Protein Tyrosine Phosphatase 1B(PTP1B) Inhibitors from Arnebia euchroma
WANG Xin1, TANG Zhi-shu2*, YANG Nan2, YUE Zheng-gang2*
1. Department of Pharmacy, The First Hospital of Xi��an, Xi��an 710002, China; 2. Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, Shaanxi University of Chinese Medicine, Xianyang 712046, China
Abstract��OBJECTIVE To study the chemical constituents of the extract of Arnebia euchroma (Royle) Johnst. and screen natural protein tyrosine phosphatase 1B (PTP1B) inhibitors.METHODS Silica gel, MCI gel, ODS gel, and Sephadex LH-20 chromatographic techniques were used to study the chemical constituents of A. euchroma, the chemical structures were elucidated by analysis of physico-chemical and spectral data, and the inhibitory activity on PTP1B enzyme was tested in vitro. RESULTS Eight compounds were obtained and their structures were identified as deoxyshikonin (1), shikonin (2), acetylshikonin (3), ��, �¡�-dimethylacrylalkannin (4), quercetin (5), kaempferol (6), kaempferide (7), and ��-sitosterol (8). Compounds 1-4 exhibited inhibitory activities on PTP1B with IC50 values of (0.80��0.16), (4.42��0.37), (1.02��0.13), and (0.36��0.08) ��mol��L-1, respectively. The study of structure-activity relationship showed that the ring of naphthoquinone might be the key skeleton structure for the inhibition activity on PTP1B, and the 2-substituted long lipo-chain of naphthoquinone significantly affected the activity of these compounds: the increase in the polarity of the lipo-chain led to the reduction of activity, while the increase in the terminal double bond of the lipo-chain led to the enhancement of activity. CONCLUSION Shikonin derivatives with 1, 4-naphthoquinone skeleton is a new type of leading compounds for the treatment of diabetes.
SUBBARANAIAH K, BULIC P, LIN Y, et al. Development and use of a gene promoter-based screen to identify novel inhibitors of cyclooxygenase-2 transcription [J]. J Biomol Screen, 2001, 6(2):101-110.
[2]
SASAKI K, YOSHIZAKI F, ABE H. The anti-Candida activity of shikon [J]. Yakugaku Zasshi, 2000,120(6):587-589.
[3]
LIN J, HAN F G, WANG K Z. Study of suppression effect of Xinjiang shikonin inhibitor on the growth cancer cells [J]. J Luzhou Med Col (����ҽѧԺѧ��), 2003, 26 (2): 102-106.
[4]
ZHAO T, WU T, LU D P. Prophylaxis of sinusoidal obstruction syndrome by Arnebia euchroma root alcoholic extract in rats model [J]. Chin Pharm J (�й�ҩѧ��־), 2005, 40 (21): 1626-1628.
[5]
LIU J Y, XU X G, LIU S Y, et al. Chemical constituents of Zicao (Radix Arnebiae) from the Changbai Mountains [J]. J Beijing Univ Tradit Chin Med (������ҽҩ��ѧѧ��), 2009, 32 (11): 773-775.
[6]
BA Y Y, LIU Q Y, SHI R B, et al. Studies on flavonoids from Euonymus alatus [J]. Chin Tradit Herb Drugs (�в�ҩ), 2012, 43 (2): 242-246.
[7]
ZHANG M W, ZHANG J W, YANG Y D, et al. Study on the dhemical constituents of Daphne genkwa [J]. Chin Pharm J (�й�ҩѧ��־), 2011, 46 (22): 1704-1706.
[8]
AHN J H, CHO S Y, HA J D, et al. Synthesis and PTP1B inhibition of 1, 2-naphthoquinone derivatives as potent anti-diabetic agents[J]. Bio Med Chem Lett, 2002, 12(15): 1941-1946.
2016, Vol. 51 
