title: Immunomodulatory and cellular anti-oxidant activities of caffeic, ferulic, and p-coumaric phenolic acids: a structure-activity relationship study.
abstract: Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses and to reduce damage to the human body. To determine whether phenolic compounds (caffeic, ferulic, and p-coumaric acids) have immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we evaluated their effect on splenocyte proliferation and lysosomal enzyme activity. We also investigated the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In addition, induction of the cellular antioxidant activity in splenocytes, macrophages, and red blood cells was determined by measuring the ﬂuorescence of the DCF product. The study first results indicated that caﬀeic, ferulic, and p-coumaric acids significantly promote LPS-stimulated splenocyte proliferation, suggesting a potential activation of B cells, and enhanced humoral immune response in hosts treated by the tested natural products. Phenolic acids significantly enhanced the killing activity of isolated NK and CTL cells but had negligible effects on mitogen-induced proliferation of splenic T cells. We showed that caffeic acid enhances lysosomal enzyme activity in murine peritoneal macrophages, suggesting a potential role in activating such cells. Immunomodulatory activity was concomitant with the cellular antioxidant effect in macrophages and splenocytes of caffeic and ferulic acids. We conclude from this study that caﬀeic, ferulic, and p-coumaric acids exhibited an immunomodulatory effect which could be ascribed, in part, to their cytoprotective effect via their antioxidant capacity. Furthermore, these results suggest that these natural products could be potentially used to modulate immune cell functions in physiological and pathological conditions.
authors.affiliation: a Laboratory of Cellular and Molecular Biology , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.|b Unit of Bioactive and Natural Substances and Biotechnology UR12ES12, Faculty of Pharmacy, University of Monastir , Monastir , Tunisia.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Kilani-Jaziri
authors.affiliation: a Laboratory of Cellular and Molecular Biology , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.|b Unit of Bioactive and Natural Substances and Biotechnology UR12ES12, Faculty of Pharmacy, University of Monastir , Monastir , Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Mokdad-Bzeouich
authors.affiliation: a Laboratory of Cellular and Molecular Biology , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.|b Unit of Bioactive and Natural Substances and Biotechnology UR12ES12, Faculty of Pharmacy, University of Monastir , Monastir , Tunisia.
authors.forename: Mounira
authors.initials: M
authors.lastname: Krifa
authors.affiliation: a Laboratory of Cellular and Molecular Biology , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.|b Unit of Bioactive and Natural Substances and Biotechnology UR12ES12, Faculty of Pharmacy, University of Monastir , Monastir , Tunisia.
authors.forename: Nouha
authors.initials: N
authors.lastname: Nasr
authors.affiliation: b Unit of Bioactive and Natural Substances and Biotechnology UR12ES12, Faculty of Pharmacy, University of Monastir , Monastir , Tunisia.
authors.forename: Kamel
authors.initials: K
authors.lastname: Ghedira
authors.affiliation: a Laboratory of Cellular and Molecular Biology , Faculty of Dental Medicine, University of Monastir , Monastir , Tunisia and.|b Unit of Bioactive and Natural Substances and Biotechnology UR12ES12, Faculty of Pharmacy, University of Monastir , Monastir , Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Chekir-Ghedira
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D002109:Caffeic Acids / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D019587:Dietary Supplements / Q000009:adverse effects; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D003373:Coumaric Acids; D007155:Immunologic Factors; D008934:Mitogens; D011422:Propionates; C004999:ferulic acid; C495469:p-coumaric acid; C040048:caffeic acid
keywords: CTL activity; Hydroxycinnamic acids; antioxidant activity; immunomodulation; natural killer cell