Red yeast rice (RYR) is a traditional fermented product produced by cultivating rice with the filamentous fungus Monascus purpureus. It has been widely utilized in East Asia both as a natural food colorant and as a lipid-lowering herb. Rapid quality assessment is critical for the production, transaction and utilization of RYR. Since empirical evidence suggests that the chromatic properties of RYR correlate closely with its quality, UV-Vis spectrophotometric analysis at specific wavelengths has become a common proxy for rapid quality evaluation of RYR. However, there has been no universal consensus on the selection of these wavelengths. In this study, an active pharmaceutical ingredient (API)-correlated wavelength selection strategy was proposed to ensure analytical accuracy and biological interpretability of the selected UV-Vis wavelengths for the rapid quality assessment of RYR. Integrated bioinformatic analysis confirmed that Monascus pigments (e.g., monascin, rubropunctatin, rubropunctamine) and monacolin K were the dominant pharmacologically active components of RYR. Notably, both the profiles and concentrations of these pigments varied significantly across RYR samples from different manufacturers. Through systematic correlation analysis and principal component analysis (PCA), three optimal characteristic wavelengths were identified: 570 nm (associated with monascin and rubropunctamine), 450 nm (associated with rubropunctatin), and 230 nm (roughly associated with monacolin K). This work not only establishes chemically rational, API-informed UV-Vis wavelengths for standardized RYR quality assessment, but also offers a transferable methodological framework for the rapid quality control of other pigment-rich fermented products.

Liuwei Anxiao San (LAS) is a traditional Mongolian and Tibetan medicinal preparation for the treatment of functional constipation, functional dyspepsia and other gastrointestinal diseases. LAS is a mixture of four herbal ingredients and two mineral ingredients, but the current drug regulations on LAS completely ignore the two mineral ingredients. For the comprehensive quality control of LAS, this research explored the X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopic identification methods for the calcined Gypsum Rubrum (GR) in LAS. It was found that the major composition of the raw GR was CaSO4.2H(2)O, while the major composition of the right calcined GR was CaSO4. The bulk XRD and FTIR spectral characteristics of CaSO4.2H(2)O, CaSO4 and CaSO4.0.5H(2)O (the incompletely calcined GR) can be observed in some LAS preparations. FTIR microspectroscopy can collect the spectra of different particles in LAS samples individually to reduce the signal overlapping to increase the specificity and sensitivity of the identification method. According to the XRD and FTIR identification results, some commercial LAS preparations may use the raw or incompletely calcined GR instead of the right calcined GR, or these products did use the right calcined GR but they turned into calcium sulfate hydrate during the production and storage. Furthermore, neither hydrous nor anhydrous calcium sulfate was found in two LAS preparations. It is very necessary to include the XRD and FTIR spectroscopic identification methods to improve the quality standards of LAS preparations to assure their efficacy and safety. Considering the accessibility of instruments, the bulk FTIR spectroscopy can be the most convenient identification method for the calcined GR in LAS preparations. If possible, the bulk XRD spectra and the microscopic FTIR spectra can be used as further evidences for the identification.

