Systems pharmacology uncover the mechanism of anti-non-small cell lung cancer for Hedyotis diffusa Willd

Su, Xing; Liu, Yueping; Jiang, Meng; Zhu, Jinglin; Zheng, Chunli; Chen, Xuetong; Zhou, Jun; Li, Yan; Xiao, Wei; Wang, Yonghua

doi:10.1016/j.biopha.2018.10.162

Cited by 30 publications

(18 citation statements)

References 52 publications

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“…Natural products have long been used widely as a significant source of therapeutically effective drugs, and their importance in the prevention and treatment of tumors is becoming increasingly evident [18]. In addition, an increasing number of Chinese herbal medicines and extracts have been shown to exhibit anti-inflammatory, antioxidative, and antiliver fibrosis and anticancer effects [19–22]. These findings suggest that Chinese herbal medicines and extracts have great potential in the treatment of many diseases.…”

Section: Discussionmentioning

confidence: 99%

TEEG Induced A549 Cell Autophagy by Regulating the PI3K/AKT/mTOR Signaling Pathway

Shi

Xia

et al. 2019

Analytical Cellular Pathology

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TEEG (3β,16β,23-trihydroxy-13,28-epoxyurs-11-ene-3-O-β-D-glucopyranoside) is derived from the chloroform extract of the Chinese medicine formula Shenqi San (CE-SS). In the present study, we aimed to elucidate the anticancer effect and possible molecular mechanism underlying the action of TEEG against the human non-small cell lung cancer (NSCLC) cell line A549 in vitro. A549 cells were incubated with different concentrations of TEEG. Cell proliferation was assessed by MTT assay. Autophagy was evaluated by immunofluorescence staining. Autophagy-associated proteins were examined by Western blot analysis. TEEG markedly inhibited A549 cell proliferation in a concentration-dependent manner. Immunofluorescence staining showed that TEEG induced autophagy in A549 cells. The LC3-II : LC3-I conversion ratio and the expression of Beclin-1, Atg5, Atg7, and Atg12 increased with the concentration of TEEG. In addition, increased TEEG concentration enhanced the expression of Class III p-PI3K and reduced the expression of Class I p-PI3K, p-AKT, p-mTOR, and p-P70S6K. These results indicate that TEEG induces autophagy of A549 cells through regulation of the PI3K/AKT/mTOR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

TEEG Induced A549 Cell Autophagy by Regulating the PI3K/AKT/mTOR Signaling Pathway

Shi

Xia

et al. 2019

Analytical Cellular Pathology

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“…We investigated human target genes/proteins that interact with active phytochemical compounds in SMT using the Search Tool for Interactions of Chemicals (STITCH) 5 [65], Similarity Ensemble Approach (SEA) [66], Swis-sTargetPrediction [67,68], and PharmMapper [69]. Computational modeling methods, including systematic drug targeting tool (SysDt) [70] and weighted ensemble similarity (WES) algorithm [71], were also employed for target identification as descried previously [72][73][74][75][76][77][78]. Subsequently, we confirmed detailed information regarding the targets, including their scientific name, relevant gene/protein ID, and organism, and further standardized the targets using Uniprot [79].…”

Section: Investigation Of the Targets Of Active Compounds In Smtmentioning

confidence: 99%

“…To identify the potential therapeutic targets of SMT, we employed an in silico approach to assess the biological interactions between the active phytochemical compounds and human genes/proteins using STITCH 5 [65], SEA [66], SwissTargetPrediction [67,68], and PharmMapper [69]. Computational modeling methods such as SysDt [70] and WES algorithm [71] were also employed for target identification as descried previously [72][73][74][75][76][77][78]. Hence, a total of 230 targets were obtained for the 16 active phytochemical compounds in SMT (Supplementary Table S3).…”

Section: Identification Of the Targets Of Active Phytochemicalmentioning

confidence: 99%

Network Pharmacology‐Based Investigation of the System‐Level Molecular Mechanisms of the Hematopoietic Activity of Samul‐Tang, a Traditional Korean Herbal Formula

