Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

Background: Staphylea arguta (Lindl.) Byng & Christenh. [Staphyleaceae] (Staphylea arguta), a tree or shrub species belonging to the Staphyleaceae family, is widely distributed in subtropical regions of China, particularly in Jiangxi Province, where it is recognized as a geo-authentic botanical drug. It thrives in humid, shaded mountainous areas at elevations of 400–700 m. Traditionally, it has been used for treating breast abscesses, paralysis, sore throat, ulcers, and contusions. Despite its widespread use, systematic reviews on its phytochemistry and pharmacology are limited, and quality control remains challenging due to the lack of standardized markers. This review aims to summarize its metabolites and pharmacological activities, and predict potential quality markers (Q-markers) based on the “five principles” of traditional Chinese medicine (TCM) quality control to address these research gaps.Methods: The metabolites and pharmacological activities of Staphylea arguta were reviewed using data retrieved from scientific databases, including PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). The “five principles” of TCM Q-markers, which include kinship and chemical specificity, traditional medicinal properties, traditional efficacy, metabolites measurability, and different origins, were applied to identify potential candidates for Staphylea arguta.Results: This review summarizes 451 metabolites from Staphylea arguta, including flavonoids, terpenoids, volatile oils and other metabolites, which exhibit anti-inflammatory, analgesic, and immunomodulatory effects. In addition, it is predicted that ligustroflavone (no.23), rhoifolin (no.24), corosolic acid-28-O-β-D-glucopyranosyl ester (no.56), 23-hydroxyoleanolic acid (no.77), squalene (no.253), α-copaene (no.225), and additional identified metabolites can serve as Q-markers for Staphylea arguta.Conclusion: This comprehensive review not only consolidates the existing knowledge on Staphylea arguta but also proposes a foundation for its quality standardization. The identified Q-markers will facilitate the development of a robust quality control system, ensuring the safety and efficacy of Staphylea arguta-based products for clinical use. This work is significant for promoting the rational utilization and further development of this medicinal resource.