Novel berberine derivatives as p300 histone acetyltransferase inhibitors in combination treatment for breast cancer.

Adenoviral E1A binding protein p300 (EP300 or p300) and its similar paralog, cyclic-AMP response element binding protein (CBP), are important histone acetyltransferases (HAT) and transcriptional co-activators in epigenetics, participating in numerous cellular pathways including proliferation, differentiation and apoptosis. The overexpression or dysregulation of p300/CBP is closely related to oncology-relevant disease. The inhibition of p300 HAT has been found to be a potential drug target. Berberine has been reported to show anticancer activity and synergistic effect in combination with some of the clinical anticancer drugs via modulation of various pathways. Here, the present study sought to discover more chemotypes of berberine derivatives as p300 HAT inhibitors and to examine the combination of these novel analogues with doxorubicin for the treatment of breast cancer. A series of novel berberine derivatives with modifications of A/B/D rings of berberine have been designed, synthesized and screened. Compound 7b was found to exhibit inhibitory potency against p300 HAT with IC50 values of 1.51 µM. Western blotting proved that 7b decreased H3K27Ac and interfered with the expression of oncology-relevant protein in MCF-7 cells. Further bioactive evaluation showed that combination of compound 7b with doxorubicin could significantly inhibit tumor growth and invasion in vitro and in vivo.

Danshen-Honghua Ameliorates Stress-Induced Menopausal Depression in Rats.

Objective: Previously, we have shown that Danshen-Honghua (DSHH) for cognitive deficits after ischemia induced impairments of the hippocampus. Here, we investigate the effects of DSHH on stress-induced depression in menopausal rats. Methods: A rat model with menopausal depression was established with bilateral ovariectomies in female SD rats followed by chronic mild stress treatment for 21 days. 40 rats were randomly divided into the sham surgery group (sham surgery and no stress treatment), surgery group (surgery with no stress treatment), surgery/stress group (surgery and stress treatment), fluoxetine group (2.4 mg·kg-1, with surgery and stress treatment), and DSHH group (35 g·kg-1, with surgery and stress treatment). The rats in the last two groups were treated with stresses together with intragastric drug administration for three weeks after the surgery. Then open-field locomotor scores and sucrose intake were tested for behavior changes. Also, the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and cortisone were determined by high-performance liquid chromatography (HPLC). Serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined by radioimmunoassay. Results: The results of open-field locomotor scores, sucrose intake in both the fluoxetine group and DSHH group, were significantly higher than those of the surgery/stress group (P < 0.01). Serum LH, FSH, and cortisone levels in both the DSHH group and fluoxetine group were significantly lower than those in the surgery/stress group (P < 0.01). Serum E2 levels in these groups were slightly increased in these medicine groups (P < 0.01). The monoamine levels in the DSHH group were much higher than those in the surgery/stress group (P < 0.01). Conclusion: DSHH can ameliorate stress-induced depressed syndromes in the surgery/stressed rats via regulating LH and FSH levels as well as monoamine levels.

[Innovative application of Yingxiang (LI 20) and Neiyingxiang (EX-HN 9) in acupuncture verses].

The ancient discussion and modern clinical application regarding Yingxiang (LI 20) and Neiyingxiang (EX-HN 9) in acupuncture verses are explored. Acupuncture verses are the summary of clinical experiences of acupuncture scholars in the past dynasties, of which the records on application of Yingxiang (LI 20) and Neiyingxiang (EX-HN 9) mainly focused on nasal, facial and head-eye diseases, which is characterized with overall summarization, brilliant exposition, simple language, and distinctive characteristics. Nowadays, based on the ancient usage, the clinical application about these two acupoints is continuously developing. If the ancient acupuncture verses could be understood thoroughly, the clinical practice could be better guided and its effects could be improved.