Fibrosis
Fibrosis refers to a pathophysiological tissue process wherein wound healing proceeds via a non-regenerative mechanism and leads instead to formation of a scar [1]. Instead of replacement of damaged tissue with its healthy counterpart, constructed with its native cellular constituents and appropriate microstructure, fibrotic tissue is largely acellular and lacks the functional properties of the tissue that it seeks to replace. In internal organs whose vital functions rely heavily on complex tissue microstructure and active cellular function, fibrotic responses manifesting throughout even limited volumes of tissue can lead to morbidity and mortality through loss of organ function and/or complete organ failure. It is for this reason that nearly half of all mortalities in the developed world are attributed to fibrosis [2]. Recent investigation has also demonstrated efficacy of these compounds for treatment of numerous other disease states including inflammation, infection, cancer, and fibrosis [3].Over-activation of the NLRP3 inflammasome triggers the abundant secretion of IL-1β and IL-18, induces pyroptosis, and promotes the release of a swathe ofpro-inflammatory proteins, all of which contribute to fibrogenic processes in multiple organs [4].
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- Ding N, Wei B, Fu X, Wang C, Wu Y. Natural Products that Target the NLRP3 Inflammasome to Treat Fibrosis. Front Pharmacol. 2020 Dec 17;11:591393. doi: 10.3389/fphar.2020.591393.
Artemisinin: [Artemisia annua] Downregulating the NF-κB/NLRP3 pathway. Significantly inhibited the nuclear transcription factor kappa B p65 (NF-κB p65) translocation into the nucleus.
5. Watanabe Y., Nagai Y., Honda H., Okamoto N., Yamamoto S., Hamashima T. et al. (2016). Isoliquiritigenin attenuates adipose tissue inflammation in vitro and adipose tissue fibrosis through inhibition of innate immune responses in mice. Sci. Rep. 6, 23097 10.1038/srep23097
6. Lai L, Chen Y, Tian X, Li X, Zhang X, Lei J, Bi Y, Fang B, Song X. Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling pathway in rats. Eur J Pharmacol. 2015 Oct 15;765:234-41. doi: 10.1016/j.ejphar.2015.08.040.
Oridonin[Rabdosia rubescens] Targeting the NACHT domain in NLRP3 via combining with the cysteine 279 to block NLRP3-NEK7 interaction in BMDMs Inhibiting TGF-β1 enhanced NLRP3 inflammasome activation in HSCs. Oridonin is an entkaurane diterpenoid isolated from Rabdosia rubenscens, was first identified as an antitumor compound in 1967Reduces the NLRP3 inflammasome activation in C57BL/6J mice with CCl4-induced liver fibrosis
7. He H., Jiang H., Chen Y., Ye J., Wang A., Wang C. et al. (2018). Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity. Nat. Commun. 9, 2550 10.1038/s41467-018-04947-6
8. Fujita E., Fujita T., Katayama H., Shibuya M. Oridonin, a new diterpenoid from Isodon species. Chem. Commun. (London) 1967;0:252–254. doi: 10.1039/c19670000252
Pterostilbene:Augmenting autophagy to inhibit NLRP3 inflammasome activation in TGF-β stimulated NRK-52E cellsEnhancing autophagy to restrain EMT-mediated NLRP3 inflammasome activation in PO-induced hyperuricemia or HAD-triggered CKD of ICR mice
9. Wang W., Wang X., Chun J., Vilaysane A., Clark S., French G. et al. (2013). Inflammasome-independent NLRP3 augments TGF-beta signaling in kidney epithelium. J. Immunol. 190, 1239–1249. 10.4049/jimmunol.1201959
Compound K:Inhibiting the priming and mitochondria-mediated NLRP3 inflammasome activation in TECs and J774A.1 macrophages. Targeting the NF-κB/NLRP3 pathway to improve fibrosis in C57BL/6 mice with renal tubulointerstitial lesions
Ginsenoside Rg1: Decreasing NOX4-induced ROS production and the subsequent NLRP3 inflammasome activation in SAMR1 and SAMP8 mice
