Neuroprotective Effects of Shogaol in Metals (Al, As and Pb) and High-fat diet-induced Neuroinflammation and Behavior in Mice

Abstract

Background: Increased exposure of humans to toxic metals and high fat diet (HFD) consumption severely damages brain health. Natural plant extracts have shown huge potential to treat multiple human diseases. Objective: The present study was designed to evaluate the protective effects of Shogaol (an active component of ginger) in neuroinflammation and behavioral paradigms in mice treated with metals and HFD. Methods: 8-11 weeks old male mice model was developed by giving a combination of metals i.e. Arsenic (As), Lead (Pb) and Aluminum (Al), 25mg/kg each mixed in drinking water with laboratory prepared HFD (40% fat) for a total duration of 72 days. Shogaol treated groups received two doses (2mg/kg & 12mg/kg) of shogaol along with metals and HFD. The biochemical parameters including body weights, blood glucose, kidney and liver functions were assessed along with the integrity of blood brain barrier (BBB). The expression analysis of neuroinflammatory genes (TNF-α, IL-1β & GFAP) was performed using q-PCR in the hippocampus and cortex. The exploratory and anxiety like behavior was assessed using open filed, and depressive behavior was assessed through forced swim test, while learning and memory were assessed using Morris water maze test and y- maze test. Results: Shogaol (2mg/kg & 12mg/kg) treatment improved metabolic profile and reduced expression of neuroinflammatory genes in the cortex and the hippocampus. Shogaol treatment improved BBB integrity. Results of behavioral analysis showed that Shogaol treatment (2mg/kg & 12mg/kg) rescued behavioral impairment and improved anxiety and depression. Conclusion: Shogaol treatment showed strong therapeutic potential in metals & HFD induced neuroinflammation and improved cognitive functions, thus, can be considered as a potential drug candidate in future.

6-Shogaol Alleviates Neuronal Cell Excessive Autophagy and Calcium Overload in Cerebral Ischemia-Reperfusion Injury via Modulating miRNA-26a-5p/DAPK1 Signaling Axis

“…Gingerol is the main pungent compound in fresh ginger, while ginger phenol is formed during heating or cooking of ginger, and 6-SH is the most abundant gingerol analogue in dry ginger [42] . Studies have shown that 6-SH exerts neuroprotective effects by inhibiting neuroin ammation [43][44][45] , suggesting its potential as a neuroprotective agent. Research by Nazim UM et al found that 6-SH treatment increases p62 expression and decreases LC3 expression levels, inhibiting autophagic ux, inhibiting tumor cell proliferation, and inducing TRAIL-mediated cell death in liver cancer cells [46] .…”

Inhibiting mitochondrial inflammation through Drp1/HK1/NLRP3 pathway: A mechanism of alpinetin attenuated aging‐associated cognitive impairment

“…are the most popular spices worldwide, especially in Asian countries, and have many distinct bioactive compounds with antiinflammatory and antioxidant properties (Ran et al, 2019). Ginger and its bioactive components, such as zerumbone, curcumin, 6-gingerol, and shokol, have been reported to enhance learning and memory in animal models (Adetuyi & Farombi, 2021;Arcusa et al, 2022;Ishaq et al, 2022;Kim et al, 2010Kim et al, , 2018Liu et al, 2019;Talebi et al, 2021;Zarei et al, 2021). Some reports have suggested that ginger extract can alleviate cognitive deficits by regulating ERK/CREB activation or inhibiting nitric oxide production (Lim et al, 2014;Mustafa et al, 2019).…”

Chronic Pb Exposure Induces Anxiety and Depression-like Behaviors in Mice via Excitatory Neuronal Hyperexcitability in Ventral Hippocampal Dentate Gyrus

“…At present, population-based studies have reported well-established positive correlations between blood/dentine Pb levels and anxiety in children. , However, most current studies in animal experiments remain at the level of validity of this relationship, , with sparse information regarding underlying neural mechanisms. A number of molecular studies have been performed to characterize the mechanisms and a few of differentially expressed molecules are identified. − However, these molecules are involved in multiple areas of research and none of them have been proven to have a role in Pb-induced anxiety and depression, making it difficult to precisely identify the research direction for us. On the other hand, behaviors can be more directly regulated by neuronal activity than molecules.…”