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Volume 28, Issue 4
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Aims and Objectives

Zuogui pill (ZGP) is the traditional Chinese medicine for tonifying kidney yin. Clinical and animal studies have shown that ZGP effectively enhances neurologic impairment after ischemic stroke, which may be related to promoting neurite outgrowth. This investigation aimed to prove the pro-neurite outgrowth impact of ZGP and define the underlying molecular pathway .

Materials and Methods

The major biochemical components in the ZGP were investigated using UPLC-QTOF-MS. All-trans retinoic acid (ATRA) was employed to stimulate SH-SY5Y cells to develop into mature neurons, followed by oxygen-glucose deprivation and reoxygenation damage (OGD/R). Then the cells were supplemented with different concentrations of ZGP, and cell viability was identified by CCK-8. The neurites' outgrowth abilities were detected by wound healing test, while immunofluorescence staining of β-III-tubulin was used to label neurites and measure their length. Western blot was employed to discover the changes in protein levels.

Results

ZGP improved the cell viability of differentiated SH-SY5Y cells following OGD/R damage, according to the CCK-8 assay. Concurrently, ZGP promoted neurite outgrowth and improved neurite crossing and migration ability. Protein expression analysis showed that ZGP upregulated the expression of GAP43, OPN, p-IGF-1R, mTOR, and p-S6 proteins but downregulated the expression of PTEN protein. Blocking assay with IGF-1R specific inhibitor Linstinib suggested IGF-1R mediated mTOR signaling pathway was involved in the pro-neurite outgrowth effect of ZGP.

Conclusion

This work illustrated the molecular mechanism underpinning ZGP's action and offered more proof of its ability to promote neurite outgrowth and regeneration following ischemic stroke.

