Association of Circulating Magnesium Levels in Patients With Alzheimer's Disease From 1991 to 2021: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) remains a medical and social challenge worldwide. Magnesium (Mg) is one of the most frequently evaluated essential minerals with diverse biological functions in human body. However, the association between circulating Mg levels and AD remains controversial. We conducted a meta-analysis of 21 studies published between 1991 and 2021 to determine whether the Mg levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data without language limitations. A pooled subject sample including 1,112 AD patients and 1,001 healthy controls (HCs) was available to assess Mg levels in serum and plasma; 284 AD patients and 117 HCs were included for Mg levels in CSF. It was found that serum and plasma levels of Mg were significantly reduced in AD patients compared with HCs (standardized mean difference [SMD] = -0.89; 95% confidence interval [CI] [-1.36, -0.43]; P = 0.000). There was statistically non-significant for Mg level in CSF between AD and HCs, whereas a decreased tendency were detected (SMD = -0.16; 95% CI [-0.50, 0.18]; P = 0.364). .In addition, when we analyzed the Mg levels of serum, plasma and CSF together, the circulating Mg levels in AD patients was significantly lower (SMD = -0.74, 95% CI [-1.13; -0.35]; P = 0.000). These results indicate that Mg deficiency may be a risk factor of AD and Mg supplementation may be a potentially valuable adjunctive treatment for AD. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/, registration number CRD42021254557.

Increased BBB permeability contributes to EGCG-caused cognitive function improvement in natural aging rats: pharmacokinetic and distribution analyses.

Previous studies report that (-)-epigallocatechin-3-gallate (EGCG), the most abundant polyphenolic ingredient in green tea, has high efficacy against Alzheimer's disease (AD) in various in vivo and in vitro models. However, as a water-soluble component, how EGCG exerts its anti-AD effects in the brain was not elucidated. In the present study, we investigated the anti-AD mechanisms of EGCG in natural aging rats with cognitive impairments (CIs) assessed using Morris water maze. The rats were treated with EGCG (100 mg/kg per day, intragastrically) for 4 weeks. The expression of ß-amyloid (Aß1-42) in the brain was detected with immunohistochemical staining. We showed that EGCG administration significantly ameliorated the CI in the aging rats with CI and decreased Aß1-42 plaque formation in their brains. Then we used an efficient ultra-performance liquid chromatography-tandem mass spectrometer method to evaluate EGCG concentrations in rat plasma and tissue distribution. We found that EGCG absorption was significantly increased in the aging with CI group compared with control young rats. After oral administration of EGCG (100 mg), EGCG could not be detected in the brain tissues of control young rats, but it was found in the brain tissue of aging rats with CI. By using Evans Blue assay, transmission electron microscopy, and Western blotting assay, we demonstrated that the permeability of blood-brain barrier (BBB) was significantly increased in aging rats with CI. These results suggest that the permeability change of BBB is the physiological structural basis for EGCG treatment to improve learning and memory, thus providing a solid evidence for EGCG druggability in anti-AD therapeutic field.

Development of a UPLC-MS/MS Method for Simultaneous Determination of Six Flavonoids in Rat Plasma after Administration of Maydis stigma Extract and Its Application to a Comparative Pharmacokinetic Study in Normal and Diabetic Rats.

Maydis stigma is an important medicine herb used in many parts of the world for treatment of diabetes mellitus, which main bioactive ingredients are flavonoids. This paper describes for the first time a study on the comparative pharmacokinetics of six active flavonoid ingredients of Maydis stigma in normal and diabetic rats orally administrated with the decoction. Therefore, an efficient and sensitive ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of six anti-diabetic ingredients (cynaroside, quercetin, luteolin, isorhamnetin, rutin and formononetin) of Maydis stigma in rat plasma has been developed and validated in plasma samples, which showed good linearity over a wide concentration range (r² > 0.99), and gave a lower limit of quantification of 1.0 ng·mL-1 for the analytes. The intra- and interday assay variability was less than 15% for all analytes. The mean extraction recoveries and matrix effect of analytes and IS from rats plasma were all more than 85.0%. The stability results showed the measured concentration for six analytes at three QC levels deviated within 15.0%. The results indicated that significant differences in the pharmacokinetic parameters of the analytes were observed between the two groups of animals, whereby the absorptions of these analytes in the diabetic group were all significantly higher than those in the normal group, which provides an experimental basis for the role of Maydis stigma in anti-diabetic treatment.

Phytoestrogenic molecule desmethylicaritin suppressed adipogenesis via Wnt/ß-catenin signaling pathway.

