Chronic kidney disease is marked by gradual functional decline driven by sustained inflammatory signaling, fibrotic remodeling, dysregulated fluid handling, and impaired mitochondrial homeostasis. Although botanical formulations used in traditional health systems are frequently described as kidney-supportive, their cellular-level actions remain insufficiently defined. In this study, a composite botanical hydrosol prepared from Alpinia oxyphylla Miq. and fermented plant materials derived from Polygonatum kingianum, Euryale ferox, and Lycium chinense was examined using renal epithelial cell–based experimental systems. The investigation focused on inflammatory modulation, fibrotic pathway activity, aquaporin-related responses, and mitochondrial-associated gene expression.

The hydrosol markedly reduced nitric oxide release in lipopolysaccharide-challenged macrophages, indicating suppression of inflammatory activation. In HEK293 cells exposed to interleukin-1β, treatment produced a temporally distinct immunomodulatory profile, characterized by early elevation of regulatory cytokines (IL-6, IL-8, and IL-10) followed by later-stage downregulation of pro-inflammatory mediators, including IL-12A and interferon-γ. In transforming growth factor-β1–stimulated fibrosis models, hydrosol exposure limited extracellular matrix deposition and maintained epithelial structural integrity. While aquaporin-3 expression exhibited only a modest, non-significant rise, the overall trend suggested supportive regulation of water transport mechanisms.

At the intracellular level, the formulation induced pronounced activation of genes linked to mitochondrial quality control and protein homeostasis. This response included a greater than fourfold increase in Parkin expression, along with notable upregulation of Ubl5, NADSYN1, Atg8, and multiple chaperonin complex components (CCT2, CCT6A, and CCT8). Collectively, these findings demonstrate that the botanical hydrosol promotes coordinated anti-inflammatory, anti-fibrotic, and mitochondrial-supportive cellular responses. The results provide mechanistic evidence supporting the development of hydrosol-based nutritional strategies aimed at maintaining renal cellular resilience and promoting healthy aging.