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2025-03-29

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References

  1. MendelsonS.J. PrabhakaranS. Diagnosis and management of transient ischemic attack and acute ischemic stroke.JAMA2021325111088109810.1001/jama.2020.26867 33724327
     [Google Scholar]
  2. SuzukiK. MatsumaruY. TakeuchiM. MorimotoM. KanazawaR. TakayamaY. KamiyaY. ShigetaK. OkuboS. HayakawaM. IshiiN. KoguchiY. TakigawaT. InoueM. NaitoH. OtaT. HiranoT. KatoN. UedaT. IguchiY. AkajiK. TsurutaW. MikiK. FujimotoS. HigashidaT. IwasakiM. AokiJ. NishiyamaY. OtsukaT. KimuraK. Effect of mechanical thrombectomy without vs. with intravenous thrombolysis on functional outcome among patients with acute ischemic stroke.JAMA2021325324425310.1001/jama.2020.23522 33464334
     [Google Scholar]
  3. ChavezJ.C. HurkoO. BaroneF.C. FeuersteinG.Z. Pharmacologic interventions for stroke: Looking beyond the thrombolysis time window into the penumbra with biomarkers, not a stopwatch.Stroke20094010e558e56310.1161/STROKEAHA.109.559914 19745180
     [Google Scholar]
  4. TakaseH. RegenhardtR. Motor tract reorganization after acute central nervous system injury: A translational perspective.Neural Regen. Res.20211661144114910.4103/1673‑5374.300330 33269763
     [Google Scholar]
  5. RegenhardtR.W. TakaseH. LoE.H. LinD.J. Translating concepts of neural repair after stroke: Structural and functional targets for recovery.Restor. Neurol. Neurosci.2020381679210.3233/RNN‑190978 31929129
     [Google Scholar]
  6. LiJ. ZhaoX. ZhangY. WanH. HeY. LiX. YuL. JinW. Comparison of traditional chinese medicine in the long-term secondary prevention for patients with ischemic stroke: A systematical analysis.Front. Pharmacol.20211272297510.3389/fphar.2021.722975 34867326
     [Google Scholar]
  7. ZhuJ.B. WangY.H. HuZ.D. LiJ. HuangW.Z. ZhuJ.B. WangY.H. HuZ.D. LiJ. Research progress on pathogenesis of ischemic stroke and traditional Chinese medicine commonly used for treatment of ischemic strokeZhongguo Zhongyao Zazhi201944342243210.19540/j.cnki.cjcmm.20180921.002 30989903
     [Google Scholar]
  8. YuT.Y. WuY.H. SunH.J. JiangS.M. Hierarchical relationships of etiology and pathogenesis of ischemic stroke.Jilin J. Trad. Chi. Med.2016360432833110.13463/j.cnki.jlzyy.2016.04.002
     [Google Scholar]
  9. HuJ.P. WangJ. JianW. LiJ. SongZ.R. ZhangH.M. Thoughts and methods of bushen shengsui therapeutic method on convalescent period of ischemic stroke.Liaoning Zhongyiyao Daxue Xuebao20121410121410.13194/j.jlunivtcm.2012.10.14.hujp.092
     [Google Scholar]
  10. LuoL.J. ZhuM.Z. ChenL. YuR. XiangY. Exploration of ischemic stroke and nerve regeneration based on the“kidney-brain-stem cell”axis.Liaoning Zhongyiyao Daxue Xuebao2020220310410710.13194/j.issn.1673‑842x.2020.03.027
     [Google Scholar]
  11. ChenW.J. ChenX.L. SunS.G. YeJ.L. Clinical observation on zuogui pill in treating 50 cases of cerebral infarction with deficiency of liver and kidney yin in the recovery period.New Chinese Medicine20104208141510.13457/j.cnki.jncm.2010.08.033
     [Google Scholar]
  12. YuQ.P. GaoX. Experience of Zuo Gui Wan in the treatment of neurological diseases.J. Prac. Trad. Chi. Med.2006222114115
     [Google Scholar]
  13. TANG W.H. Clinical observation of Zuogui Pill in treating 30 cases of myocardial ischemia with deficiency of heart Yin.J. Tradit. Chin. Med.201051116116210.1328/j.1‑216/r.2010.s1.159
     [Google Scholar]
  14. CenS. QianX. WuC. XuX. YangX. Efficacy and clinical significance of the zuogui pill on premature ovarian failure via the GDF-9/Smad2 pathway.Nutr. Cancer202375248849710.1080/01635581.2022.2123531 36194038
     [Google Scholar]
  15. ZhouJ. PanX. LinJ. ZhouQ. LanL. ZhuJ. DuanR. WangL. SunY. WangL. Effects of bushen Yiqi huoxue decoction in treatment of patients with diminished ovarian reserve: A randomized controlled trial.Chin. J. Integr. Med.202228319520110.1007/s11655‑020‑3484‑x 33423188
     [Google Scholar]
