, M.N. Review Chlorogenic acids and other cinnamates - nature, occurrence, dietary burden, absorption and metabolism. J. Sci. Food Agric., 1999, 79, 362-372.
[http://dx.doi.org/10.1002/(SICI)1097-0010(20000515)80:7<1033:AID-JSFA595>3.0.CO;2-T]
[14]
Del Rio, D.; Stalmach, A.; Calani, L.; Crozier, A. Bioavailability of coffee chlorogenic acids and green tea flavan-3-ols. Nutrients, 2010, 2, 820-833.
[http://dx.doi.org/10.3390/nu2080820]
[15]
Ludwig, I.; Clifford, M.N.; Lean, M.E.J.; Ashihara, H.; Crozier, A. Coffee: biochemistry and potential impact on health. Food Funct., 2014, 5, 1695-1717.
[http://dx.doi.org/10.1039/c4fo00042k]
[16]
Abraham, S.K.; Schupp, N.; Schmid, U.; Stopper, H. Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid. Mol. Nutr. Food Res., 2007, 51, 880-887.
[http://dx.doi.org/10.1002/mnfr.200600214]
[17]
dos Santos, M.D.; Almeida, M.C.; Lopes, N.P.; de Souza, G.E.P. Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid. Biol. Pharm. Bull., 2006, 29, 2236-2240.
[http://dx.doi.org/10.1248/bpb.29.2236]
[18]
Sato, Y.; Itagaki, S.; Kurokawa, T.; Ogura, J.; Kobayashi, M.; Hirano, T.; Sugawara, M.; Iseki, K. In vitro and in vivo antioxidant properties of chlorogenic acid and caffeic acid. Int. J. Pharm., 2011, 403, 136-138.
[http://dx.doi.org/10.1016/j.ijpharm.2010.09.035]
[19]
Gul, Z.; Demircan, D.; Bagdas, D.; Buyukuysal, R.L. Protective effects of chlorogenic acid and its metabolites on hydrogen peroxide-induced alterations in rat brain slices: a comparative study with resveratrol. Neurochem. Res., 2016, 41, 2075-2085.
[http://dx.doi.org/10.1007/s11064-016-1919-8]
[20]
Bagdas, D. Cam, Etoz B.; Gul, Z.; Ziyanok, S.; Inan, S.; Gul, NY.; Topal, A.; Cinkilic, N.; Tas, S.; Ozyigit, MO.; Turacozen, O.; Gurun, MS. In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile. Food Chem. Toxicol., 2015, 81, 54-61.
[http://dx.doi.org/10.1016/j.fct.2015.04.001]
[21]
Bagdas, D. Cam, Etoz B.; Inan, Ozturkoglu S.; Cinkilic, N.; Ozyigit, MO.; Gul, Z.; Isbil Buyukcoskun, N.; Ozluk, K.; Gurun, MS. Effects of systemic chlorogenic acid on random-pattern dorsal skin flap survival in diabetic rats. Biol. Pharm. Bull., 2014, 37, 361-370.
[http://dx.doi.org/10.1097/SAP.0000000000000313]
[22]
European Medicines Agency (EMEA). Evaluation of Medicines for Humen Use Community herbal monograph on Urtica dioca L. and Urtica urens L. Herba. Doc. 2008. Ref. EMEA/HMPC/170261/2006
[23]
Domínguez, J.A. Contribuciones a la Materia Médica Argentina. Peuser. , 1982. Buenos Aires, Argentina
[24]
Yonathan, M.; Asres, K.; Assefa, A.; Bucar, F. In vivo antiinflammatory and anti-nociceptive activities of Cheilanthes farinosa. J. Ethnopharmacol., 2006, 108, 462-70. [doi:10.1016/j.jep.2006.06.006]
[25]
American Autoimmune related diseases association. https://www.aarda.org/ (Accessed May 5, 2019)
[26]
Integrated chronic disease prevention and control.. https://www.who.int/chp/about/integrated_cd/en/ (Accessed May 5, 2019)
[27]
Lenart, N.; Brough, D.; Denes, A. Inflammasomes link vascular disease with neuroinflammation and brain disorders. J. Cereb. Blood Flow Metab., 2016, 36, 1668-1685.
[http://dx.doi.org/10.1177/ 0271678X16662043]
[28]
Jantan, I.; Ahmad, W.; Bukhari, S.N.A. Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. Front. Plant Sci., 2015, 6, 1-18.
[http://dx.doi.org/10.3389/fpls.2015.00655]
[29]
Clark, R.A. Cutaneous tissue repair: basic biologic considerations. I. J. Am. Acad. Dermatol., 1985, 13, 701-725.
[30]
Stadelmann, W.K.; Digenis, A.G.; Tobin, G.R. Physiology and healing dynamics of chronic cutaneous wounds. Am. J. Surg., 1998, 176, 26S-38S.
[31]
Nantel, F.; Denis, D.; Gordon, R.; Northey, A.; Cirino, M.; Metters, K.M.; Chan, C.C. Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation. Br. J. Pharmacol., 1999, 128, 853-859.
[http://dx.doi.org/10.1038/sj.bjp.0702866]
[32]
DiDonato, J.A.; Mercurio, F.; Karin, M. NF-κB and the link between inflammation and cancer. Immunol. Rev., 2012, 246, 379-400.
[http://dx.doi.org/10.1111/j.1600-065X.2012.01099.x]
[33]
Vitiello, M.; Galdiero, M.; Finamore, E.; Galdiero, S.; Galdiero, M. NF-κB as a potential therapeutic target in microbial diseases. Mol. Biosyst., 2012, 8, 1108-1120.
