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<p>Humic substances (HSs) have long been used in traditional medicine, but their translation into modern therapeutics has been limited by a lack of mechanistic understanding of their structure–activity relationships. This study combines bibliometric analysis of 1860 Web of Science publications (2000–2025) with a critical review to address this gap. The inclusion of 17 articles from 2025 did not alter the overall trend analysis. Bibliometric analysis reveals a pronounced disciplinary imbalance, with <i>Environmental Sciences</i> dominating the literature (480/1860) compared to <i>Pharmacology &amp; Pharmacy</i> (48/1860). Research focus has shifted from adsorption processes (2006–2010) to HS-based nanocarriers and photothermal therapy (2016–2025). However, despite growing interest in biomedical functionalities, only a limited number of studies have progressed to preclinical validation. The integrated critical review identifies specific functional groups in HSs as key determinants of biological activity, including: (1) carboxylic and phenolic hydroxyl groups enable pH-responsive drug delivery and chelation of heavy metals; (2) quinone moieties regulate redox homeostasis via reactive oxygen species scavenging and electron transfer modulation, underpinning anti-inflammatory, antioxidant, and antimicrobial effects; (3) amphiphilic architectures, comprising hydrophobic aromatic cores and hydrophilic groups, enhance solubility and intestinal permeability of poorly bioavailable drugs; (4) aromatic ring systems facilitate non-specific binding to enzymes and signaling proteins, inhibiting pro-tumorigenic pathways and attenuating inflammatory cascades. Methodological limitations include reliance on a single database and inconsistent HS characterization. Future research should prioritize standardized HS purification, clinical trials of HS-based formulations, and concerted interdisciplinary effort to bridge the gaps between structural characterization and translational applications.</p>

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Functional groups as functional drivers: structure–activity relationships in humic substances for medical applications

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Pengfei Xin,
  • Qingmei Liu,
  • Kuanshou Zhang,
  • Caifeng Zhang

摘要

Humic substances (HSs) have long been used in traditional medicine, but their translation into modern therapeutics has been limited by a lack of mechanistic understanding of their structure–activity relationships. This study combines bibliometric analysis of 1860 Web of Science publications (2000–2025) with a critical review to address this gap. The inclusion of 17 articles from 2025 did not alter the overall trend analysis. Bibliometric analysis reveals a pronounced disciplinary imbalance, with Environmental Sciences dominating the literature (480/1860) compared to Pharmacology & Pharmacy (48/1860). Research focus has shifted from adsorption processes (2006–2010) to HS-based nanocarriers and photothermal therapy (2016–2025). However, despite growing interest in biomedical functionalities, only a limited number of studies have progressed to preclinical validation. The integrated critical review identifies specific functional groups in HSs as key determinants of biological activity, including: (1) carboxylic and phenolic hydroxyl groups enable pH-responsive drug delivery and chelation of heavy metals; (2) quinone moieties regulate redox homeostasis via reactive oxygen species scavenging and electron transfer modulation, underpinning anti-inflammatory, antioxidant, and antimicrobial effects; (3) amphiphilic architectures, comprising hydrophobic aromatic cores and hydrophilic groups, enhance solubility and intestinal permeability of poorly bioavailable drugs; (4) aromatic ring systems facilitate non-specific binding to enzymes and signaling proteins, inhibiting pro-tumorigenic pathways and attenuating inflammatory cascades. Methodological limitations include reliance on a single database and inconsistent HS characterization. Future research should prioritize standardized HS purification, clinical trials of HS-based formulations, and concerted interdisciplinary effort to bridge the gaps between structural characterization and translational applications.