Deciphering the potential mechanism of Siwu decoction for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Siwu decoction(SWD)is a traditional Chinese herbal decoction commonly used for treating various symptoms of blood deficiency and blood stasis,including cancer-related anemia(CRA).However,due to its complex composition,the key active ingredients and underlying mechanisms of its therapeutic effects often remain unknown.This research aims to use network pharmacology and molecular docking technology to systematically elucidate the potential mechanisms underlying the efficacy of SWD in treating cancer-related anemia.Methods:The key constituents of SWD were procured from the TCMSP database.Leveraging the Swiss ADME and Swiss Target Prediction databases,potential targets were recognized.Disease-related targets were assembled via the GeneCards and DrugBank databases.Constructing the PPI network involved the utilization of the STRING database,followed by visualization through Cytoscape 3.9.1 software.Subsequently,GO and KEGG enrichment analysis was conducted utilizing the DAVID database,with visual analysis performed on the macrobiotic platform.For molecular docking,the Autodock software was employed,and the molecular docking outcomes were visualized using the PyMOL software.Results:In this investigation,a comprehensive revelation of 18 primary active compounds and 511 associated targets linked to CRA was accomplished.The outcomes of protein-protein interaction(PPI)analysis unequivocally identified AKT1,EGFR,SRC,VEGFA,HRAS,MAPK3,and STAT3 as pivotal proteins within the SWD’s framework for effective CRA intervention.Notably,signaling pathways such as the HIF-1,JAK-STAT,TNF-α,and PI3K-Akt pathways,intricately involved in hematopoietic stem cell proliferation,differentiation,and inflammatory response,emerged as closely intertwined with the therapeutic application of SWD for CRA treatment.The congruence between these potential targets and SWD’s primary therapeutic constituents for CRA treatment was substantiated by the outcomes of molecular docking analysis.Conclusion:This work provided a reference for further fundamental research by outlining the primary active ingredients and putative molecular mechanisms of SWD in the treatment of CRA.

Protective effect of borneol combined with safflower on neurovascular unit in rats with ischemic stroke

Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.

Deciphering the potential mechanism of Radix Rehmanniae Praeparata for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Rehmanniae Radix Praeparata(RRP,Shu Dihuang in Cinese)is a traditional Chinese herb with multiple pharmacological effects and is commonly used to treat blood deficiency syndrome,such as cancer-related anemia(CRA),alone or in combination with other herbs.However,its main active ingredients and mechanisms of action in treating CRA remain unknown.This study aims to elucidate RRP’s potential mechanism and main active components in treating CRA by using network pharmacology and molecular docking technology system.Methods:The main components of RRP were obtained by the TCMSP database and literature search,and active components and potential targets were obtained by the SwissADME and SwissTargetPridiction databases.CRA targets were collected through GeneCards,DisGeNET,and DrugBank databases.Protein-protein interaction networks of potential targets were constructed via STRING 11.5 and analyzed visually with Cytoscape 3.9.1.The Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis,which were subsequently visualized with Cytoscape 3.9.1 or SangerBox platform.Moreover,Autodock Vina was used for the molecular docking of potential targets and main active ingredients that were visualized with PyMOL software.Results:In this study,31 main active ingredients of PPR were screened,and 155 related targets related to CRA were unearthed.Protein-protein interaction results showed that PPR’s core proteins for CRA intervention correlate to STAT3,SRC,MAPK3,MAPK1,PIK3R1,PIK3CA,and AKT.Multiple signaling pathways were closely related to the treatment of CRA intervened by PPR,including the PI3K-Akt signaling pathway,HIF-1 signaling pathway,JAK-STAT3 signaling pathway,TNF-αsignaling,cytokine signaling pathway and NF-kappB signaling pathway,which are closely involved in the proliferation and differentiation of hematopoietic stem cell and inflammatory response.Molecular docking results showed that these potential targets had good conformation with the core active components of RRP for treating CRA.Conclusion:This study revealed RRP’s main active components and potential molecular mechanisms in treating CRA,providing a reference for subsequent basic research.

单眼形觉剥夺性弱视大鼠视皮层突触密度及功能的研究

目的:研究视觉发育关键期单眼形觉剥夺(MD)对弱视大鼠视皮层突触密度超微形态结构变化规律的影响,以及突触素(SYN)在视皮层的表达及意义,探讨弱视大鼠视皮层突触密度及功能的关系,为弱视的发病机制及临床治疗提供分子水平理论依据。方法:选用正常新生Long Evans大鼠随机分为正常对照组与弱视模型组,每组16只,两组大鼠均在相同环境下饲养。正常对照组不做任何处理,弱视模型组在出生后第13d采用单眼缝合的方法建立单眼形觉剥夺性弱视经典模型。两组大鼠均于出生后51d进行闪光视觉诱发电位(F-VEP)的检测。检测结束后立即取材,用透射电镜及Image J图像分析软件观察并统计两组大鼠初级视皮层V1M区第Ⅳ~Ⅵ层大锥体细胞周围神经纤维网络的突触密度变化。利用漂染法对视皮层冰冻切片进行免疫荧光组织化学染色,在激光共聚焦显微镜及荧光显微镜下对SYN阳性神经元进行定位观察和定量统计分析。结果:F-VEP检查结果显示与正常对照组相比,弱视模型组剥夺眼的P2潜伏期较正常眼明显延长,P2波振幅较正常眼明显降低(P<0.05);透射电镜结果显示,与正常对照组相比,弱视模型组双侧视皮层的突触密度显著降低(P<0.05),其中弱视眼对侧视皮层下降更加明显(P<0.05);免疫荧光染色结果显示两组大鼠视皮层脑切片形态完整,镜下组织结构清晰,与正常对照组相比,弱视模型组SYN阳性神经元表达强度值明显降低(P<0.01)。结论:视觉发育关键期存在着突触结构可塑性,单眼形觉剥夺可以造成大鼠初级视皮层突触密度的降低,SYN表达水平下降,视皮层功能下降。