Improved Biological Activities of Isoepoxypteryxin by Biotransformation |
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Authors: | Amira Mira Wael Alkhiary Qinchang Zhu Toshinori Nakagawa Hai‐Bang Tran Yhiya M. Amen Kuniyoshi Shimizu |
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Affiliation: | 1. Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt;2. Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt;3. Division of Systematic Forest and Forest Products Sciences, Department of Agro‐Environmental Sciences, Faculty of Agriculture, Graduate School of Kyushu University, Fukuoka, Japan |
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Abstract: | Isoepoxypteryxin is the major coumarin of a Japanese medicinal plant Angelica shikokiana. This research was designed to study the effect of structural changes through fungal biotransformation on the reported biological activities of isoepoxypteryxin. Among the tested microorganisms, only Cordyceps sinensis had enzymes that could catalyze the ester hydrolysis and the reductive cleavage of the epoxide ring of isoepoxypteryxin, separately, to give two more polar metabolites (+)‐cis‐khellactone ( P1 ) and a new coumarin derivative (+)‐cis‐3′‐[(2‐methyl‐3‐hydroxybutanoyl)oxy]‐4′‐acetoxy‐3′,4′‐dihydroseselin ( P2 ), respectively. The polar metabolite P2 showed stronger cytotoxicity and higher selectivity than isoepoxypteryxin. On the molecular level, P2 showed more in vitro inhibition of both tubulin polymerization and histone deacetylase 8 (HDAC8). Similarly, P2 showed more neuroprotection against amyloid beta fragment 1 – 42 (Aβ1 – 42)‐induced neurotoxicity in human neuroblastoma cells (SH‐SY5Y) and exhibited more inhibition of the in vitro aggregation of Aβ1 – 42. Both metabolites showed stronger antiplatelet aggregation by increased inhibition of thromboxane‐A2 synthase (TXS) activity and thromboxane‐A2 (TXA2) production. This study is the first to describe the improved cytotoxic, neuroprotective, and antiplatelet aggregation activities of isoepoxypteryxin through its biotransformation by C. sinensis. |
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Keywords: | Antiplatelet
Cordyceps sinensis
Cytotoxic activities Isoepoxypteryxin Neuroprotection |
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