Background: There are numerous reports on the use of polyphenol-containing foods and various medicinal plant preparations for the prophylaxis and therapy of metabolic diseases, such as metabolic syndrome and diabetes mellitus, respectively. One unifying aspect to the effect of these natural compounds is their ability to inhibit digestive enzymes, which is the focus of this review. Summary: Polyphenols inhibit nonspecifically hydrolytic enzymes included in the digestion process, e.g., amylases, proteases, lipases. By that, the digestion process is protracted with different consequences as result of the incomplete absorption of monosaccharides, fatty acids, and amino acids as well as for the enhanced availability of substrates for the microbiome in ileum and colon. The resulting postprandial blood concentration of monosaccharides, fatty, and amino acids is lowered and by that different metabolic pathways proceed more slowly. As another positive result, polyphenols can also modulate the intestinal microbiome and thus mediate additional beneficial health effects. Key Messages: Many medicinal plants possess a broad spectrum of different polyphenols, thereby mediating the nonspecific inhibition of all hydrolytic enzyme activities in the gastrointestinal digestive process. As a consequence of the slowing down of digestive processes, risk factors for the development of metabolic disorders are reduced and the health of the patients with metabolic syndrome improves.

1.
Ozdal
T
,
Yalcinkaya
IE
,
Toydemir
G
,
Capanoglu
E
.
Polyphenol-protein interactions and changes in functional properties and digestibility
. In:
Melton
L
,
Shahidi
F
,
Varelis
PBT
, editors.
Encyclopedia of food chemistry
Oxford
Academic Press
2019
. p.
566
77
.
2.
Yilmaz
H
,
Gultekin Subasi
B
,
Celebioglu
HU
,
Ozdal
T
,
Capanoglu
E
.
Chemistry of protein-phenolic interactions toward the microbiota and microbial infections
.
Front Nutr
.
2022 Jul1
9
914118
.
3.
McDougall
GJ
,
Kulkarni
NN
,
Stewart
D
.
Current developments on the inhibitory effects of berry polyphenols on digestive enzymes
.
Biofactors
.
2008
;
34
(
1
):
73
80
.
4.
Leri
M
,
Scuto
M
,
Ontario
ML
,
Calabrese
V
,
Calabrese
EJ
,
Bucciantini
M
.
Healthy effects of plant polyphenols: molecular mechanisms
.
Int J Mol Sci
.
2020 Feb 13
21
4
1250
.
5.
Martinez-Gonzalez
AI
,
Díaz-Sánchez
ÁG
,
Rosa
LA
,
Vargas-Requena
CL
,
Bustos-Jaimes
I
,
Alvarez-Parrilla
AE
.
Polyphenolic compounds and digestive enzymes: in vitro non-covalent interactions
.
Molecules
.
2017 Apr 22
22
4
669
.
6.
Shin
HS
,
Ingram
JR
,
McGill
AT
,
Poppitt
SD
.
Lipids, CHOs, proteins: can all macronutrients put a “brake” on eating
.
Physiol Behav
.
2013
;
120
:
114
23
.
7.
Madsbad
S
.
Impact of postprandial glucose control on diabetes-related complications: how is the evidence evolving
.
J Diabetes Complications
.
2016 Mar
30
2
374
85
.
8.
Boivin
M
,
Flourie
B
,
Rizza
RA
,
Go
VL
,
Di Magno
EP
.
Gastrointestinal and metabolic effects of amylase inhibition in diabetics
.
Gastroenterology
.
1988 Feb
94
2
387
94
.
9.
Russell
WR
,
Baka
A
,
Björck
I
,
Delzenne
N
,
Gao
D
,
Griffiths
HR
.
Impact of diet composition on blood glucose regulation
.
Crit Rev Food Sci Nutr
.
2016
;
56
(
4
):
541
90
.
10.
Koike
D
,
Yamadera
K
,
DiMagno
EP
.
Effect of a wheat amylase inhibitor on canine carbohydrate digestion, gastrointestinal function, and pancreatic growth
.
Gastroenterology
.
1995
;
108
(
4
):
1221
9
.
11.
Kataoka
K
,
DiMagno
EP
.
Effect of prolonged intraluminal alpha-amylase inhibition on eating, weight, and the small intestine of rats
.
Nutrition
.
1999 Feb
15
2
123
9
.
12.
Castro-Barquero
S
,
Lamuela-Raventós
RM
,
Doménech
M
,
Estruch
R
.
Relationship between mediterranean dietary polyphenol intake and obesity
.
Nutrients
.
2018 Oct 17
10
10
1523
.
13.
Hanhineva
K
,
Törrönen
R
,
Bondia-Pons
I
,
Pekkinen
J
,
Kolehmainen
M
,
Mykkänen
H
.
Impact of dietary polyphenols on carbohydrate metabolism
.
Int J Mol Sci
.
2010 Mar 31
11
4
1365
402
.
14.
Melzig
MF
,
Funke
I
.
Inhibitors of alpha-amylase from plants - a possibility to treat diabetes mellitus type II by phytotherapy
.
Wien Med Wochenschr
.
2007
157
13–14
320
4
.
15.
Sekhon-Loodu
S
,
Rupasinghe
HPV
.
Evaluation of antioxidant, antidiabetic and antiobesity potential of selected traditional medicinal plants
.
Front Nutr
.
2019
;
6
:
53
.
16.
Carey
MC
,
Hernell
O
.
Digestion and absorption of fat
.
Semin Gastroint Dis
.
1992
;
3
:
189
208
.
17.
Buchholz
T
,
Melzig
MF
.
Polyphenolic compounds as pancreatic lipase inhibitors
.
Planta Med
.
2015 Jul
81
10
771
83
.
18.
Buchholz
T
,
Melzig
MF
.
