Antimicrobial and antitumor activity and diversity of endophytic fungi from traditional Chinese medicinal plant Cephalotaxus hainanensis Li.

Endophytes from Cephalotaxus hainanensis Li, an important source of anti-leukemia drugs, have not been widely explored. In this study, 265 endophytic fungal isolates from C. hainanensis Li were screened for antimicrobial activities against tilapia, banana, rice, and rape and for antitumor activities against human leukemia cell lines (K562, NB4, and HL-60). Diversity was also analyzed. The results showed that 17.7% of the endophytic fungi had antimicrobial activities against at least three different test microbes, and activity against Fusarium oxysporum RKY102 was the highest at 15.8%. Cytotoxicity against at least one tumor cell line tested was observed in 18.5% of the endophytic fungi; with the highest value of 10.6% against K562. The endophytic fungal strains also showed relatively high activities against K562, NB4, and HL-60 while relatively fewer strains were cytotoxic against the human hepatic Hep-G2 and colon LoVo cancer cell lines. Thirty endophytic fungal strains showed both high antimicrobial and antitumor activities. Moreover, the analyses of the diversity of the 30 highly active strains showed they belonged to 20 species from 14 genera, and this is the first report of endophytic fungi Albonectria rigidiuscula, Colletotrichum magnisporum, and Nemania diffusa being isolated from Cephalotaxus plants. These findings suggest that natural antibacterial products for humans and tilapia; antifungal compounds for rice, rape, and banana; and antitumor compounds for leukemia therapy could be isolated from fungal strains derived from C. hainanensis Li.

Protection against myocardial ischaemia/reperfusion injury by PPAR-alpha activation is related to production of nitric oxide and endothelin-1.

BACKGROUND: Ligands of peroxisome proliferator-activated receptor alpha (PPAR-alpha) have been shown to reduce ischaemia/reperfusion injury. The mechanisms behind this effect are not well known. We hypothesized that activation of PPAR-alpha exerts cardioprotection via a mechanism related to nitric oxide (NO) and endothelin-1 (ET-1). METHODS: Five groups of anaesthetized open-chest Sprague-Dawley rats were given the PPAR-alpha agonist WY 14643 1 mg/kg (WY; n = 7), dimethyl sulfoxide (DMSO, vehicle for WY; n = 6), the combination of WY and the NO synthase inhibitor N-nitro-L-arginine (L-NNA, 2 mg/kg) (n = 7), L-NNA only (n = 8) or 0.9% sodium chloride (NaCl, vehicle for DMSO and L-NNA; n = 8) i.v. before a 30 min period of coronary artery occlusion followed by 2 h of reperfusion. Infarct size (IS), eNOS and iNOS protein and ET-1 mRNA expression were determined. RESULTS: There were no haemodynamic differences between the groups during the experiment. The IS was 78 +/- 3% of the area at risk in the DMSO group and 77 +/- 2% in the NaCl group (P = NS). WY reduced IS to 56 +/- 3% (P < 0.001 vs. DMSO group). When WY was administered in combination with L-NNA the cardioprotective effect was abolished (IS 73 +/- 3%, P < 0.01 vs. WY 14643). L-NNA did not affect IS per se (78 +/- 2%, P = NS). The expression of eNOS but not iNOS protein in ischaemic myocardium from rats was increased in the group given WY (P < 0.05). ET-1 mRNA levels were lower in the ischaemic myocardium following WY administration. CONCLUSION: The results suggest that the PPAR-alpha activation protects the rat myocardium against ischaemia/ reperfusion injury via a mechanism related to production of NO, and possibly ET-1.