Wannit Tongkao-on

The Role of the Vitamin D Receptor and ERp57 in Photoprotection by 1α,25-Dihydroxyvitamin D3

UV radiation (UVR) is essential for formation of vitamin D(3), which can be hydroxylated locally in the skin to 1α,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)]. Recent studies implicate 1,25-(OH)(2)D(3) in reduction of UVR-induced DNA damage, particularly thymine dimers. There is evidence that photoprotection occurs through the steroid nongenomic pathway for 1,25-(OH)(2)D(3) action. In the current study, we tested the involvement of the classical vitamin D receptor (VDR) and the endoplasmic reticulum stress protein 57 (ERp57), in the mechanisms of photoprotection. The protective effects of 1,25-(OH)(2)D(3) against thymine dimers were abolished in fibroblasts from patients with hereditary vitamin D-resistant rickets that expressed no VDR protein, indicating that the VDR is essential for photoprotection. Photoprotection remained in hereditary vitamin D-resistant rickets fibroblasts expressing a VDR with a defective DNA-binding domain or a mutation in helix H1 of the classical ligand-binding domain, both defects resulting in a failure to mediate genomic responses, implicating nongenomic responses for photoprotection. Ab099, a neutralizing antibody to ERp57, and ERp57 small interfering RNA completely blocked protection against thymine dimers in normal fibroblasts. Co-IP studies showed that the VDR and ERp57 interact in nonnuclear extracts of fibroblasts. 1,25-(OH)(2)D(3) up-regulated expression of the tumor suppressor p53 in normal fibroblasts. This up-regulation of p53, however, was observed in all mutant fibroblasts, including those with no VDR, and with Ab099; therefore, VDR and ERp57 are not essential for p53 regulation. The data implicate the VDR and ERp57 as critical components for actions of 1,25-(OH)(2)D(3) against DNA damage, but the VDR does not require normal DNA binding or classical ligand binding to mediate photoprotection.

Vitamin D and Death by Sunshine

Exposure to sunlight is the major cause of skin cancer. Ultraviolet radiation (UV) from the sun causes damage to DNA by direct absorption and can cause skin cell death. UV also causes production of reactive oxygen species that may interact with DNA to indirectly cause oxidative DNA damage. UV increases accumulation of p53 in skin cells, which upregulates repair genes but promotes death of irreparably damaged cells. A benefit of sunlight is vitamin D, which is formed following exposure of 7-dehydrocholesterol in skin cells to UV. The relatively inert vitamin D is metabolized to various biologically active compounds, including 1,25-dihydroxyvitamin D3. Therapeutic use of vitamin D compounds has proven beneficial in several cancer types, but more recently these compounds have been shown to prevent UV-induced cell death and DNA damage in human skin cells. Here, we discuss the effects of vitamin D compounds in skin cells that have been exposed to UV. Specifically, we examine the various signaling pathways involved in the vitamin D-induced protection of skin cells from UV.

Multiple chromatographic and chemometric methods for quality standardisation of Chinese herbal medicines

Abstract Quality standardisation of complementary medicine is fundamental for industry and practice as it strengthens their quality, safety and efficacy. Current herbal standardisations are often based on the quantitative analysis of a single compound, which may not reflect the total characteristic, bioactive and toxic nature of the herbs or products. Therefore, there is a need to establish internationally recognised methodology for quality standardisation of Chinese herbal medicines. The analytical methods reviewed in this article are pharmacognosy, TLC, HPLC, LCMS, CE and chemometrics. This article covers their developments and applications in quality standardisation. Recent advances show that a combination of these methods can create an overall chemical profile for each herb. This is supported by results reviewed in this article and obtained in our laboratories on medicinal herbs including Hypericum perforatum, Morinda officinalis and Centella asiatica . Significant variations in active ingredients have been observed between herbal samples and products. It is proposed that the identification of active ingredients, pharmacological activities and eventual clinical applications are required for a comprehensive quality standardisation system. The findings of this article indicate that the combination of various chromatographic and chemometric methods could advance the methodology of quality standardisation and enhance the overall confidence in herbal medicine for the health practitioner and the public.

Seasonal variation of triterpenes and phenolic compounds in australian Centella asiatica (L.) Urb

INTRODUCTION Specific triterpenes, phenolic acids and flavonoids in Centella asiatica have been found to be bioactive. Harvesting the plant when these putative bioactive compounds are at their highest concentrations would provide consistency in their chemical profile, thus ensuring the quality and efficacy of derived medicinal products. OBJECTIVE The aim of the study was to determine the impact of harvesting time on the contents of major triterpenoid and phenolic compounds in C. asiatica. METHODOLOGY Australian C. asiatica was collected from a designated area in different months. The principal triterpenes (asiaticoside, madecassoside, asiatic acid and madecassic acid), flavonoid compounds (rutin, quercetin and kaempferol) and chlorogenic acid were quantitatively determined by HPLC-DAD analysis. RESULTS Triterpenoid, kaempferol and chlorogenic acid content showed significant variation (p < 0.05) in different collecting months. The total content of the four triterpenes reached its highest levels in January and February (83.15 ± 0.16 mg/g and 78.41 ± 0.16 mg/g, respectively), the summer season of the southern hemisphere, and their lowest values in winter (June) and spring (October) seasons (35.65 ± 0.20 and 35.50 ± 0.55 mg/g, respectively). Similarly, the contents of chlorogenic acid and kaempferol were the highest in December and January (1.62 ± 0.01 and 0.33 ± 0.01 mg/g, respectively), and the lowest in June (0.06 ± 0.01 and 0.09 ± 0.01 mg/g, respectively). CONCLUSION The results indicate that harvesting C. asiatica in summer returns the highest yield of the target triterpenoids, kaempferol and chlorogenic acid.

Protection from Ultraviolet Damage and Photocarcinogenesis by Vitamin D Compounds

Vitamin D is primarily produced by a photochemical reaction in skin, using the energy of ultraviolet B radiation. Ultraviolet radiation in sunlight is also responsible for several types of DNA damage, immunosuppression and photoaging. A number of adaptive responses are known to occur in skin to increasing UV exposure, including increased pigmentation, increased thickness of the cornified layer of skin and upregulation of DNA repair pathways. In addition to these known responses, there is now sufficient evidence to suggest that the local vitamin D system in skin, which includes local production of the active hormone, 1,25 dihydroxyvitamin D, together with metabolites of over-irradiation products, and vitamin D receptor(s), also provide an adaptive response to UV. The vitamin D system in skin reduces DNA damage, inflammation and photocarcinogenesis. Because vitamin D is made in skin, sun damage is less than it would be otherwise.

Novel vitamin D compounds and skin cancer prevention

As skin cancer is one of the most costly health issues in many countries, particularly in Australia, the possibility that vitamin D compounds might contribute to prevention of this disease is becoming increasingly more attractive to researchers and health communities. In this article, important epidemiologic, mechanistic and experimental data supporting the chemopreventive potential of several vitamin D-related compounds are explored. Evidence of photoprotection by the active hormone, 1α,25dihydroxyvitamin D3, as well as a derivative of an over-irradiation product, lumisterol, a fluorinated analog and bufalin, a potential vitamin D-like compound, are provided. The aim of this article is to understand how vitamin D compounds contribute to UV adaptation and potentially, skin cancer prevention.