[Consideration about chemistry, manufacture and control (CMC) key problems in simplified registration of classical traditional Chinese medicine excellent prescriptions].

As an outstanding representative of traditional Chinese medicine(TCM) prescriptions accumulated from famous TCM doctors' clinical experiences in past dynasties, classical TCM excellent prescriptions (cTCMeP) are the most valuable part of TCM system. To support the research and development of cTCMeP, a series of regulations and measures were issued to encourage its simplified registration. There is still a long-way to go because many key problems and puzzles about technology, registration and administration in cTCMeP R&D process are not resolved. Based on the analysis of registration and management regulations of botanical drug products in FDA of USA and Japan, and EMA of Europe, the possible key problems and countermeasures in chemistry, manufacture and control (CMC) of simplified registration of cTCMeP were analyzed on the consideration of its actual situation. The method of "reference decoction extract by traditional prescription" (RDETP) was firstly proposed as standard to evaluate the quality and preparation uniformity between the new developing product under simplified registration and traditional original usages of cTCMeP, instead of Standard Decoction method in Japan. "Totality of the evidence" approach, mass balance and bioassay/biological assay of cTCMeP were emphatically suggested to introduce to the quality uniformity evaluation system in the raw drug material, drug substance and final product between the modern product and traditional decoction.

B-cell lymphoma-2 over-expression protects δ-elemene-induced apoptosis in human lung carcinoma mucoepidermoid cells via a nuclear factor kappa B-related pathway.

δ-Elemene, an antitumor component, is a chemical compound isolated from Curcuma wenyujin, a Chinese traditional herb. We examined whether δ-elemene could affect apoptosis in human lung carcinoma mucoepidermoid NCI-H292 cells, and test whether and how the over-expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma extra large (Bcl-xL) could off-set the effect of δ-elemene on cell growth. The result demonstrated that δ-elemene significantly induced apoptosis of NCI-H292, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, DNA fragmentation measurement, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. Treatment of NCI-H292 with δ-elemene increased both p38 mitogen-activated protein kinase (MAPK) and inducible nitric oxide synthese (iNOS) levels, suggesting these two molecules maybe relate to the apoptotic effect of δ-elemene. The cells with Bcl-2 or Bcl-xL over-expression showed an elevation of nuclear factor kappa B (NF-kappa B) activity, accompanying a significant reduction of δ-elemene-induced apoptosis. Furthermore, inhibition of NF-kappa B by IkBαSR, which is a powerful inhibitor of NF-kappa B, restored the ability of δ-elemene to induce apoptosis in the cells transfected with Bcl-2. These data strongly indicated that the apoptotic effect of δ-elemene on NCI-H292 was closely associated with the activity of NF-kappa B, which was up-regulated by Bcl-2 and Bcl-xL. In conclusion, δ-elemene induced apoptosis in NCI-H292 cells. The apoptotic effect of δ-elemene could be significantly offset by over-expression of either Bcl-2 or Bcl-xL. Bcl-2 and Bcl-xL were able to increase the activity of NF-kappa B, which was a known anti-apoptotic molecule in human lung cancer cells.