  16. LiJ. SunK. QiB. FengG. WangW. SunQ. ZhengC. WeiX. JiaY. An evaluation of the effects and safety of Zuogui pill for treating osteoporosis: Current evidence for an ancient Chinese herbal formula.Phytother. Res.20213541754176710.1002/ptr.6908 33089589
     [Google Scholar]
  17. WenxiongL. KuaiqiangZ. ZhuL. LiL. YanC. JichaoY. YindiS. FengY. YinJ. SunY. Effect of Zuogui pill and Yougui pill on osteoporosis: A randomized controlled trial.J. Tradit. Chin. Med.2018381334210.1016/j.jtcm.2018.01.005 32185949
     [Google Scholar]
  18. ShiT. LiuT. KouY. RongX. MengL. CuiY. GaoR. HuS. LiM. The synergistic effect of zuogui pill and eldecalcitol on improving bone mass and osteogenesis in type 2 diabetic osteoporosis.Medicina2023598141410.3390/medicina59081414 37629706
     [Google Scholar]
  19. ZhengZ.A. WenX.J. PanF. ZhongX.G. Review of clinical application and experimental studies of Zuogui Pill.Zhonghua Zhongyiyao Xuekan2014321586010.13193/j.issn.1673‑7717.2014.01.018
     [Google Scholar]
  20. LiW.L. LiL. WuM.H. Effect of Zuogui Pill on movement disorder in patients with ischemic stroke.J. Changchun Uni. Trad. Chi. Med.2019350587287510.13463/j.cnki.cczyy.2019.05.017
     [Google Scholar]
  21. WangL. ZhaoH. FanY.P. GongH.Y. LiM. QiF. LiuY. Research on the mechanism of Zuogui Pill and Yougui Pill in promoting axonal regeneration in model rats of autoimmune encephalomyelitis.Chin. J. Integr. Med.201016216717210.1007/s11655‑010‑0167‑z 20473744
     [Google Scholar]
  22. LiuH. DaiQ. YangJ. ZhangY. ZhangB. ZhongL. Zuogui Pill attenuates neuroinflammation and improves cognitive function in cerebral ischemia reperfusion-injured rats.Neuroimmunomodulation202229214315010.1159/000519010 34736255
     [Google Scholar]
  23. WangY.Z. KouS. GuL.Y. ZhengQ. LiM. QiF. ZhaoH. WangL. Effects of Zuogui Pill () and Yougui Pill () on the expression of brain-derived neurotrophic factor and cyclic adenosine monophosphate/protein kinase A signaling transduction pathways of axonal regeneration in model rats with experimental autoimmune encephalomyelitis.Chin. J. Integr. Med.2014201243010.1007/s11655‑012‑1236‑2 23212569
     [Google Scholar]
  24. TianqiW. ZiningL.I. TingC. RuiC. YaJ. Patrick KwabenaO. HanZ. YiW. Zuogui and Yougui pills improve perimenopausal syndrome regulation of apoptosis in mice.J. Tradit. Chin. Med.202343347448310.19852/j.cnki.jtcm.20220507.001 37147748
     [Google Scholar]
  25. YangA. YuC. YouF. HeC. LiZ. Mechanisms of Zuogui Pill in treating osteoporosis: perspective from bone marrow mesenchymal stem cells.Evid. Based Complement. Alternat. Med.201820181810.1155/2018/3717391 30327678
     [Google Scholar]
  26. MaX. HeL. The intervention effect of zuogui pill on chronic kidney disease-mineral and bone disorder regulatory factor.Biomed. Pharmacother.2018106546010.1016/j.biopha.2018.06.092 29957466
     [Google Scholar]
  27. LiuM. LiY. PanJ. LiuH. WangS. TengJ. ZhaoH. JuD. Effects of zuogui pill (see text) on Wnt singal transduction in rats with glucocorticoid-induced osteoporosis.J. Tradit. Chin. Med.20113129810210.1016/S0254‑6272(11)60020‑4 21977807
     [Google Scholar]
  28. FuH.E. LiJ.M. LiuY.H. Effect of Zuoguiwan on Neuro-endocrine-immune function of kidney-yin deficiency rats.Zhongguo Shiyan Fangjixue Zazhi2017232215515910.13422/j.cnki.syfjx.2017220155
     [Google Scholar]
  29. ChengB.B. ZhuL. LiC.Z. HuangQ.Z. Effect of Zuogui pill on reproductive endocrine of female Yin-deficiency mice.Mod. J.Inte. Trad. Chin. Western Med.2003121313621364
     [Google Scholar]
  30. UyedaA. MuramatsuR. Molecular mechanisms of central nervous system axonal regeneration and remyelination: A review.Int. J. Mol. Sci.20202121811610.3390/ijms21218116 33143194
     [Google Scholar]
  31. ParkK.K. LiuK. HuY. SmithP.D. WangC. CaiB. XuB. ConnollyL. KramvisI. SahinM. HeZ. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway.Science2008322590396396610.1126/science.1161566 18988856
     [Google Scholar]
  32. LiuY. WangX. LiW. ZhangQ. LiY. ZhangZ. ZhuJ. ChenB. WilliamsP.R. ZhangY. YuB. GuX. HeZ. A sensitized IGF1 treatment restores corticospinal axon-dependent functions.Neuron2017954817833.e410.1016/j.neuron.2017.07.037 28817801
