Academic Journal
Προβολή σε EDS
Συνδεδεμένο Πλήρες Κείμενο

Galactosylated Solid Lipid Nanoparticles with Swertiamarin Alleviate Cholestiatic Liver Injury via Enhancing the SIRT1/Nrf2 Pathway.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Galactosylated Solid Lipid Nanoparticles with Swertiamarin Alleviate Cholestiatic Liver Injury via Enhancing the SIRT1/Nrf2 Pathway.
Συγγραφείς: Wu J; Department of Medicine, City University of Wuhan, Wuhan, 430083, China., Wu T; Department of Hematology, The Sixth Hospital of Wuhan (Affiliated Hospital of Jianghan University), Jianghan University, Wuhan, 430014, China., Guan X; Central Laboratory, Hubei Key Laboratory of Sports Injury and Precision Therapy, Wuhan Fourth Hospital, Hanzheng street 473, Wuhan, 430000, China., Zhu X; Central Laboratory, Hubei Key Laboratory of Sports Injury and Precision Therapy, Wuhan Fourth Hospital, Hanzheng street 473, Wuhan, 430000, China., Lei L; Central Laboratory, Hubei Key Laboratory of Sports Injury and Precision Therapy, Wuhan Fourth Hospital, Hanzheng street 473, Wuhan, 430000, China., Wu T; Central Laboratory, Hubei Key Laboratory of Sports Injury and Precision Therapy, Wuhan Fourth Hospital, Hanzheng street 473, Wuhan, 430000, China. D201178413@alumni.hust.edu.cn., Zhang Q; Department of Pharmacy, General Hospital of the Yangtze River Shipping, Wuhan Brain Hospital, Wuhan, 430014, China.
Πηγή: Applied biochemistry and biotechnology [Appl Biochem Biotechnol] 2026 Oct; Vol. 198 (10), pp. 7410-7427. Date of Electronic Publication: 2026 Jun 13.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Humana Press Country of Publication: United States NLM ID: 8208561 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0291 (Electronic) Linking ISSN: 02732289 NLM ISO Abbreviation: Appl Biochem Biotechnol Subsets: MEDLINE
Imprint Name(s): Original Publication: Clifton, N.J. : Humana Press, c1981-
Ιατρικοί όροι (MeSH): Sirtuin 1*/metabolism , Nanoparticles*/chemistry , NF-E2-Related Factor 2*/metabolism , Iridoid Glucosides*/pharmacology , Iridoid Glucosides*/chemistry , Pyrones*/pharmacology , Pyrones*/chemistry , Signal Transduction*/drug effects , Galactose*/chemistry , Lipids*/chemistry , Cholestasis*/drug therapy , Cholestasis*/metabolism , Cholestasis*/pathology , Chemical and Drug Induced Liver Injury*/metabolism , Chemical and Drug Induced Liver Injury*/drug therapy , Chemical and Drug Induced Liver Injury*/pathology, Oxidative Stress/drug effects ; Apoptosis/drug effects ; Animals ; Humans ; Mice ; Hep G2 Cells ; Male ; Liposomes
Περίληψη: Swertiamarin (STM), one of the main bioactive compounds of Swertia plants, exerts its potential anti-CLI effects. The objective of this study was to prepare liver-targeting solid lipid nanoparticles (SLNs) with STM, using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA), and evaluate its cholestatic effect on alpha-naphthylisothiocyanate (ANIT)-induced CLI. STM-loaded galactosylated SLN (STM@GalSLN) was prepared using the melt-emulsification-ultrasound method. The influence of STM@GalSLN on liver damage, oxidative stress, hepatocyte apoptosis, and Sirtuin 1 (SIRT1)/NF-E2 p45-related Factor 2 (Nrf2) pathway in ANIT-injured mice was evaluated. Also the cell survival, intracellular ROS, apoptotic rate, expression of SIRT1/Nrf2 pathway ralated proteins in ANIT-induced human liver HepG2 cells were measured. The mean diameter and zeta potential of STM@GalSLN was 167.30 nm and - 13.10 mV respectively. STM@GalSLN (100 mg/kg) alleviated ANIT-induced CLI in vivo, as evidenced by improved histopathology, decreased levels of liver biochemical indicators and cholestatic markers. Also STM@GalSLN (50 µM) notably increased cell survival, reduced ROS overproduction and apoptotic rate in ANIT-injured hepatocytes. Furthermore, STM@GalSLN significantly upregulated the protein expression levels of hepatic SIRT1, pNrf2, HO-1, and NQO1 during CLI. The protective effect of STM@GalSLN in vitro was blocked using EX-527 (10 mM), a selective SIRT1 inhibitor. Taken together, STM@GalSLN alleviated experimental CLI by enhancing the SIRT1/Nrf2 pathway.
