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A liposome of Licochalcone A (LCA‐Liposomes) was purposively prepared to ameliorate the low in vivo availability and efficacy of LCA. Physical characterization of LCA‐Liposomes was carried out mainly by determining particle size, morphology, zeta potential (Z‐potential), and efficiency of LCA encapsulation (EE) via appropriate techniques. Also, the rate of LCA release in vitro and distribution in vivo (plasma and tissues) was evaluated. Evaluation of the antirenal activity of LCA‐liposomes was carried out by establishing chronic renal failure (CRF) model in mice through intragastric administration of adenine (200 mg/kg) and subsequent determination of biochemical parameters and examination of tissue sections. Respectively, the mean size of liposomal particles, Z‐potential and EE of LCA‐Liposomes were 71.78 ± 0.99 nm, −38.49 ± 0.06 mV, and 97.67 ± 1.72%. Pharmacokinetic and tissue distribution studies showed that LCA‐Liposomes could improve the availability of LCA in the blood and tissues, whereas during pharmacodynamics studies, the liposome effectively improved the therapeutic effect of LCA on CRF mice by potentially protecting the renal tissues while exhibiting antioxidant activity. In conclusion, LCA‐Liposomes could effectively improve the bioavailability of LCA and provide platform for the development of LCA‐related functional products. Practical applications: As a traditional Chinese medicine, licorice is widely used in food and pharmaceutical industries. LCA is a small molecule flavonoid extracted from the root of licorice. In this study, LCA was loaded on liposome carriers, which significantly improved the water solubility and oral bioavailability, and proved that LCA‐Liposomes have certain therapeutic effects on chronic renal failure, thereby providing a basis for the development of LCA into drugs or functional food in the future. [ABSTRACT FROM AUTHOR]

Tangwang Mingmu granule (TWMM), a traditional Chinese medicine, has been widely used in the treatment of diabetic retinopathy (DR), the most common microvascular complication in diabetes mellitus. To establish a method to select target compounds from herbs for a pharmacokinetic study using network pharmacology, which could be applied in clinical settings. First, UPLC/Q Exactive Q-Orbitrap and GCMS 2010 were used to determine the non-volatile and volatile ingredients of TWMM. Based on the identified compounds, network pharmacology was used to screen the key compounds and targets of TWMM in the treatment of DR. Based on the compound-target-pathway network and identification of components emigrant into blood, the potential compound markers in vivo were chosen. Then, Sprague-Dawley (SD) rats were administrated of TWMM at a 9.6 g/kg dose to investigating pharmacokinetic parameters using the UPLC-QQQ-MS. Ninety and forty-five compounds were identified by UPLC-MS and GC-MS, respectively. Based on the network pharmacology, nine compounds with a degree value above 15 were screened and implied that these compounds are the most active in DR treatment. Moreover, criteria of degree value greater than 7 were applied, and PTGS2, NOS2, AKT1, ESR1, TNF, and MAPK14 were inferred as the core targets in treating DR. After identification of components absorbed into blood, luteolin and formononetin were selected and used to investigate the pharmacokinetic parameters of TWMM after its oral administration. The reported strategy provides a method that combines ingredient profiling, network pharmacology, and pharmacokinetics to determine luteolin and formononetin as the pharmacokinetic markers of TWMM. This strategy provides a clinically relevant methodology that allows for the screening of pharmacokinetic markers in Chinese medicines. [ABSTRACT FROM AUTHOR]

Shenmai injection (SMI), as a patented traditional Chinese medicine, is extracted from Panax ginseng and Ophiopogon japonicus. It commonly used in the treatment of cardiovascular disease and in the control of cardiac toxicity induced by doxorubicin (DOX) treatment. However, its anti-cardiotoxicity mechanism remains unknown. The purpose of this study was to investigate the underlying mitochondrial protective mechanisms of SMI on DOX-induced myocardial injury. The cardioprotective effect of SMI against DOX-induced myocardial damage was evaluated in C57BL/6 mice and H9c2 cardiomyocytes. In vivo , myocardial injury, apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt)/glycogen synthase kinase 3 beta (GSK-3β) signaling pathway related proteins were measured. In vitro , apoptosis, mitochondrial superoxide, mitochondrial membrane potential, mitochondrial morphology, levels of mitochondrial fission/fusion associated proteins, mitochondrial respiratory function, and AMP-activated protein kinase (AMPK) activity were assessed. To further elucidate the regulating effects of SMI on AMPK and PI3K/Akt/GSK-3β signaling pathway, compound C and LY294002 were utilized. In vivo , SMI decreased mortality rate, levels of creatine kinase, and creatine kinase-MB. SMI significantly prevented DOX-induced cardiac dysfunction and apoptosis, decreased levels of Bax/Bcl-2 and cleaved-Caspase3, increased levels of PI3K, p-Akt, and p-GSK-3β. In vitro , SMI rescued DOX-injured H9c2 cardiomyocytes from apoptosis, excessive mitochondrial reactive oxygen species production and descending mitochondrial membrane potential, which were markedly suppressed by LY294002. SMI increased ratio of L-OPA1 to S-OPA1, levels of AMPK phosphorylation, and DRP1 phosphorylation (Ser637) in order to prevent DOX-induced excessive mitochondrial fission and insufficient mitochondrial fusion. In conclusion, SMI prevents DOX-induced cardiotoxicity, inhibits mitochondrial oxidative stress and mitochondrial fragmentation through activation of AMPK and PI3K/Akt/GSK-3β signaling pathway. [ABSTRACT FROM AUTHOR]

