2. Academic Validation
  3. Magnolol and honokiol target TRPC4 to regulate extracellular calcium influx and relax intestinal smooth muscle

Magnolol and honokiol target TRPC4 to regulate extracellular calcium influx and relax intestinal smooth muscle

  • J Ethnopharmacol. 2022 May 23;290:115105. doi: 10.1016/j.jep.2022.115105.
Lin Niu 1,  Jie Wang 2,  Fukui Shen 2,  Jie Gao 2,  Min Jiang 2,  Gang Bai 3
Affiliations

Affiliations

  • 1 Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, PR China.
  • 2 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, PR China.
  • 3 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, PR China. Electronic address: gangbai@nankai.edu.cn.
PMID: 35157953 DOI: 10.1016/j.jep.2022.115105
Abstract

Ethnopharmacological relevance: Magnolia officinalis Cortex (M. officinalis) is a classical traditional Chinese medicine (TCM) widely used to treat digestive system diseases. It effectively regulates gastrointestinal motility to improve abdominal pain, abdominal distension and other symptoms. Magnolol (MAG) and honokiol (HON) are the main pharmacodynamic components responsible for the gastrointestinal activity of M. officinalis.

Aim of the study: The transient receptor potential (TRP) family is highly expressed in the gastrointestinal tract and participates in the regulation of gastrointestinal motility, visceral hypersensitivity, visceral secretion and other physiological activities. In this study, the calcium-lowering mechanisms of MAG and HON contributing to the smooth muscle relaxation associated with TRP are discussed.

Materials and methods: The relaxation smooth muscle effects of MAG and HON were tested by the isolated intestine tone tests. A synthetic MAG probe (MAG-P) was used to target fishing for their possible target. The distribution of MAG on the smooth muscle was identified by a molecular tracer based on chemical biology. CA2+ imaging and dual-luciferase reporter assays were used to determine the effects on the target proteins. Finally, the calcium-mediating effects of MAG and HON on smooth muscle cells and TRPC4-knockdown cells were compared to verify the potential mechanism.

Results: After confirming the smooth muscle relaxation in the small intestine induced by MAG and HON, the relaxation effect was identified mainly due to the downregulation of intracellular calcium by controlling external calcium influx. Although MAG and HON inhibited both TRPV4 and TRPC4 channels to reduce calcium levels, the inhibitory effect on TRPC4 channels is an important mechanism of their smooth muscle relaxation effect, since TRPC4 is widely expressed in the small intestinal smooth muscle cells.

Conclusions: The inhibition of MAG and HON on TRPC4 channels contributes to the relaxation of intestinal smooth muscle.

Keywords

Calcium regulating; Honokiol; Magnolol; Smooth muscle relaxation; Transient receptor potential.

Figures
Products