Atorvastatin attenuates TNF-α-induced increase of glucose oxidation through PGC-1α upregulation in cardiomyocytes

Recent studies have shown that atorvastain has anti-inflammatory effect and can prevent cardiac hypertrophy. The development of cardiac hypertrophy and dysfunction is associated with an increase in cardiac glucose utilization. In this study, we investigated the effect of atorvastatin on glucose oxidation in tumor necrosis factor α (TNF-α)-stimulated cardiomyocytes (H9c2 cells) and the potential role of peroxisome proliferation-activated receptor coactivator 1α (PGC-1α) in this effect. Exposure of H9c2 cells to TNF-α inhibited the expressions of PGC-1α, pyruvate dehydrogenase kinase 4, and carnitine palmityl transferase 1 and induced a significant increase in glucose oxidation rate. However, the effects of TNF-α were significantly reversed by atorvastatin. Selective silence of PGC-1α in H9c2 cells resulted in the downregulation of pyruvate dehydrogenase kinase 4 and carnitine palmityl transferase 1 and further increased the TNF-α-induced glucose oxidation. Interestingly, the effect of atorvastatin on PGC-1α was almost abolished by mevalonate and partially by farnesol but not by geranylgeraniol. In conclusion, atorvastatin inhibits TNF-α-induced glucose oxidation through PGC-1α upregulation in cardiomyocytes, which might be associated with the regulation of isoprenoid metabolites.     

GJA1-20k attenuates Ang II-induced pathological cardiac hypertrophy by regulating gap junction formation and mitochondrial function

Cardiac hypertrophy(CH)is characterized by an increase in cardiomyocyte size,and is the most common cause of cardiac-related sudden death.A decrease in gap junction(GJ)coupling and mitochondrial dysfunction are important features of CH,but the mechanisms of decreased coupling and energy impairment are poorly understood.It has been reported that GJA1-20k has a strong tropism for mitochondria and is required for the trafficking of connexin 43(Cx43)to cell–cell borders.In this study,we investigated the effects of GJA1-20k on Cx43 GJ coupling and mitochondrial function in the pathogenesis of CH.We performed hematoxylin–eosin(HE)and Masson staining,and observed significant CH in 18-week-old male spontaneously hypertensive rats(SHRs)compared to age-matched normotensive Wistar-Kyoto(WKY)rats.In cardiomyocytes from SHRs,the levels of Cx43 at the intercalated disc(ID)and the expression of GJA1-20k were significantly reduced,whereas JAK-STAT signaling was activated.Furthermore,the SHR rats displayed suppressed mitochondrial GJA1-20k and mitochondrial biogenesis.Administration of valsartan(10 mg·kg^?1.d^?1,i.g.,for 8 weeks)prevented all of these changes.In neonatal rat cardiomyocytes(NRCMs),overexpression of GJA1-20k attenuated Ang II-induced cardiomyocyte hypertrophy and caused elevated levels of GJ coupling at the cell–cell borders.Pretreatment of NRCMs with the Jak2 inhibitor AG490(10μM)blocked Ang II-induced reduction in GJA1-20k expression and Cx43 gap junction formation;knockdown of Jak2 in NRCMs significantly lessened Ang II-induced cardiomyocyte hypertrophy and normalized GJA1-20k expression and Cx43 gap junction formation.Overexpression of GJA1-20k improved mitochondrial membrane potential and respiration and lowered ROS production in Ang II-induced cardiomyocyte hypertrophy.These results demonstrate the importance of GJA1-20k in regulating gap junction formation and mitochondrial function in Ang II-induced cardiomyocyte hypertrophy,thus providing a novel therapeutic strategy for patients with cardiomyocyte hypertrophy.     

