Том 27, № 6 (2024)
- Жылы: 2024
- Мақалалар: 12
- URL: https://journals.eco-vector.com/1386-2073/issue/view/10066
Chemistry
Peganum harmala L.: A Review of Botany, Traditional Use, Phytochemistry, Pharmacology, Quality Marker, and Toxicity
Аннотация
Background:Peganum harmala L. is a perennial herb of Peganum in Zygophyllaceae family. It has been used as a national medicinal herb with the efficacy of strengthening muscle, warming stomach, dispelling cold, and removing dampness in Chinese folk. Clinically, it is mainly used to treat diseases such as weak muscles and veins, joint pain, cough and phlegm, dizziness, headache, and irregular menstruation.
Methods:The relevant information about P. harmala L. in this review is based on online databases, including Elsevier, Willy, Web of Science, PubMed, ScienceDirect, SciFinder, SpringLink, Google Scholar, Baidu Scholar, ACS publications, SciHub, Scopus, and CNKI. The other information was acquired from ancient books and classical works about P. harmala L.
Results:P. harmala L. is an important medicinal plant with a variety of traditional uses according to the theory of Chinese medicine. Phytochemical research revealed that P. harmala L. contained alkaloids, volatile oils, flavonoids, triterpenoids, coumarins, lignins, anthraquinones. Modern studies showed P. harmala L. possessed multiple bioactivities, including anti-cancer, neuroprotective, anti-bacterial, anti-inflammatory, hypoglycemic, anti-hypertensive, anti-asthmatic, and insecticidal activities. Furthermore, the contents of the quality marker and toxicity of P. harmala L. were summarized and analyzed in this review.
Conclusion:The botany, traditional use, phytochemistry, pharmacology, quality marker, and toxicity of P. harmala L. were reviewed in this paper. It will not only provide an important clue for further studying P. harmala L., but also supply an important theoretical basis and valuable reference for in-depth research and exploitations of this plant in the future.



Transcriptomic Analysis of lncRNAs and their mRNA Networks in Cerebral Ischemia in Young and Aged Mice
Аннотация
Background:Ischemic stroke comprises 75% of all strokes and it is associated with a great frailty and casualty rate. Certain data suggest multiple long non-coding Ribonucleic Acids (lncRNAs) assist the transcriptional, post-transcriptional, and epigenetic regulation of genes expressed in the CNS (Central Nervous System). However, these studies generally focus on differences in the expression patterns of lncRNAs and Messenger Ribonucleic Acids (mRNAs) in tissue samples before and after cerebral ischemic injury, ignoring the effects of age.
Methods:In this study, differentially expressed lncRNA analysis was performed based on RNAseq data from the transcriptomic analysis of murine brain microglia related to cerebral ischemia injury in mice at different ages (10 weeks and 18 months).
Results:The results showed that the number of downregulate differentially expressed genes (DEGs) in aged mice was 37 less than in young mice. Among them, lncRNA Gm-15987, RP24- 80F7.5, XLOC_379730, XLOC_379726 were significantly down-regulated. Then, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these specific lncRNAs were mainly related to inflammation. Based on the lncRNA/mRNA coexpression network, the mRNA co-expressed with lncRNA was mainly enriched in pathways, such as immune system progression, immune response, cell adhesion, B cell activation, and T cell differentiation. Our results indicate that the downregulation of lncRNA, such as Gm-15987, RP24- 80F7.5, XLOC_379730, and XLOC_379726 in aged mice may attenuate microglial-induced inflammation via the progress of immune system progression immune response, cell adhesion, B cell activation, and T cell differentiation.
Conclusion:The reported lncRNAs and their target mRNA during this pathology have potentially key regulatory functions in the cerebral ischemia in aged mice while being important for diagnosing and treating cerebral ischemia in the elderly.



