Inhibitory Effects of Herbal Alkaloids on the Tumor Necrosis Factor-.ALPHA. and Nitric Oxide Production in Lipopolysaccharide-Stimulated RAW264 Macrophages

Abstract

Uncontrolled production of proinflammatory cytokines is the primary cause of chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and ulcerative colitis. 1)Among the above cytokines, tumor necrosis factor-a (TNFa) plays important multiple roles in the pathobiology of inflammation, and induces itself as well as other inflammatory cytokines. Nitric oxide (NO) is another potent proinflammatory mediator. NO at low concentrations is the essential regulator of physiological homeostasis in cardiovascular system, but its overproduction by inducible nitric oxide synthase (iNOS) in the inflammation exerts harmful effects on the bodies.2) Although many synthetic drugs and biologics have been developed for suppressing TNF-a 3) and NO, 2) application of natural products of the same activity in dietary plants without or with other functional food factors like polyunsaturated fatty acids 4) is an attractive alternative, especially for ameliorating long-lasting inflammatory condition. The benefit of this approach is a better quality of life for the patients and reduction of medical costs.The anti-inflammatories, that is, TNF-a suppressing phytochemicals so far reported are mainly phenolic compounds with antioxidative property (e.g., flavonoids and stilbenoids). 5)Another major class of natural products, alkaloids, has received little attention in this regard. The situation might be partly due to the relatively weak antioxidative property of alkaloids, because reactive oxygen species and NO (a radical) are involved in the inflammatory process. 6)We decided to investigate fourteen alkaloids from herbal plants (Fig. 1) for their effect on TNF-a and NO production. Five b-carboline alkaloids (1-5), four indole alkaloids (6-9) and three quinoline alkaloids (10-12) were arbitrarily chosen from textbooks of pharmacognosy 7) and catalogues of commercial reagents, and two Lycoris alkaloids (13, 14) were included to confirm the previous report on their anti-TNF-a activity.8) These compounds are known to have various pharmacological activities (e.g., monoamine oxidase inhibition for 3-5, 9) intellectual capacity improvement for 7, anti- It is beneficial to treat chronic inflammatory condition in patients through diets that inhibit the production of proinflammatory cytokines and mediators such as tumor necrosis factor-a a (TNF-a a) and nitric oxide (NO). Since less attention has been paid to alkaloids in the diets than to polyphenols in this regard, we aimed at investigating anti-inflammatory activity of herb-derived alkaloids through suppression of TNF-a a and NO production in lipopolysaccharide (LPS)-stimulated mouse RAW264 and/or human THP-1 cells. A harmala alkaloid, harmine, an opium alkaloid, papaverine, and Lycoris alkaloids, lycorine and lycoricidinol, showed TNF-a a suppressive activities stronger than or comparable to that of a reference polyphenol, butein, in RAW264 cells (IC 50 ‫؍‬ ‫,4؍‬ 10, 2.1, 0.02, and 8 m mM, respectively). Other alkaloids showed no or marginal to moderate inhibitory activities. Similar te...

In vitroimmunomodulatory activity andin vivoanti-inflammatory and analgesic potential with gastroprotective effect of the Mediterranean red algaLaurencia obtusa

“…Sesquiterpenes have been also shown to have an anti-inflammatory potential by the inhibition of NO and TNF-a production (Jin et al 2006). Moreover, alkaloids have been shown to possess anti-inflammatory activity by inhibiting the action of arachidonic acid metabolism via the cycloxygenase and 5-lipoxygenase pathways (Barik et al 1992;Chao et al 2009) and by inhibiting TNF-a secretion (Yui et al 2001;Yamazaki & Kawano 2011). Based in these results, the in vitro and in vivo anti-inflammatory and analgesic activities of the crude extract and its polar fractions from the red algae L. obtusa could be also attributed to the presence of various other secondary metabolites especially terpenoids and alkaloids.…”

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

“…Harmine showed stronger TNF-alpha suppressive activities than reference polyphenol and butein in RAW264 cells. Harmine was also found to suppress interleukin-6 production in RAW264 cells [42] .…”

Lycorine, a Candidate for the Control of Period Length in Mammalian Cells

“…Recently, we found that the herbal alkaloid, harmine has potential as anti-inflammatory agents that can suppress TNF-α and NO production [10]. We also found using a customdesigned assay for circadian oscillation in vitro that harmine extends the circadian period [11].…”

“…We also found using a customdesigned assay for circadian oscillation in vitro that harmine extends the circadian period [11]. The Amaryllidaceae alkaloid, lycorine (3, 12-didehydro-9, 10-[methylenebis(oxy)]-galanthan-1α, 2β-diol) also suppressed TNF-α and NO production, indicating powerful anti-inflammatory activity [10]. Lycorine also has antiviral and antimalarial properties as well as the ability to inhibit protein synthesis and cell growth [12].…”

“…Cell culture materials were obtained from Invitrogen. Lycoricidinol was prepared as described [10]. Briefly, lycoricidinol was extracted from bulbs of Lycoris radiate with ethanol and purified by silica gel column chromatography (methanol/ethyl acetate) followed by reverse phase column chromatography (Wakogel 100C18) with 0 -50% methanol in water as the solvent.…”