Effects of Ligustilide on Lipopolysaccharide-Induced Endotoxic Shock in Rabbits

Abstract

In this study, we investigated the protective effects of ligustilide against lipopolysaccharide (LPS)-induced endotoxic shock in Japanese white rabbits and attempted to elucidate the possible mechanism underlying these effects. Forty-two rabbits were randomized into 6 groups: normal group, LPS group, dexamethasone group (5 mg/kg), and 3 ligustilide groups (20, 40, and 80 mg/kg). After the rabbits had received a LPS infusion (0.3 mg/kg), dexamethasone and ligustilide were intravenously injected at the above-mentioned dosages. Heart rate (HR), mean arterial pressure (MAP), and rectal temperature (RT) were recorded throughout the experiment. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) levels were measured by radioimmunoassay every 30 minutes for the first hour and every 60 minutes thereafter until the end of the experiment. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), creatinine kinase (CK), lactate dehydrogenase (LDH), total protein (TP), creatinine (Scr), blood urea nitrogen (BUN), total bilirubin (T. BIL), and counts of formed elements of blood were measured at 0, 120, and 300 minutes after the administration of LPS. Hemorheology was assayed 300 minutes after the LPS injection. The vital organs were collected and weighed before histopathologic examination. A comparison between the LPS group and the ligustilide groups showed that ligustilide significantly inhibited the decline in MAP and RT and decreased the levels of TNF-α, IL-1β, and NO, but had no apparent effect on HR. Ligustilide also inhibited the increase in the levels of biochemical markers, such as ALT, AST, ALP, GGT, LDH, CK, BUN, and Scr, but showed no apparent effect on T. BIL and TP. Furthermore, ligustilide partly restored the function of injured vital organs, including the heart, liver, lungs, and kidneys. These results suggest that ligustilide protected the rabbits against LPS-induced endotoxic shock.

Key words

ligustilide - Angelica sinensis (Oliv.) Diels - Umbelliferae - septic shock - tumor necrosis factor‐α - interleukin‐1β

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1 These authors contributed equally to this work.