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Ultrasonic tomography, which is widely used in the study of the fracturing process of rocks, often exhibits low resolution due to insufficient ray coverage, particularly while evaluating the three-dimensional (3D) fractures. To resolve this issue, we adopted sparseness regularisation in tomography to reconstruct the ultrasonic velocity of rocks. Both numerical and laboratory experiments demonstrate that tomography with sparseness regularisation generates velocity images with clear fracture morphology than that with Tikhonov regularisation. Dynamic monitoring of the fracturing process of a granite slab with two-dimensional (2D) velocity images can reveal the accurate development of the fracturing process. The experiment on the internal structure of tight sandstone after hydraulic fracturing reveals demarcated low-velocity regions in the 3D ultrasonic velocity images of tomography with sparseness regularisation. These low-velocity regions correspond to the positions of the fractures when compared to the X-ray scanning images. Thus, tomography with sparseness regularisation can improve the resolution of ultrasonic velocity images, which can be used to accurately describe the fracture development and strain localisation during rock deformation.

Colorectal cancer (CRC) is one of the most deadly malignant tumors, which seriously threatens human health. Ferroptosis, a new type of iron-dependent cell regulatory necrosis. Inducing ferroptosis of tumor cells is regarded as a potential treatment strategy. However, the prognostic value of ferroptosis-related genes in CRC remains to be further elucidated. Gallic acid, widely used in the chemical, pharmaceutical, and food fields, is a dietary supplement with potential prescription significance. In this study, the mRNA expression profiles and corresponding clinical data of CRC patients were downloaded from public databases. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the expression levels of ferroptosis-related genes. In addition, bioinformatics analysis showed the prognostic value of ferroptosis-related genes in CRC. Molecular docking predicts the binding status of gallic acid and ferroptosis-related genes. The experiment confirmed the correctness of the predicted results. Our results show that in the TCGA cohort, 30 ferroptosis-related genes are differentially expressed between CRC and adjacent normal tissues. Among them, eight differentially expressed genes are related to overall survival. Gallic acid can bind to ferroptosis-related targets and regulate the expression of corresponding proteins, and ferroptosis inhibitors reversed the experimental results. In summary, eight new ferroptosis-related genes can be used to predict the prognosis of CRC. Gallic acid can improve CRC by regulating ferroptosis.

The high expression of fatty acid synthase (FAS) in tumor cells is consistent with their elevated requirement for fatty acids for cell membrane synthesis and energy supply to support their almost unlimited proliferation. The expression levels of FAS in tumor cells are related to their proliferation, invasion, and metastasis. This study investigated the possible bioactive ingredients (fraxin, esculetin, scopolin et al.) of Cortex Fraxini and their effects on the interaction between specific proteins. We used microscale thermophoresis (MST) to show that our target protein, FAS (screened by combining transcriptome and network pharmacology), bound to the active compounds in Cortex Fraxini. It was found that FAS bound strongly to Glucose-6-phosphate isomerase (GPI), and that scopolin could affect this interaction by proteomics and MST. The results of this study demonstrate that the active compounds in Cortex Fraxini could play an anti-tumor role by binding to FAS and inhibiting the interactions between FAS and GPI to affect glucose and lipid metabolism, and that the protein pathway is a potential novel target for tumor treatment.

Thrombotic diseases seriously threaten human life. Justicia, as a common Chinese medicine, is usually used for anti-inflammatory treatment, and further studies have found that it has an inhibitory effect on platelet aggregation. Therefore, it can be inferred that Justicia can be used as a therapeutic drug for thrombosis. This work aims to reveal the pharmacological mechanism of the anti-thrombotic effect of Justicia through network pharmacology combined with wet experimental verification. During the analysis, 461 compound targets were predicted from various databases and 881 thrombus-related targets were collected. Then, herb-compound-target network and protein–protein interaction network of disease and prediction targets were constructed and cluster analysis was applied to further explore the connection between the targets. In addition, Gene Ontology (GO) and pathway (KEGG) enrichment were used to further determine the association between target proteins and diseases. Finally, the expression of hub target proteins of the core component and the anti-thrombotic effect of Justicia’s core compounds were verified by experiments. In conclusion, the core bioactive components, especially justicidin D, can reduce thrombosis by regulating F2, MMP9, CXCL12, MET, RAC1, PDE5A, and ABCB1. The combination of network pharmacology and the experimental research strategies proposed in this paper provides a comprehensive method for systematically exploring the therapeutic mechanism of multi-component medicine.

Ethnopharmacological relevance As an important Chinese herb, Coptis chinensis Franch. (Huanglian, HL) has a long history of usage for clearing heat, eliminating dampness, purging fire and detoxification in Traditional Chinese Medicine (TCM). HL, also called goldthread, was frequently used for the treatment of typhoid, tuberculosis, epidemic cerebrospinal meningitis, pertussis, and other lung-related diseases. Modern research has shown that HL and its main compounds also have anti-tumor effects. However, studies have not reported whether its main compounds inhibit Non-small cell lung cancer (NSCLC) development and progression. Objective This study aimed to find out the potential targets and mechanisms of Oxyepiberberine (OPB) isolated from HL in the treatment of NSCLC, using network pharmacology and biological experimental. Methods Silica gel chromatography column was used to isolate OPB from HL, and the structure of OPB was elucidated using different spectroscopic analysis methods, including 1H-nuclear magnetic resonance (NMR), 13C-NMR and electrospray ionization mass spectrometry (ESI/MS). MTT assay was performed to determine cell proliferation of OPB on A549, H1975 and BEAS-2B cells. Then, the potential targets, pathways and hub genes of OPB for treating NSCLC were screened out through network pharmacology. Based on the results of network pharmacology, core targets of OPB for treating NSCLC were docking with OPB via molecular docking. Wound healing, plate clone, Hoechst staining, and western blot assay were used to verify the function of OPB in treatment of NSCLC. Results OPB was isolated from the HL, its molecular formula was identified as C20H17NO5. Through MTT, OPB significantly inhibited the proliferation of H1975 cells and A549 cells, and A549 was chosen as the test cancer cell. Through network pharmacology, 22 potential targets, 156 related-pathways, and 6 hub genes were screened out. The results of molecular docking showed that SRC, BRAF, and MMP9 were the core targets of OPB against NSCLC. Through biological experimental, it was found that OPB inhibited growth and migration of A549 cells. In addition, OPB induced apoptosis in A549 cells. Through western blot assay, the expressions of Src, ERK1/2 and other four proteins were down-regulated, which suggested that OPB inhibited the proliferation of lung cancer cells by down-regulating SRC-FAK-RAS-RAF-MEK-ERK pathway, so as to achieve the anti-NSCLC effect. Conclusion Our study demonstrated that anti-NSCLC effect of OPB through network and experiments, which provided a theoretical basis for the clinical antitumor of OPB, and provided a foundation for further study of OPB.

