Skip to content
2000
Volume 12, Issue 1
  • ISSN: 2215-0838
  • E-ISSN: 2215-0846

Abstract

Background

Cerebral ischemic stroke (CIS) severely endangers health, and there is an urgent need for effective therapeutic drugs and in-depth research on its mechanism of action. Danxi Granule has potential application in the relevant treatment.

Objective

This study aimed to explore the potential quality markers, therapeutic targets, and molecular mechanisms of Danxi Granule in treating CIS through the “Absorbed into Blood- Fingerprint-Network-Verification” paradigm.

Methods

An MCAO rat model was established. Serum samples from three groups were analyzed by UPLC-MS to identify blood-absorbed prototype components. The fingerprint and measurable chemical components of Danxi Granule were obtained using specific chromatographic conditions. Potential quality markers were determined by cross-referencing. Network pharmacology, with databases like GeneCards and OMIM, and relevant software, were used for gene identification and pathway enrichment analysis. Five identified compounds were tested in an OGD/R-induced HT22 cell model.

Results

A total of 207 blood-absorbed prototype components were identified. Ten-batch fingerprint analysis of Danxi Granules showed high similarity, with 15 common peaks (8 corresponding to measurable constituents). Five potential quality markers were determined. These compounds targeted 184 genes, intersecting with 73 disease-related ones. Network analysis revealed 10 key genes and cellular experiments confirmed the protection of HT22 cells, with TNF as a core target.

Discussion

In this study, an HPLC fingerprint was established using UPLC-MS technology, and five potential Q-markers were screened out. Through network pharmacology and cell experiments, these markers were validated to exert anti-CIS effects via mechanisms, such as anti-inflammation, thereby revealing the material basis of the pharmacological effects of Danxi Granules. The findings of this study provide a basis and new perspectives for quality standard research, clinical application, and the modernization of complex traditional Chinese medicine (TCM) systems. However, the current mechanistic investigation remains at a superficial level, and subsequent studies should further deepen the systematic exploration of the underlying action mechanisms.

Conclusion

The “absorbed into blood-fingerprint” paradigm identified five potential quality markers, namely cryptotanshinone, tanshinone IIA, aurantio-obtusin, icariin, and paeoniflorin. Validation through the “network-verification” paradigm confirmed their quality marker status and demonstrated that their anti-CIS mechanisms likely involve suppressing TNF-α, IL-6, and IL-1β expressions, thereby exerting anti-inflammatory effects.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/ctm/10.2174/0122150838378573250513090728
2025-05-19
2025-09-27
Loading full text...

Full text loading...

/deliver/fulltext/ctm/12/1/CTM-12-E22150838378573.html?itemId=/content/journals/ctm/10.2174/0122150838378573250513090728&mimeType=html&fmt=ahah

