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Atherosclerosis is the main pathological basis of cardiovascular diseases (CVDs). Fufang Danshen Tablet (FDT) is a traditional Chinese medicine that has been clinically used to treat CVDs for more than 40 years. Nevertheless, owing to the complexity of the ingredients, the pharmacological mechanism of FDT in the treatment of CVDs has not been fully elucidated. In this study, an integrated strategy of UFLC-Q-TOF-MS/MS, network pharmacology, molecular biology, and transcriptomics was used to elucidate the mechanisms of action of FDT in the treatment of atherosclerosis. In total, 22 absorbed constituents were identified in rat serum after oral administration of FDT. In silico, network pharmacology studies have shown that FDT regulates four key biological functional modules for the treatment of atherosclerosis: oxidative stress, cell apoptosis, energy metabolism, and immune/inflammation. In animal experiments, FDT exerted protective effects against atherosclerosis by reducing the plaque area and lipid levels in ApoE−/− mice. Furthermore, we found that FDT inhibited inflammatory macrophage accumulation by regulating the expression of Selp and Ccl2, which are both involved in monocyte adhesion and migration. The inhibition of monocyte recruitment by FDT is a new perspective to elucidate the anti-atherosclerotic mechanism of FDT, which has not been adopted in previous studies on FDT. Our results may help to elucidate the therapeutic mechanism of FDT against CVDs and provide potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common malignant tumours and has become the leading cause of cancer-related deaths worldwide. Abnormal microcirculation during tumour growth leads to intermittent hypoxia (IH), which is responsible for promoting cancer cell proliferation and migration. Patients with advanced lung cancers show deficiency of both Qi and Yin Syndrome (DQYS) in TCM, and studies have confirmed that IH exposure is related to DQYS. Shashen-Maidong Decoction (SMD), has been widely applied clinically targeting DQYS and has a long history for treating lung cancer by nourishing the body's "zheng qi" and resisting "xie qi". However, whether SMD could be beneficial to lung cancer under IH conditions remains unclear. This study aimed to clarify the effects and mechanism of SMD on non-small cell lung cancer (NSCLC) growth under IH conditions. C57 mice were injected subcutaneously into the right axilla with Lewis lung cancer (LLC) cells and exposed to IH conditions (21%–5% O 2 , 5 min/cycle, 8 h/day) for 21 days. SMDs were orally treated with different concentrations (2.6, 5.2 or 10.4 g/kg/day) 30 min before IH exposure. Tumour proliferation and migration were assessed by HE and IHC staining, and oxidative stress was assessed by DHE staining and MDA or SOD detection. IL-6, IL-1β and TNF-α levels were assessed by IHC staining, and the IL-6/JAK2/STAT3 signalling pathway was detected by western blotting. Our results showed that SMD treatment inhibited tumour growth and liver metastasis in LLC-bearing mice exposed to IH, decreased Ki67, CD31, VEGF, and MMP-2, and increased E-cadherin expression in tumourt tissue. SMD reduced ROS production, increased SOD levels and SOD-2 expression, and decreased MDA levels and NOX-2 expression. SMD decreased IL-6, IL-1β and TNF-α levels, reduced IL-6 expression and inhibited JAK2 and STAT3 phosphorylation. Additionally, SMD treatment improved DQYS and liver and kidney function in LLC-bearing mice under IH conditions. Our research suggests that SMD treatment can inhibit tumour growth in mice exposed to IH. The antitumour effect of SMD may be related to attenuated oxidative stress and inflammation through inactivation of the IL-6/JAK2/STAT3 signalling pathway under IH conditions. IH exposure increased ROS production and IL-6, IL-1β and TNF-α levels and activated the IL-6/JAK2/STAT3 signalling pathway, which is responsible for accelerating tumour growth. SMD inhibited the proliferation and invasion of cancer cells by inhibiting oxidative stress and the inflammatory response under IH conditions. Meanwhile, SMD effectively improved DQYS targeting Tonifying Qi and Nourishing Yin. n each factor, " ↑ " represents positive change; " ↓ " represents negative change. Black represents the change after IH exposure; Red represents the change after SMD treatment. [Display omitted] • Shashen-Maidong Decoction inhibited lung cancer proliferation under IH conditions. • Shashen-Maidong Decoction inhibited oxidative stress level under IH conditions. • Tumour inhibition of SMD is related to IL-6 signalling inactivation. • SMD improved DQYS, liver and kidney function under IH conditions. [ABSTRACT FROM AUTHOR]

