In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid

Introduction: Xanthine oxidase inhibitors with strong antioxidant activity are promising candidates for the treatment of gout and reactive oxygen species (ROS)-related disorders. 3,4,5-Trihydroxycinnamic acid (THCA), a natural hydroxycinnamic acid, exhibits strong antioxidant activities. This study...

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Main Authors: Taweesak Dhammaraj, Phoobet Kotseekieo, Tunnathon Chotikarn, Narumol Phosrithong, Wattanakarn Praison, Tossapol Prasomsub, Panupong Lumthong, Warangrat Supaporn, Bunleu Sungthong, Chawannuch Mudjupa, Pawitra Pulbutr
Format: Article
Language:English
Published: Shahrekord University of Medical Sciences 2024-07-01
Series:Journal of HerbMed Pharmacology
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Online Access:https://herbmedpharmacol.com/PDF/jhp-13-439.pdf
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author Taweesak Dhammaraj
Phoobet Kotseekieo
Tunnathon Chotikarn
Narumol Phosrithong
Wattanakarn Praison
Tossapol Prasomsub
Panupong Lumthong
Warangrat Supaporn
Bunleu Sungthong
Chawannuch Mudjupa
Pawitra Pulbutr
author_facet Taweesak Dhammaraj
Phoobet Kotseekieo
Tunnathon Chotikarn
Narumol Phosrithong
Wattanakarn Praison
Tossapol Prasomsub
Panupong Lumthong
Warangrat Supaporn
Bunleu Sungthong
Chawannuch Mudjupa
Pawitra Pulbutr
author_sort Taweesak Dhammaraj
collection DOAJ
description Introduction: Xanthine oxidase inhibitors with strong antioxidant activity are promising candidates for the treatment of gout and reactive oxygen species (ROS)-related disorders. 3,4,5-Trihydroxycinnamic acid (THCA), a natural hydroxycinnamic acid, exhibits strong antioxidant activities. This study investigated its xanthine oxidase inhibitory and antioxidant activities in comparison with sinapic acid, caffeic acid, and allopurinol. Methods: In vitro xanthine oxidase inhibitory assay and a Lineweaver-Burk plot were used to measure enzyme inhibition activity and pattern. A docking study was used to explore hydroxycinnamic acid-xanthine oxidase interactions. Antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Results: THCA (IC50 = 61.60±8.00 µM) inhibited xanthine oxidase more potently than sinapic acid and caffeic acid (IC50s = 117.00±4.00 and 214.00±5.00 µM), but less than allopurinol (IC50 = 2.84±0.41 µM) (P<0.05). THCA and allopurinol were competitive xanthine oxidase inhibitors with inhibition constants (Ki ) of 170 and 2.12 µM, respectively. The docking investigation revealed that hydroxycinnamic acids occupied the enzyme active site near the molybdopterin core. THCA formed one more hydrogen bond with the enzyme active site than the other hydroxycinnamic acids, which could account for its higher inhibitory potency. THCA had significantly the strongest DPPH-radical scavenging activity (IC50 = 16.45±3.35 μM) and higher than ascorbic acid (IC50 = 33.16±7.38 μM) (P<0.05). Conclusion: THCA inhibits xanthine oxidase and has good antioxidant properties even more than sinapic acid and caffeic acid. Thus, it is a promising natural active compound that should be further investigated for the treatment of gout and other ROS-related disorders.
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spelling doaj-art-4a70718b8f8743c1957821f4032f4aef2025-08-20T02:51:31ZengShahrekord University of Medical SciencesJournal of HerbMed Pharmacology2345-50042024-07-0113343944910.34172/jhp.2024.49420jhp-49420In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acidTaweesak Dhammaraj0Phoobet Kotseekieo1Tunnathon Chotikarn2Narumol Phosrithong3Wattanakarn Praison4Tossapol Prasomsub5Panupong Lumthong6Warangrat Supaporn7Bunleu Sungthong8Chawannuch Mudjupa9Pawitra Pulbutr10Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Siam University, Bangkok, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandFaculty of Pharmacy, Mahasarakham University, Maha Sarakham, ThailandIntroduction: Xanthine oxidase inhibitors with strong antioxidant activity are promising candidates for the treatment of gout and reactive oxygen species (ROS)-related disorders. 3,4,5-Trihydroxycinnamic acid (THCA), a natural hydroxycinnamic acid, exhibits strong antioxidant activities. This study investigated its xanthine oxidase inhibitory and antioxidant activities in comparison with sinapic acid, caffeic acid, and allopurinol. Methods: In vitro xanthine oxidase inhibitory assay and a Lineweaver-Burk plot were used to measure enzyme inhibition activity and pattern. A docking study was used to explore hydroxycinnamic acid-xanthine oxidase interactions. Antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Results: THCA (IC50 = 61.60±8.00 µM) inhibited xanthine oxidase more potently than sinapic acid and caffeic acid (IC50s = 117.00±4.00 and 214.00±5.00 µM), but less than allopurinol (IC50 = 2.84±0.41 µM) (P<0.05). THCA and allopurinol were competitive xanthine oxidase inhibitors with inhibition constants (Ki ) of 170 and 2.12 µM, respectively. The docking investigation revealed that hydroxycinnamic acids occupied the enzyme active site near the molybdopterin core. THCA formed one more hydrogen bond with the enzyme active site than the other hydroxycinnamic acids, which could account for its higher inhibitory potency. THCA had significantly the strongest DPPH-radical scavenging activity (IC50 = 16.45±3.35 μM) and higher than ascorbic acid (IC50 = 33.16±7.38 μM) (P<0.05). Conclusion: THCA inhibits xanthine oxidase and has good antioxidant properties even more than sinapic acid and caffeic acid. Thus, it is a promising natural active compound that should be further investigated for the treatment of gout and other ROS-related disorders.https://herbmedpharmacol.com/PDF/jhp-13-439.pdfhydroxycinnamic acidenzyme inhibitionxanthine oxidaseantioxidantdocking study
spellingShingle Taweesak Dhammaraj
Phoobet Kotseekieo
Tunnathon Chotikarn
Narumol Phosrithong
Wattanakarn Praison
Tossapol Prasomsub
Panupong Lumthong
Warangrat Supaporn
Bunleu Sungthong
Chawannuch Mudjupa
Pawitra Pulbutr
In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid
Journal of HerbMed Pharmacology
hydroxycinnamic acid
enzyme inhibition
xanthine oxidase
antioxidant
docking study
title In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid
title_full In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid
title_fullStr In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid
title_full_unstemmed In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid
title_short In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid
title_sort in vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3 4 5 trihydroxycinnamic acid
topic hydroxycinnamic acid
enzyme inhibition
xanthine oxidase
antioxidant
docking study
url https://herbmedpharmacol.com/PDF/jhp-13-439.pdf
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