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

Abstract

Background 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. Methods 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. Results 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. Conclusions GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

Germacrone attenuates memory impairment, hippocampal inflammation, and neurological deficits induced by Lipopolysaccharide in mice

“…Our results indicated that GE treatment prevented the LPS-induced cognitive impairments by perturbing neuroin ammation. Consistent with previous studies, GE alleviates neurological de cits in traumatic brain injury via repressing neuroin ammation and oxidative stress 25 . Multiple studies revealed that neuroin ammation is related to the neurodegenerative diseases.…”

“…The Curcuma species have been used in traditional Chinese medicine for more than one thousand years 18 . The curcuminoids and volatile oil extracted from Curcuma species have been extensively studied due to their biological activities and pharmacological effects, including anti-in ammatory, antitumor, antioxidant, antimicrobial properties, and therapeutical promise on the nervous, digestive, and cardiovascular systems [19][20][21][22][23][24][25] . Germacrone (GE) has been identi ed as one of the main ingredients in Curcumae Wenyujin Y.H.…”

“…Makabe et al reported that GE suppressed ear in ammation by 75% 22 whilst An et al showed that pro-in ammatory cytokines were suppressed signi cantly by GE 19 . Ni and coworkers reported that GE alleviates neurological de cits in traumatic brain injury via repressing neuroin ammation and oxidative stress 25 . Peng and coworkers demonstrated that GE attenuates cerebral ischemia/reperfusion injury in rats via antioxidative and antiapoptotic mechanisms 24 .…”

Effect of Topiramate on Mitochondrial Biogenesis and Neuroinflammation in Chronic Constriction Injury and Streptozotocin-induced Peripheral Neuropathy

“…Experimentally, this chronic pain condition is well established by using CCI to sciatic nerve and STZ animal model of peripheral nerve injury. 45,46 Again, these models are associated with development of characteristic symptoms of neuropathy like allodynia and hyperalgesia. The present study showed that CCI and STZ lead to elevated levels of proinflammatory cytokines like TNF-α, IL-1ꞵ, and IL-6 and total calcium in homogenate of sciatic nerve.…”

Neuroprotective and Anti-inflammatory Effects of Pioglitazone on Traumatic Brain Injury

“…The permeability of the blood-brain-barrier (BBB) increases the infiltration of circulating monocytes, lymphocytes, and neutrophils inside the brain parenchyma within 24 hours of TBI. Because of this, the complement system is stimulated and the inflammatory cytokines like tissue necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) that are proinflammatory cytokines are released [43][44][45][46]. When these inflammatory cytokines are released, BBB dysfunction and brain edema occur.…”