Background Epilepsy is a prevalent neurological disorder characterized by recurrent seizures and has limited effectiveness of available clinical treatments. Ferroptosis of neurons is one of the main mechanisms of epilepsy. Arisaema Cum Bile (ACB) is a traditional Chinese medicine that is prepared by fermenting animals bile with Rhizoma Arisaematis rhizomes, has demonstrated therapeutic effects on epilepsy and other nervous system diseases. Furthermore, the active components responsible for the anti-epileptic effects of ACB and the intrinsic mechanisms are still unclear. Purpose This study aims to clarify the principal bioactive constituents of ACB and their mechanisms in the treatment of epilepsy. It also seeks to provide data support for its clinical application in antiepileptic combination therapy. Method Pentylenetetrazol injections were used to induce epilepsy in rats. ACB and brain metabolites were identified via UPLC-Q-Exactive Orbitrap MS/MS, and active components were predicted through bioinformatics analysis. In vivo, ACB and hyodeoxycholic acid (HDCA) were administered by gavage, and the effects on oxidative stress, inflammation, and cognitive impairment were evaluated. Additionally, ferroptosis-related protein and gene expression were analyzed using western blot, PCR, immunofluorescence, and flow cytometry. In vitro, using primary neurons and HT22 cells, with electrophysiology employed to assess neuronal activity and glutamate used to induce ferroptosis in HT22 cells, in order to explore how HDCA alleviates epilepsy by inhibiting neuronal ferroptosis. Result A total of 37 chemical components were identified from the ACB, of which 10 active constituents can cross the blood-brain barrier, including steroids and terpenoids. Bioinformatics analysis suggests that HDCA may be one of the key active components responsible for ACB anti-epileptic effects and ferroptosis may represent a crucial underlying therapeutic mechanism. Studies in animals have demonstrated that treatment with ACB and HDCA reduced the frequency and severity of seizures in epileptic rats, mitigated hippocampal neuronal damage, improved post-epileptic cognitive learning capacity, alleviated neuroinflammatory injury and decreased markers of ferroptosis. This neuroprotective effect likely occurs through activation of the p53/Nrf2/GPX4 signaling pathway. Further in vitro cell experiments demonstrated that HDCA can inhibit the generation of action potentials in primary hippocampal neurons, protects HT22 neurons from glutamate-induced cell death, an effect that is reduced by Nrf2 inhibitors. These findings corroborate earlier bioinformatics analyses, confirming that the neuroprotective effects of HDCA are closely linked to Nrf2-mediated ferroptosis pathways. Conclusion HDCA is a key component of ACB anti-epileptic effects, potentially inhibiting ferroptosis through the p53/Nrf2/GPX4 pathway to reduce epilepsy.

Gegen Qinlian Decoction(GQD) is a classic prescription for the clinical treatment of ulcerative colitis(UC). This study, based on the differences in efficacy observed in UC mice under different level of bile acids treated with GQD, aims to clarify the impact of bile acids on UC and its therapeutic effects. It further investigates the expression of bile acid receptors in the liver of UC mice, and preliminarily reveals the mechanism through which GQD affects bile acid synthesis in the treatment of UC. A UC mouse model was established using dextran sulfate sodium(DSS) induction. The efficacy of GQD was evaluated by assessing the general condition, disease activity index(DAI) score, colon length, and histopathological changes in colon tissue via hematoxylin and eosin(HE) staining. ELISA and Western blot were used to evaluate the inflammatory response in colon tissue. The total bile acid(TBA) level and liver damage were quantified using an automatic biochemistry analyzer. The expression levels of bile acid receptors and bile acid synthetases in liver tissue were detected by Western blot and RT-qPCR. The results showed that compared with the model group, GQD treatment significantly improved the DAI score, colon shortening, and histopathological damage in UC mice. The levels of pro-inflammatory factors TNF-α and IL-6 in the colon were significantly reduced. Serum TBA levels were significantly decreased, while alkaline phosphatase(ALP) levels significantly increased. After administration of cholic acid(CA), UC symptoms in the CA + GQD group were significantly aggravated compared with the GQD group. The DAI score, degree of weight loss, colon injury, serum TBA, and liver injury markers all increased significantly. However, compared with the CA group, the CA + GQD group showed a marked reduction in TBA levels and a significant improvement in UC-related symptoms, indicating that GQD can alleviate UC damage exacerbated by CA. Further investigation into the expression of bile acid receptors and synthetases in the liver showed that under GQD treatment, the expression of farnesoid X receptor(FXR) and small heterodimer partner(SHP) significantly increased, while the expression of G protein-coupled receptor 5(TGR5) and cholesterol 7α-hydroxylase(Cyp7A1) significantly decreased. These findings suggest that GQD may affect bile acid receptors and synthetases, inhibiting bile acid synthesis through the FXR/SHP pathway to treat UC.

