Plumbagin exerts antiobesity effects through inhibition of pancreatic lipase and adipocyte differentiation

被引:19
作者
Pai, S. A. [1 ]
Martis, E. A. F. [2 ]
Joshi, S. G. [3 ]
Munshi, R. P. [3 ]
Juvekar, A. R. [1 ]
机构
[1] Inst Chem Technol, Dept Pharmaceut Sci & Technol, Pharmacol Res Lab 1, A-243, Bombay 400019, Maharashtra, India
[2] Bombay Coll Pharm, Dept Pharmaceut Chem, Mol Simulat Grp, Bombay 400098, Maharashtra, India
[3] TN Med Coll & BYL Nair Charitable Hosp, Dept Clin Pharmacol, Dr AL Nair Rd, Bombay 400008, Maharashtra, India
关键词
antiobesity; oral fat tolerance test; pancreatic lipase; plumbagin; FAT;
D O I
10.1002/ptr.6085
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Plumbagin is a naphthoquinone found in the roots of Plumbago zeylanica. Here, we report an investigation to evaluate its antiobesity activity. The preliminary binding affinity of plumbagin to human pancreatic lipase (PL) was determined using molecular docking simulation. The in vitro PL inhibitory potential and the kinetics of inhibition were studied to validate and confirm the results obtained from molecular docking. The IC50 for PL was found to be 82.08 +/- 9.47M, and the kinetics of inhibition was found to be of the mixed type. Further, the in vivo evaluation revealed that rats treated with plumbagin 1mg/kg showed significant decrease in serum triglycerides (TG) and area under the curve of serum TG when compared with vehicle-treated rats. It was also seen that plumbagin possessed significant antiadipogenic effect as demonstrated by reduced oil red O staining and decreased TG contents. Thus, we conclude that plumbagin is a promising molecule to combat obesity and further optimization of plumbagin to yield plumbagin analogues will result in its improved activity profile.
引用
收藏
页码:1631 / 1635
页数:5
相关论文
共 13 条
  • [1] Peripheral targets in obesity treatment: a comprehensive update
    Chatzigeorgiou, A.
    Kandaraki, E.
    Papavassiliou, A. G.
    Koutsilieris, M.
    [J]. OBESITY REVIEWS, 2014, 15 (06) : 487 - 503
  • [2] Cox M. M., 2008, Lehninger principles of biochemistry, P200
  • [3] THE 2.46-ANGSTROM RESOLUTION STRUCTURE OF THE PANCREATIC LIPASE-COLIPASE COMPLEX INHIBITED BY A C-11 ALKYL PHOSPHONATE
    EGLOFF, MP
    MARGUET, F
    BUONO, G
    VERGER, R
    CAMBILLAU, C
    VANTILBEURGH, H
    [J]. BIOCHEMISTRY, 1995, 34 (09) : 2751 - 2762
  • [4] Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
    Friesner, RA
    Banks, JL
    Murphy, RB
    Halgren, TA
    Klicic, JJ
    Mainz, DT
    Repasky, MP
    Knoll, EH
    Shelley, M
    Perry, JK
    Shaw, DE
    Francis, P
    Shenkin, PS
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (07) : 1739 - 1749
  • [5] Kumari Harshitha, 2013, Ayu, V34, P11, DOI 10.4103/0974-8520.115437
  • [6] Screening of six Ayurvedic medicinal plants for anti-obesity potential: An investigation on bioactive constituents from Oroxylum indicum (L.) Kurz bark
    Mangal, Priyanka
    Khare, Pragyanshu
    Jagtap, Sneha
    Bishnoi, Mahendra
    Kondepudi, Kanthi Kiran
    Bhutani, Kamlesh Kumar
    [J]. JOURNAL OF ETHNOPHARMACOLOGY, 2017, 197 : 138 - 146
  • [7] Plumbagin and Its Role in Chronic Diseases
    Panichayupakaranant, Pharkphoom
    Ahmad, Md Iftekhar
    [J]. DRUG DISCOVERY FROM MOTHER NATURE, 2016, 929 : 229 - 246
  • [8] Antihyperlipidemic effect of aqueous extract of Plumbago zeylanica roots in diet-induced hyperlipidemic rat
    Pendurkar, Sudha R.
    Mengi, Sushma A.
    [J]. PHARMACEUTICAL BIOLOGY, 2009, 47 (10) : 1004 - 1010
  • [9] SHARMA I, 1991, Indian Journal of Physiology and Pharmacology, V35, P10
  • [10] Screening of Selected Food and Medicinal Plant Extracts for Pancreatic Lipase Inhibition
    Slanc, Petra
    Doljak, Bojan
    Kreft, Samo
    Lunder, Mojca
    Janes, Damjan
    Strukelj, Borut
    [J]. PHYTOTHERAPY RESEARCH, 2009, 23 (06) : 874 - 877