Cinchonine: A Versatile Pharmacological Agent Derived from Natural Cinchona Alkaloids

Abstract

Background: Cinchonine is one of the Cinchona alkaloids that is commercially extracted from the Peruvian bark of Cinchona officinalis L. (Family: Rubiaceae). It is also obtained in much lower quantities from other species of Cinchona, such as Cinchona calisaya, Cinchona succirubra, and Cinchona pubescens, and in some other plants, such as Remijia peruviana. Cinchonine has been historically used as an anti-malarial agent. It also has a wide range of other biological properties, including anti-cancer, anti-obesity, anti-inflammatory, anti-parasitic, antimicrobial, anti-platelet aggregation, and anti-osteoclast differentiation. Aim and Objective: This review discusses the pharmacological activity of cinchonine under different experimental conditions, including in silico, in vitro, and in vivo. It also covers the compound's physicochemical properties, toxicological aspects, and pharmacokinetics. Methodology: A comprehensive literature search was conducted on multiple online databases, such as PubMed, Scopus, and Google Scholar. The aim was to retrieve a wide range of review/research papers and bibliographic sources. The process involved applying exclusion and inclusion criteria to ensure the selection of relevant and high-quality papers. Results: Cinchonine has numerous pharmacological properties, making it a promising compound for various therapeutic applications. It induces anticancer activity by activating caspase-3 and PARP-1, and triggers the endoplasmic reticulum stress response. It up-regulates GRP78 and promotes the phosphorylation of PERK and ETIF-2α. Cinchonine also inhibits osteoclastogenesis, inhibiting TAK1 activation and suppressing NFATc1 expression by regulating AP-1 and NF-κB. Its potential anti-inflammatory effects reduce the impact of high-fat diets, making it suitable for targeting obesity-related diseases. However, research on cinchonine is limited, and further studies are needed to fully understand its therapeutic potential. Further investigation is needed to ensure its safety and efficacy in clinical applications. Conclusion: Overall, this review article explains the pharmacological activity of cinchonine, its synthesis, and physicochemical properties, toxicological aspects, and pharmacokinetics.