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153. Pharmacokinetics of the novel 5-HT4 receptor agonist, DA-6886, in dogs.

Author

Lee, Dae Young and Kang, Hee Eun

Subjects
*BEAGLE (Dog breed), *ORAL drug administration, *FEMALE dogs, *SEROTONIN receptors, *IRRITABLE colon, *DOGS
Abstract

The pharmacokinetics of a new 5-hydroxytryptamine receptor 4 agonist, DA-6886, intended for the treatment of constipation-predominant irritable bowel syndrome, were evaluated in beagle dogs following both intravenous and oral administration of DA-6886 (1–10 mg/kg). The study also examined the effects of gender and food on the pharmacokinetics of DA-6886 in dogs. DA-6886 demonstrated dose-proportional area under the plasma concentration–time curve (AUC) values and dose-independent clearance (21.0–24.6 mL/min/kg) after administration via both routes. The steady-state volume of distribution (Vss) for DA-6886 was dose-independent and relatively large (6.76–8.57 L/kg), aligning with its observed high distribution in rat tissues. No significant differences were observed in the pharmacokinetics of DA-6886 between male and female dogs. Post oral administration, extent of absolute oral bioavailability (BA) was relatively high (48.2–96.1%) in contrast to the rates observed in rats (18.9–55.0%). Dogs that were fed exhibited a significantly lower Cmax and a delayed Tmax in comparison to those that were fasted. However, the AUC values were similar between the two groups. The extended stomach transit time in the fed state may account for this delayed absorption of DA-6886 without substantial changes in AUC. [ABSTRACT FROM AUTHOR]

Published
2023
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166. SH‐PRO extract alleviates benign prostatic hyperplasia via ROS‐mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo.

Author

Park, Ji Eon, Shin, Woo‐Cheol, Lee, Hyo‐Jung, Yoon, Dahye, Sim, Deok Yong, Ahn, Chi‐Hoon, Park, Su‐Yeon, Shim, Bum Sang, Park, So Jung, Kim, Kyung Seok, Park, Geum Duck, Kim, Sung‐Hoon, and Lee, Dae Young

Abstract

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH‐PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH‐1 cells and rats with testosterone‐induced BPH. Herein, SH‐PRO significantly reduced the viability of BPH‐1 cells and dihydrotestosterone (DHT)‐treated RWPE‐1 cells. Also, SH‐PRO increased the sub‐G1 population in BPH‐1 cells and consistently attenuated the expression of pro‐PARP, pro‐caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate‐specific antigen (PSA) in BPH‐1 cells and DHT‐treated RWPE‐1 cells. Of note, SH‐PRO generated reactive oxygen species (ROS) in BPH‐1 cells, while ROS inhibitor N‐acetyl‐l‐cysteine (NAC) disturbed the ability of SH‐PRO to reduce the expression of pro‐PARP, FOXO3a, catalase, SOD, and increase sub‐G1 population in BPH‐1 cells. Furthermore, oral treatment of SH‐PRO significantly abrogated the weight of the prostate in testosterone‐treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH‐PRO via ROS‐mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti‐BPH candidate. [ABSTRACT FROM AUTHOR]

Published
2023
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177. Aurones and Flavonols from Coreopsis lanceolata L. Flowers and Their Anti-Oxidant, Pro-Inflammatory Inhibition Effects, and Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish

Author

Kim, Hyoung-Geun, primary, Nam, Youn Hee, additional, Jung, Young Sung, additional, Oh, Seon Min, additional, Nguyen, Trong Nguyen, additional, Lee, Min-Ho, additional, Kim, Dae-Ok, additional, Kang, Tong Ho, additional, Lee, Dae Young, additional, and Baek, Nam-In, additional

Published
2021
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182. Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Author

Jung, Su-Jin, primary, Oh, Mi-Ra, additional, Lee, Dae Young, additional, Lee, Young-Seob, additional, Kim, Geum-Soog, additional, Park, Soo-Hyun, additional, Han, Soog-Kyoung, additional, Kim, Young-Ock, additional, Yoon, Sun-Jung, additional, and Chae, Soo-Wan, additional

Published
2021
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