Germacrone Protects against NF-κB-Mediated Inflammatory Signaling, Apoptosis, and Retinal Ganglion Cell Survival in a Rat Glaucoma Model

Yu Yuan¹ and Linhai Shao²

¹Department of Ophthalmology, Hanzhong Central Hospital, Hanzhong, Shaanxi, China
²Department of Urology, Hanzhong Central Hospital, Hanzhong, Shaanxi, China

Retinal ischemia-reperfusion (I/R) is a pathological phenomenon that causes cellular destruction in several ocular disorders, so there is a need for novel possible neuroprotective drugs. Researchers have reported numerous neuroprotective effects of Germacrone (GM). Therefore, this study aimed to elucidate the underlying processes of GM that may contribute to glaucoma development. 40 healthy rats underwent retinal ischemia-reperfusion (I/R) damage. The animals were divided into control, I/R-induced, GM-1d, and GM-7d. After 7 days of I/R, mice were sacrificed and retinal tissue removed. An enzyme-linked immunosorbent assay (ELISA) was used to assess retinal Malondialdehyde (MDA) and 8-OHdG levels after oxidative injury. The Fluro-Gold (FG) labelling assay counted retinal ganglion cells (RGC) before and after labelling. DNA from retinal tissue RNA was amplified. Western blotting and real-time qRT-PCR were utilised to assess Bax, Casapses-3, Bcl-2, retinal NF-kB, and COX-2 expression. Retinal cell apoptotic mediator expression was measured by a TUNEL assay. Retinal I/R damage increases ganglion cell death. Long-term GM treatment (GM-7d) reduced NF-κB activation and raised COX-2 expression, which suggests antioxidant potential. TUNEL-positive apoptotic cells were reduced in long-term GM-treated rats. In GM-treated retinas, the Bax-Bcl-2 ratio was identical to the control group and significantly different from the I/R group. GM reduces I/R-induced retinal cell damage by inhibiting RG cell death. Seven days after GM therapy, histology showed retinal tissue loss. NF-κB signaling and intrinsic mitochondrial apoptosis are possible mechanisms that may be attenuated by GM and are attributed to a retinal protective effect.

Key words —— Germacrone; glaucoma; intraocular; retina

Tohoku J. Exp. Med., 2024 July, 263(3), 185-193.

Correspondence: Linhai Shao, Department of Urology, Hanzhong Central Hospital, No.557 Middle Section of Laodong West Road, Hantai District, Hanzhong, Shaanxi 723000, China.

e-mail: linhaishao3@gmail.com or 1352057334@qq.com