Uncaria Rhynchophylla and hirsuteine as TRPV1 agonists inducing channel desensitization

Taewoong Ha; Bokeum Kang; Mi-Sun Kim; Jung Woong Chu; Kyungmin Kim; Wooseung Yoon; Soon Ho Kim; Taek Kang; Min Soo Kim; Chungho Kim; Joo Young Cha; Uhtaek Oh; Kyungreem Han; Chun Whan Choi; Gyu-Sang Hong

doi:10.1016/j.jep.2024.118869

Uncaria Rhynchophylla and hirsuteine as TRPV1 agonists inducing channel desensitization

J Ethnopharmacol. 2024 Sep 29;337(Pt 2):118869. doi: 10.1016/j.jep.2024.118869. Online ahead of print.

Authors

Taewoong Ha¹, Bokeum Kang², Mi-Sun Kim², Jung Woong Chu³, Kyungmin Kim², Wooseung Yoon², Soon Ho Kim², Taek Kang², Min Soo Kim³, Chungho Kim⁴, Joo Young Cha⁵, Uhtaek Oh⁶, Kyungreem Han³, Chun Whan Choi⁷, Gyu-Sang Hong⁸

Affiliations

¹ Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea; Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea.
² Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.
³ Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea; Division of Bio-Medical Science & Technology, University of Science and Technology KIST School, Seoul, Republic of Korea.
⁴ Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea.
⁵ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.
⁶ Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.
⁷ Natural Product Research Team, Gyeonggi Biocenter, Gyeonggido Business and Science Accelerator, Gyeonggi-Do, Republic of Korea.
⁸ Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea; Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea; Division of Bio-Medical Science & Technology, University of Science and Technology KIST School, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address: [email protected].

PMID: 39353479
DOI: 10.1016/j.jep.2024.118869

Abstract

Ethnopharmacological relevance: 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.

Materials and methods: Electrophysiological recordings and calcium imaging experiments were conducted to assess TRPV1 activation by UR extract and HST in HEK293T cells and sensory neurons.

Results: 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.

Conclusion: 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.

Keywords: Desensitization; Hirsuteine; Sensory neuron; TRPV1; Uncaria rhynchophylla.