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J Herbmed Pharmacol. 2024;13(3): 439-449.
doi: 10.34172/jhp.2024.49420
  Abstract View: 817
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Original Article

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

Taweesak Dhammaraj 1* ORCID logo, Phoobet Kotseekieo 1 ORCID logo, Tunnathon Chotikarn 1 ORCID logo, Narumol Phosrithong 2 ORCID logo, Wattanakarn Praison 1 ORCID logo, Tossapol Prasomsub 1 ORCID logo, Panupong Lumthong 1 ORCID logo, Warangrat Supaporn 1 ORCID logo, Bunleu Sungthong 1,3 ORCID logo, Chawannuch Mudjupa 1,3 ORCID logo, Pawitra Pulbutr 1,3 ORCID logo

1 Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand
2 Faculty of Pharmacy, Siam University, Bangkok, Thailand
3 Pharmaceutical Chemistry and Natural Products Research Unit, Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand
*Corresponding Author: Taweesak Dhammaraj, Email: taweesak.d@msu.ac.th

Abstract

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.


Implication for health policy/practice/research/medical education:

3,4,5-Trihydroxycinnamic acid displays substantial xanthine oxidase inhibition and antioxidant activity. Thus, it could be used as a biomarker for herbal plant screening and a lead compound for structural modification to discover a highly active molecule.

Please cite this paper as: Dhammaraj T, Kotseekieo P, Chotikarn T, Phosrithong N, Praison W, Prasomsub T, et al. In vitro investigation of xanthine oxidase inhibitory and antioxidant activities of 3,4,5-trihydroxycinnamic acid. J Herbmed Pharmacol. 2024;13(3):439-449. doi: 10.34172/jhp.2024.49420.

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Submitted: 17 Jan 2024
Accepted: 02 May 2024
ePublished: 27 Jun 2024
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