Abstract
In our previous study, fourty-eight compounds have been isolated and identified from
the roots of Picrasma quassioides, which have been widely used as a traditional Chinese medicine for clearing heat
and for detoxification as described in the Chinese Pharmacopoeia. β-Carboline alkaloids are commonly considered as main active constituents of P. quassioides, but the molecular mechanism remains yet unknown. In the present paper, one new β-carboline alkaloid together with two known β-carboline alkaloids have been investigated for their anti-inflammatory effect and
mechanism of action in cultured macrophage RAW 264.7 cells. Griess assay was used
to evaluate the inhibitory effect on the overproduction of nitric oxide. ELISA was
used to determine the level of proinflammatory cytokines including TNF-α and IL-6. The inhibitory effect on the enzymatic activity of COX-2 and inducible
nitric oxide synthase were tested by colorimetric and fluorimetric methods, respectively.
Western blot was used to detect the expression of inducible nitric oxide synthase
and COX-2. All three β-carboline alkaloids suppressed LPS-stimulated nitric oxide production and proinflammatory
cytokines secretion, including TNF-α and IL-6 in a dose-dependent manner. They also strongly inhibited the expression
of inducible nitric oxide synthase and inducible nitric oxide synthase enzymatic activity,
whereas the expression of COX-2 and COX-2 enzymatic activity were not affected. These
results indicated that potent inhibition of nitric oxide, TNF-α, and IL-6, but not COX-2 expression and COX-2 activity, might constitute the anti-inflammatory
mechanism of β-carboline alkaloids. β-Carboline alkaloids suppressed the overproduction of nitric oxide through downregulation
of inducible nitric oxide synthase expression and inducible nitric oxide synthase
enzymatic activity in an LPS-stimulated macrophage.
Key words
Picrasma quassioides
- Simarubaceae -
β-carboline alkaloids - anti-inflammatory effect - macrophage - nitric oxide - iNOS