     [Google Scholar]
  33. HeZ. Intrinsic control of axon regeneration.J. Biomed. Res.20102412510.1016/S1674‑8301(10)60002‑4 23554605
     [Google Scholar]
  34. LiuY. GaoC.C. WuM.H. LiW.L. Effect and mechanism of Zuogui Pills on neural function recovery in ischemic stroke mice based on OPN/IGF-1/mTOR.China J. Chinese Mat. Med2023481952505258
     [Google Scholar]
  35. JahnK. WieltschC. BlumerN. MehlichM. PathakH. KhanA.Q. HildebrandtH. FrielingH. A cell culture model for investigation of synapse influenceability: Epigenetics, expression and function of gene targets important for synapse formation and preservation in SH-SY5Y neuroblastoma cells differentiated by retinoic acid.J. Neural Transm.2017124111341136710.1007/s00702‑017‑1769‑9 28887651
     [Google Scholar]
  36. ZhiS.M. FangG.X. XieX.M. LiuL.H. YanJ. LiuD.B. YuH.Y. Melatonin reduces OGD/R-induced neuron injury by regulating redox/inflammation/apoptosis signaling.Eur. Rev. Med. Pharmacol. Sci.20202431524153610.26355/eurrev_202002_20211 32096202
     [Google Scholar]
  37. SunZ. ZhaoX. ZhangM. LiN. ZhaoY. ChenC. LiJ. GuoY. FengQ. MicroRNA 126 protects SH SY5Y cells from ischemia/reperfusion injury induced apoptosis by inhibiting RAB3IP.Mol. Med. Rep.20212526210.3892/mmr.2021.12578 34935056
     [Google Scholar]
  38. LiL. LiuY. ZhengY. ZhuJ. WuD. YanX. LiC. WuM. LiW. Exploring the mechanisms under Zuogui Pill’s treatment of ischemic stroke through network pharmacology and in vitro experimental verification.Front. Pharmacol.202314115347810.3389/fphar.2023.1153478 37426810
     [Google Scholar]
  39. AgapoudaA. GrimmA. LejriI. EckertA. Rhodiola rosea extract counteracts stress in an adaptogenic response curve manner via elimination of ROS and induction of neurite outgrowth.Oxid. Med. Cell. Longev.2022202211910.1155/2022/5647599 35602107
     [Google Scholar]
  40. DedoniS. OlianasM.C. IngianniA. OnaliP. Type I interferons impair BDNF‐induced cell signaling and neurotrophic activity in differentiated human SH‐SY5Y neuroblastoma cells and mouse primary cortical neurons.J. Neurochem.20121221587110.1111/j.1471‑4159.2012.07766.x 22533963
     [Google Scholar]
  41. NebieO. BarroL. WuY.W. KnutsonF. BuéeL. DevosD. PengC.W. BlumD. BurnoufT. Heat-treated human platelet pellet lysate modulates microglia activation, favors wound healing and promotes neuronal differentiation in vitro.Platelets202132222623710.1080/09537104.2020.1732324 32106742
     [Google Scholar]
  42. CaoZ.Y. LiuJ.T. HanY.Q. ZhangT.J. XuJ. Identification of Q-markers for Cistanches Herba based on HPLC-Q-TOF-MS/MS and network pharmacologyZhongguo Zhongyao Zazhi20224771790180110.19540/j.cnki.cjcmm.20211210.201 35534249
     [Google Scholar]
  43. LiuJ.F. ShuQ. ZhangY. Protective efect and mechanism of Zuogui pil-containing serum on oxygen and glucose deprivation injury of hippocampal neurons and glial cels in rats.Shaanxi Medical Journal20225101151910.3969/i.sn.1000‑7377.2022.01.004
     [Google Scholar]
  44. LiangC. JinG.Q. JiangJ.Y. ZhangX.L. GongZ.B. Effects of Zuogui Pills and its decomposed recipes on the differentiation of bone marrow mesenchymal stem cells into neuron-like cells.Zhonghua Zhongyiyao Zazhi201833832793284
     [Google Scholar]
  45. LiuH. JiaY. SunS.X. HaoD. LiuS. Experimental study of Zuogui Wan on improvement memory in cerebral ischemia model rats of kidney deficiency induced by panic.Chin. J. Clin. Pharmacol.201531161618162110.13699/j.cnki.1001‑6821.2015.16.018
     [Google Scholar]
  46. ChengJ. TangW. FangH.L. ZhangZ.L. Effect of electro-acupuncture therapy combined with zuogui pill on expressions of GAP-43 and SYN and ultrastructural changes of synapse following cerebral ischemia-reperfusion in rats.Liaoning Zhongyiyao Daxue Xuebao2013159828510.13194/j.issn.1673‑842x.2013.09.052
     [Google Scholar]
  47. WangH. RanH. YinY. XuX. JiangB. YuS. ChenY. RenH. FengS. ZhangJ. ChenY. XueQ. XuX. Catalpol improves impaired neurovascular unit in ischemic stroke rats via enhancing VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 signaling.Acta Pharmacol. Sin.20224371670168510.1038/s41401‑021‑00803‑4 34795412
