Abstract
Jujuboside B (JB) found in the seeds of Zizyphi Spinosi Semen possesses pharmacological functions, such as anti-inflammatory, antiplatelet aggregation, and antianxiety potentials. This study evaluated the effect of JB on liver failure in cecal ligation and puncture (CLP)-induced sepsis. First, we observed histopathological changes in the liver by optical microscopy and the activity of enzymes in serum such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We further measured the levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, nitric oxide (NO), and antioxidative parameters in liver homogenate. The expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), and glucocorticoid receptor (GR) in the liver was observed by Western blotting. CLP enhanced the migration of inflammatory cells, ALT and AST concentrations, and necrosis, which were reduced by JB. In addition, JB reduced 11β-HSD2 expression and levels of inflammatory mediators (TNF-α, IL-1β, and NO) in the liver, increased GR expression, enhanced endogenous antioxidative capacity. These results further suggest that JB may protect the liver against CLP-induced damage by regulating anti-inflammatory responses, downregulating 11β-HSD2 expression and antioxidation, and up-regulating GR expression.
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References
Sun S, Liu H, Xu S, Yan Y, Xie P (2014) Quality analysis of commercial samples of Ziziphi spinosae semen (suanzaoren) by means of chromatographic fingerprinting assisted by principal component analysis. J Pharm Anal 4:217–222
Jiang JG, Huang XJ, Chen J, Lin QS (2007) Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube. Nat Prod Res 21:310–320
Al-Reza SM, Yoon JI, Kim HJ, Kim JS, Kang SC (2010) Anti-inflammatory activity of seed essential oil from Zizyphus jujuba. Food Chem Toxicol 48:639–643
Cao JX, Zhang QY, Cui SY et al (2010) Hypnotic effect of jujubosides from Semen Ziziphi Spinosae. J Ethnopharmacol 130:163–166
Chen J, Lam CT, Kong AY et al (2014) The extract of Ziziphus jujuba fruit (jujube) induces expression of erythropoietin via hypoxia-inducible factor-1alpha in cultured Hep3B cells. Planta Med 80:1622–1627
Ninave PB, Patil SD (2019) Antiasthmatic potential of Zizyphus jujuba Mill and Jujuboside B.—Possible role in the treatment of asthma. Respir Physiol Neurobiol 260:28–36
Seo EJ, Lee SY, Kang SS, Jung YS (2013) Zizyphus jujuba and its active component jujuboside B inhibit platelet aggregation. Phytother Res 27:829–834
Vassiliou AG, Athanasiou N, Vassiliadi DA et al (2021) Glucocorticoid and mineralocorticoid receptor expression in critical illness: a narrative review. World J Crit Care Med 10:102–111
Diederich S, Eigendorff E, Burkhardt P et al (2002) 11beta-hydroxysteroid dehydrogenase types 1 and 2: an important pharmacokinetic determinant for the activity of synthetic mineralo- and glucocorticoids. J Clin Endocrinol Metab 87:5695–5701
Dendoncker K, Libert C (2017) Glucocorticoid resistance as a major drive in sepsis pathology. Cytokine Growth Factor Rev 35:85–96
Bae JS (2012) Role of high mobility group box 1 in inflammatory disease: focus on sepsis. Arch Pharm Res 35:1511–1523
Schefold JC, Hasper D, Reinke P, Monneret G, Volk HD (2008) Consider delayed immunosuppression into the concept of sepsis. Crit Care Med 36:3118
Yan J, Li S, Li S (2014) The role of the liver in sepsis. Int Rev Immunol 33:498–510
Dhainaut JF, Marin N, Mignon A, Vinsonneau C (2001) Hepatic response to sepsis: interaction between coagulation and inflammatory processes. Crit Care Med 29:S42–S47
Szabo G, Romics L Jr, Frendl G (2002) Liver in sepsis and systemic inflammatory response syndrome. Clin Liver Dis 6:1045–1066
Kobashi H, Toshimori J, Yamamoto K (2013) Sepsis-associated liver injury: incidence, classification and the clinical significance. Hepatol Res 43:255–266
Fang M, Zou T, Yang X et al (2021) Discovery of novel pterostilbene derivatives that might treat sepsis by attenuating oxidative stress and inflammation through modulation of MAPKs/NF-kappaB signaling pathways. Antioxidants 10:1333
Chen L, Huang Q, Zhao T et al (2021) Nanotherapies for sepsis by regulating inflammatory signals and reactive oxygen and nitrogen species: new insight for treating COVID-19. Redox Biol 45:102046
Wu Q, Wang Y, Li Q (2021) Matairesinol exerts anti-inflammatory and antioxidant effects in sepsis-mediated brain injury by repressing the MAPK and NF-kappaB pathways through up-regulating AMPK. Aging 13:23780–23795
