Acute and subacute oral toxicity of acetylated <i>Ligubtrum lucidum Ait.</i> polysaccharide in male mice

<i>Ligustrum lucidum</i> polysaccharide (FLL-P) is a class of important bioactive macromolecules extracted from the traditional Chinese medicinal herb wine-steamed <i>Ligustrum lucidum Ait</i>. As one of the key active components responsible for the pharmacological effects of this herb, its modern pharmacological value has garnered widespread attention. Research has demonstrated that FLL-P exhibits diverse and significant biological activities, with potential applications that far exceed the traditional scope of Chinese medicine. In recent years, chemical modification has been recognized as an effective strategy for enhancing the biological activity of polysaccharides. Consequently, structural modification of FLL-P is anticipated to further augment its activity and broaden its application prospects. However, current research on the chemical modification of FLL-P remains inadequate, particularly concerning the safety evaluation of modified products, which is still extremely limited. This research comprehensively explores the acetylation modifications of FLL-P, encompassing detailed characterization and toxicity assessments. The optimal product, identified as acetylated FLL-P 12.5 (FLL-PA12.5), was established through analyses of the degree of substitution (DS), FT-IR, and NMR. Toxicity tests, both acute and subacute, were conducted on male mice. The findings indicated that FLL-PA12.5 had a median lethal dose (LD₅₀) exceeding 2000 mg/kg and a no-observed adverse effect level (NOAEL) of 250 mg/kg. Administration of FLL-PA12.5 at doses between 250 and 2000 mg/kg resulted in alterations in various oxidative stress-related parameters in different organs of the mice. These findings indicate that FLL-PA12.5 is a promising therapeutic candidate with an acceptable safety profile, warranting further pharmacological exploration.