Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Anticancer Activities of Substituted Cinnamic Acid Phenethyl Esters on Human Cancer Cell Lines

Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB assay on six different human cancer cell lines. The results indicated that in the concentration of 10 μmol·L -1 the lead compound CAPE possessed anticancer activities against human HL 60, Bel 7402, and Hela cell lines, and two other compounds possessed potent anticancer activities against Bel 7402 and Hela cell lines.

Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway

AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro and treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on alpha-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively. RESULTS CAPE inhibited the proliferation and activation of HSC-T6 cells cultured in vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors. CONCLUSION CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.

Caffeic acid phenethyl ester inhibits liver fibrosis in rats

AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester(CAPE) in rats with liver fibrosis. METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group(n = 10), a vehicle group(n = 10), a model group(n = 15), a vitamin E group(n = 10), and three CAPE groups(CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE(3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin(TBil), aminotransferase(ALT) and aspartate aminotransferase(AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde(MDA), glutathione(GSH) levels, catalase(CAT) and superoxide dismutase(SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin(α-SMA), a characteristic hallmark of activated hepatic stellate cells(HSCs), and NF-E2-related factor 2(Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats(P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group(P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group(P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group(P < 0.01). CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress.

Identification of differential proteins in colorectal cancer cells treated with caffeic acid phenethyl ester

AIM: To investigate the molecular mechanisms of the anti-cancer activity of caffeic acid phenethyl ester (CAPE).

Effect of caffeic acid phenethyl ester on proliferation and apoptosis of colorectal cancer cells in vitro

AIM:To study the effect of caffeic add phenethyl ester (CAPE) on proliferation, cell cycle, apoptosis and expression of β-catenin in cultured human colorectal cancer (CRC) cell line HCT116. METHODS: HCT116 cells were treated with CAPE at serial concentrations of 80,40,20,10,5,2.5 mg/L. The proliferative status of HCT116 cells was measured by using methaben-zthiazuron (MTT) assay. Cell cycle was analyzed by using flow cytometry (FCM) with propidium iodide (PI) labeling method. The rate of apoptosis was detected by using FCM with annexin V-FITC and PI double labeling method, β-catenin levels were determined by Western blotting, β-catenin localization in HCT116 was determined by indirect immunofluorescence. RESULTS: After HCT116 cells were exposed to CAPE (80, 40, 20, 10, 5, and 2.5 mg/L) for 24, 48, 72, 96 h, CAPE displayed a strong growth inhibitory effect in a dose- and time-dependent manner against HCT116 cells. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after HCT116 cells were exposed to CAPE (10, 5, and 2.5 mg/L) for 24 h. CAPE treatment was associated with decreased cytoplasmic β-catenin, nuclear p-catenin and a concurrent increase in β-catenin protein expression at cell-cell junctions. CONCLUSION: CAPE could inhibit HCT116 cell proliferation and induce cell cycle arrest and apoptosis. Decreased β-catenin protein expression may mediate the anti-proliferative effects of CAPE.

Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involvesβ-catenin associated signaling pathway down-regulation

AIM： To study the anti-tumor effect of caffeic acid phenethyl ester （CAPE） and the influence of CAPE on β-catenin associated signaling pathway in SW480 colorectal cancer （CRC） cells. METHODS： SW480 cells were treated with CAPE at serial concentrations. The proliferative status of cells was measured by methabenzthiazuron （MTT） assay. Cell cycle and cell apoptosis were analyzed using flow cytometry （FCM）. Western blotting assay was used to evaluate the protein level of β-catenin, c-myc and cyclinD1. β-catenin localization was determined by indirect immunofluorescence. RESULTS： CAPE displayed a strong inhibitory effect in a significant dose- and time-dependent manner on SW480 cell growth. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after SW480 cells were exposed to CAPE for 24 h. Pretreatment of SW480 cells with CAPE significantly suppressed β-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of β-catenin protein in nucleus and cytoplasm, and concurrently increased its accumulation on the surface of cell membrane. CONCLUSION： CAPE can inhibit SW480 cell proliferation by inducing cell cycle arrest and apoptosis. Decreased β-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE.

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester(CAPE), which is a potent inducer of heme oxygenase 1(HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin(SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.