(© 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. All animal experiments were approved by the Animal Ethics Committee of Wuhan Myhalic Biotechnology Co. Ltd. (Code: HLK-20241023-001). This study was conducted in compliance with the National Institutes of Health guidelines for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978). Consent for publication: Not applicable. Competing interests: The authors declare no conflict of interest.
References: Allison, R., Guraka, A., & Shawa, W. K. (2023). Ali. Drug induced liver injury - a 2023 update. Journal of toxicology and environmental health Part B Critical reviews, 26(5/8), 442–467. (PMID: 10.1080/10937404.2023.226184837786264)
Nasir, A. B., Alkhouri, N., Gish, R., Jain, A. K., & Syn, W. K. (2025). Advancing the diagnosis and management of genetic cholestatic liver disease in adults. Digestive Diseases And Sciences, 71(3), 838–851.
Buechter, M., Manka, P., Bulut, K., Gerken, G., & Kahraman, A. (2025). Obeticholic acid improves cholestasis, liver fibrosis, and liver function in patients with primary biliary cholangitis with inadequate response to ursodeoxycholic acid. Journal of Personalized Medicine,15(3), 79.
Gallucci, G. M., Hayes, C. M., Boyer, J. L., Barbier, O., Assis, D. N., & Ghonem, N. S. (2024). PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases. Cells, 13(15), 1296.
Sun, H., Li, D., Wei, C., Liu, L., Xin, Z., Gao, H., & Gao, R. (2024). The relationship between SIRT1 and inflammation: a systematic review and meta-analysis. Frontiers In Immunology, 15, 1465849. (PMID: 10.3389/fimmu.2024.14658493967685311638041)
Zhang, Y., Zhang, W., Tao, L., Zhai, J., Gao, H., Song, Y., & Qu, X. (2019). Quercetin protected against isoniazide-induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway. Journal Of Biochemical And Molecular Toxicology, 33(9), e22369. (PMID: 10.1002/jbt.2236931332904)
Mosaoa, R. M., Al-Rabia, M. W., Asfour, H. Z., Alhakamy, N. A., Mansouri, R. A., El-Agamy, D. S., Abdulaal, W. H., Mohamed, G. A., Ibrahim, S. R. M., & Elshal, M. (2024). Targeting SIRT1/AMPK/Nrf2/NF-кB by sitagliptin protects against oxidative stress-mediated ER stress and inflammation during ANIT-induced cholestatic liver injury. Toxicology, 507, 153889. (PMID: 10.1016/j.tox.2024.15388939029735)
Yu, L., Liu, X., Yuan, Z., Li, X., Yang, H., Yuan, Z., Sun, L., Zhang, L., & Jiang, Z. (2017). SRT1720 Alleviates ANIT-Induced Cholestasis in a Mouse Model. Frontiers In Pharmacology, 8, 256. (PMID: 10.3389/fphar.2017.00256285532275425580)
Fan, G., Luo, W. Z., Luo, S. H., Li, Y., Meng, X. L., Zhou, X. D., & Zhang, Y. (2014). Metabolic discrimination of Swertia mussotii and Swertia chirayita known as Zangyinchen in traditional Tibetan medicine by (1)H NMR-based metabolomics. Journal Of Pharmaceutical And Biomedical Analysis, 98, 364–370. (PMID: 10.1016/j.jpba.2014.06.01424992216)
Shi, M., Tang, J., Zhang, T., & Han, H. (2022). Swertiamarin, an active iridoid glycoside from Swertia pseudochinensis H. Hara, protects against alpha-naphthylisothiocyanate-induced cholestasis by activating the farnesoid X receptor and bile acid excretion pathway. Journal Of Ethnopharmacology, 291, 115164. (PMID: 10.1016/j.jep.2022.11516435278607)
Wu, T., Li, J., Li, Y., & Song, H. (2017). Antioxidant and Hepatoprotective Effect of Swertiamarin on Carbon Tetrachloride-Induced Hepatotoxicity via the Nrf2/HO-1 Pathway. Cellular Physiology And Biochemistry, 41(6), 2242–2254. (PMID: 10.1159/00047563928448964)
Yang, H. X., Hu, Y. Y., Liang, R., Zheng, H., & Zhang, X. (2025). Progress in Pharmacokinetics, Pharmacological Effects, and Molecular Mechanisms of Swertiamarin: A Comprehensive Review. Cells, 14(15), 1173.