[http://dx.doi.org/10.1039/c2mb05335g]
[34]
Kopf, M.; Bachmann, M.F.; Marsland, B.J. Averting inflammation by targeting the cytokine environment. Nat. Rev. Drug Discov., 2010, 9, 703-718.
[http://dx.doi.org/10.1038/nrd2805]
[35]
Guzik, T.J.; Korbut, R.; Adamek-Guzik, T. Nitric oxide and superoxide in inflammation and immune regulation. J. Physiol. Pharmacol., 2003, 54, 469-487.
[36]
Zamora, R.; Vodovotz, Y.; Billiar, T.R. Inducible nitric oxide synthase and inflammatory diseases. Mol. Med., 2000, 6, 347-373.
[37]
Kim, S.R.; Jung, Y.R.; Kim, D.H.; An, H.J.; Kim, M.K.; Kim, N.D.; Chung, H.Y. Caffeic acid regulates LPS-induced NF-κB activation through NIK/IKK and c-Src/ERK signaling pathways in endothelial cells. Arch. Pharm. Res., 2014, 37, 539-547.
[http://dx.doi.org/10.1007/s12272-013-0211-6]
[38]
Remick, D.G.; Strieter, R.M.; Eskandari, M.K.; Nguyen, D.T.; Genord, M.A.; Raiford, C.L.; Kunkel, S.L. Role of tumor necrosis factor-alpha in lipopolysaccharide-induced pathologic alterations. Am. J. Pathol., 1990, 136, 49-60.
[39]
Hsu, H.Y.; Wen, M.H. Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression. J. Biol. Chem., 2002, 277, 22131-22139.
[http://dx.doi.org/10.1074/jbc.M111883200]
[40]
Shan, J.; Fu, J.; Zhao, Z.; Kong, X.; Huang, H.; Luo, L.; Yin, Z. Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264.7 cells through suppressing NF-κB and JNK/AP-1 activation. Int. Immunopharmacol., 2009, 9, 1042-1048.
[http://dx.doi.org/10.1016/j.intimp.2009.04.011]
[41]
Krakauer, T. The polyphenol chlorogenic acid inhibits staphylococcal exotoxin-induced inflammatory cytokines and chemokines. Immunopharmacol. Immunotoxicol., 2002, 24, 113-119.
[http://dx.doi.org/10.1081/ IPH-120003407]
[42]
Kang, T.Y.; Yang, H.R.; Zhang, J.; Li, D.; Lin, J.; Wang, L.; Xu, X. The studies of chlorogenic Acid antitumor mechanism by gene chip detection: the immune pathway gene expression. J. Anal. Methods Chem., 2013, 617243
[http://dx.doi.org/10.1155/2013/617243]
[43]
Zheng, Z.; Sheng, Y.; Lu, B.; Ji, L. The therapeutic detoxification of chlorogenic acid against acetaminophen-induced liver injury by ameliorating hepatic inflammation. Chem. Biol. Interact., 2015, 238, 93-101.
[http://dx.doi.org/10.1016/j.cbi.2015.05.023]
[44]
Bianchi, M.E.; Manfredi, A.A. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol. Rev., 2007, 220, 35-46.
[http://dx.doi.org/10.1111/j.1600-065X.2007.00574.x]
[45]
Lee, C.H.; Yoon, S.J.; Lee, S.M. Chlorogenic acid attenuates high mobility group box 1 (HMGB1) and enhances host defense mechanisms in murine sepsis. Mol. Med., 2012, 18, 1437-1448.
[http://dx.doi.org/10.2119/molmed.2012.00279]
[46]
Xu, Y.; Chen, J.; Yu, X.; Tao, W.; Jiang, F.; Yin, Z.; Liu, C. Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice. Inflamm. Res., 2010, 59, 871-877.
[http://dx.doi.org/10.1007/s00011-010-0199-z]
[47]
Yun, N.; Kang, J.W.; Lee, S.M. Protective effects of chlorogenic acid against ischemia/reperfusion injury in rat liver: molecular evidence of its antioxidant and anti-inflammatory properties. J. Nutr. Biochem., 2012, 23, 1249-1255.
[http://dx.doi.org/10.1016/j.jnutbio.2011.06.018]
[48]
Chen, J.; Xie, H.; Chen, D.; Yu, B.; Mao, X.; Zheng, P.; Yu, P.; Luo, Y.; Luo, J.; He, J. Chlorogenic acid improves intestinal development via suppressing Mucosa inflammation and cell apoptosis in Weaned Pigs. ACS Omega, 2018, 3, 2211-2219.
[49]
Ji, L.; Jiang, P.; Lu, B.; Sheng, Y.; Wang, X.; Wang, Z. Chlorogenic acid, a dietary polyphenol, protects acetaminophen-induced liver injury and its mechanism. J. Nutr. Biochem., 2013, 24, 1911-1919.
[http://dx.doi.org/10.1016/j.jnutbio.2013.05.007]
[50]
Gong, Y.; Jin, X.; Wang, Q.S.; Wei, S.H.; Hou, B.K.; Li, H.Y.; Zhang, M.N.; Li, Z.H. The involvement of high mobility group 1 cytokine and phospholipases A2 in diabetic retinopathy. Lipids Health Dis., 2014, 13, 156.
[http://dx.doi.org/10.1186/1476-511X-13-156]
[51]
Nogueira-Machado, J.A.; de Oliveira Volpe, C.M. HMGB-1 as a target for inflammation controlling. Recent Pat. Endocr. Metab. Immune Drug Discov., 2012, 6, 201-209.
