Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway.

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

Edgeworthia gardneri (Wall.) Meisn. Ethanolic Extract Attenuates Endothelial Activation and Alleviates Cardiac Ischemia-Reperfusion Injury.

Endothelial pro-inflammatory activation is pivotal in cardiac ischemia-reperfusion (I/R) injury pathophysiology. The dried flower bud of Edgeworthia gardneri (Wall.) Meisn. (EG) is a commonly utilized traditional Tibetan medicine. However, its role in regulating endothelium activation and cardiac I/R injury has not been investigated. Herein, we showed that the administration of EG ethanolic extract exhibited a potent therapeutic efficacy in ameliorating cardiac endothelial inflammation (p < 0.05) and thereby protecting against myocardial I/R injury in rats (p < 0.001). In line with the in vivo findings, the EG extract suppressed endothelial pro-inflammatory activation in vitro by downregulating the expression of pro-inflammatory mediators (p < 0.05) and diminishing monocytes' firm adhesion to endothelial cells (ECs) (p < 0.01). Mechanistically, we showed that EG extract inhibited the nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and p38 mitogen-activated protein kinase (MAPK) signaling pathways to attenuate EC-mediated inflammation (p < 0.05). Collectively, for the first time, this study demonstrated the therapeutic potential of EG ethanolic extract in alleviating I/R-induced inflammation and the resulting cardiac injury through its inhibitory role in regulating endothelium activation.

Do high soil geochemical backgrounds of selenium and associated heavy metals affect human hepatic and renal health? Evidence from Enshi County, China.

It is unclear whether the United States Environmental Protection Agency (US EPA) method can accurately assess heavy metal risks in high-Se areas. Herein, a black shale outcropping in Enshi County, China, was taken as the study area, and a carbonate outcropping in Lichuan County was the control area. Selenium and associated heavy metal concentrations in rock, soil, rice, human blood and urine samples and human sensitive hepatic and renal biomarkers were measured. The results showed that the contents of selenium, cadmium, molybdenum and copper in the study area were 3.68 ± 2.72 µg/g, 2.65 ± 1.42 µg/g, 16.3 ± 15.5 µg/g, and 57.3 ± 17.6 µg/g, respectively, in soil (n = 47) and 1.072 ± 0.924 µg/g, 0.252 ± 0.310 µg/g, 2.800 ± 2.167 µg/g, and 10.91 ± 27.42 µg/g, respectively, in rice (n = 47). The daily adult intake levels of selenium, cadmium and molybdenum from rice consumption in the study area (exposure group) exceed the recommended tolerance values in China. According to the US EPA method, these environmental media pose a significant risk to human health. However, in the exposure group (n = 111), the median levels of the sensitive hepatic biomarkers alanine aminotransferase (18 U/L), aspartate aminotransferase (28 U/L) and total bilirubin (10.9 µmol/L) and the sensitive renal biomarkers serum creatinine (70.1 µmol/L), urinary nitrogen (5.73 mmol/L) and uric acid (303.80 µmol/L) were within reference ranges and had values equivalent to those of the control group (P > 0.05). The elements tended to differentiate during migration from one medium to another. Due to the complex interaction between selenium and heavy metals, a survey of human health indicators is indispensable when the US EPA method is used to assess the heavy metal risks in high-Se areas. The recommended molybdenum tolerable intake in the U.S. (2000 µg/d) is reasonable based on a comparison.

The ethanol extract of Edgeworthia gardneri (Wall.) Meisn attenuates macrophage foam cell formation and atherogenesis in ApoE-/- mice.

