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A hesperetin derivative plays a role in immunoregulatory effect on human macrophages
Corresponding Author(s) : Jian-li Ma
Cellular and Molecular Biology,
Vol. 65 No. 4: Issue 4
Abstract
The immune system is an important physiological defense system. Its balance and stability are closely related to the body's health. Once the immune system loses its dynamic balance, the immune response will be blocked, which will lead to the occurrence of various diseases. Hesperetin is a kind of natural flavonoids extracted from citrus fruits of Rutaceae and it has many pharmacological activities. However, its water solubility and liposolubility are poor, and it is easy to be quickly metabolized in vivo, so it is difficult to maintain high blood drug concentration. Therefore, its derivative (HES) was found by structural modification. In this study, THP-1 cells were used as experimental model to investigate the immunomodulatory effect of HES in vitro. The results showed that HES participates in immune response by enhancing phagocytosis of macrophages to promote the release of NO, IL-6 and IL-1β, and enhancing immunity by up-regulating the expression of Bcl-2 and Bcl-XL proteins. This study provides a theoretical and practical basis for the development of HES as an immunomodulator in the future.
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- Yazid FB, Gnanasegaran N, Kunasekaran W, Govindasamy V, Musa S. Comparison of immunodulatory properties of dental pulp stem cells derived from healthy and inflamed teeth. Clin Oral Investig 2014; 18: 2103-2112.
- Benhamou PY, Kenmochi T, Miyamoto M, Nakagawa Y, Une S, Stein E, et al. Fetal pancreas transplantation in miniature swine. V. The functional and immunodulatory effects of ultraviolet light on fetal pig islets. Transplantation 1995; 59: 1660.
- Dalmo RA, Seljelid R. The immunomodulatory effect of LPS, laminaran and sulphated laminaran [β(l,3)-D-glucan] on Atlantic salmon, Salmo salar L., macrophages in vitro. J Fish Dis 2010; 18: 175-185.
- Song Y, Chen GT, Sun BH, Huang J, Li X, Wu LJ. Chemical constituents of water-soluble part of Mentha spicata L. J Shenyang PharmUniv 2008.
- Walle T, Vincent TS, Walle UK. Evidence of covalent binding of the dietary flavonoid quercetin to DNA and protein in human intestinal and hepatic cells. Biochem Pharmacol 2003; 65: 1603-1610.
- Lin X, Kong LN, Huang C, Ma TT, Meng XM, He Y, et al. Hesperetin derivative-7 inhibits PDGF-BB-induced hepatic stellate cell activation and proliferation by targeting Wnt/β-catenin pathway. Int Immunopharmacol 2015; 25: 311-320.
- Erlund I, Meririnne E, G, Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr 2001; 131: 235-241.
- Ameer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL. Therapeutics: Flavanone absorption after naringin, hesperidin, and citrus administration. Clin Pharmacol Ther 1996; 60: 34-40.
- Park HJ, Kim MJ, Ha E, Chung JH. Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine 2008; 15: 147-151.
- Yeh CC, Kao SJ, Lin CC, Wang SD, Liu CJ, Kao ST. The immunomodulation of endotoxin-induced acute lung injury by hesperidin in vivo and in vitro. Life Sci 2007; 80: 1821-1831.
- Garg A, Garg S, Zaneveld LJ, Singla AK. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res 2001; 15: 655-669.
- Chen MJ, Liang T, Zhou KY. [Effect of proanthocyanidins on COX-2 enzyme activity and COX-2 mRNA /protein expression in LPS-induced RAW264.7 cells]. Yao Xue Xue Bao 2005; 40: 406.
- Yang DJ, Lin JT, Chen YC, Liu SC, Lu FJ, Chang TJ, et al. Suppressive effect of carotenoid extract of Dunaliella salina alga on production of LPS-stimulated pro-inflammatory mediators in RAW264.7 cells via NF-κB and JNK inactivation. J Funct Foods 2013; 5: 607-615.
