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Updated: Jan 6, 2026
Quantification of Humic and Fulvic Acids in Humate Ores, DOC, Humified Materials and Humic Substance-Containing Commercial Products
Published on: March 18, 2022
Functional groups as functional drivers: structure-activity relationships in humic substances for medical
Pengfei Xin1, Qingmei Liu2, Kuanshou Zhang3
1Department of Stomatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China. xinpengfei@sxbqeh.com.cn.
Abstract:
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.
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