The Antioxidant and Immunomodulatory Potential of Coccoloba alnifolia Leaf Extracts

Oxidative stress has been associated with different diseases, and different medicinal plants have been used to treat or prevent this condition. The leaf ethanolic extract (EE) and aqueous extract (AE) from Coccoloba alnifolia have previously been characterized to have antioxidant potential in vitro and in vivo. In this study, we worked with EE and AE and two partition phases, AF (ethyl acetate) and BF (butanol), from AE extract. These extracts and partition phases did not display cytotoxicity. The EE and AE reduced NO production and ROS in all three concentrations tested. Furthermore, it was observed that EE and AE at 500 μg/mL concentration were able to reduce phagocytic activity by 30 and 50%, respectively. A scratch assay using a fibroblast cell line (NHI/3T3) showed that extracts and fractions induced cell migration with 60% wound recovery within 24 h, especially for BF. It was also observed that AF and BF had antioxidant potential in all the assays evaluated. In addition, copper chelation was observed. This activity was previously not detected in AE. The HPLC-DAD analysis showed the presence of phenolic compounds such as p-cumaric acid and vitexin for extracts, while the GNPS annotated the presence of isoorientin, vitexin, kanakugiol, and tryptamine in the BF partition phase. The data presented here demonstrated that the EE, AE, AF, and BF of C. alnifolia have potential immunomodulatory effects, antioxidant effects, as well as in vitro wound healing characteristics, which are important for dynamic inflammation process control.

[1]  J. Thyssen,et al.  Cytokines and Venous Leg Ulcer Healing—A Systematic Review , 2022, International journal of molecular sciences.

[2]  A. Serban,et al.  Wound healing, anti-inflammatory and anti-melanogenic activities of ursane-type triterpenes from Semialarium mexicanum (Miers) Mennega. , 2022, Journal of ethnopharmacology.

[3]  E. Matovu,et al.  Plasma cytokines quantification among Trypanosoma brucei rhodesiense sleeping sickness cases and controls in Rumphi, Malawi , 2021, Malawi medical journal : the journal of Medical Association of Malawi.

[4]  Hongqiao Zhang,et al.  Targeting oxidative stress in disease: promise and limitations of antioxidant therapy , 2021, Nature Reviews Drug Discovery.

[5]  H. Young,et al.  Cytokines: From Clinical Significance to Quantification , 2021, Advanced science.

[6]  M. McGeachy,et al.  IL-17 in the Pathogenesis of Disease: Good Intentions Gone Awry. , 2021, Annual review of immunology.

[7]  Y. Zhang,et al.  Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[8]  D. Y. D. dos Santos,et al.  Coccoloba alnifolia Leaf Extract as a Potential Antioxidant Molecule Using In Vitro and In Vivo Assays , 2020, Oxidative medicine and cellular longevity.

[9]  Vuanghao Lim,et al.  Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants , 2020, Plants.

[10]  M. Koyutürk,et al.  Efficacy of resveratrol in the wound healing process by reducing oxidative stress and promoting fibroblast cell proliferation and migration , 2020, Dermatologic therapy.

[11]  Yongde Luo,et al.  The Significance of Mitochondrial Dysfunction in Cancer , 2020, International journal of molecular sciences.

[12]  S. Fakurazi,et al.  In Vitro Wound Healing Potential of Flavonoid C-Glycosides from Oil Palm (Elaeis guineensis Jacq.) Leaves on 3T3 Fibroblast Cells , 2020, Antioxidants.

[13]  Ashish,et al.  Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells , 2020, Oxidative medicine and cellular longevity.

[14]  A. Macho,et al.  Sorocea guilleminiana Gaudich.: Wound healing activity, action mechanisms, and chemical characterization of the leaf infusion. , 2020, Journal of ethnopharmacology.

[15]  M. Rahimifard,et al.  Bioassay-guided fractionation and identification of wound healing active compound from Pistacia vera L. hull extract. , 2020, Journal of ethnopharmacology.

[16]  M. Sugaya The Role of Th17-Related Cytokines in Atopic Dermatitis , 2020, International journal of molecular sciences.

[17]  Muhammad Ali,et al.  Anticancer Plants: A Review of the Active Phytochemicals, Applications in Animal Models, and Regulatory Aspects , 2019, Biomolecules.

[18]  F. Ghorat,et al.  Anti-Inflammatory and Immunomodulatory Effects of Barberry (Berberis vulgaris) and Its Main Compounds , 2019, Oxidative medicine and cellular longevity.

[19]  Xiaoxia Li,et al.  The role of interleukin-17 in tumor development and progression , 2019, The Journal of experimental medicine.

[20]  Alexander van Oudenaarden,et al.  Unravelling cellular relationships during development and regeneration using genetic lineage tracing , 2019, Nature Reviews Molecular Cell Biology.

[21]  M. Dianat,et al.  p-Coumaric Acid Attenuates Lipopolysaccharide-Induced Lung Inflammation in Rats by Scavenging ROS Production: an In Vivo and In Vitro Study , 2019, Inflammation.