Baiyaojian is a product co-fermented from Chinese gallnut, tea leaves, and distillers' grains. Baiyaojian shows a significant therapeutic effect in the treatment of pulmonary inflammation. In the process of fermentation, the content of components in Baiyaojian changes all the time, resulting in different anti-inflammatory effects. As a fermentation drug, the time of fermentation plays a decisive role in the efficacy and quality standards of Baiyaojian. Therefore, the determination of the right endpoint of the fermentation time is the primary quality standard for the fermentation of Baiyaojian. In this study, the best fermentation time of Baiyaojian was determined by mid-infrared (MIR) spectroscopy and high-performance liquid chromatography (HPLC), combined with the in vitro anti-inflammatory effect of Baiyaojian. MIR spectra showed that organic compounds such as tannins were gradually decomposed into gallic acid during fermentation, and Baiyaojian with different fermentation days could be clearly distinguished in the PCA score map of MIR; HPLC showed that tannins and gallic acid derivatives were decomposed during fermentation, and the content of gallic acid continued to increase; Cell activity, NO, ROS, inflammatory factors and mRNA expression levels of inflammatory factors clearly showed that with the increase of fermentation days, the anti-inflammatory effect of Baiyaojian was significantly improved, which means Baiyaojian has a good prospect in the treatment of respiratory diseases. Meanwhile, MIR spectroscopy can identify the right-fermented Baiyaojian simply and rapidly.

BACKGROUND:Hyperuricemia, a prevalent chronic metabolic disorder caused by purine metabolism disturbances, is characterized by elevated serum uric acid (UA) levels. Prolonged hyperuricemia can cause severe complications such as gout or kidney damage. However, the toxic side effects of and adverse reactions to UA-lowering drugs are becoming increasingly prominent. Therefore, new targets and drugs for hyperuricemia are needed. PURPOSE:This review aims to summarize recent research progress on the prevention and treatment mechanisms for gut microbiota-hyperuricemia from the perspective of plant-derived natural products. METHODS:Data from PubMed, Web of Science, ScienceDirect, and the CNKI databases spanning from January 2020 to December 2024 were reviewed. The aim of this study is to categorize and summarize the relevant mechanisms through which natural products improve hyperuricemia via the gut microbiota. The retrieved data followed PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-Analyses). RESULTS:Regulating gut microbiota as a treatment for hyperuricemia. Targeting the gut microbiota could reduce host UA levels by promoting purine degradation, reducing UA production, and increasing UA excretion. Moreover, the gut microbiota also exerts anti-inflammatory and antioxidant effects that alleviate complications such as renal damage caused by hyperuricemia. Due to their diverse sources, multicomponent synergy, multitarget effects, and minimal side effects, plant-derived natural products have been extensively utilized in the management of hyperuricemia. Especially, utilizing natural products from plants to regulate the gut microbiota has become a new strategy for reducing UA levels. CONCLUSION:This review comprehensively summarizes recent advances in understanding the preventive and therapeutic mechanisms of plant-derived natural products in ameliorating hyperuricemia and its comorbidities through gut microbiota modulation. This review contributes a novel perspective for the development of safer and more efficacious UA-lowering products.

Clinical and experimental evidences have confirmed the significant therapeutic effects of rhubarb on ulcerative colitis (UC), but the strong purgative function of rhubarb also aggravates UC symptoms such as bloody diarrhea. Stir -baking to scorch is a traditional Chinese medicinal processing method that can eliminate the adverse purgative function while keep or even enhance the UC therapeutic function of rhubarb. However, the under -baked rhubarb still have the undesirable purgative function, but the over -baked rhubarb may lose the required medicinal functions. Therefore, the determination of the right endpoint is the primary quality concern about the baking process of rhubarb. In this research, typical anthraquinone compounds and mid -infrared (MIR) spectra were recruited to determine the best baking degree of rhubarb for UC therapy. Raw rhubarb slices were baked at 180 degrees C with rotation to prepare the rhubarbs with different baking degrees. The right -baked rhubarb was defined according to the UC therapeutic responses as well as the traditional color criterion. Referring to the typical anthraquinone compounds in rhubarb slices and extracts, the baking degree of rhubarb may be assessed by the conversion ratio of anthraquinone glycosides to anthraquinone aglycones. MIR spectra showed the gradual decompositions of organic compounds including anthraquinone glycosides and tannins during the baking process. Rhubarbs with different baking degrees can be distinguished clearly by MIR-based principal component analysis. In conclusion, the ratio of anthraquinone glycosides to anthraquinone aglycones may be a reasonable chemical indicator of the right -baked rhubarb. Meanwhile, MIR spectroscopy can identify the right -baked rhubarb simply and rapidly.

