PTP1B Inhibitory and Anti-Inflammatory Effects of Secondary Metabolites Isolated from the Marine-Derived Fungus Penicillium sp. JF-55

Marine Drugs

Dong-Sung Lee²  Jae-Hyuk Jang¹  Wonmin Ko⁴  Kyoung-Su Kim⁴  Jae Hak Sohn³  Myeong-Suk Kang³  Jong Seog Ahn¹  Youn-Chul Kim² 

[1] Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Cheongwon 363-883, Korea; E-Mails:;Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea; E-Mail:;College of Medical and Life Sciences, Silla University, Busan 617-736, Korea; E-Mails:;College of Pharmacy, Wonkwang University, Iksan 570-749, Korea; E-Mails:

关键词: Penicillium sp.;    marine-derived fungi;    PTP1B inhibitors;    anti-inflammatory effect;    heme oxygenase-1;   

DOI  :  10.3390/md11041409

来源: mdpi

【 摘 要 】

Protein tyrosine phosphatase 1B (PTP1B) plays a major role in the negative regulation of insulin signaling, and is thus considered as an attractive therapeutic target for the treatment of diabetes. Bioassay-guided investigation of the methylethylketone extract of marine-derived fungus Penicillium sp. JF-55 cultures afforded a new PTP1B inhibitory styrylpyrone-type metabolite named penstyrylpyrone (1), and two known metabolites, anhydrofulvic acid (2) and citromycetin (3). Compounds 1 and 2 inhibited PTP1B activity in a dose-dependent manner, and kinetic analyses of PTP1B inhibition suggested that these compounds inhibited PTP1B activity in a competitive manner. In an effort to gain more biological potential of the isolated compounds, the anti-inflammatory effects of compounds 1–3 were also evaluated. Among the tested compounds, only compound 1 inhibited the production of NO and PGE₂, due to the inhibition of the expression of iNOS and COX-2. Penstyrylpyrone (1) also reduced TNF-α and IL-1β production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of penstyrylpyrone (1) on the pro-inflammatory mediators and NF-κB DNA binding activity were associated with the HO-1 expression. Therefore, these results suggest that penstyrylpyrone (1) suppresses PTP1B activity, as well as the production of pro-inflammatory mediators via NF-κB pathway, through expression of anti-inflammatory HO-1.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.