TABLE 1.
The phytochemicals reported to inhibit NLRP3 inflammasome activation in various fibrotic diseases.
| No | Phytochemicals | Sources | In vitro | In vivo |
|---|---|---|---|---|
| 1 | Sweroside (Gousiadou et al., 2015; Yang et al., 2020) | Manulea altissima (Scrophulariaceae) | Inhibiting activation of NLRP3 inflammasome and formation of ASC speck in BMDMs | Blocking the de novo synthesis of mtDNA to suppress NLRP3 inflammasome activation in the liver of NASH C57BL/6 mice |
| 2 | Artemisinin (Wen et al., 2019) | Artemisia annua L | Downregulating the NF-κB/NLRP3 pathway in HK-2 | Downregulating the NF-κB/NLRP3 pathway in SNx Sprague-Dawley rats |
| 3 | Oridonin (He et al., 2018) | 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 | Reducing the NLRP3 inflammasome activation in C57BL/6J mice with CCl4-induced liver fibrosis |
| 4 | Andrographolide (Cabrera et al., 2017) | Andrographis paniculata | Inhibiting NF-κB pathway and NLRP3 inflammasome assembly in fat-laden HepG2 cells | Suppressing NLRP3 inflammasome activation in C57BL/6 mice with alcoholic steatohepatitis to improve liver fibrosis |
| 5 | Triptolide (Li et al., 2017b; Pan et al., 2019) | Tripterygium wilfordii Hook F | Interrupting NLRP3/ASC interaction to reduce the AngII-triggered collagen production in CFs | Alleviating chronic pressure-overloaded or isoproterenol-induced cardiac fibrosis by inhibiting NLRP3/TGFβ1/Smad signaling in C57BL/6 mice |
| 6 | 25-OCH3-PPD (Han et al., 2018) | Panax notoginseng | Promoting activity of LXRs to ameliorate P2X7R-mediated NLRP3 inflammasome activation to decrease a-SMA expression in HSC-T6 | Affecting P2X7R to suppress NLRP3 inflammasome activation in TAA-stimulated liver fibrosis in C57BL/6 mice |
| 7 | Compound K (Hsu et al., 2020) | Metabolite of ginsenoside Rb1 | 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 |
| 8 | Ginsenoside Rg1 (Shen et al., 2020) | Ginseng | NA | Decreasing NOX4-induced ROS production and the subsequent NLRP3 inflammasome activation in SAMR1 and SAMP8 mice |
| 9 | Glycyrrhizin (Yan et al., 2018) | Glycyrrhiza glabra | Inhibiting deoxycholic acid-triggered NLRP3 inflammasome activation in raw 264.7 | Decreasing bile acids accumulation to suppress NLRP3 inflammasome activation in C57BL/6 mice with MCD diet-induced NASH |
| 10 | Saikosaponin A (Cui et al., 2020b) | Bupleurum falcatum | Inhibiting AMPK/mTOR-mediated autophagy and NLRP3 inflammasome activation in pancreatic stellate cells | NA |
| 11 | Anemoside B4 (Gong et al., 2019) | Pulsatilla radix | NA | Reducing the fiber collagen and expression of NLRP3, caspase-1, ASC, IL-1β, and IL-18 in adenine-induced renal injury Wistar rats |
| 12 | Quercetin (Choe and Kim, 2017; Liu et al., 2018) | Multiple plants | Regulating TXNIP to suppress ROS production and NLRP3 inflammasome activation in fructose-induced U937 and THP-1 macrophages | Activating Nrf2 to upregulate expression of OH-1 to modulate ROS/NF-κB/NLRP3 pathway in Wistar rats |
| 13 | Dihydroquercetin (Ding et al., 2018) | Larix sibirica (Pinaceae) and Pseudotsuga taxifolia (Pinaceae) | Suppressing mitochondrial ROS generation and NLRP3 inflammasome activation in high glucose stimulated HBZY-1 and HK2 cells | Decreasing ROS production and NLRP3 inflammasome activation to improve fibrosis in SD rats with HFD/streptozotocin-induced diabetic nephropathy |