Curcumin attenuates isoniazid-induced hepatotoxicity by upregulating the SIRT1/PGC-1α/NRF1 pathway

As a serious infectious disease, tuberculosis threatens global public health. Isoniazid is the first-line drug not only in active tuberculosis but also in its prevention. Severe hepatotoxicity greatly limits its use. Curcumin, extracted from turmeric, has been found to relieve isoniazid-induced hepatotoxicity. However, the mechanism of isoniazid-induced hepatotoxicity and the protective effects of curcumin are not yet understood completely. We established both cell and animal models about isoniazid-induced hepatotoxicity and investigated the new mechanism of curcumin against isoniazid-induced liver injury. The experimental data in our study demonstrated that curcumin ameliorated isoniazid-mediated liver oxidative stress. The protective effects of curcumin were demonstrated and confirmed to be correlated with upregulating SIRT1/PGC-1α/NRF1 pathway. Western blot revealed that while inhibiting SIRT1 by the siRNA1 (a SIRT1 inhibitor), the expressions of SIRT1, PGC-1α/Ac-PGC-1α, and NRF1 decreased, and the protective effect that curcumin exerted on isoniazid-treated L-02 cells was significantly attenuated. Furthermore, curcumin improved liver functions and reduced necrosis of the isoniazid-treated BALB/c mice, accompanied by downregulating oxidative stress and inflammation in liver. Western blot revealed that curcumin treatment activates the SIRT1/PGC-1α/NRF1 pathway in the isoniazid-treated BALB/c mice. In conclusion, we found one mechanism of isoniazid-induced hepatotoxicity downregulating the SIRT1/PGC-1α/NRF1 pathway, and curcumin attenuated this hepatotoxicity by activating it. Our study provided a novel approach and mechanism for the treatment of isoniazid-induced hepatotoxicity.     

Amlodipine inhibits TNF-α production and attenuates cardiac dysfunction induced by lipopolysaccharide involving PI3K/Akt pathway

Calcium channel blockers (CCBs) are widely used in the therapy of cardiovascular diseases. Recent studies have shown that several CCBs exerted distinct anti-inflammatory effect in myocardial dysfunction models. The purpose of the present study was to evaluate therapeutic effect and possible mechanism of action of amlodipine, one of the widely used CCBs, on rat cardiac dysfunction during sepsis induced by lipopolysaccharide (LPS). Pretreatment of the rats with amlodipine (10 or 30 mg/kg, i.v.) delayed the fall of mean arterial blood pressure caused by LPS. Amlodipine also significantly inhibited the elevation of plasma tumor necrosis factor α (TNF-α) and decreased levels of inducible nitric oxide synthase (iNOS) in response to LPS challenge. To investigate the mechanism of the action of amlodipine, neonatal rat cardiomyocytes were used as a model. Amlodipine concentration-dependently decreased the release of TNF-α and iNOS protein expression, and suppressed the degradation and phosphorylation of inhibitor of κB-α (IκB-α) in LPS-activated neonatal rat cardiomyocytes. Further studies revealed that amlodipine markedly activated phosphatidylinositiol 3-kinase (PI3K) and Akt, downstream of the PI3K signal cascade. Application of PI3K inhibitors, wortmannin and LY294002 attenuated the depression of TNF-α and iNOS expression by amlodipine in LPS-induced cardiomyocytes. These findings may explain some cardioprotective effects of amlodipine in LPS-mediated sepsis and suggest that the inhibition of TNF-α and iNOS expression by amlodipine is, at least in part, dependent on PI3K/Akt signaling pathway.     

Stachydrine ameliorates isoproterenol-induced cardiac hypertrophy and fibrosis by suppressing inflammation and oxidative stress through inhibiting NF-κB and JAK/STAT signaling pathways in rats

Cardiac hypertrophy (CH), as one of the major causes of morbidity and mortality in the world, has become an independent and predictive risk factor for adverse cardiovascular events. However, progress in treatment remains sluggish in recent years. Therefore, compounds derived from non-toxic nature plants are urgently needed. Stachydrine (STA), which is isolated from Leonurus, has various activities, including resistance to cardiovascular disease, but little is known about its effect on CH or the mechanisms. We herein investigated the effect of STA on isoproterenol-induced CH and the underlying mechanisms. Treatment with STA significantly increased the ratios of heart weight/body weight, left ventricle weight/body weight and the cross-sectional areas of cardiomyocytes. In addition, STA significantly decreased the mRNA levels of atrial natriuretic peptide, B-type natriuretic peptide and β-myosin heavy chain. Furthermore, isoproterenol-induced fibrosis in rats receiving STA was significant attenuated, as evidenced by decreased ratio of fibrotic area/total area and decreased mRNA levels of collagens I and III. Given down-regulation of interleukin-6, tumor necrosis factor-α, interferon-γ (IFN-γ) and IFN-1β, treatment with STA significantly reversed the expressions of pro-inflammatory induced by isoproterenol. Moreover, STA attenuated the oxidative stress level in serum of isoproterenol-induced CH rats, as shown by increased activity of superoxide dismutase and decreased malondialdehyde level. STA inhibited the expressions of phosphorylated IκBα, NF-κB p65, JAK2 and STAT3 in vivo. Thus, both NF-κB and JAK/STAT signalings played essential roles in mediating the anti-CH effect of STA. Collectively, STA has a potent protective effect on isoproterenol-induced CH, with therapeutic implication for CH.     