Osteoblast Biospecific Extraction Conjugated with HPLC Analysis for Screening Bone Regeneration Active Components from Moutan Cortex
Аннотация
Introduction:The function of promoting bone regeneration of Moutan Cortex (MC), a traditional Chinese medicine, has been widely known but, the effective components of MC in promoting osteoblast-mediated bone regeneration were still unclear.
Objective:The method of osteoblast membrane bio-specific extraction conjugated with HPLC analysis was established to screen bone regeneration active components from MC.
Methods:The fingerprints, washing eluate and desorption eluate of MC extract were analyzed by the established HPLC-DAD method. The established MC3T3-E1 cells membrane chromatography method was used for the bio-specific extraction of MC. The isolated compounds were identified by MS spectrometry. The effects and possible mechanisms of the isolated compounds were evaluated by molecular docking, ALP activity, cell viability by MTT Assay and proteins expression by Western Blot Analysis.
Results:The active compound responsible for bone regeneration from MC was isolated using the established method of osteoblast membrane bio-specific extraction conjugated with HPLC analysis, and it was identified as 1,2,3,4,6-penta-O-β-galloyl-D-glucose (PGG) by MS spectrometry. It was further demonstrated through molecular docking that PGG could fit well into the functional ALP, BMP2, and Samd1 binding pocket. The proliferation of osteoblasts was promoted, the level of ALP was increased, and the protein expression of BMP2 and Smad1 was increased as shown by further pharmacological verification.
Conclusion:It was concluded that PGG, the bone regeneration active compound from MC, could stimulate the proliferation of osteoblasts to promote osteoblast differentiation, and its mechanism might be related to the BMP/Smad1 pathway.



Correlation Analysis between T790M Status and Clinical Characteristics of Patients with EGFR-sensitive Mutation Advanced NSCLC who Progressed after the First Generation and First-line EGFR-TKIs Administration: A Real-world Exploratory Study
Аннотация
Aims:The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFRTKIs) administration.
Methods:A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively. The clinical and demographic characteristics of these patients were collected, which were manifested as pathological type, metastasis location, initial biopsy method, initial genetic test specimens, and baseline gene mutations status. Correlation analysis between T790M status and these characteristics was performed and prognostic analysis regarding the different subgroups was carried out accordingly.
Results:The prevalence of secondary T790M after resistance to initial EGFR-TKIs among the 167 patients was 52.7%. Correlation analysis indicated that the median progression-free Survival (PFS) to initial EGFR-TKIs >12 months were more likely to develop secondary T790M in univariate analysis. However, the conclusion failed to show statistically significant in multivariate analysis. Additionally, patients with intracranial progression of initial EGFR-TKIs therapy were associated with secondary EGFR-T790M. However, it should be noted that those whose best overall response was partial response (PR) during the EGFR-TKI therapy were relevant to secondary T790M. Furthermore, The median PFS of the initial EGFR-TKIs administration was longer among patients with T790M positive mutation and patients with PR reaction than those without T790M mutation and patients with stable disease (SD), respectively (median PFS: 13.6 vs. 10.9 months, P=0.023) and (median PFS: 14.0 vs. 10.1 months, P=0.001).
Conclusion:This retrospective study highlighted the real-world evidence that the best efficacy and intracranial progression with initial EGFR-TKIs therapy among patients with advanced NSCLC might be the promising indicators to predict the occurrence of EGFR-T790M. Patients with PR reaction and T790M positive mutation conferred longer PFS of the initial EGFR-TKIs administration. Also, the conclusion should be confirmed in more patients with advanced NSCLC subsequently.



Zhilong Huoxue Tongyu Capsule Ameliorates Platelet Aggregation and Thrombus Induced by Aspirin in Rats by Regulating Lipid Metabolism and MicroRNA Pathway
Аннотация
Introduction:Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported.
Objectives:This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats.
Methods:An AR model was established through treatment with a high-fat, high-sugar, and highsalt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9-12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6- keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA- 126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction.
Results:Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p.
Conclusion:This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.



