{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T09:04:32Z","timestamp":1769763872320,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council of Taiwan","award":["NSC 112-2311-B-A49-002"],"award-info":[{"award-number":["NSC 112-2311-B-A49-002"]}]},{"name":"National Science and Technology Council of Taiwan","award":["112-2327-B-182-005"],"award-info":[{"award-number":["112-2327-B-182-005"]}]},{"name":"National Science and Technology Council of Taiwan","award":["112-2321-B-A49-006"],"award-info":[{"award-number":["112-2321-B-A49-006"]}]},{"name":"National Science and Technology Council of Taiwan","award":["MOST 106-2320-B-077-002-MY3"],"award-info":[{"award-number":["MOST 106-2320-B-077-002-MY3"]}]},{"name":"Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University","award":["NSC 112-2311-B-A49-002"],"award-info":[{"award-number":["NSC 112-2311-B-A49-002"]}]},{"name":"Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University","award":["112-2327-B-182-005"],"award-info":[{"award-number":["112-2327-B-182-005"]}]},{"name":"Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University","award":["112-2321-B-A49-006"],"award-info":[{"award-number":["112-2321-B-A49-006"]}]},{"name":"Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University","award":["MOST 106-2320-B-077-002-MY3"],"award-info":[{"award-number":["MOST 106-2320-B-077-002-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-\u03baB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-\u03b1, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-\u03b1 and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-\u03b1, IL-6, and iNOS in the lungs and decreased TNF-\u03b1 and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.<\/jats:p>","DOI":"10.3390\/ijms242316572","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T10:24:13Z","timestamp":1700562253000},"page":"16572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Galgravin Isolated from Piper kadsura Ameliorates Lipopolysaccharide (LPS)-Induced Endotoxemia in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Shih-Ming","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11467, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8109-7390","authenticated-orcid":false,"given":"Yin-Chieh","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Ling","family":"Fu","sequence":"additional","affiliation":[{"name":"Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6426-9696","authenticated-orcid":false,"given":"Lie-Chwen","family":"Lin","sequence":"additional","affiliation":[{"name":"National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6344-271X","authenticated-orcid":false,"given":"Chao-Hsiung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1705716","article-title":"Hydrocortisone plus Fludrocortisone for Adults with Septic Shock","volume":"378","author":"Annane","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1209438","DOI":"10.3389\/fimmu.2023.1209438","article-title":"The role of macrophages polarization in sepsis-induced acute lung injury","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"952337","DOI":"10.3389\/fphar.2022.952337","article-title":"Protective effects of menthol against sepsis-induced hepatic injury: Role of mediators of hepatic inflammation, apoptosis, and regeneration","volume":"13","author":"Matouk","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"981578","DOI":"10.3389\/fphar.2022.981578","article-title":"Sepsis-induced AKI: From pathogenesis to therapeutic approaches","volume":"13","author":"He","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s00018-020-03656-y","article-title":"TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling","volume":"78","author":"Ciesielska","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2014.00316","article-title":"A comparative review of toll-like receptor 4 expression and functionality in different animal species","volume":"5","author":"Vaure","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106861","DOI":"10.1016\/j.phrs.2023.106861","article-title":"Degradation of MK2 with natural compound andrographolide: A new modality for anti-inflammatory therapy","volume":"194","author":"Tran","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"949502","DOI":"10.3389\/fphar.2022.949502","article-title":"Andrographolide contributes to spinal cord injury repair via inhibition of apoptosis, oxidative stress and inflammation","volume":"13","author":"Li","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.2147\/DDDT.S327378","article-title":"Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures","volume":"15","author":"Peng","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1075804","DOI":"10.3389\/fimmu.2022.1075804","article-title":"Dual targeting of mTOR\/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation","volume":"13","author":"Roy","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.intimp.2013.01.008","article-title":"Suppression of LPS-induced inflammatory responses by gossypol in RAW 264.7 cells and mouse models","volume":"15","author":"Huo","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.intimp.2011.11.018","article-title":"Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge","volume":"12","author":"Kang","year":"2012","journal-title":"Int. Immunopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cheng, C., and Yu, X. (2021). Research Progress in Chinese Herbal Medicines for Treatment of Sepsis: Pharmacological Action, Phytochemistry, and Pharmacokinetics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011078"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113336","DOI":"10.1016\/j.phytochem.2022.113336","article-title":"Neolignans and amide alkaloids from the stems of Piper kadsura and their neuroprotective