A network pharmacology approach and experimental validation to investigate the anticancer mechanism and potential active targets of ethanol extract of Wei-Tong-Xin against colorectal cancer through induction of apoptosis via PI3K/AKT signaling pathway

Lin, Fei; Zhang, Guanglin; Yang, Xihan; Wang, Mengshi; Wang, Ruixuan; Wan, Meiqi; Wang, Jinyu; Wu, Bo; Yan, Tingxu; Jia, Ying

doi:10.1016/j.jep.2022.115933

Cited by 27 publications

(8 citation statements)

References 51 publications

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“…Additionally, Zhang and others conducted in vivo mouse experiments to validate the apoptotic role of Wei-Tong-Xin in colorectal cancer. They also confirmed the apoptotic effect of Wei-Tong-Xin on colorectal cancer through in vivo mouse experiments ( Lin et al, 2023 ). Contrast to the previous western blot analysis, Weichang’an formula (WCAF) plays an important role in inducing CRC apoptosis through TUNEL assay.…”

Section: Application Of Prescriptions In Crcsupporting

confidence: 54%

Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms

Sun,

Wei,

Wang

et al. 2024

Front. Pharmacol.

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Colorectal cancer (CRC) is a significant global health burden, with high morbidity and mortality rates. It is often diagnosed at middle to advanced stage, affecting approximately 35% of patients at the time of diagnosis. Currently, chemotherapy has been used to improve patient prognosis and increase overall survival. However, chemotherapy can also have cytotoxic effects and lead to adverse reactions, such as inhibiting bone marrow hematopoiesis, causing digestive dysfunction, hand-foot syndrome, and even life-threatening conditions. In response to these adverse effects, researchers have proposed using Traditional Chinese Medicine (TCM) as an option to treat cancer. TCM research focuses on prescriptions, herbs, and components, which form essential components of the current research in Chinese medicine. The study and implementation of TCM prescriptions and herbs demonstrate its distinctive holistic approach to therapy, characterized by applying multi-component and multi-target treatment. TMC components have advantages in developing new drugs as they consist of single ingredients, require smaller medication dosages, have a precise measure of pharmacodynamic effects, and have a clear mechanism of action compared to TCM prescriptions and herbs. However, further research is still needed to determine whether TMC components can fully substitute the therapeutic efficacy of TCM prescriptions. This paper presents a comprehensive analysis of the research advancements made in TCM prescriptions, herbs, and components. The findings of this study can serve as a theoretical basis for researchers who are interested in exploring the potential of TCM for the treatment of colorectal cancer.

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Section: Application Of Prescriptions In Crcsupporting

confidence: 54%

Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms

Sun,

Wei,

Wang

et al. 2024

Front. Pharmacol.

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“…However, in instances where the inflammatory response is chronic or inordinately intense, it evolves into a pivotal etiological component of the disease progression. [49][50][51] The correlation between inflammation and gastric malignancy has been extensively corroborated by research. On the one hand, the progression of gastric malignancy is intimately associated with chronic gastritis, a persistent inflammation of the gastric mucosa typically due to H pylori infection, longterm NSAID use, or other etiological factors.…”

Section: Discussionmentioning

confidence: 99%

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

Yang,

Lv,

et al. 2024

Medicine

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This study aimed to elucidate the potential causative links between inflammatory biomarkers and gastric cancer risk via a two-sample Mendelian randomization approach. Leveraging genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization analysis. Instrumental variable selection for inflammatory markers – namely, tissue factor, monocyte chemotactic protein-1, E-selectin, interleukin 6 receptor, and fatty acid-binding protein 4 – was informed by SNP data from the IEU database. Strongly associated SNPs served as instrumental variables. We applied a suite of statistical methods, including Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), MR-Egger, and mode-based estimates, to compute the odds ratios (ORs) that articulate the impact of these markers on gastric cancer susceptibility. The IVW method revealed that the interleukin 6 receptor was inversely correlated with gastric cancer progression (OR = 0.86, 95% CI = 0.74–0.99, P = .03), whereas fatty acid-binding protein 4 was found to elevate the risk (OR = 1.21, 95% CI = 1.05–1.39, P = .03). Instrumental variables comprised 5, 4, 7, 2, and 3 SNPs respectively. Convergent findings from WME, MR-Egger, and mode-based analyses corroborated these associations. Sensitivity checks, including heterogeneity, horizontal pleiotropy assessments, and leave-one-out diagnostics, affirmed the robustness and reliability of our instruments across diverse gastric malignancy tissues without substantial bias. Our research suggests that the interleukin 6 receptor potentially mitigates, while fatty acid-binding protein 4 may contribute to the pathogenesis of gastric cancer (GC). Unraveling the intricate biological interplay between inflammation and oncogenesis offers valuable insights for preemptive strategies and therapeutic interventions in gastric malignancy management.

