Tingli Dazao Xiefei Decoction ameliorates asthma in vivo and in vitro from lung to intestine by modifying NO–CO metabolic disorder mediated inflammation, immune imbalance, cellular barrier damage, oxidative stress and intestinal bacterial disorders

Ruan, Yuan; Yuan, Peipei; Li, Pan-Ying; Chen, Yi; Fu, Yang; Gao, Liyuan; Wei, Yaxin; Zheng, Y.; Li, Sai-Fei; Feng, Weisheng; Zheng, Xiaoke

doi:10.1016/j.jep.2023.116503

Cited by 28 publications

(4 citation statements)

References 74 publications

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“…22 Accordingly, the TDXD dosages in the studies were selected as 5.85 and 11.7 g/kg (two folders of equivalent human dose) for low-dose and high-dose groups, respectively, which are equivalent as those used in rat studies. 23 , 24…”

Section: Methodsmentioning

confidence: 99%

Network Pharmacology and Experimental Validation of the Anti-Inflammatory Effect of Tingli Dazao Xiefei Decoction in Acute Lung Injury Treatment

Zhang,

Li,

Gao

et al. 2023

JIR

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Purpose Tingli Dazao Xiefei Decoction (TDXD) is a Traditional Chinese Medicine (TCM) formula used to treat acute lung injury (ALI). However, the precise mechanism of TDXD in treating ALI remains unclear. We investigated the therapeutic mechanism of TDXD against ALI using a complementary approach combining network pharmacology, molecular docking, and in vitro and in vivo experiments. Material and Methods Potential drug targets of TDXD and relevant target genes associated with ALI were retrieved from Chinese medicines and disease genes databases. Bioinformatics technology was employed to screen potential active ingredients and core targets. Validation experiments were conducted using a lipopolysaccharide (LPS)-induced ALI mouse (C57BL/6J) model, LPS-induced inflammatory RAW264.7 cells, and molecular docking between active compounds of TDXD and potential targets. Results Network pharmacology suggested that the mechanism of TDXD against ALI involved phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) / phosphatase and tensin homolog (PTEN) and Janus kinase 2 (JAK2) / signal transducer and activator of transcription 3 (STAT3) pathways. Quercetin, β-sitosterol, kaempferol, isorhamnetin, and L-stepholidine were identified as the main active compounds of TDXD that exerted anti-ALI effects. Molecular docking indicated that these compounds exhibited good binding capabilities (≤ −5kcal/mol) to key targets in PI3K/AKT/PTEN and JAK2/STAT3 signaling pathways. In the animal model, TDXD alleviated injuries and inflammatory responses in lung tissues, accompanied by inhibition of expression of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), STAT3, and Suppressor of Cytokine Signaling 3 (SOCS3) mRNA, and key proteins in PI3K/AKT/PTEN and JAK2/STAT3 pathways (all P values < 0.05). Cell based experiments showed that TDXD dose-dependently inhibited the expression of essential proteins in PI3K/AKT/PTEN and JAK2/STAT3 pathways (P < 0.05). Conclusion This study revealed that the mechanism of TDXD in ALI treatment might involve simultaneous regulation of PI3K/AKT/PTEN and JAK2/STAT3 pathways.

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Section: Methodsmentioning

confidence: 99%

Network Pharmacology and Experimental Validation of the Anti-Inflammatory Effect of Tingli Dazao Xiefei Decoction in Acute Lung Injury Treatment

Zhang,

Li,

Gao

et al. 2023

JIR

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“…GAPDH was used as the reference gene, and the 2 −ΔΔCt method was used to calculate the relative expression of the target gene. 22 The sequences for the primers used in our study are listed in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

“…After the cells were treated with apoptosis kit (BD Biosciences, Franklin Lakes, NJ, USA), mitochondrial membrane potential detection kit and Ca 2+ detection kit (Beyotime Biotechnology, Shanghai, China), the apoptosis rate, mitochondrial membrane potential change and intracellular Ca 2+ content were detected by flow cytometry (BD Biosciences, Franklin Lakes, NJ, USA). 22 In vivo Method…”

Section: Determination Of Apoptosis Mitochondrial Levels and Cell Via...mentioning

confidence: 99%

“…18 Previous studies have shown that Descurainia sophia can reduce pulmonary inflammation, inhibit lung cancer cell proliferation, and attenuate myocardial injury and cardiac remodeling. [19][20][21] Our laboratory has previously conducted a systematic study on Descurainia sophia, and found that Descurainia sophia has good effects in treating lung diseases 22 and improving pulmonary hypertension, and can significantly inhibit the expression of PLC. 23 According to the types and polarity of Descurainia sophia, the fractions were divided into five fractions: fatty oil, oligosaccharides, flavonoid glycosides, flavonoid aglycones, and polysaccharides.…”

Section: Introductionmentioning

confidence: 99%

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Fatty Oil of Descurainia Sophia Nanoparticles Improve Monocrotaline-Induced Pulmonary Hypertension in Rats Through PLC/IP3R/Ca2+ Signaling Pathway

Zheng,

Yuan,

Zhang

et al. 2023

IJN

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Purpose Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied. Methods We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca 2+ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca 2+ signal pathway of pulmonary hypertension rats. Results We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca 2+ signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca 2+ signal pathway. Conclusion OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca 2+ signal pathway.

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Therapeutic targeting of cGAS–STING pathway in lung cancer

Wang,

Xing

2024

Cell Biology International

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The presence of DNA in the cytosol triggers a protective response from the innate immune system. Cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS–STING) is an essential cytosolic DNA sensor that triggers a potent innate immune response. As a result of this signaling cascade reaction, type I interferon and other immune mediators activate an immune response. The cGAS–STING pathway has great anticancer immunity‐boosting potential since it produces type I interferons. The detection of double‐stranded DNA (dsDNA) in response to various stimuli initiates a protective host's cGAS–STING signals. So, it is clear that a substantial relationship is expected between cancer biotherapy and the functioning of the cGAS–STING pathway. Several STING agonists with promising outcomes have been created for preclinical cancer therapy research. Notably, immunotherapy has dramatically extended patient survival and radically altered the course of lung cancer treatment, particularly in more advanced instances. However, this method is still ineffective for a large number of lung cancer patients. cGAS–STING can overcome resistance and boost anticancer immunity by stimulating the activity of many pro‐inflammatory mediators, augmenting dendritic cell cross‐presentation, and initiating a tumor‐specific CD8+ T cell response. This review aims to present the most recent results on the functionality of the cGAS–STING pathway in cancer progression and its potential as an immunotherapy target, with a focus on lung cancer.

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Tingli Dazao Xiefei Decoction ameliorates asthma in vivo and in vitro from lung to intestine by modifying NO–CO metabolic disorder mediated inflammation, immune imbalance, cellular barrier damage, oxidative stress and intestinal bacterial disorders

Cited by 28 publications

References 74 publications

Network Pharmacology and Experimental Validation of the Anti-Inflammatory Effect of Tingli Dazao Xiefei Decoction in Acute Lung Injury Treatment

Network Pharmacology and Experimental Validation of the Anti-Inflammatory Effect of Tingli Dazao Xiefei Decoction in Acute Lung Injury Treatment

Fatty Oil of Descurainia Sophia Nanoparticles Improve Monocrotaline-Induced Pulmonary Hypertension in Rats Through PLC/IP3R/Ca2+ Signaling Pathway

Therapeutic targeting of cGAS–STING pathway in lung cancer

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