Fufang Danshen Tablet (FDT) is a traditional Chinese medicine (TCM) formula composed of three Chinese medicinal materials comprising Salviae Miltiorrhizar Radix et Rhizoma (Dan-Shen in Chinese), Notoginseng Radix et Rhizoma (San-Qi), and Borneolum Syntheticum (Bing-Pian). It has been documented to exert significant effects in promoting blood circulation and removing blood stasis, and become a frequently used formula in the treatment of cardiovascular and cerebrovascular diseases. To systematically analyze and summarize the research findings concerning the chemical composition, quality control, pharmacokinetics, pharmacological properties, clinical applications, and toxicity of FDT, so as to point out some typical problems and provides opinions for future study. Literatures involving FDT were collected from online scientific databases including China National Knowledge Infrastructure, WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and Google Scholar up to March 2021. All eligible studies are analyzed and summarized in this review. This review summarizes reported results concerning the post-marketing quality and efficacy of FDT. Some problems are pointed out for FDT. Hereon we propose several directions for future study: (a) improvement of quality control based on exact overall chemical profiles, entire production process monitoring, and biopotency-associated multi-index content determination method; (b) clarification of functional mechanisms focused on pharmacokinetic profiles in human, interplay with gut microbiota, and integration of multi-omics technologies; (c) reconfirmation of clinical effectiveness and safety from large-scale clinical studies based on evidence-based medicine. FDT is a typical TCM formula in treating cardiovascular and cerebrovascular diseases, but there are also some troubles. Future studies should focus on the improvement of quality control, the clarification of functional mechanisms, as well as the reconfirmation of clinical effectiveness and safety. [Display omitted] [ABSTRACT FROM AUTHOR]

Fufang Xueshuantong Capsule (FXC) is a traditional Chinese medicine (TCM) formula composed of four herbs including Panax notoginseng , Astragalus membranaceus , Salvia miltiorrhiza , and Scrophularia ningpoensis. Long-term and extensive clinical applications have confirmed that FXC could exert significant effects on fundus, cardiovascular and cerebrovascular occlusive diseases. To systematically analyze and summarize the existing researches involving quality and efficacy re-evaluation of FXC, point out the typical problems, and further propose some opinions to contribute to future study. Literatures concerning FXC were collected from online scientific databases including China National Knowledge Infrastructure, WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link up to June 2020. All eligible studies are analyzed and summarized in this review. This review outlines the chemical profiles, quality control, pharmacokinetic and pharmacological properties of FXC based on reported results. Some problems are pointed out for FXC: the quality control needs further improvement, the pharmacokinetic properties have not been comprehensively investigated, and in-depth and systematic mechanism researches are scarce. Hereon we propose several directions for future study: (a) establishment of feasible HPLC or LC-MS based quantitative methods for simultaneous determination of multiple components to monitor the overall quality; (b) pharmacokinetic studies concerning humans, drug-drug interactions, and correlation with pharmacodynamics; (c) pharmacological mechanism researches integrating multi-omics technologies (gut microbiome, metabolomics, etc.). This review highlights the researches on quality and efficacy re-evaluation of FXC, and points out some typical problems. Further in-depth studies should focus on the promotion of quality control, pharmacokinetic properties, and pharmacological mechanism. Image 1 [ABSTRACT FROM AUTHOR]

Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM) for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in human have not been well investigated. ECG was extracted using boiling water and then provided to volunteers for oral administration. Following the ingestion, urine samples were collected from volunteers over 48 h. The extract and urine samples were analyzed using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS) system to screen and identify flavonoids and derived in vivo metabolites. A total of 18 flavonoids were identified in the ECG extract, and 20 metabolites, mainly glucuronide and sulfate conjugates, were screened in urine samples collected post consumption. The overall excretion of naringenin metabolites corresponded to 5.45% of intake and occurred mainly within 4–12 h after the ingestion. Meanwhile, another 29 phenolic catabolites were detected in urine. Obtained data revealed that flavonoids were abundant in the ECG extract, and these components underwent extensive phase II metabolism in humans. These results provided valuable information for further study of the pharmacology and mechanism of action of ECG. [ABSTRACT FROM AUTHOR]

