TY - JOUR
T1 - Affinity crystallography reveals the bioactive compounds of industrial juicing byproducts of Punica granatum for glycogen phosphorylase
AU - Stravodimos, George A.
AU - Kantsadi, Anastassia L.
AU - Apostolou, Anna
AU - Kyriakis, Efthimios
AU - Kafaski-Kanelli, Vassiliki Nafsika
AU - Solovou, Theodora
AU - Gatzona, Pagona
AU - Liggri, Panagiota G.V.
AU - Theofanous, Stavroula
AU - Gorgogietas, Vyron A.
AU - Kissa, Apostolia
AU - Psachoula, Chariklia
AU - Lemonakis, Angelos
AU - Chatzileontiadou, Demetra S.M.
AU - Psarra, Anna Maria G.
AU - Skamnaki, Vassiliki T.
AU - Haroutounian, Serkos A.
AU - Leonidas, Demetres D.
PY - 2018/1/1
Y1 - 2018/1/1
N2 -
Background: Glycogen phosphorylase (GP) is a pharmaceutical target for the discovery of new antihyperglycaemic agents. Punica granatum is a well-known plant for its potent antioxidant and antimicrobial activities but so far has not been examined for antihyperglycaemic activity. Objective: The aim was to examine the inhibitory potency of eighteen polyphenolic extracts obtained from Punica granatum fruits and industrial juicing byproducts against GP and discover their most bioactive ingredients. Method: Kinetic experiments were conducted to measure the IC50 values of the extracts while affinity crystallography was used to identify the most bioactive ingredient. The inhibitory effect of one of the polyphenolic extracts was also verified ex vivo, in HepG2 cells. Results: All extracts exhibited significant in vitro inhibitory potency (IC50 values in the range of low μg/mL). Affinity crystallography revealed that the most bioactive ingredients of the extracts were chlorogenic and ellagic acids, found bound in the active and the inhibitor site of GP, respectively.While ellagic acid is an established GP inhibitor, the inhibition of chlorogenic acid is reported for the first time. Kinetic analysis indicated that chlorogenic acid is an inhibitor with Ki=2.5 x 10
-3
M that acts synergistically with ellagic acid. Conclusion: Our study provides the first evidence for a potential antidiabetic usage of Punica granatum extracts as antidiabetic food supplements. Although, more in vivo studies have to be performed before these extracts reach the stage of antidiabetic food supplements, our study provides a first positive step towards this process.
AB -
Background: Glycogen phosphorylase (GP) is a pharmaceutical target for the discovery of new antihyperglycaemic agents. Punica granatum is a well-known plant for its potent antioxidant and antimicrobial activities but so far has not been examined for antihyperglycaemic activity. Objective: The aim was to examine the inhibitory potency of eighteen polyphenolic extracts obtained from Punica granatum fruits and industrial juicing byproducts against GP and discover their most bioactive ingredients. Method: Kinetic experiments were conducted to measure the IC50 values of the extracts while affinity crystallography was used to identify the most bioactive ingredient. The inhibitory effect of one of the polyphenolic extracts was also verified ex vivo, in HepG2 cells. Results: All extracts exhibited significant in vitro inhibitory potency (IC50 values in the range of low μg/mL). Affinity crystallography revealed that the most bioactive ingredients of the extracts were chlorogenic and ellagic acids, found bound in the active and the inhibitor site of GP, respectively.While ellagic acid is an established GP inhibitor, the inhibition of chlorogenic acid is reported for the first time. Kinetic analysis indicated that chlorogenic acid is an inhibitor with Ki=2.5 x 10
-3
M that acts synergistically with ellagic acid. Conclusion: Our study provides the first evidence for a potential antidiabetic usage of Punica granatum extracts as antidiabetic food supplements. Although, more in vivo studies have to be performed before these extracts reach the stage of antidiabetic food supplements, our study provides a first positive step towards this process.
KW - Affinity crystallography
KW - Bioactive polyphenols
KW - Glycogen metabolism
KW - Glycogen phosphorylase
KW - Punica granatum
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85048587101&partnerID=8YFLogxK
U2 - 10.2174/1570163814666170619091736
DO - 10.2174/1570163814666170619091736
M3 - Article
C2 - 28625148
AN - SCOPUS:85048587101
VL - 15
SP - 41
EP - 53
JO - Current Drug Discovery Technologies
JF - Current Drug Discovery Technologies
SN - 1570-1638
IS - 1
ER -