[52]
Park, S.H.; Baek, S.I.; Yun, J.; Lee, S.; Yoon, D.Y.; Jung, J.K.; Jung, S.H.; Hwang, B.Y.; Hong, J.T.; Han, S.B.; Kim, Y. IRAK4 as a molecular target in the amelioration of innate immunity-related endotoxic shock and acute liver injury by chlorogenic acid. J. Immunol., 2015, 194, 1122-1130.
[http://dx.doi.org/10.4049/jimmunol.1402101]
[53]
Lou, Z.; Wang, H.; Zhu, S.; Ma, C.; Wang, Z. Antibacterial activity and mechanism of action of chlorogenic acid. J. Food Sci., 2011, 76, 398-403.
[http://dx.doi.org/10.1111/j.1750-3841.2011.02213.x]
[54]
Shibata, H.; Sakamoto, Y.; Oka, M.; Kono, Y. Natural antioxidant, chlorogenic acid, protects against DNA breakage caused by monochloramine. Biosci. Biotechnol. Biochem., 1999, 63, 1295-1297.
[http://dx.doi.org/10.1271/bbb.63.1295]
[55]
Kim, J.; Lee, S.; Shim, J.; Kim, H.W.; Kim, J.; Jang, Y.J.; Yang, H.; Park, J.; Choi, S.H.; Yoon, J.H.; Lee, K.W.; Lee, H.J. Caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid up-regulate NQO1 expression and prevent H2O2-induced apoptosis in primary cortical neurons. Neurochem. Int., 2012, 60, 466-474.
[http://dx.doi.org/10.1016/j.neuint.2012.02.004]
[56]
Bagdas, D.; Gul, N.Y.; Topal, A.; Tas, S.; Ozyigit, M.O.; Cinkilic, N.; Gul, Z.; Etoz, B.C.; Ziyanok, S.; Inan, S.; Turacozen, O.; Gurun, M.S. Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound healing. Naunyn Schmiedebergs Arch. Pharmacol., 2014, 387, 1101-1116.
[http://dx.doi.org/10.1007/s00210-014-1034-9]
[57]
Domitrović, R.; Jakovac, H.; Romić, Z.; Rahelić, D.; Tadić, Z. Antifibrotic activity of Taraxacum officinale root in carbon tetrachloride-induced liver damage in mice. J. Ethnopharmacol., 2010, 130, 569-577.
[http://dx.doi.org/10.1016/j.jep.2010.05.046]
[58]
Hwang, S.J.; Kim, Y.W.; Park, Y.; Lee, H.J.; Kim, K.W. Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells. Inflamm. Res., 2014, 63, 81-90.
[http://dx.doi.org/10.1007/s00011-013-0674-4]
[59]
Shi, H.; Dong, L.; Jiang, J.; Zhao, J.; Zhao, G.; Dang, X.; Lu, X.; Jia, M. Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology, 2013, 303, 107-114.
[http://dx.doi.org/10.1016/j.tox.2012.10.025]
[60]
Liu, Y.; Zeng, G. Cancer and innate immune system interactions: translational potentials for cancer immunotherapy. J. Immunother., 2012, 35, 299-308.
[http://dx.doi.org/10.1097/CJI.0b013e3182518e83]
[61]
Osborn, O.; Olefsky, J.M. The cellular and signaling networks linking the immune system and metabolism in disease. Nat. Med., 2012, 18, 363-374.
[http://dx.doi.org/10.1038/nm.2627]
[62]
Chen, W.P.; Wu, L.D. Chlorogenic acid suppresses interleukin-1β-induced inflammatory mediators in human chondrocytes. Int. J. Clin. Exp. Pathol., 2014, 7, 8797-8801.
[63]
Bagdas, D.; Cam, E.B.; Gul, Z.; Ozyigit, M.O.; Cinkilic, N.; Inan, O.S.; Isbil, B.N.; Ozluk, K.; Gurun, M.S. Chlorogenic Acid enhances abdominal skin flap survival based on superficial inferior epigastric artery in nondiabetic and diabetic rats. Ann. Plast. Surg., 2016, 77, 21-25.
[http://dx.doi.org/10.1097/SAP.0000000000000313]
[64]
Jang, H.; Ahn, H.R.; Jo, H.; Kim, K.A.; Lee, E.H.; Lee, K.W.; Jung, S.H.; Lee, C.Y. Chlorogenic acid and coffee prevent hypoxia-induced retinal degeneration. J. Agric. Food Chem., 2014, 62, 182-191.
[http://dx.doi.org/10.1021/jf404285v]
[65]
Jang, H.; Choi, Y.; Ahn, H.R.; Jung, S.H.; Lee, C.Y. Effects of phenolic acid metabolites formed after chlorogenic acid consumption on retinal degeneration in vivo. Mol. Nutr. Food Res., 2015, 59, 1918-1929.
[http://dx.doi.org/10.1002/mnfr.201400897]
[66]
Shen, W.; Qi, R.; Zhang, J.; Wang, Z.; Wang, H.; Hu, C.; Zhao, Y.; Bie, M.; Wang, Y.; Fu, Y.; Chen, M.; Lu, D. Chlorogenic acid inhibits LPS-induced microglial activation and improves survival of dopaminergic neurons. Brain Res. Bull., 2012, 8, 487-494.
[http://dx.doi.org/10.1016/j.brainresbull.2012.04.010]
[67]
Oboh, G.; Agunloye, O.M.; Akinyemi, A.J.; Ademiluyi, A.O.; Adefegha, S.A. Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer’s disease and some pro-oxidant induced oxidative stress in rats’ brain-in vitro. Neurochem. Res., 2013, 38, 413-419.
