{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:20:29Z","timestamp":1787494829371,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273047"],"award-info":[{"award-number":["32273047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2024NSFSC0372"],"award-info":[{"award-number":["2024NSFSC0372"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background\/Objectives: Andrographolide (Andro), a natural diterpenoid lactone, possesses a wide range of pharmacological properties, including notable anti-inflammatory, antioxidant, antitumor, and immunomodulatory activities. Despite its acknowledged therapeutic promise, the exact protective mechanisms underlying its efficacy against acute liver injury (ALI) are still not fully understood. Consequently, determining the molecular mechanisms through which andrographolide alleviates ALI is of substantial scientific and clinical relevance. Methods: Andrographolide\u2019s potential targets and pharmacological mechanisms against liver injury were initially identified using network pharmacology and molecular docking. An acute liver injury (ALI) rat model was induced by intraperitoneal injection of lipopolysaccharide (LPS). The therapeutic efficacy of andrographolide in ALI was evaluated by examining liver histopathology, measuring liver function and oxidative stress markers, and quantifying pro-inflammatory cytokine levels. Meanwhile, the expression of key constituents along the NLRP3\/caspase-1\/GSDMD signaling axis was quantified using RT-qPCR and Western blotting. In parallel, the protective effect of andrographolide via the canonical NLRP3\/caspase-1\/GSDMD pyroptosis pathway was further examined in vitro using LPS-plus-ATP-stimulated rat hepatocyte BRL-3A cells. Results: Network pharmacology analysis predicted that andrographolide (Andro) protects against liver injury mainly by targeting core regulators of pyroptosis. Molecular docking simulations further indicated stable binding interactions between Andro and key proteins involved in the pyroptotic pathway, such as NLRP3, ASC, GSDMD, and CASP1. These predictions were experimentally confirmed. Andro administration notably mitigated histopathological alterations, restored serum liver function indicators, lowered pro-inflammatory cytokine levels, and alleviated oxidative stress. Importantly, Andro substantially suppressed the expression of critical mediators along the pyroptosis signaling cascade. Conclusions: This study demonstrates that andrographolide (Andro) ameliorates acute liver injury (ALI) by specifically inhibiting the NLRP3\/Caspase-1\/GSDMD-mediated pyroptosis pathway. By elucidating this underlying molecular mechanism, our work highlights Andro\u2019s potential as a novel and promising therapeutic candidate for ALI.<\/jats:p>","DOI":"10.3390\/biom15121743","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:36:53Z","timestamp":1765895813000},"page":"1743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrating Network Pharmacology, Molecular Docking, and Experimental Validation: Andrographolide Attenuates Acute Liver Injury via the NLRP3\/Caspase-1\/GSDMD-Mediated Pyroptosis Pathway"],"prefix":"10.3390","volume":"15","author":[{"given":"Yankun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Veterinary, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanghui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Liang","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8893-9538","authenticated-orcid":false,"given":"Lizi","family":"Yin","sequence":"additional","affiliation":[{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-5832","authenticated-orcid":false,"given":"Changliang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e15739","DOI":"10.1111\/liv.15739","article-title":"Mechanisms and aetiology-dependent treatment of acute liver failure","volume":"45","author":"Lemmer","year":"2025","journal-title":"Liver Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9131","DOI":"10.7150\/thno.119357","article-title":"Nanotuner targeting mitochondrial redox and iron homeostasis imbalance for the treatment of acute liver injury","volume":"15","author":"Li","year":"2025","journal-title":"Theranostics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103787","DOI":"10.1016\/j.redox.2025.103787","article-title":"Decoding Parkinson\u2019s Disease: The interplay of cell death pathways, oxidative stress, and therapeutic innovations","volume":"85","author":"Liu","year":"2025","journal-title":"Redox Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e186420","DOI":"10.1172\/JCI186420","article-title":"MASH: The nexus of metabolism, inflammation, and fibrosis","volume":"135","author":"Steinberg","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.21037\/tgh-23-118","article-title":"Global burden of adult non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) has been steadily increasing over the past decades