A new neolignan, named (7′S,8′R)-5,3′-dimethoxy-4,4′,9′-trihydroxy-2-8′,9-O-7′-neolignan (1), along with two known compounds, secoisolariciresinol (2) and lariciresinol (3), was isolated from the whole plant of Justicia procumbens L. The structure of 1 was established by spectroscopic methods, and the absolute configuration was determined using circular dichroic (CD) spectra.

Objective 14-Deoxycoleon U is a natural abietane-type diterpene and exerts an inhibitory effect on tumor cells proliferation, which suggests that 14-Deoxycoleon U may be a potent anti-cancerous lead compound for lung cancer treatment. This study was to evaluate potential of 14-Deoxycoleon U to treat lung adenocarcinoma in vitro and in vivo. Methods In the present study, the cell viability and apoptosis morphology of 14-Deoxycoleon U-treated A549 and LLC cells were explored using cell counting kit-8 assay and Hoechst 33258 staining. Then, the protein expressions about apoptosis, endoplasmic reticulum (ER) stress, autophagy and cell cycle were measured using Western blot. The autophagosome formation of 14-Deoxycoleon U-treated A549 cells was visualized using a confocal microscopy. LLC lung adenocarcinoma model was established. Results The results indicated that 14-Deoxycoleon U significantly inhibited A549 and LLC cell proliferation in a dose-dependent manner via caspase-dependent apoptosis. Furthermore, apoptosis of both cells was mediated by 14-Deoxycoleon U-induced ER stress. In addition, 14-Deoxycoleon U-induced A549 and LLC cell autophagy, thus promoting their death. Moreover, 14-Deoxycoleon U-induced cell cycle arrest in both cells via inhibition of cyclin D3, cyclin-dependent kinase 6, CDC2 and up-regulation of p21. In vivo results showed that administration of 14-Deoxycoleon U significantly suppressed LLC growth and adverse effects of 14-Deoxycoleon U on organs might be lower than of adriamycin. Conclusion Overall, our results demonstrated that 14-Deoxycoleon U represses in vitro and in vivo growth of lung adenocarcinoma through ER stress-mediated apoptosis accompanied by autophagy and cell cycle arrest.

This study explored the possible bioactive ingredients and target protein of Rostellularia procumbens (L.) Nees. The results of optical turbidimetry revealed that the ethyl acetate extraction obtained from R. procumbens (L.) Nees could inhibit platelet aggregation. Gene chip was used to investigate differentially expressed genes. According to the results of the gene chip, the targets of compounds isolated from the ethyl acetate extraction were predicted by network pharmacology. Computational studies revealed that chinensinaphthol methyl ether and neojusticin B may target the integrin αIIbβ3 protein. The results of Prometheus NT.48 and microscale thermophoresis suggested that the molecular interactions between the two compounds with purified integrin αIIbβ3 protein in the optimal test conditions were coherent with the docking results. To our best knowledge, this is the first report to state that chinensinaphthol methyl ether and neojusticin B target the integrin αIIbβ3 protein.

Yu Gan Long (YGL) is a Chinese traditional herbal medicine that has been used in the treatment of liver fibrosis for many years in clinical practice. However, its anti-hepatofibrotic mechanism has not been studied yet. In this study, the effect and mechanism of YGL in reducing liver fibrosis was demonstrated in vivo. Our results showed that liver fibrosis biomarkers collagen IV (Col IV), type III precollagen (PCIII), hyaluronuc acid (HA) and laminin (LN), were increased after CCl4 treatment and decreased by YGL. Among the liver fibrosis indicators, α-smooth muscle actin (α-SMA) was decreased by YGL in the CCl4-treated rats, while MMP2 and MMP9 was upregulated followed by TIMP1 downregulation. Proteins involved in liver fibrosis such as p-Smad2, p-Smad3 and Smad4 were down-regulated, while Smad7 protein was up-regulated by YGL after CCl4-induced liver damage. YGL also suppressed the increase of TGF-β1, TNF-α, IL-1β, IL-6, IL-4 and IL-17 A induced by CCl4 treatment, while promoted IFN-γ expression. Finally, the transcription factors ROR-γt and GATA3 were decreased, while T-bet was increased after YGL treatment. These results suggested that YGL attenuated CCl4-induced hepatic fibrosis by accelerating the extracellular matrix degradation, blocking the TGF-β1/Smad signaling pathway and modulating the balance among IL-4, IL-17 A and IFN-γ, demonstrating YGL protective effect and its potential mechanisms in treating liver fibrosis.