Dan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. This study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. The comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE−/− mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. A total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE−/− mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. This study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis. [Display omitted] [ABSTRACT FROM AUTHOR]

Traditional Chinese drugs, including Buyang Huanwu decoction (BYHWD), have been used in traditional practice to manage cardiovascular and cerebrovascular diseases. However, the effect and mechanisms by which this decoction alleviates diabetes-accelerated atherosclerosis are unknown and require exploration. This study aims to investigate the pharmacological effects of BYHWD on preventing diabetes-accelerated atherosclerosis, and elucidate its underlying mechanism. Streptozotocin (STZ)-induced diabetic ApoE−/− mice were treated with BYHWD. Atherosclerotic aortic lesions, endothelial function, mitochondrial morphology, and mitochondrial dynamics-related proteins were evaluated in isolated aortas. High glucose-exposed human umbilical endothelial cells (HUVECs) were treated with BYHWD and its components. AMPK siRNA transfection, Drp1 molecular docking, Drp1 enzyme activity measurement, and so on were used to explore and verify the mechanism. BYHWD treatment inhibited the worsening of diabetes-accelerated atherosclerosis by lessening atherosclerotic lesions in diabetic ApoE−/− mice, by impeding endothelial dysfunction under diabetic conditions, and by inhibiting mitochondrial fragmentation by lowering protein expression levels of Drp1 and mitochondrial fission-1 protein (Fis1) in diabetic aortic endothelium. In high glucose-exposed HUVECs, BYHWD treatment also downgraded reactive oxygen species, promoted nitric oxide levels, and abated mitochondrial fission by reducing protein expression levels of Drp1 and fis1, but not mitofusin-1 and optic atrophy-1. Interestingly, we found that BYHWD's protective effect against mitochondrial fission is mediated by AMPK activation-dependent reduction of Drp1 levels. The main serum chemical components of BYHWD, ferulic acid, and calycosin-7-glucoside, can reduce the expression of Drp1 by regulating AMPK, and can inhibit the activity of GTPase of Drp1. The above findings support the conclusion that BYHWD suppresses diabetes-accelerated atherosclerosis by reducing mitochondrial fission through modulation of the AMPK/Drp1 pathway. [Display omitted] • Buyang Huanwu decoction suppresses diabetes-accelerated atherosclerosis. • Buyang Huanwu decoction attenuates endothelial dysfunction and atherosclerosis by inhibiting Drp1-dependent mitochondrial fission. • Calycosin-7-glucoside and ferulic acid, two main active compounds in Buying Huanwu decoction, reduces Drp1 expression and GTPase activity. [ABSTRACT FROM AUTHOR]

