Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Biochem Pharmacol ; 225: 116279, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38740221

ABSTRACT

Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects, but the pharmacological targets and mechanisms remain elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced intracellular Ca2+ oscillations, mediated through an inhibition of the muscarinic subtype 3 (M3) receptor. Patch-clamp recordings and confocal Ca2+ imaging were applied to acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca2+ oscillations. Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca2+ oscillations in a concentration-dependent manner, and this inhibition also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl-) channels, and store-operated Ca2+ channels. Together, the results demonstrate that berberine directly inhibits the muscarinic M3 receptors, further confirmed by evidence of the interaction between berberine and M3 receptors in pancreatic acinar cells.


Subject(s)
Acinar Cells , Berberine , Calcium Signaling , Receptor, Muscarinic M3 , Animals , Berberine/pharmacology , Receptor, Muscarinic M3/metabolism , Receptor, Muscarinic M3/antagonists & inhibitors , Mice , Acinar Cells/drug effects , Acinar Cells/metabolism , Calcium Signaling/drug effects , Calcium Signaling/physiology , Pancreas/drug effects , Pancreas/metabolism , Male , Acetylcholine/metabolism , Calcium/metabolism , Dose-Response Relationship, Drug
2.
Acta Pharmacol Sin ; 42(9): 1507-1515, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33311599

ABSTRACT

Astroglioma is the most common primary tumor in the central nervous system without effective treatment strategies. Temozolomide (TMZ) is a chemotherapeutic drug to treat astroglioma but exhibits low potency and has side effects. Therefore, there is an urgent need to develop new compounds to treat astroglioma. Dalbergia sissoo Roxb was the source of Dalbergia odorifera in traditional Chinese medicine (TCM) and has been clinically used as an anti-tumor medicine. 4-Methoxydalbergione (4MOD) is purified from Dalbergia sissoo Roxb., and shows an inhibitory effect on osteosarcoma, but its effects on astroglioma have not been reported. Here, we evaluate its anti-astroglioma effects on both in vitro and in vivo models. In cultured astroglioma U87 cells, 4MOD inhibited cell proliferation and induced cell apoptosis in a time- and concentration-dependent manner. Compared with TMZ, 4MOD exhibited a tenfold greater potency of anti-astroglioma effects. 4MOD effectively stalled the cell cycle in G2 phase. Transcriptome sequencing (RNA-seq) showed that 4MOD upregulated 158 genes and downregulated 204 genes that are mainly enriched in cell membrane, cell division, cell cycle, p53, TNF, and MAPK signaling pathways, which may underlie its anti-tumor mechanisms. In a nude mouse xenograft model transplanted with U87 cells, 10 mg/kg 4MOD slowed down tumor growth rate, while at 30 mg/kg dose, it reduced tumor size. Collectively, this study demonstrates that 4MOD is a potent native compound that remarkably inhibits U87 astroglioma growth in both in vitro and in vivo models.


Subject(s)
Astrocytoma/drug therapy , Astrocytoma/metabolism , Benzoquinones/pharmacology , Animals , Apoptosis/drug effects , Astrocytoma/genetics , Astrocytoma/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Dalbergia , Drug Resistance, Neoplasm/drug effects , Gene Expression , Heterografts , Humans , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude
SELECTION OF CITATIONS
SEARCH DETAIL
...