[http://dx.doi.org/10.1007/ s11064-012-0935-6]
[68]
Saitou, K.; Ochiai, R.; Kozuma, K.; Sato, H.; Koikeda, T.; Osaki, N.; Katsuragi, Y. Effect of chlorogenic acids on cognitive function: A randomized, double-blind, placebo-controlled trial. Nutrients, 2018, 10, 1337.
[69]
Poljsak, B.; Milisav, I. The neglected significance of “antioxidative stress”. Oxid. Med. Cell. Longev., 2012, 2012, 1-12.
[http://dx.doi.org/10.1155/2012/480895]
[70]
Yordi, E.G.; Pérez, E.M.; Matos, M.J.; Villares, E.U. Antioxidant and pro-oxidant effects of polyphenolic compounds and structure-activity relationship evidence; Jaouad Bouayed and Torsten Bohn, IntechOpen, 2012.
[http://dx.doi.org/10.5772/29471]
[71]
Sakihama, Y.; Cohen, M.F.; Grace, S.C.; Yamasaki, H. Plant phenolic antioxidant and prooxidant activities: Phenolics-induced oxidative damage mediated by metals in plants. Toxicology, 2002, 177, 67-80.
[http://dx.doi.org/10.1016/S0300-483X(02)00196-8]
[72]
Burgos-Morón, E.; Calderón-Montaño, J.M.; Orta, M.L.; Pastor, N.; Pérez-Guerrero, C.; Austin, C.; López-Lázaro, M. The coffee constituent chlorogenic acid induces cellular DNA damage and formation of topoisomerase I-and II-DNA complexes in cells. J. Agric. Food Chem., 2012, 60, 7384-7391.
[73]
Du, W.Y.; Chang, C.; Zhang, Y.; Liu, Y.Y.; Sun, K.; Wang, C.S.; Wang, M.X.; Liu, Y.; Wang, F.; Fan, J.Y. High-dose chlorogenic acid induces inflammation reactions and oxidative stress injury in rats without implication of mast cell degranulation. J. Ethnopharmacol., 2013, 147, 74-83.
[74]
Olthof, M.R.; Hollman, P.C.; Zock, P.L.; Katan, M.B. Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am. J. Clin. Nutr., 2001, 73, 532-538.
[75]
Onakpoya, I.; Terry, R.; Ernst, E. The use of green coffee extract as a weight loss supplement: a systematic review and meta-analysis of randomised clinical trials. Gastroenterol. Res. Pract., 2011, 2011(382852), 1-6.
[http://dx.doi.org/10.1155/2011/382852]
[76]
Rajan, R.K.; Hussein, M.Z.; Fakurazi, S.; Yusoff, K.; Masarudin, M.J. Increased ROS scavenging and antioxidant efficiency of chlorogenic acid compound delivered via a chitosan nanoparticulate system for efficient In Vitro visualization and accumulation in human renal adenocarcinoma cells. Int. J. Mol. Sci., 2019, 20, 4667.
[http://dx.doi.org/10.3390/ijms20194667]
[77]
Barahuie, F.; Hussein, M.Z.; Arulselvan, P.; Fakurazi, S.; Zainal, Z. Controlled in vitro release of the anticancer drug chlorogenic acid using magnesium/aluminium-layered double hydroxide as a nanomatrix. Sci. Adv. Mater., 2016, 8, 501-513.
[78]
Cheng, B.C.Y.; Ma, X.Q.; Kwan, H.Y.; Tse, K.W.; Cao, H.H.; Su, T.; Shu, X.; Wu, Z.; Yu, Z. A herbal formula consisting of Rosae Multiflorae Fructus and Lonicerae Japonicae Flos inhibits inflammatory mediators in LPS-stimulated RAW 264.7 macrophages. J. Ethnopharmacol., 2014, 153, 922-7.
[http://dx.doi.org/10.1016/j.jep. 2014.02.029]
[79]
Búfalo, M.C.; Ferreira, I.; Costa, G.; Francisco, V.; Liberal, J.; Cruz, M.T.; Lopes, M.C.; Batista, M.T.; Sforcin, J.M. Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages. J. Ethnopharmacol., 2013, 149, 84-92.
[http://dx.doi.org/10. 1016/j.jep.2013.06.004]
[80]
Yang, W.S.; Jeong, D.; Yi, Y.S.; Park, J.G.; Seo, H.; Moh, S.H.; Hong, S.; Cho, J.Y. IRAK1/4-targeted anti-inflammatory action of caffeic acid. Mediators Inflamm., 2013, 518183.
[http://dx.doi.org/10.1155/2013/518183]
[81]
Das, U.; Manna, K.; Sinha, M.; Datta, S.; Das, D.K.; Chakraborty, A.; Ghosh, M.; Saha, K.D.; Dey, S. Role of ferulic acid in the amelioration of ionizing radiation induced inflammation: a murine model. PLoS One, 2014, 9 e97599
[http://dx.doi.org/10.1371/journal.pone. 0097599]
[82]
Navarrete, S.; Alarcón, M.; Palomo, I. Aqueous extract of tomato (Solanum lycopersicum L.) and ferulic acid reduce the expression of TNF-α and IL-1β in LPS-activated macrophages. Molecules, 2015, 20, 15319-15329.