| 14 | Casticin (Li et al., 2020) | Vitex fructus | Suppressing NLRP3 components in primary synovial fibroblasts | Targeting HIF-1α/NLRP3 inflammasome pathway in MIA-induced knee osteoarthritis of SD rats |
| 15 | Isoliquiritigenin (Peng et al., 2015; Watanabe et al., 2016) | Several plants of the genus Glycyrrhiza | Inhibiting NLRP3 inflammasome activation in raw 264.7 and 3T3-L1 cells | Inhibiting NLRP3 inflammasome and PPAR-γ activation in the adipose tissue of HFD-fed C57BL/6 mice |
| 16 | Phloretin (Cui et al., 2020a) | Apples and strawberries | Repressing NLRP3 components in HK-2 cells | Co-inhibiting NLRP3 inflammasome activation and uric acid reabsorption inhyperuricemia-induced renal fibrosis of C57BL/6 mice |
| 17 | Icariin (Zhang et al., 2017) | Several species of the genus Epimedium | NA | Inhibiting the NF-κB and NLRP3 signaling pathways in BGG-induced IgAN of Sprague–Dawley rats |
| 18 | Pelargonidin (Shi et al., 2020) | Red geraniums and berries | Activating Nrf2 to attenuate cellular oxidative stress and suppress NLRP3 inflammasome activation in TGF-β-challenged HSCs | Suppressing the ROS/NLRP3/il-1β axis via activating the Nrf2 pathway in In CCl4-induced C57BL/6J mice |
| 19 | Resveratrol (Ding et al., 2019) | Wine and grapes | Inhibiting autophagy to attenuate particulate matter (PM2.5)-induced cytotoxicity in PM2.5-treated BEAS-2B cells | Downregulating the autophagy-related NLRP3 inflammasome activation in PM2.5-triggered lung fibrosis of BALB/c mice |
| 20 | Pterostilbene (Wang et al., 2020d) | Multiple foods and herbs | Augmenting autophagy to inhibit NLRP3 inflammasome activation in TGF-β stimulated NRK-52E cells | Enhancing autophagy to restrain EMT-mediated NLRP3 inflammasome activation in PO-induced hyperuricemia or HAD-triggered CKD of ICR mice |
| 21 | Polydatin (Tang et al., 2019) | Polygonum cuspidatum | Inhibiting fibrotic markers in BEAS-2B cells | Suppressing activation of NF-κB/NLRP3 signaling pathway in mp- infected BALB/c mice |
| 22 | Apocynin (Xin et al., 2018) | Picrorhiza kurroa | NA | Inhibiting NLRP3/XIAP signaling pathway of Sprague-Dawley rats with DN |
| 23 | Lycorine (Liang et al., 2020) | Amaryllis and daffodil | Targeting the PYD of ASC on Leu9, Leu50 and Thr53 to interrupt NLRP3-ASC interaction in BMDMs | Inhibiting NLRP3 inflammasome activation and pyroptosis in bleomycin-induced pulmonary fibrosis of C57BL/6 mice |
| 24 | Matrine (Mahzari et al., 2019) | Plants of the genus Sophora | NA | Decreasing fibrotic markers partially via inhibiting NLRP3 inflammasome activation in NASH C57BL/6J mice |
| 25 | Tetramethylpyrazine (Zhang et al., 2014; Wu et al., 2015) | Ligusticum wallichii Franch | Targeting PDGF-βR/NLRP3/caspase-1 pathway in PDGF or Angiotensin II treated HSCs | Targeting PDGF-βr/NLRP3/caspase-1 pathway in CCl4-induced liver fibrosis of Sprague-Dawley rats |
| 26 | Cinnamaldehyde (Kang et al., 2016) | Species of the genus Cinnamomum | Repressing NLRP3 inflammasome activation via CD-36-mediated TLR4/6-IRAK4/1 pathway in fructose-exposed H9c2 cells | Attenuating CD-36 mediated TLR4/6-IRAK4/1 signaling to inhibit NLRP3 inflammasome activation in fructose-induced cardiac fibrosis of Sprague-Dawley rats |
| 27 | Astaxanthin (Liu et al., 2015) | Microalgae and seafood | NA | Promoting Nrf2 expression to inhibit NLRP3 inflammasome activation in doxorubicin-induced focal segmental glomerulosclerosis of BALB/c |