Lipase-catalyzed Synthesis of Caffeic Acid Phenethyl Ester in Ionic Liquids： Effect of Specific Ions and Reaction Parameters

Caffeic acid phenethyl ester(CAPE)is a rare,naturally occurring phenolic food additive.This work systematically reported fundamental data on conversion of caffeic acid(CA),yield of CAPE,and reactive selectivity during the lipase-catalyzed esterification process of CA and phenylethanol(PE)in ionic liquids(ILs).Sixteen ILs were selected as the reaction media,and the relative lipase-catalyzed synthesis properties of CAPE were measured in an effort to enhance the yield of CAPE with high selectivity.The results indicated that ILs containing weakly coordinating anions and cations with adequate alkyl chain length improved the synthesis of CAPE.[Emim][Tf2N]was selected as the optimal reaction media.The optimal parameters were as follows by response surface methodology(RSM):reaction temperature,84.0°C;mass ratio of Novozym 435 to CA,14︰1;and molar ratio of PE to CA,16︰1.The highest reactive selectivity of CAPE catalyzed by Novozym 435 in[Emim][Tf2N]reached 64.55%(CA conversion 98.76%and CAPE yield 63.75%,respectively).Thus,lipase-catalyzed esterification in ILs is a promising method suitable for CAPE production.

Therapeutic effect of caffeic acid phenethyl ester on cerulein-induced acute pancreatitis

AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of ceruleaninduced acute pancreatitis (AP).METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 μg/kg) four times at 1-h intervals. CAPE (30 mg/kg) was given by subcutaneous injection at the beginning (CAPE 1 group) and 12 h after the last cerulein injection (CAPE 2 group). Serum amylase, lipase, white blood cell count, and tumor necrosis factor (TNF)-α levels were measured, and pancreatic histopathology was assessed. RESULTS: In the AP group, amylase and lipase levels were found to be elevated and the histopathological evaluation showed massive edema and inflammation of the pancreas, with less fatty necrosis when compared with sham and control groups. Amylase and lipase levels and edema formation decreased signif icantly in the CAPE therapy groups (P < 0001); especially in the CAPE 2 group, edema was improved nearly completely (P = 0001). Inflammation and fatty necrosis were partially recovered by CAPE treatment. The pathologicalresults and amylase level in the placebo groups were similar to those in the AP group. White blood cell count and TNF-α concentration was nearly the same in the CAPE and placebo groups.CONCLUSION: CAPE may be useful agent in treatment of AP but more experimental and clinical studies are needed to support our observation of benef icial effects of CAPE before clinical usage of this agent.

Effects of caffeic acid phenethyl ester on proliferation of vascular smooth muscle cells in rats

Objective： To investigate the inhibitory effect of caffeic acid phenethyl ester（CAPE） on the proliferation of vascular smooth muscle cells （VSMC） activated by lipopolysaccharide （LPS） and to clarify its mechanism. Methods： VSMC activated by LPS （1 mg-L^-1） were treated with CAPE at different concentrations. The inhibitory effecfs of CAPE on the proliferation of VSMC were determined by methabenzthiazuron（MTT） colorimetry. The effects of CAPE on the expression of proliferating cell nuclear antigen （PCNA） and Survivin protein in VSMC were evaluated by immunocytochemistry staining technique （SABC method）. Cell cycle was analyzed by flow cytometry（FCM） with propidiumiodide （PI） labeling method. The relative expression level of Survivin mRNA was measured with real-time quantified RT-PCR technique. Results. CAPE exerted significant inhibitory effects on. proliferation of VSMC at concentrations ranging from 5 mg·L^-1 to 80 mg·L^-1, decreased the rate of cells positive for PCNA and Survivin protein and repressed the expressioh of Survivin mRNA in a dose- and time-dependent manner （P 〈 0.05）. FCM analysis displayed that CAPE up-regulated the ratio of G0/G1 stages and reduced the percentage of VSMC in S stage （P 〈 0.05）. Conclusion： CAPE can significantly inhibit the proliferation of VSMC activated by LPS in a dose- and time-dependent manner, which may be carded out through regulating cell cycle and repressing the expression of PCNA and Survivin.

Enhancement of Lipase-catalyzed Synthesis of Caffeic Acid Phenethyl Ester in Ionic Liquid with DMSO Co-solvent

Caffeic acid phenethyl ester(CAPE) is a natural and rare ingredient with several biological activities, but its industrial production using lipase-catalyzed esterification of caffeic acid(CA) and 2-phenylethanol(PE) in ionic liquids(ILs) is hindered by low substrate concentrations and long reaction time. To set up a high-efficiency bioprocess for production of CAPE, a novel dimethyl sulfoxide(DMSO)–IL co-solvent system was established in this study.The 2%(by volume) DMSO–[Bmim][Tf2N] system was found to be the best medium with higher substrate solubility and conversion of CA. Under the optimum conditions, the substrate concentration of CA was raised 8-fold,the reaction time was reduced by half, and the conversion reached 96.23%. The kinetics follows a ping-pong bi-bi mechanism with inhibition by PE, with kinetic parameters as follows: Vmax= 0.89 mmol · min-1· g-1, Km,CA=42.9 mmol · L-1, Km,PE= 165.7 mmol · L-1, and Ki,PE= 146.2 mmol · L-1. The results suggest that the DMSO cosolvent effect has great potential to enhance the enzymatic synthesis efficiency of CAPE in ILs.