Xuefu Zhuyu Decoction (XZD), a renowned traditional Chinese medicine prescription, is widely employed for the management of conditions characterized by qi- stagnation and blood stasis. Although its anti-thrombotic effect on deep vein thrombosis (DVT) patients has been clinically observed, the underlying mechanism remains largely unexplored. Our aim was to investigate the mechanisms by which XZD exerted its effect on DVT. The ultra performance liquid chromatography (UPLC) technique was employed to evaluate quality of XZD. To examine the effect of XZD on DVT, a DVT rat model with inferior vena cava (IVC) stenosis was established. The 4D-label-free proteomics approach was then utilized to uncover the possible mechanisms of XZD against DVT. Based on proteomics, citrullinated histone H3 (CitH3), along with serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were observed the inhibitory activity of XZD on neutrophil activation. Subsequently, the marker of platelet activation, specifically glycoprotein IIb (CD41) and glycoprotein IIIa (CD61), were assessed along with the secretion of von Willebrand factor (vWF) to investigate the inhibitory activity of XZD on platelet activation. Finally, we explored the impact of XZD on the sirtuin 1 (SIRT1)/nuclear factor kappa-B (NF-κB) pathway, which was associated with the activation of platelets and neutrophils. Eight distinct components were identified for the quality control of XZD. XZD effectively reduced thrombus weight and length in DVT rats, without affecting the coagulation function or hematological parameters in the systemic circulation. Proteomics analysis revealed that XZD alleviated DVT by inhibiting the activation of platelets and neutrophils. The protein expression of CitH3, along with serum levels of TNF-α and IL-1β, were reduced in XZD-treated DVT rats. Similarly, protein expressions of CD41 and CD61, along with the release of vWF, were markedly down-regulated in XZD-treated DVT rats. Finally, treatment with XZD resulted in an up-regulation of SIRT1 protein expression and a down-regulation of both acetylated NF-κB/p65 and phosphorylated NF-κB/p65 protein expressions in endothelium. XZD alleviates DVT by inhibiting the activation of platelets and neutrophils at the injured endothelium via the regulation of SIRT1/NF-κB pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

• The components and in vivo metabolism of JEXS were analyzed by LC-MS/MS. • 142 compounds in JEXS were characterized, 54 of which were identified by standards. • 52 prototypes and 126 metabolites of JEXS were characterized in bio-samples of rats. • The in vivo metabolic modes of chrysin- C -glycosyls were clarified for the first time. [Display omitted] Jian'er Xiaoshi oral liquid (JEXS), a traditional Chinese medicine (TCM) prescription, has been principally applied to treat spleen deficiency with gastrointestinal dysfunction in children caused by improper diet. However, due to a lack of research on the holistic component and metabolism of JEXS, the bioactive components of it remain unclear, hindering further study on its quality control and in vivo activity mechanism. In present study, an integrated analysis strategy based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) was established to systematically screen the components and the in vivo xenobiotics of JEXS. Totally 142 compounds in JEXS were characterized, 54 of which were identified. Besides, 178 xenobiotics were detected, including 52 prototypes and 126 metabolites, while the in vivo metabolic modes of chrysin- C -glycosyls and sinapinic acid derivatives were elucidated for the first time. Our investigation gave a comprehensive analysis of the compounds and metabolic characteristics of JEXS which indicated the direction of finding the bioactive ingredients and will provide an important basis for quality control and further study on the pharmacodynamic mechanism of JEXS. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which is associated with cognitive impairment. Previous study suggested CIH exposure could induce similar symptoms and signs to the clinical features of Deficiency of both Qi and Yin Syndrome (DQYS) in Traditional Chinese Medicine (TCM). Shashen-Maidong Decoction (SMD) has been applied clinically for DQYS for hundred years. However, SMD treatment could be beneficial to CIH induced cognitive impairment is still unclear. Therefore, the aim of this study was to investigate the effect of SMD treatment on CIH induced cognitive impairment, and to explore the related neuroprotective mechanism. Mice were exposed to CIH for 5 weeks (8 h/day) and were orally treated with either vehicle or SMD (5.265 g/kg/day) 30 min before CIH exposure. Spatial memory was evaluated by Morris Water Maze and Y-Maze test. Synaptic morphology in hippocampus was observed by Golgi-Cox staining and Electron microscope, and NR2B-ERK signaling pathway were detected by western blotting. Our results showed that SMD treatment improved performance in either Morris Water Maze or Y-Maze test in mice exposed to CIH, increased spine density and postsynaptic density (PSD) thickness in hippocampus. SMD treatment suppressed the over-activation of NR2B/CaMKII/SynGAP induced by CIH exposure, enhanced ERK/CREB phosphorylation and increased PSD-95 and BDNF expression. SMD attenuates the CIH-induced cognitive impairment through regulating NR2B-ERK signaling pathway. Additionally, our findings provided that DQYS may be the potential therapeutic target for neurocognitive diseases in patients with OSA. [Display omitted] • Shashen-Maidong Decoction attenuated Chronic Intermittent Hypixia-induced amnesia. • Shashen-Maidong Decoction improved CIH-induced synaptic damage in hippocampus. • Neuroprotection of Shashen-Maidong Decoction is related to glutamatergic signaling. • Shashen-Maidong Decoction actvated ERK/CREB and increased BDNF and PSD-95 expression. [ABSTRACT FROM AUTHOR]