Shenlian Extract Against Myocardial Injury Induced by Ischemia Through the Regulation of NF-κB/IκB Signaling Axis

Guo, Yuan; Yang, Qing; Weng, Xiaogang; Wang, Yajie; Hu, Xueqi; Zheng, Xiaojun; Li, Yujie; Zhu, Xiaoxin

doi:10.3389/fphar.2020.00134

Cited by 12 publications

(16 citation statements)

References 42 publications

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“…Previous studies revealed that SL had significant inhibitory effects on IL-1 and IL-6 expression. SL can inhibit the inflammatory response of macrophages, and its mechanism may be related to an influence on the phenotypic transformation of macrophages, the secretion of M1 inflammatory factors, and activation of the NF-κB signaling pathway in macrophages [16,17,18]. Another study reported that SL can significantly improve the imbalance of pro-inflammatory and pro-resolving mediators during atherosclerotic inflammation [54].…”

Section: Discussionmentioning

confidence: 99%

Shenlian Extract in the Treatment of Ultrafine Particulate Matter- Aggravated Myocardial Ischemic Injury: Integrating Network Pharmacology and in vivo Pharmacological Evaluation

Yang

et al. 2020

Preprint

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Background: Air pollution is a growing public health burden associated with several negative health effects, especially cardiovascular disease. Shenlian extract (SL), a traditional Chinese medicine, has the effects of clearing heat-toxin and promoting blood circulation for removing blood stasis, and it has long been used to treat cardiovascular diseases and atherosclerosis. This study explored the underlying action mechanism of SL against ultrafine particle-induced myocardial ischemic injury (UFP-MI) through network pharmacology prediction and experimental verification. Methods: Male Sprague-Dawley rats with UFP-MI were pre-treated with SL intragastrically for 7 days, all the animals were randomly divided into five groups: Sham, Model (UFP+MI), SLL( 31.08mg/ kg×d) + UFP+ MI, SLM (62.16 mg/ kg×d) + UFP+MI, and SLH (124.32 mg/ kg×d) + UFP+ MI. SL or saline was administrated 7 days before UFP instillation (100 μg/kg), followed by 24 h of ischemia. Inflammatory cytokine detection and histopathological analysis were performed to assess the protective effects of SL. For the mechanism study, differentially expressed genes were identified in UFP-MI rats treated with SL through transcriptomic analysis. Subsequently, in combination with network pharmacology, potential pathways involved in the effects of SL treatment were identified using the Internet-based Computation Platform (www.tcmip.cn) and Cytoscape 3.6.0. Further validation experiments were performed to reveal the mechanism of the therapeutic effects of SL on UFP-MI.Results: In pharmacodynamics experiments, SL significantly suppressed inflammatory cell infiltration into myocardial tissue and exhibited significant anti -inflammatory activity. Transcriptomic analysis revealed that the differentially expressed genes after SL treatment had significant anti-inflammatory, immunomodulatory, and anti-viral activities. Network pharmacology analysis illustrated that the targets of SL participate in the inflammatory response, apoptotic process, innate immune response, platelet activation, and other processes. By combining transcriptomic and network pharmacology data, we found that SL may exert anti-inflammatory effects by acting on the NOD-like signaling pathway to regulate immune response activation and inhibit systemic inflammation. Verification experiments revealed that SL suppressed NLRP3 inflammasome active and inflammasomes are cytosolic protein complexes that stimulate the activation of Caspase-1, which in turn induces the secretion of the inflammatory cytokines Interleukin-1 (IL-1), Interleukin-18(IL-18) and Interleukin-33(IL-33) Conclusion: UFP can induce the activation of NLRP3 inflammasome, leading to the release of downstream the inflammatory cytokines, aggravate the pathological conditions of inflammatory infiltration, and further aggravate the myocardial ischemic injury. Experimental verification indicated that SL can directly inhibit the activation of NLRP3 inflammasomes in the NOD-like signaling pathway and reduce cytokines release. In conclusion, our results confirmed that SL may prevent UFP-MI by acting on the NOD-like signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Shenlian Extract in the Treatment of Ultrafine Particulate Matter- Aggravated Myocardial Ischemic Injury: Integrating Network Pharmacology and in vivo Pharmacological Evaluation