Supplemental material, Table S1, for Investigation of Anti-SARS, MERS, and COVID-19 Effect of Jinhua Qinggan Granules Based on a Network Pharmacology and Molecular Docking Approach by Ying Zhang, Yunfeng Yao, Yanfang Yang and Hezhen Wu in Natural Product Communications

In Uygur medicine, Huganbuzure granule (HBG) is one of the classical prescriptions for liver protection. However, its role in immune liver injury remains unknown. This study evaluates the effect of HBG on concanavalin-A- (ConA-) induced immune liver injury and investigates its protective underlying mechanism. BALB/c mice were randomly divided into five groups (n = 24 mice per group): control, ConA, 1.6 g/kg HBG + ConA, 3.2 g/kg HBG + ConA, and 6 mg/kg prednisolone + ConA. HBG was intragastrically administrated once daily for ten consecutive days, prior to ConA (20 mg/kg) injection. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), superoxide dismutase (SOD), and malondialdehyde (MDA) in mouse serum were measured after ConA injection. Moreover, liver-related mRNA levels were evaluated by qPCR. The detection of liver-related proteins was assessed by immunohistochemistry and western blot analysis. Compared with the ConA group, HBG reduced the mRNA expression of IL-17A and IFN-γ and the protein expression of T-bet and ROR-γt. In addition, HBG increased the mRNA expression of IL-4 and TGF-β and protein expression of GATA3 and Foxp3, indicating that HBG regulated the balance of Th1/Th2 and Th17/Treg. Furthermore, HBG alleviated immune liver injury by reducing oxidative stress, inhibiting apoptosis, and decreasing the expression of p-JNK, p-ERK, p-p38, p-JAK1, p-STAT1, p-STAT3, and IRF1. Our data suggested that HBG attenuated ConA-induced immune liver injury by regulating the immune balance and inhibiting JAK1/STATs/IRF1 signaling, thereby reducing apoptosis induced by JNK activation. The findings indicate that HBG may be a promising drug for immune liver injury.

Supplemental material, Supplementary Material 1, for Network Pharmacology Integrated Molecular Docking Analysis of Potential Common Mechanisms of Shu-Feng-Jie-Du Capsule in the Treatment of SARS, MERS, and COVID-19 by Ying Zhang, Yi Xie, Bing Yu, Chong Yuan, Zixin Yuan, Zongchao Hong, Hezhen Wu and Yanfang Yang in Natural Product Communications

It remains a technical challenge to accurately identify close species of herbal medicines, especially from adulterants, because of their highly identical phenotypes and chemical compositions. Here, we report a direct, sequencing-free, high-curvature nanostructuring-based electrochemical herb sensor (nanoE-herb sensor) to identify herbal species quickly and accurately using ITS2 barcodes. We engineer a nano-roughened carbon-supported gold nanostructuring array by photolithograph-free, one-step electrodeposition. The 3D fractal nanostructures exhibit a high deflection angle that largely enhances DNA hybridization efficiency, particularly for the midcomplementary hybridization, as compared to the 2D planar surface. More importantly, such a trans-scale array biointerface (including macroscale carbon and nanoscale gold branches) can overcome the detection barrier of slow diffusion of a long genomic sequence and inaccessibility of the sequestered variations in ITS2 secondary structures through the out-protruded 3D functional nanostructures. Our nanoE-herb sensor achieves a detection limit of 0.18 fM for the 64-mer fragment of saffron ITS2 barcode with midhybridization and shows superior specificity against even single-base mismatch. The sensor also precisely differentiates saffron from six other adulterants by directly detecting unpurified asymmetric PCR amplicons (∼500 bp) with ITS2 sequences, suggesting its great potential in the field identification of herbal medicinal species and pathogenic bacteria with specific DNA barcodes.

In vitro and in vivo studies indicate that scutellarin (SCU) exerts anti-inflammatory effects in the central nervous system (CNS) and inhibits microglia activation. This study investigated the anti-neuroinflammation molecular mechanisms exerted by scutellarin in LPS-induced BV-2 cells. The results showed that production of TNF-α, IL-1β, IL-6, and NO and TNF-α, IL-1β, IL-6, and iNOS mRNA were inhibited by scutellarin, which was independent of cytotoxicity as assessed by a CCK8 assay. Western blot analysis indicated that NF-κB-p65 phosphorylation was suppressed by scutellarin via inhibition of IκB degradation and IKKβ activation, which coincided with blockage of nuclear translocation of NF-κB as shown by immunofluorescent staining. Consistent with the inhibition of NF-κB, scutellarin inhibited the phosphorylation of p38, JNK, and AKT without affecting phosphorylation of ERK1/2 or PI3K in LPS-induced BV-2 cells. Overall, the present study suggests that scutellarin inhibits the production of pro-inflammatory mediators via inhibition of the IKK-dependent NF-κB and p38/JNK signaling pathway, which inhibits microglia activation and exerts anti-inflammation, indicating its potential therapeutic effect for neurodegenerative and cerebrovascular diseases.

Ethnopharmacological relevance Actinidia chinensis Planch. (ACP) is a common traditional Chinese medicine, which is mostly used for cancer treatment clinically. Liver cancer is a refractory tumor with a high incidence. Although ACP has been reported in the treatment of liver cancer, its possible mechanism of action is little known. Aim of study The aim of this paper was to investigate the active components of ACP in the treatment of liver cancer and the related mechanisms by a network pharmacology approach. Methods The active components of ACP and the corresponding targets were obtained from multiple databases. Cytoscape software and STRING database were used to build the "herb-component-target (H-C-T)" network and protein–protein interactions (PPI) network. The key components and targets were further predicted by the Cytohubba plug-in in Cytoscape. Then, experiments were carried out on HepG2 cell line and Huh7 cell line to verify the effects and related mechanisms of the key compounds in ACP. Results 28 active components in ACP and 1299 related targets were screened out according to two indicators, oral bioavailability (OB) and drug-likeness (DL). The key compounds predicted include rutinum, astragalin, and L-epicatechin, and the main signaling pathways focus on apoptosis. Astragalin, a key compound in ACP, could inhibit the expression of Bcl-2, up-regulate the expression of Bax, cleaved caspase 3, cleaved caspase 8, and cleaved caspase 9, and regulate the apoptosis signaling pathway to inhibit the proliferation of liver cancer cells to play a therapeutic role in anti-liver cancer. Conclusions These results suggest that ACP can alleviate the progression of liver cancer through the mechanisms predicted by network pharmacology, and provide a basis for the further understanding of the application of ACP in anti-cancer.