[http://dx.doi.org/10.3390/molecules200815319]
[83]
Yun, K.J.; Koh, D.J.; Kim, S.H.; Park, S.J.; Ryu, J.H.; Kim, D.G.; Lee, J.Y.; Lee, K.T. Anti-inflammatory effects of sinapic acid through the suppression of inducible nitric oxide synthase, cyclooxygase-2, and proinflammatory cytokines expressions via nuclear factor-kappaB inactivation. J. Agric. Food Chem., 2008, 56, 10265-10272.
[http://dx.doi.org/10.1021/jf802095g]
[84]
Jin, X.H.; Ohgami, K.; Shiratori, K.; Suzuki, Y.; Koyama, Y.; Yoshida, K.; Ilieva, I.; Tanaka, T.; Onoe, K.; Ohno, S. Effects of blue honeysuckle (Lonicera caerulea L.) extract on lipopolysaccharide-induced inflammation in vitro and in vivo. Exp. Eye Res., 2006, 82, 860-867.
[http://dx.doi.org/10.1016/j.exer.2005.10.024]
[85]
Costigan, M.; Scholz, J.; Woolf, C.J. Neuropathic pain: A maladaptive response of the nervous system to damage. Annu. Rev. Neurosci., 2009, 32, 1-32.
[http://dx.doi.org/10.1146/annurev.neuro.051508.135531]
[86]
Price, T.J.; Cervero, F.; Gold, M.S.; Hammond, D.L.; Prescott, S.A. Chloride regulation in the pain pathway. Brain Res. Rev., 2009, 60, 149-170.
[http://dx.doi.org/10.1016/j.brainresrev.2008.12.015]
[87]
Woolf, C.J. Overcoming obstacles to developing new analgesics. Nat. Med., 2010, 16, 1241-1247.
[http://dx.doi.org/10.1038/nm.2230]
[88]
Moalem, G.; Tracey, D.J. Immune and inflammatory mechanisms in neuropathic pain. Brain Res. Rev., 2006, 51, 240-264.
[http://dx.doi.org/10.1016/j.brainresrev.2005.11.004]
[89]
O’Neill, L.A.J. Targeting signal transduction as a strategy to treat inflammatory diseases. Nat. Rev. Drug Discov., 2006, 5, 549-563.
[http://dx.doi.org/10.1038/nrd2070]
[90]
Kim, H.; Song, M.J. Oral traditional plant-based therapeutic applications for pain relief recorded in North Jeolla province, Korea. Indian J. Tradit. Knowl., 2013, 12, 4, 573-584.
[91]
Lim, E.Y.; Kim, J.G.; Lee, J.; Lee, C.; Shim, J.; Kim, Y.T. Analgesic effects of Cnidium officinale extracts on postoperative, neuropathic, and menopausal pain in rat models. Evid. Based Complement. Alternat. Med., 2019, 9698727, 1-8.
[http://dx.doi.org/10.1155/ 2019/9698727]
[92]
Pagani, E.; Santos, J.F.L.; Rodrigues, E. Culture-Bound syndromes of a Brazilian Amazon riverine population : tentative correspondence between traditional and conventional medicine terms and possible ethnopharmacological implications. J. Ethnopharmacol., 2017, 203, 80-89.
[http://dx.doi.org/10.1016/j.jep.2017.03.024]
[93]
Hamanna, F.R.; Bruscoa, I.; Severo, G.C.; Carvalho, L.M.; Faccin, H.; Gobo, L.; Oliveira, S.M.; Rubin, M.A. Mansoa alliacea extract presents antinociceptive effect in a chronic inflammatory pain model in mice through opioid mechanisms. Neurochem. Int., 2019, 122, 157-169.
[http://dx.doi.org/10.1016/j.neuint.2018.11.017]
[94]
Bagdas, D.; Ozboluk, H.Y.; Cinkilic, N.; Gurun, M.S. Antinociceptive effect of chlorogenic acid in rats with painful diabetic neuropathy. J. Med. Food, 2014, 17, 730-732.
[http://dx.doi.org/10.1089/jmf.2013.2966]
[95]
Bagdas, D.; Cinkilic, N.; Ozboluk, H.Y.; Ozyigit, M.O.; Gurun, M.S. Antihyperalgesic activity of chlorogenic acid in experimental neuropathic pain. J. Nat. Med., 2013, 67, 698-704.
[http://dx.doi.org/10.1007/s11418-012-0726-z]
[96]
Hara, K.; Haranishi, Y.; Kataoka, K.; Takahashi, Y.; Terada, T.; Nakamura, M.; Sata, T. Chlorogenic acid administered intrathecally alleviates mechanical and cold hyperalgesia in a rat neuropathic pain model. Eur. J. Pharmacol., 2014, 723, 459-64.
[http://dx.doi.org/10. 1016/j.ejphar.2013.10.046]
[97]
Chauhan, P.S.; Satti, N.K.; Sharma, P.; Sharma, V.K.; Suri, K.A.; Bani, S. Differential effects of chlorogenic acid on various immunological parameters relevant to rheumatoid arthritis. Phytother. Res., 2012, 26, 1156-1165.
[http://dx.doi.org/10.1002/ptr.3684]
[98]
Morishita, H.; Ohnishi, M. Bioactive natural products (Part F). Stud. Nat. Prod. Chem., 2001, 25, 919-953.
[http://dx.doi.org/10.1016/S1572-5995(01)80024-7]
[99]
Zhang, X.; Huang, H.; Yang, T.; Ye, Y.; Shan, J.; Yin, Z.; Luo, L. Chlorogenic acid protects mice against lipopolysaccharide-induced acute lung injury. Injury, 2010, 41, 746-752.
[http://dx.doi.org/10.1016/j.injury. 2010.02.029]
[100]
Bennett, G.J.; Xie, Y.K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain, 1988, 33, 87-107.
