Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α

Kangsamaksin, Thaned; Chaithongyot, Supattra; Wootthichairangsan, Chanida; Hanchaina, Rattanavinan; Tangshewinsirikul, Chayada; Svasti, Jisnuson

doi:10.1371/journal.pone.0189628

Cited by 154 publications

(102 citation statements)

References 33 publications

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“…30 Stigmasterol itself decreased inflammation by modulating the MAPK/NF-κB ROCK1 pathway, 31 combined stigmasterols achieved more obvious anti-proliferation in Caco-2 cells than a single stigmasterol, 32 and reduced TNF-ɑ and VEGFR-2 signaling by affecting phosphorylated Src, Akt, PCL, and FAK. 33 It can be inferred that our approach is reliable and the screened active compounds act synergistically in the treatment of AM.…”

Section: Active Compounds Of Szc In Treating Ammentioning

confidence: 84%

<p>Anti-Inflammatory Activity of Sanjie Zhentong Capsule Assessed By Network Pharmacology Analysis of Adenomyosis Treatment </p>

Du¹,

Du²,

Chen³

et al. 2020

DDDT

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Background: Sanjie Zhentong capsule (SZC) offers excellent effect in treating adenomyosis (AM), which is a common and difficult gynecological disease in the clinic. However, the systematic analysis of its mechanism has not been carried out yet and further studies are needed to reveal the role of SZC. Methods: A systematic network pharmacology analysis was conducted by integrating construction of SZC compound database and AM target database, prediction of potential active compounds and targets by molecular docking combined with compound-target prediction graph (CTPG), protein-protein interaction (PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then, the anti-inflammation experiments in vitro were performed by investigating SZC and the representative compounds regulating nitric oxide (NO), interleukin-6 (IL-6), and interleukin-10 (IL-10). Results: Our findings show that SZC mainly treated AM by stimulating 28 core targets through 30 key potential active compounds, and affecting 4 crucial pathways. The treatment was associated with inflammation reaction, hormone regulation, cell adhesion, proliferation, and angiogenesis. Additionally, SZC achieved the anti-inflammatory activity by the cooperation of the compounds through inhibiting NO and IL-6, both promoting and inhibiting IL-10. Conclusion: This study investigated the anti-inflammatory activity of SZC based on a systematic analysis of SZC remedying AM, which was revealed to be one of the essential mechanisms. These findings will provide valuable guidance for further research of the SZC treatment of AM, and help improve the comprehension of SZC pharmacological basis as well as AM pathogenesis.

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Section: Active Compounds Of Szc In Treating Ammentioning

confidence: 84%

<p>Anti-Inflammatory Activity of Sanjie Zhentong Capsule Assessed By Network Pharmacology Analysis of Adenomyosis Treatment </p>

Du¹,

Du²,

Chen³

et al. 2020

DDDT

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“…Isorhamnetin, a avonoid metabolite, has been demonstrated to be able to produce anti-tumor effects by inhibiting the expression of NF-κB [26] . With regard to stigmasterol, it's a major phytosterol in herbal plants, which can downregulate levels of in ammatory cytokines involving TNF-α, repress VEGF signaling, produce anti-angiogenic effects, thus inhibit cholangiocarcinoma growth in mice [27] . On the whole, it was speculated that YCHD is a multicomponent formula with multitarget therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Based Research into the Effect and Mechanism of Yinchenhao Decoction Against Cholangiocarcinoma

Chen

Lin

Liao

et al. 2020

Preprint

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Background: This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma. Methods: By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods. Results: 32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions. Conclusion: As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effects through multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.

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“…Accordingly, Stigmasterol was reported to have anti-arthritic, anti-venom, and glucose regulatory activities 45 . Nonetheless, the antiangiogenic activity of campesterol has already reported 46 .…”

Section: Discussionmentioning

confidence: 99%

Untitled

2019

IJPSR

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Sida acuta is one of the medically active plants used for the treatment of multifaceted diseases. However, an elaborated investigation on the phytochemical composition of the ethanolic extract of the leaves of this plant is yet to be deciphered. So, in this quantification of phytochemicals, in-vitro free radical scavenging activity, enzymatic and non-enzymatic antioxidant levels in the fresh leaves, HPTLC fingerprinting and GC-MS analysis in the ethanolic extract of Sida acuta leaves were done. In-vitro antioxidant activities were assayed using DPPH, ABTS, nitric oxide, hydroxyl radical and ferric ions, while ascorbic acid is used as the standard. The results indicated the presence of flavonoids, tannins, phenols, and alkaloids in a reasonably good amount which has substantiated the results of HPTLC. All the tested antioxidants were present prominently in the leaves, specifically catalase and glutathione peroxidase, which may be responsible for the prominent radical scavenging tendency of the extract against the tested free radicals. The GC-MS analysis observed the presence of 35 different compounds each belonging to different classes such as sterols, flavonoids, terpenes, heterocyclic aromatic compounds, phenols, fatty acids, vitamins, alkaloids, and sesquiterpenoids. The results indicate that the ethanolic extract of Sida acuta leaves collected from the Tuticorin District of Tamil Nadu is an effective scavenger of free radicals and has the potential to be used as a natural antioxidant which is attributable to the rich presence of its secondary metabolites.

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Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α

Cited by 154 publications

References 33 publications

<p>Anti-Inflammatory Activity of Sanjie Zhentong Capsule Assessed By Network Pharmacology Analysis of Adenomyosis Treatment </p>

<p>Anti-Inflammatory Activity of Sanjie Zhentong Capsule Assessed By Network Pharmacology Analysis of Adenomyosis Treatment </p>

Network Pharmacology Based Research into the Effect and Mechanism of Yinchenhao Decoction Against Cholangiocarcinoma

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