     [Google Scholar]
  48. WanD. ZhuF.H. Catalpol promotes corticospinal tract sprouting and remodeling after focal cerebral ischemic stroke in rats.Zhongguo Yaolixue Tongbao20132981057106310.3969/j.issn.1001‑1978.2013.08.006
     [Google Scholar]
  49. SunM. ShenX. MaY. Rehmannioside A attenuates cognitive deficits in rats with vascular dementia (VD) through suppressing oxidative stress, inflammation and apoptosis.Biomed. Pharmacother.201912010949210.1016/j.biopha.2019.109492 31593895
     [Google Scholar]
  50. FuC. WuY. LiuS. LuoC. LuY. LiuM. WangL. ZhangY. LiuX. Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia.J. Ethnopharmacol.202228911502110.1016/j.jep.2022.115021 35091012
     [Google Scholar]
  51. WangY.Q. ZhouX. LiuX. Efects of Zuogui Pill on GAP - 43 and Nogo: A expressions in retina of adult rat after optic nerve crushed.Zhonghua Zhongyiyao Xuekan20112992054205610.13193/j.archtcm.2011.09.130.wangyq.050
     [Google Scholar]
  52. BeiF. LeeH.H.C. LiuX. GunnerG. JinH. MaL. WangC. Hou; Hensch, T.K.; Frank, E.; Sanes, J.R.; Chen, C.; Fagiolini, M.; He, Z. Restoration of visual function by enhancing conduction in regenerated axons.Cell20161641-221923210.1016/j.cell.2015.11.036 26771493
     [Google Scholar]
  53. LiuK. LuY. LeeJ.K. SamaraR. WillenbergR. Sears-KraxbergerI. TedeschiA. ParkK.K. JinD. CaiB. XuB. ConnollyL. StewardO. ZhengB. HeZ. PTEN deletion enhances the regenerative ability of adult corticospinal neurons.Nat. Neurosci.20101391075108110.1038/nn.2603 20694004
     [Google Scholar]
  54. HoE.S. ChowS.F. TsangC.K. LiM-X. WengJ-W. Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury.Neural Regen. Res.202217102157216510.4103/1673‑5374.335830 35259823
     [Google Scholar]
  55. MaC. TengL. LinG. GuoB. ZhuoR. QianX. GuanT. WuR. LiuY. LiuM. L‐leucine promotes axonal outgrowth and regeneration via mTOR activation.FASEB J.2021355e2152610.1096/fj.202001798RR 33813773
     [Google Scholar]
  56. YanY.P. LangB.T. VemugantiR. DempseyR.J. Osteopontin is a mediator of the lateral migration of neuroblasts from the subventricular zone after focal cerebral ischemia.Neurochem. Int.200955882683210.1016/j.neuint.2009.08.007 19686792
     [Google Scholar]
  57. KurataM. OkuraT. KumonY. TagawaM. WatanabeH. NakaharaT. MiyazakiT. HigakiJ. NoseM. Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients.Hypertens. Res.201235220721210.1038/hr.2011.177 22113358
     [Google Scholar]
  58. MendiorozM. Fernández-CadenasI. RosellA. DelgadoP. Domingues-MontanariS. RibóM. PenalbaA. QuintanaM. Álvarez-SabínJ. MontanerJ. Osteopontin predicts long-term functional outcome among ischemic stroke patients.J. Neurol.2011258348649310.1007/s00415‑010‑5785‑z 20967551
     [Google Scholar]
  59. BakeS. OkoreehA.K. AlanizR.C. SohrabjiF. Insulin-like growth factor (IGF)-I modulates endothelial blood-brain barrier function in ischemic middle-aged female rats.Endocrinology20161571616910.1210/en.2015‑1840 26556536
     [Google Scholar]
  60. ChenP. WangW. LiuR. LyuJ. ZhangL. LiB. QiuB. TianA. JiangW. YingH. JingR. WangQ. ZhuK. BaiR. ZengL. DuanS. LiuC. Olfactory sensory experience regulates gliomagenesis via neuronal IGF1.Nature2022606791455055610.1038/s41586‑022‑04719‑9 35545672
     [Google Scholar]
  61. BakeS. OkoreehA. KhosravianH. SohrabjiF. Insulin-like Growth Factor (IGF)-1 treatment stabilizes the microvascular cytoskeleton under ischemic conditions.Exp. Neurol.201931116217210.1016/j.expneurol.2018.09.016 30287160
     [Google Scholar]
  62. ZhangY. WilliamsP.R. JacobiA. WangC. GoelA. HiranoA.A. BrechaN.C. KerschensteinerD. HeZ. Elevating growth factor responsiveness and axon regeneration by modulating presynaptic inputs.Neuron201910313951.e510.1016/j.neuron.2019.04.033 31122676
     [Google Scholar]
  63. HausottB. GlueckertR. Schrott-FischerA. KlimaschewskiL. Signal transduction regulators in axonal regeneration.Cells2022119153710.3390/cells11091537 35563843
