Abstract

Huang-Lian-Jie-Du Decoction (HLJDD), traditional Chinese medicine (TCM), is proven to have ameliorative effects on learning and memory deficits of Alzheimer's disease (AD). The current study aims to reveal the underlying mechanism of HLJDD in the treatment of AD by simultaneous determination on the regulation of HLJDD on oxidative stress, neurotransmitters, and AMPK-SIRT1 pathway in AD. AD model rat was successfully established by injection of D-galactose and Aβ25-35-ibotenic acid. Morris Water Maze (MWM) test was used to evaluate the success of AD modelling. On this basis, an advanced technique with UPLC-QqQ MS/MS was built up and applied to determine the levels of 8 neurotransmitters in rat plasma. Significant alternation in methionine, glutamine, and tryptophan was observed in AD rats' plasma after the administration of HLJDD, relative to the model group. Meanwhile, HLJDD could upregulate the levels of SOD, GSH-Px, AMPK, and SIRT1 and downregulate the content of MDA in the peripheral system of the AD rats. The underlying therapeutic mechanism of HLJDD for the treatment of AD was associated with alleviating oxidation stress, inflammation, neurotransmitters, and energy metabolism. These data provide solid foundation for the potential use of HLJDD to treat AD.

Highlights

  • Huang-Lian-Jie-Du Decoction (HLJDD), a classical traditional Chinese medicine (TCM) formula used for heat clearance and detoxification, consists of Rhizoma coptidis (Rc), Radix scutellariae (Rs), Cortex phellodendr (Cp), and Fructus Gardeniae (Fg) with a weight ratio of 3 : 2 : 2 : 3. In clinic, HLJDD has been used to treat Alzheimer’s disease (AD) in China and other Asian countries recently [1, 2]

  • HLJDD, a classical TCM formula used for heat clearance and detoxification, consists of Rhizoma coptidis (Rc), Radix scutellariae (Rs), Cortex phellodendr (Cp), and Fructus Gardeniae (Fg) with a weight ratio of 3 : 2 : 2 : 3. In clinic, HLJDD has been used to treat AD in China and other Asian countries recently [1, 2]

  • Guedes et al reported that the accumulation of diverse forms of Aβ in the AD brain occurred before the development of visible senile plaques and formation of senile plaques and neurofibrillary tangles (NFTs) [11]. e presence of methionine at 35 position of Aβ is critical to Aβ-induced oxidative stress and neurotoxicity [12,13,14]. e activities of antioxidant enzymes including glutathione peroxidase (GSH-Px) and catalase displayed an age-dependent decline in both brain and plasma [15]

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Summary

Introduction

HLJDD, a classical TCM formula used for heat clearance and detoxification, consists of Rhizoma coptidis (Rc), Radix scutellariae (Rs), Cortex phellodendr (Cp), and Fructus Gardeniae (Fg) with a weight ratio of 3 : 2 : 2 : 3. In clinic, HLJDD has been used to treat AD in China and other Asian countries recently [1, 2]. HLJDD has been used to treat AD in China and other Asian countries recently [1, 2]. HLJDD has made remarkable achievement in the treatment of AD with the specific characteristics of anti-inflammation, oxidation resistance, preserving energy metabolism, reducing the production of amyloid beta-peptide (Aβ), and improving memory in AD mice [5,6,7,8]. E major pathological hallmarks of AD are neuronal loss, amyloid senile plaques, and neurofibrillary tangles (NFTs) within the cerebral cortex. E activities of antioxidant enzymes including glutathione peroxidase (GSH-Px) and catalase displayed an age-dependent decline in both brain and plasma [15]. Neurons, which contribute to Evidence-Based Complementary and Alternative Medicine

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