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Puerarin is the main isoflavone found in Pueraria lobata (Willd) Ohwi, which has been used in therapy for various cardiovascular diseases. The present study examined the effects of puerarin on the large-conductance voltage-and Ca 2ϩ -activated potassium (BK Ca ) channel and on rat thoracic aortas. BK Ca channels encoded with either ␣ (BK-␣) or ␣/␤ subunits (BK-␣ϩ␤1) were heterologously expressed in Xenopus oocytes or human embryonic kidney 293 cells. The activities of BK Ca channels were measured using excised patch-clamp recordings. Puerarin activated BK-␣ϩ␤1 currents with a half-maximal concentration (EC 50 ) of 0.8 nM and a Hill coefficient of 1.11 at 10 M Ca 2ϩ and with an EC 50 of 12.6 nM and a Hill coefficient of 1.08 at 0 M Ca 2ϩ . Puerarin (1 nM) induced a 16-mV leftward shift in the conductance-voltage curve for BK-␣ϩ␤1 currents at 10 M Ca 2ϩ and at 100 nM induced a 26-mV leftward shift at 0 M Ca 2ϩ . Puerarin mainly increased the BK-␣ϩ␤1 channel open probability without changing the unitary conductance. Activation was also detected in the absence of the ␤1 subunit. A deglycosylated analog of puerarin, daidzein, also activated BK Ca channels with weaker potency. In addition, puerarin (0.1 to 1000 M) caused concentration-dependent relaxations of rat thoracic aortic rings contracted with 1 M noradrenaline bitartrate (EC 50 ϭ 1.1 M). These were significantly inhibited by 50 nM iberiotoxin, a specific blocker of BK Ca channels. This is the first study demonstrating that puerarin activates BK Ca channels, especially BK-␣ϩ␤1 channels. The activation of the BK Ca channel probably contributes to the puerarin-mediated vasodilation action.

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Background Postmenopausal osteoporosis, a common disease among elderly women, is linked to estrogen deficiency, mechanical loading, and genotype. Circular RNAs (circRNAs) are formed through reverse splicing of the splice donor at the 3′ end and the splice accepter at the 5′ end in pre-mRNA and have been shown to be involved in the development of multiple diseases. Based on their high sequence conservation and stability, circRNAs may be useful biomarkers in different diseases. However, the roles of circRNAs in postmenopausal osteoporosis remain incompletely understood. Material/Methods Fifty-three postmenopausal women were assigned to either the postmenopausal osteoporosis group (n=28) or the control group (n=25). Reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the differential expression of circRNAs between the 2 groups. Receiver-operating characteristic (ROC) curve analysis was conducted to evaluate the clinical diagnostic value of circRNA. Prediction of the binding sites between circRNA and miRNAs was conducted using miRanda and RNAhybrid. The function of the circRNA in osteoclastogenesis was determined by circRNA overexpression followed by tartrate-resistant acid phosphatase staining and RT-qPCR analysis. Results Among 4 circRNAs previously identified by RNA-sequencing analysis as differentially expressed in patients with postmenopausal osteoporosis, only hsa_circ_0021739 showed a significant difference in expression between the groups and was downregulated in patients with postmenopausal osteoporosis. The hsa_circ_0021739 expression level was determined to be correlated with the lumbar vertebra, femur, and forearm T-scores. Overexpression of hsa_circ_0021739 decreased the level of hsa-miR-502-5p and inhibited the differentiation of osteoclasts. Conclusions The circRNA hsa_circ_0021739 is a potential blood biomarker for postmenopausal osteoporosis. In addition, hsa-miR-502-5p is a likely target of hsa_circ_0021739, which acts to regulate the differentiation of osteoclasts.