Cyclooxygenase-1 and -2 (COX-1/2) catalyze the initial step in the formation of prostaglandins. Very recently their role in carcinogenesis has become more evident. They influence apoptosis, angiogenesis, and invasion, and play a key role in the production of carcinogens. Usually, a high level of COX-2 expression is found in cancer cells. Large epidemiological trials studying users and non-users of aspirin have shown that cyclooxygenase inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) could be of benefit against the development and growth of malignancies. Moreover, clinical trials in patients with familial adenomatosis polyposis syndrome have shown the efficacy of selective COX-2 inhibitors in the reduction of the number and size of colorectal polyps. Several preclinical studies show promising results with combinatorial treatments of either chemotherapy or radiotherapy with COX inhibitors. Preclinical studies with the simultaneous use of inhibitors of the epidermal growth factor receptor and COX-2 inhibitors have shown also promising results. Encouraging results from the first clinical trials combining chemotherapy with COX-2 inhibitors in patients with cancer in the advanced and neoadjuvant setting have recently been reported. Thus, it appears that targeting the COX-2 pathway is a promising strategy in the prevention and treatment of solid tumors.

Oxidative stress has been consistently linked to ageing-related neurodegenerative diseases. Neurodegenerative diseases are characterized by progressive dysfunction and death of neurons. Oxidative stress is associated with dysfunction of the mitochondria and endoplasmic reticulum, inducing apoptosis and protein misfolding in neurons. Decreased activities of antioxidant enzymes like SOD, catalase, glutathione, glutathione peroxidase in neurodegenerative states signifies role of reduced antioxidant potential in neurodegeneration. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include Hsp70, heme oxygenase-1, thioredoxin and sirtuins. Cellular signalling pathways and molecular mechanisms that mediate hormetic responses typically involve antioxidant enzymes and transcription factors such as Nrf-2 and NFκB. Vitagenes, either individually or by acting in concert, contribute to counteract the ROS mediated damage. In this review the importance of oxidative stress and the potential use of antioxidants in the prevention and treatment of neurodegenerative disorders are discussed.

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Out of the several leads obtained from plant sources as potential hepatoprotective agents, silymarin, andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have been established as potent hepatoprotective agents. The hepatoprotective potential of several herbal medicines has been clinically evaluated. Significant efficacy has been seen with silymarin, glycyrrhizin and Liv-52 in treatment of hepatitis, alcoholic liver disease and liver cirrhosis.

Rationale: Diabetic heart disease (DHD) is a debilitating manifestation of type 2 diabetes. Exercise has been proposed as a potential therapy for DHD, although the effectiveness of exercise in preventing or reversing the progression of DHD remains controversial. Cardiac function is critically dependent on the preservation of coronary vascular function. Objective: We aimed to elucidate the effectiveness and mechanisms by which exercise facilitates coronary and cardiac-protection during the onset and progression of DHD. Methods and Results: Diabetic db/db and non-diabetic mice, with or without underlying cardiac dysfunction (16 and 8 weeks old, respectively) were subjected to either moderate-intensity exercise (MIE) or high-IE (HIE) for eight weeks. Subsequently, synchrotron microangiography, immunohistochemistry, Western blot, and RT-PCR were used to assess time-dependent changes in cardiac and coronary structure and function associated with diabetes and exercise, and determine whether these changes reflect the observed changes in cardiac-enriched and vascular-enriched microRNAs (miRNAs). We show that, if exercise is initiated from 8 weeks of age, both MIE and HIE prevented the onset of coronary and cardiac dysfunction, apoptosis, fibrosis, microvascular rarefaction, and disruption of miRNA signaling, as seen in the non-exercised diabetic mice. Conversely, the cardiovascular benefits of MIE were absent if the exercise was initiated after the diabetic mice had already established cardiac dysfunction (i.e. from 16 weeks of age). The experimental silencing or upregulation of miRNA-126 activity suggests the mechanism underpinning the cardiovascular benefits of exercise were mediated, at least in part, through tissue-specific miRNAs. Conclusions: Our findings provide the first experimental evidence for the critical importance of early exercise intervention in ameliorating the onset and progression of DHD. Our results also suggest that the beneficial effects of exercise are mediated through the normalization of cardiovascular-enriched miRNAs, which are dysregulated in DHD.