Ethnopharmacological relevance “Huai Hua San” (HHS) is one of the first hundred ancient classic prescriptions drugs, which is commonly used to treat hemorrhoids, colitis, and other symptoms of wind heat in stool. However, the potential molecular mechanism of action of this substance remains unclear. Aims of the study: In this study, we explored the active compounds of HHS for the treatment of ulcerative colitis (UC), predicted the potential targets of the drug, and studied its mechanism of action through network pharmacology via in vitro and in vivo experiments. Materials and methods First, we identified the active compounds and key targets of HHS for treating UC via network pharmacology. The key signaling pathways associated with the anti-inflammatory effect of HHS were analyzed. The anti-inflammatory effects of HHS and its active compounds were studied using the RAW264.7 inflammatory cell model in vitro. Furthermore, we used the dextran sulfate sodium (DSS) mouse model to explore the efficacy and mechanism of HHS in UC in vivo, and the expression level of key proteins were detected by Western blotting. Results In all, 23 compounds and 97 targets were obtained from TCMSP database, PharmMapper database, and GeneCards database. After enrichment via Kyoto Encyclopedia of Genes and Genomes (KEGG), HIF-1 signaling pathway, PI3K/AKT signaling pathway, and VEGF signaling pathway were identified to be the top three signaling pathways associated with UC treatment. The results of molecular docking showed that the docking scores of the top 10 active compounds were higher than the threshold values. In vitro, different concentrations of HHS and the four main active compounds could effectively inhibit the release of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)–α, and IL-1 β. In vivo, HHS could alleviate UC symptoms. Conclusion Taken together, the treatment of UC with HHS may alleviate the inflammatory response of the colon, and HHS mainly inhibits the EGFR/PI3K/AKT/HIF-1/VEGF signaling pathways.

Introduction Angong Niuhuang Pills (AGNH), a Chinese patent medicine recommended in the “Diagnosis and Treatment Plan for COVID-19 (8th Edition),” may be clinically effective in treating COVID-19. The active components and signal pathways of AGNH through network pharmacology have been examined, and its potential mechanisms determined. Methods We screened the components in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) via Drug-like properties (DL) and Oral bioavailability (OB); PharmMapper and GeneCards databases were used to collect components and COVID-19 related targets; KEGG pathway annotation and GO bioinformatics analysis were based on KOBAS3.0 database; “herb-components-targets-pathways” (H-C-T-P) network and protein-protein interaction network (PPI) were constructed by Cytoscape 3.6.1 software and STRING 10.5 database; we utilized virtual molecular docking to predict the binding ability of the active components and key proteins. Results A total of 87 components and 40 targets were screened in AGNH. The molecular docking results showed that the docking scores of the top 3 active components and the targets were all greater than 90. Conclusion Through network pharmacology research, we found that moslosooflavone, oroxylin A, and salvigenin in AGNH can combine with ACE2 and 3CL, and then are involved in the MAPK and JAK-STAT signaling pathways. Finally, it is suggested that AGNH may have a role in the treatment of COVID-19.

Objective Jinhua Qinggan Granules (JQGs) have achieved certain results in the prevention and treatment of COVID-19 in China during this coronavirus storm. In this study, we aimed to analyze the common mechanisms of JQG in the treatment of coronavirus-induced diseases, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 via network pharmacology and molecular docking. Methods The active compounds of JQG were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The common targets associated with these 3 diseases were screened from GeneCards database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of JQG’s core targets were analyzed using The Database for Annotation, Visualization, and Integrated Discovery and KOBAS 3.0 system. Further, the protein-protein interaction network was built using STRING database. The compound-target- signaling pathway network was constructed using Cytoscape 3.7.2. The core components of JQG were docked with core targets, COVID-19 coronavirus 3 Cl hydrolase, and angiotensin-converting enzyme 2 (ACE2) via Discovery Studio 2016 software. Results A total of 139 active compounds, 50 core targets, and 122 signaling pathways were screened out. The results of molecular docking showed that arctiin and linarin had a higher docking score with 3 Cl, ACE2, and core targets of JQH for antiviral effect. Conclusion The potential mechanism of action of JHQ in the treatment of MERS, SARS, and COVID-19 may be associated with the regulation of genes co-expressed with ACE2 and immune- related signaling pathways.

Scopoletin is a natural anticarcinogenic and antiviral coumarin component. Many studies have proved its anti-cancer effect, and after the preliminary screening of this study, Scopoletin had the best inhibitory effect on Non-small cell lung cancer (NSCLC). But its mechanism for treating NSCLC is still unclear. Therefore, network pharmacology and molecular docking technology were used to explore the potential anti-NSCLC targets and pathways of Scopoletin. The results were verified in vitro.First, Scopoletin was isolated from Fennel and screened to conduct cell proliferation assay on Human lung cancer cell line A549, Human colon cancer cell line HCT-116 and Human hepatoma cell line HepG2 respectively, through the MTT test. Then, the key targets and related pathways were screened through Protein-protein Interaction (PPI) network and "component-target-pathway" (C-TP) network constructed by network pharmacology. And the key targets were selected to dock with Scopoletin via molecular docking. A549 and Human normal lung epithelial cell BEAS-2B were used to verify the results, finally.Through MTT, A549 was chosen as the test cancer cell. From network pharmacology, 16 targets, 27 signaling pathways and 16 GO items were obtained (P 0.05). The results of PPI network and molecular docking showed that EGFR, BRAF and AKT1 were the key targets of Scopoletin against NSCLC, which were consistent with the western-blot results.Through network pharmacology, molecular docking and experiments in vitro, Scopoletin was verified to against NSCLC through RAS-RAF-MEK-ERK pathway and PI3K/AKT pathway.