- Lin HW, Liu CW, Yang DJ, Chen CC, Chen SY, Tseng JK, et al. Dunaliella salina alga extract inhibits the production of interleukin-6, nitric oxide, and reactive oxygen species by regulating nuclear factor-펺B/Janus kinase/signal transducer and activator of transcription in virus-infected RAW264.7í‚ cells. J Food Drug Anal 2017; 25: 908-918.
- Noel S, Panin N, Beka M, Dhooghe B, Huaux F, Leal T. Vardenafil reduces macrophage pro-inflammatory overresponses in Cystic Fibrosis through PDE5- and CFTR-dependent mechanisms. Clin Sci (Lond) 2017; 131: 20160749.
- Lin HW, Chen YC, Liu CW, Yang DJ, Chen SY, Chang TJ, et al. Regulation of virus-induced inflammatory response by Dunaliella salina alga extract in macrophages. Food Chem Toxicol 2014; 71: 159-165.
- Liu CW, Lin HW, Yang DJ, Chen SY, Tseng JK, Chang TJ, et al. Medicine: Luteolin inhibits viral-induced inflammatory response in RAW264.7 cells via suppression of STAT1/3 dependent NF-κB and activation of HO-1. Free Radic Biol Med 2016; 95: 180-189.
- Almutary A, Sanderson BJ. The MTT and Crystal Violet Assays: Potential Confounders in Nanoparticle Toxicity Testing. Int J Toxicol 2016; 35: 454.
- Dalmo RA, Seljelid R. The immunomodulatory effect of LPS, laminaran and sulphated laminaran [β(l,3)"D"glucan] on Atlantic salmon, Salmo salar L., macrophages in vitro. J Fish Dis 2010; 18: 175-185.
- Christian B. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol 2015; 36: 161-178.
- Zhu H, Wang Q, Yao Y, Fang J, Sun F, Ni Y, et al. Microarray analysis of Long non-coding RNA expression profiles in human gastric cells and tissues withHelicobacter pyloriInfection. BMC Med Genomics 2015; 8: 1-11.
- Carlos AJ, Tong L, Prieto GA, Cotman CW. IL-1β impairs retrograde flow of BDNF signaling by attenuating endosome trafficking. J Neuroinflammation 2017; 14: 29.
- Atreya R, Neurath MF. Signaling molecules: the pathogenic role of the IL-6/STAT-3 trans signaling pathway in intestinal inflammation and in colonic cancer. Curr Drug Targets 2008; 9: 369-374.
- Hwang JH, Kim KJ, Ryu SJ, Lee BY. Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish. Chem Biol Interact 2016; 248: 1-7.
References
Yazid FB, Gnanasegaran N, Kunasekaran W, Govindasamy V, Musa S. Comparison of immunodulatory properties of dental pulp stem cells derived from healthy and inflamed teeth. Clin Oral Investig 2014; 18: 2103-2112.
Benhamou PY, Kenmochi T, Miyamoto M, Nakagawa Y, Une S, Stein E, et al. Fetal pancreas transplantation in miniature swine. V. The functional and immunodulatory effects of ultraviolet light on fetal pig islets. Transplantation 1995; 59: 1660.
Dalmo RA, Seljelid R. The immunomodulatory effect of LPS, laminaran and sulphated laminaran [β(l,3)-D-glucan] on Atlantic salmon, Salmo salar L., macrophages in vitro. J Fish Dis 2010; 18: 175-185.
Song Y, Chen GT, Sun BH, Huang J, Li X, Wu LJ. Chemical constituents of water-soluble part of Mentha spicata L. J Shenyang PharmUniv 2008.
Walle T, Vincent TS, Walle UK. Evidence of covalent binding of the dietary flavonoid quercetin to DNA and protein in human intestinal and hepatic cells. Biochem Pharmacol 2003; 65: 1603-1610.
Lin X, Kong LN, Huang C, Ma TT, Meng XM, He Y, et al. Hesperetin derivative-7 inhibits PDGF-BB-induced hepatic stellate cell activation and proliferation by targeting Wnt/β-catenin pathway. Int Immunopharmacol 2015; 25: 311-320.