[101]
Muthuraman, A.; Singh, N. Attenuating effect of Acorus calamus extract in chronic constriction injury induced neuropathic pain in rats: an evidence of anti-oxidative, anti-inflammatory, neuroprotective and calcium inhibitory effects. BMC Complement. Altern. Med., 2011, 11, 14.
[http://dx.doi.org/10.1186/1472-6882-11-24]
[102]
Enna, S.J.; McCarson, K.E. The role of GABA in the mediation and perception of pain. Adv. Pharmacol., 2006, 54, 1-27.
[http://dx.doi.org/10.1016/S1054-3589(06)54001-3]
[103]
Zeilhofer, H.U.; Benke, D.; Yevenes, G.E. Chronic pain states: pharmacological strategies to restore diminished inhibitory spinal pain control. Annu. Rev. Pharmacol. Toxicol., 2012, 52, 111-133.
[http://dx.doi.org/10.1146/annurev-pharmtox-010611-134636]
[104]
Hwang, J.H.; Hwang, K.S.; Kim, J.U.; Choi, I.C.; Park, P.H.; Han, S.M. The interaction between intrathecal neostigmine and GABA receptor agonists in rats with nerve ligation Injury. Anesth. Analg., 2001, 93, 1297-1303.
[http://dx.doi.org/10.1097/00000539-200111000-00054]
[105]
Hwang, J.H.; Yaksh, T.L. The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the rat. Pain, 1997, 70, 15-22.
[http://dx.doi.org/10.1016/S0304-3959(96)03249-6]
[106]
Malan, T.P.; Mata, H.P.; Porreca, F. Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain. Anesthesiology, 2002, 96, 1161-1167.
[107]
Zhang, A.; Gao, Y.; Zhong, X.; Xu, C.; Li, G.; Liu, S.; Lin, J.; Li, X.; Zhang, Y.; Liu, H.; Linag, S. Effect of sodium ferulate on the hyperalgesia mediated by P2X3 receptor in the neuropathic pain rats. Brain Res., 2010, 1313, 215-221.
[http://dx.doi.org/10.1016/j.brainres. 2009.11.067]
[108]
Carrasco, C.; Naziroǧlu, M.; Rodríguez, A.B.; Pariente, J.A. Neuropathic pain: Delving into the oxidative origin and the possible Implication of transient receptor potential channels. Front. Physiol., 2018, 14, 9-95. eCollection 2018
[http://dx.doi.org/10.3389/fphys.2018.00095]
[109]
Duggett, N.A.; Griffiths, L.A.; McKenna, O.E.; de Santis, V.; Yongsanguanchai, N.; Mokori, E.B.; Flatters, S.J. Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy. Neuroscience, 2016, 333, 13-26.
[http://dx.doi.org/10.1016/j.neuroscience.2016.06.050]
[110]
Gao, X.; Kim, H.K.; Chung, J.M.; Chung, K. Reactive oxygen species (ROS) are involved in enhancement of NMDA-receptor phosphorylation in animal models of pain. Pain, 2007, 131, 262-271.
[http://dx.doi.org/10.1016/j.pain.2007.01.011]
[111]
Kim, H.K.; Park, S.K.; Zhou, J.L.; Taglialatela, G.; Chung, K.; Coggeshall, R.E.; Chung, J.M. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain, 2004, 111, 116-124.
[http://dx.doi.org/10.1016/j.pain.2004.06.008]
[112]
Park, E.S.; Gao, X.; Chung, J.M.; Chung, K. Levels of mitochondrial reactive oxygen species increase in rat neuropathic spinal dorsal horn neurons. Neurosci. Lett., 2006, 391, 108-111.
[http://dx.doi.org/10. 1016/j.neulet.2005.08.055]
[113]
Yowtak, J.; Lee, K.Y.; Kim, H.Y.; Wang, J.; Kim, H.K.; Chung, K.; Chung, J.M. Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release. Pain, 2011, 152, 844-852.
[http://dx.doi.org/10.1016/j.pain.2010.12.034]
[114]
Mehrotra, A.; Shanbhag, R.; Chamallamudi, M.R.; Singh, V.P.; Mudgal, J. Ameliorative effect of caffeic acid against inflammatory pain in rodents. Eur. J. Pharmacol., 2011, 666, 80-86.
[http://dx.doi.org/10.1016/ j.ejphar.2011.05.039]
[115]
Zhang, A.; Xu, C.; Liang, S.; Gao, Y.; Li, G.; Wei, J.; Wan, F.; Liu, S.; Lin, J. Role of sodium ferulate in the nociceptive sensory facilitation of neuropathic pain injury mediated by P2X3 receptor. Neurochem. Int., 2008, 53, 278-282.
[http://dx.doi.org/10.1016/j.neuint.2008.08.008]
[116]
Rasband, M.N.; Park, E.W.; Vanderah, T.W.; Lai, J.; Porreca, F.; Trimmer, J.S. Distinct potassium channels on pain-sensing neurons. Proc. Natl. Acad. Sci. U. S. A., 2001, 98, 13373-8.
[http://dx.doi.org/10. 1073/pnas.231376298]
[117]
Takeda, M.; Tanimoto, T.; Ikeda, M.; Kadoi, J.; Nasu, M.; Matsumoto, S. Opioidergic modulation of excitability of rat trigeminal root ganglion neuron projections to the superficial layer of cervical dorsal horn. Neuroscience, 2004, 125, 995-1008.
