The Therapeutic Effects of the Herbal Medicine, Juzen-taiho-to, on Amyloid-β Burden in a Mouse Model of Alzheimer's Disease

Abstract

Abstract. Innate immunity, especially that involving macrophage function, reportedly diminishes with advancing age and in patients with Alzheimer's disease (AD). In this study, we tried to elicit the non-specific activation of peripheral macrophages by oral administration of the herbal medicine Juzen-taiho-to (JTT), to assess its effect as a possible treatment for AD patients. Amyloid-β protein precursor transgenic mice were used as a model of AD to clarify the effect of JTT. Activated macrophages derived from bone marrow cross the blood-brain barrier, and then develop into microglia, which phagocytose aggregated amyloid-β (Aβ) in senile plaques. Here we show that orally administered JTT increased the number of CD11b-positive ramified microglia in the mouse brain. The immunohistochemical examination of brain sections stained with polyclonal anti-Aβ antibody showed reduced Aβ burden, and Aβ levels were also decreased in the insoluble fractions of brain homogenates, as determined by ELISA. Thus, the activation of peripheral macrophages by JTT might be a potential new therapeutic strategy for AD.

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>

“…Moreover, bone marrow-derived macrophages from JTT-administered mice showed enhanced phagocytosis of fAβ 42 (liu et al 2008). Hara et al (2010) demonstrated that oral JTT decreased Aβ burden in AD transgenic mice by activating bone marrow-derived macrophages. They speculated that bone marrow-derived macrophages crossed BBB, developed into microglia, and phagocytosed aggregated Aβ in senile plaques.…”

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.…”

Burn injury induces gelsolin expression and cleavage in the brain of mice

“…CD11b, a constitutive marker of myeloid cells, is expressed by mature monocyte (Barbizan and Oliveira, 2010) and monocyte-derived microglia-like cells (Hara et al, 2010). Clinical studies have associated gelsolin with a number of pathological conditions including inflammation, cell invasion and glial phagocytotic activity (Dong et al, 2006).…”

“…Following transfer, proteins were probed using a polyclonal anti-human gelsolin antibody (Ab) (Hara et al, 2010) (1:300; Abcam) in TBS-T. Horseradish peroxidase-conjugated secondary Ab was used at a 1:1000 dilution in TBS-T. After extensive washing, protein bands were visualized by electrochemiluminescence (ECL) reagent (Applygen Technologies Inc.) after exposure on autoradiograph film (Fuji Film, Kodak Scientific Imaging Film, Beijing, China). Membranes were then stripped and re-probed with b-actin (1:1000; Santa Cruz Biotechnology, Santa Cruz, CA, USA) to confirm equal protein loading.…”