Abstract

Phellinus linteus, a natural growing mushroom, has been known to exhibit anti-tumor, anti-inflammatory, anti-allergic and anti-oxidant effects. Aiming to exploit the neuroprotective effects of P. linteus, we evaluated its effects on infarct volume reduction in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion. Filtrate of P. linteus broth culture (various doses), fractionated filtrate (based on molecular weight) or control medium was administered intraperitoneally to rats before or after ischemia induction. Rats were killed at 24 h after the stroke surgery. Cortical and caudoputaminal infarct volumes were determined separately using an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. Significant cortical infarct volume reductions were found in the pre-treatment groups (30 and 60 minutes before onset of cerebral ischemia) compared with the control group, showing dose dependence. Posttreatment (30 minutes after ischemic onset) also significantly reduced cortical infarct volume. Furthermore, the higher molecular weight (≥12 000) fraction of the culture filtrate was more effective compared with the lower molecular weight fraction. The present findings suggest that P. linteus may be a new promising approach for the treatment of focal cerebral ischemia, with the additional benefit of a wide therapeutic time window since significant infarct volume reduction is obtained by administration even after the ischemic event. Our finding that the higher molecular weight fraction of the P. linteus culture filtrate demonstrated more prominent effect may provide a clue to identify the neuroprotective substances and mechanisms.

Highlights

  • It would appear that the antioxidant effect of P. linteus may be due to caffeic acid

  • The present results demonstrated that treatment with the 20% culture filtrate 30 and 60 min before Middle Cerebral Artery (MCA) occlusion effectively reduced the volume of brain ischemia

  • From the clinical points of view, these results suggest a possibility that P. linteus culture filtrate is very promising in providing wide therapeutic time windows for the treatment of cerebral ischemia

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Summary

Introduction

Investigations of the pharmacologic effects of P. linteus were started in Japan about 40 years ago, and this mushroom showed the strongest anti-tumor effects compared to other mushrooms [1]. P. linteus is attracting attention for its anti-inflammatory, anti-allergic, anti-tumor and anti-oxidant effects [2,3,4]. Tea catechins are known to act as antioxidants by scavenging free radicals and chelating metal ions [5, 6]. Caffeic acid possesses a catechol moiety in its structure. Caffeic acid may exhibit antioxidant effect by the same mechanism as that of tea catechins. Caffeic acid was extracted from the culture of P. linteus mycelia [7]. It would appear that the antioxidant effect of P. linteus may be due to caffeic acid

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