Nitrate Upcycling Mediated by Organonickel Catalysis.

Nitrogen oxides (NOx) are major environmental pollutants and to neutralize this long-term environmental threat, new catalytic methods are needed. Although there are biological denitrification processes involving four different enzymatic reactions to convert nitrate (NO3-) to dinitrogen (N2), it is unfortunately difficult to apply in industry due to the complexity of the processes. In particular, nitrate is difficult to functionalize because of its chemical stability. Thus, there is no organometallic catalysis to convert nitrate to useful chemicals. In this article, we present that a nickel pincer complex is effective as a bifunctional catalyst to stepwise deoxygenate NO3- by carbonylation and further to C-N coupling. By using this nickel catalysis, nitrate salts can be selectively transformed into various oximes (>20 substrates) with excellent conversion (>90%). Here, we demonstrate for the first time that the highly inert nitrate ion can be functionalized to produce useful chemicals by a new organonickel catalysis. Our results show that the NOx conversion and utilization (NCU) technology is a successful pathway for environmental restoration coupled with value-added chemical generation.

Anti-Neuroinflammatory Effect of the Ethanolic Extract of Black Ginseng through TLR4-MyD88-Regulated Inhibition of NF-κB and MAPK Signaling Pathways in LPS-Induced BV2 Microglial Cells.

Korean ginseng (Panax ginseng) contains various ginsenosides as active ingredients, and they show diverse biological activities. Black ginseng is manufactured by repeated steaming and drying of white ginseng, which alters the polarity of ginsenosides and improves biological activities. The aim of the present investigation was to examine the anti-neuroinflammatory effects of the ethanolic extract of black ginseng (BGE) in lipopolysaccharide (LPS)-induced BV2 microglial cells. Pre-treatment with BGE inhibited the overproduction of pro-inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in LPS-induced BV2 cells. In addition, BGE reduced the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) MAPK signaling pathways induced by LPS. These anti-neuroinflammatory effects were mediated through the negative regulation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) signaling pathway. Among the four ginsenosides contained in BGE, ginsenosides Rd and Rg3 inhibited the production of inflammatory mediators. Taken together, this investigation suggests that BGE represents potential anti-neuroinflammatory candidates for the prevention and treatment of neurodegenerative diseases.

"Lighting up" fluoride: cellular imaging and zebrafish model interrogations using a simple ESIPT-based mycophenolic acid precursor-based probe.

The discovery and implementation of media that derive from bioinspired designs and bear optical readouts featuring large Stokes shifts are of continued interest to a wide variety of researchers and clinicians. Myco-F, a novel mycophenolic acid precursor-based probe features a cleavable tert-butyldimethylsiloxy group to allow for fluoride detection. Myco-F exhibits high selectivity and specificity towards F- (Stokes shift = 120 nm). All measurements were performed in complete aqueous media (LOD=0.38 µM). Myco-F enables detection of fluoride ions in living HEK293 cells and localizes in the eye region (among other regions) of the zebrafish. DFT calculations support the proposed ESIPT working photomechanism.

Two-Electron-Induced Reorganization of Cobalt Coordination and Metal-Ligand Cooperative Redox Shifting Co(I) Reactivity toward CO2 Reduction.

Electrochemical reorganization of complex structures is directly related to catalytic reactivity; thus, the geometric changes of catalysts induced by electron transfer should be considered to scrutinize the reaction mechanism. Herein, we studied electron-induced reorganization patterns of six-coordinate Co complexes with neutral N-donor ligands. Upon two-electron transfer into a Co center enclosed within a bulky π-acceptor ligand, the catalytic site exhibited different reorganization patterns depending on the ligand characteristics. While a bipyridyl ligand released Co-bound solvent (CH3CN) to open a reaction site, a phenanthroline ligand caused Co-Narm (side "arm" of NNN-ligand) bond dissociation. The first electron transfer occurred in the Co(II/I) reduction step and the second electron entered the bulky π-acceptor, of which redox steps were assigned from cyclic voltammograms, magnetic moment measurements, and DFT calculations. In comparison, the Co complex of [NNNNCH3-Co(CH3CN)3](PF6)2 ([1-(CH3CN)3](PF6)2) showed a high H2 evolution reactivity (HER), whereas a series of Co complexes with bulky π-acceptors such as [NNNNCH3-Co(L)(CH3CN)](PF6)2 (L = phen ([2-CH3CN](PF6)2), bpy ([3-CH3CN](PF6)2), [NNNNCH3-Co(tpy)](PF6)2 ([4](PF6)2), and [NNNCH2-Co(phen)(CH3CN)](PF6)2 ([5-CH3CN](PF6)2)) suppressed the HER but rather enhanced the CO2 reduction reaction. The metal-ligand cooperative redox steps enabled the shift of Co(I) reactivity toward CO2 reduction. Additionally, the amine pendant attached to the NNNNCH3-ligand could stabilize the CO2 reduction intermediate through the hydrogen-bonding interaction with the Co-CO2H adduct.

