TY  - JOUR
T1  - In Vitro and In Silico Evaluation of the Therapeutic Potential of Ginseng and Its Principal Bioactive Constituents in Ischaemic Stroke
A1  - Anna Katarina Lundqvist
A1  - Erik Magnus Johansson
JF  - Journal of Medical Sciences and Interdisciplinary Research
JO  - J Med Sci Interdiscip Res
SN  - 3108-4826
Y1  - 2021
VL  - 1
IS  - 1
DO  - 10.51847/Jex3JAr2r6
SP  - 61
EP  - 82
N2  - Ischemic stroke (IS) represents a major global health burden and remains a leading cause of disability and mortality, underscoring the urgent need for improved therapeutic strategies. Tianjiangxueshuantong (TJXST) pills are widely prescribed for cerebrovascular disorders and include ginseng as a key herbal constituent; however, the specific contribution and mechanistic role of ginseng in IS therapy have not been comprehensively clarified. The present study aims to systematically evaluate the protective effects of ginseng against IS and to elucidate its underlying molecular mechanisms.To investigate the neuroprotective potential of ginseng, oxygen–glucose deprivation/reperfusion (OGD/R) injury was induced in bEnd.3 endothelial cells, while glutamate-mediated neurotoxicity was established in PC12 cells. Cell viability following ginseng extract treatment was assessed using CCK8 assays. Subsequently, an integrated network pharmacology strategy combined with Gene Expression Omnibus (GEO) database analysis was applied to screen the principal bioactive constituents of ginseng, identify key therapeutic targets in IS, and uncover relevant signaling pathways. Molecular docking was performed to evaluate the binding affinity between core components and hub targets, and surface plasmon resonance (SPR) was employed to experimentally verify these interactions. Furthermore, quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were conducted to assess alterations in gene and protein expression levels. SRC knockdown experiments were additionally carried out to determine its functional involvement in the neuroprotective actions of ginseng.The analysis revealed arachidonate, kaempferol, celabenzine, suchilactone, ginsenoside Re, and ginsenoside Rg1 as the principal active ingredients of ginseng. Core intervention targets associated with IS included PTPN11, JAK2, PIK3R1, EGFR, PIK3CA, PIK3CB, SRC, and PTK2. Molecular docking demonstrated stable binding interactions between the identified active components and hub targets. SPR assays further confirmed that the major ginseng constituents exhibited quantifiable binding affinity toward SRC. Both qRT-PCR and WB analyses indicated significant modulation of core target expression in the two cellular injury models. Importantly, ablation of SRC eliminated the protective effects of ginseng extract, highlighting SRC as a pivotal mediator of its neuroprotective activity. Additionally, CCK8 and ELISA assays confirmed enhanced cell survival and suppressed inflammatory responses, evidenced by reduced secretion of TNF-α (Tumor Necrosis Factor-alpha), IL-1β (Interleukin-1 beta), VEGF (Vascular Endothelial Growth Factor), and Ang-1 (Angiopoietin-1), following treatment with the identified active compounds.This study provides a systematic mechanistic insight into how ginseng exerts therapeutic effects in IS. The identification of critical bioactive constituents and their molecular targets offers a valuable foundation for the development of novel, multi-target therapeutic strategies for ischemic stroke.
UR  - https://smerpub.com/article/in-vitro-and-in-silico-evaluation-of-the-therapeutic-potential-of-ginseng-and-its-principal-bioactiv-q7hd30mao6ofos9
ER  -