Introduction: Atherosclerotic cardiovascular disease is the leading cause of death worldwide. The Edgeworthia gardneri (Wall.) Meisn is a Tibetan medicine commonly used to prepare herbal tea to alleviate the local people's metabolic diseases. However, the anti-atherosclerotic effect of ethanol extract of the flower of E. gardneri (Wall.) Meisn (EEEG) and its underlying mechanism remain unknown. Methods: EEEG was used to treat low-density lipoprotein (ox-LDL)-induced macrophages to detect macrophage foaminess, cholesterol binding and uptake, and lipid transport-related gene expression. eEEG treated ApoE-/- mice fed a high-fat diet for 16 weeks to detect atherosclerotic plaque area, macrophage infiltration, and liver and small intestine lipid transport-related gene expression. Results: EEEG inhibited macrophage-derived foam cell formation induced by oxidized low-density lipoprotein (ox-LDL) by reducing CD36-mediated lipoprotein uptake. EEEG significantly alleviated atherosclerosis in ApoE-/- mice fed a high-fat diet for 16 weeks. EEEG treatment significantly decreased atherosclerotic plaque area, macrophage infiltration, and increased collagen content. Moreover, EEEG treatment significantly downregulated mRNA expression of hepatic Srb1 and intestinal Npc1l1 and increased expression of hepatic Cyp7a1. Conclusion: Our study highlighted that EEEG played a role in attenuating atherosclerotic plaque formation by reducing macrophage foam cell formation.

Edgeworthia gardneri (Wall.) Meisn. extract protects against myocardial infarction by inhibiting NF-κB-and MAPK-mediated endothelial inflammation.

Background: Experimental and clinical evidence has demonstrated a pivotal role of inflammation in the pathogenesis of ischemic heart disease, and targeting inflammation has been shown to provide clinical benefits for patients with coronary disease. Endothelial cells constitute the majority of non-cardiomyocytes in the heart. Endothelial pro-inflammatory activation is recognized as a critical component in the pathophysiology of cardiovascular disease. The dried flowers of Edgeworthia gardneri (Wall.) Meisn. (EG) have been widely used as Tibetan folk medicine to ameliorate a range of metabolic disorders, such as diabetes mellitus, hyperlipidemia, hypertension, and obesity. However, its role in modulating endothelial inflammation and ischemic heart disease has not been evaluated. Methods and results: Herein, using a preclinical rat model of coronary artery ligation-induced myocardial infarction (MI), we demonstrated that systemic administration of EG extract (EEEG) attenuated ischemic cardiac injury. EEEG reduced myocardial infarct size, improved cardiac function, and ameliorated adverse cardiac remodeling. Moreover, the cardioprotective effects of EEEG were associated with decreased MI-induced myocardial inflammation. Consistent with the anti-inflammatory role of EEEG in vivo, EEEG attenuated TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) activation and monocyte-endothelial cell firm adhesion in vitro. Mechanistically, our data showed that EEEG's mode of action suppresses the activation of NF-κB, ERK, and p38 MAPK signaling pathways in ECs. Importantly, we demonstrated that EEEG inhibits endothelial inflammation in an NF-κB- and p38 MAPK-dependent manner using pharmacological inhibitors. Conclusion: Collectively, this study identified EG as a potential therapeutic agent in attenuating endothelial inflammation and managing ischemic cardiovascular disease.

Therapeutic implications of functional tea ingredients for ameliorating inflammatory bowel disease: a focused review.

Inflammatory bowel disease (IBD) is a chronic gastro-intestinal disorders of unknown etiology. There are several drugs approved for treating IBD patients with active disease, including first-line use of aminosalicylates, and secondary choices of immunomodulators and other therapies. These medications might manage disease symptoms, but have also shown significant side-effects in IBD patients. Tea is the second largest beverage in the world and its main active ingredients including tea polyphenols, polysaccharides and tea pigments have been shown promising anti-inflammatory and antioxidant properties. In this review, we summarize the influence of different tea varieties including green tea, black tea and dark tea as potential nutritional therapy for preventing and treating IBD, and discuss the mechanisms of tea ingredients involved in the regulation of oxidative stress, inflammation, signaling pathways, and gut microbiota that could benefit for IBD disease management. Our observation directs further basic and clinical investigations on tea polyphenols and their derivatives as novel IBD therapeutic agents.