The ethanolic extract of Curcuma longa grown in Korea exhibits anti-neuroinflammatory effects by activating of nuclear transcription factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.

BACKGROUND: Curcuma longa has been used as spices, food preservative, coloring material, and traditional medicine. This plant also has long been used for a variety of diseases including dyslipidemia, stomach disorders, arthritis, and hepatic diseases. The aim of the present investigation was to examine the anti-neuroinflammatory effects of the 50% ethanolic extract of C. longa in lipopolysaccharide (LPS)-induced BV2 microglial cells. METHODS: Griess reaction was employed to measure the production of nitric oxide (NO), and the levels of prostaglandin E2 (PGE2) and pro-inflammatory cytokines such as interleukin 1-beta (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) were determined by using profit ELISA kits. Western blotting was used to determine the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), mitogen activated protein kinases (MAPKs), heme oxygenase-1 (HO-1) and nuclear factor erythroid-2-related factor 2 (Nrf2). RESULTS: Pre-treatment with CLE inhibited the overproduction and overexpression of pro-inflammatory mediators including NO, PGE2, iNOS, COX-2, and pro-inflammatory cytokines such as IL-1ß, IL-6 and TNF-α in LPS-induced BV2 cells. In addition, CLE suppressed the activation of the NF-κB and three MAPK signaling pathways. Treatment with CLE induced HO-1 protein expression by activating Nrf2 pathway, and inhibiting the HO-1 expression reversed the anti-inflammatory effect of CLE. CONCLUSION: CLE showed anti-neuroinflammatory effects against LPS-induced microglial cells activation through the inhibition of production and expression of pro-inflammatory mediators by negative regulation of the NF-κB and MAPK signaling pathways. These anti-neuroinflammatory effects of CLE were mediated by HO-1/Nrf2 signaling pathway. Taken together, the present study suggests a potent effect of CLE to prevent neuroinflammatory diseases. It is necessary to perform additional efficacy evaluation through in vivo experiments.

Chemical Profiles and Antiobesity Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract in High Fat Diet Fed Mice.

The present study aimed to evaluate the antiobesity potential and synergistic effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extracts, in HFD-induced obese mice. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD + AM, HFD + LE or HFD + ALM16 (50, 100, and 200 mg/kg) daily for 5 weeks. Compared to the ND group, HFD-fed mice showed significant increases in body weight, food efficiency ratio, weights of white adipose tissues, adipocytes size, liver weight, and hepatic steatosis grade. However, ALM16 significantly reduced those increases induced by HFD. Moreover, as compared to the HFD group, the ALM16 group significantly ameliorated serum levels of lipid profiles (TG, TC, HDL, and LDL), adipokines (leptin and adiponectin), and liver damage markers (AST and ALT levels). Notably, ALM16 was more effective than AM or LE alone and had a similar or more potent effect than Garcinia cambogia extracts, as a positive control, at the same dose. These results demonstrate that ALM16 synergistically exerts anti-obesity effects based on complementary interactions between each component. Also, metabolic profiling between each extract and the ALM16 was confirmed by UPLC-QTOF/MS, and the difference was confirmed by relative quantification.

Heme compound II models in chemoselectivity and disproportionation reactions.

