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白毛藤碱是乌头属植物白毛藤的一种生物活性化合物，具有很强的抗登革热活性。

Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity.

机构信息

Translational Health, Molecular Medicine Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

Division of Virus Research and Therapeutics, CSIR-Central Drug Research Institute, Lucknow, India.

出版信息

Sci Rep. 2023 Jan 19;13(1):1026. doi: 10.1038/s41598-023-27927-3.

DOI:10.1038/s41598-023-27927-3
PMID:36658277
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9852271/
Abstract

Dengue virus (DENV) infection has increased worldwide, with over 400 million infections annually, and has become a serious public health concern. Several drug candidates, new and repurposed, have failed to meet the primary efficacy endpoints. We have recently shown that Aqueous Extract of the stem of Cocculus hirsutus (AQCH) was effective in vitro and in vivo against DENV and was safe in humans. We now report that an active ingredient of AQCH, Sinococuline, protects against the antibody-mediated secondary-DENV infection in the AG129 mouse model. DENV infection markers were assessed, viz. serum viremia and vital organs pathologies-viral load, proinflammatory cytokines and intestinal vascular leakage. The treatment with Sinococuline at 2.0 mg/kg/day; BID (twice a day), was the most effective in protecting the severely DENV-infected AG129 mice. Also, this dose effectively reduced serum viremia and tissue-viral load and inhibited the elevated expression levels of proinflammatory cytokines (TNF-α and IL-6) in several vital organs. Based on these findings, it could be explored further for pre-clinical and clinical developments for the treatment of dengue.

摘要

登革热病毒（DENV）感染在全球范围内呈上升趋势，每年有超过 4 亿人感染，已成为严重的公共卫生问题。一些候选药物，无论是新的还是重新定位的，都未能达到主要疗效终点。我们最近表明，海风藤水提物（AQCH）在体外和体内对 DENV 有效，并且对人体安全。我们现在报告说，AQCH 的一种活性成分，辛可宁，可在 AG129 小鼠模型中预防抗体介导的二次 DENV 感染。评估了 DENV 感染标志物，即血清病毒血症和重要器官病理学-病毒载量、促炎细胞因子和肠道血管渗漏。辛可宁以 2.0mg/kg/天的剂量；BID（每天两次）治疗，对严重感染 DENV 的 AG129 小鼠的保护作用最为有效。此外，该剂量还能有效降低血清病毒血症和组织病毒载量，并抑制几种重要器官中促炎细胞因子（TNF-α 和 IL-6）的升高表达水平。基于这些发现，它可以进一步探索用于治疗登革热的临床前和临床开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/fd712af4b45d/41598_2023_27927_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/6e42b0dd7c73/41598_2023_27927_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/064051feb946/41598_2023_27927_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/849364e8f132/41598_2023_27927_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/859c1be27704/41598_2023_27927_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/99e3bba4ee55/41598_2023_27927_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/fd712af4b45d/41598_2023_27927_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/6e42b0dd7c73/41598_2023_27927_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/064051feb946/41598_2023_27927_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/849364e8f132/41598_2023_27927_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/859c1be27704/41598_2023_27927_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/99e3bba4ee55/41598_2023_27927_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67f0/9852271/fd712af4b45d/41598_2023_27927_Fig6_HTML.jpg

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2
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Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine.
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