Ripened Pu-erh Tea Extract Promotes Gut Microbiota Resilience against Dextran Sulfate Sodium Induced Colitis.

Ripened Pu-erh tea (RPT) has been shown to be an effective natural ingredient to defend against experimentally induced colitis. We hypothesized that RPT would alleviate dextran sulfate sodium (DSS) induced colitis via modulating intestinal microbiota. The effect of RPT on mice gut microbiota was evaluated using 16S rRNA gene amplicon sequencing, broad-spectrum antibiotic (ABX) treatment, and fecal microbiota transplantation (FMT). Pretreatment with RPT enhanced intestinal barrier function, reduced colonic and serum proinflammatory cytokine and macrophage infiltration, and preserved the resilience of gut microbiota in mice during a DSS challenge. Administration of either RPT-regulated or healthy control-derived gut microbiota showed similar protection against colitis, and such protection could not be recapitulated with fecal microbiota from ABX-treated mice, suggesting a key role of protective consortium in the disease protection. Mechanistically, cecal contents of short-chain fatty acids (SCFAs) and colonic peroxisome proliferator activated receptor-γ (PPAR-γ) expression in colitis mice increased significantly by RPT intervention. Collectively, RPT treatment improved DSS-induced colitis by partially reversing the dysbiosis state of gut microbiota, which might be associated with an increase in SCFA level and PPAR-γ expression.

Hot-water extract of ripened Pu-erh tea attenuates DSS-induced colitis through modulation of the NF-κB and HIF-1α signaling pathways in mice.

Tea consumption has been found to be associated with low incidence of inflammatory bowel disease in Asian countries. However, there is very limited knowledge of such potential protection and its underlying mechanism. Ripened Pu-erh tea (RPT) belongs to the variety of microbial fermented tea, but its function regarding anti-inflammation remains unclear. In the present study, we investigated the effects of RPT on dextran sulfate sodium (DSS)-induced colitis in mice. The results demonstrated that RPT significantly relieved the loss of body weight, disease severity and shortening of colon length, and remarkably inhibited the secretion of pro-inflammatory cytokines by lessening the infiltration of inflammatory cells. Furthermore, we found that RPT suppressed the activation of the NF-κB pathway and down-regulated the expression of HIF-1α. Thus, it was concluded that RPT attenuated the progress of colitis via suppressing the HIF-1α/NF-κB signaling pathways thus reducing inflammation. This suggests that RPT may be a potential anti-inflammatory nutraceutical for the prevention and treatment of colonic colitis.

Autologous Blood Transfusion and Pringle Maneuver in Laparoscopic Segmental Hepatectomy for Benign Hepatic Neoplasms: A Retrospective Study.

Objectives: To investigate the effect of autologous blood transfusion (ABT) and Pringle maneuver (PM) on postoperative early liver function and short-term postoperative results following laparoscopic liver resection in patients with benign hepatic neoplasms. Materials and Methods: We retrospectively analyzed the clinical data for 125 consecutive patients who underwent laparoscopic segmental hepatectomy from January 2015 to May 2018 (68 in the ABT group versus 57 in the PM group). We compared patients' characteristics and intra- and postoperative short-term outcomes between the groups. Results: The 2 groups were well matched regarding patients' clinical characteristics, types of liver resection, operative time, and histopathological findings (P > .05). Median blood loss was significantly lower in the PM group versus the ABT group (200 mL versus 750 mL, respectively; P < .01), and overall complication rates were similar (n = 12 [17%] versus n = 9 [16%], respectively; P > .05). The ABT group had significantly lower mean levels of total bilirubin, indirect bilirubin, aspartate transaminase, and alanine aminotransferase on postoperative days 1 and 3 (P < .05). The ABT group had a shorter hospital stay compared with the PM group (5.8 days versus 7.7 days, respectively; P < .05) and lower hospitalization costs (55,400 ± 15,400 versus 667,000 ± 21,600 CN dollars, respectively; P < .05). Conclusions: Compared with Pringle's maneuver, laparoscopic hepatectomy with ABT promoted early recovery of liver function and reduced hospitalization costs in select patients with benign hepatic neoplasms.