A single dose of caffeic acid phenethyl ester prevents initiation in a medium-term rat hepatocarcinogenesis model

AIM： To study of the effect of caffeic acid phenethyl ester （CAPE） on the initiation period in a medium-term assay of hepatocarcinogenesis. METHODS： Male Wistar rats were subjected to a carcinogenic treatment （CT） and sacrificed at 25^th d; altered hepatic foci （AHF） were generated efficiently. To a second group of rats a single 20 mg/kg doses of CAPE was given 12 h before initiation with CT and were sacrificed at 25^th d. We evaluated the expression of preneoplastic markers as Y-glutamyltranspeptidase （GGT） and glutathione S-transferase type pi protein （GSTp） by histochemistry, RT-PCR and Western blot analyses, respectively. We measured thiobarbituric acid reactive substances （TBARS） in homogenates of liver and used Unscheduled DNA Synthesis （UDS） assay by incorporation of [^3H] thymidine （^3HdT） in primary hepatocyte cultures （PHC）. RESULTS： At 25^th d after CT CAPE reduced the observed increase of GGT^＋AHF by 84% and liver expression ofggt mRNA by 100%. In case of the GSTp protein, the level was reduced by 90%. As indicative of oxidative stress generated by diethylnitrosamine （DEN） 12 h after its administration, we detected a 68% increase of TBARS. When CAPE was administered before DEN, it completely protected from liver TBARS induction. To have an indication of the sole effect of CAPE on initiation, two carcinogens were tested in a UDS assay in PHC, we used methyl-n-nitrosoguanidine as a direct carcinogen and DEN, as indirect carcinogen. In this assay, genotoxic damage caused by carcinogens was abolished at 5μM CAPE concentration. CONCLUSION： Our results demonstrated that CAPE possesses anti-genotoxic and antineoplastic capabilities, by an anti-oxidative and free-radical scavenging mechanism.

Ultra-fast and high-efficient synthesis of caffeic acid phenethyl ester by microwave assistant ionic liquids catalysis

Caffeic acid phenethyl ester (CAPE), a natural and rare ingredient with several biological activities, was successfully synthesized from caffeic acid (CA) and phenylethanol (PE) by microwave assistant coupled with ionic liquids (ILs) catalysis. Four ILs, acted as both solvent and catalyst in this chemical synthesis, were optimized. Among them, [Bmim] [PF6] was the best with the highest CA conversion. 95% conversion was achieved under substrate molar ratio 4:1 (PE/CA, n/n), IL content 7:1 (IL/CA, w/w), microwave power 200 W, at 135 oC for 7 min. This study might be attributed to developing new chemical reaction system to produce caffeic acid derived esters.

Caffeic acid phenethyl ester and its benzoyl derivatives:synthesis and X-ray structural analysis

Caffeic acid phenethyl ester （CAPE）, the main biologically active component of propolis, has been successfully synthesized from caffeic acid and β-bromoethylbenzene catalyzed by Na2CO3 in a mixed solvent of HMPA-CH3CN. To better understand the struc^re-activity relationship of CAPE, phenylethyl-monobenzoylcinnamate and phenylethyl-dibenzoylcinnamate were prepared. Meanwhile, the structure of phenylethyl-monobenzoylcinnamate was confirmed by single-crystal X-ray diffiaction.

Design, synthesis and pharmacological evaluation of caffeic acid phenethyl ester acylation as multifunctional neuroprotective agents against oxidative stress injury

4-Acylated or 3,4-diacylated caffeic acid phenethyl ester （CAPE） was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H202 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC 12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.

Anti-catabolic effect of caffeic acid phenethyl ester, an active component of honeybee propolis on bone loss in ovariectomized mice： a micro-computed tomography study and histological analysis

Background Osteoporosis （OP） is a common bone disease,which adversely affects life quality.Effective treatments are necessary to combat both the loss and fracture of bone.Recent studies indicated that caffeic acid phenethyl ester （CAPE） is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption.Therefore,this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography （CT） and histology.Methods Eighteen mice were prepared and evenly divided into three groups.The six mice in the sham＋PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period.Twelve mice were ovariectomized （OVX） to induce OP.Six of them in the OVX＋CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy.The other six OVX mice in OVX＋PBS group were treated with PBS.All the mice were sacrificed 4 weeks after ovariectomy.The tibias were bilaterally excised for micro-CT scan and histological analysis.The Mann-Whitney U test was used to test the statistical differences among groups.Results Bone loss occurred in OVX mice.Compared with the sham＋PBS group,mice in the OVX＋PBS group exhibited a significant decrease in bone mineral density （BMD,P ＜0.05）,bone volume fraction （BV/TV,P ＜0.01）,trabecular thickness （Tb.Th,P ＜0.05）,and trabecular number （Tb.N,P ＜0.01）,as well as a non-insignificant increase in the number of osteoclasts （N.Oc/B.Pm）.With CAPE treatment,the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation.Compared with the OVX＋PBS group,BV/TV in the OVX＋CAPE group was significantly increased by 33.9％ （P ＜0.05）.Conclusion CAPE therapy results in the protection of bone loss induced by OVX.