A simple and intuitive method for optimizing the chemical constituents of Coptis Chinensis Franch. is important to assess its quality and clinical efficacy. An high performance liquid chromatography and ultraviolet spectrophotometry method was developed for the determination of berberine hydrochloride, palmatine chloride, jatrorrhizine hydrochloride, epiberberine, coptisine, columbamine and magnoflorine in various tissues (i.e., phloem, xylem and medulla) and rizhome of C. Chinensis Franch. The transection of rhizome from outside-in includes cork layer, cortex, phloem, cambium, xylem and medulla. Cork layer consists of dead cells, and therefore is not of any research significance. Cortex, phloem and cambium were almost impossible to separate, therefore they were studied as a whole in our experiments. They were collectively referred to as "phloem". The analytes were separated on a Gemini-NX C18 (250 mm × 4.6 mm, 5 μm) reversed phase column using a gradient elution of acetonitrile-0.03 mol/L ammonium acetate solution (containing 0.1% triethylamine and 0.6% ammonium hydroxide) as the mobile phase at a flow rate of 1.0 mL/min and UV detection at 270 nm. The method allowing the simultaneous quantification of seven major active constituents was optimized and validated for linearity, precision, accuracy, limits of detection (LOD) and quantification. The LOD ranged from 0.102 to 0.651 mg/mL (r ≥ 0.9993). Accuracy, precision and recovery were all within the required limits. The average recovery was between 100.14% and 102.75% and the relative standard deviations were

Objective 14-Deoxycoleon U is a natural abietane-type diterpene and exerts an inhibitory effect on tumor cells proliferation, which suggests that 14-Deoxycoleon U may be a potent anti-cancerous lead compound for lung cancer treatment. This study was to evaluate potential of 14-Deoxycoleon U to treat lung adenocarcinoma in vitro and in vivo. Methods In the present study, the cell viability and apoptosis morphology of 14-Deoxycoleon U-treated A549 and LLC cells were explored using cell counting kit-8 assay and Hoechst 33258 staining. Then, the protein expressions about apoptosis, endoplasmic reticulum (ER) stress, autophagy and cell cycle were measured using Western blot. The autophagosome formation of 14-Deoxycoleon U-treated A549 cells was visualized using a confocal microscopy. LLC lung adenocarcinoma model was established. Results The results indicated that 14-Deoxycoleon U significantly inhibited A549 and LLC cell proliferation in a dose-dependent manner via caspase-dependent apoptosis. Furthermore, apoptosis of both cells was mediated by 14-Deoxycoleon U-induced ER stress. In addition, 14-Deoxycoleon U-induced A549 and LLC cell autophagy, thus promoting their death. Moreover, 14-Deoxycoleon U-induced cell cycle arrest in both cells via inhibition of cyclin D3, cyclin-dependent kinase 6, CDC2 and up-regulation of p21. In vivo results showed that administration of 14-Deoxycoleon U significantly suppressed LLC growth and adverse effects of 14-Deoxycoleon U on organs might be lower than of adriamycin. Conclusion Overall, our results demonstrated that 14-Deoxycoleon U represses in vitro and in vivo growth of lung adenocarcinoma through ER stress-mediated apoptosis accompanied by autophagy and cell cycle arrest.

Rubia cordifolia L. is widely used in Asia and its antihepatoma effect has been proved by in vitro and in vivo experiments. However, there are few studies on its specific mechanism. In the present study, the network pharmacology method was used to construct the component/target/pathway molecular regulatory network for the antihepatoma effect of Rubia cordifolia L. to explore the effective components of Rubia cordifolia L. and its potential mechanism. The chemical components of Rubia cordifolia L. were identified through literature and databases, and the components were evaluated and screened by drug likeness and pharmacokinetic characteristics (ADMET). The targets of active components were predicted according to the reverse pharmacophore matching model. The hepatic carcinoma-related genes were found in databases, and antihepatoma-related gene targets were selected through comparison. The functions of target genes and related pathways were analyzed and screened using the Database for Annotation, Visualization and Integrated Discovery, and the component/target/pathways network of antihepatoma effect of Rubia cordifolia L. was constructed using Cytoscape software. Finally, 16 active compounds were screened from Rubia cordifolia L., and 39 gene targets, including AKT1, mitogen-activated protein kinase 1, and epidermal growth factor receptor, were involved. Rubia cordifolia L. also affected the hepatitis B, phosphoinositide-3-kinase-protein kinase B, and mitogen-activated protein kinase signaling pathways. Many direct-acting tumor-related signaling pathways and indirect-acting hepatitis pathways inhibit the generation of liver cancer. The present study provided a scientific basis for further elucidating the mechanism of Rubia cordifolia L. against liver cancer.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), is often accompanied by injury to pulmonary function and pulmonary fibrosis. Feiluoning (FLN) is a new Chinese medicine prescription which is available for the treatment of severe and critical convalescence of COVID-19 patients. FLN also has a positive effect on pulmonary function injury and pulmonary fibrosis. We explored the potential mechanism of FLN’s effect on the convalescent treatment of COVID-19. According to the pharmacodynamic activity parameters, we screened the active chemical constituents of FLN by comparing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The Uniprot database was used to querying the corresponding target genes, and Cytoscape 3.6.1 was used to construct a herb-compound-target network. Protein interaction analysis, target gene function enrichment analysis, and signal pathway analysis were performed using the STRING, DAVID, and Kyoto Encyclopedia of Genes and Genomes pathway databases. Molecular docking was used to predict the binding capacity of the core compound with COVID-19 hydrolase 3 Cl and angiotensin-converting enzyme 2 (ACE2). The herb-compound-target network was successfully constructed and key targets identified, including prostaglandin G/H synthase 2, estrogen receptor 1, heat shock protein HSP 90, and androgen receptor. The major affected metabolic pathways were pathways in cancer, pancreatic cancer, nonsmall cell lung cancer, and toll-like receptor signaling. The core compounds of FLN, including quercetin, luteolin, kaempferol, and stigmasterol, could strongly bind to COVID-19 3 Cl hydrolase, and other compounds, including 7-O-methylisomucronulatol and medicocarpin, could strongly bind to ACE2. Thus, it is predicted that FLN has the characteristics of a multicomponent, multitarget, and multichannel overall control compound. FLN’s mechanism of action in the treatment of COVID-19 may be associated with the regulation of inflammation and immune-related signaling pathways, and the influence of COVID-19 3 Cl hydrolase binding ability.