Heme compound II models bearing electron-deficient and -rich porphyrins, [FeIV(O)(TPFPP)(Cl)]- (1a) and [FeIV(O)(TMP)(Cl)]- (2a), respectively, are synthesized, spectroscopically characterized, and investigated in chemoselectivity and disproportionation reactions using cyclohexene as a mechanistic probe. Interestingly, cyclohexene oxidation by 1a occurs at the allylic C-H bonds with a high kinetic isotope effect (KIE) of 41, yielding 2-cyclohexen-1-ol product; this chemoselectivity is the same as that of nonheme iron(iv)-oxo intermediates. In contrast, as observed in heme compound I models, 2a yields cyclohexene oxide product with a KIE of 1, demonstrating a preference for C[double bond, length as m-dash]C epoxidation. The latter result is interpreted as 2a disproportionating to form [FeIV(O)(TMP+˙)]+ (2b) and FeIII(OH)(TMP), and 2b becoming the active oxidant to conduct the cyclohexene epoxidation. In contrast to 2a, 1a does not disproportionate under the present reaction conditions. DFT calculations confirm that compound II models prefer C-H bond hydroxylation and that disproportionation of compound II models is controlled thermodynamically by the porphyrin ligands. Other aspects, such as acid and base effects on the disproportionation of compound II models, have been discussed as well.

Validation of a Quantification Method for Curcumin Derivatives and Their Hepatoprotective Effects on Nonalcoholic Fatty Liver Disease.

Curcumin (CM), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are major curcumin derivatives found in the rhizome of turmeric (Curcuma longa L.), and have yielded impressive properties to halt various diseases. In the present study, we carried out a method validation for curcumin derivatives and analyzed the contents simultaneously using HPLC with UV detection. For validation, HPLC was used to estimate linearity, range, specificity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ). Results showed a high linearity of the calibration curve, with a coefficient of correlation (R2) for CM, DMC, and BDMC of 0.9999, 0.9999, and 0.9997, respectively. The LOD values for CM, DMC, and BDMC were 1.16, 1.03, and 2.53 ng/µL and LOQ values were 3.50, 3.11, and 7.67 ng/µL, respectively. Moreover, to evaluate the ability of curcumin derivatives to reduce liver lipogenesis and compare curcumin derivatives' therapeutic effects, a HepG2 cell model was established to analyze their hepatoprotective properties. Regarding the in vivo study, we investigated the effect of DMC, CM, and BDMC on nonalcoholic fatty liver disease (NAFLD) caused by a methionine choline deficient (MCD)-diet in the C57BL/6J mice model. From the in vitro and in vivo results, curcumin derivatives alleviated MCD-diet-induced lipid accumulation as well as high triglyceride (TG) and total cholesterol (TC) levels, and the protein and gene expression of the transcription factors related to liver adipogenesis were suppressed. Furthermore, in MCD-diet mice, curcumin derivatives suppressed the upregulation of toll-like receptors (TLRs) and the production of pro-inflammatory cytokines. In conclusion, our findings indicated that all of the three curcuminoids exerted a hepatoprotective effect in the HepG2 cell model and the MCD-diet-induced NAFLD model, suggesting a potential for curcuminoids derived from turmeric as novel therapeutic agents for NAFLD.

Pivotal role of PD-1/PD-L1 immune checkpoints in immune escape and cancer progression: Their interplay with platelets and FOXP3+Tregs related molecules, clinical implications and combinational potential with phytochemicals.

Immune checkpoint proteins including programmed cell death protein 1 (PD-1), its ligand PD-L1 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are involved in proliferation, angiogenesis, metastasis, chemoresistance via immune escape and immune tolerance by disturbing cytotoxic T cell activation. Though many clinical trials have been completed in several cancers by using immune checkpoint inhibitors alone or in combination with other agents to date, recently multi-target therapy is considered more attractive than monotherapy, since immune checkpoint proteins work with other components such as surrounding blood vessels, dendritic cells, fibroblasts, macrophages, platelets and extracellular matrix within tumor microenvironment. Thus, in the current review, we look back on research history of immune checkpoint proteins and discuss their associations with platelets or tumor cell induced platelet aggregation (TCIPA) and FOXP3+ regulatory T cells (Tregs) related molecules involved in immune evasion and tumor progression, clinical implications of completed trial results and signaling networks by phytochemicals for combination therapy with immune checkpoint inhibitors and suggest future research perspectives.

Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

Noble 3,4-Seco-triterpenoid Glycosides from the Fruits of Acanthopanax sessiliflorus and Their Anti-Neuroinflammatory Effects.