Yang

et al. 2020

Preprint

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“…After AS plaque has formed, TCM treatment of AS should be based on principle of clearing away heat and removing blood stasis. ShenLian (SL), extracted from Salvia miltiorrhiza Bunge and Andrographis paniculata which are the fully proved anti-atherosclerotic TCM formula (Guo et al, 2016;Guo et al, 2020). Salvia miltiorrhiza Bunge endowed with potent ability to promote blood circulation and remove blood stasis (Chen and Chen, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…These functions of SL beneficial for prevent and treat atherosclerosis and cardiovascular diseases (Zhou et al, 2013;Guo et al, 2016). In our previous studies, we used high performance liquid chromatography (HPLC) to confirm the identity of the three main components (Andrographolide, Tanshinone IIA, Salvianolic acid B) of SL and revealed that these three active components existed in a certain ratio (Guo et al, 2020). Notably, Danshen dripping pills, whose main active components were extracted from Salvia miltiorrhiza Bunge, have been widely applied in the clinical treatment of CVDs since introduction into the Chinese drug market in 1994, and its pills were the first traditional Chinese medicine to complete Phase III clinical trials by the United States Food and Drug Administration (Writing Group of Recommendations of Expert Panel from Chinese Geriatrics Society on the Clinical Use of Compound Danshen Dripping Pills, 2017; Jia et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Notably, Danshen dripping pills, whose main active components were extracted from Salvia miltiorrhiza Bunge, have been widely applied in the clinical treatment of CVDs since introduction into the Chinese drug market in 1994, and its pills were the first traditional Chinese medicine to complete Phase III clinical trials by the United States Food and Drug Administration (Writing Group of Recommendations of Expert Panel from Chinese Geriatrics Society on the Clinical Use of Compound Danshen Dripping Pills, 2017; Jia et al, 2018). Modern pharmacological studies have indicated that SL has the effect on intervene to atherosclerosis involving reduction of the atherosclerotic plaque area, an increase of blood flow in the proximal carotid artery, and regulation of lipids levels in the blood (Li et al, 2011;Guo et al, 2016;Guo et al, 2020). This study aimed to elucidate whether SL could enhance the bio-activity of macrophages to support the SMC phenotypic transformation and functionally reconstruct the ECM which would be beneficial for AS plaque stabilization.…”

Section: Introductionmentioning

confidence: 99%

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ShenLian Extract Enhances TGF-β Functions in the Macrophage-SMC Unit and Stabilizes Atherosclerotic Plaques

Liu

Yin

et al. 2021

Front. Pharmacol.

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Background/Aim: Macrophage polarization and phenotypic switching of smooth muscle cells (SMCs) are multi-faceted events dominating atherosclerosis (AS) progression. TGF-β was proved to been one of the bridge on the crosstalk between macrophage and SMC. ShenLian (SL) was extracted from a potent anti-atherosclerotic formula. However, its exact mechanism rebalancing inflammatory microenvironment of AS remain largely unknown. Within the entirety of macrophage and SMC, this study investigated the pharmacological effects of SL on stabilizing atherosclerotic plaques.Methods: The main components of SL were examined by high performance liquid chromatography. Co-culture and conditioned medium models of macrophage/SMC interactions were designed to identify the relationship between macrophage polarization and switching of SMC phenotypes. Flow cytometry, immunofluorescent staining, RT-PCR, western blotting, and ELISA were used to determine the expression of molecules relating to AS progression. An atherosclerosis animal model, established by placing a perivascular collar on the right common carotid artery in ApoE−/− mice, was used to investigate whether TGF-β is the key molecular mediator of SL in crosstalk between macrophage and SMC. Plaque size was defined by nuclear magnetic resonance imaging. Key markers related to phenotypic transformation of macrophage and SMC were determined by immunohistochemical staining.Results: Results revealed that, accompanied by rebalanced M2 macrophage polarization, SL supported SMC phenotypic transformation and functionally reconstruct the ECM of plaques specifically in macrophage-SMC co-cultural model. Molecularly, such activity of SL closely related to the activation of STAT3/SOCS3 pathway. Furthermore, in co-culture system, up-regulation of α-SMA induced by SL could neutralized by 1D11, a TGF-β neutralizing antibody, indicating that SL mediated Macrophage-SMC communication by enhancing TGF-β. In the AS model constructed by ApoE−/− mice, effects of SL on phenotypic transformation of macrophage and SMC has been well verified. Specific blocking of TGF-β largely attenuated the aforementioned effects of SL.Conclusion: Our findings highlighted that TGF-β might be the responsive factor of SL within macrophage and SMC communication. This study revealed that crosstalk between macrophage and SMC forms a holistic entirety promoting atherosclerotic plaque stability.

