Anti-inflammatory and antitumoural effects of Uncaria guianensis bark

• Published in: Journal of ethnopharmacology 2013-12, Vol.150 (3), p.1154-1162
• Main Authors: Urdanibia, I., Michelangeli, F., Ruiz, M.-C., Milano, B., Taylor, P.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; arthritis; bark; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Carrageenan; Cell Line; Cell Line, Tumor; Cell Survival - drug effects; COX-2; cytotoxicity; diabetes; Dinoprostone - metabolism; edema; Edema - chemically induced; Edema - drug therapy; enzyme-linked immunosorbent assay; Female; flow cytometry; fractionation; Humans; I-kappa B Proteins - metabolism; Il-6; immunohistochemistry; inflammation; Inflammation - chemically induced; Inflammation - drug therapy; iNOS; interleukin-6; Interleukin-6 - metabolism; Lipopolysaccharides; luciferase; Lung Neoplasms - drug therapy; Lung Neoplasms - secondary; macrophages; Male; mammary neoplasms (animal); medicinal plants; metastasis; Mice; Mice, Inbred BALB C; necrosis; neutrophils; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; NF-κB; nitric oxide; Nitric Oxide - metabolism; nitric oxide synthase; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Phytotherapy; Plant Bark; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; prostaglandin synthase; prostaglandins; rats; Rats, Sprague-Dawley; T-lymphocytes; TNF-α; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - metabolism; Uncaria; Uncaria guianensis
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2013.10.055

Uncaria guianensis (Aublet) Gmell (Rubiaceae) is a medicinal plant from the jungles of South and Central America, used to treat cancer, arthritis, diabetes, and inflammation. Evaluate the anti-inflammatory and anti-tumor effects of Uncaria guianensis preparations. Bio-guided fractionation of a hydroethanolic extract of Uncaria guianensis was performed, evaluating the fractions and subfractions for their effect on inflammatory mediators, tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) by ELISA and nitric oxide (NO) by the Griess reaction in cultured supernatant from RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). The expression of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and inhibitor of κB (IκB) were investigated in RAW 264.7 macrophages by flow cytometry. The activity of NF-κB in HeLa cells transfected with a luciferase reporter system was determined. The effect of Uncaria guianensis on the inflammatory response in vivo was assessed in BALB/c mice stimulated with LPS, on rat paw oedema induced by carrageenan, and on tumour growth and lung metastasis in BALB/c mice inoculated with 4T1 mammary tumour cells. Immune cell infiltrates and inflammatory mediators were evaluated in the tumour by immunohistochemistry. Sub-fraction Ug AIV inhibited, to varying degrees, NO, TNF-α, IL-6 and PGE2 production by macrophages in vitro (30μg/ml) and in the serum of LPS-challenged mice (5mg/kg). Macrophage expression of Cox-2 was inhibited (35%), IκB degradation was completely inhibited and NF-κB activation was inhibited (70%) by Ug AIV at 30μg/ml. Ug AIV decreased paw oedema by 86% (5mg/kg) and serum NO and TNF-α by 45% and 65% respectively. Ug AIV reduced 4T1 mammary tumour growth by 91% on day 33 post-inoculation as well as the levels of serum NO, IL-6 and TNF-α in the same animals. Ug AIV decreased the number of tumour-infiltrating T lymphocytes, macrophages and neutrophils as well as the number of cells positive for COX-2, iNOS, IL-6, TNF-α and p65. As Ug AIV was not cytotoxic for tumour cells or macrophages, its anti-tumour effect may be due to a reduction in pro-tumoural inflammatory processes in the tumour microenvironment, possibly mediated through NF-κB. [Display omitted]