[http://dx.doi.org/10.1016/j. neuroscience.2004.02.029]
[118]
Pearce, R.J.; Duchen, M.R. Differential expression of membrane currents in dissociated mouse primary sensory neurons. Neuroscience, 1994, 63, 1041-1056.
[http://dx.doi.org/10.1016/0306-4522(94)90571-1]
[119]
Judge, S.; Lee, J.M.; Bever, C.T.; Hoffman, P.M. Voltage-gated potassium channels in multiple sclerosis: Overview and new implications for treatment of central nervous system inflammation and degeneration. J. Rehabil. Res. Dev., 2006, 43, 111-122.
[http://dx.doi.org/10.1682/JRRD.2004.09.0116]
[120]
Du, X.; Gamper, N. Potassium channels in peripheral pain pathways: Expression, function and therapeutic potential. Curr. Neuropharmacol., 2013, 11, 621-640.
[121]
Zhang, Y.J.; Lu, X.W.; Song, N.; Kou, L.; Wu, M.K.; Liu, F.; Wang, H.; Shen, J.F. Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons. Int. J. Oral Sci., 2014, 6, 233-240.
[http://dx.doi.org/10.1038/ijos.2014.58]
[122]
Liu, F.; Lub, X.W.; Zhang, Y.J.; Koub, L.; Songa, N.; Wua, M.K.; Wanga, M.; Wanga, H.; Shen, J.F. Effects of chlorogenic acid on voltage-gated potassium channels of trigeminal ganglion neurons in an inflammatory environment. Brain Res. Bull., 2016, 127, 119-125.
[http://dx.doi.org/10.1016/j.brainresbull.2016.09.005]
[123]
Birinyi-Strachan, L.C.; Gunning, S.J.; Lewis, R.J.; Nicholson, G.M. Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons. oxicol. Appl. Pharmacol., 2005, 204, 175-86.
[http://dx.doi.org/10. 1016/j.taap.2004.08.020]
[124]
Everill, B.; Kocsis, J.D. Reduction in potassium currents in identified cutaneous afferent dorsal root ganglion neurons after axotomy. J. Neurophysiol., 1999, 82, 700-8.
[http://dx.doi.org/10.1152/jn.1999.82. 2.700]
[125]
Harriott, A.M.; Gold, M.S. Contribution of primary afferent channels to neuropathic pain. Curr. Pain Headache Rep., 2009, 13, 197-207.
[http://dx.doi.org/10.1007/s11916-009-0034-9]
[126]
Qu, Z.W.; Liu, T.T.; Qiu, C.Y.; Li, J.D.; Hu, W.P. Inhibition of acid-sensing ion channels by chlorogenic acid in rat dorsal root ganglion neurons. Neurosci. Lett., 2014, 567, 35-39.
[http://dx.doi.org/10.1021/ acsomega.7b01971]
[127]
Kakita, K.; Tsubouchi, H.; Adachi, M.; Takehana, S.; Shimazu, Y.; Takeda, M. Local subcutaneous injection of chlorogenic acid inhibits the nociceptive trigeminal spinal nucleus caudalis neurons in rats. Neurosci. Res., 2018, 134, 49-55.
[http://dx.doi.org/10.1016/j.neures. 2017.11.009]
[128]
Mahomoodally, M.F. Traditional medicines in Africa: an appraisal of ten potent African medicinal plants. Evid. Based Complement. Alternat. Med., 2013, Article ID, 617459, 14.
[http://dx.doi.org/10.1155/2013/617459]
[129]
Akhtar, N.; Haqqi, T.M. Current nutraceuticals in the management of osteoarthritis: a review. Ther. Adv. Musculoskelet. Dis., 2012, 4, 181-207.
[http://dx.doi.org/10.1177/1759720X11436238]
[130]
Wang, M.; Li, K.; Nie, Y.; Wei, Y.; Li, X. Antirheumatoid arthritis Activities and chemical compositions of phenolic compounds-rich fraction from Urtica atrichocaulis, an endemic plant to China. Evid. Based Complement. Alternat. Med., 2012, 818230
[http://dx.doi.org/10.1155/2012/818230]
[131]
Yang, C.L.H.; Or, T.C.T.; Ho, M.H.K.; Lau, A.S.Y. Scientific basis of botanical medicine as alternative remedies for rheumatoid Arthritis. Clin. Rev. Allergy Immunol., 2013, 44, 284-300.
[http://dx.doi.org/10.1007/s12016-012-8329-8]
[132]
Dion, C.; Haug, C.; Guan, H.; Ripoll, C.; Spiteller, P.; Coussaert, A.; Boulet, E.; Schmidt, D.; Wei, J.; Zhou, Y.; Lamottke, K. Evaluation of the anti-inflammatory and antioxidative potential of four fern species from China intended for use as food supplements. Nat. Prod. Commun., 2015, 10, 597-603.
[133]
Sales, C.; Oliviero, F.; Spinella, P. The mediterranean diet model in inflammatory rheumatic diseases. Reumatismo, 2009, 61, 10-14.
[http://dx.doi.org/10.4081/reumatismo.2009.10]
[134]
Setty, A.R.; Sigal, L.H. Herbal medications commonly used in the practice of rheumatology: Mechanisms of action, efficacy, and side effects. Semin. Arthritis Rheum., 2005, 34, 773-784.
[http://dx.doi.org/10.1016/ j.semarthrit.2005.01.011]
[135]
Chen, Z.; Liao, L.; Zhang, Z.; Wu, L.; Wang, Z. Comparison of active constituents, acute toxicity, anti-nociceptive and anti-inflammatory activities of Porana sinensis Hemsl., Erycibe obtusifolia Benth. and Erycibe schmidtii Craib. J. Ethnopharmacol., 2013, 150, 501-506.