• The metabolites between U. rhynchophylla (Miq.) Miq. ex Havil. and U. hirsuta Havil. by LC-MS based metabolomics were investigated. • Utilizing chemometrics including PCA and OPLS-DA to identify 16 distinguished compounds between URM and UHH. • By combining multivariate statistical analysis and correlation analysis, the potential anti-hypertension compounds were discovered. • The activities of the potential compounds were fully validated. The genus Uncaria belongs to the family of Rubiaceae, which contains approximately 34 species. It has been widely used as a traditional Chinese medicine (TCM) in China to treat hypertension, fevers, headaches, gastrointestinal illness, epilepsy, wounds, and ulcers. Uncaria rhynchophylla. (Miq.) Miq. ex Hvail.(URM) and Uncaria hirsuta Havil.(UHH) are mainly used as remedies for hypertension, which both belong to the resource of "Gou-teng" in the Chinese Pharmacopoeia. However, the authentic antihypertensive components of Uncaria still have not been fully elucidated until now. In this work, we firstly explored and compared the vasorelaxation effect of URM and UHH on the isolated rat mesenteric artery ring. Then, the variations of metabolite profiles between URM and UHH samples were investigated by UHPLC/Q-Orbitrap-MS, and 16 different metabolites have been found through multivariate statistical analysis. Further, the potential vasodilative compounds which include corynoxeine, isocorynoxeine, isorhynchophylline, rhynchophylline, hirsuteine and hirsutine were screened through the correlation analysis between metabolites and anti-hypertension activities. And the relaxation effects of the six compounds on the mesenteric artery have verified. The results indicated that metabolomics combined with correlation analysis could be effective strategies to rapid explore the active compounds from TCM. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are one of the leading causes of death worldwide and cardiac fibrosis is a common pathological process for cardiac remodeling in cardiovascular diseases. Cardiac fibrosis not only accelerates the deterioration progress of diseases but also becomes a pivotal contributor for futile treatment in clinical cardiovascular trials. Although cardiac fibrosis is common and prevalent, effective medicines to provide sufficient clinical intervention for cardiac fibrosis are still unavailable. Traditional Chinese medicine (TCM) is the natural essence experienced boiling, fry, and other processing methods, including active ingredients, extracts, and herbal formulas, which have been applied to treat human diseases for a long history. Recently, research has increasingly focused on the great potential of TCM for the prevention and treatment of cardiac fibrosis. Here, we aim to clarify the identified pro-fibrotic mechanisms and intensively summarize the application of TCM in improving cardiac fibrosis by working on these mechanisms. Through comprehensively analyzing, TCM mainly regulates the following pathways during ameliorating cardiac fibrosis: attenuation of inflammation and oxidative stress, inhibition of cardiac fibroblasts activation, reduction of extracellular matrix accumulation, modulation of the renin-angiotensin-aldosterone system, modulation of autophagy, regulation of metabolic-dependent mechanisms, and targeting microRNAs. We also discussed the deficiencies and the development direction of anti-fibrotic therapies on cardiac fibrosis. The data reviewed here demonstrates that TCM shows a robust effect on alleviating cardiac fibrosis, which provides us a rich source of new drugs or drug candidates. Besides, we also hope this review may give some enlightenment for treating cardiac fibrosis in clinical practice. [Display omitted] • Fibrosis is a fundamental process during cardiac remodeling and associated with adverse outcomes. • To date, effective therapeutic interventions for cardiac fibrosis are still lacking. • TCM targets multiple mechanisms and pathways in the fibrotic process to relieve cardiac fibrosis. • TCM provides us a rich source of new drugs or drug candidates for cardiac fibrosis. [ABSTRACT FROM AUTHOR]

• AMPK inactivation, mitochondrial fission, ER stress, and inflammasome activation contribute to endothelial dysfunction in diabetes mellitus. • Clinically used antidiabetic drugs and Traditional Chinese Medicines improve diabetes-induced endothelial dysfunction via modulation of cellular processes. • TCM formula ingredients plus western hypoglycemic drugs effectively ameliorate endothelial dysfunction induced by diabetes. Diabetes, a worldwide health concern while burdening significant populace of countries with time due to a hefty increase in both incidence and prevalence rates. Hyperglycemia has been buttressed both in clinical and experimental studies to modulate widespread molecular actions that effect macro and microvascular dysfunctions. Endothelial dysfunction, activation, inflammation, and endothelial barrier leakage are key factors contributing to vascular complications in diabetes, plus the development of diabetes-induced cardiovascular diseases. The recent increase in molecular, transcriptional, and clinical studies has brought a new scope to the understanding of molecular mechanisms and the therapeutic targets for endothelial dysfunction in diabetes. In this review, an attempt made to discuss up to date critical and emerging molecular signaling pathways involved in the pathophysiology of endothelial dysfunction and viable pharmacological management targets. Importantly, we exploit some Traditional Chinese Medicines (TCM)/TCM isolated bioactive compounds modulating effects on endothelial dysfunction in diabetes. Finally, clinical studies data on biomarkers and biochemical parameters involved in the assessment of the efficacy of treatment in vascular endothelial dysfunction in diabetes was compared between clinically used western hypoglycemic drugs and TCM formulas. [ABSTRACT FROM AUTHOR]

Dan-Lou tablet (DLT) is developed from the traditional Chinese medicine (TCM) formula Gualou Xiebai Baijiu Tang which has been used for at least 2000 years in China. DLT has been widely used in clinical practice to treat cardiovascular diseases. This study aimed to uncover the pharmacological mechanism of the compounds absorbed into the blood of Dan-Lou tablet (DLT) on coronary heart disease (CHD) using a network pharmacology integrated pharmacokinetics strategy. A rapid and sensitive method was developed for the simultaneous determination of the six compounds (puerarin, formononetin, calycosin, paeoniflorin, cryptotanshinone and tanshinone IIA) in rat plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS). Then, the pharmacology network was established based on the relationship between five compounds absorbed into the blood targets (puerarin, formononetin, calycosin, cryptotanshinone and tanshinone IIA) and CHD targets. The intra-and inter-day precision were less than 11% and the accuracy ranged from 88.2% to 112%, which demonstrated that the LC-MS/MS method could be used to evaluate the pharmacokinetic feature of the six compounds in rats after oral administration of DLT. The pathway enrichment analysis revealed that the significant bioprocess networks of DLT on CHD were positive regulation of estradiol secretion, negative regulation of transcription from RNA polymerase II promoter, lipopolysaccharide-mediated signaling pathway and cytokine activity. The proposed network pharmacology integrated pharmacokinetics strategy provides a combination method to explore the therapeutic mechanism of the compounds absorbed into the blood of multi-component drugs on a systematic level. Image 1 [ABSTRACT FROM AUTHOR]