Targeting Integrin β3: novel antiplatelet lignans 6'-Hydroxyjusticidin B and Neojusticin A from Justicia procumbens unveiled via multi-omics and biophysical validation

doi:10.1007/s13659-025-00577-w

Natural Products and Bioprospecting ›› 2026, Vol. 16 ›› Issue (2): 26-26.DOI: 10.1007/s13659-025-00577-w

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Targeting Integrin β3: novel antiplatelet lignans 6'-Hydroxyjusticidin B and Neojusticin A from Justicia procumbens unveiled via multi-omics and biophysical validation

Meixian Xiang¹, Songtao Wu^2,3, Hanxiang Mei², Xiang Zheng², Cong Wang²

1. School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, China;
2. Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China;
3. Hubei Shizhen Laboratory, Wuhan 430061, China

Received:2025-09-24 Online:2026-04-22 Published:2026-04-22
Contact: Songtao Wu,Email:songt1wu@hbtcm.edu.cn
Supported by:
We are deeply grateful for the Hubei Provincial Department of Education Guiding Program [NO.B2023089]; the Hubei Provincial Natural Science Foundation of China [NO.2024AFD252]; the Fundamental Research Funds for the Central Universities South-Central MinZu University [NO. CZZ24017]; The Natural Science Foundation Project of Hubei Provincial Administration of Traditional Chinese Medicine [NO.ZY2025D020], Open Fund of Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine and Hubei Provincial Department of Education Guiding Program (KLRCCM2414).

Targeting Integrin β3: novel antiplatelet lignans 6'-Hydroxyjusticidin B and Neojusticin A from Justicia procumbens unveiled via multi-omics and biophysical validation

Meixian Xiang¹, Songtao Wu^2,3, Hanxiang Mei², Xiang Zheng², Cong Wang²

1. School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan 430074, China;
2. Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China;
3. Hubei Shizhen Laboratory, Wuhan 430061, China

通讯作者: Songtao Wu,Email:songt1wu@hbtcm.edu.cn
基金资助:
We are deeply grateful for the Hubei Provincial Department of Education Guiding Program [NO.B2023089]; the Hubei Provincial Natural Science Foundation of China [NO.2024AFD252]; the Fundamental Research Funds for the Central Universities South-Central MinZu University [NO. CZZ24017]; The Natural Science Foundation Project of Hubei Provincial Administration of Traditional Chinese Medicine [NO.ZY2025D020], Open Fund of Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine and Hubei Provincial Department of Education Guiding Program (KLRCCM2414).

Abstract

Abstract: Thrombotic disorders remain a global health burden, necessitating novel antiplatelet agents with improved safety and efficacy. This study investigates the molecular mechanisms of two lignans, 6'-Hydroxyjusticidin B (6'-HJB) and Neojusticin A (Neo-A), isolated from Justicia procumbens L., through an innovative target-driven strategy integrating LC/MS, proteomics, network pharmacology, and biophysical validation. For the first time, integrin β₃ (ITGB3) was identified as their direct molecular target, with microscale thermophoresis (MST) confirming high-affinity binding, the dissociation constant (Kd) = 0.0642 ± 0.005 μM for 6'-HJB; 0.0097 ± 0.001 μM for Neo-A. This study not only elucidates the structural basis of their activity-C-6 hydroxylation in 6'-HJB enhances ITGB3 specificity, whereas Neo-A's fused furan ring optimizes COX-1 interaction, but also establishes a paradigm shift from phenotypic screening to target-validated natural product research. The findings position 6'-HJB and Neo-A as promising candidates for the development of safer, ITGB3-mediated antithrombotic therapies, with future efforts directed toward structural optimization and preclinical validation.

Key words: Justicia procumbens, Lignans, Antiplatelet aggregation, ITGB3, Molecular mechanism

摘要： Thrombotic disorders remain a global health burden, necessitating novel antiplatelet agents with improved safety and efficacy. This study investigates the molecular mechanisms of two lignans, 6'-Hydroxyjusticidin B (6'-HJB) and Neojusticin A (Neo-A), isolated from Justicia procumbens L., through an innovative target-driven strategy integrating LC/MS, proteomics, network pharmacology, and biophysical validation. For the first time, integrin β₃ (ITGB3) was identified as their direct molecular target, with microscale thermophoresis (MST) confirming high-affinity binding, the dissociation constant (Kd) = 0.0642 ± 0.005 μM for 6'-HJB; 0.0097 ± 0.001 μM for Neo-A. This study not only elucidates the structural basis of their activity-C-6 hydroxylation in 6'-HJB enhances ITGB3 specificity, whereas Neo-A's fused furan ring optimizes COX-1 interaction, but also establishes a paradigm shift from phenotypic screening to target-validated natural product research. The findings position 6'-HJB and Neo-A as promising candidates for the development of safer, ITGB3-mediated antithrombotic therapies, with future efforts directed toward structural optimization and preclinical validation.

关键词: Justicia procumbens, Lignans, Antiplatelet aggregation, ITGB3, Molecular mechanism

Meixian Xiang, Songtao Wu, Hanxiang Mei, Xiang Zheng, Cong Wang. Targeting Integrin β3: novel antiplatelet lignans 6'-Hydroxyjusticidin B and Neojusticin A from Justicia procumbens unveiled via multi-omics and biophysical validation[J]. Natural Products and Bioprospecting, 2026, 16(2): 26-26.

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Targeting Integrin β3: novel antiplatelet lignans 6'-Hydroxyjusticidin B and Neojusticin A from Justicia procumbens unveiled via multi-omics and biophysical validation

Targeting Integrin β3: novel antiplatelet lignans 6'-Hydroxyjusticidin B and Neojusticin A from Justicia procumbens unveiled via multi-omics and biophysical validation

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