Erlund I, Meririnne E, G, Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr 2001; 131: 235-241.
Ameer B, Weintraub RA, Johnson JV, Yost RA, Rouseff RL. Therapeutics: Flavanone absorption after naringin, hesperidin, and citrus administration. Clin Pharmacol Ther 1996; 60: 34-40.
Park HJ, Kim MJ, Ha E, Chung JH. Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine 2008; 15: 147-151.
Yeh CC, Kao SJ, Lin CC, Wang SD, Liu CJ, Kao ST. The immunomodulation of endotoxin-induced acute lung injury by hesperidin in vivo and in vitro. Life Sci 2007; 80: 1821-1831.
Garg A, Garg S, Zaneveld LJ, Singla AK. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res 2001; 15: 655-669.
Chen MJ, Liang T, Zhou KY. [Effect of proanthocyanidins on COX-2 enzyme activity and COX-2 mRNA /protein expression in LPS-induced RAW264.7 cells]. Yao Xue Xue Bao 2005; 40: 406.
Yang DJ, Lin JT, Chen YC, Liu SC, Lu FJ, Chang TJ, et al. Suppressive effect of carotenoid extract of Dunaliella salina alga on production of LPS-stimulated pro-inflammatory mediators in RAW264.7 cells via NF-κB and JNK inactivation. J Funct Foods 2013; 5: 607-615.
Lin HW, Liu CW, Yang DJ, Chen CC, Chen SY, Tseng JK, et al. Dunaliella salina alga extract inhibits the production of interleukin-6, nitric oxide, and reactive oxygen species by regulating nuclear factor-펺B/Janus kinase/signal transducer and activator of transcription in virus-infected RAW264.7í‚ cells. J Food Drug Anal 2017; 25: 908-918.
Noel S, Panin N, Beka M, Dhooghe B, Huaux F, Leal T. Vardenafil reduces macrophage pro-inflammatory overresponses in Cystic Fibrosis through PDE5- and CFTR-dependent mechanisms. Clin Sci (Lond) 2017; 131: 20160749.
Lin HW, Chen YC, Liu CW, Yang DJ, Chen SY, Chang TJ, et al. Regulation of virus-induced inflammatory response by Dunaliella salina alga extract in macrophages. Food Chem Toxicol 2014; 71: 159-165.
Liu CW, Lin HW, Yang DJ, Chen SY, Tseng JK, Chang TJ, et al. Medicine: Luteolin inhibits viral-induced inflammatory response in RAW264.7 cells via suppression of STAT1/3 dependent NF-κB and activation of HO-1. Free Radic Biol Med 2016; 95: 180-189.
Almutary A, Sanderson BJ. The MTT and Crystal Violet Assays: Potential Confounders in Nanoparticle Toxicity Testing. Int J Toxicol 2016; 35: 454.
Dalmo RA, Seljelid R. The immunomodulatory effect of LPS, laminaran and sulphated laminaran [β(l,3)"D"glucan] on Atlantic salmon, Salmo salar L., macrophages in vitro. J Fish Dis 2010; 18: 175-185.
Christian B. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol 2015; 36: 161-178.
Zhu H, Wang Q, Yao Y, Fang J, Sun F, Ni Y, et al. Microarray analysis of Long non-coding RNA expression profiles in human gastric cells and tissues withHelicobacter pyloriInfection. BMC Med Genomics 2015; 8: 1-11.
Carlos AJ, Tong L, Prieto GA, Cotman CW. IL-1β impairs retrograde flow of BDNF signaling by attenuating endosome trafficking. J Neuroinflammation 2017; 14: 29.
Atreya R, Neurath MF. Signaling molecules: the pathogenic role of the IL-6/STAT-3 trans signaling pathway in intestinal inflammation and in colonic cancer. Curr Drug Targets 2008; 9: 369-374.
Hwang JH, Kim KJ, Ryu SJ, Lee BY. Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish. Chem Biol Interact 2016; 248: 1-7.