Humic Substances as Master Regulators of Plant Stress Resilience: From Supramolecular Chemistry to Climate-Smart Agriculture

Humic substances (HS) are increasingly recognized not merely as soil conditioners but as dynamic biological regulators that orchestrate plant resilience through complex signaling networks. This review synthesizes recent advances in understanding how HS function as master regulators of plant adaptation to abiotic stress. We present a mechanistic framework integrating three interconnected themes: (1) the supramolecular chemistry of HS and its relationship to bioactivity, (2) the early signaling events, encompassing reactive oxygen species (ROS), calcium (Ca²⁺), and phytohormone crosstalk that translate HS perception into systemic stress responses, and (3) the tripartite interaction among plants, HS, and the rhizosphere microbiome. Emerging evidence demonstrates that HS act as chemical priming agents, inducing a state of "eustress" that preconditions plants for enhanced tolerance to subsequent drought, salinity, heat, and heavy metal stress. This preconditioning involves transcriptional reprogramming through transcription factors such as WRKY, NAC, and MYB, leading to enhanced antioxidant defenses, osmotic adjustment, photosynthetic protection, and nutrient homeostasis. We critically evaluate the structure-function relationships of HS, the molecular players in HS signaling, and the synergistic potential of HS with plant growth-promoting microorganisms. Finally, we identify critical knowledge gaps, including the identity of plant HS receptors, the relative contribution of direct versus microbiome-mediated effects, and the performance of HS under multifactorial stress combinations and propose future research directions. By bridging supramolecular chemistry, plant physiology, and microbiome science, this review positions HS as a cornerstone of climate-smart agriculture and provides a roadmap for developing next-generation, mechanism-based HS biostimulants.