Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus.

NADPH oxidase 4 (Nox4) has recently been implicated as driving force in cellular senescence. Thus, there is growing interest to develop Nox4 inhibitors, which might be valuable agents for cosmeceutical applications. Alpine plants represent a valuable source for the identification of novel bioactive natural products with anti-ageing effects, especially substances that protect plants against UV radiation, which is also known to contribute to the ageing of human skin. Therefore, the aim of this study was to identify novel Nox4 inhibitors from alpine plants. Within an initial screening of extracts of alpine plants on their ability to inhibit Nox4 activity in HEK cells, the methanolic extract of the subaerial parts of Lycopus europaeus showed a strong inhibition of Nox4 (81% chemiluminescence quenching) and a simultaneously high cell viability (91% vitality). Rosmarinic acid was isolated and identified as the major compound in this bioactive extract. It showed a dose dependent inhibitory activity on Nox4 with an IC50 of 1 µM. Moreover, it also showed a significant inhibitory activity on Nox2 in the low micromolar range, whereas no inhibition of Nox5 was detected. Further investigations confirmed that the observed effects of rosmarinic acid on Nox2 and Nox4 are real inhibitory activities, and not due to ROS scavenging effects. Therefore, L. europaeus, which we demonstrated to be a good source of rosmarinic acid, has great potential for usage in cosmeceutical products with anti-ageing activity.

A pilot study of the effect of Kinesiology tape on knee proprioception after physical activity in healthy women.

OBJECTIVES: Kinesiology tape has gained significant popularity in recent years and is widely used as an adjunct for treatment and prevention of musculoskeletal injuries. However, evidence regarding its influence on knee proprioception is scarce. The purpose of this study was to evaluate the effect of Kinesiology tape on knee proprioception after physical activity in healthy women. It was hypothesized that Kinesiology tape enhances knee proprioception. DESIGN: Longitudinal analysis, pretest-posttest design. METHODS: Twelve young women with healthy knees were tested for knee proprioception without the use of Kinesiology tape and wearing Kinesiology tape at the knee. The joint position sense was measured at the start and after a 30-min uphill walking protocol on a treadmill. Outcome was the knee angle deviation. RESULTS: No significant difference of proprioceptive performance between the application with Kinesiology tape and without Kinesiology tape was found after uphill walking (p > 0.05). However, when the participants' results for knee angle deviation were graded into good (< 6.1°) and poor ( > 6.1°), Kinesiology tape significantly enhanced those with poor proprioceptive ability after uphill walking, compared to the untaped knee (p = 0.002). CONCLUSIONS: This study has shown that the application of Kinesiology tape did not improve knee proprioception in a group of healthy young women. However, it also has demonstrated that Kinesiology tape provided significant proprioceptive enhancement at the knee joint after uphill walking in healthy women with poor proprioceptive ability. This may support its use in sports medicine for preventing knee injuries.

Characterisation of Nox4 inhibitors from edible plants.

NADPH oxidases transport electrons from cytosolic NADPH through biological membranes to generate reactive oxygen species. NADPH oxidase 4, broadly expressed in humans, is an interesting pharmacological target, since its activity is deregulated in several diseases, including pulmonary fibrosis, diabetic nephropathy, and cardiac hypertrophy. Whereas several candidate NADPH oxidase 4 inhibitors were recently described, most of these compounds are either unspecific or toxic. Here we set out to identify new NADPH oxidase 4 inhibitors from edible plants, in an attempt to decrease the number of hits with toxic side effects. We screened a compound library prepared from edible plants for new bioactives with the ability to inhibit the activity of NADPH oxidase 4. Using both cell-based and cell-free assays, we identified several compounds with significant inhibitory activity towards NADPH oxidase 4. For selected compounds, the activity profile towards NADPH oxidase 2 and NADPH oxidase 5 was established, and controls were carried out to exclude general reactive oxygen species scavengers. A number of promising NADPH oxidase 4 inhibitors from edible plants was identified and characterised. Several new chemical entities are disclosed which act as NADPH oxidase 4 inhibitors, and the efficacies of our best hits, in particular several diarylheptanoids and lignans, are comparable to the best available pharmacological NADPH oxidase 4 inhibitors. These findings will provide valuable tools to study mechanisms of NADPH oxidase inhibition.