BACKGROUND:Ginseng volatile oil (GVO) is a valuable active ingredient in ginseng (Panax ginseng C. A. Mey.) with high research potential. Drying procedures alter the real composition of the fresh material, for example, the evaporation of compounds with low boiling point. In this study, the composition of volatile oil in fresh ginseng (FG), sun-dried ginseng (SDG), and red ginseng (RD) was systematically analyzed to clarify the dominant components of FG and their potential pharmacological effects, which provides a basis for application and development of FG. METHODOLOGY:GVO was obtained through water vapor distillation and analyzed using GC-MS. Pattern recognition analysis was employed to differentiate components in three processed types of ginseng. Based on this analysis, the active ingredients and key targets were screened. The binding mode and affinity were verified using molecular docking technology. Finally, the anticancer activity of GVO was verified by cell experiments. RESULTS:A total of 53 components were identified in three processed types of ginseng by GC-MS. Among them, 32 differential components were screened by pattern recognition analysis. Ultimately, 6 active ingredients (panaxydol, nerolidyl acetate, falcarinol, cis-β-farnesene, γ-elemene, and β-elemene) and 15 key targets were determined by network pharmacology analysis. Molecular docking results revealed that β-elemene exhibited a higher affinity with EGFR, ESR1, and ERK2. Cell experiments indicated that GVO promotes apoptosis in cancer cells. CONCLUSION:This research proposed a strategy that integrated "component detection-virtual multitarget screening-active component prediction-experimental verification" to expedite the identification of active ingredients, providing insights for application of FG and the development of functional products.

Objective: To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge (S. miltiorrhiza, Dan Shen) and C. tinctorius L. (C. tinctorius, Hong Hua) as an herb pair through network pharmacology and subsequent experimental validation. Methods: Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of S. miltiorrhiza and C. tinctorius as herb pair. Molecular docking was used to verify the binding of the components of these herbs and their potential targets. An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects, which were evaluated using the combination index. Western blot was performed to detect the protein expression of these targets. Results: Network pharmacology analysis revealed 5 pathways and 8 core targets of S. miltiorrhiza and C. tinctorius in myocardial protection. Five of the core targets were enriched in the hypoxia-inducible factor-1 (HIF-1) signaling pathway. S. miltiorrhiza-C. tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway. As an upstream gene of the HIF-1 pathway, STAT3 can be activated by the active ingredients cryptotanshinone (Ctan), salvianolic acid B (Sal. B), and myricetin (Myric). Cell experiments revealed that Myric, Sal. B, and Ctan also exhibited synergistic myocardial protective activity. Molecular docking verified the strong binding of Myric, Sal. B, and Ctan to STAT3. Western blot further showed that the active ingredients synergistically upregulated the protein expression of STAT3. Conclusion: The pharmacodynamic transmission analysis revealed that the active ingredients of S. miltiorrhiza and C. tinctorius can synergistically resist ischemia through various targets and pathways. This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

