Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress

• Published in: BMC complementary and alternative medicine 2021-01, Vol.21 (1), p.6-6, Article 6
• Main Authors: Zhuang, Sujing, Liu, Baogui, Guo, Shifeng, Xue, Yanzhong, Wu, Lin, Liu, Shiqi, Zhang, Chunling, Ni, Xiuyan
• Format: Article
• Language: English
• Subjects: Alternative medicine; Analysis; Animals; Antioxidants; Apoptosis; Assaying; Brain; Brain - drug effects; Brain - metabolism; Brain Edema - drug therapy; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - metabolism; Colorimetry; Curcuma; Cytokines; Cytokines - metabolism; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Enzyme-linked immunosorbent assay; Enzymes; Experiments; Germacrone; Head injuries; IL-1β; Inflammation; Inflammatory response; Injuries; Interleukin 6; Interleukins; Ischemia; Learning; Male; Malondialdehyde; Markers; Medical prognosis; Memory - drug effects; Mice; Mice, Inbred C57BL; Microglia - drug effects; Motor skill learning; Nervous System Diseases - drug therapy; Nervous System Diseases - etiology; Nervous System Diseases - metabolism; Neurological diseases; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB; Oxidative stress; Oxidative Stress - drug effects; Peroxidase; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Proteins; Recovery of function; Recovery of Function - drug effects; Sesquiterpenes, Germacrane - pharmacology; Sesquiterpenes, Germacrane - therapeutic use; Spatial discrimination learning; Spatial Learning - drug effects; Spatial memory; Superoxide; Superoxide dismutase; Swimming; Traumatic brain injury; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-020-03175-0

Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.