[22]  N. Cech,et al.  Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. , 2019, Natural product reports.

[23]  H. Nouri,et al.  Propolis attenuates lipopolysaccharide-induced inflammatory responses through intracellular ROS and NO levels along with downregulation of IL-1β and IL-6 expressions in murine RAW 264.7 macrophages. , 2019, Journal of food biochemistry.

[24]  Haidy A. Gad,et al.  Biological and phytochemical review on the genus Coccoloba (Polygonaceae) , 2019, Archives of Pharmaceutical Sciences Ain Shams University.

[25]  Yi Zhang,et al.  Anti-inflammatory constituents from Cortex Dictamni. , 2019, Fitoterapia.

[26]  S. Srichairatanakool,et al.  Anti-inflammatory and Antioxidant Activities of the Extracts from Leaves and Stems of Polygonum odoratum Lour , 2019, Anti-inflammatory & anti-allergy agents in medicinal chemistry.

[27]  H. Rocha,et al.  In Vitro Immunostimulating Activity of Sulfated Polysaccharides from Caulerpa cupressoides Var. Flabellata , 2019, Marine drugs.

[28]  B. Liu,et al.  Molecular pharmacology of inflammation: Medicinal plants as anti‐inflammatory agents , 2019, Pharmacological research.

[29]  D. P. de Sousa,et al.  An Overview on the Anti-inflammatory Potential and Antioxidant Profile of Eugenol , 2018, Oxidative medicine and cellular longevity.

[30]  Yeonhwa Park,et al.  p-Coumaric acid improves oxidative and osmosis stress responses in Caenorhabditis elegans. , 2018, Journal of the science of food and agriculture.

[31]  M. Prasanth,et al.  Vitexin inhibits Aβ25-35 induced toxicity in Neuro-2a cells by augmenting Nrf-2/HO-1 dependent antioxidant pathway and regulating lipid homeostasis by the activation of LXR-α. , 2018, Toxicology in vitro : an international journal published in association with BIBRA.

[32]  Arielle Rowe,et al.  Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Drug Discovery , 2018, International journal of molecular sciences.

[33]  H. Rodrigues,et al.  Wound Healing and Omega-6 Fatty Acids: From Inflammation to Repair , 2018, Mediators of inflammation.

[34]  J. Bastos,et al.  Brazilian medicinal plants with corroborated anti-inflammatory activities: a review , 2018, Pharmaceutical biology.

[35]  Hee Kang,et al.  Comparison of Anti-Inflammatory Effects of Flavonoid-Rich Common and Tartary Buckwheat Sprout Extracts in Lipopolysaccharide-Stimulated RAW 264.7 and Peritoneal Macrophages , 2017, Oxidative medicine and cellular longevity.

[36]  Longhuo Wu,et al.  Anti-inflammatory and antioxidative effects of Camellia oleifera Abel components. , 2017, Future medicinal chemistry.

[37]  Y. Hiraku,et al.  Crosstalk between DNA Damage and Inflammation in the Multiple Steps of Carcinogenesis , 2017, International journal of molecular sciences.

[38]  C. Zazueta,et al.  Oxidative Stress and Inflammation in Cardiovascular Disease , 2017, Oxidative medicine and cellular longevity.

[39]  Chin Chew Quah,et al.  Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum , 2017, BMC Complementary and Alternative Medicine.

[40]  B. Peng,et al.  A review on the pharmacological effects of vitexin and isovitexin. , 2016, Fitoterapia.

[41]  M. Serafini,et al.  Functional Foods for Health: The Interrelated Antioxidant and Anti-Inflammatory Role of Fruits, Vegetables, Herbs, Spices and Cocoa in Humans , 2016, Current pharmaceutical design.

[42]  A. Azab,et al.  Anti-Inflammatory Activity of Natural Products , 2016, Molecules.

[43]  Yulong Yin,et al.  Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? , 2016, Oxidative medicine and cellular longevity.

[44]  Ying Liu,et al.  The anti-inflammatory activity of licorice, a widely used Chinese herb , 2016, Pharmaceutical biology.

[45]  J. R. Santin,et al.  Rubus imperialis (Rosaceae) extract and pure compound niga-ichigoside F1: wound healing and anti-inflammatory effects , 2016, Naunyn-Schmiedeberg's Archives of Pharmacology.

[46]  L. C. Spolidorio,et al.  Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet. , 2016, Food & function.

[47]  S. F. Arruda,et al.  Phytochemical Compounds and Antioxidant Capacity of Tucum-Do-Cerrado (Bactris setosa Mart), Brazil’s Native Fruit , 2016, Nutrients.

[48]  Won‐Kyo Jung,et al.  Gallic Acid-g-Chitosan Modulates Inflammatory Responses in LPS-Stimulated RAW264.7 Cells Via NF-κB, AP-1, and MAPK Pathways , 2016, Inflammation.