Phenethyl isothiocyanate as an anti-nutritional factor attenuates deoxynivalenol-induced IPEC-J2 cell injury through inhibiting ROSmediated autophagy

Deoxynivalenol(DON)is considered to be the most harmful mycotoxin that affects the intestinal health of animals and humans.Phenethyl isothiocyanate(PEITC)in feedstuff is an anti-nutritional factor and impairs nutrient digestion and absorption in the animal intestinal.In the current study,we aimed to explore the effects of PEITC on DON-induced apoptosis,intestinal tight junction disorder,and its potential molecular mechanism in the porcine jejunum epithelial cell line(IPEC-J2).Our results indicated that PEITC treatment markedly alleviated DON-induced cytotoxicity,decreasing the apoptotic cell percentage and pro-apoptotic mRNA/protein levels,and increasing zonula occludens-1(ZO-1),occludin and claudin-1 mRNA/protein expression.Meanwhile,PEITC treatment ameliorated DON-induced an increase of the inducible nitric oxide synthase(iNOS)and cyclooxygenase 2(COX-2)mRNA levels and intracellular reactive oxygen species(ROS)level,and a decrease of glutathione peroxidase 1(GPx1),superoxide dismutase 2(SOD2),catalase(CAT)and heme oxygenase 1(HO-1)mRNA levels.Additionally,PEITC treatment significantly down-regulated autophagy-related protein 5(ATG5),beclin-1 and microtubuleassociated protein 1 light chain 3B(LC3-II)mRNA/protein levels,decreased the number of green fluorescent protein-microtubule-associated protein 1 light-chain 3(GFP-LC3)puncta and phosphatidylinositol 3 kinase(PI3K)protein expression,and up-regulated phospho-protein kinase B(p-Akt)and phospho-mammalian target of rapamycin(p-mTOR)protein expression against DON.However,the activation of autophagy by rapamycin,an autophagy agonist,abolished the protective effects of PEITC against DON-induced cytotoxicity,apoptosis and intestinal tight junction disorder.Collectively,PEITC could confer protection against DON-induced porcine intestinal epithelial cell injury by suppressing ROSmediated autophagy.

连翘叶的化学成分研究

目的研究连翘叶的化学成分。方法采用硅胶柱色谱,葡聚糖凝胶柱色谱和高效液相色谱等方法进行分离,根据MS和NMR等数据进行化合物结构鉴定。结果从连翘叶中共分离鉴定了7个化合物,分别鉴定为对羟基苯乙基-O-β-D-葡萄糖苷(1)、2-(4-羟基-3-甲氧基苯基)-乙基-O-β-D-葡萄糖苷(2)、(+)-8-羟基松脂醇-4-O-β-葡萄糖苷(3)、异樱花素-5-O-芸香糖苷(4)、山柰酚(5)、槲皮素(6)和芦丁(7)。结论化合物1~4为首次从连翘叶中分离鉴定。

咖啡酸苯乙酯对HepG2细胞氧化应激和脂质代谢的调节作用

咖啡酸苯乙酯(caffeic acid phenethyl ester,CAPE)是来源于蜂胶中的一种天然多酚物质,具有良好的调节脂代谢生物活性,但其调节脂代谢的分子机制尚不明确,本研究利用CAPE处理油酸诱导的人肝脏肿瘤细胞HepG2,通过转录组学探讨其在细胞水平上改善脂代谢的作用与机制。结果表明,与高脂肪组相比,经过CAPE干预后的细胞脂质积累情况得到明显的改善,转录组水平上共筛选出3270个差异表达基因(differentially expressed genes,DEGs),其中表达上调的DEGs有1351个,表达下调的DEGs有1919个。经京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)功能注释分析发现,CAPE处理后的DEGs显著注释到脂质代谢相关通路上。由KEGG信号通路富集分析显示,富集较显著的信号通路为HIF-1α通路和脂肪酸分解代谢通路,其中CAPE组HIF-1α、PPARα、CPT1A、FABP5等基因表达水平比高脂肪组分别提高了0.326、0.661、1.039、1.598倍。综上,CAPE可能通过HIF-1α通路改善高脂细胞氧化应激,并通过PPARα和脂肪酸氧化分解途径改善高脂诱导细胞的脂代谢紊乱。本实验可为CAPE调节脂代谢的分子机制及调节高脂膳食脂代谢紊乱的深入研究提供一定的理论参考。