Neuroprotection by herbal formula FBD and its active compounds

Abstract

FBD, a Chinese herbal formula, composed of Fu Ling [the sclerotium of the fungus of Poria cocos (Schw.) Wolf (Polyporaceae)], Bai Zhu [the rhizome of Atractylodes macrocephala Koidz.(Compositae)], and Danggui [the root of Angelica sinensis (Oliv.) Diels (Umbelliferae)], has been found beneficial in treating brain ischemia-reperfusion (I/R). In this work, oral pretreatment with supercritical CO₂ extract (FBD-CO₂, 37. 5 mg/kg) twice daily for 3.5 days, significantly attenuated brain infarction (p < 0.05), blocked neuron specific enolase (NSE) efflux (p < 0.05) in mice subjected to repetitive 10 min of common carotid artery occlusion following 24 h reperfusion, whether coupled with aqueous extract (FBD-H₂O, 150 mg/kg) or not. Except atractylenolide I and pachymic acid, atractylenolide II, III, levistolid A, and ferulic acid isolated from FBD-CO₂ alone protected neuron-like PC12 cells obviously and concentration-dependently against I/R-like insults (p < 0.05 ~ 0.01) induced by sodium dithionite (10 mM), monosodium glutamate (2 mM), KCl (0.2 M), or hydrogen peroxide (0.2 mM) at 1-100 μM. Even though at sub-active concentrations (< 1 μM), the combination of the six components contained in FBD-CO₂ (10 μg/mL), protected markedly PC12 cells (p < 0.01), in a synergistic fashion. Moreover, intraperitoneal treatment with dual doses of 37. 5 mg/kg FBD-CO₂ and 1. 2 mg/kg combination reduced both infarct size (p < 0.01 and p > 0.05, respectively) and NSE efflux (p < 0.05 and p > 0.05, respectively). Therefore, neuroprotection by FBD on I/R induced neuronal injury originated partially from the synergies of its compounds atractylenolide II, atractylenolide III, levistolid A and ferulic acid.

Keywords::

• Angelica sinensis
• Atractylodes macrocephala
• ischemia-reperfusion
• Poria cocos

Acknowledgements

The authors thank Yi Cao and Lan Luo for experimental assistance.

Decleration of interest: This work was supported by various grants from the National New Drug Foundation of China (969010538), from the National Natural Science Foundation of China (30271604 & 30500683), and from the Doctoral Innovative Foundation of Jiangsu Province of China (200593).