Saikosaponin A alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting ferroptosis via SIRT1/Nrf2 pathway.

Abstract

Mastitis is a common and serious bacterial infection of the mammary gland. Saikosaponin A (SSA) is a triterpenoid saponin isolated from Bupleurum falcatum that has the ability to treat various diseases. However, little is known about the role of SSA in achieving mastitis remission. Here, we found that SSA alleviated Staphylococcus aureus (S. aureus)-induced mastitis by attenuating inflammation and maintaining blood-milk barrier integrity. Furthermore, S. aureus activated nuclear factor kappa B (NF-κB) pathway by upregulated p-p65 and p-IκB. S. aureus also induced ferroptosis in mammary gland in mice, mainly characterized by excessive iron accumulation, mitochondrial morphological changes and impaired antioxidant production. However, S. aureus-induced NF-κB activation and ferroptosis were prevented by SSA. Moreover, SAA could upregulate the expression of SIRT1, Nrf2, HO-1 and GPX4. And the inhibitory effects of SAA on inflammation and ferroptosis were reversed by SIRT1 inhibitor EX-527. In conclusion, SAA protected S. aureus-induced mastitis through suppressing inflammation and ferroptosis by activating SIRT1/Nrf2 pathway.

• Authors: Lihua Zhao, Lei Jin, Bin Yang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 27 Issue 22 Pg. 3443-3450 (Nov 2023) ISSN: 1582-4934 [Electronic] England
• PMID: 37644785 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• NF-kappa B
• saikosaponin D
• NF-E2-Related Factor 2
• Sirtuin 1
• SIRT1 protein, human

Topics

• Humans
• Female
• Animals
• Mice
• NF-kappa B (metabolism)
• Staphylococcus aureus
• NF-E2-Related Factor 2 (metabolism)
• Sirtuin 1
• Ferroptosis
• Mastitis (drug therapy, metabolism, microbiology)
• Inflammation (metabolism)