No abstract

Polyphenolic compounds are widely distributed in higher plants and are an integral part of the human diet. Recent interest in these substances has been stimulated by their potential health benefits, which are believed to arise mainly from their antioxidant activity. In the past years, the antioxidant activity of flavonoids has been studied in detail. An important but often overlooked group of polyphenols is that of the proanthocyanidins. Therefore, the present review is focused mainly on the antioxidant activity of proanthocyanidins and its relevancy in vivo. The three most important mechanisms of their antioxidant action will be discussed, i.e. free radical scavenging activity, chelation of transition metals, and inhibition of enzymes. In addition, the protective role of proanthocyanidins against lipid peroxidation and peroxynitrite, as well as their antimicrobial properties will be discussed. To study the in vivo relevancy of the proanthocyanidin activities, the knowledge of their pharmacokinetic parameters is crucial. Although bioavailability and metabolism data on polyphenols in general and proanthocyanidins in particular are still largely unavailable, the first reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed. There is also considerable scientific and public interest in the important role that antioxidants may play in health care, e.g. by acting as cancer chemopreventive and anti-inflammatory agents and by reducing risk of cardiovascular mortality. Each of these aspects will be discussed, with special attention to the role of proanthocyanidins on apoptosis, gene expression and transcription factors, such as NF-kappa B.

Despite the continuous advances made in antiretroviral combination therapy, AIDS has become the leading cause of death in Africa and the fourth worldwide. Today, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action. In this review, plant substances showing a promising anti-HIV activity are discussed according to the viral targets with which they interact. Most of these compounds, however, interfere with early steps in the HIV replication, such as the virus entry steps and the viral enzymes reverse transcriptase and integrase, whereas until now almost no plant compounds have been found to interact with the many other viral targets. Since some plant substances are known to modulate several cellular factors, such as NF-kappa B and TNF-alpha, which are also involved in the replication of HIV, their role as potential anti-HIV products is also discussed. In conclusion, several plant-derived antiviral agents are good candidates to be further studied for their potential in the systemic therapy and/or prophylaxis of HIV infections, most probably in combination with other anti-HIV drugs.

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase which modulates the function of its substrates, among which are insulin-releasing incretins. DPP4 inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. Inhibition of DPP4 exhibits protective effects on ischemia-reperfusion injury (IRI) of the heart and lung. As DPP4 and its substrates are also expressed in the kidney, we studied the effect of the DPP4 inhibitor vildagliptin on the outcome of IRI-induced acute kidney injury in rats in a model of 30-min unilateral renal ischemia, followed by contralateral nephrectomy. Saline, 1, or 10 mg/kg vildagliptin (VG1/VG10) was administered intravenously 15 min before the surgery. Animals were euthanized after 2, 12, amd 48 h of reperfusion. DPP4 inhibition resulted in a significant dose-dependent decrease in serum creatinine (1.31 ± 0.32 and 0.70 ± 0.19 mg/dl for VG1 and VG10, respectively, vs. 1.91 ± 0.28 mg/dl for controls at 12 h; P < 0.01). Tubular morphology (PAS-PCNA) revealed significantly reduced tubular necrosis at 12 h (62.1 ± 18.0 and 77.5 ± 22.0% in VG10 and saline, respectively). VG did not affect regeneration but decreased apoptosis, as shown by twofold decreased Bax/Bcl-2 mRNA expression and a threefold decrease in apoptotic bodies on terminal deoxynucleotidyl transferase dUTP nick-end labeling-stained sections. VG treatment significantly reduced serum malondialdehyde twofold in both VG1- and VG10-treated ischemic and sham-operated animals compared with controls and also resulted in a significant decrease in mRNA expression of the proinflammatory marker CXCL10 at 2 h of reperfusion. Through a mechanism yet to be fully understood, VG treatment results in a functional protection of the kidney against IRI. This protection was associated with antiapoptotic, immunological, and antioxidative changes.

Attention-deficit hyperactivity disorder (ADHD) etiology is not completely understood, but common comorbid dysfunction of the gastrointestinal and immune system suggests that these systems may be affected by a common genetic background and molecular mechanisms. For example, increased levels of specific cytokines were observed in ADHD. Moreover, ADHD has a high comorbidity with both Th1- and Th2-mediated disorders like ear infections, eczema and asthma. A common pathophysiological mechanism was suggested to underlie both asthma and ADHD, while several genes that are linked to ADHD have immune functions. Furthermore, immunological recognition of food provoking ADHD-like behavior was suggested. An immune imbalance, probably requiring a predisposing genetic background, is therefore suggested to contribute to ADHD etiology, with immune dysregulation being more likely than a single subcellular defect. However, next to allergic mechanisms, also pharmacological mechanisms (especially in case of food additives) might be involved. In addition, though cellular (cytokine-related) rather than antibody-mediated immune mechanisms seem involved, specific immune-inflammatory markers other than antibodies have not been systematically studied in ADHD. Substantial alterations implicated in ADHD apparently occur in the immune system and epigenetic regulation of gene expression. As a result, chronic inflammation and oxidative stress could develop, which can lead to ADHD symptoms, for example by chronic T-cell-mediated neuroinflammation. If immune pathways contribute to ADHD, both its diagnosis and treatment should be reconsidered. Modulation of immune system activity might have potential in ADHD treatment, for example by nutritional approaches providing safe and low-cost ADHD therapy, but further research in these fields is implicated.