Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide with complex pathogenesis and no approved specific therapy. Siraitia grosvenorii is a widely used medicinal and edible herb, yet its efficacy and underlying mechanisms against MAFLD remain poorly defined. This study explored the protective effects and potential mechanisms of aqueous extract of Siraitia grosvenorii (AESG) on MAFLD. Based on ultra-high-performance liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) analysis, 38 components in AESG were tentatively assigned, with tetracyclic triterpene saponins being the most abundant. In high-fat diet (HFD)-induced MAFLD mice, AESG significantly attenuated body weight gain, reduced plasma total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C) levels, and dramatically decreased hepatic triglyceride (TG) accumulation from 0.0141 mmol/g in the model group to 0.0063 mmol/g in the low-dose AESG group, corresponding to a reduction of 55.00%. AESG also alleviated plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and improved hepatocyte steatosis. Furthermore, AESG restored HFD-induced gut dysbiosis by enriching beneficial bacteria including Akkermansia and suppressing harmful bacteria such as Ruminococcus. In free fatty acids (FFA) stimulated HepG2 cells, AESG suppressed de novo lipogenesis via downregulating Fatty Acid Synthase (FASN), Acetyl-CoA Carboxylase (ACC) and Sterol Regulatory Element-Binding Protein 1c (SREBP1c), and enhanced antioxidant capacity via activating the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase 1 (HO-1)/Sirtuin 1 (SIRT1) pathway, thereby attenuating lipid accumulation and oxidative stress. In conclusion, AESG ameliorates MAFLD by inhibiting lipogenesis, improving oxidative stress, and regulating gut microbiota. These findings support Siraitia grosvenorii as a promising natural dietary intervention for MAFLD prevention and adjuvant therapy.

Those minor, even trace natural products sometimes exhibit exciting activities and possess unique structures; however, it is challenging to pursue and identify such components using routine LC-MS/MS platforms attributing to their low distribution levels in herbs, the overlapping effects from the abundant ingredients and the high-level structural diversity. Here, an off-line two-dimensional liquid chromatography hook up hybrid ion trap time-of-flight mass spectrometry program was exploited to facilitate the exposure of those minor components in chromatographic domain and to acquire high-resolution multi-stage mass spectra, and the less abundant 2-(2-phenylethyl)chromone (PEC) oligomers from Chinese agarwood that is one of the most precious herbal medicines were concerned to illustrate and assess the applicability towards capturing and structurally annotating those minor components. The mass fragmentation pathways of PEC dimers, in particular the linkage fission between monomers, were proposed by assaying eighteen authentic compounds that covered different conjugation manners, and subsequently applied for the tentative structural identification of observed components. Thereafter, targeted purification was conducted to generate eight new, trace PEC dimers to justify the annotated structures. As a result, heterocyclic ring fission was the diagnostic fragmentation pathways for PEC dimers. In total, 199 PECs were discovered and characterized, consisting of 74 dimers and five trimers. Noteworthily, after structural identification with NMR assays, the confirmative structures of those eight new PEC dimers agreed well with the identities suggested by mass fragmentation rules. Above all, PEC derivatives, notably trace oligomers, in Chinese agarwood were profiled in depth, resulting in a number of interesting structures.