The Effect of Quercetin in the Yishen Tongluo Jiedu Recipe on the Development of Prostate Cancer through the Akt1-related CXCL12/ CXCR4 Pathway
Аннотация
Background:It remains a challenge to effectively treat prostate cancer (PCa) that affects global men's health. It is essential to find a natural alternative drug and explore its antitumor mechanism due to the serious toxic side effects of chemotherapy.
Methods:The targets and signaling pathways were analyzed by network pharmacology and verified by molecular docking and LC-MS. The proliferation, apoptosis, invasion, and migration of DU145 cells were detected by the CCK-8 method, flow cytometry, and Transwell, respectively. The Bcl-2, caspase-3, CXCL12, and CXCR4 expressions and Akt1 phosphorylation were determined by Western blot. Akt1 overexpression was applied to identify the involvement of the Akt1- related CXCL12/CXCR4 pathway in regulating PCa. Nude mouse tumorigenesis was performed to analyze the effect of quercetin on PCa in vivo.
Results:Network pharmacology analysis displayed that quercetin was the main active component of the Yishen Tongluo Jiedu recipe and Akt1 was the therapy target of PCa. LC-MS analysis showed that quercetin existed in the Yishen Tongluo Jiedu recipe, and molecular docking proved that quercetin bound to Akt1. Quercetin inhibited the proliferation of DU145 cells by upregulating caspase-3 and downregulating Bcl-2 expression, promoting apoptosis and reducing invasion and migration abilities. In vivo, quercetin downregulated CXCL12 and CXCR4 expressions and inhibited PCa development by the Akt1-related CXCL12/CXCR4 pathway.
Conclusion:As the active component of the Yishen Tongluo Jiedu recipe, quercetin inhibited PCa development through the Akt1-related CXCL12/CXCR4 pathway. This study provided a new idea for PCa treatment and a theoretical basis for further research.



Effect of ω-9MUFAs in Fat Emulsion on Serum Interleukin-6 in Rats with Lipopolysaccharide-induced Lung Injury
Аннотация
Aim:This study aimed to investigate how ω-9 MUFAs in fat emulsion affect serum IL- 6 levels in rats with lipopolysaccharide (LPS)-induced lung injury.
Background:Research suggests that acute lung injury (ALI) develops acute respiratory distress syndrome (ARDS) due to the activation of many inflammatory factors. ALI may be treated by reducing inflammation. Fat emulsion is used in parenteral nutrition for critically ill patients to regulate the body's inflammatory response. It is mostly made up of ω-9 MUFAs (Clinoleic), which can regulate the inflammatory response.
Objective:The effect of ω-9MUFAs on the secretion of IL-6 in ALI rats was studied in order to provide a basis for the rational use of fat emulsion in clinical practice and provide new ideas for the diagnosis and treatment of ALI.
Methods:The control, model, and -9MUFAs groups consisted of 18 female Sprageue-Dawley (SD) young rats (180 ± 20 g). The SD young rats received normal saline and were not operated. LPS-induced ALI animals received tail vein injections of normal saline. SD young rats were first triggered with acute lung injury by LPS (3 mg/kg) and then injected with 3 mg/kg of ω-9MUFAs via the tail vein. The expression levels of IL-6, an activator of signal transduction transcription 3 (STAT3), transforming growth factor-β (TGF-β), and glycoprotein 130 (GP130) in serum and lung tissues were determined by ELISA and Western blot methods.
Results:Compared with the model group, the survival rate of rats in the ω-9 MUFAs group was significantly increased, and the difference was statistically significant (p(<0.05). Compared with the model group, the lung pathology of rats in the ω-9 MUFAs group was significantly improved, and the expression levels of IL-6, TGF-β1, GP130, IL-1 and other proteins were significantly decreased. The difference was statistically significant (p(<0.05).
Conclusion:In LPS-induced lung injury, ω-9MUFAs may alleviate symptoms by inhibiting the IL-6/GP130/STAT3 pathway.



