MRI detection of the activated region in the rat brain by Hochuekki-to, a traditional oriental medicine, and the related expression of BNIP-3 mRNA, a candidate of depression-related factor

Abstract

Japanese-Chinese traditional medicine (Wakan-yaku) contains various treatment prescriptions for the depression based on the peculiar theory, "mood, blood and water theory", "five elements theory" and others. I am studying to find treatment targets and therapeutic drugs of the depression by using the Wakan-yaku, mainly Hochuekki-to (HET). We have been reported that HET-and typical antidepressants-treatment enhance BINP-3 mRNA expression in cultured neuronal cell line, suggesting that BNIP-3 mRNA expression may be involved in depression. In this report, I found that 1) BNIP-3 mRNA was highly expressed in the hippocampus and the posterior hypothalamic neucleus in the rat brain by using the in-situ hybridization method and 2) HET stimulated the activity in the basal brain area at 15 min after oral administration by using MRI detection. Interestingly, the activated area is almost same as one of the expression region of BNIP-3. Although these results are in preliminary stage and further expression must be necessary, these results may suggest that HET rapidly stimulated the basal brain area probably through neuron from digestive system, and BNIP-3 may contribute in transduction mechanisms for anti-depressive effects of HET at that area.

Profiling of 120 types of herbal extracts and their effects on morphology in cultured neuronal or glial cell lines, followed by RNA extraction for a cDNA library: Consideration for use in studies based on Kampo theories

“…As described in the Introduction, we previously demonstrated that HET as well as an antidepressant treatment increased the expression levels of BNIP‐3 in NG108‐15 cells [1,2]. Previous studies also examined the function of BNIP‐3 [3,4,15]. The findings obtained are shown in Table 1, and 10 crude drugs comprising HET are shown with ‘#’ in the HET column.…”

“…We previously reported the significant upregulation of BNIP‐3 mRNA expression when Hochuekkito (Bu Zhong Yi Qi Tang) [1], as well as many antidepressants [1,2], were added to a culture medium of NG108‐15 cells, which is a hybrid cell of neuroblastoma N18TG‐2 and glioma cell C6Bu‐1. Starting from those results, we also found that BNIP‐3 mRNA expression was also detected in brain regions with highly active nerves [3] and contributed to synaptic enhancement [4], suggesting the functional significance of BNIP‐3 in the brain. As in the case of BNIP‐3 described above, studying the effects of crude drugs and Kampo prescriptions on cultured cell lines makes it possible to obtain new findings on effects triggered by them.…”

Effects of herbal extracts on mRNA expression of intrinsic antidepressant‐related candidate factor BNIP‐3 in cultured neuronal and glial cell lines: Relationship with the Kampo concept of Qi

“…Based on these facts, BNIP‐3 is considered to be a candidate as a factor in the brain related to the antidepressant effect. Studies have been conducted by us on changes in the expression during neuronal growth [4] and on analysis of the site of expression in the brain [5].…”