Chlorogenic acid alleviated testicular inflammation and apoptosis in tunicamycin induced endoplasmic reticulum stress

Physiol Int. 2023 Mar 6;110(1):19-33. doi: 10.1556/2060.2023.00132. Print 2023 Mar 10.

Abstract

Purpose: Chlorogenic acid (CA) is a polyphenolic compound, found in many herbs and foods including coffee, berries and potatoes. Anti-inflammatory, anti-oxidant, anti-cancer and anti-apoptotic effects of CA have been proven in many tissues. Testicular inflammation and apoptosis are essential factors in male infertility that could result from endoplasmic reticulum (ER) stress. ER stress leads to unfolding and misfolding of nascent proteins and thereby provokes cellular inflammatory and apoptotic pathways. This study was designed to assess the effects of CA on ER stress-induced testis inflammation and apoptosis.

Methods: To do this, male mice were divided into six groups. The control, vehicle and CA groups received saline, DMSO and 50 mg kg-1 CA. Tunicamycin (TM (was injected to induce ER stress (TM group). In the CA20-TM and CA50-TM groups, 20 mg kg-1 CA and 50 mg kg-1 CA were administered one hour before TM injection. After thirty hours, animals were sacrificed and testes were removed. Hematoxylin & eosin staining, ELISA assay and real-time PCR were performed.

Results: CA administration significantly downregulated gene expression of TNFα, IL6, P53, Bax/Bcl2 ratio and caspase3. It also reduced testis levels of ALP, NF-κB, TNFα and caspse3. Finally, CA relieved structural changes in seminiferous tubules.

Conclusions: This study demonstrated that the positive effects of CA on the attenuation of ER-stress induced inflammation and apoptosis might be due to the inhibition of NF-κB and thereby suppression of inflammatory and apoptotic pathways.

Keywords: ER stress; NF-κB; apoptosis; chlorogenic acid; inflammation; testis.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis
  • Chlorogenic Acid* / pharmacology
  • Endoplasmic Reticulum Stress
  • Inflammation
  • Male
  • Mice
  • NF-kappa B
  • Tumor Necrosis Factor-alpha*
  • Tunicamycin / pharmacology

Substances

  • Tumor Necrosis Factor-alpha
  • Chlorogenic Acid
  • Tunicamycin
  • NF-kappa B
  • Antioxidants