     [Google Scholar]
  64. WuQ. TianA.L. KroemerG. KeppO. Autophagy induction by IGF1R inhibition with picropodophyllin and linsitinib.Autophagy20211782046204710.1080/15548627.2021.1936934 34110249
     [Google Scholar]
  65. De MartinoM.C. van KoetsveldP.M. FeeldersR.A. de HerderW.W. DoganF. JanssenJ.A.M.J.L. Hofste op Bruinink, D.; Pivonello, C.; Waaijers, A.M.; Colao, A.; de Krijger, R.R.; Pivonello, R.; Hofland, L.J. IGF and mTOR pathway expression and in vitro effects of linsitinib and mTOR inhibitors in adrenocortical cancer.Endocrine201964367368410.1007/s12020‑019‑01869‑1 30838516
     [Google Scholar]
  66. HuangJ. ZhangY. DongL. GaoQ. YinL. QuanH. ChenR. FuX. LinD. Ethnopharmacology, phytochemistry, and pharmacology of Cornus officinalis Sieb. et Zucc.J. Ethnopharmacol.201821328030110.1016/j.jep.2017.11.010 29155174
     [Google Scholar]
  67. GaoX. LiuY. AnZ. NiJ. Active components and pharmacological effects of cornus officinalis: Literature review.Front. Pharmacol.20211263344710.3389/fphar.2021.633447 33912050
     [Google Scholar]
  68. ZhangR.X. LiM.X. JiaZ.P. Rehmannia glutinosa: Review of botany, chemistry and pharmacology.J. Ethnopharmacol.2008117219921410.1016/j.jep.2008.02.018 18407446
     [Google Scholar]
  69. LiangJ. CaiJ. ZhangY. XieM. LiX. HuT. LiangS. XianM. WangS. Cyclo-(Phe-Tyr) reduces cerebral ischemia/reperfusion-induced blood–brain barrier dysfunction through regulation of autophagy.Food Funct.20221323122781229010.1039/D2FO02367A 36345882
     [Google Scholar]
  70. ShiZ. DengZ. PengX. TianY. Study on the pharmacodynamic effect of Rhizoma Dioscoreae polysaccharides on cerebral ischemia-reperfusion injury in rats and the possible mechanism.J. Ethnopharmacol.202229611551710.1016/j.jep.2022.115517 35777608
     [Google Scholar]
  71. GaoK. LiuM. DingY. YaoM. ZhuY. ZhaoJ. ChengL. BaiJ. WangF. CaoJ. LiJ. TangH. JiaY. WenA. A phenolic amide (LyA) isolated from the fruits of Lycium barbarum protects against cerebral ischemia–reperfusion injury via PKCε/Nrf2/HO-1 pathway.Aging20191124123611237410.18632/aging.102578 31881005
     [Google Scholar]
  72. CaiE. ChengQ. YuS. DingF. Achyranthes bidentata polypeptide k enhances the survival, growth and axonal regeneration of spinal cord motor neurons in vitro.Neuroreport202132651852410.1097/WNR.0000000000001621 33788819
     [Google Scholar]
  73. HeX. WangX. FangJ. ChangY. NingN. GuoH. HuangL. HuangX. The genus Achyranthes: A review on traditional uses, phytochemistry, and pharmacological activities.J. Ethnopharmacol.201720326027810.1016/j.jep.2017.03.035 28347832
     [Google Scholar]
  74. ChengQ. TongF. ShenY. HeC. WangC. DingF. Achyranthes bidentata polypeptide k improves long-term neurological outcomes through reducing downstream microvascular thrombosis in experimental ischemic stroke.Brain Res.2019170616617610.1016/j.brainres.2018.11.010 30414726
     [Google Scholar]
  75. LiX.Y. WangX.Y. Effect of Zuogui Pill () on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack.Chin. J. Integr. Med.201723319019510.1007/s11655‑016‑2095‑4 27928707
     [Google Scholar]
  76. YinH. WangS. ZhangY. WuM. WangJ. MaY. Zuogui Pill improves the dexamethasone-induced osteoporosis progression in zebrafish larvae.Biomed. Pharmacother.20189799599910.1016/j.biopha.2017.11.029 29136778
     [Google Scholar]
/content/journals/cchts/10.2174/0113862073295309240214060857
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Zuogui Pill Promotes Neurite Outgrowth by Regulating OPN/ IGF-1R/PTEN and Downstream mTOR Signaling Pathway
Comb Chem High Throughput Screen 28, 675 (2025); https://doi.org/10.2174/0113862073295309240214060857
/content/journals/cchts/10.2174/0113862073295309240214060857
/content/journals/cchts/10.2174/0113862073295309240214060857
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  • Article Type:     Research Article
Keyword(s): IGF-1R; linstinib; neurite outgrowth; oxygen-glucose deprivation reperfusion; SH-SY5Y; Zuogui pill

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