New pectin-induced green fabrication of Ag@AgCl/ZnO nanocomposites for visible-light triggered antibacterial activity.

The pectin (CEP) was used as matrix material to prepare Ag@AgCl/ZnO nanocomposites with a green method for photocatalytic antibacterial activity in visible-light. Briefly, Ag@AgCl plasmonic hybrids were prepared in the CEP macromolecule matrix with size control, which was attributed to the stability of carboxyl and hydroxyl groups on the CEP. Subsequently, an effective and green two-steps approach was explored for the fabrication of CEP-Ag@AgCl/ZnO nanocomposites with resource saving and environment friendly. Interestingly, more Ag+ was converted into metallic Ag in the CEP-Ag@AgCl/ZnO than that in the CEP-Ag@AgCl. This phenomenon was attributed that the reducibility of free hemiacetal hydroxyl groups on CEP was realized with the help of NaOH in the preparation of CEP-ZnO. In addition, the CEP chains were not obviously destroyed except for the change in the crystallinity after the preparation of the CEP-Ag@AgCl/ZnO nanocomposites, indicating that the method was non-destructive. Moreover, the pH triggered release of Zn2+ and low release of Ag+ in CEP-Ag@AgCl/ZnO nanocomposites with excellent photocatalytic antibacterial activity were confirmed in this work. The proposed green process provides a new idea for the large-scale production of antibacterial pectin-based nanocomposites in industry with a low-cost.

Lactobacillus plantarum ZDY04 exhibits a strain-specific property of lowering TMAO via the modulation of gut microbiota in mice.

Trimethylamine N-oxide (TMAO), which is oxidized from trimethylamine (TMA) by hepatic flavin-containing monooxygenases (FMOs), promotes the development of atherosclerosis and is a new target for the prevention and treatment of cardiovascular disease from the perspective of intestinal flora. TMA is transformed by intestinal flora from TMA-containing nutrients, such as choline. Some small molecular agents lower serum TMAO and/or cecal TMA levels. However, probiotics that can effectively reduce serum TMAO levels are currently lacking. In this work, five potentially probiotic strains were administered to mice supplemented with 1.3% choline. Only Lactobacillus plantarum ZDY04 significantly reduced serum TMAO and cecal TMA levels by modulating the relative abundance of the families Lachnospiraceae, Erysipelotrichaceae and Bacteroidaceae and the genus Mucispirillum in mice and not by influencing the expression levels of hepatic FMO3 and metabolizing choline, TMA, and TMAO. In addition, L. plantarum ZDY04 can significantly inhibit the development of TMAO-induced atherosclerosis in ApoE-/- 1.3% choline-fed mice as compared with the untreated PBS group. In conclusion, the use of L. plantarum ZDY04 may be an alternative approach to reduce serum TMAO levels and TMAO-induced atherosclerosis in mice.

Enterobacter aerogenes ZDY01 Attenuates Choline-Induced Trimethylamine N-Oxide Levels by Remodeling Gut Microbiota in Mice.

Trimethylamine N-oxide (TMAO), which is transformed from trimethylamine (TMA) through hepatic flavin-containing monooxygenases, can promote atherosclerosis. TMA is produced from dietary carnitine, phosphatidylcholine, and choline via the gut microbes. Previous works have shown that some small molecules, such as allicin, resveratrol, and 3,3-dimethyl-1-butanol, are used to reduce circulating TMAO levels. However, the use of bacteria as an effective therapy to reduce TMAO levels has not been reported. In the present study, 82 isolates were screened from healthy Chinese fecal samples on a basal salt medium supplemented with TMA as the sole carbon source. The isolates belonged to the family Enterobacteriaceae, particularly to genera Klebsiella, Escherichia, Cronobacter, and Enterobacter. Serum TMAO and cecal TMA levels were significantly decreased in choline-fed mice treated with Enterobacter aerogenes ZDY01 compared with those in choline-fed mice treated with phosphate-buffered saline. The proportions of Bacteroidales family S24-7 were significantly increased, whereas the proportions of Helicobacteraceae and Prevotellaceae were significantly decreased through the administration of E. aerogenes ZDY01. Results indicated that the use of probiotics to act directly on the TMA in the gut might be an alternative approach to reduce serum TMAO levels and to prevent the development of atherosclerosis and "fish odor syndrome" through the effect of TMA on the gut microbiota.