Fifteen previously undescribed flavan derivatives (1-15), along with 13 known analogues (5a, 16-24) were isolated from the fruits of Daemonorops draco Bl. Six pairs of isomers (1a/1b, 2a/2b, 3a/3b, 4a/4b, 6a/6b, and 18a/18b) were resolved by using chiral-phase HPLC separation. Their structures were elucidated by spectroscopic data analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1a/1b possess an unusual spiro[benzofuran-2,4'-chromen] skeleton, and compounds 2a/2b feature a rare 2,5-methanobenzo[d][1,3]dioxepan moiety in their structures. Compunds 16 and 17 were isolated from a natural source for the first time. All the isolates were evaluated for their protective effects on the human umbilical vein endothelial cells (HUVECs) injury induced by oxygen-glucose deprivation (OGD). Among them, compounds 2a, 2b, 18a, 18b, 20a, 20b, 23, and 24 exhibited significant protection against OGD-induced HUVECs injury. Notably, compound 2b rescued HUVECs from OGD-induced injury by inhibiting apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE:Chinese agarwood (Aquilaria sinensis) has been a traditional treatment for digestive disorders in South and East Asia. While sesquiterpenes are recognized as the key active constituents of Chinese agarwood, the efficacy and mechanism of the sesquiterpene-enriched extract of Chinese agarwood (PEE) on bile reflux gastritis (BRG) remain unclear. AIM OF THE STUDY:To explore the protective impact of PEE against BRG and unveil its underlying mechanism in suppressing apoptosis of gastric mucosal cells. MATERIALS AND METHODS:A taurocholic acid (TCA)-induced BRG mouse model was used to assess PEE's protective effects on gastric mucosa histopathology. Transcriptomic analysis was conducted to identify the key signaling pathways affected by PEE. The impact of PEE on apoptosis modulation and Wnt/β-catenin signaling in GES-1 cells was examined. Additionally, the influence of PEE on the Wnt/β-catenin pathway in BRG mouse gastric mucosa was evaluated. RESULTS:PEE substantially improved gastric tissue damage and inflammation in BRG mice. Transcriptomic analysis revealed that PEE modulates genes linked to apoptosis and the Wnt/β-catenin pathway. In TCA-induced GES-1 cells, PEE enhanced cell viability and mitigated apoptosis via the Wnt/β-catenin pathway, a process potentially mediated by IWP-2, an antagonist of this pathway. Similar regulatory effects were noted in the gastric mucosa of BRG mice. CONCLUSION:Our research suggests that PEE exerts a protective effect on the gastric tissue through modulating the Wnt/β-catenin pathway to combat apoptosis, which highlights the potential of PEE as a natural remedy for BRG and warrants further investigation into its therapeutic benefits.

ETHNOPHARMACOLOGICAL RELEVANCE:Sanguis draconis act traditional Chinese medicine has now been used clinically for the treatment of cardiovascular diseases, and the polyphenol are recognized as their main active ingredients. AIM OF THE STUDY:Given that flavonoids have been identified as the primary active ingredients of Sanguis draconis, this research intends to explore the anti-atherosclerotic effect and underlying mechanism of action of (2S)-5-methoxy-6-methyl-flavan-7-ol (XJ8) in Sanguis draconis. MATERIALS AND METHODS:Atherosclerosis was induced in the aortic sinus of ApoE-/- mice via a high-fat diet, and the protective efficacy of XJ8 against atherosclerosis was examined. Network pharmacology was used to explore the potential target of XJ8 in the treatment of atherosclerosis. An endothelial cell model was established using nitric oxide (NO) to initiate cellular inflammatory responses and monocyte-endothelial cell adhesion, wherein the effects and the underlying mechanism of XJ8 on cellular adhesion were observed. RESULTS:This study demonstrated that XJ8 attenuated the atherosclerotic burden in the aortic sinus of the high-fat diet-induced ApoE-/- mice, concurrently reducing body fat levels. Network pharmacology analysis identified potential targets of action of XJ8, predominantly involving inflammatory pathways. Subsequent investigations revealed that XJ8 treatment remarkably suppressed NO-induced monocyte-endothelial cell adhesion by downregulating intercellular adhesion molecule-1 (ICAM-1) expression. Mechanistically, XJ8 inhibited the NO-induced endothelial inflammation through the regulation of JNK/Stat3 and NF-κB/IκBα pathways. CONCLUSION:This study demonstrates that XJ8 inhibits intercellular adhesion by downregulating ICAM-1 expression through the NF-κB/IκBα and JNK/Stat3 signaling pathways, thereby ameliorating atherosclerosis. These mechanistic insights offer novel therapeutic strategies for clinical atherosclerosis management.