The Protective Effect of Sanggenol L Against DMBA-induced Hamster Buccal Pouch Carcinogenesis Induces Apoptosis and Inhibits Cell Proliferative Signalling Pathway
Аннотация
Background:Oral squamous cell carcinoma (OSCC) has a poor prognosis when treated with surgery and chemotherapy. Therefore, a new therapy and preventative strategy for OSCC and its underlying mechanisms are desperately needed. The purpose of this study was to examine the chemopreventive effects of sanggenol L on oral squamous cell carcinoma (OSCC). The research focused on molecular signalling pathways in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis.
Aim:The purpose of this study was to look at the biochemical and chemopreventive effects of sanggenol L on 7,12-dimethylbenz(a)anthracene (DMBA)-induced HBP (hamster buccal pouch) carcinogenesis via cell proliferation and the apoptotic pathway.
Methods:After developing squamous cell carcinoma, oral tumours continued to progress leftward into the pouch 3 times per week for 10 weeks while being exposed to 0.5 % reactive DMBA three times per week. Tumour growth was caused by biochemical abnormalities that induced inflammation, increased cell proliferation, and decreased apoptosis.
Results:Oral sanggenol L (10 mg/kg bw) supplementation with cancer-induced model DMBApainted hamsters prevented tumour occurrences, improved biochemistry, inhibited inflammatory markers, decreased cell proliferation marker expression of tumour necrosis factor-alpha (TNF- α), nuclear factor (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and induced apoptosis.
Conclusion:Sanggenol L could be developed into a new medicine for the treatment of oral carcinogenesis.



HPTLC Stability Indicating Analytical Method of Andrographolide and 5-fluorouracil with Network Pharmacology Analysis against Cancer
Аннотация
Background:Herbal drugs when used in combination with chemotherapeutic drugs can reduce the side effects and increase the efficacy by acting on multiple targets. Andrographolide (AG), a diterpene lactone isolated from Andrographis paniculata Nees, is a bioactive compound with anticancer potential, and 5-fluorouracil (FU), a pyrimidine analogue, is used in the treatment of cancer. Both drugs are used to formulate combination nanoformulation to increase absorption, thereby increasing their oral bioavailability.
Objective:The study aimed to develop and validate stability indicating simultaneous HPTLC method for quantification of FU and AG in combination nanoformulation along with in silico docking and network pharmacology analysis to understand the interaction between the drugs and cancer targets.
Methods:Chromatographic separation was performed using mobile phase chloroform: methanol: formic acid (9: 0.5: 0.5, v/v/v) on HPTLC silica plates 60 F254 as a stationary phase using UV-Vis detector and HPTLC scanner at 254 nm. Further, in silico docking analysis was performed to predict the binding affinity of AG and FU with different proteins and network pharmacology to find out the exact biomolecular relationship of AG and FU in alleviating cancer.
Results:The data from the calibration curve showed a good linear regression relationship with r² = 0.9981 (FU) and r² = 0.9977 (AG) in the concentration range of 0.1-2.0 µg/mL. The developed method was validated according to the ICH guidelines. Stability studies showed changes in peak patterns and areas. Bioinformatic and network pharmacology analyses of AG and FU with target proteins and genes associated with cancer play a multimechanistic role in alleviating cancer.
Conclusion:The developed method has been concluded to be robust, simple, precise, reproducible, accurate, and stability indicating for simultaneous quantification of AG and FU, and the molecular interaction studies have further indicated that the combination nanoformulation of AG and FU could be effective against cancer.



Evaluation of Therapeutic Mechanism of Hedyotis Diffusa Willd (HDW)‒ Scutellaria Barbata (SB) in Clear Cell Renal Cell Carcinoma via Singlecell RNA Sequencing and Network Pharmacology
Аннотация
Objective:The present study aimed to investigate the therapeutic mechanism of Hedyotis diffusa Willd (HDW) and Scutellaria barbata (SB) in ccRCC using a combination of single-cell RNA sequencing (scRNA-seq) and network pharmacology.
Methods:The active ingredients and potential molecular targets of HDW-SB were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Gene expression data (GSE53757) were obtained from the Gene Expression Omnibus database. The hub genes of HDW-SB against ccRCC were identified via the proteinprotein interaction network, and further analyzed by molecular complex detection. The roles of these genes in the diagnosis and immune infiltration of ccRCC were analyzed. The clinical significance of hub genes was verified using scRNA-seq data (GSE121638) and molecular docking.
Results:Following the PPI network analysis, 29 hub genes of HDW-SB against ccRCC were identified. All hub genes, except for CENPE, had significantly different expressions in tumor tissue and a more accurate diagnosis of ccRCC. Fifteen cell clusters were defined based on the scRNA-seq dataset, and the clusters were annotated as six cell types using marker genes. TYMS and KIAA0101 from hub genes were highly expressed in NK cells. Three active compounds, quercetin, luteolin, and baicalein, were found to target TYMS and KIAA0101 from the compound-target interaction network.
Conclusion:29 hub genes of HDW-SB against ccRCC were identified and showed good performance in terms of diagnosis and prognosis. Moreover, among these hub genes docking with the main ingredients of HDW-SB, TYMS and KIAA0101 exerted anti-ccRCC effects through NK cells.