Epimedium flavonoids inhibit extravascular lipid deposition during prevention of steroid-associated osteonecrosis. Desmethylicaritin is a bioactive metabolite of Epimedium flavonoids in serum. As it is well known that estrogen inhibits aidpogenesis, so we hypothesized that desmethylicaritin as a phytoestrogen might have the potential to inhibit lipid deposition. This study was designed to investigate the effect of desmethylicaritin on adipogenesis and its underlying mechanism in vitro. Adipogenesis was assessed by Oil Red O staining in 3T3-L1 preadipocytes. Bromodeoxyuridine was used to test the clonal expansion. Further, the mRNA level and protein expression of adipgenic and related factors were detected by qRT-PCR and western blot, respectively. The nuclear location of ß-catenin was identified using immunofluoresence assay. Our results showed that desmethylicaritin suppressed the adipogenesis in 3T3-L1 cells in a dose-dependent manner. In addition, desmethylicaritin inhibited clonal expansion during adipogenesis. Desmethylicaritin did not affect CCAAT/enhancer binding protein δ and ß mRNA expression, but decreased the mRNA expression of CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, adipocyte lipid-binding protein and lipoprotein lipase. Desmethylicaritin up-regulated the mRNA expression of Wnt10b that was however down-regulated after adipogenic induction. Desmethylicaritin increased the protein expression of ß-catenin both in the cytoplasm and nuclei and immunofluorescence results confirmed that desmethylicaritin increased nuclear translocation of ß-catenin. Above findings implied that desmethylicaritin was able to inhibit adipogenesis and Wnt/ß-catenin signaling pathway was regulated by desmethylicaritin in the process of suppression of adipogenesis. Above findings supported desmethylicaritin as a novel phytochemical agent for potential prevention of disorders involving lipid metabolism.

Anti-amnesic effect of pseudoginsenoside-F11 in two mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by amyloid ß (Aß) deposits, elevated oxidative stress, and apoptosis of the neurons. Pseudoginsenoside-F11 (PF11), a component of Panax quinquefolium (American ginseng), has been demonstrated to antagonize the learning and memory deficits induced by scopolamine, morphine and methamphetamine in mice. In the present study, we investigated the effect of PF11 on AD-like cognitive impairment both in mice induced by intracerebroventricular injection of Aß1-42 (410 pmol) and in Tg-APPswe/PS1dE9 (APP/PS1) mice. It was found that oral treatment with PF11 significantly mitigated learning and memory impairment in mice given Aß1-42-treated mice for 15 days at doses of 1.6 and 8 mg/kg and APP/PS1 for 4 weeks at a dose of 8 mg/kg as measured by the Morris water maze and step-through tests. In APP/PS1 mice, PF11 8 mg/kg significantly inhibited the expressions of ß-amyloid precursor protein (APP) and Aß1-40 in the cortex and hippocampus, restored the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the production of malondialdehyde (MDA) in the cortex. It also noticeably improved the histopathological changes in the cortex and hippocampus and downregulated the expressions of JNK 2, p53 and cleaved caspase 3 in the hippocampus. These findings suggested that the inhibitory effect on amyloidogenesis and oxidative stress and some beneficial effects on neuronal functions might contribute to the recognition improvement effect of PF11 in APP/PS1 mice. Cumulatively, the present study indicated that PF11 may serve as a potential therapeutic agent for the treatment of AD.

[Research on EGCG improving the degenerative changes of the brain in AD model mice induced with chemical drugs].

OBJECTIVE: To study the effect and mechanism of (-)-Epigallocatechin-3-gallate (EGCG) on the degeneretive changes of the brain in Alzheimer's disease (AD) model mice induced with chemical drugs. METHODS: AD model mice were established by subcutaneously injecting with 3% D-gal at the dose of 150 mg/kg body weight once daily for 6 weeks. From the third week, the mice of D-gal + V(E) 280 U/kg group, D-gal + EGCG 2 mg/(kg x d) group and D-gal + EGCG 6 mg/(kg x d) group were intragastricly given with 5.6% V(E) at the dose of 280 IU/kg and EGCG at the dose of 2 mg/kg x d or 6 mg/kg x d respectively after injection of D-gal. The mice of control group, D-gal + dd H2O group and D-gal + oil group were administered with same volume vehicle distilled water and soybean oil respectively. The pathological changes of the brain in AD model mice were observed by HE staining analysis, the immunohistochemical analysis of beta-amyloid (Abeta) and evaluating the expression of amyloid precursor protein (APP) in the hippocampus of mice by Western blot analysis. RESULTS: EGCG 2 mg/(kg x d) or 6 mg/(kg x d) 4 weeks, ig evidently released neuronal injury in the hippocampus of the AD mice induced by D-gal, and significantly reduced the express of Abeta and APP in the hippocampus of AD model mice induced by D-gal (P < 0.01). CONCLUSION: EGCG has a protective effect on AD model mice induced by D-gal by decreasing the expression of APP and beta-Amyloid in the hippocampus of mice.

[The progress of the concentration technology of extract of traditional Chinese medicine].

The concentration of extract of traditional Chinese medicine (TCM) is one of the important unit operations that affect the quality of the pharmaceutical products. However, there are some problems to be solved. The concentration process has the shortages of relatively high temperature, relatively long time or low efficient, some losses of active and volatile ingredients, more operation steps, easy fouling and emission of waste water. In order to solve these problems, many new technologies and installations have been developed in the past thirty years, including suspension freeze-concentration, progressive freeze-concentration, single- or multi-effect evaporation with an external natural circulating flow, on-line preventing fouling evaporation with vapor-liquid-solid flow, reverse osmosis concentration, membrane distillation, osmotic distillation, macro-porous resin adsorption etc. The system of the extract of TCM is very complex. The extract includes water and alcohol extracts. The composition of TCM is made of active and inactive ingredients. Hence, it is necessary to master the features of every concentration technologies and installations, including their merits and demerits, flexibilities, degree of maturations of techniques and so on to get a wise choice for the industry applications. New concentration technologies and installations of the extract of TCM developed recently are reviewed in this paper. The characteristics of each method are analyzed and discussed in order to guide the industry applications. At the same time, the further research directions of concentration techniques of extract of TCM are also given.