Neferine attenuates development of testosterone-induced benign prostatic hyperplasia in mice by regulating androgen and TGF-β/Smad signaling pathways

Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear.A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment.1–100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.     

Isochlorogenic acid A attenuates progression of liver fibrosis through regulating HMGB1/TLR4/NF-κB signaling pathways

OBJECTIVE Liver fibrosis is a chronic damage process related to the further progression of hepatic cirrhosis and has yet no truly effective treatment is available. This study aimed to investigate the effects of isochlorogenic acid A(ICQA) on liver fibrosis induced by carbon tetrachloride(CCl4) and clarify the underlying mechanism. METHODS Rats were treated with CCl4 for eight weeks in order to induce liver fibrosis and simultaneously orally administered with ICQA(10, 20 and 40 mg·kg~(-1)). RESULTS ICQA had significant protective effect on liver injury, inflammation, and fibrosis in rats. Meanwhile, ICQA prevented the activation of hepatic stellate cells(HSC) as indicated by inhibiting the overexpression of a-smooth muscle actin(a-SMA). In addition, reduced fibrosis was found to be associated with decreased protein expression of high-mobility group box 1(HMGB1) and toll like receptor(TLR)4. Moreover, ICQA supressed the cytoplasmic translocation of HMGB1 in rat liver. Further investigations indicated that ICQA treatment significantly attenuated nuclear translocation of the nuclear factor-κB(NF-κB) p65 and inhibited degradation of IkB a expression in the liver of rats with liver fibrosis. CONCLUSION ICQA has hepatoprotective and anti-fibrotic effects in rats with liver fibrosis through modulating the HMGB1/TLR4/NF-κB signaling pathways.     

Anti-arthritis effect of berberine associated with regulating energy metabolism of macrophage through AMPK/HIF-1α pathway

OBJECTIVE To investigate berberine(BBR) attenuates arthritis in adjuvant-induced arthritic(AA) rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of AMP-activated protein kinase(AMPK) and inhibition of hypoxia inducible factor 1α(HIF-1α). METHODS AA rats were treated with BBR(40, 80, or 160 mg·kg~(-1)) from days 15 to 29 after immunization. The histopathology of ankle joint was examined through hematoxylin-eosin(HE) staining. The concentrations of tumour necrosis factor-α(TNF-α), interleukin-6(IL-6), IL~(-1)β, IL-2, IL~(-1)7 A, interferon-gamma(IFN-γ), monocyte chemotactic protein 1(MCP-1), IL-4, IL~(-1)0, transforming growth factor-β1(TGF-β1), ATP, and lactic acid were measured by using ELISA kits. The percentage of M1 and M2 macrophage cells in joint tissues were evaluated by immune-fluorescence. The expressions of p-AMPK and HIF-1α in joint of AA rats were determined according to immunohistochemistry analysis. The migration of macrophage was detected by Transwell assays. The expression of inducible nitric oxide synthase(iN OS), Arginase-1(Arg1), p-AMPK, AMPK and HIF-1αwere examined by Western blotting. The labeled macrophages were observed with laser confocal microscopy.RESULTS BBR relieved signs and symptoms of AA rats and reversed pathological changes. BBR treatment group exhibited decreases in pro-inflammatory cytokines(TNF-α, IL~(-1)β, IL-6, IL-2, IL~(-1)7 A, IFN-γ, and MCP-1) coupled with increases anti-inflammatory cytokines(IL-4, IL~(-1)0, TGF-β1) in the serum. The number of M1 macrophage was reduced,while the number of M2 macrophage was increased in BBR group joint tissues. Moreover, BBR showed marked up-regulation the expression of p-AMPK and down-regulation the expression of HIF-1α in joint of AA rats. Next in vitro study, we found BBR up-regulated the expression of p-AMPK, Arg1(M2 marker) and down-regulated the expression of HIF-1α,i NOS(M1 marker) induced by LPS in peritoneal macrophages from normal SD rat. Furthermore, BBR treatment inhibited the migration of macrophages stimulated by LPS. The level of ATP was elevated and lactic acid was reduced in LPSinduced macrophages after treated by BBR. However, Compound C significantly attenuated the effects of BBR on activated macrophages. CONCLUSION BBR alleviates inflammation by regulating energy metabolism and correcting the polarization of macrophage through AMPK-HIF-1α pathway. BBR might have great therapeutic value for RA.     

