No abstract

In order to clarify the mechanism involved in the antiinflammatory activity of atractylenolide I and atractylenolide III from the rhizomes of Atractylodes macrocephala Koidz, their effects on tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production in peritoneal macrophages were examined. Atractylenolide I and atractylenolide III decreased the TNF-alpha level in LPS-stimulated peritoneal macrophages in a dose-dependent manner, their IC(50) values were 23.1 microm and 56.3 microm, respectively. RT-PCR analysis indicated that they inhibited TNF-alpha mRNA expression. Furthermore, they inhibited NO production in LPS-activated peritoneal macrophages, the IC(50) value of atractylenolide I was 41.0 microm, and the inhibition ratio of 100 microm of atractylenolide III was 45.1% +/- 6.2%. The activity analysis of inducible nitric oxide synthase (iNOS) indicated that they could inhibit the activity of iNOS, their IC(50) values were 67.3 microm and 76.1 microm, respectively. Western blot analysis showed that atractylenolide I and atractylenolide III attenuated LPS-induced synthesis of iNOS protein in the macrophages, in parallel. These results imply that the antiinflammatory mechanism of atractylenolide I and atractylenolide III may be explained at least in part, by the inhibition of TNF-alpha and NO production. Atractylenolide I showed more potent inhibition than atractylenolide III in the production of TNF-alpha and NO in LPS-activated peritoneal macrophages. So, atractylenolide I could be a candidate for the development of new drugs to treat inflammatory diseases accompanied by the overproduction of TNF-alpha and NO.

No abstract

The purpose of this study was to investigate the molecular mechanisms that are responsible for the antiinflammatory effect of usnic acid (UA). UA is one of the most common and abundant lichen metabolites. The present study examined the effects of UA on the tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and the underlying molecular mechanisms. UA decreased the TNF-alpha level in LPS-stimulated RAW264.7 macrophages in dose-dependent manner, the IC(50) value was 12.8 microM. RT-PCR analysis indicated that it inhibited TNF-alpha mRNA expression. Furthermore, it inhibited NO production in LPS-activated RAW264.7 macrophages, the IC(50) value was 4.7 microM. Western blot analysis showed that UA attenuated LPS-induced synthesis of iNOS protein and nuclear translocation of NF-kappaB p65 in the macrophages, in parallel. UA also inhibited LPS-mediated I-kappaBalpha degradation. Taken together, this suggests that UA has an antiinflammatory effect by inhibiting TNF-alpha and iNOS expression, possibly through suppression of nuclear translocation of NF-kappaB p65 and I-kappaBalpha degradation.

BOBA (4‐[3‐(3, 5‐di‐tert‐butyl‐4‐methoxyphenyl)‐3‐oxo‐propenyl]benzoic acid), a substituted chalcone derivative, exhibits an excellent inducing differentiation on neoplastic cellular differentiation. FUDR (5‐fluoro‐2′‐deoxyuridine, floxuridine) inhibits DNA biosynthesis and has been used extensively to treat various cancers. In our efforts to find a new dual‐action antitumor prodrug, 3′‐floxuridinyl 4‐[3‐(3, 5‐di‐t‐butyl‐4‐methoxyphenyl)‐3‐oxo‐propenyl] benzoate (3′‐O‐BOBA‐ FUDR) was synthesized, and its antiproliferative activity in vitro and antitumor efficacy in vivo were evaluated. Compared with FUDR, the antiproliferative activity of 3′‐O‐BOBA‐FUDR was improved by 3–7‐fold. In rat hepatocellular carcinoma xenografts, 3′‐O‐BOBA‐FUDR‐treated rats had smaller tumors than were found in controls. In addition, the expression of Bcl‐2 protein was significantly downgraded, whereas the expression of Bax protein was upregulated in neoplastic tissues. The early apoptotic ratio of 3′‐O‐BOBA‐FUDR‐treated rat group was increased dose‐dependently. These findings strongly support the concept that 3′‐O‐BOBA‐FUDR may be a novel and effective dual‐action antitumor prodrug. Drug Dev Res 72:1–9, 2011. © 2011 Wiley Periodicals, Inc.