Andrographolide Suppresses Pyroptosis in <i>Mycobacterium tuberculosis-Infected</i> Macrophages via the microRNA‐155/Nrf2 Axis
Yan Fu, Jingjing Shen, Fanglin Liu, Hemin Zhang, Yuejuan Zheng, Xin Jiang
Abstract
Tuberculosis (TB) remains a leading threat to public health worldwide with Mycobacterium tuberculosis (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 in vitro macrophage model of Mtb infection to evaluate the effects of andrographolide (Andro), extracted from Andrographis paniculata , 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.