Ameliorating Effects of HX106N, a Water-Soluble Botanical Formulation, on Aβ_25-35-Induced Memory Impairment and Oxidative Stress in Mice

Abstract

It is well-established that amyloid β (Aβ)-induced oxidative stress plays a crucial role in Alzheimer's disease (AD) and its cognitive deficits. HX106N is a water-soluble extract prepared from a mixture of the plants Dimocarpus longan, Liriope platyphylla, Salvia miltiorrhiza, and Gastrodia elata. These ingredients are traditionally used in various plant-based medicines for the treatment of neurological disease. In this study, we examined the effects of HX106N on memory impairment and oxidative stress caused by the intracerebroventricular injection of Aβ 25 Key words HX106N; amyloid β [25][26][27][28][29][30][31][32][33][34][35] ; memory impairment; oxidative stress; heme oxygenase-1; Alzheimer's disease Dementia is a clinical syndrome characterized by the progressive deterioration of global cognitive function that is severe enough to interfere with daily activities. Alzheimer's disease (AD) is the most common type of dementia. The amyloid cascade hypothesis, one of the leading theories for the pathogenesis of AD, proposes that amyloid-β (Aβ) peptide, which is derived from the proteolytic cleavage of the amyloid precursor protein, accumulates in the brain and plays a crucial role in the pathology of AD.1,2) In fact, there have been many reports demonstrating that high levels of the Aβ peptide are neurotoxic and that its deleterious effects are mediated by the generation of reactive oxygen species, 3) neuroinflammation, 4) and a dysregulation of ionic homeostasis. 5) Consequently, much of the focus of AD research has been placed on controlling brain levels of Aβ and preventing Aβ-induced neurotoxicity.Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the degradation of heme to carbon monoxide, biliverdin, and free iron. 6) HO-1 expression is increased in many neurodegenerative diseases, such as AD and Parkinson's disease (PD), and it is correlated with oxidative damage and inflammation.7,8) Elevated levels of HO-1 are believed to produce antioxidative responses, restore redox homeostasis, and confer neuroprotection against various oxidative stimuli.9-11) Given the beneficial effects of HO-1, the pharmacological modulation of HO-1 levels has been considered an important therapeutic approach to counter neurodegenerative diseases.HX106N is a water-soluble extract prepared from four plants: Dimocarpus longan LOUR. (Sapindaceae), Liriope platyphylla WANG et TANG. (Liliaceae), Salvia miltiorrhiza BUNGE (Lamiaceae), and Gastrodia elata BLUME (Orchidaceae). These plants were selected based on previous publications describing their activities and functions and based on information accumulated during the practice of traditional phytomedicine in Asia. For example, Dimocarpus longan is known to have anti-amnesic and anxiolytic effects and has been reported to enhance cognitive performance in a mouse passive avoidance test.12-14) Liriope platyphylla has been described as effective in the treatment of inflammatory diseases such as bronchitis and pneumonia, 13,14) and it contains a compound, spicatoside A, that has ...

Effects of HX106N, a Water-Soluble Botanical Formulation on Scopolamine-Induced Memory Impairment in Mice

“…In a previous study, oral administration of HX106N ameliorated memory impairment and reduced the level of thiobarbituric acid-reactive substances, which is an indicator for lipid peroxidation, in the brain of Aβ 25-35 -treated mice (Lee et al 2014). …”

“…HX106N was prepared using a protocol described previously (Lee et al 2014 Gastrodiae Rhizoma). In an effort to make HX106N in a consistent manner at different times, high-performance liquid chromatography analysis was employed, using salvianolic acid B, gastrodin, and spicatoside A for Salvia miltiorrhiza, Gastrodia elata, and Liriope platyphylla, respectively.…”

“…For Dimocarpus longan, liquid chromatography-tandem mass spectrometry analysis was performed, using ellagic acid as a marker. The cell-based bioassays, as reported by Lee et al (2014), have also been used to control the quality of HX106N in consistent manner.…”

“…and Gastrodia elata Blume (Orchidaceae). We previously demon-strated that HX106N could ameliorate the memory impairment induced by amyloid β (Aβ) peptide with the inhibition of oxidative stress (Lee et al 2014). In this study, we tested whether HX106N has an anti-amnesic effect against memory impairment caused by cholinergic dysfunction.…”

Effective suppression of nitric oxide production by HX106N through transcriptional control of heme oxygenase-1

“…(Liriopes Radix), Salvia miltiorrhiza Bunge (Salvia miltiorrhiza Radix), and Gastrodia elata Blume (Gastrodiae Rhizoma). To prepare HX106N in a consistent manner, a cell-based bioassay was also used as reported by Lee et al 23 …”