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“…Natural products and their derivatives have played an important role in the discovery and development of new drugs to treat MIR [12][13][14][15]. Shenlian extract could protect against MIR through the NF-kB signaling pathway [12]. Luteolin can attenuate MIR by activating peroxiredoxin II [13].…”

Section: Introductionmentioning

confidence: 99%

A novel Danshensu/tetramethylpyrazine protects against Myocardial Ischemia Reperfusion Injury in rats

Wang

Fan

et al. 2021

Int. J. Med. Sci.

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A new Danshensu/tetramethylpyrazine derivative (ADTM) with cardio-protection effects such as antioxidant, arterial relaxation, pro-angiogenesis and antiplatelet activities. Platelet activating factor receptor (PAFR) plays a key role in myocardial ischemia reperfusion (MIR) injury. This study aims to investigate the protective role of ADTM in MIR injury and clarify the potential role of PAFR. We measured the effects of ADTM on MIR injury in rats in vivo and hypoxia re-oxygenation (HR) injury in neonatal rat ventricular myocytes (NRVMs) in vitro. The results show that ADTM can significantly improve the IR-induced decline in heart function as increasing EF and FS, and restore the decreased cardiac hemodynamic parameters (LVSP, ± dp/dt max) and increased the level of LVEDP, decrease the infarct size of damaged myocardium and lactate dehydrogenase (LDH) activity in serum. Additionally, ADTM inhibits cardiomyocytes apoptosis, caspase-3 activity, and inflammatory response as well as down-regulates the MIR-induced IL-1β and TNFα production. Next, PAFR expression was significantly down-regulated in cardiomyocytes of MIR model in vivo and in vitro after treated with ADTM compare to IR group. At the same time, ADTM and PAFR small interfering RNA (siRNA) could inhibit cardiomyocytes apoptosis and inflammation during HR, while PAF presents the opposite effect. Furthermore, the above effects of PAF in HR induced cardiomyocytes were reversed by co-treatment of ADTM. Our findings demonstrate for the first time that ADTM protects against MIR injury through inhibition of PAFR signaling, which provides a new treatment for MIR.

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Shenlian Extract Against Myocardial Injury Induced by Ischemia Through the Regulation of NF-κB/IκB Signaling Axis

Cited by 12 publications

References 42 publications

Shenlian Extract in the Treatment of Ultrafine Particulate Matter- Aggravated Myocardial Ischemic Injury: Integrating Network Pharmacology and in vivo Pharmacological Evaluation

Shenlian Extract in the Treatment of Ultrafine Particulate Matter- Aggravated Myocardial Ischemic Injury: Integrating Network Pharmacology and in vivo Pharmacological Evaluation

ShenLian Extract Enhances TGF-β Functions in the Macrophage-SMC Unit and Stabilizes Atherosclerotic Plaques

A novel Danshensu/tetramethylpyrazine protects against Myocardial Ischemia Reperfusion Injury in rats

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