Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions

Arginase (Arg) plays a pivotal role in numerous pathological processes, with its dysregulated expression being intricately associated with tumor progression and immune evasion. This review comprehensively examines the diversity, mechanisms, and clinical potential of natural Arg modulators, encompass...

Full description

Saved in:
Bibliographic Details
Main Authors: Ting Li, Jieying Wang, Huan Wang, Bowei Zhang, Lijuan Duan
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1514400/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850178457117392896
author Ting Li
Ting Li
Ting Li
Jieying Wang
Huan Wang
Bowei Zhang
Lijuan Duan
Lijuan Duan
author_facet Ting Li
Ting Li
Ting Li
Jieying Wang
Huan Wang
Bowei Zhang
Lijuan Duan
Lijuan Duan
author_sort Ting Li
collection DOAJ
description Arginase (Arg) plays a pivotal role in numerous pathological processes, with its dysregulated expression being intricately associated with tumor progression and immune evasion. This review comprehensively examines the diversity, mechanisms, and clinical potential of natural Arg modulators, encompassing polyphenols, flavonoids, and terpenoids. These bioactive compounds exert their modulatory effects on Arg activity through multiple mechanisms, including direct enzyme interaction, regulation of signaling pathways, and modulation of cellular metabolism. The therapeutic potential of these metabolites spans across various medical domains, notably in cardiovascular diseases, oncology, neurological disorders, and inflammatory conditions. Specifically, polyphenol metabolites such as resveratrol and curcumin have demonstrated significant benefits in cardiovascular health and neuroprotection, while flavonoids including rutin and quercetin have shown promising effects on intracellular inflammatory factors and tumor cell proliferation. Similarly, terpenoids like perillyl alcohol and triptolide have been found to influence cell polarization processes. However, despite their substantial therapeutic potential demonstrated in experimental studies, the development of natural Arg modulators faces several significant challenges. These include complexities in drug design attributed to the intricate structure and multiple isoforms of Arg, difficulties in elucidating precise mechanisms due to Arg’s multifaceted roles in various metabolic pathways, and limitations in current drug delivery systems. To overcome these challenges, future research should focus on continuous optimization of experimental design paradigms, enhancement of experimental models and data quality, thorough evaluation of therapeutic efficacy, and strategic integration of natural Arg modulators with precision medicine approaches.
format Article
id doaj-art-c93fd3d4d7bc42c782877386d3aec3ab
institution OA Journals
issn 1663-9812
language English
publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj-art-c93fd3d4d7bc42c782877386d3aec3ab2025-08-20T02:18:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15144001514400Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directionsTing Li0Ting Li1Ting Li2Jieying Wang3Huan Wang4Bowei Zhang5Lijuan Duan6Lijuan Duan7Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaClinical Trial Center, West China Hospital, Sichuan University, Chengdu, ChinaWest China School of Nursing, Sichuan University, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSouthwest Institute of Technical Physics, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaWest China School of Nursing, Sichuan University, Chengdu, ChinaArginase (Arg) plays a pivotal role in numerous pathological processes, with its dysregulated expression being intricately associated with tumor progression and immune evasion. This review comprehensively examines the diversity, mechanisms, and clinical potential of natural Arg modulators, encompassing polyphenols, flavonoids, and terpenoids. These bioactive compounds exert their modulatory effects on Arg activity through multiple mechanisms, including direct enzyme interaction, regulation of signaling pathways, and modulation of cellular metabolism. The therapeutic potential of these metabolites spans across various medical domains, notably in cardiovascular diseases, oncology, neurological disorders, and inflammatory conditions. Specifically, polyphenol metabolites such as resveratrol and curcumin have demonstrated significant benefits in cardiovascular health and neuroprotection, while flavonoids including rutin and quercetin have shown promising effects on intracellular inflammatory factors and tumor cell proliferation. Similarly, terpenoids like perillyl alcohol and triptolide have been found to influence cell polarization processes. However, despite their substantial therapeutic potential demonstrated in experimental studies, the development of natural Arg modulators faces several significant challenges. These include complexities in drug design attributed to the intricate structure and multiple isoforms of Arg, difficulties in elucidating precise mechanisms due to Arg’s multifaceted roles in various metabolic pathways, and limitations in current drug delivery systems. To overcome these challenges, future research should focus on continuous optimization of experimental design paradigms, enhancement of experimental models and data quality, thorough evaluation of therapeutic efficacy, and strategic integration of natural Arg modulators with precision medicine approaches.https://www.frontiersin.org/articles/10.3389/fphar.2025.1514400/fullnatural arginase modulatorcancer therapycardiovascular diseaseneuroprotectionmacrophage polarization
spellingShingle Ting Li
Ting Li
Ting Li
Jieying Wang
Huan Wang
Bowei Zhang
Lijuan Duan
Lijuan Duan
Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions
Frontiers in Pharmacology
natural arginase modulator
cancer therapy
cardiovascular disease
neuroprotection
macrophage polarization
title Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions
title_full Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions
title_fullStr Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions
title_full_unstemmed Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions
title_short Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions
title_sort therapeutic potential of natural arginase modulators mechanisms challenges and future directions
topic natural arginase modulator
cancer therapy
cardiovascular disease
neuroprotection
macrophage polarization
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1514400/full
work_keys_str_mv AT tingli therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections
AT tingli therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections
AT tingli therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections
AT jieyingwang therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections
AT huanwang therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections
AT boweizhang therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections
AT lijuanduan therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections
AT lijuanduan therapeuticpotentialofnaturalarginasemodulatorsmechanismschallengesandfuturedirections