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“…This file was then imported into Cytoscape 3.9.1, where isolated nodes were removed. The CytoHubba plugin identified the top 10 core targets, facilitating the creation of a visual PPI network ( Lin et al, 2023 ).…”

Section: Methodsmentioning

confidence: 99%

Erjingwan and Alzheimer’s disease: research based on network pharmacology and experimental confirmation

Xu,

Zhang,

2024

Front. Pharmacol.

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BackgroundAlzheimer’s disease (AD), a challenging neurodegenerative condition, has emerged as a significant global public health concern. The Chinese medicine decoction Erjingwan (EJW) has shown promising efficacy in AD treatment, though its mechanism remains unclear.ObjectiveThis study aims to elucidate the mechanism by which EJW treats AD through network pharmacology analysis and in vivo experiments.MethodsWe identified EJW’s components using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and determined AD-related targets from various databases. A network comprising herbs-compounds-targets was established, and EJW’s core targets were ascertained through protein-protein interaction (PPI) analysis. This study assessed the cognitive abilities of APP/PS1 mice using Morris water mazes and Y mazes, in addition to analyzing blood samples for triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Brain tissues were examined histologically with HE staining, Nissl staining, and immunohistochemistry (IHC) for amyloid β-protein (Aβ) detection. Superoxide dismutase (SOD), reactive oxygen species (ROS), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6) levels in the hippocampal region were measured by ELISA. mRNA expression of apolipoprotein A-I (APOA-I), apolipoprotein B (APOB), apolipoprotein E4 (APOE4), advanced glycation end products (AGE), the receptor for AGE (RAGE), and nuclear factor kappa-B (NF-κB) was evaluated by quantitative PCR (q-PCR). Western blotting was used to detect the expression of AGE, RAGE, NF-κB, and Tau protein.ResultsScreening identified 57 chemical components and 222 potential targets of EJW. Ten core targets for AD treatment were identified, with enrichment analysis suggesting EJW’s effects are related to lipid metabolism and AGEs/RAGE pathways. EJW enhanced learning and memory in APP/PS1 mice, protected neuronal structure in the hippocampal region, reduced Aβ deposition, and altered levels of TG, TC, LDL, IL-1β, and IL-6, and the expression of APOE4, AGEs, RAGE, NF-κB, and Tau protein, while increasing SOD, APOA-I, and APOB mRNA expression.ConclusionThe study identified four core components of EJW—iosgenin, baicalein, beta-sitosterol, quercetin—and ten core targets including AKT1, IL6, VEGFA, TP53, CASP3, for treating AD. Experimental results demonstrate EJW’s capacity to modulate lipid profiles, reduce pathological markers such as Aβ1-42, Tau, IL-6, IL-1β, reactive oxygen species, SOD, and enhance cognitive functions in APP/PS1 mice, potentially through inhibiting the AGEs/RAGE/NF-κB pathway.

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A network pharmacology approach and experimental validation to investigate the anticancer mechanism and potential active targets of ethanol extract of Wei-Tong-Xin against colorectal cancer through induction of apoptosis via PI3K/AKT signaling pathway

Cited by 27 publications

References 51 publications

Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms

Treatment of colorectal cancer by traditional Chinese medicine: prevention and treatment mechanisms

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

Erjingwan and Alzheimer’s disease: research based on network pharmacology and experimental confirmation

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