Hypoaconitine (HA), a major secondary metabolite of aconite (a plant-derived rodenticide), is a highly toxic di-ester alkaloidal constituent. The toxicity of HA is intense with a low LD50. However, studies on its toxicity mechanism have mainly focused on cardiotoxicity, with few reports on the mechanism of hepatotoxicity. In this study, we combined metabolomics and network toxicology to investigate the effects of HA on the liver and analyzed the mechanisms by which it causes hepatotoxicity. The results of metabolomics studies indicated diethyl phosphate, sphingosine-1-phosphate, glycerophosphorylcholine, 2,8-quinolinediol, guanidinosuccinic acid, and D-proline as differential metabolites after HA exposure. These metabolites are involved in eight metabolic pathways including arginine and proline metabolism, ether lipid metabolism, β-alanine metabolism, sphingolipid metabolism, glutathione metabolism, and glycerophospholipid metabolism. Network toxicology analysis of HA may affect the HIF-1 signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and so on by regulating the targets of ALB, HSP90AA1, MMP9, CASP3, and so on. Integrating the results of metabolomics and network toxicology, it was concluded that HA may induce hepatotoxicity by triggering physiological processes such as oxidative stress, inflammatory response, and inducing apoptosis in hepatocytes.

Objective To establish a progressive research strategy for “colonic components analysis - efficacy verification and mechanism exploration - gut microbiota”, screen pharmacodynamic substances, and investigate their mechanism via gut microbiota. Methods The pharmacodynamics of Gegen Qinlian decoction (GQD) were assessed using a mouse model of dextran sulfate sodium-induced ulcerative colitis (UC). Ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometer was used to identify the prototype and metabolic components of GQD in the colon during UC. To analyze the structure and function of characteristic genera of GQD and its active components, 16S rRNA sequencing was performed. Results We identified 67 prototypic and 14 metabolic components of GQD in the UC colon. The primary prototype components are flavonoids and alkaloids, including puerarin (PUE), baicalin (BAI), and berberine (BER). The metabolism was predominantly sulfonation. Efficacy verification showed that the main active components, puerarin, baicalin, and berberine, had good therapeutic effects on UC. The results of 16S rRNA gene sequencing showed that GQD improved UC by regulating the structure and function of the gut microbiota. The abundance of gut microbiota involved in the metabolism of the prototype components was influenced by the corresponding components. The function prediction results showed that PUE was the most comparable to GQD, with 24 consistent pathways. BAI and BER showed comparable gut microbiota regulation pathways. Characteristic pathways of BER include glucometabolic processes. Conclusion This study focused on the key issues in the gut microbiota pathway and developed a progressive research strategy to understand the transformation mechanisms of colonic components. This research systematically analyzed the active components and metabolic transformation of GQD in the colon during the pathological state of UC, as well as changes in the structure and function of the gut microbiota, clarified the mechanism of GQD and its active components in improving UC via the gut microbiota pathway.

ETHNOPHARMACOLOGICAL RELEVANCE:The pathophysiological mechanism of thromboinflammation involves the intricate interplay between the inflammatory responses and coagulation cascades. Rhubarb is frequently used in traditional Chinese medicine to treat thromboinflammatory diseases. The scorched rhubarb (prepared by stir-baking the dried raw rhubarb till it partly turns to charcoal) is believed to possess enhanced blood-cooling and stasis-removing functions compared to the raw rhubarb, thereby augmenting the therapeutic effects on thromboinflammation. AIM OF THE STUDY:This study aimed to explore the chemical and pharmacological foundations of the scorch processing of rhubarb in order to ensure and enhance the efficacy and safety of the scorched rhubarb for treating thromboinflammatory diseases. MATERIALS AND METHODS:The dried raw rhubarb pieces were subjected to stir-baking at 180 °C for 10∼80 min to obtain the rhubarbs with varying degrees of scorching. Typical ingredients present in rhubarb pieces and extracts were determined by high-performance liquid chromatography. The therapeutic effects of the raw and scorched rhubarb on thromboinflammation were evaluated using a rat model. Proteomics analysis was employed to screen potential biological pathways associated with thromboinflammation treatment by the raw and scorched rhubarb, which were further verified using a cell model. RESULTS:Morphological properties indicated that the rhubarb baked at 180 °C for 50 min in this research showed the optimal degree of scorching. Compared to the raw rhubarb, the properly scorched rhubarb exhibited lower levels of anthraquinone glucosides, higher levels of anthraquinone aglycones, superior anti-thromboinflammatory effects, and no purgative side effects. Proteomics analysis revealed that the complement and coagulation cascades pathway played a significant role in mediating the therapeutic effects of the raw and scorched rhubarb on thromboinflammation. Furthermore, it was found that anthraquinone aglycones were more effective than their glucoside counterparts in restoring the impaired vascular endothelial cells as well as regulating the complement and coagulation cascades pathway. CONCLUSIONS:Proper scorch processing may augment the therapeutic effects of rhubarb on thromboinflammation via relieving inflammation and oxidative stress, repairing vascular endothelial cells, restoring coagulation cascades and blood rheology, and regulating some other biological processes. This may be partly caused by the scorch-induced thermolysis of anthraquinone glucosides into their aglycone counterparts that seemed to perform better in regulating the complement and coagulation cascades pathway.