References

  1. WangY.J. LiZ.X. GuH.Q. Chinese stroke report 2020 (Chinese version) (1).Chin. J. Stroke20221705433447
    [Google Scholar]
  2. Pharmacopoeia of the People’s Republic of China:VolI.BeijingChina Medical Science Press2020719720
    [Google Scholar]
  3. XiongS.M. YangJ. LiJ.P. Salvia miltiorrhiza assisted treatment of hyperlipidemic acute pancreatitis.Chin. J. Integrat. Tradit. Chin. West. Med. Surg.2016224360362
    [Google Scholar]
  4. LiF.Y. Analysis of antioxidant effects of active ingredients of ligustrazine in stroke patients.Drug Human20142704283284
    [Google Scholar]
  5. XuH.Y. ZhangY.B. ZhangD.M. Research progress on the mechanism of ferroptosis and the intervention of traditional Chinese medicine in neuronal ferroptosis after stroke.Chin. J. Exper. Formul.20222820232240
    [Google Scholar]
  6. ZhuT WangL WangLP Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke: Applications for natural compounds from medicinal herbs.Biomed. Pharmacother.202214811271910.1016/j.biopha.2022.112719
    [Google Scholar]
  7. LongaE.Z. WeinsteinP.R. CarlsonS. CumminsR. Reversible middle cerebral artery occlusion without craniectomy in rats.Stroke1989201849110.1161/01.STR.20.1.842643202
    [Google Scholar]
  8. National Medical Products Administration.Tech. Require. Fingerp. Anal. Tradit. Chin. Med. Inject.200022102329
    [Google Scholar]
  9. MiaoQ. WangR. SunX. DuS. LiuL. Combination of puerarin and tanshinone IIA alleviates ischaemic stroke injury in rats via activating the Nrf2/ARE signalling pathway.Pharm. Biol.20226011022103110.1080/13880209.2022.207022135635784
    [Google Scholar]
  10. CaiM GuoYX WangSQ Tanshinone IIA elicits neuroprotective effect through activating the nuclear factor erythroid 2-related factor-dependent antioxidant response.Rejuvenat. Res.201720428629710.1089/rej.2016.1912
    [Google Scholar]
  11. ZhuX. HeL. GaoW. ZhaoZ. Neuroprotective investigation of tanshinone in the cerebral infarction model in the Keap1-Nrf2/ARE pathway.Cell Cycle202322439040210.1080/15384101.2022.211968736066030
    [Google Scholar]
  12. TangZ. YangG. LiaoZ. ChenF. ChenS. WangW. HuoG. SunX. WangX. Tanshinone IIA reduces AQP4 expression and astrocyte swelling after OGD/R by inhibiting the HMGB1/RAGE/NF-κB/IL-6 pro-inflammatory axis.Sci. Rep.20221211411010.1038/s41598‑022‑17491‑735982135
    [Google Scholar]
  13. SongZ. FengJ. ZhangQ. DengS. YuD. ZhangY. LiT. Tanshinone IIA protects against cerebral ischemia reperfusion injury by regulating microglial activation and polarization via NF - κB pathway.Front. Pharmacol.20211264184810.3389/fphar.2021.64184833953677
    [Google Scholar]
  14. WangJ. TongH. WangX. WangX. WangY. Tanshinone IIA alleviates the damage of neurocytes by targeting GLUT1 in ischaemia reperfusion model (in vivo and in vitro experiments).Folia Neuropathol.202058217619310.5114/fn.2020.9698332729296
    [Google Scholar]
  15. ChenH.H. ZhuW.X. ZhangX.J. Study on the effect of cryptotanshinone on the PI3K/AKT eNOS signaling pathway in stroke rats.Zhongguo Xiandai Zhongyao202260014246
    [Google Scholar]
  16. ZhaoYM XuPX HuSQ Tanshinone II A, a multiple target neuroprotectant, promotes caveolae-dependent neuronal differentiation.Eur. J. Pharmacol.201576543744610.1016/j.ejphar.2015.09.006
    [Google Scholar]
  17. CaiL YiXB YuanLB [The protective effect of tanshinone IIA on oxygen-glucose deprivation and reperfusion injury of microgliathrough the NLRP3 inflammatory signaling pathway].J. Sich. Univer.2016475660664
    [Google Scholar]
  18. WangJ. NiG. LiuY. HanY. JiaL. WangY. Tanshinone IIA promotes axonal regeneration in rats with focal cerebral ischemia through the inhibition of Nogo-A/NgR1/RhoA/ROCKII/MLC signaling.Drug Des. Devel. Ther.2020142775278710.2147/DDDT.S25328032764877
    [Google Scholar]
  19. ZhouL. BondyS.C. JianL. WenP. YangF. LuoH. LiW. ZhouJ. Tanshinone IIA attenuates the cerebral ischemic injury-induced increase in levels of GFAP and of caspases-3 and -8.Neuroscience201528810511110.1016/j.neuroscience.2014.12.02825575944
    [Google Scholar]
  20. FengJ.J. LiT.J. ZhangY.F. Research progress on the mechanism of the effect of tanshinone IIA on inflammatory response after cerebral ischemia.J. Pharm. Pract.20183624
    [Google Scholar]
  21. HuangY. LongX. TangJ. LiX. ZhangX. LuoC. ZhouY. ZhangP. The attenuation of traumatic brain injury via inhibition of oxidative stress and apoptosis by tanshinone IIA.Oxid. Med. Cell. Longev.2020202011210.1155/2020/417015632454938
    [Google Scholar]
  22. ChenJJ MaXC YangQ The effect of paeoniflorin regulating the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate response element binding protein pathway on stroke rats.Anhui Med. J.2022260610731078
    [Google Scholar]
  23. LiuL.B. ZhangH.F. Cassia seed extract reduces myocardial ischemia/reperfusion injury in type 2 diabetes rats.Basic Med. Clin.2015350116
    [Google Scholar]
  24. DaiMM ChenB WangXZ Icariin enhance mild hypothermia-induced neuroprotection via inhibiting the activation of NF-κB in experimental ischemic stroke.Metab. Brain Dis.20213671779179010.1007/s11011‑021‑00731‑6
    [Google Scholar]
  25. HeC. LuoH.L. JiH. Based on TNF- α The mechanism of cerebral ischemia-reperfusion injury and related drug research progress.China Pharmacy2016272840164020
    [Google Scholar]
  26. GuerrieroM.L. DudkaA. Underhill-DayN. HeathJ.K. PriamiC. Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.BMC Syst. Biol.2009314010.1186/1752‑0509‑3‑4019368721
    [Google Scholar]
  27. ZhangL.H. WeiE.Q. The role and regulation of ICAM-1 and VCAM-1 in the inflammatory mechanism of cerebral ischemic injury.Zhongguo Yaolixue Tongbao2005211112811285
    [Google Scholar]
  28. SunY. CaiY. ShenB.B. Study on the molecular mechanism of Gardenia jasminoides Ellis against ischemic stroke based on network pharmacology and molecular docking.Tradit. Chin. Pat. Med. Simp. Preparat.2021430923522359
    [Google Scholar]
  29. WangY. WuJ. The effect of Buyang Huanwu Tang on neurological function and related immune factors in patients with ischemic stroke.World J. Integrat. Chin. West. Med.201914710101013
    [Google Scholar]
  30. YangJ. YaoY. ChenT. ZhangT. VEGF ameliorates cognitive impairment in in vivo and in vitro ischemia via improving neuronal viability and function.Neuromolecular Med.201416237638810.1007/s12017‑013‑8284‑424338641
    [Google Scholar]
  31. MoonS. ChangM.S. KohS.H. ChoiY.K. Repair mechanisms of the neurovascular unit after ischemic stroke with a focus on VEGF.Int. J. Mol. Sci.20212216854310.3390/ijms2216854334445248
    [Google Scholar]
/content/journals/ctm/10.2174/0122150838378573250513090728
Loading
/content/journals/ctm/10.2174/0122150838378573250513090728
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test