The study by Bian et al. (1) raises many important deliberations. Briefly, they found that luteolin (LUT), a flavonoid found in many vegetables, fruits and seeds, inhibits ischemia/reperfusion induced myocardial injury (IRI) in rats.The first question is: how relevant to the clinical situation are results on IRI alleviation in the experimental setting. The number of successful interventions in animals is legion. However, against these promising results, the very important position paper of the Working Group of Cellular Biology of the Heart of the European Society of Cardiology (2) should be remembered: the experts producing this paper concluded only 3 years ago that there is no effective proven therapy against IRI. It is widely recognized that it is not always possible to translate animal experiments into clinical therapy.According to Bian et al.(1), LUT joins a long list of herbal medicines proposed to have wonder qualities, such as quercetin, curcumin, resveratrol, and many others. LUT is followed by an impressive list of references, supporting it as an antineoplastic and cardioprotective agent. In its latter role LUT has been given only in rodents, mostly on isolated cardiomyocytes (3,4) or hearts under Langendorff perfusion as in the present study (3,5) or both (4,6). Sun et al. (7) used the drug in diabetic rats undergoing coronary artery occlusion for 30 minutes followed by 3 hours of reperfusion. The drug was administered via tail vein injection, which makes it a feasible agent for employment in the clinical arena as an adjunct to primary percutaneous coronary intervention.Many mechanisms have been proposed for the cardioprotective effects of LUT against IRI. Thus in previous studies, Qi et al. (8) from the same group found that LUT decreased both necrosis and apoptosis. As regards apoptosis, they found that LUT upregulated Bcl-2, decreased the ratio of Bax to Bcl-2 and inhibited the activation of caspase-3. These findings are important since IRI engenders both necrosis and apoptosis (9). Xu et al. (3) again from the same group in a review recapitulate the action of LUT on the following processes, involved in apoptosis: upregulation of phosphorylated Akt, suppression of NF-κF activation, increase of Bcl-2, inhibition of caspase-8 and -3. Fang et al. (4) additionally reported that LUT increased phosphorylated SERCA-2 and phospholamban as opposed to control, through the p13K/Akt pathway. Also, Wu et al. (6) found that it activates pERK and inhibits the JNK pathway. Reduction of JNK, and p38 MAPK are also reported by Cheng et al. (10) in rat cortical necrosis.Sun et al. (7) also showed that LUT inhibits LDH release (suggestive of necrosis inhibition) and in addition to its decrease of the Bax to Bcl-2 ratio, it upregulated the anti-apoptotic proteins FGFR2 and LIF and increased BAD phosphorylation. It also inhibited MPO expression and inflammatory cytokine production, including IL-6, IL-1a and TNFα. They also found that LUT decreased infarct size as measured by Evans Blue/TTC staining, and myocardial apopto...
