Protective effects of ligustilide, a natural product from Aaugellica sinensis (Oliv.) Diels, in a rabbit model of endotoxic shock

Tumor necrosis factor-α (TNF-α) is one of the biological mediators that play a critical role in endotoxic shock [1]. Ligustilide, isolated from the rhizome of Aaugellica sinensis (Oliv.) Diels, has been shown to inhibit lipopolysaccharide (LPS)-induced TNF-α production in the monocytes [2]. In this study, we investigated the effects of Ligustilide in the rabbit model of LPS-induced endotoxicity. We randomly separated 42 New Zealand rabbits into 6 groups: normal group, model group, dexamethasone group (5mg/kg), and ligustilide groups (10 mg/kg, 20 mg/kg, and 40mg/kg). The LPS infusion (0.3mg/kg) was administered to the rabbits, and the abovementioned doses of dexamethasone and ligustilide were intravenously injected in the rabbits of the respective groups. The respiratory rate, heart rate, mean arterial pressure (MAP), and rectal temperature (RT) were recorded throughout the experiment. The TNF-α and IL-1β levels were measured by radioimmunoassay every 30 minutes during the first hour, and then every 60 minutes till the end of experiment. The levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK), blood urea nitrogen (BUN), and serum creatinine (Scr) were measured at 0, 120, and 300 minutes. The administration of L PS caused a significant increase in the serum levels of TNF-α, IL-1, ALT, AST, ALP, GGT, LDH, CK, BUN, and Scr and a marked decrease in MAP and RT. Treatment with ligustilide (20 mg/kg and 40mg/kg) significantly attenuated the reduction in MAP and RT, suppressed the release of the proinflammatory cytokines (TNF-α, IL-1), and decreased the levels of the above mentioned markers of organ injury. These results show that ligustilide affords protection against LPS-induced shock in rabbits.

References: [1] Karima, R. et al. (1999) Mol. Med. Today 5:123–132.

[2] Liu, L. et al. (2005) Planta Med. 71:808–813.