Acanthopanax sessiliflorus (Araliaceae) have been reported to exhibit many pharmacological activities. Our preliminary study suggested that A. sessiliflorus fruits include many bioactive 3,4-seco-triterpenoids. A. sessiliflorus fruits were extracted in aqueous EtOH and fractionated into EtOAc, n-BuOH, and H2O fractions. Repeated column chromatographies for the organic fractions led to the isolation of 3,4-seco-triterpenoid glycosides, including new compounds. Ultra-high-performance liquid chromatography (UPLC) mass spectrometry (MS) systems were used for quantitation and quantification. BV2 and RAW264.7 cells were induced by LPS, and the levels of pro-inflammatory cytokines and mediators and their underlying mechanisms were measured by ELISA and Western blotting. NMR, IR, and HR-MS analyses revealed the chemical structures of the nine noble 3,4-seco-triterpenoid glycosides, acanthosessilioside G-O, and two known ones. The amounts of the compounds were 0.01-2.806 mg/g, respectively. Acanthosessilioside K, L, and M were the most effective in inhibiting NO, PGE2, TNF-α, IL-1ß, and IL-6 production and reducing iNOS and COX-2 expression. In addition, it had inhibitory effects on the LPS-induced p38 and ERK MAPK phosphorylation in both BV2 and RAW264.7 cells. Nine noble 3,4-seco-triterpenoid glycosides were isolated from A. sessiliflorus fruits, and acanthosessilioside K, L, and M showed high anti-inflammatory and anti-neuroinflammatory effects.

NMR-Based Metabolomics Approach to Investigate the Effects of Fruits of Acanthopanax sessiliflorus in a High-Fat Diet Induced Mouse Model.

The prevalence of obesity is rapidly increasing and is recognized as a serious health problem. To investigate metabolic changes in an obese model after administration of Acanthopanax sessiliflorus, mice were divided into four groups: normal diet, high-fat diet (HFD), HFD with treatment fenofibrate, and A. sessiliflorus fruit extract. The liver tissue of mice was analyzed using nuclear magnetic resonance (NMR) spectrometry-based metabolomics. In multivariate statistical analyses, the HFD group was discriminated from the normal diet group, and the group fed A. sessiliflorus fruit was discriminated from the HFD group. In biomarker analysis between the HFD group and the group fed A. sessiliflorus fruit, alanine, inosine, formate, pyroglutamate, taurine, and tyrosine, with AUC values of 0.7 or more, were found. The levels of these metabolites were distinguished from the HFD mouse model. Changes in these metabolites were confirmed to act on metabolic pathways related to antioxidant activity.

Comparison of Antivirulence Activities of Black Ginseng against Methicillin-Resistant Staphylococcus aureus According to the Number of Repeated Steaming and Drying Cycles.

Korean ginseng has been widely used in Eastern medicine for thousands of years. The contents of the compounds in ginseng roots change depending on the amount of steaming and drying, and the drying method used. Black ginseng (BG) is the Korean ginseng processed by repeated steaming and drying. In this study, 5-year-old fresh Korean ginseng roots were steamed and dried 3 or 5 times, and we investigated how many cycles of steaming and drying are preferable for antivirulence activities against methicillin-resistant Staphylococcus aureus (MRSA). As a result, the antivirulence activities was increased by the treatment of BG that was steamed and dried three times, and the effect was further increased by five-time processed BG. Moreover, an ELISA showed that the TNF-α production of RAW264.7 cells stimulated by MRSA supernatants was inhibited by subinhibitory concentrations of BG extract. The expression of Hla, staphylococcal enterotoxin A (SEA), and staphylococcal enterotoxin B (SEB), an important virulence factor in the pathogenicity of MRSA, was found to decrease when bacterial cells were treated with BG extract. The antivirulence activities of BG were not simply due to pathogen growth inhibition; the BG extract was shown to decrease agrA, hla, sea, and seb expression in MRSA. Therefore, BG strongly reduces the secretion of the virulence factors produced by Staphylococcus aureus, suggesting that a BG-based structure may be used for the development of drugs aimed at staphylococcal virulence-related exoproteins. This study suggests that BG could be used as a promising natural compound in the food and pharmaceutical industry.

