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, and kidney and liver functions, were assessed
along with the integrity of the 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 an open field test, and
depressive behavior was assessed through the forced swim test, while learning and memory were
assessed using the 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 the 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 a potential drug
candidate in the future.
Keywords:
Anxiety, Neuroinflammation, Blood Brain Barrier, Heavy Metals, Shogaol, Metabolic Profile
Graphical Abstract
[4]
Garbarino, J.R.; Hayes, H.C.; Roth, D.A.; Antweiler, R.C.; Brinton, T.I.; Taylor, H.E. Heavy metals in the Mississippi River. US Geological Survey Circular Usgs. Circulation, 1996, 53-72.
[21]
Shakir, S.K.; Azizullah, A.; Waheed, M.; Farhat, N.; Shafiq, R. Toxic
Metal Pollution in Pakistan and Its Possible Risks to Public Health;
de Voogt Ed,;.Reviews of Environmental Contamination and Toxicology.
Springer, Cham. Vol. 242. 2016.
[28]
Wu, Z.; Du, Y.; Xue, H.; Wu, Y.; Zhou, B. Aluminum induces neurodegeneration and its toxicity arises from increased iron accumulation and Reactive Oxygen Species (ROS) production. Neurobiol. Aging, 2012, 33(1), 199.
[58]
National Research Council. Guide for the Care and Use of Laboratory Animals; 8th edi; National Academies Press: Washington, D.C., 2010.
[67]
Islam, R.; Faysal, S.M.; Amin, R.; Juliana, F.M.; Islam, M.J.; Alam, M.J.; Hossain, M.N.; Asaduzzaman, M. Assessment of pH and Total Dissolved Substances (TDS) in the commercially available bottled drinking water. IORS J. Nurs. Health Sci. Ver., 2017, 6(5), 35-40.
[69]
Mahurpawar, M. Effects of heavy metals on human health. Int. J. Res. Granthaalayah, 2015, 3(9), 2394-3629.
[103]
Duc, H. N.; Oh, H.; Kim, M. S. The effect of mixture of heavy metals
on obesity in individuals ≥ 50 years of age. 2022, 200(8), 3554-3571.
[112]
Walker, H.K.; Hall, W.D.; Hurst, J.W. Clinical methods: The history,
physical, and laboratory examinations. 3rd edi; , 1990.
[118]
Rao, M.; Acharya, Y.; Naik, J.; Fatteh, S.; Fateh, A.; Pawar, A.; Jayalakshmi, G.; Sandhya, B.; Arja, S.B. Effect of heavy metals on the activity levels of hepatic enzymes in the maternal and embryonic tissue of viviparous scorpion (H. Fulvipes). Int. J. Life Sci. Sci. Res., 2017, 3, 1-186.
[120]
Song, L. Chapter one - Calcium and bone metabolism indices. In: Advances in Clinical Chemistry; Makowski, G.S., Ed.; Elsevier: Amsterefam, 2017; Vol. 82, pp. 1-46.
[161]
Harsha, S.; Anilakumar, K. Anxiolytic effects of the extracts of Zingiber officinale in mice. J. Pharm. Res., 2012, 5(1), 219-13.
[162]
Yadav, N.; Gaidhani, S. Anxiolytic activity of 6-Shogaol in experimental models of anxiety in mice. Adv. Pharmacol. Toxicol., 2015, 16(2), 11.