There is increasing evidence indicating that re- active oxygen species (ROS, e.g., O 2- and OH - ) and free radical-meditated reactions can cause ox- idative damage to biomolecules (e.g., lipids, pro- teins, and DNA), eventually contributing to, for example, aging, cancer, atherosclerosis, coronary heart ailment, diabetes, Alzheimer’s disease, and other neurodegenerative disorders (Finkel and Holbrook 2000; Halliwell 1994). Antioxidants are thought to be highly effective in the manage- ment of ROS-mediated tissue impairments. Many antioxidant compounds possess anti- inflammatory, antiatherosclerotic, antitumor, an- timutagenic, anticarcinogenic, antibacterial, or antiviral activities to a greater or lesser extent (Cozma 2004; Halliwell 1994; Mitscher et al. 1996; Owen et al. 2000; Sala et al. 2002). Natu- rally derived antioxidants have received much at- tention in recent years (Hu and Kitts 2000; Schulz et al. 2002). Endophytes are fungi or bacteria residing in- side healthy plant tissues without any discernible infectious symptoms (Wilson 1995). They could be a potential source of novel natural products for medicinal, agricultural, and industrial uses. Because they are relatively unstudied, much at- tention is now being paid to endophytic biodi- versity, the chemistry and bioactivity of endo- phytic metabolites, and the relationships between endophytes and host plants (Schulz et al. 2002; Tan and Zou 2001). Endophytes provide a wide variety of structurally unique bioactive natural products, such as alkaloids, benzopyranones, chi- nones, flavonoids, phenolic acids, quinones, ste- A Potential Antioxidant Resource: Endophytic Fungi from Medicinal Plants 1 Wu-Yang Huang 2 , Yi-Zhong Cai 3 , Jie Xing 4 , Harold Corke 3 , and Mei Sun 2,* 2 Department of Zoology, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China 3 Department of Botany, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China 4 Republic Polytechnic, Woodlands Avenue 9, Singapore 738964 * Corresponding author; e-mail: meisun@hku.hk A Potential Antioxidant Resource: Endophytic Fungi from Medicinal Plants. Medicinal plants and their endophytes are important resources for discovery of natural products. Sev- eral previous studies have found a positive correlation between total antioxidant capacity (TAC) and total phenolic content (TPC) of many medicinal plant extracts. However, no in- formation is available on whether such a relationship also exists in their endophytic fungal metabolites. We investigated the relationship between TAC and TPC for 292 morphologi- cally distinct endophytic fungi isolated from 29 traditional Chinese medicinal plants. The an- tioxidant capacities of the endophytic fungal cultures were significantly correlated with their total phenolic contents, suggesting that phenolics were also the major antioxidant con- stituents of the endophytes. Some of the endophytes were found to produce metabolites possessing strong antioxidant activities. Several bioactive constituents from the fungal cul- tures and host plant extracts were identified. This investigation reveals that the metabolites produced by a wide diversity of endophytic fungi in culture can be a potential source of novel natural antioxidants. Key Words: Endophytic fungi, metabolites, medicinal plants, antioxidant activity, phenolic compounds, Chinese medicinal plants, traditional Chinese medicine, TCM. Economic Botany, 61(1), 2007, pp. 14–30. © 2007, by The New York Botanical Garden Press, Bronx, NY 10458-5126 U.S.A. 1 Received 4 August 2006; accepted 9 November 2006.