Correction to: The antibacterial activity and toxin production control of bee venom in mouse MRSA pneumonia model.

An amendment to this paper has been published and can be accessed via the original article.

Serum Metabonomic Research of the Anti-Hypertensive Effects of Ogaja on Spontaneously Hypertensive Rats.

Our previous studies have shown that Ogaja Acanthopanax sessiliflorus has an important role in decreasing blood pressure, but its biochemical change characteristic has not been clarified completely at the metabolic level. Therefore, in this study, a combination method of nuclear magnetic resonance (NMR) spectroscopy-based metabonomics and multivariate statistical analyses was employed to explore the metabolic changes of serum samples from spontaneously hypertensive rats treated with Ogaja extracts. In the results of multivariate statistical analysis, the spontaneously hypertensive rat (SHR) groups treated with Ogaja were separated from the SHR group. The group of SHR treated with 200 mg/kg Ogaja was clustered with the positive control (captopril) group, and the 400 and 600 mg/kg Ogaja treatment SHR groups were clustered together. Quantified metabolites were statistically analyzed to find the metabolites showing the effects of Ogaja. Succinate and betaine had variable importance in projection (VIP) scores over 2.0. Succinate, which is related to renin release, and betaine, which is related to lowering blood pressure, increased dose-dependently.

Mitigating Effects of Liriope platyphylla on Nicotine-Induced Behavioral Sensitization and Quality Control of Compounds.

In this study we investigated the mitigating effects of Liriope platyphylla Wang et Tang extract on behavioral sensitization and the quantification of its major compounds. The extract of L. platyphylla reduces the expression of tyrosine hydroxylase (TH) protein, which is increased by nicotine, back to normal levels, and increases the expression of dopamine transporter (DAT) protein, which is reduced by nicotine, back to normal levels in PC12 cells. In this study, rats received nicotine (0.4 mg/kg, subcutaneously) only for seven days and then received extract of L. platyphylla (200 or 400 mg/kg, oral) 1 h prior to nicotine administration for an additional seven days. The extract of L. platyphylla reduced locomotor activity compared to the nicotine control group in rats. The extract of L. platyphylla significantly attenuated the repeated nicotine-induced DAT protein expression in the nucleus accumbens (NAc), but there was no effect on increased TH protein expression in the dorsal striatum. These findings suggest that L. platyphylla extract has a mitigating effect on nicotine-induced behavioral sensitization by modulating DAT protein expression in the NAc. For quality control of L. plathyphylla, spicatoside A and D, which are saponin compounds, were quantified in the L. platyphylla extract. The amounts of spicatoside A and D in L. platyphylla extract obtained from ultra-high-performance liquid chromatography with tandem mass spectrometry were 0.148 and 0.272 mg/g, respectively. The identification of these compounds in L. platyphylla, which can be used for quality control, provides important information for the development of drugs to treat nicotine dependence.

Serum Metabolic Profiling Reveals Potential Anti-Inflammatory Effects of the Intake of Black Ginseng Extracts in Beagle Dogs.

Black ginseng (BG) has better health benefits than white ginseng. The intake of BG changes the levels of metabolites, such as amino acids, fatty acids, and other metabolites. However, there is no research on the effect of BG extract intake on the metabolic profile of dog serum. In this study, serum metabolic profiling was conducted to investigate metabolic differences following the intake of BG extracts in beagle dogs. The beagle dogs were separated into three groups and fed either a regular diet (RD, control), RD with a medium concentration of BG extract (BG-M), or RD with a high concentration of BG extract (BG-H). Differences were observed among the three groups after the dogs ingested the experimental diet for eight weeks. The concentrations of alanine, leucine, isoleucine, and valine changed with the intake of BG extracts. Furthermore, levels of glycine and ß-alanine increased in the BG-H group compared to the control and BG-M groups, indicating that BG extracts are associated with anti-inflammatory processes. Our study is the first to demonstrate the potential anti-inflammatory effect of BG extract in beagle dogs. Glycine and ß-alanine are proposed as candidate serum biomarkers in dogs that can discriminate between the effects of ingesting BG-H.

The antibacterial activity and toxin production control of bee venom in mouse MRSA pneumonia model.

