2. Academic Validation
  3. Novel antidepressant mechanism of hypericin: Role of connexin 43-based gap junctions

Novel antidepressant mechanism of hypericin: Role of connexin 43-based gap junctions

  • Biomed Pharmacother. 2023 Sep 19;167:115545. doi: 10.1016/j.biopha.2023.115545.
Huiqin Wang 1,  Xueying Yang 2,  Huaqing Lai 3,  Yang Sun 4,  Xu Yan 5,  Qidi Ai 4,  Meiyu Lin 4,  Songwei Yang 4,  Yantao Yang 4,  Shifeng Chu 5,  Zhenzhen Wang 6,  Naihong Chen 7
Affiliations

Affiliations

  • 1 Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, Hunan, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2 School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China.
  • 3 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.
  • 4 Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, Hunan, China.
  • 5 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 6 State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 7 Hunan University of Chinese Medicine & Hunan Engineering Technology Center of Standardization and Function of Chinese Herbal Decoction Pieces, Changsha 410208, Hunan, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
PMID: 37734259 DOI: 10.1016/j.biopha.2023.115545
Abstract

Hypericin is widely utilized for its precise antidepressant properties, but its exact antidepressant mechanism remains unclear. Gap junctions, which were predominantly expressed in astrocytes in the central nervous system, are concerned with the pathogenesis of depression. However, the role of hypericin in gap junctional dysfunction in depression has rarely been investigated. Here, we found that gap junctions were ultra-structurally broadened in the chronic unpredictable stress (CUS) rat model of depression, while hypericin repaired the dysfunction of gap junctions. Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin. Meanwhile, hypericin failed to show antidepressant benefits. Furthermore, in corticosterone (CORT)-stimulated primary astrocytes derived from neonatal rats, hypericin dramatically reversed the phosphorylation of connexin 43 (Cx43), normalizing the expression of Cx43 and thereby ameliorating gap junctional dysfunction. Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.

Keywords

Antidepressant mechanism; Astrocyte; Connexin 43; Depression; Gap junction; Hypericin.

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