Endophytes coevolve with plant hosts and thus are more probable to acquire the character (in favor) of producing novel bioactive metabolites. Consequently, the topic has been intensely investigated for over two decades, but endophytic metabolites with neuro-protective effect remain scarce. Here we present the discovery of eight undescribed (named solanapyrones S–X and prosolanapy-rones A and B) and six known pyrones (solanapyrones A–C, E-G) from the culture of Nigrospora oryzae, an endophytic fungus associ-ated with Taxus chinensis var. mairei. The structures and absolute configurations of new pyrones were elucidated by extensive spec-troscopic analysis, modified Mosher’s method, and induced circular dichroism (ICD) spectrum. Solanapyrones A and B and an un-described pyrone (solanapyrone S) were demonstrated to be more neuroprotective than clenbuterol in inducing bone marrow mesenchymal stem cells (bMSCs) to secret nerve growth factor (NGF). The work updates the pyrone chemodiversity in nature and extends the biofunction repertoire of solanapyrone-related polyketides.