In the process of fighting against COVID-19 in China, Xingnaojing injection has been recommended for its clinical treatment, but the information about its active components and mechanism is still lacking. Therefore, in this work, using network pharmacology and molecular docking, we studied the active components of Xingnaojing injection having anti-COVID-19 properties. Using the DL parameter, TCMSP and CNKI databases were used to screen the active components of the Xingnaojing injection. Then, the SwissTargetPrediction webserver was used to collect the corresponding gene targets, and the gene targets related to COVID-19 were searched in the Genecards database. The DAVID database was used to enrich the function of gene targets, and the KOBAS3.0 database for the annotation of related KEGG pathways. The “components–targets–pathways” network of Xingnaojing injection was constructed with Cytoscape 3.6.1 software. The protein–protein interaction networks were analyzed using the String database. Specific proteins, SARS-COV-2 3 Cl, ACE2, and the active components were imported into Discovery Studio 2016 Client for molecular docking studies. From the Xingnaojing injection, a total of 58 active components, including Divanillalaceton and Q27139023, were screened. These were linked to 53 gene targets including mitogen-activated protein kinase 1 (MAPK1), tumor necrosis factorTNF, epidermal growth factor receptor, MAPK3, and 196 signaling pathways related to COVID-19, such as apoptosis, C-type lectin receptor signaling pathway, and hypoxia-inducible factor 1 signaling pathway. Furthermore, molecular docking studies were performed to study potential binding between the key targets and selected active components. Xingnaojing injection exhibits anti-COVID-19 effects via multiple components, multiple targets, and multiple pathways. These results set a scientific basis for further elucidation of the anti-COVID-19 mechanism of Xingnaojing injection.

Shu-Feng-Jie-Du Capsules (SFJDCs) have been clinically proven to have a good therapeutic effect on COVID-19 in China. This study aimed to analyze the common mechanisms of SFJDC in the treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 via network pharmacology and molecular docking. We further explored the potential application value of SFJDC in the treatment of coronavirus infection. All components of SFJDC were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The viral associated targets of the active components were forecast using the Pharmmapper database and GeneCards. The Database for Annotation, Visualization, and Integrated Discovery and KOBAS 3.0 system were used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of SFJDC’s core targets. Further, the protein–protein interaction network was built using STRING database. The herb–component network and component–target–pathway network were constructed using Cytoscape 3.7.2. The core active components of SFJDC were docked with core targets and COVID-19 coronavirus 3 Cl hydrolase and angiotensin-converting enzyme 2 (ACE2) via Discovery Studio 2016 software. A total of 110 active components were filtered from SFJDC, with 47 core targets, including epidermal growth factor receptor, mitogen-activated protein kinase 1, mitogen-activated protein kinase 3, and interleukin 6. There were 416 GO items in the GO enrichment analysis ( P < .05) and 57 signaling pathways ( P < .05) in KEGG, mainly including pathways in cancer, pancreatic cancer, colorectal cancer, apoptosis, and neurotrophin signaling pathway, among others. The results of molecular docking showed that luteolin and rhein had a higher docking score with 3 Cl, ACE2, and core targets of SFJDC for antiviral effect. SFJDC is characterized by multicomponent, multitarget, and multisignaling pathways for the treatment of coronavirus infection. The mechanism of action of SFJDC in the treatment of MERS, SARS, and COVID-19 may be associated with the regulation of genes coexpressed with ACE2 and immune- related signaling pathways.

Systemic lupus erythematosus (SLE) is a serious disorder of immune regulation characterized by overproduction of autoantibodies, lupus nephritis, CD4+ T cell aberrant activation, and immune complex-mediated inflammation. The chronic graft vs. host disease (cGVHD) mouse model is a well-established model of SLE. Quercitrin is a natural compound found in Tartary buckwheat with a potential anti-inflammatory effect that is used to treat heart and vascular conditions. In our previous study, we determined that quercitrin is an immunosuppressant with beneficial effects in mouse models of immune diseases. We hypothesized that quercitrin could prevent lupus nephritis in the cGVHD mouse model by decreasing the production of autoantibodies and inflammatory cytokines, and reducing immune cell activation. cGVHD was induced by injecting DBA/2 spleen cells into the tail vein of BDF1 mice. The cGVHD mice exhibited significant proteinuria, which is a marker of nephritis. Quercitrin decreased the number of serum antibodies, CD4+ T cell activation, as well as the expression levels of T-bet, GATA-3, and selected cytokines. Moreover, quercitrin treatment decreased the expression of inflammatory genes and cytokines in the kidney, as well as in peritoneal macrophages. In addition, quercitrin inhibited LPS-induced cytokines as well as the phosphorylation of ERK, p38 MAPK, and JNK in Raw264.7 cells. Overall, quercitrin ameliorated the symptoms of lupus nephritis in the cGVHD mouse model, which may be due to the inhibition of CD4 T cell activation and anti-inflammatory effects on macrophages.

Juechuang, a traditional Chinese herbal medicine, is originated from Rostellularia procumbens (L.) Nees. Many studies have shown that the ethyl acetate extract from Juechaung may inhibit platelet aggregation. However, the antiplatelet aggregation mechanism of Juechuang requires more systematic research. In this article, network pharmacology was used to explore the antiplatelet aggregation components and its antiplatelet aggregation mechanism. Different components were evaluated and screened by pharmacokinetic characteristics. The potential targets of active ingredients were predicted by a reverse pharmacophore matching method, and the targets were screened according to targets related to antiplatelet aggregation in the GeneCards database. Thus, an interaction network of component-target-pathway of Juechuang was generated using Cytoscape 3.2.1. software. Furthermore, the binding energy of relevant active components with key targets was calculated using a Lamarck genetic algorithm in the molecular docking calculations. Finally, the study identified 28 potentially active ingredients in Juechuang, providing further evidence that the active ingredients act on 277 targets, and 38 protein targets related to antiplatelet aggregation were screened. Through the Kyoto encyclopedia of genes and genome pathway enrichment analysis, we found that the mechanism of antiplatelet aggregation may be related to the Ras signaling pathway, platelet activation signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, etc. Via molecular docking of 2 targets, non-receptor tyrosine kinases(SRC) and MAPK were selected for molecular docking. By comparing the molecular docking results of Chinensinaphthol, Taiwanin E, Tuberculatin, Cycloeucalenol, and Justicidin B to the control drug, we found that those test molecules combined with targets and lead to high binding activity. These molecular docking results were also consistent with the literature values, and they helped identify the active ingredients and assured the reliability of the network analysis. This study may further provide a reference for the systematic study of the pharmacodynamic effect and the antiplatelet aggregation mechanism of Juechuang.

Coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly infectious viral disease. Clinical observations have shown that Qing-Fei-Da-Yuan (QFDY) granules have good anti-COVID-19 effects, but the underlying molecular mechanisms are unclear. In this study, we explored the potential mechanism of QFDY with regard to its anti-COVID-19 effect. We first screened the active chemical constituents of QFDY based on the pharmacodynamic activity parameters, followed by screening with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The Uniprot database was used for querying the corresponding genes of the target, and Cyoscape 3.6.1 software was used to construct the network of herb-compound-target. Protein interaction analysis, target gene function enrichment analysis, and signal pathway analysis were performed via STRING database, Database for Annotation, Visualization, and Integrated Discovery, and KEGG Pathway database. Molecular docking was used to predict the binding capacity of the core compound with COVID-19 hydrolase 3CL and angiotensin converting enzyme 2 (ACE2). The results showed that a network of herb-compound-target was successfully constructed, with key targets involving PTGS2, HSP90AA1, CAMKK2, NCOA2, and ESR1. Major metabolic pathways affected were those in cancer, procancer, nonsmall cell lung cancer, and apoptosis. The core compounds, such as quercetin, luteolin, and naringenin, showed a strong binding ability with COVID-19 3CL hydrolase; compounds such as anemasaponin C and medicocarpin showed a strong binding ability with ACE2. Thus, it is predicted that QFDY has the characteristics for multicomponent, multitarget, and multichannel overall control. The mechanism of action of QFDY in the treatment of COVID-19 may be associated with the regulation of genes co-expressed with ACE2, the regulation of inflammation and immune-related signaling pathways, and the influence of COVID-19 3CL hydrolase and ACE2 binding ability.

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by mesangial cell proliferation, inflammation, and extracellular matrix deposition in the mesangial area, which develops into glomerulosclerosis and contributes to end-stage renal disease. Justicidin B is a bioactive compound isolated from Justicia procumbens L., a traditional herbal remedy that reduces proteinuria in nephritis. However, the mechanism of Justicidin B’s therapeutic effect on MsPGN remains unclear. This study was aimed to explore the positive effect of Justicidin B on MsPGN. The results showed that Justicidin B attenuated the proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in MCs and blocked cell cycle progression. Likewise, inflammatory factors, including monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor alpha (TNF-α), in MCs were decreased after treatment with Justicidin B. In addition, Justicidin B exhibited antioxidant activity in PDGF-BB-induced MCs, shown by the decreased production of malondialdehyde and T-AOC, and increased the expression of superoxide dismutase. Besides, Justicidin B suppressed extracellular matrix (ECM) deposition by reducing the protein levels of collagen IV and fibronectin. Furthermore, we found that Justicidin B significantly inhibited activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in MCs induced by PDGF-BB, but enhanced the levels of proteins in the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Taken together, Justicidin B prevented PDGF-BB-induced proliferation, inflammation, oxidative stress, and ECM accumulation via regulating the activation of the Nrf2/HO-1 pathway and the Akt/mTOR signaling pathway.

Gegen Qinlian decoction (GQD) is a traditional Chinese medicine that is used to treat non-alcoholic fatty liver disease (NAFLD) in the clinic. The pharmacodynamics and cellular pathways governing the effects of GQD on NAFLD remain undefined. In this study, we investigated GQD pharmacology through assessment of its chemical constituents and evaluated and screened its components using drug likeness, pharmacokinetic characteristics (absorption, distribution, metabolism, excretion, and toxicity), and appropriate compensation mechanisms. We performed predictions of the active GQD ingredients based on reverse pharmacophore matching and compared multiple NAFLD-related genes to determine potential GQD targets. Molecular docking experiments of the active components were performed to reveal cellular targets. Annotation analysis of both target genes and related pathways were assessed through the DAVID database. Cytoscape software was used to construct a “component-target-path” network for the treatment of NAFLD by GQD. Through data analysis, 9 active GQD substances and 10 targets related to NAFLD encompassing 4 cellular pathways were identified. Data were verified through enzyme-linked immunosorbent assay and Western blot analysis. These findings provide new references for the network pharmacology of Chinese medicinal compounds and NAFLD treatment.

Asthma is characterized by airway inflammatory infiltration, which leads to airway remodeling and airway hyperreactivity. Coleus forskohlii (CFK) has been used to treat asthma, however, the mechanism involved is not clear. To explore the antiasthma mechanism of extracts of Coleus forskohlii (ECFK), guinea pigs were administered with a spray of phosphoric acid histamine, and rats were sensitized with ovalbumin (OVA). Hematoxylin and eosin staining (H&E) were used to evaluate pathological changes in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine levels in serum and bronchoalveolar lavage fluid (BALF). Immunohistochemistry and Western blot analysis were used to assess the expression of intercellular cell adhesion molecule-1 (ICAM-1), phosphorylation of p65 (p-p65), matrix metallopeptidase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1). After ECFK treatment, the asthma incubation period of guinea pigs was significantly prolonged. The H&E results showed that the number of eosinophils in the 12.8 g/kg ECFK group was significantly lower when compared with the control group. Moreover, ELISA results demonstrated that interleukin (IL)-4, IL-5, and IL-17 in serum and BALF were significantly decreased, and interferon-γ (IFN-γ) and IL-10 were increased after ECFK treatment. In addition, ECFK treatment resulted in downregulation of ICAM-1, p-p65, MMP-9, and TIMP-1 in lung tissue after being sensitized by OVA. In conclusion, our findings indicated that ECFK significantly alleviated OVA-induced inflammatory infiltration and airway remodeling in asthma. This study laid a theoretical foundation for the clinical use of ECFK.

