Synthesis and Physiological Activity of Novel Berberine Derivatives / 中国实验方剂学杂志

Objective: TO synthesize novel berberine derivatives with a variety of physiological activities,and study their antitumor activity and acetylcholinesterase inhibitory activity. Method: Berberines with a variety of physiological activities were pieced together isohydroxamic acid,o-phenylenediamine,and sulfhydryl pharmacophore with effects in inhibiting histones and removing acetylases. Totally 7 novel berberine derivatives were obtained by means of organic synthesis. The structures of these derivatives were characterized and confirmed by 1H-NMR,13 C-NMR and MS spectral data.Thiazolyl blue tetrazolium bromide(MTT) method was used in the determination of the cytotoxic activity of HCT116,HepG2,HeLa and CCRF-CEM human cancer cell lines in vitro. Ellman method was used to reveal the inhibitory activities of acetylcholinesterase and butyrylcholinesterase. Result: The results showed that the berberine derivatives containing methyl ketone had good antitumor and acetylcholinesterase inhibitory activities. The results demonstrated that compound 5b had the highest anti-proliferative activity against CCRF-CEM cell line and the acetylcholinesterase inhibitory activities, with IC50=1.48 μmol · L-1 and IC50=0.38 μmol · L-1,respectivly. Conclusion: This paper provides a reference for the synthesis and biological evaluation of this kind of alkaloid derivatives. Compound 5b is a promising candidate drug and worth further study.

Regulation of BuShen ZhuYun Decotion on gonadotropin in rat pituitary cells / 医学研究生学报

Objective The mechanism of luteal phase defect remains unclear. To investigate the mechanism of BuShen ZhuYun Decoction on the gonadotropin secretion in the pituitary gland, we observed the effects of medicated serum of BuShen ZhuYun Decotion on the secretion of gonadotropin-follicle-stimulating hormone (FSH) and luteotropic hormone (LH) in rat pituitary cells.Methods The BuShen ZhuYun Decotion was administered to the female SD rats by gavage to prepare the serum containing BuShen ZhuYun Decoction. The CCK-8 method was used to detect the effect of cetrorelix acetate powder for injection, medicated serum and gonadotropin releasing hormone (GnRH) on cell activity. In the maximum non-toxic concentration, we used cetrorelix acetate powder for injection to block the GnRH receptor (GnRHR) in pituitary cells and established the GnRHR antagonistic model. Then we treat the model group with medicated serum (model group). Moreover, we established the blank group (normal pituitary cells), the cetrorelix group (intervented with cetrorelix for 6 hours), and medicated serum group (intervented with medicated serum for 24 hours). 20nmol/L GnRH was used to stimulate cells for 6h. The contents of FSH and LH in the supernatant of each group and the mRNA expression of FSHβ, LHβ and GnRHR were detected.Results Compared with that of the blank group, the supernatant levels of FSH and LH in the Cetrorelix group decreased significantly \[(3.91±0.36) mIU/mL vs (2.26±0.22) mIU/mL, (8.94±0.57) mIU/mL vs (3.35±0.59) mIU/mL, P<0.05)\]. In contrast, the levels of LH significantly increased \[(8.94±0.57) mIU/mL vs (10.79±0.60) mIU/mL, P<0.05)\]; Compared with the cetrorelix group, the levels of FSH and LH in both medicated serum group and model group increased significantly (P<0.05). Compared with the blank group, the mRNA level of FSH and LH in the cetrorelix group decreased significantly \[(0.95±0.23) mIU/mL vs (0.58±0.12) mIU/mL, (0.98±0.14) mIU/mL vs (0.27±0.21) mIU/mL, P<0.01) \], and the mRNA expression of GnRHR increased in the cetrorelix group \[(0.97±0.13) mIU/mL vs (1.77±0.26) mIU/mL, P<0.01) \]; The mRNA levels of FSH and LH in the medicated serum group were increased (P<0.05). Compared with the cetrorelix group, the mRNA expression of FSHβ mRNA and LHβ were both increased in the medicated serum group and model group (P<0.05), the mRNA expression of GnRHR decreased (P<0.01).Conclusion It is suggested that the therapeutic mechanism of BuShen ZhuYun Decotion may be related to the improvement of GnRH receptor expression.

Synthesis and in vitro glucose-lowering effect of 8-alkyl-coptisine / 中草药

Objective: To investigate the effect of 8-alkyl-coptisine on glycometabolism in vitro. Methods: HepG2 cells similar to human hepatic cells were used to test the glucose consumption (GC) in cultural solution in 24 h and MTT assay was used to monitor the proliferation of HepG2 cells. Results: The results indicated that 8-alkyl-coptisine could increase the amounts of GC of HepG2 cells. In glucose concentration (10 mmol/L), 8-hexyl-coptisine was the most significant. 8-Alkyl-coptisine had notable inhibition in proliferation of HepG2 cells. Conclusion: 8-Alkyl-coptisine was successfully synthesized. GC could increase as the length of the aliphatic chain increases firstly and the GC could decrease when the length of the aliphatic chain exceeds six atoms. 8-Hexyl-coptisine is a potential hypoglycemic leading compound.

Analysis of the main components of coptis-evodia herb couple by HPLC-DAD-MS / 药学学报

A comprehensive HPLC-DAD-MS method was developed to study the chemical components of semi-bionic extract of Coptis-Evodia herb couple. The extract was isolated on a Hypersil BDS C18 column (4.6 mm x 200 mm, 5 microm) using acetonitrile-ammonium formic buffer as mobile phase by gradient elution. Detection was performed on DAD and MS equipped with an electrospray ionization (ESI) source by full scan and product full scan on positive mode. The chromatogram of Coptis-Evodia showed seventeen main peaks, eight of which were from Evodia while the others were from Coptis. By comparison of the retention time, the on-line UV spectra and MS spectra, four peaks were identified as jatrorrhizine, hydroxevodiamine, palmatine and berberine, and three peaks were deduced as epiberberine, columbamine and coptisine. In addition, berberine and palmatine were quantitatively determined. No new component was created in the semi-bionic extract of the herb couple, yet the solubilities of berberine and palmatine decreased.

Multidrug-resistant Clinical Enterobacter cloacae Isolates: Analysis of Their ESBLs Gene Types and Molecular Epidemiology / 中华医院感染学杂志

OBJECTIVE To understand the distribution and epidemiology of ESBLs in ceftazidime or cefotaxime-(resistant) clinical Enterobacter cloacae isolates.METHODS Twenty seven ceftazidime or cefotaxime-resistant(nonrepetitive) E.cloacae were collected from 27 patients hospitalized at the Huashan Hospital,Shanghai.PCR and(sequencing) were performed to understand the distribution of ESBLs in E.cloacae;rep-PCR was(performed) to(understand) the epidemiology of ESBLs in E.cloacae.RESULTS CTX-M-3 like(ESBLs) were the most prevalent in our study(48%);this was the first report of VEB-1-like ESBLs in the member of(Enterobacteriaceae) in China,and the first report of the ESBLs VEB-1-like and CTX-M-3-like in an isolate simultaneously;the majority of(ESBLs) producers exhibited the same rep-PCR pattern,but harbored different ESBLs gene.(CONCLUSIONS) In our study,ESBLs have become prevalent in clinical E.cloacae isolates,and become an important factor of E.cloacae isolates resistant to extended-spectrum beta(-lactams).