Structural modifications of berberine and the lipid-regulating effects of its derivatives

Hyperlipidemia refers to one or more diseases with unbalanced lipid structure in plasma, which is called dyslipidemia in modern medicine. Natural ingredients are an essential source for developing new medications. Berberine (BBR), the tricyclic triterpene quaternary ammonium molecule, is commonly found in the plant world and exhibits significant biological activity in various therapeutic areas, including cancer, inflammation, metabolic disorders, cardiovascular and allergic diseases, and more. Many BBR derivatives have been created and are being developed to address their drawbacks, such as adverse effects due to poor action due to poor water solubility and limited bioavailability. Recently, researchers have modified the many positions that affect cholesterol-lowering activity because of their distinct mechanisms of action, including C-2,3, C-7, C-8, C-9, C-10, C-11, and C-12. This paper reviews the properties of BBR in lipid-lowering, including structural diversity, structural modifications with lipid-lowering effects, synthesis of BBR derivatives, lipid-lowering properties of its derivatives, and corresponding SAR values. These reviews will help to investigate the lipid-lowering effects of BBR and provide guidance for the development of new lipid-lowering drugs. Ultimately, this review is intended to serve as a foundation for future chemical research and assist in the search for potential cholesterol-lowering therapeutics.