Safflomide (
N-caffeoyltryptamine) is a phenolic
amide with
serotonin receptor antagonist and
antioxidant activities. We investigated the potential effects of
safflomide on the expression of
adipokines in vitro and in vivo.
Safflomide did not affect the expressions of TNF-α,
IL-6, and MCP-1/CCL2 in hypertrophic 3T3-L1 cells but upregulated
adiponectin mRNA 1-5-fold at concentrations between 1 and 20 μM (p < 0.05). Because
safflomide is a non-selective
5-HT receptor antagonist and because the expression of
5-HT2A receptor is often inversely correlated to
adiponectin expression, the potential effects of
5-HT receptor antagonist activity of
safflomide on the expression of
adiponectin was further investigated in 3T3-L1 cells. At the concentration of 10 μM,
safflomide was able to increase
adiponectin protein production in 3T3-L1 cells more than 4-fold (p < 0.05), which was greater than the
5-HT2A antagonist ketanserin. The upregulation was partially suppressed by treatment with 5-HT2A agonists (serotonin and α-Me-5-HT), suggesting that
safflomide may upregulate
adiponectin expression more than by blocking 5-HT2A receptors in 3T3-L1 cells. Likely, the upregulation was also attributed to the
antioxidant activity of
safflomide because two
safflomide analogues (N-cinnamoyltryptamine and N-coumaroyltryptamine) with less
antioxidant activity were not as potent as
safflomide. Rats supplemented with
safflomide (3 mg/day) in a high-fat diet showed a significant plasma
adiponectin increase (more than 30%) with a significant reduction in
body weight, visceral fat, and improved
insulin resistance compared to non-supplemented rats, demonstrating the in vivo activity of
safflomide. These data suggest that
safflomide may have beneficial effects on
obesity-related conditions, such as low
adiponectin,
visceral obesity, and
insulin resistance.