Effect of pinocembrin on thymocyte proliferation and death

• Main Authors: Gulnoza Toshtemirova (Author), Sarvinoz Rustamova (Author), Nargiza Tsiferova (Author), Galina Maksimcheva (Author), Petr Merzlyak (Author), Ranohon Kurbannazarova (Author), Ravshan Sabirov (Author)
• Format: Book
• Published: Shahrekord University of Medical Sciences, 2024-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2345-5004; 10.34172/jhp.2024.48225
• Keywords: flavonoids; dexamethasone; cell death; necrosis; apoptosis; Medicine (General); R5-920; Therapeutics. Pharmacology; RM1-950
• Source: Journal of HerbMed Pharmacology, Vol 13, Iss 1, Pp 137-143 (2024)

Introduction: Cell volume regulation is critical for cellular proliferation and death. Pinocembrin effectively suppresses the volume regulation in thymocytes under hypoosmotic stress by blocking the volume-sensitive anion channel. This study aims to evaluate the effects of this flavonoid on thymocyte proliferation and death. Methods: Thymocytes were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, and the cell number was determined by cloud-based automated cell counting (Corning). Necrotic and apoptotic cell death were evaluated by propidium iodide- and annexin V-staining, respectively. Results: Pinocembrin at 10-50 μM caused suppression of primary cultured thymocyte proliferation with a half-maximal effect of 28.4 ± 0.2 μM. The cell counts did not fall below the control level at the doses of 100-150 μM. The fraction of spontaneously necrotic cells was ~26% of the total population and increased to ~51% in the presence of dexamethasone. The fraction of spontaneously apoptotic cells increased by this glucocorticoid from 3.6% to 16.7%. Pinocembrin protected thymocytes from necrosis both in spontaneous and dexamethasone-induced death, reducing the fraction of necrotic cells by ~40-50% at 150 μM. Pinocembrin attenuated dexamethasone-induced apoptotic death, reducing the fraction of annexin-positive cells to the control (spontaneous) level. Conclusion: Our results suggest that pinocembrin arrests thymocyte proliferation without essential killing. Under conditions of massive death (e.g., during inflammation, when the level of glucocorticoids increases sharply both physiologically and as a result of pharmacotherapy), pinocembrin protects immuno-competent cells from necrotic and apoptotic death.