The hypothalamus plays a fundamental role in controlling lipid metabolism through neuroendocrine signals. However, there are currently no available drug targets in the hypothalamus that can effectively improve human lipid metabolism. In this study, we found that the antimalarial drug artemether (ART) significantly improved lipid metabolism by specifically inhibiting microglial activation in the hypothalamus of high-fat diet-induced mice. Mechanically, ART protects the thyrotropin-releasing hormone (TRH) neurons surrounding microglial cells from inflammatory damage and promotes the release of TRH into the peripheral circulation. As a result, TRH stimulates the synthesis of thyroid hormone (TH), leading to a significant improvement in hepatic lipid disorders. Subsequently, we employed a biotin-labeled ART chemical probe to identify the direct cellular target in microglial cells as protein kinase Cδ (PKCδ). Importantly, ART directly targeted PKCδ to inhibit its palmitoylation modification by blocking the binding of zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5), which resulted in the inhibition of downstream neuroinflammation signaling. In vivo, hypothalamic microglia-specific PKCδ knockdown markedly impaired ART-dependent neuroendocrine regulation and lipid metabolism improvement in mice. Furthermore, single-cell transcriptomics analysis in human brain tissues revealed that the level of PKCδ in microglia positively correlated with individuals who had hyperlipemia, thereby highlighting a clinical translational value. Collectively, these data suggest that the palmitoylation of microglial PKCδ in the hypothalamus plays a role in modulating peripheral lipid metabolism through hypothalamus-liver communication, and provides a promising therapeutic target for fatty liver diseases.

Background: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated. Purpose: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation. Study Design and Methods: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages. Results: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPAR gamma. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages. Conclusions: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.

Plasma phospholipid transfer protein (PLTP) is a risk factor for cardiovascular diseases. Sphingosine-1-phosphate (S1P), carried by high-density lipoprotein (HDL), is a potent lipid mediator and is also associated with cardiovascular diseases. We found that germline Pltp gene knockout (KO) mice have decreased circulating S1P without influencing apoM, a major S1P carrier on HDL. We then hypothesized that, like apoM, PLTP is another S1P carrier. We established inducible Pltp-KO, Apom-KO, and Pltp/Apom double KO mice and measured plasma lipoprotein and S1P levels under different diets. We found that PLTP deficiency, and the double deficiency have a similar effect on HDL reduction. Importantly, we found that all mice have about 50% reduction in plasma S1P levels, compared to WT mice, and PLTP deficiency significantly reduces apoM levels (about 40%), while apoM deficiency has no effect on PLTP activity, indicating that PLTP depletion reduces S1P through HDL reduction. To further evaluate this HDL reduction-mediated effect, we overexpressed PLTP which also caused a reduction of HDL. We found that the overexpression reduces S1P and apoM as well as apoA-I, a major apolipoprotein on HDL. Furthermore, we found that albumin (another reported S1P carrier) deficiency in mice has no effect on plasma S1P. We also found that the influence of PLTP on HDL may not require its direct binding to the particle. In conclusion, PLTP is not a direct S1P carrier. PLTP depletion or overexpression in adulthood dramatically reduces plasma S1P through HDL reduction. ApoM, but not albumin, deficiency reduces plasma S1P levels.

