Center for Traditional Chinese Medicine and Immunology Research, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
The Research Center for Traditional Chinese Medicine, Shanghai Institute for Major Infectious Diseases and Biosafety, Shanghai 200032, China.
Oxid Med Cell Longev. 2022 Apr 28;2022:1885066. doi: 10.1155/2022/1885066. eCollection 2022.
Tuberculosis (TB) remains a leading threat to public health worldwide with (Mtb) infections causing long-term abnormal and excessive inflammatory responses, which in turn lead to lung damage and fibrosis, and ultimately death. Host-directed therapy (HDT) has been shown to be an effective anti-TB strategy in the absence of effective anti-TB drugs. Here, we used an macrophage model of Mtb infection to evaluate the effects of andrographolide (Andro), extracted from , on pyroptosis in Mtb-infected macrophages. We evaluated the molecular mechanisms underlying these outcomes. These evaluations revealed that Andro downregulated the expression of proinflammatory miR-155-5p, which then promoted the expression of Nrf2 to suppress pyroptosis in Mtb-infected macrophages. Further study also demonstrated that siNrf2 could attenuate the inhibitory effect of Andro on TXNIP, validating our mechanistic studies. Thus, our data suggest that Andro may be a potential candidate adjuvant drug for anti-TB therapy as it inhibits pyroptosis in Mtb-infected macrophages, potentially improving clinical outcomes.
结核病（TB）仍然是全球公共卫生的主要威胁，（Mtb）感染导致长期异常和过度的炎症反应，进而导致肺损伤和纤维化，并最终导致死亡。在缺乏有效抗结核药物的情况下，宿主定向治疗（HDT）已被证明是一种有效的抗结核策略。在这里，我们使用 Mtb 感染的巨噬细胞模型来评估穿心莲内酯（Andro）对 Mtb 感染巨噬细胞中细胞焦亡的影响，穿心莲内酯是从穿心莲中提取的。我们评估了这些结果的潜在分子机制。这些评估表明，Andro 下调了促炎 miR-155-5p 的表达，从而促进了 Nrf2 的表达，以抑制 Mtb 感染巨噬细胞中的细胞焦亡。进一步的研究还表明，siNrf2 可以减弱 Andro 对 TXNIP 的抑制作用，验证了我们的机制研究。因此，我们的数据表明，Andro 可能是一种潜在的抗结核治疗辅助药物，因为它抑制了 Mtb 感染巨噬细胞中的细胞焦亡，可能改善临床结局。
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