Clinical efficacy and mechanism of Qishen Yiqi Dripping Pills(QSYQ)have been well researched,but the compatibility mechanism underlying its therapeutic effect still requires further analysis.This study aims to explore the compatibility mechanism of QSYQ in treating myocardial ischemia.UPLC-Q-Exactive Orbitrap-MS technique was used to obtain the absorbed blood components of QSYQ.Target proteins of the absorbed components were collected and screened using TCMSP,TCMIP,and SwissTargetPrediction da-tabases.Disease proteins related to myocardial ischemia were obtained through GeneCards,OMIM,and DisGeNET databases.Core targets and core components were obtained using online plotting software Venny 2.1.0,STRING,and Cytoscape 3.9.1 software.David database was used for GO functional annotation and KEGG pathway enrichment of core targets,obtaining the main pathways of QSYQ in treating myocardial ischemia and drawing visualized network diagrams.The compatibility mechanism was analyzed based on"compo-nent-target","drug-pathway",and"PI3K-AKT"characteristic pathways,and molecular docking was used for validation.This study obtained 42 absorbed blood components of QSYQ,556 component targets,1 980 disease targets,69 core targets,and 15 core compo-nents.QSYQ can exert therapeutic effects on myocardial ischemia by regulating proteins such as MAPK1,RELA,SRC,JUN,and STAT3,acting on signaling pathways such as HIF-1,PI3K-AKT,Toll-like,MAPK,VEGF,etc.The interaction network diagrams of"component-target"and"drug-pathway"preliminarily elucidated the synergy among the four drugs in this prescription at the level of targets and pathways.The PI3K-AKT characteristic pathway indicated that the sovereign drug Huangqi(Astragali Radix)and minister drug Danshen(Salviae Miltiorrhizae Radix et Rhizoma)could regulate most targets in this pathway,while the assistant drug Sanqi(No-toginseng Radix et Rhizoma)cooperated with Huangqi and Danshen on IL6 and AKT proteins,and the envoy drug Jiangxiang(Dalber-giae Odoriferae Lignum)acted on AKT and RXRA proteins,with all drugs acting synergistically on proteins such as AKT,RXRA,NFKB to regulate cell survival and promote angiogenesis.Molecular docking indicated that hydrogen bonding and hydrophobic interac-tions might be the main forms of action,also validating the distribution of binding energy of the PI3K-AKT signaling pathway.This study analyzed the compatibility connotation of QSYQ from multiple dimensions including drugs,components,targets,and pathways,providing reference basis for the study of the mechanism of action and compatibility rules of QSYQ.

