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大黄素甲醚,一种抗鹦鹉热衣原体感染的新型蒽醌衍生物。

Physcion, a novel anthraquinone derivative against Chlamydia psittaci infection.

作者信息

Liu Xinyi, Hu Huilong, Liu Jiaqi, Chen Jiaqi, Chu Jun, Cheng He

机构信息

National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Animal Science and Technology College, Beijing University of Agriculture, Beijing, China.

出版信息

Vet Microbiol. 2023 Apr;279:109664. doi: 10.1016/j.vetmic.2023.109664. Epub 2023 Jan 24.

Abstract

Physcion, a natural anthraquinone derivative, has been reported to exert remarkable antibacterial activities against Staphylococcus aureus,Staphylococcus epidermidis and Pseudomonas aeruginosa. However, it is not fully illustrated as anti-Chlamydia substance. In the present study, minimum inhibitory concentration(MIC)values for physcion against Chlamydia psittaci(C.psittaci) 6BC, C.psittaci SBL and C.psittaci HJ were 128 μg/mL,256 μg/mL and 128 μg/mL while minimum bactericidal concentration (MBC) values were 256 μg/mL,512 μg/mL and 256 μg/mL,respectively. Moreover, Chlamydial adhesion to Hela 229 cells was blocked in a dose-dependent manner and RB-to-EB differentiation was inhibited by physcion from 28 to 48 hpi.Post treatment,upregulation of LC3-II was in a dose-dependent manner, indicating physcion activated autophagy and bacterial clearance.To validate clinical efficacy,49 SPF chickens aged 21days were divided into 5 groups and infected intra-laryngeally with 0.2 mL of 1 × 10 IFU/mL C.psittaci 6 BCE.Three days later, birds received orally with serial doses of physcion (4 mg/kg to 9 mg/kg), or 3 mg/kg of doxycycline for 6 days.Chickens with difficulty in breathing were alleviated significantly with increasing concentrations of physicon.Postmortem,lesions of air sacs were reduced significantly in a dose-dependent manner.More importantly,birds with 9 mg/kg of physcion could alleviate lesions of air sacs and lungs, and reduce bacterial loads in spleens, which was comparable to doxycycline treatment. Based on above evidences, physcion is a promising cost-effective natural drug by blocking Chlamydial adhesions to host cells, RB-to-EB differentiation and activating bacterial autophagy and it will be a good alternative to doxycycline combating virulent C.psittaci infection, contributing to eradication of Chlamydial transmission from animals to human beings.

摘要

大黄素甲醚是一种天然蒽醌衍生物,据报道对金黄色葡萄球菌、表皮葡萄球菌和铜绿假单胞菌具有显著的抗菌活性。然而,它作为抗衣原体物质的作用尚未得到充分阐明。在本研究中,大黄素甲醚对鹦鹉热衣原体(C.psittaci)6BC、鹦鹉热衣原体SBL和鹦鹉热衣原体HJ的最低抑菌浓度(MIC)值分别为128μg/mL、256μg/mL和128μg/mL,而最低杀菌浓度(MBC)值分别为256μg/mL、512μg/mL和256μg/mL。此外,大黄素甲醚以剂量依赖的方式阻断衣原体对Hela 229细胞的粘附,并在感染后28至48小时抑制RB向EB的分化。处理后,LC3-II的上调呈剂量依赖性,表明大黄素甲醚激活了自噬并促进了细菌清除。为验证临床疗效,将49只21日龄的SPF鸡分为5组,经喉内接种0.2 mL 1×10⁷ IFU/mL的鹦鹉热衣原体6BCE。三天后,给鸡口服不同剂量的大黄素甲醚(4mg/kg至9mg/kg)或3mg/kg的强力霉素,持续6天。随着大黄素甲醚浓度增加,呼吸困难的鸡得到显著缓解。剖检后,气囊病变以剂量依赖的方式显著减少。更重要的是,9mg/kg大黄素甲醚组的鸡能够减轻气囊和肺部病变,并降低脾脏中的细菌载量,这与强力霉素治疗相当。基于以上证据,大黄素甲醚通过阻断衣原体对宿主细胞的粘附、RB向EB的分化以及激活细菌自噬,是一种有前景的经济有效的天然药物,它将是强力霉素对抗毒力强的鹦鹉热衣原体感染的良好替代品,有助于根除衣原体从动物到人类的传播。

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