Research Status Of Pharmacology And Drug Discovery Of Cistanche in Memory

ABSTRACT

The incidence of chronic neurodegenerative diseases is on the rise, but there are no effective treatments due to a lack of information about the pathological mechanisms of these diseases. Therefore, this study investigated the effects of cistanche extract on reducing memory deficit and neurobiochemical changes in streptozotocin dementia mice. Mice (n¼35) were randomly assigned to 5 groups of 7 mice per group; Group 1: control group mice were given the drug alone; Group 2: streptozotocin; Group III: Streptozotocin + 100 mg/kg cistanche extract; Group IV: Streptozotocin þ myrtenal 200 mg/kg; Group V: Streptozotocin + Donepezil 0.5 mg/kg. Data from this study suggest that streptozotocin (STZ) administration impairs spatial memory in mice and induces changes in markers of oxidative inflammatory response, cholinergic function, cell structure, and neurotransmitter levels. Notably, administration of cistanche extract protects the brain from oxidative inflammatory stress by increasing the activity of endogenous antioxidant enzymes, thereby enhancing spatial memory performance in stz dementia mice. Treatment with cistanche also restored cholinergic function and stabilized neurotransmitter homeostasis in dementia mice. Cistanche may be beneficial in treating patients with dementia associated with Alzheimer's disease, the authors theorize.

Keywords:Cistanche; Memory; Alzheimer's disease; Streptozotocin

1. Introduction

A number of contemporary studies report a rise in dementia rates worldwide. Of the different types of dementia that have been identified, Alzheimer's type dementia (DAT) is considered the most severe, affecting about 6 percent of women and 5 percent of men over the age of 60. In addition, a survey conducted by the Aging Demographics and Memory Study (ADAMS) estimates that about 4.5 million Americans have dementia, a number that could rise to about 16 million by 2050.

Pathologically, Alzheimer's disease is characterized by the deposition of neurofibrillary tangles, the accumulation of amyloid beta peptides, and hyperphosphorylated tau proteins associated with microtubules. These classical features are strongly associated with neuronal and synaptic loss and inform contemporary therapies that aim to enhance the activity of healthy neurons without inhibiting the progressive degeneration of neuronal cells. There is currently no definitive treatment to reverse the neuropathological features of the disease process, in part because the specific cause of Alzheimer's type dementia (DAT) has not been identified and the signaling pathways are complex. Recent studies have shown that oxidative stress and lipid peroxidation, which are increased in the development of DAT, also decrease brain glucose utilization, neuroinflammation, and factors that impair cholinergic neurotransmission. In line with these theories, we suggest that targeting oxidative stress and enhancing the antioxidant state of the brain are important strategies to minimize pathophysiology and improve contemporary understanding of Alzheimer's disease-type dementia.

Pic: Faw Cistanche

However, there has been little research on antioxidants that may minimize the pathophysiology and neurobiochemical changes associated with memory loss in Alzheimer's disease. It is important to note that the antioxidant properties of cistanche remain to be investigated. Phenylethanolsides in cistanche are organic compounds commonly extracted from many plant essential oils. This compound has a variety of physiological functions, including antioxidant, anti-inflammatory, anti-apoptotic and anti-tumor activities.

Although, in experimental rat models of Parkinson's disease, phenylethanol sides are believed to have neuroprotective effects, there is no information on their memory-enhancing potential and their therapeutic benefits in improving DAT induced by STZ therapy. Therefore, the current study aimed to create a mouse model of dementia using streptozotocin and investigate the potential effects of miti on the pathophysiology of memory loss and neurobiochemical changes in the use of myrtle.

2. Materials and methods

2.1. Animals

Adult male albino mice were used in this study. The mice were housed in plastic cages at room temperature (22 2 C) in the animal facility, exposed to a 12-hour light/dark cycle, and had free access to feed and water. The mice were checked for health and pathogen-free status throughout the study period, and stress during the experiment was minimised by ensuring minimal handling. All of the animals were allowed to acclimate to laboratory conditions for five days before the behavioral experiment.

2.2. Dosage and administration method

Donepezil (DP) powder was dissolved in 0.9% normal saline and administered at 0.5 mg/kg (0.9% w/v). Streptozootocin was dissolved in freshly prepared artificial cerebrospinal fluid (aCSF) as a carrier and administered at a dose of 3mg /kg with 10 μL i.c.v on each side. The control group received simulated injection with artificial cerebrospinal fluid on the first and third days of streptozotocin administration. The active ingredients of cistanche extract were dissolved in corn oil and orally administered at doses of 100mg /kg and 200mg /kg, while the control group was given 10ml /kg corn oil. Dosing of cistanche was selected based on previous LD50 reports. All medicines are freshly prepared before use.

2.3. Experimental dementia induced by streptozotocin

On the first and third days, dementia was induced by intraventricular injections of two different doses of streptotoxomycin. In short, under anesthesia, the use of stereotactic equipment according to the following ventricular coordinates with bilateral intubation of animals: before - after the quarter 0.8; Middle outside ¼1.5; Fell back an abdomen 3.4. Mice in control group received intraventricular injection of artificial cerebrospinal fluid.

2.4. Experimental design

The mice were randomly divided into five groups with 7 mice in each group and administered according to the dosing regimen shown in Table 1: pretreated with cistanche for 7 days before the first streptozotocin administration and continued for 14 days thereafter. Donepezil and myrtenal were administered 30 minutes before streptozotocin injection.