and is expected to persist in the future","volume":"9","author":"Dong","year":"2024","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jhep.2024.04.034","article-title":"FGF21 agonists: An emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond","volume":"81","author":"Harrison","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s12664-024-01577-3","article-title":"Determinants, profile and outcomes of hepatitis A virus\u2013associated severe acute liver injury in adults","volume":"43","author":"Roy","year":"2024","journal-title":"Indian J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"pgaf004","DOI":"10.1093\/pnasnexus\/pgaf004","article-title":"Stratifying and predicting progression to acute liver failure during the early phase of acute liver injury","volume":"4","author":"Yoshimura","year":"2025","journal-title":"PNAS Nexus"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Huang, Z., Wang, H., Chun, C., Li, X., Xu, S., and Zhao, Y. (2022). Self-assembled FGF21 nanoparticles alleviate drug-induced acute liver injury. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1084799"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2147\/IDR.S500291","article-title":"Association Between Artificial Liver Support System and Prognosis in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure","volume":"18","author":"Cui","year":"2025","journal-title":"Infect. Drug Resist."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s12664-024-01708-w","article-title":"Acute liver failure and liver transplantation","volume":"44","author":"Jothimani","year":"2025","journal-title":"Indian J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.2147\/DMSO.S309641","article-title":"Prognostic Factors Related to the Mortality Rate of Acute-on-Chronic Liver Failure Patients","volume":"14","author":"Zhang","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3350\/cmh.2024.0854","article-title":"Stem cell exosomes: New hope and future potential for relieving liver fibrosis","volume":"31","author":"Li","year":"2025","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12943-025-02344-4","article-title":"Targeting pyroptosis for cancer immunotherapy: Mechanistic insights and clinical perspectives","volume":"24","author":"Huang","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41580-025-00842-3","article-title":"p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases","volume":"26","author":"Liu","year":"2025","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41580-025-00837-0","article-title":"Mechanistic insights into gasdermin-mediated pyroptosis","volume":"26","author":"Bai","year":"2025","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s10020-022-00594-2","article-title":"The emerging role of pyroptosis-related inflammasome pathway in atherosclerosis","volume":"28","author":"Xu","year":"2022","journal-title":"Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121498","DOI":"10.1016\/j.lfs.2023.121498","article-title":"Pyroptosis as a double-edged sword: The pathogenic and therapeutic roles in inflammatory diseases and cancers","volume":"318","author":"Liu","year":"2023","journal-title":"Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12943-024-02217-2","article-title":"Ferroptosis and pyroptosis are connected through autophagy: A new perspective of overcoming drug resistance","volume":"24","author":"Zhao","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"116350","DOI":"10.1016\/j.ecoenv.2024.116350","article-title":"The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs\/Th1\/Th2\/Th17\/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver","volume":"277","author":"Li","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2021.11.026","article-title":"Myeloid Ikaros\u2013SIRT1 signaling axis regulates hepatic inflammation and pyroptosis in ischemia-stressed mouse and human liver","volume":"76","author":"Kadono","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ijbiomac.2017.04.029","article-title":"Molecular cloning and functional characterization of multiple NADPH-cytochrome P450 reductases from Andrographis paniculata","volume":"102","author":"Lin","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117306","DOI":"10.1016\/j.taap.2025.117306","article-title":"Molecular mechanisms of andrographolide-induced kidney injury and senescence via SIRT3 inhibition","volume":"498","author":"Cai","year":"2025","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Huang, L., Halihaman, B., Han, Y., Zhou, J., Liu, C., Bai, H., and Ding, X. (2025). New insight into the epidemiological trends of respiratory syncytial virus infection and the underlying anti-respiratory syncytial virus mechanisms of andrographolide: Integrating Global Burden of Disease database, network pharmacological analysis, and in vitro