activity","volume":"203","author":"Chen","year":"2022","journal-title":"Phytochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.chroma.2017.06.020","article-title":"Rapid purification of diastereoisomers from Piper kadsura using supercritical fluid chromatography with chiral stationary phases","volume":"1509","author":"Xin","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yu, N., Gu, H., Wei, Y., Zhu, N., Wang, Y., Zhang, H., Zhu, Y., Zhang, X., Ma, C., and Sun, A. (2016). Suitable DNA Barcoding for Identification and Supervision of Piper kadsura in Chinese Medicine Markets. Molecules, 21.","DOI":"10.3390\/molecules21091221"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhao, L., Wang, S., Huang, X., Fan, Y., Xue, Z., Yang, D., Ouyang, H., Chang, Y., and He, J. (2021). Pharmacokinetic and Bioavailability Studies of Galgravin after Oral and Intravenous Administration to Rats Using HPLC-MS\/MS Method. Biomed. Res. Int., 2021.","DOI":"10.1155\/2021\/9919789"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3236768","DOI":"10.1155\/2020\/3236768","article-title":"Revealing the Pharmacological Mechanism of Acorus tatarinowii in the Treatment of Ischemic Stroke Based on Network Pharmacology","volume":"2020","author":"Liu","year":"2020","journal-title":"Evid. Based Complement. Alternat Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12757","DOI":"10.3390\/molecules200712757","article-title":"Neolignans from Nectandra megapotamica (Lauraceae) Display in vitro Cytotoxic Activity and Induce Apoptosis in Leukemia Cells","volume":"20","author":"Ponci","year":"2015","journal-title":"Molecules"},{"key":"ref_20","first-page":"569","article-title":"Chemical constituents from rhizomes of Acorus tatarinowii","volume":"38","author":"Ni","year":"2013","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.jep.2013.09.002","article-title":"Moderation of hematological and plasma biochemical indices of sub-chronic salt-loaded rats by aqueous extract of the sclerotia of Pleurotus tuberregium (Fr) Sing\u2019s: Implications for the reduction of cardiovascular risk","volume":"150","author":"Ikewuchi","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s10616-011-9416-z","article-title":"Effects of veraguensin and galgravin on osteoclast differentiation and function","volume":"64","author":"Asai","year":"2012","journal-title":"Cytotechnology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6636","DOI":"10.1021\/jo200968f","article-title":"Asymmetric synthesis of (+)-galbelgin, (-)-kadangustin J, (-)-cyclogalgravin and (-)-pycnanthulignenes A and B, three structurally distinct lignan classes, using a common chiral precursor","volume":"76","author":"Rye","year":"2011","journal-title":"J. Org. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1248\/bpb.28.289","article-title":"Neuroprotective effects of 2,5-diaryl-3,4-dimethyltetrahydrofuran neolignans","volume":"28","author":"Zhai","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1211\/0022357044058","article-title":"Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats","volume":"56","author":"Carvalho","year":"2004","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbrc.2005.11.005","article-title":"Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and induces cytokine expression in macrophages","volume":"339","author":"Fu","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41419-023-05975-x","article-title":"GOLPH3 promotes endotoxemia-induced liver and kidney injury through Golgi stress-mediated apoptosis and inflammatory response","volume":"14","author":"Dusabimana","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.molimm.2019.02.020","article-title":"Molecular mechanism of action responsible for carrageenan-induced inflammatory response","volume":"109","author":"Myers","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fphys.2020.00036","article-title":"Molecular Dynamics of Lipopolysaccharide-Induced Lung Injury in Rodents","volume":"11","author":"Domscheit","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1177\/0192623315598399","article-title":"Mouse Models of Acute Respiratory Distress Syndrome: A Review of Analytical Approaches, Pathologic Features, and Common Measurements","volume":"43","author":"Aeffner","year":"2015","journal-title":"Toxicol. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1021\/np0505521","article-title":"Anti-inflammatory neolignans from Piper kadsura","volume":"69","author":"Lin","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chiu, L.C., Wang, J.Y., Lin, C.H., Hsu, C.H., Lin, L.C., and Fu, S.L. (2021). Diterpenoid Compounds Isolated from Chloranthus oldhamii Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK\/NF-kappaB Pathway. Molecules, 26.","DOI":"10.3390\/molecules26216540"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tsai, Y.C., Wang, S.L., Wu, M.Y., Liao, C.H., Lin, C.H., Chen, J.J., Fu, S.L., and Pilloin, A. (2018). Flavonoid Isolated from Aquilaria sinensis, Exhibits Anti-Inflammatory Activity In Vitro and In Vivo. Molecules, 23.","DOI":"10.3390\/molecules23123177"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Huang, C.Y., Deng, J.S., Huang, W.C., Jiang, W.P., and Huang, G.J. (2020). Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Hispolon in Mice, Through Regulating the TLR4\/PI3K\/Akt\/mTOR and Keap1\/Nrf2\/HO-1 Pathways, and Suppressing Oxidative Stress-Mediated ER Stress-Induced Apoptosis and Autophagy. Nutrients, 12.","DOI":"10.3390\/nu12061742"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/16572\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:26:16Z","timestamp":1760131576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/16572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,21]]},"references-count":34,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242316572"],"URL":"https:\/\/doi.org\/10.3390\/ijms242316572","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,21]]}}}