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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Effect and Mechanism of Specnuezhenide on Chemotherapy-induced Myelosuppression

Author(s): Jiahong Han, Nian Sun, Junjia Xing, Xuan Fei, Enbo Cai* and Fengyan Su*

Volume 26, Issue 13, 2023

Published on: 10 April, 2023

Page: [2393 - 2400] Pages: 8

DOI: 10.2174/1386207326666230228120608

Price: $65

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Abstract

Objective: This study aimed to investigate the therapeutic effect of Specnuezhenide on myelosuppression induced by chemotherapy and clarify its mechanism.

Methods: In this study, we measured peripheral blood cells, thymus index, spleen index, bone marrow nucleated cells (BMNCs), and the number of cell colonies counted in vitro by hematopoietic progenitor cells (HPCs) to determine the effect of SPN on cyclophosphamide (CTX)-induced myelosuppression. The alterations in the expression of relevant proteins, the cell cycle, and cytokines associated with hematopoietic cells were examined to better understand how it works.

Results: In the cyclophosphamide-induced mouse model, our study discovered that SPN can increase the number of peripheral blood cells and BMNCs after treatment, increase the thymus index and decrease the spleen index, and promote the proliferation and differentiation of HPCs. SPN can improve the production of cultured colonies in vitro, reduce the level of hematopoietic factors in vivo, regulate the proportion of G0/G1 phase cells, and promote the normal growth and development of cells. SPN can increase the expression levels of key proteins MEK and p-ERK in the MAPK signaling pathway, which may be one of the important mechanisms for improving myelosuppression.

Conclusion: SPN can enhance the hematological and immunological functions of myelosuppressionmice, and it is hypothesized that SPN is extremely helpful to the hematopoietic and immune functions of tumor patients following chemotherapy. SPN might be used to treat myelosuppression. Additionally, high doses of SPN have a stronger therapeutic effect than low levels of SPN.

Keywords: Specnuezhenide, ligustrum lucidum, cyclophosphamide, chemotherapy, myelosuppression, bone marrow.

