Inhibition of pancreatic lipase by black tea theaflavins: Comparative enzymology and in silico modeling studies.
Few studies have examined the effect of black tea (Camellia sinensis) theaflavins on obesity-related targets. Pancreatic lipase (PL) plays a central role in fat metabolism and is a validated target for weight loss. We compared the inhibitory efficacy of individual theaflavins and explored the underlying mechanism. Theaflavin-3,3'-digallate (TFdiG), theaflavin-3'-gallate, theaflavin-3-gallate, and theaflavin inhibited PL with IC50 of 1.9, 4.2, 3.0, and >10μmol/L. The presence and location of the galloyl ester moiety were essential for inhibitory potency. TFdiG exhibited mixed inhibition with respect to substrate concentration. In silico modeling showed that theaflavins bind to Asn263 and Asp206, which form a pocket adjacent to the active site, and galloyl-containing theaflavins are then predicted to perturb the protonation of His264. These data provide a putative mechanism to explain the anti-obesity effects of tea.
Department of Food Science, The Pennsylvania State University, University Park, PA, United States.
Shannon L
SL
Glisan
Department of Food Science, The Pennsylvania State University, University Park, PA, United States.
Kimberly A
KA
Grove
The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United States.
Neela H
NH
Yennawar
Department of Food Science, The Pennsylvania State University, University Park, PA, United States; The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, United States. Electronic address: jdl134@psu.edu.
Joshua D
JD
Lambert
D000818:Animals; D044946:Biflavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013552:Swine; D013662:Tea / Q000737:chemistry
D044946:Biflavonoids; D004791:Enzyme Inhibitors; D013662:Tea; C585473:theaflavin-3,3'-digallate; C056068:theaflavin; D002392:Catechin; D008049:Lipase
Camellia sinensis; Obesity; Pancreatic lipase; Tea; Theaflavin (PubChem CID: 114777); Theaflavin-3,3′-gallate (PubChem CID: 3589471); Theaflavin-3-gallate (PubChem CID: 169167); Theaflavin-3′-gallate (PubChem CID: 71307578); Theaflavins