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.

Integrating network pharmacology and experimental models to identify notoginsenoside R1 ameliorates atherosclerosis by inhibiting macrophage NLRP3 inflammasome activation.

Atherosclerosis is a cardiovascular disease, accounting for the most common mortality cause worldwide. Notoginsenoside R1 (NGR1) is a characteristic saponin of Radix notoginseng that exhibits anti-inflammatory and antioxidant effects while modulating lipid metabolism. Evidence suggests that NGR1 exerts cardioprotective, neuroprotective, and anti-atherosclerosis effects. However, underlying NGR1 mechanisms alleviating atherosclerosis (AS) have not been examined. This study used a network pharmacology approach to construct the drug-target-disease correlation and protein-protein interaction (PPI) network of NGR1 and AS. Moreover, functional annotation and pathway enrichment analyses deciphered the critical biological processes and signaling pathways potentially regulated by NGR1. The protective effect of NGR1 against AS and the underlying mechanism(s) was assessed in an atherogenic apolipoprotein E-deficient (ApoE-/-) mice in vivo and an oxidized low-density lipoprotein (ox-LDL)-induced macrophage model in vitro. The network pharmacology and molecular docking analyses revealed that NGR1 protects against AS by targeting the NLRP3/caspase-1/IL-1ß pathway. NGR1 reduced foam cell formation in ox-LDL-induced macrophages and decreased atherosclerotic lesion formation, serum lipid metabolism, and inflammatory cytokines in AS mice in vivo. Therefore, NGR1 downregulates the NLRP3 inflammasome complex gene expression of NLRP3, caspase-1, ASC, IL-1ß, and IL-18, in vivo and in vitro.

Comparative effects of acupuncture and metformin on insulin sensitivity in overweight/obese and lean women with polycystic ovary syndrome and insulin resistance: a post hoc analysis of a randomized trial.

Objective: This study explored the efficacy of acupuncture and metformin in enhancing insulin sensitivity among women with polycystic ovary syndrome (PCOS) and insulin resistance (IR), distinguishing between overweight/obese and lean groups. Methods: A post-hoc analysis of a randomized trial (NCT02491333) was undertaken. Participants were women aged 18-40 with PCOS and IR. They were randomized to receive true acupuncture with a placebo, metformin with sham acupuncture, or sham acupuncture with a placebo for 4 months, with follow-up visits over 3 months. Our study, involving 339 women, assessed the differential impact of acupuncture and metformin on insulin sensitivity in overweight/obese [body mass index (BMI) ≥ 24] versus lean women (BMI < 24). Primary outcomes measured changes in the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 4 and 7 months. Secondary outcomes assessed changes in glucose area under the curve (glucoseAUC) during the oral glucose tolerance test (OGTT) and BMI changes at 4 months. Results: Overweight/obese participants were generally older with higher measurements in various health metrics, but lower levels in specific hormonal metrics compared to lean women (p < 0.05). Among overweight/obese women, metformin outperformed acupuncture in reducing HOMA-IR levels (p = 0.004) and showed a significant drop from the baseline after 4 months (p < 0.05). In contrast, acupuncture's effect on HOMA-IR did not significantly differ from sham acupuncture at 4 and 7 months. For lean women, metformin and acupuncture showed comparable improvements in HOMA-IR, with notable declines at 4 and 7 months (p < 0.05). Acupuncture proved more beneficial for lean women than their overweight/obese counterparts after 4 months (p = 0.021). Conclusion: In overweight/obese women with PCOS and IR, acupuncture was less effective than metformin in enhancing insulin sensitivity. However, in lean women, acupuncture's efficacy was comparable to metformin. Further studies are required to validate these observations.

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.

Senegenin Ameliorate Acute Lung Injury Through Reduction of Oxidative Stress and Inhibition of Inflammation in Cecal Ligation and Puncture-Induced Sepsis Rats.

The purpose of this study was to assess the protective effect of senegenin on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into five groups: group 1 (control), group 2 (CLP), group 3 (CLP + senegenin 15 mg/kg), group 4 (CLP + senegenin 30 mg/kg), and group 5 (CLP + senegenin 60 mg/kg). CLP + senegenin groups received senegenin by gavage daily for consecutive 5 days, respectively, while the mice in control and CLP groups were given an equivalent volume of saline. We detected the lung wet/dry weight ratios and the histopathology of the lung. The levels of lung tissue myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-alpha (TNF-α), and interleukin-1ß (IL-1ß) levels were studied. The results demonstrated that senegenin treatment significantly attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, protein leak, infiltration of leukocytes, and MPO activity. In addition, senegenin markedly decreased MDA content and increased SOD activity and GSH level. Serum levels of TNF-α and IL-1ß were also decreased by senegenin administration. Furthermore, senegenin administration inhibited the nuclear translocation of NF-κB in the lungs. These findings indicate that senegenin exerts protective effects on CLP-induced septic rats. Senegenin may be a potential therapeutic agent against sepsis.

Activity of several kinds of drugs against Neospora caninum.