Wang, K., Sun, J., Zhao, H., Wang, F., Zhang, X., Zhao, X., Li, Z., Zhang, L., Ren, H., & Guo, B. (2025). Advances and Challenges in Nano-Delivery Systems for Glioblastoma Treatment: A Comprehensive Review. Int J Nanomedicine, 20, 9597–9620. (PMID: 10.2147/IJN.S5314514078595012333657)
Zhang, Y., Liu, H., Zhen, W., Jiang, T., & Cui, J. (2025). Advancement of drugs conjugated with GalNAc in the targeted delivery to hepatocytes based on asialoglycoprotein receptor. Carbohydrate Research, 552, 109426. (PMID: 10.1016/j.carres.2025.10942640068307)
Wang, W., Zhao, X., Hu, H., Chen, D., Gu, J., Deng, Y., & Sun, J. (2010). Galactosylated solid lipid nanoparticles with cucurbitacin B improves the liver targetability. Drug Deliv, 17(3), 114–122. (PMID: 10.3109/1071754090358017620148709)
Hsu, S. J., Hsu, Y. C., Yen, P. L., Lung, C. F., Li, C., Huang, H. C., & Lee, Y. H. (2026). Asialoglycoprotein receptor-bound PLGA nanoparticles loaded with Riociguat targetedly ameliorate portal hypertension in liver cirrhosis. International Journal Of Biological Macromolecules, 360, 151957. (PMID: 10.1016/j.ijbiomac.2026.15195741967542)
Liang, Z., Li, S., Huang, H., Luo, S., Jiang, H., Luo, L., Li, J., & Zhao, K. (2026). GalNAc-modified five-component lipid nanoparticles for liver-targeted delivery of p65 siRNA to alleviate cytokine storm in liver injury via NF-κB targeting. Journal of Materials Chemistry B. Published online May 15, 2026.
Ma, X., Jiang, Y., Zhang, W., Wang, J., Wang, R., Wang, L., Wei, S., Wen, J., Li, H., & Zhao, Y. (2020). Natural products for the prevention and treatment of cholestasis: A review. Phytotherapy Research: Ptr, 34(6), 1291–1309. (PMID: 10.1002/ptr.662132026542)
Gijbels, E., Pieters, A., De Muynck, K., Vinken, M., & Devisscher, L. (2021). Rodent models of cholestatic liver disease: A practical guide for translational research. Liver International : Official Journal Of The International Association For The Study Of The Liver, 41(4), 656–682. (PMID: 10.1111/liv.14800334868848048655)
El-Hawari, A. M., & Plaa, G. L. (1979). Impairment of hepatic mixed-function oxidase activity by alpha- and beta-naphthylisothiocyanate: relationship to hepatotoxicity. Toxicol Appl Pharmacol, 48(3), 445–458. (PMID: 10.1016/0041-008X(79)90428-9112719)
Xu, G. L., Li, H. L., He, J. C., Feng, E. F., Shi, P. P., Liu, Y. Q., & Liu, C. X. (2013). Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone, Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid. Journal Of Ethnopharmacology, 149(1), 49–54. (PMID: 10.1016/j.jep.2013.05.01623791808)
Villanueva-Paz, M., Morán, L., López-Alcántara, N., Freixo, C., Andrade, R. J., Lucena, M. I., & Cubero, F. J. (2021). Oxidative stress in Drug-Induced Liver Injury (DILI): From mechanisms to biomarkers for use in clinical practice. Antioxidants (Basel), 10(3), 390.
