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.

The dynamic changes and mechanisms of Rehmanniae radix processing based on Maillard reaction

Background:Traditional Chinese medicines are usually processed before they are used for clinical treatment.This is done in a way associated with the Maillard reaction.Methods:Based on the Maillard reaction,this paper analyzed the degree of processing of rehmannia root(Rehmanniae radix)relative to the dynamic variation rules of Maillard reaction index parameters,including pH,A420,amino acids,and 5-hydroxymethylfurfural.Furthermore,this study introduced thermal analysis techniques and pyrolysis kinetics to assess the influence of the correlation between processing raw rehmannia root and the Maillard reaction during carbonization.It then went through the whole process of transforming the raw material to end-product in order to explain the scientific connotation of processing it.Results:The results showed that each time rehmannia root was processed,its pH value and amino acid content decreased,while the A420 value and 5-HMF increased.Processing with wine shows a significant difference in these experimental indexes.The position and intensity of the maximum thermal weight loss rate peak of processed rehmannia root at different degrees of processing are different.Comprehensive quantitative 221±0.2°C for processed rehmannia root carbonization was the processing temperature limit.Moreover,the kinetic solution verified that the activation energy corresponding to the carbonization temperature was close to the maximum value of the activation energy of the whole carbonization process,and the optimal mechanism function was g(α)=((1−α)−1/3−1)2.Conclusion:The Maillard reaction occurred during the processing of rehmannia root mixed with carbonization.With each increase of the number of steaming and drying cycles involved in the processing,the level of Maillard reaction increased significantly.The wine-steaming method had a significant effect on the quality of the processed product.

Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis

Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional deterioration.Recently,ferroptosis,a newly recognized form of programmed cell death,has been implicated in IRI.Rehmanniae Radix Praeparata(RRP),extensively used in Chinese herbal medicine for its hepatoprotective,anti-inflammatory,and antioxidant properties,presents a potential therapeutic approach.However,the mechanisms by which RRP mitigates HIRI,particularly through the regulation of ferroptosis,remain unclear.In this study,we developed a HIRI mouse model and monocrotaline(MCT)-and erastin-induced in vitro hepatocyte injury models.We conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on HIRI.The RRP aqueous extract was characterized by the presence of acteoside,rehmannioside D,and 5-hydroxymethylfurfural.Our results demonstrate that the RRP aqueous extract ameliorated oxidative stress,reduced intracellular iron accumulation,and attenuated HIRI-induced liver damage.Additionally,RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in vitro.Mechanistically,the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake,promoting hepcidin-and ferroportin-mediated iron efflux,and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 expression.Moreover,siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract's inhibitory effect on ferroptosis.In conclusion,our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI,highlighting the restoration of iron metabolic balance.These findings position RRP as a promising candidate for clinical intervention in HIRI treatment.

Correlation between 5-hydroxymethylfurfural content and color of Rehmanniae Radix and Rehmanniae Radix Praeparata

In the present study,we explored the correlation between 5-hydroxymethylfurfural(5-HMF)and color of Rehmanniae Radix(RR)and Rehmanniae Radix Praeparata(RRP).The color was observed by human eyes under sunlight.The chromatic value and color difference were detected by a colorimeter.The water content was determined by an oven-drying method.The 5-HMF content was determined by an HPLC method.The correlation between the 5-HMF content and the color was analyzed by bivariate correlation analysis.The results showed that the color was greyish-brown and dark brown for RR,and it was black for RRP.The deepening color of RRP was reflected in the decrease of L^*,a^*and b^*values.The water content was in accord with the requirement of Chinese Pharmacopoeia.The 5-HMF contents of RR and RRP were 0.9711–25.71μg/g and 213.4–4010μg/g,respectively.The average 5-HMF contents of RR and RRP were 8.059μg/g and 1433μg/g,respectively.The 5-HMF content in RRP was higher than that in RR.The correlations between 5-HMF content and L^*,a^*and b^*values were significant.The color of RRP was deeper than that of RR.The 5-HMF content of RRP was higher than 0.02%,while it was less than 0.02%of RR,which could be used as a marker component for judging RR and RRP.