Marantodes pumilum (Blume) Kuntze Inhibited Secretion of Lipopolysaccharide- and Monosodium Urate Crystal-stimulated Cytokines and Plasma Prostaglandin E(2)

BACKGROUND: Marantodes pumilum is traditionally used for dysentery, gonorrhea, and sickness in the bones. Previous studies revealed its antibacterial and xanthine oxidase inhibitory activities. OBJECTIVE: To evaluate the inhibitory effects of three M. pumilum varieties on the secretion of lipopolysaccharide (LPS)- and monosodium urate crystal (MSU)-induced cytokines and plasma prostaglandin E(2) (PGE(2)) in vitro. MATERIALS AND METHODS: The leaves and roots of M. pumilum var. alata (MPA), M. pumilum var. pumila (MPP), and M. pumilum var. lanceolata (MPL) were successively extracted with dichloromethane (DCM), methanol, and water. Human peripheral blood mononuclear cells and ELISA technique were used for the cytokine assay, whereas human plasma and radioimmunoassay technique were used in the PGE(2) assay. Flavonoids content was determined using a reversed-phase high-performance liquid chromatography. RESULTS: DCM extract of MPL roots showed the highest inhibition of LPS-stimulated cytokine secretion with IC(50) values of 29.87, 7.62, 5.84, 25.33, and 5.40 μg/mL for interleukin (IL)-1α, IL-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, respectively; while that of plasma PGE(2) secretion was given by DCM extract of MPP roots (IC(50) 31.10 μg/mL). Similarly, the DCM extract of MPL roots demonstrated the highest inhibition against MSU-stimulated IL-1α, IL-1β, IL-6, IL-8, TNF-α, and PGE(2) secretion with IC(50) values of 11.2, 8.92, 12.29, 49.51, 9.60, and 31.58 μg/mL, respectively. Apigenin in DCM extracts of MPL (0.051 mg/g) and MPP (0.064 mg/g) roots could be responsible for the strong inhibitory activity against IL-1β, IL-6, TNF-α, and PGE(2). CONCLUSION: The results suggested that DCM extracts of MPL and MPP roots are potential anti-inflammatory agents by inhibiting the secretion of LPS- and MSU-stimulated pro-inflammatory cytokines and PGE(2). SUMMARY: Amongst 18 tested extracts, DCM extracts of MPL and MPP roots remarkably inhibited LPS- and MSU-stimulated pro-inflammatory cytokines and PGE(2) secretion. Phytochemical analysis was performed for the active extracts using RP-HPLC system. The presence of flavonoids particularly apigenin could be responsible for the anti-inflammatory activity. [Image: see text] Abbreviations used: BSA: Bovine serum albumin, COX-2: Cyclooxygenase-2, CPM: Count per minute, DAMP: Danger-associated molecular pattern, DCM: Dichloromethane, DMSO: Dimethyl sulfoxide, ELISA: Enzyme-linked immunosorbent assay, FBS: Fetal bovine serum, H(2)O: Water, HEPES: 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, HMC-1: Human mast cell-1, HMGB1: High-mobility group box 1, ICAM: Intercellular adhesion molecule, IFN: Interferon, IgG: Immunoglobulin G, IKK: IkB kinase, IL: Interleukin, iNOS: Inducible nitric oxide synthase, LPS: Lipopolysaccharide, MeOH: Methanol, MPA: Marantodes pumilum var. alata, MPL: Marantodes pumilum var. lanceolata, MPP: Marantodes pumilum var. pumila, MSU: Monosodium urate, MTT: Methylthiazole tetrazolium, NF-κB: Nuclear factor-kappa B, NLR: NOD-like receptor, NLRP3: NLR family pyrin domain containing protein 3, NO: Nitric oxide, NOD: Nucleotide-binding oligomerization domain, NSAID: Nonsteroidal anti-inflammatory drug, PAMP: Pathogen-associated molecular pattern, PBMC: Peripheral blood mononuclear cell, PBS: Phosphate buffered saline, PGE(2): Prostaglandin E(2,) PMACI: Phorbol-12-myristate 13-acetate and calcium ionosphere A23187, PRR: Pathogen recognition receptor, PTFE: Polytetrafluoroethylene, RIA: Radioimmunoassay, RIG: Retinoic acid-inducible gene I, RLR: RIG I-like receptor, RP-HPLC: Reversed-phase high-performance liquid chromatography, RPMI-1640: Roswell Park Memorial Institute-1640, TLR: Toll-like receptor, TNF: Tumor necrosis factor, VCAM: Vascular cell adhesion molecule.