Macrophage‑driven pathogenesis in acute lung injury/acute respiratory disease syndrome: Harnessing natural products for therapeutic interventions (Review)

Abstract

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a common respiratory disease characterized by hypoxemia and respiratory distress. It is associated with high morbidity and mortality. Due to the complex pathogenesis of ALI, the clinical management of patients with ALI/ARDS is challenging, resulting in numerous post‑treatment sequelae and compromising the quality of life of patients. Macrophages, as a class of innate immune cells, play an important role in ALI/ARDS. In recent years, the functions and phenotypes of macrophages have been better understood due to the development of flow cytometry, immunofluorescence, single‑cell sequencing and spatial genomics. However, no macrophage‑targeted drugs for the treatment of ALI/ARDS currently exist in clinical practice. Natural products are important for drug development, and it has been shown that numerous natural compounds from herbal medicine can alleviate ALI/ARDS caused by various factors by modulating macrophage abnormalities. In the present review, the natural products from herbal medicine that can modulate macrophage abnormalities in ALI/ARDS to treat ALI/ARDS are introduced, and their mechanisms of action, discovered in the previous five years (2019‑2024), are presented. This will provide novel ideas and directions for further research, to develop new drugs for the treatment of ALI/ARDS.

Keywords: acute lung injury; acute respiratory distress syndrome; macrophages; natural products.

Figure 1.

Molecules of natural products interfering with macrophage polarization. Created using BioRender.com. ↑ indicates promotion and ⊥ indicates inhibition. PPARγ, peroxisome proliferator-activated receptor γ; Nrf2, nuclear factor erythroid 2-related factor 2; α7nAChR, α7 nicotinic acetylcholine receptor; Erg-1, early growth response 1; NLRP3, pyrin domain-containing protein 3; Trem2, triggering receptor expressed on myeloid cells; GSDMD, gasdermin D; TLR4, Toll-like receptor 4; STAT3, signal transducer and activator of transcription 3; IRF4, interferon regulatory factor 4; FBXW7, F-box and WD repeat domain containing 7; HIF, hypoxia-inducible factor; SOCS3, suppressor of cytokine signaling 3; G9a, euchromatic histone-lysine N-methyltransferase 2; NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells; ERK, extracellular regulated protein kinases; Egr-1, early growth response 1; JNK, c-Jun N-terminal kinase; PKM2, pyruvate kinase M2; AMPK, adenosine 5′-monophosphate-activated protein kinase; NFACT1, nuclear factor of activated T cells 1; STRT1, silent information regulator 1.

Figure 2.

Molecular mechanisms through which natural products regulate macrophage pyroptosis. Created using BioRender.com. ↑ indicates promotion and ⊥ indicates inhibition. PKM2, pyruvate kinase M2; SIRT1, Sirtuin 1; PLK1, polo-like kinase 1; DRP1, dynamin-related protein 1; ROS, reactive oxygen species; EP300, E1A binding protein p300; NLRP3, pyrin domain-containing protein 3; GSDMD, gasdermin D; EBP-δ, enhancer binding protein δ; GSDME, Gasdermin E.

Table I.

Natural products that modulate macrophage polarization

Table II.

Natural products that modulate macrophage pyroptosis.

Table III.

Natural products that regulate macrophage phagocytosis.

Table IV.

Natural products that regulate macrophage autophagy.