Neolignans in Magnolia officinalis as natural anti-Alzheimer's disease agents: A systematic review

Background: Magnolia officinalis, a traditional herbal medicine widely used in clinical practice, exerts antibacterial, anti-tumor, anti-inflammatory, antioxidant, and anti-aging activities. Neolignans are the main active ingredients of M. officinalis and exert a wide range of pharmacological effects, including anti-Alzheimer's disease (AD) activity. Objective: To summarize the published data on the therapeutic effect and mechanism of neolignans on AD in vivo and in vitro. Methods: PubMed, Web of Science, Google Scholar, and Scopus were systematically reviewed (up to March 1, 2024) for pre-clinical studies. Results: M. officinalis-derived neolignans (honokiol, magnolol, 4-O-methylhonokiol, and obovatol) alleviated behavioral abnormalities, including learning and cognitive impairments, in AD animal models. Mechanistically, neolignans inhibited A beta generation or aggregation, neuroinflammation, and acetylcholinesterase activity; promoted microglial phagocytosis and anti-oxidative stress; alleviated mitochondrial dysfunction and energy metabolism, as well as anti-cholinergic deficiency; and regulated intestinal flora. Furthermore, neolignans may achieve neuroprotection by regulating different molecular pathways, including the NF-kappa B, ERK, AMPK/mTOR/ ULK1, and cAMP/PKA/CREB pathways. Conclusions: Neolignans exert anti-AD effects through multiple mechanisms and pathways. However, the exact targets, pharmacokinetics, safety, and clinical efficacy in patients with AD need further investigation in multicenter clinical case-control studies.