Ethnopharmacological relevance: Chinese agarwood, derived from the Aquilaria sinensis (Lour.) Gilg (Thymelaea-ceae), has a long history of use in Traditional Chinese Medicine for the management of cardiovascular disease. However, the specific active ingredients responsible for its impact on atherosclerosis are yet to be fully understood.Aim of the study: The aim of this study is to investigate the anti-atherosclerotic effectiveness of the 2-(2-phe-nylethyl)chromone-enriched extract derived from Chinese agarwood (CPE) through the ER stress-mediated CD36 pathway.Materials and methods: To assess the effectiveness of CPE, an atherosclerotic mouse model was established using ApoE- /-mice with a high-fat diet. Then we assessed the impact of CPE on lipid accumulation in THP-1 macrophages that were exposed to oxLDL. Subsequently, the effect of CPE on the expression of CD36 and markers related to ER stress was characterized.Results: Our in vivo research confirmed that CPE effectively reduces the formation of aortic plaques in athero-sclerotic ApoE-/-mice. Additionally, our in vitro study observed that CPE inhibits the uptake of oxLDL and hinders the generation of foam cells. This effect is achieved by downregulating the level of CD36 in macrophages. Furthermore, our study revealed that the increase in CD36 expression, resulting from oxLDL exposure, is governed by the activation of JNK1/2/3 signaling pathways and the initiation of ER stress.Conclusion: CPE demonstrated significant efficacy to inhibit the atherosclerosis. The ER stress/P-JNK/PPAR gamma/ CD36 signaling pathway plays critical involvement in modulating the foam cell formation in vitro and in vivo. These findings underscore the efficacy of CPE as a viable therapeutic intervention for the treatment of atherosclerosis.

This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.

目的 研究没药(地丁树Commiphora myrrha的干燥树脂)的化学成分.方法 采用硅胶、ODS、Sephadex LH-20柱色谱和半制备高效液相色谱技术对没药的化学成分进行分离纯化,结合理化性质和NMR、MS等谱学数据进行结构鉴定.结果 从没药正己烷部位共分离得到了 8个倍半萜类化合物,分别鉴定为(4R,5S)-呋喃杜松-6(1),7(8),9(10)-三烯-5-醇乙酸酯(1)、(1E,3S,4R,8S)-吉玛-3-甲氧基-8-羟基-1,10(15),7(11)-三烯-6-羰基-8,12-内酯(2)、gajutsulactone A(3)、1-hydroxyeudesma-3,7(11)-dien-8-one(4)、1-hydroxyeudesma-4(14),7(11)-dien-8-one(5)、5β-10α-hydroxy-2α-methoxy-6-oxoguaia-7(11),8-dien-8,12-olide(6)、(2R,4R,5S)-2-甲氧基-5-乙酰基-呋喃吉玛-1(10)E-烯-6-酮(7)、1(10)Z,4Z-蓬莪术二烯-6-酮(8).结论 化合物1和2为新化合物,命名为去甲氧基没药萜烯B和没药萜G.化合物3～5为首次从没药属植物中分离得到.化合物5对人肝癌HepG2细胞增殖具有明显的抑制作用,其半数抑制浓度(median inhibition concentration,IC50)为(4.43±1.39)μmol/L.

Abstract Two pairs of flavonoid enantiomers (1a/1b and 2a/2b) together with three known analogues (3–5) were isolated from the heartwood of Dalbergia odorifera T. Chen. Their structures were elucidated by extensive spectroscopic analysis (1 D and 2 D NMR, UV, IR, and HRMS) and experimental and calculated ECD data. Compound 2 features an unusual 2-methyl-3(2H)-furanone moiety forming the C-ring of flavonoid, and its putative biosynthetic pathway is also proposed. Compounds 3‒5 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values of 14.7 ± 0.3 μM, 40.2 ± 1.1 μM, and 3.2 ± 0.1 μM, respectively. Graphical Abstract

Eleven undescribed isoquinoline analogues, namely edulisines A-K, along with sixteen known alkaloids, were isolated from the whole plants of Corydalis edulis. The structures of the isolated alkaloids were established on the basis of extensive spectroscopic data (1D and 2D NMR, UV, IR, and HRESIMS). Their absolute configurations were determined by single-crystal X-ray crystallographic analysis and ECD. Compounds (+)-1 and (-)-1 are a pair of undescribed isoquinoline alkaloids bearing a unique coupled pattern of coptisine and ferulic acid via Diels-Alder [4 + 2] cycloaddition, while compounds (+)-2 and (-)-2 feature benzo [1,2-d:3,4-d]bis [1,3]dioxole moiety. Compounds (+)-2, (-)-2, (-)-5, 10, 13, 15, 20, 22, and 23 significantly triggered the secretion of insulin in the HIT-T15 cells at a concentration of 40 mu M.