Lee¹,

Park²,

Lee

2020

Evidence-Based Complementary and Alternative Medicine

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Hematopoiesis is a dynamic process of the continuous production of diverse blood cell types to meet the body’s physiological demands and involves complex regulation of multiple cellular mechanisms in hematopoietic stem cells, including proliferation, self-renewal, differentiation, and apoptosis. Disruption of the hematopoietic system is known to cause various hematological disorders such as myelosuppression. There is growing evidence on the beneficial effects of herbal medicines on hematopoiesis; however, their mechanism of action remains unclear. In this study, we conducted a network pharmacological-based investigation of the system-level mechanisms underlying the hematopoietic activity of Samul-tang, which is an herbal formula consisting of four herbal medicines, including Angelicae Gigantis Radix, Rehmanniae Radix Preparata, Paeoniae Radix Alba, and Cnidii Rhizoma. In silico analysis of the absorption-distribution-metabolism-excretion model identified 16 active phytochemical compounds contained in Samul-tang that may target 158 genes/proteins associated with myelosuppression to exert pharmacological effects. Functional enrichment analysis suggested that the targets of Samul-tang were significantly enriched in multiple pathways closely related to the hematopoiesis and myelosuppression development, including the PI3K-Akt, MAPK, IL-17, TNF, FoxO, HIF-1, NF-kappa B, and p53 signaling pathways. Our study provides novel evidence regarding the system-level mechanisms underlying the hematopoiesis-promoting effect of herbal medicines for hematological disorder treatment.

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“…In TCM formula, the characteristics "multi-component, multi-target, and multi-pathway" present a tremendous challenge in understanding of the interactions between components and their mechanisms of action (Jiang et al, 2019). Fortunately, systems pharmacology, as a new discipline based on the basic theories of pharmacology and systems biology pharmacology, integrating pharmacology feature mapping, multiple targeting techniques, network pharmacology, and pathway analyses, has gradually become a powerful tool to investigate the therapeutic mechanisms of TCM (Su et al, 2019;Zhou et al, 2019). For example, Liu et al found 33 compounds with potential anticancer effects from Scutellaria barbata D. Don and investigated their mechanisms in treating non-small cell lung cancer by systems pharmacology method (Liu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology

Chen

Yan

et al. 2020

Front. Pharmacol.

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Objective: Investigate the active ingredients and underlying hypolipidemic mechanisms of Danhe granule (DHG). Methods: The lipid-lowering effect of DHG was evaluated in hyperlipidemic hamsters induced by a high-fat diet. The ingredients absorbed into the blood after oral administration of DHG in hamsters were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). A systems pharmacology approach incorporating target prediction and network construction, gene ontology (GO) enrichment and pathway analysis was performed to predict the active compounds and map the compounds-targets-disease network. Real-time polymerase chain reaction (RT-PCR) and Western blot were utilized to analyze the mRNA and protein expression levels of predicted targets. Results: DHG remarkably lowered the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and arteriosclerosis index (AI), at the same time, elevated the levels of serum high-density lipoprotein cholesterol (HDL-c) and HDL-c/TC ratio in hyperlipidemic hamsters. Sixteen ingredients absorbed into blood after oral administration of DHG were identified as the possible components interacted with targets. Moreover, 65 potential targets were predicted after targets intersection and compounds-targets-disease network mapping. Then, compounds-targets-pathways network mapping revealed that six active compounds (emodin, naringenin, etc.) compounds could interact with 10 targets such as sterol regulatory element binding protein (SREBP) 1c, SREBP-2 and peroxisome proliferation-activated receptor (PPAR) a, regulate three lipid metabolism-related pathways including SREBP control of lipid synthesis pathway, PPAR signaling pathway and nuclear receptors in lipid metabolism and toxicity pathway, and further affect lipid metabolic processes including fatty acid biosynthesis, low-density lipoprotein receptor (LDLR)-mediated cholesterol uptake, bile acid biosynthesis, and cholesterol efflux. Experimental results indicated that DHG significantly increased SREBP-2, LDLR, PPARa, liver X receptor alpha (LXRa),

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Systems pharmacology uncover the mechanism of anti-non-small cell lung cancer for Hedyotis diffusa Willd

Cited by 30 publications

References 52 publications

TEEG Induced A549 Cell Autophagy by Regulating the PI3K/AKT/mTOR Signaling Pathway

TEEG Induced A549 Cell Autophagy by Regulating the PI3K/AKT/mTOR Signaling Pathway

Network Pharmacology‐Based Investigation of the System‐Level Molecular Mechanisms of the Hematopoietic Activity of Samul‐Tang, a Traditional Korean Herbal Formula

Investigation of the Lipid-Lowering Mechanisms and Active Ingredients of Danhe Granule on Hyperlipidemia Based on Systems Pharmacology

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