Alzheimer's disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive decline and irreversible memory impairment. Currently, several studies have failed to fully elucidate AD's cellular and molecular mechanisms. For this purpose, research on related cellular models may propose potential predictive models for the drug development of AD. Therefore, many cells characterized by neuronal properties are widely used to mimic the pathological process of AD, such as PC12, SH-SY5Y, and N2a, especially the PC12 pheochromocytoma cell line. Thus, this review covers the most systematic essay that used PC12 cells to study AD. We depict the cellular source, culture condition, differentiation methods, transfection methods, drugs inducing AD, general approaches (evaluation methods and metrics), and in vitro cellular models used in parallel with PC12 cells.

Alzheimer’s disease (AD) is a degenerative disease of the nervous system. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a drug used to treat type 2 diabetes, have been shown to have neuroprotective effects. This systematic review and meta-analysis evaluated the effects and potential mechanisms of GLP-1 RAs in AD animal models. 26 studies were included by searching relevant studies from seven databases according to a predefined search strategy and inclusion criteria. Methodological quality was assessed using SYRCLE’s risk of bias tool, and statistical analysis was performed using ReviewManger 5.3. The results showed that, in terms of behavioral tests, GLP-1 RAs could improve the learning and memory abilities of AD rodents; in terms of pathology, GLP-1 RAs could reduce Aβ deposition and phosphorylated tau levels in the brains of AD rodents. The therapeutic potential of GLP-1 RAs in AD involves a range of mechanisms that work synergistically to enhance the alleviation of various pathological manifestations associated with the condition. A total of five clinical trials were retrieved fromClinicalTrials.gov. More large-scale and high-quality preclinical trials should be conducted to more accurately assess the therapeutic effects of GLP-1 RAs on AD.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were initially approved for type 2 diabetes mellitus. Recent evidence suggests their therapeutic potential in various diseases, though their efficacy and safety remain incompletely understood. Here, we conduct an umbrella review including 123 meta-analyses covering 464 outcomes from 5617 articles to comprehensively assess the effectiveness and adverse events (AEs) of GLP-1 RAs across diverse outcomes. GLP-1 RAs showed trends toward improvements in endocrine and metabolic, cardiovascular, renal, and respiratory outcomes, cognitive function, with a potential reduction in fracture risk and all-cause mortality in certain populations. However, increased risks of certain AEs, including diabetic retinopathy, ketoacidosis, gastrointestinal events, and treatment discontinuation, were also observed. AMSTAR 2 assessments indicate that the existing evidence is limited by methodological shortcomings, including incomplete reporting of excluded studies, suboptimal literature search strategies, and insufficient evaluation of how bias in primary studies may influence meta-analytic estimates. Some outcomes did not reach statistical significance in all populations, highlighting the need for further high-quality clinical research. Careful consideration of potential benefits and risks is essential for optimizing treatment outcomes and ensuring patient safety when using GLP-1 RAs in clinical practice.

With the increase of the aging population, the high mortality and disability rates caused by ischemic stroke are some of the major problems facing the world, and they dramatically burden the society. Panax notoginseng (Burk) F. H. Chen, a traditional Chinese medicine, is commonly used for promoting blood circulation and removing blood stasis, and its main bioactive components are Panax notoginseng saponins (PNS). Therefore, we performed a meta-analysis on focal cerebral ischemia-reperfusion animal models established with middle cerebral artery occlusion (MCAO) surgery to evaluate the therapeutic effect of PNS. We systematically searched the reports of PNS in MCAO animal experiments in seven databases. We assessed the study quality using two literature quality evaluation criteria; evaluated the efficacy of PNS treatment based on the outcomes of the neurological deficit score (NDS), cerebral infarct volume (CIV), and biochemical indicators via a random/fixed-effects model; and performed a subgroup analysis utilizing ischemia duration, drug dosage, intervention time, and administration duration. We also compared the efficacy of PNS with positive control drugs or combination treatment. As a result, we selected 14 eligible studies from the 3,581 searched publications based on the predefined exclusion-inclusion criteria. PNS were significantly associated with reduced NDS, reduced CIV, and inhibited release of the inflammatory factors IL-1β and TNF-α in the focal MCAO rat models. The PNS combination therapy outperformed the PNS alone. In addition, ischemia time, drug dosage, intervention time, and administration duration in the rat models all had significant effects on the efficacy of PNS. Although more high-quality studies are needed to further determine the clinical efficacy and guiding parameters of PNS, our results also confirmed that PNS significantly relieves the focal cerebral ischemia-reperfusion in rat models. In the animal trials, it was suggested that an early intervention had significant efficacy with PNS alone or PNS combination treatment at a dosage lower than 25 mg/kg or 100–150 mg/kg for 4 days or longer. These findings further guide the therapeutic strategy for clinical cerebral ischemic stroke.