experiments. Microbiol. Spectr., e0234125.","DOI":"10.1128\/spectrum.02341-25"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118042","DOI":"10.1016\/j.ejmech.2025.118042","article-title":"Design and synthesis of lactam analogs of andrographolide and discovery of their anticancer activity as dual EGFR and VEGFR2 inhibitors","volume":"299","author":"Chen","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1002\/JLB.3MA1119-584RRR","article-title":"Andrographolide exerts anti-inflammatory effects in Mycobacterium tuberculosis-infected macrophages by regulating the Notch1\/Akt\/NF-\u03baB axis","volume":"108","author":"He","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1002\/tox.24046","article-title":"TXNIP-NLRP3-GSDMD axis-mediated inflammation and pyroptosis of islet \u03b2-cells is involved in cigarette smoke-induced hyperglycemia, which is alleviated by andrographolide","volume":"39","author":"Xu","year":"2024","journal-title":"Environ. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s12291-019-00866-5","article-title":"Andrographolide: Regulating the Master Regulator NF-\u03baB","volume":"36","author":"Mishra","year":"2021","journal-title":"Indian J. Clin. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13596535231207499","DOI":"10.1177\/13596535231207499","article-title":"Andrographolide inhibits infectious bronchitis virus-induced apoptosis, pyroptosis, and inflammation","volume":"28","author":"Shen","year":"2023","journal-title":"Antivir. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1007\/s40618-025-02631-3","article-title":"Time trends and health inequalities of cirrhosis caused by metabolic Dysfunction-associated steatotic liver disease from 1990 to 2021: A global burden of disease study","volume":"48","author":"Wu","year":"2025","journal-title":"J. Endocrinol. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"112539","DOI":"10.1016\/j.intimp.2024.112539","article-title":"TRPV1\/cPLA2\/AA pathway contributes to ferroptosis-mediated acute liver injury in heatstroke","volume":"138","author":"Tang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.freeradbiomed.2025.11.005","article-title":"Ammonium tetrathiomolybdate ameliorates heat stroke-induced murine liver injury by activating the Nrf2\/HO-1 signaling pathway and inhibiting oxidative stress","volume":"242","author":"Jiang","year":"2025","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"156323","DOI":"10.1016\/j.phymed.2024.156323","article-title":"Unveiling the hepatoprotective mechanisms of Desmodium heterocarpon (L.) DC: Novel flavonoid identification and Keap1\/Nrf2 pathway activation","volume":"136","author":"Pu","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11508","DOI":"10.1039\/D5TB01185J","article-title":"Advances of Chinese herbal medicine-derived polysaccharides as carrier-free and carrier agents in anti-melanoma therapy","volume":"13","author":"Mao","year":"2025","journal-title":"J. Mater. Chem. B"},{"key":"ref_35","first-page":"914","article-title":"Targeting TLR4 and regulating the Keap1\/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury","volume":"22","author":"Li","year":"2024","journal-title":"Chin. J. Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.jtcme.2024.05.004","article-title":"In vivo evaluation of Andrographis paniculata and Boesenbergia rotunda extract activity against SARS-CoV-2 Delta variant in Golden Syrian hamsters: Potential herbal alternative for COVID-19 treatment","volume":"14","author":"Kongsomros","year":"2024","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"154753","DOI":"10.1016\/j.phymed.2023.154753","article-title":"The effects and mechanisms of the anti-COVID-19 traditional Chinese medicine, Dehydroandrographolide from Andrographis paniculata (Burm.f.) Wall, on acute lung injury by the inhibition of NLRP3-mediated pyroptosis","volume":"114","author":"Pu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1007\/s10565-023-09832-7","article-title":"Andrographolide attenuated MCT-induced HSOS via regulating NRF2-initiated mitochondrial biogenesis and antioxidant response","volume":"39","author":"Huang","year":"2023","journal-title":"Cell Biol. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ge, S., Lian, W., Bai, Y., Wang, L., Zhao, F., Li, H., Wang, D., and Pang, Q. (2023). TMT-based quantitative proteomics reveals the targets of andrographolide on LPS-induced liver injury. BMC Vet.-Res., 19.","DOI":"10.1186\/s12917-023-03758-2"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, Y.-T., Chen, H.-W., Lii, C.-K., Jhuang, J.-H., Huang, C.-S., Li, M.-L., and Yao, H.