Puerarin exerts antipyretic effect on lipopolysaccharide-induced fever in rats involving inhibition of pyrogen production from macrophages

• Xiu-Juan Yao^a, 
• Ji-Ai Yin^a, 
• Yu-Feng Xia^b, 
• Zhi-Feng Wei^a, 
• Yu-Bin Luo^a, 
• Mei Liu^a, 
• Carlos Feleder^c, 
• Yue Dai

Abstract

Ethnopharmacological relevance

Puerarin is the most abundant isoflavonoid in Radix Puerariae (Gegen), which has been prescribed as a medicinal herb for treating fever in China for a long history.

Aim of the study

The present study aimed at evaluating the antipyretic effect of puerarin and revealing the related mechanisms.

Materials and methods

Lipopolysaccharide (LPS)-induced fever in rats was used to assess the antipyretic effect of puerarin. After an intraperitoneal injection of LPS (100 μg/kg), body temperature was tested every 30 min up to 8 h. Different doses of puerarin (25, 50, 100 mg/kg) were intraperitoneally administered 30 min before LPS injection. In vitro, LPS-stimulated RAW 264.7 cells were treated with various concentrations of puerarin (25–200 μM). The pyrogenic mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E₂ (PGE₂) and nitric oxide (NO), were examined on both transcription and expression levels. Furthermore, the influences of the activation of nuclear factor-kappa B (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) by puerarin were assayed by western blot.

Results

The intraperitoneal administration of puerarin at test doses clearly demonstrated apparent antipyretic effect through the declines in body temperature elevated by LPS in rats. The in vitro data showed that puerarininhibited the production of IL-1β, TNF-α, IL-6, PGE₂ and NO; moreover, the RT-PCR analysis and the western blot analysis indicated that puerarin regulated the transcriptional level via suppression of NF-κB activation and blockade of MAPK signal pathway.

Conclusions

In summary, the antipyretic property of puerarin might result, at least in part, from an inhibition of endogenous pyrogen production and expression. Taken in this sense, our findings provide an explanation forpuerarin acting as an important constituent in Gegen, thus, provide scientific basis for the wide use of Radix Puerariae in China as a traditional antipyretic