Summary: Aims: Baicalin (BAI), a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, has been established to have potent anti‐inflammation and neuroprotective properties; however, its effects during Alzheimer's disease (AD) treatment have not been well studied. This study aimed to investigate the effects of BAI pretreatment on cognitive impairment and neuronal protection against microglia‐induced neuroinflammation and to explore the mechanisms underlying its anti‐inflammation effects.Methods: To determine whether BAI plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin‐1) mice, behavioral experiments were conducted. We assessed the effects of BAI on microglial activation, the production of proinflammatory cytokines, and neuroinflammation‐mediated neuron apoptosis in vivo and in vitro using Western blot, RT‐PCR, ELISA, immunohistochemistry, and immunofluorescence. Finally, to elucidate the anti‐inflammation mechanisms underlying the effects of BAI, the protein expression of NLRP3 inflammasomes and the expression of proteins involved in the TLR4/NF‐κB signaling pathway were measured using Western blot and immunofluorescence.Results: The results indicated that BAI treatment attenuated spatial memory dysfunction in APP/PS1 mice, as assessed by the passive avoidance test and the Morris water maze test. Additionally, BAI administration effectively decreased the number of activated microglia and proinflammatory cytokines, as well as neuroinflammation‐mediated neuron apoptosis, in APP/PS1 mice and LPS (lipopolysaccharides)/Aβ‐stimulated BV2 microglial cells. Lastly, the molecular mechanistic study revealed that BAI inhibited microglia‐induced neuroinflammation via suppression of the activation of NLRP3 inflammasomes and the TLR4/NF‐κB signaling pathway.Conclusion: Overall, the results of the present study indicated that BAI is a promising neuroprotective compound for use in the prevention and treatment of microglia‐mediated neuroinflammation during AD progression.

Monoterpenoid indole alkaloids (MIAs) represent a major class of active ingredients from the plants of the genus Gelsemium. Gelsemium MIAs with diverse chemical structures can be divided into six categories: gelsedine-, gelsemine-, humantenine-, koumine-, sarpagine- and yohimbane-type. Additionally, gelsemium MIAs exert a wide range of bioactivities, including anti-tumour, immunosuppression, anti-anxiety, analgesia, and so on. Owing to their fascinating structures and potent pharmaceutical properties, these gelsemium MIAs arouse significant organic chemists’ interest to design state-of-the-art synthetic strategies for their total synthesis. In this review, we comprehensively summarised recently reported novel gelsemium MIAs, potential pharmacological activities of some active molecules, and total synthetic strategies covering the period from 2013 to 2022. It is expected that this study may open the window to timely illuminate and guide further study and development of gelsemium MIAs and their derivatives in clinical practice. Graphical abstract