Evaluation of kudzu root extract-induced hepatotoxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Kudzu root, the root of Pueraria lobata (Willd.) Ohwi, has been used as food and medicine for centuries, but few studies indicate that kudzu root may cause liver damage. AIM OF STUDY: We studied the hepatotoxicity of kudzu root extract in mice, HepG2 cells and mice hepatocytes. MATERIALS AND METHODS: Mice were administrated with kudzu root extract (10mg/day) for 4 weeks, and then the biochemical analysis and histopathological changes were carried out. To explore the potential mechanism by which kudzu root extract-induced hepatotoxicity, HepG2 cells and mice hepatocytes were co-cultured with kudzu root extract or puerarin, which is a kudzu root isoflavone, for 2h. RESULTS: The increase of serum ALT and AST and histopathological changes in treated mice revealed that kudzu root extract was hepatotoxic. The increase of LDH leakage for HepG2 cells and mice hepatocytes further confirmed hepatotoxicity of kudzu root extract. Kudzu root extract and puerarin significantly up-regulated Mt1 mRNA involved in the acute phase response and Bax which is crucial for apoptosis. Gclc, Nrf2 and Ho-1 mRNA expressions did not change in treatment group. CONCLUSIONS: Kudzu root extract may be hepatotoxic and caution may be required for its use.

Effects of phlegm-dispelling and blood stasis-resolving traditional Chinese drugs on the blood pressure and cell cycle of left ventricular cardiac myocytes in hypertensive rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of phlegm-dispelling and blood stasis-resolving traditional Chinese drugs on the cell cycle of cardiac myocytes and left ventricular reconstruction in hypertensive rats.</p><p><b>METHODS</b>Bilateral renal artery stenosis was conducted to induce hypertension in rats, which were randomly divided into hypertensive model group (n = 10), sham-operated group (n = 8), high-dose drug group (n = 11) and low-dose drug group (n = 11), with 8 normal untreated rats as the normal control group. The systolic blood pressure (SBP) was measured in the tail artery of the rats. Two months after the operation, the left ventricular mass (LVM) and LVM index (LVI) were calculated in all the rats. The cell cycle changes in the left ventricular cardiac myocytes were evaluated using flow cytometry.</p><p><b>RESULTS</b>The mean blood pressure and LVI of the hypertensive model group were significantly higher than those of the normal control (P < 0.05) and sham-operated group (P < 0.01). After treatment with preparation of the traditional Chinese drugs at either high or low dose, the mean blood pressure and LVM of the rats showed obvious reduction, and LVI was decreased significantly compared with that of the model group (P < 0.05). Compared with the hypertensive model group which showed obviously decreased cell percentage in G0/G1 phase and increased S phase cells, the treatment at both doses significantly increased the cells in G0/G1 phase (P < 0.05) and decreased the S-phase cells (P < 0.05) to levels comparable to those in the normal control and sham-operated groups (P > 0.05). The percentage of G2/M-phase cells showed no significant difference between the groups (P > 0.05).</p><p><b>CONCLUSION</b>The traditional Chinese drugs can significantly decrease blood pressure and LVI in hypertensive rats, and induce cell cycle arrest in G0/G1 phase to reverse left ventricular hypertrophy by regulating the cell cycle and inhibiting the division and proliferation of the cardiac myocytes.</p>

[Effects of tea polyphenols on cell proliferation and hTERT of human Tca8113 cell lines].

