Effects of Yukmijihwang-tang Derivatives (YMJd) on Ibotenic Acid-Induced Amnesia in the Rat

Abstract

The consistent findings in Alzheimer's disease (AD) patients are impairment in cognitive performances such as attention, learning and memory, and change of cholinergic markers, including levels of acetylcholine (ACh) and choline acetyltransferase (ChAT). [1][2][3] Since cholinergic deficits are found to be associated with cognitive decline or dementia, increase of the central cholinergic system by selective inhibition of cholinesterase is one of the more promising current therapeutic tools for treating AD.4) Cholinergic neurons originating in the nucleus basalis of Meynert (NBM) and the medial septum (MS) project to areas such as the cortex and hippocampus, where play the role of ACh in cognition. 5,6) Lesioning these pathways in rodents decreases ACh release and produces an impairment of memory-related task performance.7) The observations that impairment can be reversed by cholinergic agonists suggest that the cholinergic system is damaged in AD and that drugs which induce cholinergic activity may treat AD. 8) For the testing of putative, cognitionenhancing agents, the establishment and standardization of animal cognitive deficit models are required. Lesion of the MS in animals has been widely approved as an animal model of memory loss.9,10) Cognitive dysfunctions after lesioning the MS are mainly considered to be due to deafferentiation of the hippocampus, which plays a major role in learning and memory. Coordinated action of acetylcholine and glutamate is important for the production of memory.11,12) ACh facilitates glutamate activity by coordinating the states of acquisition and recall in the cortex and hippocampus 13) and the activation of N-methyl-D-aspartate (NMDA) receptors is a prerequisite for the stimulation of long-term potentiation (LTP) in the septohippocampal cholinergic system, which is involved in the memory performance of rats in some learning tasks that depend on hippocampal functions. 14) Ibotenic acid stimulates neuronal necrosis by a hyperstimulation of the NMDA glutamate receptors leading to calcium overload. Its excitotoxic properties are confined to somata of neurons and therefore axons and blood vessels that course through the target areas remain intact.15) Injections of ibotenic acid into the MS in rats result in a significant deficit in the Morris water maze, which has been designed to measure spatial learning and memory, 16) and provide a more advanced stage of the neurodegeneration as an animal model of AD.7) Herbal medicines, such as Ginko biloba, Ginseng, or Melisa officinalis, have been commonly used as memory or cognition enhancers. The effects of these enhancers have been demonstrated scientifically.17,18) Yukmijihwang-tang (YMJ or Luweidihuang-wang) is another memory or cognition enhancer. YMJ is composed of 6 herbal medicines, including steamed Rehmannia radix, Discoreae radix, Corni fructus, Hoelen, Mountain cortex radicis, and Alismatis radix. YMJ has long been applied in the treatment of diabetes mellitus and neurosis. Ancient Chinese herbal textbooks also refer to YMJ as ...

Inhibitory effect of Yukmijihwang-tang, a traditional herbal formula against testosterone-induced benign prostatic hyperplasia in rats

“…Traditionally, Yukmijihwang-tang is applied in treating renal disorders, diabetes mellitus, and neurosis [13]. There have been many studies on the pharmacological effects of Yukmijihwang-tang, such as protection against renal ischemia/reperfusion [14], memory enhancement [15], stimulation of spermatogenesis [16], inhibition of bone loss [17], anti-asthmatic effects [18] and antidiabetic effects [13]. Although many researchers have investigated the pharmacological effects of Yukmijihwang-tang, there has been no study on its possible protective effects against BPH.…”

Safety and efficacy assessment of standardized herbal formula PM012

“…In addition, PM012 treatment accelerated the speed of information processing and enhanced cognitive abilities in normal subjects [28]. PM012 may repair cognitive impairment induced by dementia through an increase of acetylcholine synthesis in combination with the other advantageous effects mentioned above, thus helping to alleviate the symptoms of dementia patients [15,27,28]. …”

“…Ancient Chinese herbal textbooks also reference YMJ as an anti-aging treatment. In a previous study, YMJ derivatives (PM012) containing Lycii fructus , in addition to the other components of YMJ, enhanced memory retention by protecting neuronal cells and enhancing cell proliferation and neurite growth [15]. In addition, PM012 accelerated the speed of information processing and enhanced cognitive abilities in normal subjects [16].…”

Subacute Oral Toxicity of Yukmijiwhang‐Tang in Crl:CD Sprague‐Dawley Rats and Its Cytotoxicity

“…YMJ has been used traditionally for the treatment of renal diseases, edema, diabetes, neurosis, and aging in Korea and China. Modern research has reported various biological activities of YMJ or YMJ derivatives (YMJD), such as antiosteoporotic [ 2 , 3 ], antiamnesia [ 4 , 5 ], antiasthmatic [ 6 ], and memory-enhancing [ 7 ] effects. In addition, our group recently reported the efficacy of YMJ treatment against benign prostatic hyperplasia in vivo [ 8 ].…”