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Reactive oxygen species (ROS), such as hydroxyl (˙OH), superoxide anion radical (O 2 Ϫ ), and hydrogen peroxide (H 2 O 2 ), are highly reactive molecules that consequently generate metabolic products that attack lipids in cell membranes or DNA. A series of free radical chain reaction processes is associated with several types of biological damage, carcinogenesis, and cellular degeneration related to aging. Cells are protected from such damage by their endogenous scavenging systems or by other compounds. 1) Thus ROS play an important role in physiological and pathological states and are constantly produced in living organisms. 2)Aging has been associated with free radical formation in many reports.3) Oxidative stresses can be generated in the connective tissues and the skin cells by photodamage and inflammatory processes. When the skin is exposed to ultraviolet (UV) or visible light, it will produce free radicals, 4) which can then induce skin damage such as occurs in phototoxicity and aging.5) Previous studies also indicated that skin exposure to UV irradiation regulates matrix-degrading enzymes, such as metalloproteinases (MMPs)-1, -2, -3, -7, -8, -9 and -12.6,7) The MMPs are a family of zinc-dependent endopeptidases that play a key role in the turnover of extracellular matrix in skin.8) Aging and exposure to environmental insults, such as UV irradiation, increase the expression of MMPs. 9,10) Excessive MMP activity, which causes the collapse of the meshwork in the extracellular matrix, produces UV irradiation-like skin damage, including wrinkling, loss of elasticity, and dilation of surface microcapillary vessels.11) MMP-1 belongs to the subfamily of collagenases, which are the key enzymes in collagen turnover required for the remodeling of the dermal matrix. Several studies have demonstrated that the decreased elasticity of skin with aging is significantly correlated with increased elastase activity. 12)Recently, the bioactivities of several natural plants and plant-derived phytochemicals have been studied. For example, previous reports on various Malus (apple) species, which are common fruit worldwide, showed that they contain antioxidative phenolics such as dihydrochalcones and flavonoids. 13,14) There are many reports in the literature describing the strong antioxidant activities of polyphenols 15) and their benefits in treating or preventing human diseases. The ingredients in apples have also been shown to be associated with lowered risk of cardiovascular diseases and various cancers. 14)Malus doumeri A. CHEV. var. formosana (KAWAK. & KOIDZ.) S. S. YING (Rosaceae) is a Taiwanese indigenous plant with horticultural use and edible fruit. Among the Taiwanese, it is sometimes used to treat heatstroke and heat-related hyperactivity and as a tonic to reinforce vital energy. 16) However, there are few reported phytochemical examinations of this species. In this study, DPPH scavenging activity was used to identify the active constituents in M. doumeri var. formosana. The isolated components were also investigated...

Commercial pectins with different degrees of esterification (DE) were reacted with equal volumes of 2 M alkaline hydroxylamine (pH 12.0) at room temperature for 4 h to prepare pectin hydroxamic acids (PHAs; DE94T4, DE65T4, and DE25T4) according to a previously reported method (Hou et al., J. Agric. Food Chem. 2003, 51, 6362-6366) and were used to test the antioxidant and antiradical activities in comparison with those of DE94, DE65, and DE25 pectins. The half-inhibition concentrations, IC(50), of scavenging activity against DPPH were 1.51, 5.43, and 5.63 mg/mL for DE94T4, DE65T4, and DE25T4, respectively, and were much lower than those of corresponding DE pectins under the same concentrations. The scavenging activities of PHAs for DPPH radicals were positively correlated with original DE values of pectin. The optimal pH of DE94T4 for scavenging DPPH radicals was 7.9 or 8.0. Using electron spin resonance (ESR) for scavenging hydroxyl radicals, under the same concentrations of 125 microg/mL, DE94T4, DE65T4, and DE25T4, respectively, exhibited 73.53, 69.01, and 55.17% antiradical activities. PHAs also exhibited protection against hydroxyl radical-mediated DNA damage and anti-human low-density lipoprotein peroxidation tests.

DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.

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Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Aberrant activation of WNT/β-catenin signaling present in the vast majority of CRC cases is indispensable for CRC initiation and progression, and thus is a promising target for CRC therapeutics. Hispolon is a fungal-derived polyphenol with a pronounced anticancer effect. Several hispolon derivatives, including dehydroxyhispolon methyl ether (DHME), have been chemically synthesized for developing lead molecules with stronger anticancer activity. Herein, a DHME-elicited anti-CRC effect with the underlying mechanism is reported for the first time. Specifically, DHME was found to be more cytotoxic than hispolon against a panel of human CRC cell lines, while exerting limited toxicity to normal human colon cell line CCD 841 CoN. Additionally, the cytotoxic effect of DHME appeared to rely on inducing apoptosis. This notion was evidenced by DHME-elicited upregulation of poly (ADP-ribose) polymerase (PARP) cleavage and a cell population positively stained by annexin V, alongside the downregulation of antiapoptotic B-cell lymphoma 2 (BCL-2), whereas the blockade of apoptosis by the pan-caspase inhibitor z-VAD-fmk attenuated DHME-induced cytotoxicity. Further mechanistic inquiry revealed the inhibitory action of DHME on β-catenin-mediated, T-cell factor (TCF)-dependent transcription activity, suggesting that DHME thwarted the aberrantly active WNT/β-catenin signaling in CRC cells. Notably, ectopic expression of a dominant–active β-catenin mutant (∆N90-β-catenin) abolished DHME-induced apoptosis while also restoring BCL-2 expression. Collectively, we identified DHME as a selective proapoptotic agent against CRC cells, exerting more potent cytotoxicity than hispolon, and provoking CRC cell apoptosis via suppression of the WNT/β-catenin signaling axis.

For identification of genuine and counterfeit samples of Cordyceps sinensis, an RAPD (random amplified polymorphic DNA) analysis was performed. In the study, twelve samples were collected, of which six were genuine and six were counterfeit samples. Genuine samples of Cordyceps sinensis contain two parasitic larvae produced from each of the three provinces, Sichuan (SC), Chinghai (CH), and Tibet (TB). The counterfeits contain two products of each of the three species, Cordyceps hawkesii, Stachys geobombycis, and Stachys sieboldii. In the RAPD analysis, twenty arbitrary decamer primers were screened to obtain primers appropriate for differentiating the genuine and counterfeit samples. The result of twelve RAPD markers generated from four primers, OPT-08, OPT-12, OPT-13, and OPT-17, were selected. The primers can easily distinguish between genuine and counterfeit samples of Cordyceps sinensis.