目的 研究普洱茶素Ⅱ对高脂血症诱发动脉硬化ApoE基因敲除小鼠(ApoE-/-)的治疗效果及作用机制.方法 ApoE-/-小鼠通过喂养高脂饲料建立动脉粥样硬化动物模型,造模成功后将小鼠随机分为对照组、模型组、阿托伐他汀(30 mg/kg)组和普洱茶素Ⅱ低、高剂量(50、100mg/kg)组,给药6周后检测小鼠血浆总胆固醇(total cholesterol,TC)、三酰甘油(triglycerides,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)和非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol,non-HDL-C)水平,以及主动脉流出道斑块面积等指标的差异.体外培养人脐静脉内皮细胞HUVEC和人外周血单核细胞THP-1,检测普洱茶素Ⅱ对氧化低密度脂蛋白(oxidized low density protein,ox-LDL)诱发单核与内皮细胞黏附的影响,利用Western blotting对蛋白激酶B(protein kinase B,Akt)/核因子-κB(nuclear factor-κB,NF-κB)/血管细胞黏附因子(vascular cell adhesion molecule-1,VCAM-1)通路相关蛋白表达进行检测.结果 普洱茶素Ⅱ显著抑制了高脂饮食诱导ApoE-/-小鼠的体质量、肝脏质量、肝脏指数、附睾脂肪质量和附睾脂肪指数(P＜0.05、0.01),降低血浆TC、TG、non-HDL-C水平(P＜0.05、0.01),升高HDL-C水平(P＜0.05),减少主动脉流出道脂质沉积.体外实验证实,普洱茶素Ⅱ显著抑制HUVEC与THP-1细胞间的黏附(P＜0.05),抑制ox-LDL诱导的HUVEC细胞中VCAM-1、单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)和Akt/NF-κB通路相关蛋白表达(P＜0.05、0.01).结论 普洱茶素Ⅱ能够显著改善ApoE-/-小鼠的肥胖、脂代谢紊乱、主动脉斑块沉积,通过调控Akt/NF-κB/VCAM-1通路抑制内皮细胞与单核细胞的黏附,进而抑制动脉粥样硬化的发生与发展.

This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.

Six previously unprecedented 2-(2-phenylethyl)chromone-sesquiterpene hybrids, aquisinenins A-F (1 - 6), were isolated from the resinous wood of Aquilaria sinensis by a LC-MS-guided fractionation procedure. Their structures were determined by extensive spectroscopic analysis (1D and 2D NMR, UV, IR, and HRMS) and experimental and computed ECD data. Compounds 1 - 6 were rare dimeric 2-(2-phenylethyl)chromone-sesquiterpene derivatives featuring 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone hybridized with different sesquiterpene (eudesmane/guaiane type) moieties via ester bond. Furthermore, all the isolated compounds were evaluated for their protective effects on taurocholic acid (TCA)-induced GES-1 cell injury. The most effective aquisinenin F (6) was used to elucidate the involved mechanism on protection against TCA-induced gastric mucosal damage. Our results indicated that 6 protected against gastric mucosal cell insult by downregulation of the ER stress triggered by TCA.