OBJECTIVE: To investigate the effects of tea polyphenols (TP) on cell proliferation and human telomerase reverse transcriptase (hTERT). METHODS: The experiment was divided into tea polyphenols 0.100 g/L, tea polyphenols 0.050 g/L and blank control groups. The inhibitory ratio of cell proliferation was assayed with MTT, and hTERT mRNA was detected by RT-PCR, and hTERT protein analyzed by Western-blotting. The data were analyzed by one-way ANOVA and Student-Newman-Keuls of SPSS 11.0 for windows. RESULTS: Cell proliferations were significantly inhibited after exposure to TP. The proliferation inhibiting rate of TP 0.025, 0.050, 0.100, 0.200 g/L on Tca8113 cell at 72 h was 69.75% +/- 3.24%, 63.17% +/- 3.19%, 50.35% +/- 4.21% and 34.75% +/- 3.71%, respectively (F = 270.19, P < 0.05). At the end of 72 h, the hTERT mRNA expression in TP 0.100 g/L, 0.050 g/L and control group were 0.32 +/- 0.05, 0.41 +/- 0.04, 0.72 +/- 0.05, respectively (P < 0.05). The Western-blotting assay showed that hTERT protein was also decreased by tea polyphenols compared to control group. CONCLUSIONS: Tea polyphenols could inhibit the proliferation of Tca8113 cells and expression of the hTERT mRNA and protein in Tca8113 cell lines. This effect might be one of the mechanisms for anticancer function of tea polyphenols.

Effects of tea polyphenols on cell proliferation and hTERT of human Tca8113 cell lines / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of tea polyphenols (TP) on cell proliferation and human telomerase reverse transcriptase (hTERT).</p><p><b>METHODS</b>The experiment was divided into tea polyphenols 0.100 g/L, tea polyphenols 0.050 g/L and blank control groups. The inhibitory ratio of cell proliferation was assayed with MTT, and hTERT mRNA was detected by RT-PCR, and hTERT protein analyzed by Western-blotting. The data were analyzed by one-way ANOVA and Student-Newman-Keuls of SPSS 11.0 for windows.</p><p><b>RESULTS</b>Cell proliferations were significantly inhibited after exposure to TP. The proliferation inhibiting rate of TP 0.025, 0.050, 0.100, 0.200 g/L on Tca8113 cell at 72 h was 69.75% +/- 3.24%, 63.17% +/- 3.19%, 50.35% +/- 4.21% and 34.75% +/- 3.71%, respectively (F = 270.19, P < 0.05). At the end of 72 h, the hTERT mRNA expression in TP 0.100 g/L, 0.050 g/L and control group were 0.32 +/- 0.05, 0.41 +/- 0.04, 0.72 +/- 0.05, respectively (P < 0.05). The Western-blotting assay showed that hTERT protein was also decreased by tea polyphenols compared to control group.</p><p><b>CONCLUSIONS</b>Tea polyphenols could inhibit the proliferation of Tca8113 cells and expression of the hTERT mRNA and protein in Tca8113 cell lines. This effect might be one of the mechanisms for anticancer function of tea polyphenols.</p>

Validation method for bacteria and fungi count in microbial limit test of drugs / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the validation method and criteria for counting bacteria and fungi in microbial limit test which is described in the Pharmacopeia of China (ChP) 2005.</p><p><b>METHOD</b>According to the method set up for validation, the tested microorganisms with known counts were added to samples followed by the determination of the recovery.</p><p><b>RESULT</b>With different preparing method for testing samples, the recoveries for the tested microorganisms in testing samples were found to be over 70%.</p><p><b>CONCLUSION</b>Validation method for counting contaminated bacteria and fungi in drugs is recommended to follow the method established in this paper. The recovery for tested microorganisms should be not less than 70%.</p>