Wu, S., Zhao, J., Fang, X., Liao, P., & Liu, G. (2026). From Toxicity Assessment to In Vivo Validation: Exploring the Molecular Mechanisms of Triclosan-Induced Liver Injury. Chemical Research In Toxicology, 39(1), 117–129. (PMID: 10.1021/acs.chemrestox.5c0038041424291)
Yao, H., Xu, Y., Yin, L., Tao, X., Xu, L., Qi, Y., Han, X., Sun, P., Liu, K., & Peng, J. (2017). Dioscin Protects ANIT-Induced Intrahepatic Cholestasis Through Regulating Transporters, Apoptosis and Oxidative Stress. Frontiers In Pharmacology, 8, 116. (PMID: 10.3389/fphar.2017.00116283371455340742)
Verma, M. K., Jaiswal, A., Sharma, P., Kumar, P., & Singh, A. N. (2019). Oxidative stress and biomarker of TNF-α, MDA and FRAP in hypertension. Journal Of Medicine And Life, 12(3), 253–259. (PMID: 10.25122/jml-2019-0031316668276814874)
Jaishree, V., & Badami, S. (2010). Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against D-galactosamine induced acute liver damage in rats. Journal Of Ethnopharmacology, 130(1), 103–106. (PMID: 10.1016/j.jep.2010.04.01920420896)
Wang, T., Wu, S., Ibrahim, I. A. A., & Fan, L. (2023). Cardioprotective Role of Swertiamarin, a Plant Glycoside Against Experimentally Induced Myocardial Infarction via Antioxidant and Anti-inflammatory Functions. Applied Biochemistry And Biotechnology, 195(9), 5394–5408. (PMID: 10.1007/s12010-022-04094-135960488)
He, J., Feng, X., Liu, Y., Wang, Y., Ge, C., Liu, S., & Jiang, Y. (2024). Graveoline attenuates D-GalN/LPS-induced acute liver injury via inhibition of JAK1/STAT3 signaling pathway. Biomedicine & Pharmacotherapy, 177, 117163. (PMID: 10.1016/j.biopha.2024.117163)
Li, W. R., Li, Y. K., Ren, H., Guo, Z., Xiao, C. L., & Luo, J. Q. (2025). Lactobacillus reuteri attenuates methotrexate-induced liver injury via modulation of oxidative stress and inflammation through HO-1/GPX4 and NF-κB/NLRP3 pathways. European Journal Of Pharmacology, 1006, 178185. (PMID: 10.1016/j.ejphar.2025.17818540992648)
Yang, H., Chen, X., Huang, S., Dai, H., Xiao, Z., Fan, J., Zhang, H., Du, K., & Qin (2026). Y. A novel GSH depletor for simultaneous ferroptosis and cuproptosis Activation in hepatocellular carcinoma. Biochemical Pharmacology, 243(Pt 1), 117488. (PMID: 10.1016/j.bcp.2025.11748841173053)
Woolbright, B. L., Antoine, D. J., Jenkins, R. E., Bajt, M. L., Park, B. K., & Jaeschke, H. (2013). Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice. Toxicol Appl Pharmacol, 273(3), 524–531. (PMID: 10.1016/j.taap.2013.09.023240960363860754)
Tao, X., Wan, X., Xu, Y., Xu, L., Qi, Y., Yin, L., Han, X., Lin, Y., & Peng, J. (2014). Dioscin attenuates hepatic ischemia-reperfusion injury in rats through inhibition of oxidative-nitrative stress, inflammation and apoptosis. Transplantation, 98(6), 604–611. (PMID: 10.1097/TP.000000000000026225083618)
Zou, B., Zhang, S., Zhao, J., Song, G., Weng, F., Xu, X., Li, F., Jin, J., Yan, D., Huang, K., Liu, C., Li, Y., & Qiu, F. (2023). Glycyrrhetinic acid attenuates endoplasmic reticulum stress-induced hepatocyte apoptosis via CHOP/DR5/Caspase 8 pathway in cholestasis. European Journal Of Pharmacology, 961, 176193. (PMID: 10.1016/j.ejphar.2023.17619337981257)
Xiang, D., Liu, Y., Zu, Y., Yang, J., He, W., Zhang, C., & Liu, D. (2023). Calculus Bovis Sativus alleviates estrogen cholestasis-induced gut and liver injury in rats by regulating inflammation, oxidative stress, apoptosis, and bile acid profiles. Journal Of Ethnopharmacology. 302(Pt A):115854.
Mavaddat, H., Ale-Ebrahim, M., & Sabouni Aghdam, D. (2025). Effects of saponin on testes oxidative stress, apoptosis, and steroid hormone synthesis pathway in bile duct ligation model of obstructive cholestasis in male Wistar rats. Journal Of Nutritional Biochemistry, 145, 110020. (PMID: 10.1016/j.jnutbio.2025.11002040633625)
He, L., Guo, C., Peng, C., & Li, Y. (2021). Advances of natural activators for Nrf2 signaling pathway on cholestatic liver injury protection: a review. European Journal Of Pharmacology, 910, 174447. (PMID: 10.1016/j.ejphar.2021.17444734461126)
Gao, W., Zhao, C., Shang, X., Li, B., Guo, J., Wang, J., Wu, B., & Fu, Y. (2024). Ameliorative Effects of raisin polyphenol extract on oxidative stress and aging in vitro and in vivo via regulation of Sirt1-Nrf2 signaling pathway. Foods, 14(1), 71.