We appreciate the positive comment, from Drs. Menno Hoekstra, Ezra J. van der Wel, and Miranda Van Eck, on our recent work of PLTP deficiency-mediated atherosclerosis regression [ [1] Zhang K. Zheng J. Chen Y. Dong J. Li Z. Chiang Y.P. He M. Huang Q. Tang H. Jiang X.C. Inducible phospholipid transfer protein deficiency ameliorates atherosclerosis. Atherosclerosis. 2021; 324: 9-17 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ]. We agree that the lesion regression effect observed by us can also be attributed to the effect of PLTP deficiency specifically in macrophages, although the mechanism remains unclear. Atherosclerosis regression is associated with both infiltration of new leukocytes into the plaque and a shift in macrophage polarization towards a more migratory phenotypeAtherosclerosisVol. 356PreviewIn light of our mission to find novel therapeutic targets to stimulate atherosclerotic lesion regression, we have reviewed with great interest the data presented by Zhang et al. in Atherosclerosis which suggest that global inhibition of PLTP activity facilitates the disappearance of macrophages from regressing atherosclerotic lesions [1]. Full-Text PDF Inducible phospholipid transfer protein deficiency ameliorates atherosclerosisAtherosclerosisVol. 324PreviewAtherosclerosis progression and regression studies are related to its prevention and treatment. Although we have gained extensive knowledge on germline phospholipid transfer protein (PLTP) deficiency, the effect of inducible PLTP deficiency in atherosclerosis remains unexplored. Full-Text PDF

BACKGROUND:Injury of gastric epithelial cells is one of the most important pathological features of bile reflux gastritis. Chinese agarwood (the resinous heartwood of Aquilaria sinensis) has been used to treat stomach problems for thousands of years in China. However, the pathological mechanism of epithelial cells death induced by bile acids and the therapeutic target of Chinese agarwood for improving bile reflux gastritis have not yet been fully clarified. PURPOSE:This study aimed to investigate the pro-apoptotic effect of taurocholic acid (TCA) by regulating the ER stress pathway. Moreover, the role of Chinese agarwood 2-(2-phenylethyl)chromone-enriched extract (CPE) to inhibit gastric epithelial cell death induced by TCA was also been demonstrated. METHODS:We adopted human gastric epithelial GES-1 cells to explore the mechanism of TCA-induced cell death in vitro. Then the cell viability, apoptosis rate, and protein expressions were evaluated to explore the protective effects of CPE on GES-1 cells by TCA injury. The therapeutic effect of CPE on bile reflux gastritis was further confirmed by the bile reflux mice in vivo. RESULTS:Our results demonstrated that TCA activated GES-1 cell apoptosis by increased cleavage of caspase-7 and PARP. Further experiments showed that TCA up-regulated endoplasmic reticulum (ER) stress, subsequently triggered the apoptosis of the epithelial cells. Our research explored that CPE is the main effective fraction in Chinese agarwood by preventing the TCA-induced gastric epithelial cell injury. CPE effectively suppressed GES-1 cell apoptosis activated by TCA through inhibiting Perk/eIF2α/CHOP pathway. The anti-apoptotic effect of CPE on gastric mucosa had also been confirmed in vivo. Moreover, the main effective components in CPE corresponding to the protection of epithelial cells were also been identified. CONCLUSION:Our finding suggested that CPE recovered the TCA-induced epithelial cell apoptosis by mediating the activation of ER stress, which explored potential medicine to treat bile reflux gastritis.

Seven undescribed sesquiterpenoid dimers, commiphomyrones A - G, together with three known analogs, were isolated from the resin of Commiphora myrrha Engl.. The structures of the undescribed compounds were elucidated based on a comprehensive analysis of spectroscopic data (NMR, UV, IR, and MS), and the absolute configurations were defined by comparing the experimental and calculated ECD spectra as well as by performing Xray crystallographic analysis. All the isolated dimeric sesquiterpenoids feature a 7-oxabicyclo [2.2.1] hept-2-ene moiety formed by the [4 + 2] cycloaddition of two sesquiterpenoids. Commiphomyrones C and G and commiphoratone D showed cytotoxic activity against the HGC-27 cell line with IC50 values of 22.76, 25.01, and 27.51 mu M, respectively.

Four new phenolic glucosides, cannabifolins G–J (1–4), together with four known ones (5–8), were isolated from the leaves of Vitex negundo var. cannabifolia. Their structures were established by comprehensive analysis of 1D and 2D NMR data and comparison of their spectroscopic and physical data with the literature values. Compound 7 exhibited weak inhibition of nitric oxide production stimulated by lipopolysaccharide in BV‐2 microglial cells with IC50 value of 132.8 μM.