Based on the differences in the protective effects of fresh Panax ginseng and its processed products on myocardial ischemia in mice, this study identified the advantageous aspects of fresh P. ginseng. By using network pharmacology combined with cell model validation, the molecular mechanisms of fresh P. ginseng in regulating the FoxO signaling pathway were preliminarily revealed. A mouse model of myocardial ischemia was established via intraperitoneal injection of isoproterenol hydrochloride(ISO). The comparison of the protective effects of fresh P. ginseng and its processed products on myocardial ischemia indicated that fresh P. ginseng had a more pronounced effect in reducing lipid peroxidation and alleviating myocardial ischemia in mice. On this basis, network pharmacology research was conducted, showing that fresh P. ginseng contained 19 dominant active ingredients and 38 key targets, including albumin(ALB), serine/threonine protein kinase(AKT1), epidermal growth factor receptor(EGFR), extracellular signal-regulated kinases(ERK1/2), and mitogen-activated protein kinase(P38). Fresh P. ginseng could regulate various biological functions such as cell proliferation, apoptosis, inflammation, and oxidative stress through signaling pathways including Ras, FoxO, IL-17, and Rap1, thereby protecting cardiomyocytes. Among them, the FoxO signaling pathway was identified as a characteristic pathway for fresh P. ginseng. It was further discovered that the dominant active components of fresh P. ginseng, such as ginsenoside Re, ginsenoside Rg_1, and β-elemene, could regulate this pathway through targets such as AKT, JNK, EGFR, and P38. Biological validation results showed that ginsenoside Re, ginsenoside Rg_1, and β-elemene could enhance cell viability, reduce lactate dehydrogenase(LDH) content, and decrease reactive oxygen species(ROS) levels in the cell supernatant. Target validation results indicated that ginsenoside Rg_1 and β-elemene significantly down-regulated the expression of EGFR protein in the FoxO signaling pathway, while ginsenoside Re and β-elemene significantly down-regulated the expression of ERK1/2 and P38 proteins. This study revealed the advantageous mechanisms of fresh P. ginseng in protecting against myocardial ischemia, providing a theoretical basis for the further development of fresh P. ginseng and related products.

This study compared the therapeutic difference effects of the raw and scorched rhubarb for the treatment of ulcerative colitis(UC)and explored their difference in chemical components and mechanisms by using ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-QE-Orbitrap-MS)and network pharmacology.The UC therapeutic effects of Shaoyao Decoction with the raw rhubarb or the scorched rhubarb were evaluated by dextran sulfate sodium(DSS)-induced mouse model.The results showed that Shaoyao Decoction with either the raw rhubarb or the scorched rhubarb could relieve the UC symptoms of mice to different extents,while the scorched rhubarb-based formula showed advantages in reducing hemorrhagic diarrhea and inflammation levels.UPLC-QE-Orbitrap-MS was used to identify a total of 78 small molecules in the water decoction of the raw and scorched rhubarb.Multivariate statistical methods were used to screen components increasing significantly after the scorching process.The seven compounds included five free anthraquinones,gallic acid,and 5-hydroxymethylfurfural(HMF).Meanwhile,the nine compounds decreasing scorching were mainly combined anthraquinones and catechins-related compounds.Network pharmacology and molecular docking suggested that free anthraquinones,gallic acid,and 5-HMF may act on core targets such as B-cell lymphoma-2(BCL2),epidermal growth factor receptor(EGFR),tumor necrosis factor(TNF),and caspase-3(CASP3)and influence the signaling pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt),hypoxia inducible factor-1(HIF-1),TNF,and mitogen-activated protein kinase(MAPK),so as to regulate the inflammation response,oxidative stress,and cell apoptosis to relieve UC symptoms.This study compared the therapeutic effects and chemical components of the raw and scorched rhubarb,providing the clinical reference for using rhubarb to treat UC.

BACKGROUND:Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification" to screen potential nephrotoxic substances rapidly. METHOD:The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened. RESULTS:Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi. CONCLUSIONS:Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.

BACKGROUND:Myocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely.PURPOSE:It is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process.METHODS:The MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology.RESULTS:CDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1-7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14-21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids.CONCLUSION:The dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.