Transcriptomic and Metabolomic Analysis of Liver Cirrhosis
Аннотация
Background:Liver cirrhosis is one of the leading causes of decreased life expectancy worldwide. However, the molecular mechanisms underlying liver cirrhosis remain unclear. In this study, we performed a comprehensive analysis using transcriptome and metabolome sequencing to explore the genes, pathways, and interactions associated with liver cirrhosis.
Methods:We performed transcriptome and metabolome sequencing of blood samples from patients with cirrhosis and healthy controls (1:1 matched for sex and age). We validated the differentially expressed microRNA (miRNA) and mRNAs using real-time quantitative polymerase chain reaction.
Results:For transcriptome analysis, we screened for differentially expressed miRNAs and mRNAs, analyzed mRNAs to identify possible core genes and pathways, and performed coanalysis of miRNA and mRNA sequencing results. In terms of the metabolome, we screened five pathways that were substantially enriched in the differential metabolites. Next, we identified the metabolites with the most pronounced differences among these five metabolic pathways. We performed receiver operating characteristic (ROC) curve analysis of these five metabolites to determine their diagnostic efficacy for cirrhosis. Finally, we explored possible links between the transcriptome and metabolome.
Conclusion:Based on sequencing and bioinformatics, we identified miRNAs and genes that were differentially expressed in the blood of patients with liver cirrhosis. By exploring pathways and disease-specific networks, we identified unique biological mechanisms. In terms of metabolomes, we identified novel biomarkers and explored their diagnostic efficacy. We identified possible common pathways in the transcriptome and metabolome that could serve as candidates for further studies.



PGD2/PTGDR2 Signal Affects the Viability, Invasion, Apoptosis, and Stemness of Gastric Cancer Stem Cells and Prevents the Progression of Gastric Cancer
Аннотация
Background:Prostaglandin D2 (PGD2) has been shown to restrict the occurrence and development of multiple cancers; nevertheless, its underlying molecular mechanism has not been fully elucidated. The present study investigated the effect of PGD2 on the biological function of the enriched gastric cancer stem cells (GCSCs), as well as its underlying molecular mechanism, to provide a theoretical basis and potential therapeutic drugs for gastric cancer (GC) treatment.
Methods:The plasma PGD2 levels were detected by Enzyme-linked immunosorbent assay (ELISA). Silencing of lipocalin prostaglandin D synthetases (L-PTGDS) and prostaglandin D2 receptor 2 (PTGDR2) was carried out in GCSCs from SGC-7901 and HGC-27 cell lines. Cell Counting Kit-8, transwell, flow cytometry, and western blotting assays were used to determine cell viability, invasion, apoptosis, and stemness of GCSCs. In vivo xenograft models were used to assess tumor growth.
Results:Clinically, it was found that the plasma PGD2 level decreased significantly in patients with GC. PGD2 suppressed viability, invasion, and stemness and increased the apoptosis of GCSCs. Downregulating L-PTGDS and PTGDR2 promoted viability, invasion, and stemness and reduced the apoptosis of GCSCs. Moreover, the inhibition of GCSCs induced by PGD2 was eliminated by downregulating the expression of PTGDR2. The results of in vivo experiments were consistent with those of in vitro experiments.
Conclusion:Our data suggest that PGD2 may be an important marker and potential therapeutic target in the clinical management of GC. L-PTGDS/PTGDR2 may be one of the critical targets for GC therapy. The PGD2/PTGDR2 signal affects the viability, invasion, apoptosis, and stemness of GCSCs and prevents the progression of GC.