Donnelly MC, Hayes PC, Simpson KJ (2016) Role of inflammation and infection in the pathogenesis of human acute liver failure: clinical implications for monitoring and therapy. World J Gastroenterol 22:5958–5970
Pacher P, Beckman JS, Liaudet L (2007) Nitric oxide and peroxynitrite in health and disease. Physiol Rev 87:315–424
Bradham CA, Plumpe J, Manns MP, Brenner DA, Trautwein C (1998) Mechanisms of hepatic toxicity. I TNF-induced liver injury. Am J Physiol 275:G387-392
Crespo J, Cayon A, Fernandez-Gil P et al (2001) Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 34:1158–1163
Zang GQ, Zhou XQ, Yu H et al (2000) Effect of hepatocyte apoptosis induced by TNF-alpha on acute severe hepatitis in mouse models. World J Gastroenterol 6:688–692
Honore PM, Hoste E, Molnar Z et al (2019) Cytokine removal in human septic shock: where are we and where are we going? Ann Intensive Care 9:56
Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL (2016) Sepsis and septic shock. Nat Rev Dis Primers 2:16045
Ronchetti S, Ayroldi E, Ricci E, Gentili M, Migliorati G, Riccardi C (2021) A glance at the use of glucocorticoids in rare inflammatory and autoimmune diseases: still an indispensable pharmacological tool? Front Immunol 11:613435
Miller AH (2008) Inflammation versus glucocorticoids as purveyors of pathology during stress: have we reached the tipping point? Biol Psychiatry 64:263–265
Schein RM, Sprung CL, Marcial E, Napolitano L, Chernow B (1990) Plasma cortisol levels in patients with septic shock. Crit Care Med 18:259–263
Oakley RH, Cidlowski JA (2013) The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease. J Allergy Clin Immunol 132:1033–1044
Xin W, Zhang L, Fan H, Jiang N, Wang T, Fu F (2011) Escin attenuates acute lung injury induced by endotoxin in mice. Eur J Pharm Sci 42:73–80
Zhang L, Huang Y, Wu C et al (2019) Network Pharmacology based research on the combination mechanism between escin and low dose glucocorticoids in anti-rheumatoid arthritis. Front Pharmacol 10:280
Song Y, Zhao F, Zhang L, Du Y, Wang T, Fu F (2013) Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro. Fitoterapia 91:173–179
Bermejo-Martin JF, Martin-Fernandez M, Lopez-Mestanza C, Duque P, Almansa R (2018) Shared features of endothelial dysfunction between sepsis and its preceding risk factors (aging and chronic disease). J Clin Med 7:400
Lee W, Lee H, Lee T, Park EK, Bae JS (2020) Inhibitory functions of maslinic acid, a natural triterpene, on HMGB1-mediated septic responses. Phytomedicine 69:153200
Jeong SY, Kim M, Park EK, Kim J-S, Hahn D, Bae J-S (2020) Inhibitory functions of novel compounds from dioscorea batatas decne peel on HMGB1-mediated septic responses. Biotechnol Bioproc Eng 25:1–8
Lee W, Ku SK, Kim JE, Cho GE, Song GY, Bae JS (2019) Pulmonary protective functions of rare ginsenoside Rg4 on particulate matter-induced inflammatory responses. Biotechnol Bioproc Eng 24:445–453
Lee I-C, Ryu C-W, Bae J-S (2020) Novel herbal medicine C-KOK suppresses the inflammatory gene iNOS via the Inhibition of p-STAT-1 and NF-κB. Biotechnol Bioproc Eng 25:536–542
Lee WH, Choo S, Sim H, Bae JS (2021) Inhibitory activities of ononin on particulate matter-induced oxidative stress. Biotechnol Bioproc Eng 26:208–215
Lee W, Jeong GS, Baek MC, Ku SK, Bae JS (2019) Renal protective effects of aloin in a mouse model of sepsis. Food Chem Toxicol 132:110651
Lee IC, Bae JS (2019) Pelargonidin protects against renal injury in a mouse model of sepsis. J Med Food 22:57–61
Sim H, Noh Y, Choo S, Kim N, Lee T, Bae JS (2021) Suppressive activities of fisetin on particulate matter-induced oxidative stress. Biotechnol Bioproc Eng 26:568–574
Acknowledgements
This study was financially supported by a grant of the Korean Health Technology R and D Project, Ministry of Health and Welfare, Republic of Korea (HI15C0001) and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2020R1A2C1004131).
Funding
The work of Jong-Sup Bae was supported by Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea, HI15C0001, and National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT), 2020R1A2C1004131.
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Kim, C., Jeong, Y.H., Kim, N. et al. Hepatoprotective functions of jujuboside B. J Nat Med 77, 87–95 (2023). https://doi.org/10.1007/s11418-022-01648-9
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DOI: https://doi.org/10.1007/s11418-022-01648-9