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Natural Product Research
Formerly Natural Product Letters
Volume 38, 2024 - Issue 12
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Research Articles

Comparative study on inhibitory effects of ginsenosides on human pancreatic lipase and porcine pancreatic lipase: structure-activity relationships and inhibitory mechanism

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Pages 2031-2039 | Received 25 Mar 2023, Accepted 03 Jul 2023, Published online: 20 Jul 2023
 

Abstract

The inhibitory effects of twenty-six ginsenosides on human pancreatic lipase (hPL) and porcine pancreatic lipase (pPL) were studied. Study reveals that nine ginsenosides have moderate inhibitory effects against hPL, and good selectivity over pPL. By contrast, (S)-Rh2 showed good inhibitory effects on pPL over hPL. SAR analysis indicated that introduction of the O-glycosyl group(s) at C-3/C-7 site is unbeneficial for hPL inhibition, ginsenosides with A-skeleton is more beneficial than ginsenosides with B-/C-skeleton. Inhibition kinetic analysis indicated that Rg3 and (S)-Rh2 inhibited hPL-catalyzed DDAO-ol hydrolysis in a mixed manner. Molecular docking studies have confirmed that Rg3 and (S)-Rh2 inhibit hPL via many Pi-hydrogen interactions and hydrogen bonds with catalytic residues of hPL. These results indicated that pPL as an enzyme source could not fully represent the inhibitory effect of the tested compounds on hPL, and hPL should be used as far as possible to evaluate the inhibitory effect of PL.

Graphical Abstract

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by the Shanghai Three-year Action Plan to Further Accelerate the Development of Traditional Chinese Medicine [ZY(2021-2023)-0103] and the NSF of China [81973393].

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