A modified formulation of Huanglian-Jie-Du-Tang reduces memory impairments and β-amyloid plaques in a triple transgenic mouse model of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of β-amyloid peptide (Aβ)-rich senile plaques. Recently we have identified a novel function of a patented formulation of modified Huanglian-Jie-Tu-Tang (HLJDT-M), a Chinese herbal medicine, in treating AD in in vitro studies (US patent No. 9,375,457). HLJDT-M is a formulation composed of Rhizoma Coptitis, Cortex Phellodendri and Fructus Gardeniae without Radix Scutellariae. Here, we assessed the efficacy of HLJDT-M on a triple transgenic mouse model of AD (3XTg-AD). Oral administration of HLJDT-M ameliorated the cognitive dysfunction of 3XTg-AD mice and lessened the plaque burden. In addition, biochemical assays revealed a significant decrease in levels of detergent-soluble and acid-soluble Aβ via decreasing the levels of full length amyloid-β precursor protein (FL-APP) and C-terminal fragments of APP (CTFs) in brain lysates of HLJDT-M-treated mice. HLJDT-M treatment also significantly reduced the levels of FL-APP and CTFs in N2a/SweAPP cells. In contrast, treatment using the classical formula HLJDT did not reduce the memory impairment of 3XTg-AD mice and, rather, increased the Aβ/Fl-APP/CTFs in both animal and cell culture studies. Altogether, our study indicates that HLJDT-M is a promising herbal formulation to prevent and/or cure AD.

Protective effects of Huang-Lian-Jie-Du-Tang against Aβ25–35-induced memory deficits and oxidative stress in rats

“…Therapy with HLJDT significantly improved these parameters, with a higher activity of SOD and GSH and a lower level of MDA. These findings indicate that HLJDT could effectively attenuate OS induced by Ab [25][26][27][28][29][30][31][32][33][34][35] injection.…”

“…25 Our results showed that administration of HLJDT reduced Ab and APP protein levels in hippocampal tissue from rats in which Ab 25-35 had experimentally induced AD. In the triple transgenic mouse model, modified HLJDT was shown to mediate the reduction of both the plaque load and memory impairment and HLJDT treatment increased APP and Ab; 26 HLJDT and baicalein treatment was shown to increase the amyloidogenic metabolism of APP in TgCRND8 mice expressing human APP with Swedish (K670N/M671L) and Indiana (V717F) mutations. 27 However, our study likely differs from the previous reports because the model systems used are different, and thus, physiological differences could possibly give rise to the varying results.…”

“…In the present study, we investigated the protective effects of HLJDT on ameliorating the deficits in learning and memory induced by injection of Ab [25][26][27][28][29][30][31][32][33][34][35] in rats. The current study results reveal that animals with experimental AD (induced by hippocampal CA1 injection of Ab [25][26][27][28][29][30][31][32][33][34][35] showed increased deposition of Ab in the hippocampal CA1 region and a noticeable decline in learning and memory compared with controls. However, experimental AD rats treated with HLJDT showed decreased Ab and APP levels in the hippocampus and improvements in learning and memory, as shown by the MWM test.…”

Systematic Review of Basic Research on Alzheimer’s Disease with Shen Zhi Ling Oral Liquid

“…9,375,457), in which Rhizoma coptidis (RC), Cortex phellodendri (CP), and Fructus gardeniae (FG) are prepared in a dry weight ratio of 2:2:3. According to animal studies, HTJDT-M could improve the cognitive dysfunction of 3XTg-AD mice by reducing A β deposition, decreasing the level of detergent soluble and acid-soluble A β via decreasing the levels of full length amyloid- β precursor protein and C-terminal fragments of APP [33, 34]. In addition, it can relieve cognitive impairment caused by cerebral ischemia and disturbance of the cholinergic system [33, 35].…”

Herbal Medicine (Sihogayonggolmoryeo‐Tang or Chai‐Hu‐Jia‐Long‐Gu‐Mu‐Li‐Tang) for Treating Hypertension:A Systematic Review and Meta‐Analysis

“…We included studies on SYM as a treatment intervention. HMs are known as “modified HMs” when the components are altered to achieve increased efficacy [ 23 , 24 ]. Thus, we also included studies in which modified forms of SYM, described as “modified SYM” and containing more than 50% of the components of the original prescription, were used as treatment interventions.…”