Juzen-Taiho-To, an Herbal Medicine, Promotes the Differentiation of Transplanted Bone Marrow Cells into Microglia in the Mouse Brain Injected with Fibrillar Amyloid <i>β</i>

Abstract

Microglia are the main immunocompetent and phagocytic cells in Alzheimer's disease (AD). Bone marrowderived microglia have been demonstrated to be more effective in antigen presentation and phagocytosis than inherent microglia in AD. Thus, microglia have received much attention in the pathogenesis of AD. The herbal medicine Juzen-taiho-to (JTT) has been reported to reduce β-amyloid (Aβ) burden in the mouse brain of an AD model. In this study, we explored the effects of JTT on the migration and differentiation of bone marrow-derived cells in the mouse brain of acutely induced AD. To chase bone marrow-derived cells, we made a chimeric mouse line in C57BL/6 by transplanting fresh bone marrow cells, isolated from the transgenic mice expressing enhanced green fluorescent protein gene. The chimeric mice were orally administrated with JTT or distilled water, and were left untreated or given intrahippocampal injection of fibrillar Aβ 1-42 (fAβ 42 ) or vehicle. In the hippocampus of the vehicle-injected mouse, JTT treatment for 37 days caused a significant increase in the number of microglial cells. In the fAβ 42 -injected mouse hippocampus, a larger number of bone marrow-derived cells were detected in JTT-treated mice than control mice in the non-neighboring regions of the fAβ 42 -injected site but not around the injected site. These results suggest that JTT might contribute to the reduction of Aβ burden and the immune surveillance in non-pathological as well as pathological brain regions. The results also implicate the therapeutic potential of JTT in AD.

Abundance of Plant-Associated Gammaproteobacteria Correlates with Immunostimulatory Activity of Angelica sinensis

“…Both JTT and A. sinensis are known to stimulate innate immune cells [22,43]. In particular, it is well-recognized that JTT exhibits “LPS-like” immunological effects [44,45] as evidenced by very similar gene expression profiles of JTT and LPS [22,46]. The current study further corroborates the emerging notion that humans may be benefiting from plant-associated bacteria through the practice of herbal medicine.…”

Fermented Sipjeondaebo-tang Alleviates Memory Deficits and Loss of Hippocampal Neurogenesis in Scopolamine-induced Amnesia in Mice

“…Previous papers have reported that SJ possesses various biological properties, including anti-inflammatory properties, anti-cancer activity, gastroprotective effects and immune cell activation 8 9 10 11 . Recent studies using the AD animal model have suggested that the neuroprotective effects of SJ are due to reduced Aβ aggregation and reduced activation of microglia 12 13 . However, the effects of SJ on hippocampal neurogenesis and cognitive functioning have not been studied.…”

Uncovering potential ‘herbal probiotics’ in Juzen-taiho-to through the study of associated bacterial populations

“…First, JTT has been known for “LPS-like” immunostimulatory activity; 20,21 both JTT and LPS induce similar gene expression profiles in monocytes. 22,23 Second, many of the component herbs of JTT are roots (Table S1), which directly interact with a wide variety of soil bacteria.…”