BACKGROUND: The current antimicrobial therapy is still important for the treatment of pneumonia due to MRSA infection, but there are some limitations, including the route of administration, side effect profile, and increased microbial resistance patterns. Therefore, we investigated whether BV, which shows a strong antimicrobial effect against MRSA, would be effective in a pneumonia model. METHODS: In vitro, we checked MIC, qRT-PCR, western blot, ELISA, LDH-assay. In vivo, we checked survival rate, gross pathological change, histopathology, lung bacterial clearance assay, and the expression of inflammatory related gene. RESULTS: The minimum inhibitory concentration of BV against MRSA is 15.6 µg/ml by broth dilution method. The production of toxins and related gene were reduced by BV in MRSA. The secretion of cytokines were decreased by treatment with BV in 264.7 RAW macrophages stimulated by MRSA Also, BV protected A549 from pathogenicity of MRSA. Bee venom reduced the number of bacteria in the lungs and alleviated the symptoms of MRSA-induced pneumonia in mouse. CONCLUSION: BV inhibited the virulence of the bacterium and the number of bacterial cells present in lung tissue, thereby alleviating the symptoms of pneumonia in mice. This study suggested that BV may be a candidate substance for the treatment of pneumonia caused by MRSA infection.

LC-MS-Based Lipidomic Analysis of Serum Samples from Spontaneously Hypertensive Rats Treated with an Extract of Acanthopanax sessiliflorus Fruits.

Recently, lipidomics has revealed that many diseases are highly associated with altered lipid metabolism, as in the case of hypertension affecting serum lipid metabolism. In this study, an LC-MS-based lipidomic approach was used to profile serum lipids in spontaneously hypertensive rats (SHRs) treated with an extract of Acanthopanax sessiliflorus fruits (ASF), to elucidate the serum lipid metabolism alteration by hypertension and the treatment of a drug or ASF. First, UPLC-QTOF/MS profiled a total of 208 lipids from six pooled samples of normal controls, SHR, SHR + 100 mg/kg of drug, and SHR + ASF 200, 400, or 600 mg/kg. These six groups were differentiated by the PCA and sPLS-DA, and 120 lipid species were identified as differentially regulated lipids (DRLs) by ANOVA (p values < 0.05). Second, UPLC-QqQ/MS was used for the target profiling of 120 DRLs from individual samples of the six groups. Using an ANOVA, 67 lipids (38 TGs, 4 DGs, 17 PCs, 2 PEs, and 6 LPCs) were selected as validated DRLs. The mostly altered lipids, such as TG (62:13), TG (60:13), PC (34:4), PC (36:5), and PC (38:2), were decreased in SHR compared to the normal control, and received little by treatment with ASF. These results demonstrated the correlation between hypertension and serum lipid metabolism. Furthermore, both drug and ASF treatment similarly altered the lipid profiles of SHRs. Finally, we found that DRLs have the potential to help us to interpret the lipid metabolism of hypertension.

Protective Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract against Hepatic Steatosis in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mice.

The present study aimed to evaluate the potential synergistic and protective effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extract in a ratio of 7 : 3, against hepatic steatosis in high fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) mice. Forty-eight mice were randomly divided into eight groups and orally administered daily for 6 weeks with a normal diet (ND) or high fat diet alone (HFD), HFD with AM (HFD + 100 mg/kg AM extract), HFD with LE (HFD + 100 mg/kg LE extract), HFD with ALM16 (HFD + 50, 100, and 200 mg/kg ALM16), or HFD with MT (HFD + 100 mg/kg Milk thistle extract) as a positive control. ALM16 significantly decreased the body and liver weight, serum and hepatic lipid profiles, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL), and low-density lipoprotein-cholesterol (LDL), and serum glucose levels, compared to the HFD group. Moreover, ALM16 significantly ameliorated the HFD-induced increased hepatic injury markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT)-1. Furthermore, as compared to the mice fed HFD alone, ALM16 increased the levels of phosphorylated AMP-activated protein kinase (p-AMPK) and acetyl-CoA carboxylase (p-ACC), thereby upregulating the expression of carnitine palmitoyltransferase (CPT)-1 and downregulating the expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS). These results demonstrated that ALM16 markedly inhibited HFD-induced hepatic steatosis in NAFLD mice by modulating AMPK and ACC signaling pathways, and may be more effective than the single extracts of AM or LE.