[http://dx.doi.org/10.1016/j.jep.2013.08.059]
[136]
Hohmann, M.S.N.; Cardoso, R.D.R.; Fattori, V.; Arakawa, N.S.; Tomaz, J.C.; Lopes, N.P.; Casagrande, R.; Verri, W.A. Hypericum perforatum reduces paracetamol-induced hepatotoxicity and lethality in mice by modulating inflammation and oxidative stress. Phytother. Res., 2015, 29, 1097-1101.
[http://dx.doi.org/10.1002/ptr.5350]
[137]
Abdel-Salam, O.M.E. Anti-inflammatory, antinociceptive, and gastric effects of Hypericum perforatum in rats. Sci World J., 2005, 5, 586-595.
[http://dx.doi.org/10.1100/tsw.2005.78]
[138]
Apaydin, S.; Zeybek, U.; Ince, I.; Elgin, G.; Karamenderes, C.; Ozturk, B.; Tuglular, I. Hypericum triquetrifolium Turra. extract exhibits antinociceptive activity in the mouse. J. Ethnopharmacol., 1999, 67, 307-312.
[http://dx.doi.org/10.1016/S0378-8741(99)00071-9]
[139]
Bukhari, I.A.; Dar, A.; Khan, R.A. Antinociceptive activity of methanolic extracts of St. John’s Wort (Hypericum perforatum) preparation. Pak. J. Pharm. Sci., 2004, 17, 13-19.
[140]
Subhan, F.; Khan, M.; Ibrar, M. Nazar-ul-Islam, Khan, A.; Gilani, A.H. Antagonism of antinociceptive effect of hydro-ethanolic extract of Hypericum perforatum Linn. by a non selective opioid receptor antagonist, naloxone. Pak. J. Biol. Sci., 2007, 10, 792-796.
[141]
Uchida, S.; Hirai, K.; Hatanaka, J.; Hanato, J.; Umegaki, K.; Yamada, S. Antinociceptive effects of St. John’s wort, Harpagophytum procumbens extract and Grape seed proanthocyanidins extract in mice. Biol. Pharm. Bull., 2008, 31, 240-5.
[http://dx.doi.org/10.1248/bpb. 31.240]
[142]
Viana, A.F.; Heckler, A.P.; Fenner, R.; Rates, S.M.K. Antinociceptive activity of Hypericum caprifoliatum and Hypericum polyanthemum (Guttiferae). Braz. J. Med. Biol. Res., 2003, 36, 631-634.
[143]
Hammer, K.D.P.; Hillwig, M.L.; Neighbors, J.D.; Sim, Y.J.; Kohut, M.L.; Wiemer, D.F.; Wurtele, E.S.; Birt, D.F. Pseudohypericin is necessary for the light-activated inhibition of prostaglandin E2 pathways by a 4 component system mimicking an Hypericum perforatum fraction. Phytochemistry, 2008, 69, 2354-2362.
[http://dx.doi.org/1016/j.phytochem.2008.06.010]
[144]
Birt, D.F.; Widrlechner, M.P.; Hammer, K.D.P.; Hillwig, M.L.; Wei, J.; Kraus, G.; Murphy, P.; Mccoy, J.; Eve, S.; Neighbors, J.D.; Wiemer, D.F.; Maury, W.J.; Jason, P. Hypericum in infection: Identification of anti-viral and anti- inflammatory constituents. Pharm. Biol., 2009, 47, 774-782. Hypericum
[http://dx.doi.org/10.1080/13880200902988645]
[145]
Lou, L.; Liu, Y.; Zhou, J.; Wei, Y.; Deng, J.; Dong, B.; Chai, L. Chlorogenic acid and luteolin synergistically inhibit the proliferation of interleukin-1 β -induced fibroblast-like synoviocytes through regulating the activation of NF-κB and JAK/STAT-signaling pathways. Immunopharmacol. Immunotoxicol., 2015, 3973, 1-9.
[http://dx.doi.org/10.3109/08923973.2015.1095763]
[146]
Agudelo-Ochoa, G.M.; Pulgarín-Zapata, I.C.; Velásquez-Rodriguez, C.M.; Duque-Ramírez, M.; Naranjo-Cano, M.; Quintero-Ortiz, M.M.; Lara-Guzmán, O.J.; Muñoz-Durango, K. Coffee consumption increases the antioxidant capacity of plasma and has no effect on the lipid profile or vascular function in healthy adults in a randomized controlled trial. J. Nutr., 2016, 146, 524-531.
[http://dx.doi.org/10.3945/jn.115.224774]
[147]
Corrêa, T.A.; Monteiro, M.P.; Mendes, T.M.; de Oliveira, D.M.; Rogero, M.M.; Benites, C.I.; Vinagre, C.G.; Mioto, B.M.; Tarasoutchi, D.; Tuda, V.L. Medium light and medium roast paper-filtered coffee increased antioxidant capacity in healthy volunteers: results of a randomized trial. Plant Foods Hum. Nutr., 2012, 67, 277-282.
[http://dx.doi.org/10.1007/s11130-012-0297-x]
[148]
Shimoyama, A.T.; Santin, J.R.; Machado, I.D. de Oliveira e Silva, A.M.; de Melo, I.L.P.; Mancini-Filho, J.; Farsky, S.H.P. Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer. Naunyn Schmiedebergs Arch. Pharmacol., 2013, 386, 5-14.
[http://dx.doi.org/10.1007/s00210-012-0807-2]


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