Zhang, H., Wu, D., Wu, Q., Wu, Y., Guo, Z., Wang, L., Wang, Y., Zeng, Q., Shi, L., Shi, B., Yu, G., & Lv, W. (2025). The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi-target Therapeutic Strategies. J Clin Transl Hepatol, 13(10), 878–898. (PMID: 4108971512515640)
Colak, Y., Yesil, A., Mutlu, H. H., Caklili, O. T., Ulasoglu, C., Senates, E., Takir, M., Kostek, O., Yilmaz, Y., Yilmaz Enc, F., & Tasan, G. (2014). Tuncer I. A potential treatment of non-alcoholic fatty liver disease with SIRT1 activators. J Gastrointestin Liver Dis, 23(3), 311–319. (PMID: 10.15403/jgld.2014.1121.233.yck25267960)
Elmorsy, E. A., Elsisi, H. A., Alkhamiss, A. S., Alsoqih, N. S., Khodeir, M. M., Alsalloom, A. A., Almeman, A. A., Elghandour, S. R., Nadwa, E. H., Khalifa, A. K., Khaled, B. E. A., Ramadan, A., Kamal, M. M., et al. (2025). Activation of SIRT1 by SRT1720 alleviates dyslipidemia, improves insulin sensitivity and exhibits liver-protective effects in diabetic rats on a high-fat diet: New insights into the SIRT1/Nrf2/NFκB signaling pathway. European Journal Of Pharmaceutical Sciences, 206, 107002. (PMID: 10.1016/j.ejps.2025.10700239778687)
Gao, Q., Li, G., Zu, Y., Xu, Y., Wang, C., Xiang, D., He, W., Shang, T., Cheng, X., Liu, D., & Zhang, C. (2024). Ginsenoside Rg1 alleviates ANIT-induced cholestatic liver injury by inhibiting hepatic inflammation and oxidative stress via SIRT1 activation. Journal Of Ethnopharmacology, 319(Pt 1), 117089. (PMID: 10.1016/j.jep.2023.11708937634749)
Yan, M., Guo, L., Ma, J., Yang, Y., Tang, T., Zhang, B., Zhou, W., Zou, W., Hou, Z., Gu, H., & Gong, H. (2023). Liquiritin alleviates alpha-naphthylisothiocyanate-induced intrahepatic cholestasis through the Sirt1/FXR/Nrf2 pathway. Journal Of Applied Toxicology, 43(3), 350–359. (PMID: 10.1002/jat.438536008890)
Xiang, J., Chen, S., & Tan, S. (2026). A comprehensive review of the Maillard reaction in solid pharmaceutical dosage forms: a focus on lactose. Expert Opinion On Drug Delivery, 23(4), 697–716. (PMID: 10.1080/17425247.2026.261392141496557)
Zeng, J., Zhang, Y., Gao, Y., Jia, M., Guo, Y., Li, X., Wang, Y., Zhao, C., Qiu, J., McGinty, S., Miao, W., Wang, G., & Wang, Y. (2025). Biomimetic Ginsenoside Rb1 and Probucol Co-Assembled Nanoparticles for Targeted Atherosclerosis Therapy via Inhibition of Oxidative Stress, Inflammation, and Lipid Deposition. Acs Nano, 19(25), 22968–22987. (PMID: 10.1021/acsnano.5c0249240534137)
Grant Information: 2023020201010195 Wuhan Municipal Science and Technology Bureau
Contributed Indexing: Keywords: Cholestatici liver injury; Galactosylated lipid; SIRT1; Solid lipid nanoparticles; Swertiamarin
Substance Nomenclature: EC 3.5.1.- (Sirtuin 1)
0 (NF-E2-Related Factor 2)
0 (Iridoid Glucosides)
0 (Pyrones)
4038595T7Y (swertiamarin)
X2RN3Q8DNE (Galactose)
0 (Lipids)
0 (NFE2L2 protein, human)
EC 3.5.1.- (Sirt1 protein, mouse)
0 (Lipid Nanoparticles)
0 (Nfe2l2 protein, mouse)
0 (Liposomes)
Entry Date(s): Date Created: 20260613 Date Completed: 20260923 Latest Revision: 20260923
Update Code: 20260924
DOI: 10.1007/s12010-026-05774-y
PMID: 42287535
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1559-0291
DOI:10.1007/s12010-026-05774-y