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[1]
Chen, W.Q.; Zheng, R.S.; Zhang, S.W.; Zeng, H.M.; Zuo, T.T.; Jia, M.M.; Xia, C.F.; Zou, X.N.; He, J. Report of cancer incidence and mortality in China, 2011. Chin. Cancer, 2015, 24(1), 1-10.
[2]
Ayhanci, A.; Günes, S.; Sahinturk, V.; Appak, S.; Uyar, R.; Cengiz, M.; Altuner, Y.; Yaman, S. Seleno L-methionine acts on cyclophosphamide-induced kidney toxicity. Biol. Trace Elem. Res., 2010, 136(2), 171-179.
[http://dx.doi.org/10.1007/s12011-009-8535-2] [PMID: 19826776]
[3]
Zheng, J.P. Experience in clinical application of danggui sini decoction. J. Chin. Integr. Med., 2005, 3(4), 289-293, 293.
[http://dx.doi.org/10.3736/jcim20050412] [PMID: 16009108]
[4]
Quesenberry, P.J. Biomodulation of chemotherapyinduced myelosuppression. Semin. Oncol., 1992, 19(3), 8-13.
[5]
Zhu, Q.; Xu, L.H. Related factors analysis of myelosuppression caused by antineoplastic. Pharm. Clin. Res., 2015, 23(1), 68-70.
[6]
Alyamkina, E.A.; Nikolin, V.P.; Popova, N.A.; Dolgova, E.V.; Proskurina, A.S.; Orishchenko, K.E.; Efremov, Y.R.; Chernykh, E.R.; Ostanin, A.A.; Sidorov, S.V.; Ponomarenko, D.M.; Zagrebelniy, S.N.; Bogachev, S.S.; Shurdov, M.A. A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation. Genet. Vaccines Ther., 2010, 8(1), 7-17.
[http://dx.doi.org/10.1186/1479-0556-8-7] [PMID: 21040569]
[7]
Yin, J.H.; Shen, X.H. Progress of experimental animal studies on the interventional effect of Chinese medicine on myelosuppression induced by chemotherapy in malignant tumors. J. Shanghai Univ. Tradit. Chin. Med., 2010, 24, 78.
[8]
Hoekman, K.; Wagstaff, J. Effects of recombinant human granulocyte- macrophage colony-stimulating factor on myelosuppression induced by multiple cycles of high-dose chemotherapy in patients with advanced breast cancer. J. Natl. Cancer Inst., 1991, 83(21), 1546e53.
[9]
Molyneux, G.; Andrews, M.; Sones, W.; York, M.; Barnett, A.; Quirk, E.; Yeung, W.; Turton, J. Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophos-phamide in the female BALB/c mouse using a brief regimen of drug admin-istration. Cell Biol. Toxicol., 2011, 27(1), 13e40.
[10]
Toussaint, O.; Medrano, E.E.; Von, Z.T. Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes. Exp. Gerontol., 2000, 35(8), 927e45.
[11]
Wickremasinghe, R.G.; Hoffbrand, A.V. Biochemical and genetic control of apoptosis: Relevance to normal hematopoiesis and hematological malig-nancies. Blood, 1999, 93(11), 3587e600.
[12]
Huang, X.P.; Wang, W.C. Chemical constitutents of Ligustrum lucidum fruits: Research advances. Int. J. Pharm. Res., 2011, 38(1), 47-51.
[13]
Liu, M.; Zhang, J.; Xiao, J.C.; Liu, H.N.; Cao, Z.J.; Li, X.K.; Ma, L. Determination of Content of Specnuezhenide and establishment of fingerprint for Ligustri lucidi fructus by HPLC. Zhongguo Xiandai Zhongyao, 2019, 12(21), 1647-1652.
[14]
Luo, J.; Luo, Y.P.; Luo, R.F.; Luo, J.J. Optimization of extracting process of Ligustri lucidi fructus. Farm Prod. Proc., 2020, (11), 48-51.
[15]
Xi, Y.Y.; Diao, J.W.; Zhang, X.L.; Li, Z.M.; Guo, C.C.; Li, H.F.; Xu, B.X.; Luan, R.Q.; Qu, C.C. Pharmacokinetic behaviors of four constituents in Ligustrum lucidum in rat plasma. Zhongchengyao, 2018, 40(8), 1721-1726.
[16]
Hu, D.M.; Lu, Y.; Fang, M.F.; Wang, J.W.; Wen, A.D. Protective effects of specnuezhenide against carbon tetrachloride-induced acute hepatic damage in mice. Chin Pharmacol. Bull., 2016, (09), 1260-1263.
[17]
Cai, Z.; Shi, L.F.; Hu, J.H.; Shen, Q. Effects of specnuezhenide on the proliferation ability of lymphocytes and cytotoxicity of natural killer cells in murine splenocytes in vitro. Acad. J. Sec. Mil. Med. Univ., 1998, 19(1), 76-78.
[18]
Gu, W.; Liu, T.; Chen, J.L.; Shen, D.Z.; Xing, S.L.; Yu, Z.H.; Chen, C. Effect of specnuezhenide reducing the oxidative damage of vascular endothelial cells. Chin. J. Int. Tradit. West. Med., 2018, 38(9), 1093-1098.
[19]
Li, Y. Study on the composition of cleaved cyclic cyclic enol ether terpene glycosides in chasteberry., MS Thesis, Northwest University, 2007.
[20]
Tian, G.; Chen, J.; Luo, Y.; Yang, J.; Gao, T.; Shi, J. Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo. Cancer Cell Int., 2019, 19(1), 246.
[http://dx.doi.org/10.1186/s12935-019-0960-5] [PMID: 31572063]
[21]
Han, J.; Wang, Y.; Cai, E.; Zhang, L.; Zhao, Y.; Sun, N.; Zheng, X.; Wang, S. Study of the effects and mechanisms of ginsenoside compound K on Myelosuppression. J. Agric. Food Chem., 2019, 67(5), 1402-1408.
[http://dx.doi.org/10.1021/acs.jafc.8b06073] [PMID: 30629411]
[22]
Patra, K.; Bose, S.; Sarkar, S.; Rakshit, J.; Jana, S.; Mukherjee, A.; Roy, A.; Mandal, D.P.; Bhattacharjee, S. Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid. Chem. Biol. Interact., 2012, 195(3), 231-239.