Yanhusuo (Corydalis Rhizoma) extracts are widely used for the treatment of pain and inflammation. The effects of Yanhusuo in pain assays were assessed in a few studies. However, there are few studies on its analgesic mechanism. In this paper, network pharmacology was used to explore the analgesic components of Yanhusuo and its analgesic mechanism. The active components of Yanhusuo were screened by TCMSP database, combined with literature data. PharmMapper and GeneCards databases were used for screening the analgesic targets of the components. The protein interaction network diagram was drawn by String database and Cytoscape software, the gene ontology and KEGG pathway analyses of the target were performed by DAVID database, and the component–target–pathway interaction network diagram was further drawn by Cytoscape3.6.1 software. System Dock Web Site verified the molecular docking among components and targets. Finally, an interaction network of the component–target–pathway of Yanhusuo was constructed, and the functions and pathways were analyzed for preliminarily investigating the mechanism of Yanhusuo in analgesia. The results showed that the active components of analgesic in Yanhusuo were Corynoline, 13-methylpalmatrubine, dehydrocorydaline, saulatine, 2,3,9,10-tetramethoxy-13-methyl-5,6-dihydroisoquinolino[2,1-b]isoquinolin-8-on-e, and Capaurine. The mechanisms were involved in metabolic pathways, PI3k-Akt signaling pathway, pathways in cancer, and so on. The top 3 targets were NOS3, glucose-6-phosphate dehydrogenase, and glucose-6-phosphate isomerase in components-target-pathways network, and they were all enriched in metabolic pathways. Meanwhile the molecular docking showed that there was a high binding activity between the 6 components and the important target proteins, as a further certification for the subsequent network analysis. This study reveals the relationship of the components, targets, and pathways of active components in Yanhusuo, and provides new ideas and methods for further research on the analgesic mechanism of Yanhusuo.

Isogarcinol is a new immunosuppressant that we extracted from Garcinia mangostana L. In the present study, we elucidate its beneficial effect in chronic graft-versus-host disease (cGVHD) in mice -- a model for systemic lupus erythematosus (SLE) in human. The oral administration of 60 mg/kg isogarcinol significantly reduced proteinuria, corrected the abnormal serum biochemical indicator, and decreased the amount of serum antibodies and lowered the renal histopathology score. In addition, isogarcinol alleviated the abnormal activation of CD4 T cells and decreased the expression of inflammatory genes and cytokines in the kidneys and peritoneal macrophages. The mechanism of action of isogarcinol is associated with downregulation of CD4 T cells and inflammatory effects. Therefore, we believe that isogarcinol may be a potential therapeutic drug candidate for future treatment of SLE.

Brevilin A is a sesquiterpene lactone isolated from Centipeda minima and possesses inhibitory effects on proliferation of various tumor cells. In this study, Brevilin A inhibitory effect on proliferation and its molecular mechanism of action were investigated both in vivo and in vitro in colon adenocarcinoma CT26 cells. The results indicated that the inhibitory effect of Brevilin A in CT26 proliferation was dose-dependent and this effect was due to apoptosis. Furthermore, Brevilin A increased ROS levels, decreased mitochondrial membrane potential (MMP) and induced apoptosis of CT26 cell in a dose-dependent manner. Apoptosis induced by Brevilin A was higher than that induced by adriamycin under the same dose. Cleaved-caspase-8, cleaved-caspase-9 and cleaved-caspase-3 were up-regulated after Brevilin A treatment, together with an increase of Bax protein expression, while Bcl-2 was reduced. Further investigation revealed that Brevilin A inhibited the phosphorylation of PI3K, AKT and mTOR and promoted the expressions of autophagy-related proteins LC3-II, Beclin1 and Atg5 and consequent formation of autophagosomes, whereas 3-methyladenine (3-MA), a type III PI3K inhibitor, inhibited autophagosomes formation induced by Brevilin A. In vivo investigation suggested that Brevilin A significantly inhibited the growth of CT26 tumor compared to adriamycin and concurrently promoted the expressions of LC3-II and cleaved-caspase-3 in tumor tissues. Our results demonstrated that the anti-tumor activity of Brevilin A was mainly achieved by the induction of cell apoptosis and autophagy, suggesting a promising potential as antitumor drug against colon adenocarcinoma.

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy efficacy. In the present study, 6-O-angeloylplenolin repressed the overexpression of ATP binding cassette subfamily B member 1 (MDR1) and increasing the intracellular concentration of anticancer drugs. A reduction in P-glycoprotein expression (encoded by MDR1) was observed in parallel with a decline in mRNA expression in vincristine-resistant HCT (HCT-8/VCR) cells treated with 6-O-angeloylplenolin. In addition, 6-O-angeloylplenolin suppressed the activity of the MDR1 gene promoter. Treatment with 6-O-angeloylplenolin also decreased the amount of the specific protein complex that interacted with the MDR1 gene promoter in HCT-8/VCR cells, potentially leading to the suppression of MDR1 expression. Treatment with 6-O-angeloylplenolin inhibited the nuclear translocation of Y-box binding protein-1 in HCT-8/VCR cells treated with 6-O-angeloylplenolin, contributing to the negative regulation of MDR1. Finally, 6-O-angeloylplenolin reversed VCR resistance in an HCT/VCR xenograft model. In conclusion, 6-O-angeloylplenolin exhibited a MDR-reversing effect by downregulating MDR1 expression and could represent a novel adjuvant agent for chemotherapy.

In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.

Isogarcinol (YDIS), a natural compound extracted from Garcinia mangostana L., has a significant immunosuppressive effect on systemic lupus erythematosus and rheumatoid arthritis. This paper reports that it reduced imiquimod-induced psoriasis-like skin lesions in mice. It strongly attenuated the aberrant proliferation and differentiation of keratinocytes. Moreover, the expression of genes involving the interleukin-23 (IL-23)/T-helper 17 (Th17) axis was significantly inhibited in the dorsal skin of the YDIS-treated mice, as was that of the other pro-inflammatory factors TNF-α, IL-2, and even interferon (IFN)-γ. Furthermore, YDIS prevented the abnormal distribution of T cell types and suppressed the differentiation of CD4+ T cells into Th17 cells in the spleens of mice exposed to imiquimod. Interestingly, it elevated numbers of regulatory T cells (Tregs) in the spleen and boosted IL-10 expression in the skin. In agreement with the above, YDIS increased serum IL-10 and reduced serum IL-17. It also caused less...