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OBJECTIVE：To struc turally modify shikimic acid ，and to investigate the reversal effects of its derivatives on paclitaxel-resistant human breast cancer cells MCF- 7/PTX. METHODS ：Using shikimic acid as the lead structure ，1-position carboxyl group was structurally modified to synthesize a series of shikimic acid derivatives through esterification ，amidation， hydrogenation and reduction ，etc. Using non-drug resistant cells MCF- 7 as reference ，MTT assay was used to screen derivatives with inhibitory activity as well as half-inhibitory concentration （IC50）and reversal index （RI）of derivatives to MCF- 7/PTX. With the drug resistance-related transgelin 2 as the target ，the molecular docking of the active derivatives with the drug resistance-related protein was carried out by using Glide 1.0 computer-aided design software. RESULTS ：Totally 15 derivatives were obtained （T1-T15）， of which T 4-T15 were obtained for the first time. MTT assay showed that （3R， 4S， 5R） -N-benzyl-3， 4， 5-trihydroxy-1-cyclohexene-1-formamide（T7），（3R，4S，5R）-N-（3，4，5-trihydroxy-1-cyclohexenylmethyl）-benzylamine（T14）， （3R，4S，5R）-3，4-O-isopropyl-5-O-acetyl-1-cyclohexene-1-methyl formate （T15）inhibited MCF- 7 and MCF- 7/PTX cells to a certain extent ；IC50 values of T 7，T14 and T 15 combined with pacliaxel to MCF- 7/PTX cells were significantly lower than that in negative control （Paclitaxel alone ）group（P＜0.05）. RIs of T 14 and T 15 were higher ，and RIs of the highest dose were 8.8 and 9.3， which were equivalent to positive control verapamil （10.8）. Th e results of molecular docking showed that the hydroxyl groups at positions 3，4 of T 7 could form multiple hydrogen bonds with ； Arg625 and Asp 627 in the catalytic region of transgelin 2. In addition to the hydrogen bond mentioned above at T 7，the mail：batistuta28@126.com secondary amine side chain at position 1 of T 14 could also form hydrogen bond with Glu 657 of transgelin 2. When the hydroxyl group on the T 15 mother nucleus was derived from the donor group ，the binding of the hydroxyl group to transgelin 2 was closer and the inhibition was enhanced. CONCLUSIONS ： The derivatives T 7，T14 and T 15 have certain reverse activity to paclitaxel-resistant human breast cancer cells. The polyhydroxy structure of the mother nucleus is the main structural region of the hydrogen bond between shikimic acid and its derivatives and transgelin 2. The derivation of its power supply group or the introduction of secondary amines and hydrophobic groups into the 1-carboxyl group of shikimic acid is benifit for enhancing the drug resistance reversal effect of derivative .
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Objective To analyze the clinical utility of TCM decoction pieces for reinforcing deficiency in the First Affiliated Hospital of Xi'an Jiaotong University (hereinafter referred to as our hospital).Methods By using Microsoft Office Excel 2013 software, use frequency, classifications of pharmacological actions and doses of the TCM decoction pieces for reinforcing deficiency from 2013 to 2015 were analyzed.Results From 2013 to 2015, some TCM decoction pieces for reinforcing deficiency showed relatively high use frequency in our hospital (>30%). In top 15 TCM decoction pieces for reinforcing deficiency, the amounts of medicine for tonifying qi were more than 40%, whose average doses exceeded the upper limit of pharmacopoeia dosage reaching 30%. The total over-use rate of TCM decoction pieces for reinforcing deficiency>50% and the not exceeded part accounted for 36.0%.Conclusion It is suggested that the use of TCM decoction pieces should be careful differentiation of symptoms, and the dose should also meet the specifications.
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Objective To understand the clinic usage of TCM decoction pieces in the First Affiliated Hospital of Xi’an Jiaotong University (hereinafter referred to as our hospital).Methods By using Microsoft Office Excel software, the medicine doses, classification of functions and clinic application of the TCM decoction pieces, which were among the top 50 most frequently used TCM decoction pieces were analyzed.Results In 2014, 60% of the top 50 most frequently used TCM decoction pieces in our hospital exceed the medicine dosage inChinese Pharmacopoeia. According to the functions, the top 3 TCM decoction pieces were medicine for reinforcing deficiency, clearing heat and promoting qi, respectively. Medicine for reinforcing deficiency was mainly used in gastroenteropathy, menopathy and nephropathy. Medicine for clearing heat was mainly used in gastroenteropathy, menopathy and infection of the upper respiratory tract. Medicine for promoting qi was mainly used in gastroenteropathy, tumor and disease of cardiovascular system.Conclusion TCM decoction pieces in our hospital exceed the medicine dosage in Chinese Pharmacopoeia, which requires attention. The top 3 TCM decoction pieces are respectively medicine for reinforcing deficiency, clearing heat and promoting qi, whose clinic applications are basically rational.
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<p><b>OBJECTIVE</b>To study the processing principles of different processed products of Aconitum pendulum.</p><p><b>METHOD</b>Using high performance liquid chromatography and acute toxicity test to compare the changes in chemical composition and toxicity of the roots and processed products of A. pendulum.</p><p><b>RESULT</b>The main toxic components of the roots of A. pendulum were aconitine, deoxyaconitine and 3-acetylaconitine. The contents of these three alkaloids were significantly reduced in processed products, while benzoylaconitine significantly increased. In addition, processed products emerged aconine, polyschistine-D, beyzoyldeoxyaconine, 16-epi-pyroaconitine and 16-epi-pyrodeoxyaconitine. From the structural analysis, these new emerged compounds transformed from the aconitine, deoxyaconitine and 3-acetylaconitine.</p><p><b>CONCLUSION</b>Different processing methods can reduce the toxicity of the roots of A. pendulum. Processing principle is ester hydrolysis and high-temperature pyrolysis.</p>