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以本產芸香為基礎的天然物組合來同時緩解抗藥性細菌及禽類冠狀病毒

Combination of Natural Ingredients Based on Indigenous rue Simultaneously Alleviates Antimicrobial Resistant (AMR) Bacteria and Avian Coronavirus

摘要


抗微生物製劑的抗藥性問題,一直都是公共衛生上被關注的議題,甚至於COVID-19(Coronavirus Disease-2019)疫情爆發更是如此。面對抗藥性問題,可從藥物開發以提供解方。本研究從本土芸香預防保健的豐富性來擴展實際應用,以指標成分肉桂芸香鹼(harmine)為基礎,搭配卵轉鐵蛋白(ovotransferrin,OTRF)作為加成劑,測試其複方的抗微生物活性。除收集臨床抗藥性菌株進行複方抑菌測試外,復以有禽類冠狀病毒(Avian coronavirus, AvCoV)之稱的傳染性支氣管炎病毒(infectious bronchitis virus, IBV)作為標的,觀測其改善病毒感染後胚蛋病變及存活情形。本研究使用傳染性支氣管炎病毒減毒疫苗IB 4-91作為起始病毒株,接種於胚蛋二輪後收集尿囊(allantoic)液以取得活化病毒。本產芸香萃取之肉桂芸香鹼在搭配卵轉鐵蛋白之下,對呼吸道分離的臨床菌株,不論是對格蘭氏陰性或是陽性菌皆具協同性的抑菌活性。對於病毒而言,活化後的傳染性支氣管炎病毒,較原始疫苗病毒株有更強之感染性與毒性,縮短了胚胎死亡時間;以複方處理後,可減少雞胚的病毒異常毒化情形,並且將存活率由33%提升至66~100%。以本產芸香萃取出的肉桂芸香鹼為主體,搭配卵轉鐵蛋白設計成複方,不僅具協同性作用,可抑制抗藥性臨床菌株,同時亦可抑制傳染性支氣管病毒,此廣效之抗微生物的效果,具有開發成外用消毒或治療藥物的潛力。

並列摘要


The problem of drug resistance arising from the use of antimicrobial agents has long been a public health issue and concern, especially in the era of the current outbreak of COVID-19 (Coronavirus Disease-2019), are obvious and profound. Faced the challenge of antimicrobial resistance (AMR) head-on, new drug development may provide reasonable solutions. The success of our previous works suggested that the indigenous rue may further provide the tool to conquer pathogen-bone diseases. This study was performed based on the combination of the index component - harmine, of the indigenous rue, together with ovotransferrin (OTRF) as an additive; to evaluate the antimicrobial activity. In addition to use clinical AMR strains for antibacterial testing, the infectious bronchitis virus (IBV), also known as avian coronavirus (AvCoV), was used to test the same combination for possible improvement of embryonic viral infection. Firstly, we used the attenuated vaccine strain IB 4-91 as the starting inoculated virus, and subsequently collected the allantoic fluid to obtain the activated virus. The harmine preparation extracted from the indigenous rue, when combined with ovotransferrin, had a synergistic antibacterial activity against clinical AMR bacteria isolated from the respiratory tract, irrespective the Gram stain patterns. Furthermore, the activated AvCoV had enhanced infectivity and toxicity in chicken embryos, and consequently shortens the lifespan of embryos. However, the harmine / ovotransferrin increased the survival rate from 33% to 66~100%. The harmine preparation extracted from the rue, compounded with ovotransferrin, demonstrated not only a synergistic effect, but also simultaneously alleviates AMR bacteria and AvCoV. Thus such an effect may have a potential to be further developed into a topical disinfectant or therapeutic drugs.

並列關鍵字

Indigenous rue harmine antimicrobial

參考文獻


Ramakrishnan S, Kappala D. 2019. Avian Infectious Bronchitis Virus, p 301-319. In Malik YS, Singh RK, Yadav MP (ed), Recent Advances in Animal Virology doi:10.1007/978-981-13-9073-9_16. Springer Singapore, Singapore.
Anonymous. 2022. COVID-19: U.S. Impact on Antimicrobial Resistance, Special Report 2022. https://dx.doi.org/10.15620/cdc:117915, Hyattsville, MD.
Wu J, Acero-Lopez A. 2012. Ovotransferrin: Structure, bioactivities, and preparation. Food Research International 46:480-487.
Giansanti F, Rossi P, Massucci MT, Botti D, Antonini G, Valenti P, Seganti L. 2002. Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin. Biochem Cell Biol 80:125-30.
Giansanti F, Massucci MT, Giardi MF, Nozza F, Pulsinelli E, Nicolini C, Botti D, Antonini G. 2005. Antiviral activity of ovotransferrin derived peptides. Biochem Biophys Res Commun 331:69-73.

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