[http://dx.doi.org/10.1016/j.cbi.2012.01.001] [PMID: 22285266]
[23]
Feng, L.; Huang, Q.; Huang, Z.; Li, H.; Qi, X.; Wang, Y.; Liu, Z.; Liu, X.; Lu, L. Optimized animal model of cyclophosphamide-induced bone marrow suppression. Basic Clin. Pharmacol. Toxicol., 2016, 119(5), 428-435.
[http://dx.doi.org/10.1111/bcpt.12600] [PMID: 27061017]
[24]
Chen, X-Y.; Zhao, A.; Yu, B.; Wu, X-L.; Cao, K-J.; Li, E.Q.; Li, Q-M. Protective effects on myelosuppression mice treated by three different classic Chinese medicine formulae. Pharmacogn. Mag., 2011, 7(26), 133-140.
[http://dx.doi.org/10.4103/0973-1296.80671] [PMID: 21716623]
[25]
Wang, C.; Gao, H.; Cai, E.; Zhang, L.; Zheng, X.; Zhang, S.; Sun, N.; Zhao, Y. Protective effects of Acanthopanax senticosus-Ligustrum lucidum combination on bone marrow suppression induced by chemotherapy in mice. Biomed. Pharmacother., 2019, 109, 2062-2069.
[http://dx.doi.org/10.1016/j.biopha.2018.11.071] [PMID: 30551462]
[26]
Han, J.H. Chemical composition analysis of Ginseng, Ligustri Lucidi Fructus compatibility and its protective effect on cyclophosphamide- induced myelosuppression in mice., PD Thesis, Jilin Agricultural University 2019.
[27]
Han, J.; Fei, X.; Sun, N.; Xing, J.; Cai, E.; Yang, L. Effect of Ligustri Lucidi Fructus on myelosuppression in mice induced by cytoxan. Biomed. Chromatogr., 2023, 37(1), e5524.
[http://dx.doi.org/10.1002/bmc.5524] [PMID: 36241188]
[28]
An, R.; Yi, W.W.; Ju, Z.Y. Review: Progress in hematopoietic stem cell ageing research. Prog. Biochem. Biophys., 2014, 41(3), 238-246.
[29]
Li, F.F. Effect of Jingyuankang capsule on peripheral blood and p53 proteincontent in marrow nuclear cells of myelosuppression mice induced by chemotherapy. MS Thesis, Henan University of Chinese Medicine, 2015.
[30]
Guo, J.S.; Peng, Y.; Zhan, K.; Qin, W. Effects of Lvjiaobuxue Corpuscle on Ghymus and spleen of rats with the deficiencies of both Qi and blood. Guid. J. Tradit. Chin. Med. Pharm., 2007, 13(1), 15-16.
[31]
Li, W.; Zhao, Y.; Li, X. Effect of Zishenshengxue capsule on myelosuppression in mice induced by cyclophosphamide. J. Tradit. Chin. Med., 2013, 33(2), 233-237.
[http://dx.doi.org/10.1016/S0254-6272(13)60131-4] [PMID: 23789223]
[32]
Javarappa, K.K.; Tsallos, D.; Heckman, C.A. A multiplexed screening assay to evaluate chemotherapy-induced myelosuppression using healthy peripheral blood and bone marrow. SLAS Discov., 2018, 23(7), 687-696.
[http://dx.doi.org/10.1177/2472555218777968] [PMID: 29865911]
[33]
Sun, W.W.; Sun, Q.; Sun, D.; Sun, W.Z. Effects of marrow-supplementing and blood-engendering granule at different dosage on the bone marrow of wistar rats with aplastic anemia. Acta Chin. Med. Pharm., 2009, 37(4), 12-14.
[34]
Xiao, W.C. The comparative study of LDPs and GDPs on hematopoiesis of myelosuppressed mice resulted from radiotherapy and chemotherapy. MS Thesis, Chengdu University of Traditional Chinese Medicine, 2009.
[35]
Kittler, E.L.; McGrath, H.; Temeles, D.; Crittenden, R.B.; Kister, V.K.; Quesenberry, P.J. Biologic significance of constitutive and subliminal growth factor production by bone marrow stroma. Blood, 1992, 79(12), 3168-3178.
[http://dx.doi.org/10.1182/blood.V79.12.3168.bloodjournal79123168] [PMID: 1375843]
[36]
Thalmeier, K.; Meissner, P.; Reisbach, G.; Hültner, L.; Mortensen, B.T.; Brechtel, A.; Oostendorp, R.A.; Dörmer, P. Constitutive and modulated cytokine expression in two permanent human bone marrow stromal cell lines. Exp. Hematol., 1996, 24(1), 1-10.
[PMID: 8536785]
[37]
Kaushansky, K. Thrombopoietin: Basic biology, clinical promise. Int. J. Hematol., 1995, 62(1), 7-15.
[http://dx.doi.org/10.1016/0925-5710(95)00379-7] [PMID: 7670009]
[38]
Sun, H.P.; Shen, Z.X.; Qian, L.M. The effects of several recombinant cytokines on human megakaryocytopoiesis. Acta Univ. Med. Sec. Shanghai, 1997, 17(3), 170-172.
[39]
Israels, E.D.; Israels, L.G. The cell cycle. Stem Cells, 2001, 19(1), 88-91.
[http://dx.doi.org/10.1634/stemcells.19-1-88] [PMID: 11209094]
[40]
Sherr, C.J. Cancer cell cycles. Science, 1996, 274(5293), 1672-1677.
[http://dx.doi.org/10.1126/science.274.5293.1672] [PMID: 8939849]
[41]
Lu, M.; Cao, D.M.; Zhao, X.X.; Li, D.M.; Li, J.W.; Jin, Y.P.; Qin, Q.G.; Gao, Y. Study on daynamic effect of acupuncture on marrow cell cycle regulatory protein Cyclin D1 expression and cell cycle in mice with cyclophosphamide induced myelosuppression. Chin. J. Int. Tradit. West. Med., 2007, 31(02), 238-243.
[42]
Chang, C. Linkage of Ras/Raf/MEK/ERK signaling pathway to cell fate. Chin. Med. Biotechnol., 2008, 3(4), 310-312.
[43]
Li, Z.H. Mechanism of Ras/Raf/MEK/Erk pathway regulating cell function. Sect. Pathophysiol. Clin. Med., 2000, 20(1), 12-14.

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