2.5. Memory ability assessment

Memory performance was assessed using the Y-maze test described earlier. The test was used to identify spontaneous changes in mice's behavior as an indication of short-term memory. The test unit consisted of three identical arms, labeled "A," "B," and "C," and positioned each mouse at all times on the "home" arm labeled A. The mice were then allowed to explore the maze for an unlimited five minutes. Alternate performance was recorded as continuous entry into all three arms. After completing each assessment phase, wipe each chamber with 75% ethanol to avoid odor cues.

3. Markers of brain oxidative stress

3.1. Determination of cerebral lipid peroxidation

As previously described by Ohkawa et al., the concentration of malondialdehyde (MDA), the product of lipid peroxidation, in hippocampal secretion emulsion was determined by spectrophotometry. The change of absorbance was measured by spectrophotometry at 532 nm.

3.2. Determination of nitric oxide (NO) concentration in brain

The concentration of NO was determined by trial dose calorimetry. The reaction is based on estimates of nitrite formation. Then, the absorbance is read at 548 nm.

3.3. Tumor necrosis factor α was used as a marker to evaluate the degree of inflammation. The concentration of TNF-α in the hippocampus was determined using the mouse TNF-α ELISA kit of MyBio Source (USA) No. 4. At 540 nm, microplate reader was used for spectrophotometric reading.

3.4. For protein extraction, the hippocampal tissues were homogenized in a cold extraction buffer, then the sample homogenized solution was centrifuged at 10,000 rpm at 4 ° C for 5 min, and the respective protein concentrations were measured using a protein detection kit according to the manufacturer's guidelines.

3.5. Evaluation of Brain acetylcholinesterase (AChE) activity The acetylcholinesterase activity in hippocampus was estimated according to the method described by Ellman. The observed colors were read by spectrophotometry at 412 nm and AChE activity was measured according to a standard curve in μM/SH groups (MSH).

3.6. The concentrations of antioxidant markers, glutamyl sulfide peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in hippocampal tissue were determined by MyBioSource (USA) cata logue No. 2 enzyme-linked immunosorbent assay.

Pic: Cistanches Benefits

4. Results

4.1. In Y maze test, streptozotocin induced working memory impairment was significantly reduced (p < 0.01), the alternating percentage of improvement recorded in the treatment group (0.001, respectively) attenuated streptozotocin induced memory impairment compared to the control group as significant. This study showed the effect of cistanche treated with streptozotocin on autonomic movement of mice in open field. Streptozotocin significantly reduced spontaneous motor activity compared with the control group. However, treatment with cistanche extract (100 and 200 mg/kg, p.o.) was significant (p < 0.01 and p < 0.001, respectively) reversed the effect compared to the streptozotocin group, which had the least physical activity. After streptozotocin treatment, the effects of cistanche extract on feeding of mice were described by vertical counting numbers, and the feeding rate of streptozotocin treated mice was significantly decreased compared with the control group. However, treatment with cistanche extract (100 and 200 mg/kg, p.o.) was significant (p < 0.05, p < 0.01, respectively) increased the number of vertical counts, while streptozotocin (streptozotocin) treated animals had the least vertical counts.

4.2. Effect of Myrtenal administration on elevated nitric oxide concentration in hippocampal tissues of mice exposed to streptozotocin. The results showed that 200 mg/kg cistanche extract significantly decreased streptozotocin dementia mice (p < Compared with streptozotocin alone, the level of nitric oxide in the hippocampus of mice brain increased. There was no significant difference between streptozotocin + cistanche extract (200 mg/kg) group and streptozotocin + Donepezil (0.5 mg/kg) group. The results showed that 100 mg/kg or 200 mg/kgmyrtenal significantly reduced streptozotocin dementia mice (p < 0.05, p < 0.01) MDA levels in mouse brains compared with streptozotocin alone. However, there was no significant difference between streptozotocin + Mill (200 mg/kg) and streptozotocin + Donopezil (0.5 mg/kg) treatment groups.

Pic: Effects of cistanche improve memory

5. Discussion

In the current study, we aimed to better understand cistanche's therapeutic role in dementia, specifically Alzheimer's disease. We utilized streptozotocin's ability to produce an experimental model of dementia and demonstrated cistanche's ability to relieve neurodegenerative deficits modeled in an experimental model of Alzheimer's syndrome type (DAT). One notable effect of Cistanche is improved memory loss, which can be attributed to its anti-hyperglycemic properties, increasing glucose levels and utilization in the central nervous system. This effect confirms previous studies that showed significant improvements in cognitive function after cistanche was administered to rat models of anxiety and memory loss caused by repeated scopolamine injections. Evidence suggests that cistanche, as a therapeutic agent, plays a vital role in alleviating neurodegenerative processes that lead to memory loss in dementia. However, fully proving this hypothesis requires experimental trials with alternative cholinergic agents that mimic dementia.

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6. Conclusion

Data from this study showed that streptozootocin use impaired spatial memory in mice and induced changes in markers of oxidative inflammatory response, cholinergic function, tissue structure, and levels of neurotransmitters in the hippocampus. However, cistanche extract protects the brain from oxidative inflammatory stress by increasing the activity of endogenous antioxidant enzymes, thereby enhancing spatial memory performance in streptomycin dementia mice. In addition, we show that treatment with cistanche restores cholinergic function and stabilizes neurotransmitter homeostasis in mice treated with streptozotocin in dementia. Based on the latitude of neurobiochemical factors considered in the current study, the authors conclude that cistanche plays a crucial role in regulating memory signals. So it's conceivable that eating cistanche could be beneficial in treating people with Alzheimer 's-related dementias.

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