[49]  Ting‐Jun Hu,et al.  Flavonoids of Polygonum hydropiper L. attenuates lipopolysaccharide-induced inflammatory injury via suppressing phosphorylation in MAPKs pathways , 2015, BMC Complementary and Alternative Medicine.

[50]  M. Serafini,et al.  Flavonoids and Immune Function in Human: A Systematic Review , 2015, Critical reviews in food science and nutrition.

[51]  Jong-Hoon Kim,et al.  In vivo and in vitro anti-inflammatory activities of Persicaria chinensis methanolic extract targeting Src/Syk/NF-κB. , 2015, Journal of ethnopharmacology.

[52]  M. Correa,et al.  Synthesis, antioxidant and photoprotection activities of hybrid derivatives useful to prevent skin cancer. , 2014, Bioorganic & medicinal chemistry.

[53]  B. Bermas Non-steroidal anti inflammatory drugs, glucocorticoids and disease modifying anti-rheumatic drugs for the management of rheumatoid arthritis before and during pregnancy , 2014, Current opinion in rheumatology.

[54]  W. Assavalapsakul,et al.  Studies of the in vitro cytotoxic, antioxidant, lipase inhibitory and antimicrobial activities of selected Thai medicinal plants , 2012, BMC Complementary and Alternative Medicine.

[55]  N. G. Katkam,et al.  Evaluation of the wound healing potential of Wedelia trilobata (L.) leaves. , 2012, Journal of ethnopharmacology.

[56]  P. Mandrekar,et al.  Oxidative Stress and Inflammation: Essential Partners in Alcoholic Liver Disease , 2012, International journal of hepatology.

[57]  Jurandir Pereira Pinto,et al.  Phytochemical and antifungal activity of anthraquinones and root and leaf extracts of Coccoloba mollis on phytopathogens , 2011 .

[58]  P. Rasoanaivo,et al.  Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions , 2011, Malaria Journal.

[59]  B. Aggarwal,et al.  Oxidative stress, inflammation, and cancer: how are they linked? , 2010, Free radical biology & medicine.

[60]  R. C. Luiz,et al.  In vitro evaluation of the genotoxic activity and apoptosis induction of the extracts of roots and leaves from the medicinal plant Coccoloba mollis (Polygonaceae). , 2010, Journal of medicinal food.

[61]  A. Giulietti,et al.  Larvicidal activity of 94 extracts from ten plant species of northeastern of Brazil against Aedes aegypti L. (Diptera: Culicidae) , 2010, Parasitology Research.

[62]  R. Medzhitov Inflammation 2010: New Adventures of an Old Flame , 2010, Cell.

[63]  M. Pasparakis,et al.  Regulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseases , 2009, Nature Reviews Immunology.

[64]  L. D. Di Stasi,et al.  Effects of Coccoloba uvifera L. on UV‐stimulated melanocytes , 2008, Photodermatology, photoimmunology & photomedicine.

[65]  W. Scheible,et al.  Eleven Golden Rules of Quantitative RT-PCR , 2008, The Plant Cell Online.

[66]  Quanbin Zhang,et al.  Antioxidant activity of sulfated polysaccharide fractions extracted from Laminaria japonica. , 2008, International journal of biological macromolecules.

[67]  W. Scheible,et al.  MicroRNA399 is a long-distance signal for the regulation of plant phosphate homeostasis , 2008, The Plant journal : for cell and molecular biology.

[68]  F. Koehn,et al.  The evolving role of natural products in drug discovery , 2005, Nature Reviews Drug Discovery.

[69]  B. De,et al.  Antioxidant activity of Piper betle L. leaf extract in vitro , 2004 .

[70]  F. Braga,et al.  Antimicrobial activity and constituents of Coccoloba acrostichoides. , 2003, Fitoterapia.

[71]  A. Moorman,et al.  Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data , 2003, Neuroscience Letters.

[72]  P. Prieto,et al.  Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. , 1999, Analytical biochemistry.

[73]  K. Shimada,et al.  Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion , 1992 .

[74]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[75]  S. Tannenbaum,et al.  Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. , 1982, Analytical biochemistry.

[76]  A. Serban,et al.  Wound Healing, Anti-Inflammatory and Anti-Melanogenic Activities Of Ursane-Type Triterpenes From  Semialarium mexicanum (Miers) Mennega , 2021, SSRN Electronic Journal.

[77]  J. Hošek,et al.  Flavonoids as Anti-inflammatory Agents , 2015 .

[78]  Won‐Kyo Jung,et al.  Protective effect of aquacultured flounder fish-derived peptide against oxidative stress in zebrafish. , 2014, Fish & shellfish immunology.

[79]  R. F. Melo-Silveira,et al.  Molecular Sciences in Vitro Antioxidant, Anticoagulant and Antimicrobial Activity and in Inhibition of Cancer Cell Proliferation by Xylan Extracted from Corn Cobs , 2022 .