Uncaria Rhynchophylla and hirsuteine as TRPV1 agonists inducing channel desensitization

• Published in: Journal of ethnopharmacology 2025-01, Vol.337 (Pt 2), p.118869, Article 118869
• Main Authors: Ha, Taewoong, Kang, Bokeum, Kim, Mi-Sun, Chu, Jung Woong, Kim, Kyungmin, Yoon, Wooseung, Kim, Soon Ho, Kang, Taek, Kim, Min Soo, Kim, Chungho, Cha, Joo Young, Oh, Uhtaek, Han, Kyungreem, Choi, Chun Whan, Hong, Gyu-Sang
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Capsaicin - pharmacology; Desensitization; HEK293 Cells; Hirsuteine; Humans; Plant Extracts - pharmacology; Sensory neuron; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; TRPV Cation Channels - agonists; TRPV Cation Channels - metabolism; TRPV1; Uncaria - chemistry; Uncaria rhynchophylla
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118869

Uncaria rhynchophylla (UR) is recognized for its therapeutic applications in treating hypertension and inflammation. However, the specific molecular mechanisms how UR and its bioactive constituents modulate inflammatory pathways remain unknown. This study investigates the effects of UR extract and its constituent, hirsuteine (HST), on TRPV1 channel modulation which is related to hypertension and inflammation. Electrophysiological recordings and calcium imaging experiments were conducted to assess TRPV1 activation by UR extract and HST in HEK293T cells and sensory neurons. UR extract and HST activated TRPV1 in HEK293T cells, with repeated applications causing channel desensitization. HST application on TRPV1-positive sensory neurons significantly reduced electrical activity compared to capsaicin. This study demonstrated UR extract and HST are a novel TRPV1 agonists inducing channel desensitization and a potent agent for treatment of TRPV1 dependent pain relief. [Display omitted] •Identification of the selective activation and subsequent desensitization of TRPV1 by UR extract and hirsuteine.•Detailed characterization of the interaction between hirsuteine and TRPV1.•Hirsuteine modulates neuronal excitability in TRPV1-positive sensory neurons.