Neosporosis caused by Neospora caninum is a serious disease in cattle and dogs worldwide. It is the major cause of abortion and neonatal mortality in cattle. In this study, we evaluated the anti-N. caninum activity of Chinese medicine extracts (curcumin, artemether), herbicides (atrazine, glyphosate), anticoccidiosis drugs (toltrazuril and ponazuril), cyclophosphamide, diminazene aceturate and praziquantel in vitro using parasite growth, replication and host cell invasion assays in human foreskin fibroblast cultures. Curcumin, artemether, atrazine, toltrazuril and ponazuril exhibited inhibitory activity with 50% growth inhibitory concentration (IC50) of 1.1±0.4, 1.0±0.05, 11.2±2.7, 30.3±2.0 and 33.3±4.1µg/ml, respectively, in the growth inhibition assay. They were also active against protozoa replication, but only curcumin was effective against host cell invasion. Glyphosate, cyclophosphamide, diminazene aceturate and praziquantel were ineffective. In an in vivo infection model, curcumin showed no activity against N. caninum infection. We showed that curcumin, artemether, atrazine, toltrazuril, and ponazuril exhibited anti-N. caninum activity in vitro, providing important information for further studies on anti-N. caninum drugs.

Mass effect of redox reactions: A novel mode for surface plasmon resonance-based bioanalysis.

The pursuit of more specific and sensitive response is a perpetual goal for modern bioassays. This work proposed a novel label-free strategy about redox-related mass effect based on the surface plasmon resonance (SPR) technique for ultrasensitive determination of DNA. The protocol starts with the modification of SPR gilded disk with the capture DNA (cDNA). After the conjugation of immobilized cDNA with the target DNA (tDNA), the hybridization chain reaction was triggered by the introduction of mutual partial complementary primers to elongate the terminal into a nanoscale duplex. As it is reported that porphyrin could intercalate into the grooves of the double-stranded DNA (dsDNA) scaffold, multiple positive-charged Fe(III)meso-tetra(N-methyl-4-pyridyl) porphine (FeTMPyP) with symmetric structure were uptaken for in situ formation of porphyrin-dsDNA complex. Given FeTMPyP a highly efficient catalysis for the peroxide reduction, its presence as a biomimetic cofactor was validated via circular dichroism and UV-vis spectroscopy, demonstrating a tight binding as well as high catalytic activity and stability. Using 4-chloro-1-naphthol as a proton donor, the catalytic reduction of H2O2 would oxidize it into insoluble benzo-4-chloro-hexadienone, which simultaneously deposited on the heterogeneous interface, leading to a significant amplification in both SPR response and topological height profile. The signal increment was proportional to the concentration of tDNA, thus an ultrasensitive SPR-based DNA assay was developed with a linear range over four orders of magnitudes and a sub-femtomolar detection limit of 0.73 fM. The developed methodology exemplifies a different way of thinking about mass-sensing modes, extending conventional SPR-based DNA analysis to relevant biomedical applications.

Carbon nitride nanosheet-supported porphyrin: a new biomimetic catalyst for highly efficient bioanalysis.

A highly efficient biomimetic catalyst was fabricated based on ultrathin carbon nitride nanosheets (C3N4)-supported cobalt(II) proto-porphyrin IX (CoPPIX). The periodical pyridinic nitrogen units in C3N4 backbone could serve as electron donors for great affinity with Co(2+) in PPIX, which resembled the local electronic structure as vitamin B12 and heme cofactor of hemoglobin. UV-vis kinetics and electrochemistry revealed its competitive (electro)catalysis with conventional peroxidase, while X-ray photoelectron spectroscopy and theoretical calculations suggest that the rehybridization of Co 3d with N orbitals from the backside can result in significant changes in enthalpy and charge density, which greatly promoted the activity of CoPPIX. The prepared nanocatalyst was further conjugated with streptavidin via multiple amines on the edge plane of C3N4 for facile tagging. Using biotinylated molecular beacon as the capture probe, a sensitive electrochemiluminescence-based DNA assay was developed via the electroreduction of H2O2 as the coreactant after the hairpin unfolded by the target, exhibiting linearity from 1.0 fM to 0.1 nM and a detection limit of 0.37 fM. Our results demonstrate a new paradigm to rationally design inexpensive and durable biomimics for electrochemiluminescence quenching strategy, showing great promise in bioanalytical applications.

Potential for nutrient removal by integrated remediation methods in a eutrophicated artificial lake - a case study in Dishui Lake, Lingang New City, China.

A new integrated water remediation technology, including a floating bed, a buffer zone of floating plants, enclosed 'water hyacinth' purification, economic aquatic plants and near-shore aquatic plant purification, was used in Dishui Lake to improve its water quality. A channel of 1,000 m length and 30 m width was selected to implement pilot-scale experiments both in the static period and the continuous water diversion period. The results showed that the new integrated water remediation technology exhibited the highest removal rate for permanganate index in a static period, which achieved 40.6%. The average removal rates of total nitrogen (TN), ammonia nitrogen (NH3-N) and total phosphorus (TP) in a static period were 23.2, 21.6 and 19.1%, respectively. However, it did not exhibit an excellent removal rate for pollutants in the continuous water diversion period. The average removal rates for all pollutants were below 10%. In winter, the new integrated remediation technology showed efficient effects compared to others. The average removal rate for CODMn, TN, NH3-N and TP were 7, 5.3, 7.6 and 6.5%, respectively. Based on our results, the new integrated water remediation technology was highly efficient as a purification system, especially during the static period in winter.