Objective:To screen potential quality markers of rhubarb charcoal and analyze the changes in potential quality markers during the processing of rhubarb charcoal,providing reference for the study of the processing mechanism of rhubarb charcoal and the determination of the processing endpoint.Methods:Based on network pharmacology and literature mining,the potential quality markers of rhubarb charcoal were preliminarily screened.The LPS induced vascular endothelial cells(HUVEC)were used as the model of TCM efficacy of"cooling blood and removing blood stasis".The colorimeter was used to study the colority of samples heated under different conditions,and to analyze the correlation between potential quality markers processing of rhubarb charcoal and color values.Results:The potential quality markers of rhubarb charcoal were divided into two categories.The first is the one-way decrease of potential quality markers with purgative effect,including the combination of anthraquinone and sennoside,and the second is the first increase and then decrease of potential quality markers for anti-inflammatory and hemostasis,including free anthraquinone,gallic acid and 5-HMF.Conclusion:The combined anthraquinone in rhubarb charcoal can be used as the quality marker of"detoxification",and the free anthraquinone can be used as the quality marker of"enhancement".

The cause of rheumatoid arthritis (RA) is unclear. Xiaohuoluo wan (XHLW) is a classical Chinese medicine that is particularly effective in the treatment of RA. Given the chemical composition of XHLW at the overall level has been little studied and the molecular mechanism for the treatment of RA is not clear, we searched for the potential active compounds of XHLW and explored their anti-inflammatory mechanism in the treatment of RA by flexibly integrating the high-resolution ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based in vitro and in vivo chemomics, network pharmacology, and other means. The results of the study identified that the active compounds of XHLW, such as alkaloids, nucleosides, and fatty acids, may play an anti-inflammatory role by regulating key targets such as IL-2, STAT1, JAK3, and MAPK8, inducing immune response through IL-17 signaling pathway, T-cell receptor, FoxO, tumor necrosis factor (TNF), and so forth, inhibiting the release of inflammatory factors and resisting oxidative stress and other pathways to treat RA. The results of this study provide referable data for the screening of active compounds and the exploration of molecular mechanisms of XHLW in the treatment of RA.

Objective We aimed to explore the effect of myocardial infarction（MI） on the intestinal absorption of the active ingredients of Qishen Yiqi Dripping Pills（QSYQ）.Methods Twenty-five male Sprague-Dawley rats were used. Fifteen rats were randomly selected to establish the MI model by ligating the left anterior descending coronary artery; the remaining rats were used as the normal group. Seven-day postoperative MI model rats were taken to confirm the model was successfully established and to determine the physiological status of the intestinal mucosal barrier by electrocardiography（ECG）, by analyzing myocardial and intestinal tissue sections, and by measuring the levels of the serum biomarkers 5-hydroxytryptamine（5-HT） and lipopolysaccharides（LPS）. In normal and seven to nine day postoperative MI model rats, the intestinal absorption of the active ingredients of QSYQ was studied by the single-pass intestinal perfusion method. The final concentration of perfusate was 30 g/L. Values and differences of parameters related to intestinal absorption such as the effective permeability coefficient, absorption rate constant, and absorption fraction were obtained by the weight difference method.Results The ECGs of MI model rats showed 6-8 Q waves and ST-segment elevation. Cytomorphological changes in HE-stained pathological sections of myocardial and intestinal tissues of rats were observed in the model group, with more inflammatory cell infiltration. The serum concentrations of 5-HT and LPS were higher in the model group（P＜0.05）. The rate and extent of absorption of the different components varied in MI rats compared to normal rats. The trans-intestinal membrane absorption rates of danshensu, protocatechualdehyde, tanshinone IIA, calycosin, ginsenoside Rb1, and trans-nerolidol were higher in MI rats（P＜0.05）, and the in vivo absorption fractions of ginsenoside Rb1 and trans-nerolidol were also simultaneously increased（P＜0.05）. Danshensu and calycosin changed from low to high permeability. There were no significant differences in parameters related to intestinal absorption of salvianolic acid A, rosmarinic acid, ginsenoside Rg1, notoginsenoside R1, and astragaloside Ⅳ in the disease state.Conclusion The MI rat model was established successfully after ligating the left anterior descending coronary artery. Morphological changes in myocardial and intestinal tissues of rats were observed. MI changed the mucosal barrier function of the intestine. The effects of the infarct state on the absorption of different types of components were complex and non-specific.