-T. (2020). A Diterpenoid, 14-Deoxy-11, 12-Didehydroandrographolide, in Andrographis paniculata Reduces Steatohepatitis and Liver Injury in Mice Fed a High-Fat and High-Cholesterol Diet. Nutrients, 12.","DOI":"10.3390\/nu12020523"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ali, S.K., Makeen, H.A., Khuwaja, G., Alhazmi, H.A., Sharma, M., Koty, A., Mazahirul, I., Parveen, H., Mohammed, A., and Mukhtar, S. (2023). Assessment of the Phytochemical Profile, Antioxidant Capacity, and Hepatoprotective Effect of Andrographis paniculata against CCl 4-Induced Liver Dysfunction in Wistar Albino Rats. Medicina, 59.","DOI":"10.3390\/medicina59071260"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"eadl3629","DOI":"10.1126\/sciadv.adl3629","article-title":"Distinct sequential death complexes regulate pyroptosis and IL-1\u03b2 release in response to Yersinia blockade of immune signaling","volume":"10","author":"Wertman","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wertman, R.S., Go, C.K., Saller, B.S., Gro\u00df, O., Scott, P., and Brodsky, I.E. (2023). Sequentially activated death complexes regulate pyroptosis and IL-1\u03b2 release in response to Yersinia blockade of immune signaling. bioRxiv.","DOI":"10.1101\/2023.09.14.557714"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eESP00142021","DOI":"10.1128\/ecosalplus.ESP-0014-2021","article-title":"Role of the Yersinia pseudotuberculosis Virulence Plasmid in Pathogen-Phagocyte Interactions in Mesenteric Lymph Nodes","volume":"9","author":"Bliska","year":"2021","journal-title":"EcoSal Plus"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113581","DOI":"10.1016\/j.celrep.2023.113581","article-title":"The tetrapeptide sequence of IL-18 and IL-1\u03b2 regulates their recruitment and activation by inflammatory caspases","volume":"42","author":"Exconde","year":"2023","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"135726","DOI":"10.1016\/j.chemosphere.2022.135726","article-title":"Wood smoke particulate matter (WSPM2.5) induces pyroptosis through both Caspase-1\/IL-1\u03b2\/IL-18 and ATP\/P2Y-dependent mechanisms in human bronchial epithelial cells","volume":"307","author":"Fu","year":"2022","journal-title":"Chemosphere"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1016\/j.cell.2021.06.028","article-title":"Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway","volume":"184","author":"Evavold","year":"2021","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41586-024-07373-5","article-title":"ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D","volume":"630","author":"Du","year":"2024","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3892\/ijmm.2022.5130","article-title":"Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review)","volume":"49","author":"Zhang","year":"2022","journal-title":"Int. J. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.molimm.2018.09.010","article-title":"The role of mitochondria in NLRP3 inflammasome activation","volume":"103","author":"Liu","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbi.2020.05.063","article-title":"Acute stress induces chronic neuroinflammatory, microglial and behavioral priming: A role for potentiated NLRP3 inflammasome activation","volume":"89","author":"Frank","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113968","DOI":"10.1016\/j.biopha.2022.113968","article-title":"Insight into the regulation of NLRP3 inflammasome activation by mitochondria in liver injury and the protective role of natural products","volume":"156","author":"Liu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Huang, F., Wang, Z., Zhou, M., Zhang, Q., and Feng, J. (2025). Fisetin Attenuates Zinc Overload-Induced Hepatotoxicity in Mice via Autophagy-Dependent Nrf2 Activation. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26114978"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101480","DOI":"10.1016\/j.jcmgh.2025.101480","article-title":"An Nrf2-NF-\u03baB Crosstalk Controls Hepatocyte Proliferation in the Normal and Injured Liver","volume":"19","author":"Kuklin","year":"2025","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1080\/01480545.2025.2525149","article-title":"Heavy metal mixture induced hippocampal toxicity involve biometal accumulation, increase in oxidative stress, inflammation, and caspase-3 activation in rats via Nrf-2\/HO-1\/BDNF pathway","volume":"48","author":"Dooka","year":"2025","journal-title":"Drug Chem. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bbi.2020.09.017","article-title":"Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease","volume":"91","author":"Ahmed","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Albornoz, A., Pardo, B., Apaoblaza, S., Henriquez, C., Ojeda, J., Uberti, B., Hancke, J., Burgos, R.A., and Moran, G. (2024). Andrographolide Inhibits Expression of NLPR3 Inflammasome in Canine Mononuclear Leukocytes. Animals, 14.","DOI":"10.3390\/ani14142036"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1743\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:46:11Z","timestamp":1765896371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":57,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["biom15121743"],"URL":"https:\/\/doi.org\/10.3390\/biom15121743","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,16]]}}}