Remission roles of the herbal formula B401 in mice with manganese-induced neurotoxicity

Chih-Hsiang Hsu,¹ Sheue-Er Wang,² Ching-Lung Lin,¹ Shuenn-Jyi Sheu,³ Chung-Hsin Wu<sup>1

1</sup>Department of Life Sciences, National Taiwan Normal University, Taipei City, ²Department of Pathological Inspection, Saint Paul’s Hospital, Taoyuan City, ³Brion Research Institute of Taiwan, New Taipei City, Taiwan


Abstract: Excessive exposure to manganese (Mn), mainly by occupational inhalation, may cause brain and motor defects that are known as manganism. There are a few pharmacological studies aimed at treating the symptoms of manganism. The herbal formula B401 may serve as a new lead in ameliorating Mn-induced neurotoxicity. In this study, we aimed to investigate the possible protective mechanisms of the herbal formula B401 against Mn-induced neurotoxicity. Thirty-two ICR mice were divided into four groups that were administered sham treatment, B401 treatment, Mn treatment, and B401 plus Mn treatment, respectively (n=8 for each group). Rotarod performance was used in these mice to compare their motor coordination. In addition, chemiluminescence analysis was used to examine the reactive oxygen species in their blood. Furthermore, immunostaining and Western blotting techniques were used to examine the expression of dopaminergic receptors, dopamine, brain-derived neurotrophic factor (BDNF), and oxidative stress and apoptosis-related protein markers in their brain tissue. We found that the mice given Mn treatment showed brain and motor defects in comparison to the mice undergoing sham treatment. Immunostaining and Western blotting revealed that the mice given Mn treatment had reduced dopaminergic and BDNF expressions, but enhanced oxidative stress and apoptosis-related protein markers in their brain tissue. While the mice administered B401 plus Mn treatment had significantly improved motor coordination and enhanced dopaminergic and BDNF expressions, they showed reduced oxidative stress and apoptosis-related protein markers in their brain tissue in comparison with the mice given Mn treatment. Our findings provide evidence that oral B401 treatment may alleviate the symptoms of Mn-induced neurotoxicity in mice by enhancing dopaminergic and BDNF expressions and suppressing oxidative stress and apoptosis in their brain tissue. Therefore, we suggest that the herbal formula B401 may be developed as a potential health supplement for ameliorating Mn-induced neurotoxicity.

Keywords: manganism, neurodegeneration, motor disorder, dopaminergic receptor, dopamine, brain-derived neurotrophic
factor, oxidative stress, apoptosis