The history of studies in biology regarding reactive oxygen species (ROS) is approximately 40 years. During the initial 30 years, it appeared that these studies were mainly focused on the toxicity or microbicidal-related agents of ROS. However, recent studies have identified another action regarding oxidative signaling, other than toxicity of ROS. Basically, it is suggested that ROS are reactive, and degenerate to biomacromolecules such as DNA and proteins, leading to deterioration of cellular functions as an oxidative stress. On the other hand, recent studies have shown that ROS act as oxidative signaling in cells, resulting in various gene expressions. For example, NADPH oxidase, a major source of superoxide radicals (O(2)(-)), expresses in various tissues such as leukocytes and cardiovascular systems, and ROS derived from the enzyme play important roles in cell proliferation, differentiation, and cell death. In this review, we have focused on and described the basic properties, toxicity, and roles of ROS.

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Exposure to UV radiation up-regulates the synthesis of matrix metalloproteinases (MMPs), a group of matrix-degrading enzymes. MMPs are regarded as promising therapeutic targets and the development of effective inhibitors is an important research focus. The plant Pothomorphe umbellata has been shown to exert a potent antioxidant activity on the skin and to delay the onset and reduce the incidence of UVB-induced chronic skin damage. The aim of the present study was to determine the effect of P. umbellata ethanolic root extract on MMP-2 and MMP-9. The in vitro inhibition of MMP-2 and MMP-9 was measured by gelatin zymography in the presence of different concentrations of P. umbellata extract, as well as in the presence of its isolated active principle 4-nerolidylcatechol (4-NC). The inhibitory effect of the P. umbellata extract was stronger than that of 4-NC. Gelatin zymography and histological analysis revealed that P. umbellata was able to inhibit constitutive MMP-9 activity in vivo in mice sacrificed 2 h after UVB irradiation. The intensity of the MMP-2 band was unchanged. Our data contribute to the elucidation of the mechanism of prevention of photoaging by P. umbellata and may provide a rational basis for the use of this plant in prophylaxis against and treatment of skin cancer.

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In this study we evaluated the activity of Pothomorphe umbellata root extract on hairless mice chronically exposed to UVB radiation (76.5 mJ/cm(2), 4 days per week for 22 weeks). Mouse dorsal surfaces were treated topically with 20 mg/cm(2) of a carbomer 940 gel (vehicle) with or without P. umbellata root extract to a final concentration of 0.1%, for 2 h before irradiation. Another irradiated group received no topical treatment. A fourth group received no treatment and was not irradiated. Visible skin wrinkling was evaluated using a scale ranging from 0 to 4, where 0 corresponds to no skin modification, and 4 to the maximum visual skin alteration observed in our experiments. Histological measurements were carried out on standard haematoxylin & eosin stained sections. The mean distances between the outermost surface of the epidermis (excluding the stratum corneum) and the dermal-epidermal junction were determined by morphometric analysis. These distances were statistically increased in the irradiated control groups when compared to the nonirradiated control group and to the irradiated group using P. umbellata root extract. These data demonstrate that P. umbellata may be successfully used as a topical skin-protecting agent against the deleterious effects of UV radiation.

Schistosomiasis is a disease caused by parasites of the genus Schistosoma, currently affecting more than 200 million people. Among the various species of this parasite that infect humans, S. mansoni is the most common. Pharmacological treatment is limited to the use of a single drug, praziquantel (PZQ), despite reports of parasite resistance and low efficacy. It is therefore necessary to investigate new potential schistosomicidal compounds. In this study, we tested the efficacy of epiisopilosine (EPIIS) in a murine model of schistosomiasis. A single dose of EPIIS (100 or 400 mg/kg) administered orally to mice infected with adult S. mansoni resulted in reduced worm burden and egg production. The treatment with the lower dose of EPIIS (100 mg/kg) significantly reduced total worm burden by 60.61% (P < 0.001), as well as decreasing hepatosplenomegaly and egg excretion. Scanning electron microscopy revealed morphological changes in the worm tegument after treatment. Despite good activity of EPIIS in adult S. mansoni, oral treatment with single dose of EPIIS 100 mg/kg had only moderate effects in mice infected with juvenile S. mansoni. In addition, we performed cytotoxicity and toxicological studies with EPIIS and found no in vitro cytotoxicity (in HaCaT, and NIH-3T3 cells) at a concentration of 512 μg/mL. We also performed in silico analysis of toxicological properties and showed that EPIIS had low predicted toxicity. To confirm this, we investigated systemic acute toxicity in vivo by orally administering a 2000 mg/kg dose to Swiss mice. Treated mice showed no significant changes in hematological, biochemical, or histological parameters compared to non-treated animals. Epiisopilosine showed potential as a schistosomicidal drug: it did not cause acute toxicity and it displayed an acceptable safety profile in the animal model.

In this work we evaluated the influence of topical application of P. umbellata root extract gel, containing 0.1% of 4-nerolidylcathecol, on the antioxidant network in UV-induced oxidative damage in hairless mouse skin. The UV-irradiation had no influence on ascorbic acid levels or on the antioxidant enzyme (superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase) activities, but topical P. umbellata treatment protected alpha-tocopherol from being depleted after UV-irradiation. alpha-Tocopherol concentration decreased significantly (approximately 40%, P < 0.01) in the irradiated control groups, whereas in the P. umbellata-treated group, alpha-tocopherol was totally preserved (approximately 100%, P > 0.05). These data demonstrate that P. umbellata may be successfully used as a topical photoprotective agent.