Pipeline

Inflammaging, a sustained state of low-level inflammatory activity with age, is a driving factor in age-related changes in skin structure, function, and appearance. The objective of this study was to investigate the anti-inflammatory and anti-aging potential of naringenin, a natural flavonoid, using a combination of mechanistic in vitro analyses and a controlled human clinical evaluation. The activities and mechanism of action of naringenin were tested on normal human epidermal keratinocytes and in complementary acellular assays. A placebo-controlled clinical study was conducted to assess the effects of topical naringenin on multiple skin parameters. Transcriptomic analysis was applied as a discovery-driven strategy to characterize the molecular responses induced by naringenin. Naringenin was found to have anti-inflammatory properties, including downregulation of proinflammatory pathway genes, a significant reduction in biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in keratinocytes, and a reduction in visible redness in clinical trial participants. In addition to its anti-inflammatory activity, naringenin exhibited a multimodal anti-aging profile, including gene expression changes consistent with modulation of skin aging, radical-scavenging capacity, inhibition of elastase activity, and reduced protein glycation. Topical application led to statistically significant improvements in multiple skin attributes.

The epidermal barrier is essential for skin function, resilience, and tolerance to environmental and procedural stress. Disruption of this barrier is common after cosmetic treatments such as chemical peeling, underscoring the need for ingredients with proven biological and clinical support for barrier recovery. This study evaluated dihydrokaempferol (DHK) using molecular, preclinical, and clinical approaches. Gene expression profiling in keratinocytes and dermal fibroblasts revealed that DHK enhanced barrier-related genes, reduced inflammation-associated markers, and modulated genes involved in extracellular matrix remodeling. Functional assays confirmed antioxidant activity, suppression of stress-induced interleukin 6 (IL-6) release, increased elastin production, and improved fibroblast migration. Clinically, a randomized, placebo-controlled, split-face study following standardized chemical peeling demonstrated that DHK-treated skin showed significant improvements in dermatologist-assessed skin attributes versus placebo. Together, these findings indicate that DHK supports epidermal barrier integrity, modulates dermal repair mechanisms, and enhances recovery from controlled skin stress. The effects observed at the molecular and cellular levels translated into measurable improvements in visible skin quality, highlighting DHK’s potential as a bioactive ingredient.