title: Modulation of humoral immune responses and inhibition of proinflammatory cytokines and nitric oxide production by 10-methoxycanthin-6-one.
abstract: Plant-derived natural products such as alkaloids, flavonoids, terpenoids, and polysaccharides have received considerable attention in recent years due to their diverse pharmacological properties such as immunomodulatory, anti-inflammatory, cytotoxic, cancer chemopreventive effects, and so on. 10-Methoxycanthin-6-one, a β-carboline alkaloid from the medicinal plant Aerva lanata, was assessed for immunomodulatory activity in Balb/c mice. Intraperitoneal administration of five doses of the compound at 0.5 mg/kg body weight was found to enhance the total WBC count (13,975.50 ± 324.27 cells/mm³ on the 12th day), bone marrow cellularity (23.08 ± 0.86 × 10⁶ cells/femur), and number of α-esterase-positive cells (1283.16 ± 21.10 cells/4000 cells). Treatment with the compound along with the antigen, sheep red blood cells, produced an enhancement in the circulating antibody titer (1024 on Days 12 and 15) and the number of plaque-forming cells (PFC) in the spleen. In treated group, maximum number of PFC (264.83 PFC/10⁶ spleen cells) was observed on the sixth day after antigen administration. At the same time, administration of 10-methoxycanthin-6-one could significantly reduce the elevated levels of proinflammatory cytokines and nitric oxide production by lipopolysaccharide (LPS)-stimulated macrophages. There was also a significant reduction in the mRNA levels of inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor alpha (TNF)-α, and interleukin (IL)-1β and IL-6 in LPS-stimulated macrophages after treatment with 10-methoxycanthin-6-one.
authors.affiliation: Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
authors.forename: K S
authors.initials: KS
authors.lastname: Siveen
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D027703:Amaranthaceae / Q000737:chemistry; D000818:Animals; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects*; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000276:immunology; D012756:Sheep
chemical_list: C548385:10-hydroxy-11-methoxycanthin-6-one; D002243:Carbolines; D016207:Cytokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse