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Pedunculoside alleviates cheilitis-like inflammation by suppressing the TLR3/TRIF/NF-κB signaling
Anming Zhu1, Junxi Liu2, Xianxian Cao2
1Yunnan Characteristic Plant Extraction Laboratory, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Kunming 650106, China; Yunnan Botanee Bio-Technology Group Co., Ltd., Kunming 650106, China; Botanee Research Institute, Shanghai Jiyan Biomedical Development Co., Ltd, Shanghai 201702, China.
Background:
Cheilitis is a lip-specific inflammatory disorder lacking safe long-term therapies. Topical glucocorticoids are limited by adverse effects, highlighting the need for plant-derived immunomodulators with dual anti-inflammatory and barrier-repairing effects.
Objective:
To evaluate the therapeutic potential, mechanism and human efficacy of pedunculoside in cheilitis.
Methods:
Pedunculoside was evaluated in vitro using CCK-8, scratch, ELISA, immunofluorescence, RT-qPCR, western blot, molecular docking and SPR. In human efficacy evaluation, pedunculoside formulation were assessed by VISIA-CR imaging, skin hydration and transepidermal water loss on the lips.
Results:
Pedunculoside (≤120 μM) showed no cytotoxicity and increased scratch wound closure 4.5-fold (N = 4). It upregulated barrier genes (AQP3: 1.7-fold, FLG: 2.3-fold, SPINK5: 11.16-fold, IVL: 7.96-fold, ZO-1: 2.26-fold, OCLN: 2.22-fold and KRT1: 4.41-fold) (N = 4) and suppressed inflammatory cytokines (IL-6: 0.68-fold, IL-8: 0.53-fold, IL-1β: 0.65-fold, TSLP: 0.69-fold, CCL5: 0.55-fold and CCL17: 0.58-fold) (N = 3). Mechanistically, pedunculoside directly bound with TLR3 and suppressed TLR3/TRIF/NF-κB signaling. In human efficacy, the pedunculoside formulation reduced lip redness by 0.3-fold (4 h, N = 32) and 0.23-fold (at 28 days, N = 20), decreased TEWL value by 0.22-fold (at 4 h) and 0.27-fold (at 28 days) and improved hydration by 0.22-fold (at 4 h) and 0.27-fold (at 28 days) versus baseline.
Conclusion:
Pedunculoside is a novel TLR3-targeting immunomodulator that enhances barrier repair and suppresses inflammation in vitro, while its formulation improves cheilitis symptoms. The absence of animal studies before human testing represents a limitation; larger trials are warranted to confirm long-term safety and efficacy.
