Topical application of Nexrutine inhibits ultraviolet B-induced cutaneous inflammatory responses in SKH-1 hairless mouse.

BACKGROUND: Ultraviolet B (UVB) radiation is the major contributor to skin inflammation which leads to the development of skin cancer. Hence, in this study, we studied the effect of Nexrutine (NX) on UVB-induced cutaneous inflammation and its mediators. METHODS: Ultraviolet absorption spectra of NX were measured by spectrophotometer. To conduct the photoprotective studies, SKH-1 hairless mice were topically treated with NX, 30 minutes before to the UVB (180 mJ/cm2 ) exposure. Twenty hours of post-UVB irradiation, mouse skin was used for edema measurements, H & E staining, myeloperoxidase (MPO) activity, and estimation of plasma cytokines. In addition, expression levels of inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were also determined by Western blot analysis. RESULTS: Nexrutine displayed absorbance over the UVB spectrum. NX significantly decreased the UVB-induced epidermal edema, skin thickness, leukocyte infiltration, number of the sunburn, and TUNEL-positive cells. NX treatment also decreased the number of mast cells, MPO activity, expression of pro-inflammatory cytokines, and inflammation mediator protein in mouse skin. CONCLUSION: These results provide evidences that NX inhibits the UVB-induced cutaneous inflammatory responses in SKH-1 mouse skin.

Nexrutine inhibits azoxymethane-induced colonic aberrant crypt formation in rat colon and induced apoptotic cell death in colon adenocarcinoma cells.

Colon cancer is the third most common cause of death in the United States. Therefore, new preventive strategies are warranted for preventing colon cancer. Nexrutine (NX), an herbal extract from Phellodendron amurense, has been shown to have anti-inflammatory, anti-microbial and anti-cancer activity for various tissue specific cancers, but its chemopreventive efficacy has not been evaluated against colon cancer. Here, we explored the mechanism of chemopreventive/chemotherapeutic efficacy of NX against colon cancer. We found that dietary exposure of NX significantly reduced the number of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. In addition, significant inhibition in AOM-induced cell proliferation and reduced expression of the inflammatory markers COX-2, iNOS as well as the proliferative markers PCNA and cyclin D1 were also seen. Moreover, NX exposure significantly enhanced apoptosis in the colon of AOM treated rats. Furthermore, in in vitro studies, NX (2.5, 5, 10 µg/ml, 48 h) decreased cell survival and colony formation while inducing G0/G1 cell cycle arrest and apoptosis in colon adenocarcinoma cells COLO205 and HCT-15. However, NX had minimal cytotoxic effect on IEC-6 normal rat intestinal cells, suggesting its high therapeutic index. NX treatment also modulates the level of Bax and Bcl-2 proteins along with cytochrome c release, cleavage and enhanced expression of poly (adenosine diphosphate-ribose) polymerase as well as the catalytic activity of caspase 3 and caspase 9 in both COLO205 and HCT-15 cells. Based on these in vivo and in vitro findings, we suggest that NX could be useful candidate agent for colon cancer chemoprevention and treatment. © 2015 Wiley Periodicals, Inc.

Protective effect of topical application of α-tocopherol and/or N-acetyl cysteine on argemone oil/alkaloid-induced skin tumorigenesis in mice.

Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.