Medicinal plants traditionally used for treatment of obesity and diabetes mellitus: screening for pancreatic lipase and α-amylase inhibition
.
Phytother Res
.
2016
;
30
(
2
):
260
6
.
19.
Siegień
J
,
Buchholz
T
,
Popowski
D
,
Granica
S
,
Osińska
E
,
Melzig
MF
.
Pancreatic lipase and α-amylase inhibitory activity of extracts from selected plant materials after gastrointestinal digestion in vitro
.
Food Chem
.
2021 Sep 1
355
129414
.
20.
Payab
M
,
Hasani-Ranjbar
S
,
Shahbal
N
,
Qorbani
M
,
Aletaha
A
,
Haghi-Aminjan
H
.
Effect of the herbal medicines in obesity and metabolic syndrome: a systematic review and meta-analysis of clinical trials
.
Phytother Res
.
2020 Mar
34
3
526
45
.
21.
Amiot
MJ
,
Riva
C
,
Vinet
A
.
Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review
.
Obes Rev
.
2016 Jul
17
7
573
86
.
22.
Griffiths
DW
.
The inhibition of digestive enzymes by polyphenolic compounds
.
Adv Exp Med Biol
.
1986
;
199
:
509
16
.
23.
Gonçalves
R
,
Soares
S
,
Mateus
N
,
de Freitas
V
.
Inhibition of trypsin by condensed tannins and wine
.
J Agric Food Chem
.
2007 Sep 5
55
18
7596
601
.
24.
Zhang
H
,
Lu
M
,
Jiang
H
,
Wang
X
,
Yang
FQ
.
Evaluation inhibitory activity of catechins on trypsin by capillary electrophoresis-based immobilized enzyme microreactor with chromogenic substrate
.
J Sep Sci
.
2020 Aug
43
15
3136
45
.
25.
Schreck
K
,
Melzig
MF
.
Traditionally Used Plants in the Treatment of Diabetes Mellitus: Screening for Uptake Inhibition of Glucose and Fructose in the Caco2-Cell Model
.
Front Pharmacol
.
2021
;
12
:
692566
.
26.
Schreck
K
,
Melzig
MF
.
Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells
.
Molecules
.
2018
;
23
(
10
):
2544
.
27.
Vrieze
A
,
Van Nood
E
,
Holleman
F
,
Salojärvi
J
,
Kootte
RS
,
Bartelsman
JF
.
Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome
.
Gastroenterology
.
2012 Oct
143
4
913
6
. e7.
28.
Su
B
,
Liu
H
,
Li
J
,
Sunli
Y
,
Liu
B
,
Liu
D
.
Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus
.
J Diabetes
.
2015 Sep
7
5
729
39
.
29.
Moco
S
,
Martin
FP
,
Rezzi
S
.
Metabolomics view on gut microbiome modulation by polyphenol-rich foods
.
J Proteome Res
.
2012 Oct 5
11
10
4781
90
.
30.
Rowland
I
,
Gibson
G
,
Heinken
A
,
Scott
K
,
Swann
J
,
Thiele
I
.
Gut microbiota functions: metabolism of nutrients and other food components
.
Eur J Nutr
.
2018 Feb
57
1
1
24
.
31.
Kiss
AK
,
Piwowarski
JP
.
Ellagitannins, gallotannins and their metabolites- the contribution to the anti-inflammatory effect of food products and medicinal plants
.
Curr Med Chem
.
2018
;
25
(
37
):
4946
67
.
32.
Etxeberria
U
,
Fernandez-Quintela
A
,
Milagro
FI
,
Aguirre
L
,
Martinez
JA
,
Portillo
MP
.
Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition
.
J Agric Food Chem
.
2013 Oct 9
61
40
9517
33
.
33.
Sharma
BR
,
Jaiswal
S
,
Ravindra
PV
.
Modulation of gut microbiota by bioactive compounds for prevention and management of type 2 diabetes
.
Biomed Pharmacother
.
2022 Aug
152
113148
.
34.
Santa
K
,
Kumazawa
Y
,
Nagaoka
I
.
Prevention of metabolic syndrome by phytochemicals and vitamin D
.
Int J Mol Sci
.
2023 Feb
24
3
2627
.
35.
Greiner
AK
,
Papineni
RV
,
Umar
S
.
Chemoprevention in gastrointestinal physiology and disease. Natural products and microbiome
.
Am J Physiol Gastrointest Liver Physiol
.
2014 Jul 1
307
1
G1
15
.
36.
Chen
F
,
Wen
Q
,
Jiang
J
,
Li
HL
,
Tan
YF
,
Li
YH
.
Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs
.
J Ethnopharmacol
.
2016 Feb 17
179
253
64
.
37.
Morrison
DJ
,
Preston
T
.
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism
.
Gut Microb
.
2016
;
7
(
3
):
189
200
.
38.
Galati
G
,
O’Brien
PJ
.
Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties
.
Free Radic Biol Med
.
2004 Aug 1
37
3
287
303
.
39.
Maugeri
A
,
Lombardo
GE
,
Cirmi
S
,
Süntar
I
,
Barreca
D
,
Laganà
G
.
Pharmacology and toxicology of tannins
.
Arch Toxicol
.
2022 May
96
5
1257
77
.
40.
Chung
KT
,
Wong
TY
,
Wei
CI
,
Huang
YW
,
Lin
Y
.
Tannins and human health: a review
.
Crit Rev Food Sci Nutr
.
1998 Aug
38
6
421
64
.
41.
Rana
A
,
Samtiya
M
,
Dhewa
T
,
Mishra
V
,
Aluko
RE
.
Health benefits of polyphenols: a concise review
.
J Food Biochem
.
2022 Oct
46
10
e14264
.
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