Artin M enhances TNF-α production and phagocytosis of Candida albicans mediated by dectin-1 and mannose receptors

The activities of dectin-1 and mannose receptors on phagocytosis of Candida albicans and the production of TNF-α by macrophages from mice pretreated for 3 days with extract of Artocarpus intergrifolia seeds (jack extract), Artin M or jacalin were studied. Macrophages from these mice were coincubated with C. albicans CR15 (yeast), in the presence of mannose (50mM) plus mannan (100 μg) or laminarin (1mg). Phagocytosis was significantly enhanced to 52% in macrophages from mice pretreated intraperitoneally for 3 days with jack extract (500 μg/250 μl PBS). Reduction in phagocytosis from 52% to 34% (P<0.05) occurred in the presence of mannose receptor inhibitors and from 52% to 16% (P<0.01) in the presence of dectin-1 inhibitor laminarin, whereas only 20% of control macrophages phagocytosed blastoconidia. Similar results were verified for pretreatment of mice with Artin M (2.5 μg/250 μl PBS), but not for jacalin (25 μg/250 μl PBS). Macrophages from mice pretreated 3 days previously with jack extract or Artin M and then coincubated for 2h with C. albicans presented a significant increase in TNF-α production, correlating with significantly less transition of yeast to filamentous forms compared to pretreatment with jacalin. These results suggest that Artin M, but not jacalin present in jack extract significantly increased TNF-α production and the activity of mannose and dectin-1 receptors.     

IL-10 ameliorates PM2.5-induced lung injury by activating the AMPK/SIRT1/PGC-1α pathway

Exposure to fine particulate matter with a diameter ≤2.5 μm (PM2.5) can cause a number of respiratory diseases. However, there is currently no safe treatment for PM2.5-induced lung damage. This study investigated the protective effect of IL-10 against lung injury and the possible involvement of AMPK/SIRT1/PGC-1α signaling. The mean diameter, particle size distribution, and zeta potential of PM2.5 samples were assessed using a Zetasizer Nano ZS90 analyzer. Thereafter, Wistar rats were exposed to PM2.5 (1.8, 5.4, or 16.2 mg/kg) alone or high-dose PM2.5 with recombinant rat IL-10 (rrIL-10; 5 μg/rat). Treatment with rrIL-10 ameliorated PM2.5-induced acute lung injury, reduced mitochondrial damage, and inhibited inflammation, oxidative stress, and apoptosis in the PM2.5-treated rats. Moreover, the mRNA and protein expression of AMPK, SIRT1, and PGC-1α were upregulated by rrIL-10 treatment. In conclusion, rrIL-10 protected lung tissues against PM2.5-induced inflammation by reducing oxidative stress and apoptosis via activating AMPK/SIRT1/PGC-1α signaling.     

Rosiglitazone attenuates endothelial progenitor cell apoptosis induced by TNF-α via ERK/MAPK and NF-κB signal pathways

The discovery of endothelial progenitor cells (EPCs) provides us with a novel treatment strategy for complications requiring therapeutic revascularization and vascular repair. However, the feasibility of this strategy may be limited due to reduced number and impaired function of EPCs under stimulation of TNF-α. The present study was designed to investigate the effect of rosiglitazone on EPC apoptosis induced by TNF-α and the molecular mechanisms involved. Rosiglitazone attenuated apoptosis of TNF-α-stimulated EPCs in a dose-dependent manner. Rosiglitazone decreased caspase-3 activity and cleavages of caspase-3, caspase-7, and parp. Rosiglitazone also moderated the dissipation of mitochondrial membrane potential caused by TNF-α treatment and reduced the expression of bax and the release of cytochrome c. Furthermore, rosiglitazone inhibited phosphorylations of ERK/MAPK and NF-κB signal molecules. Both ERK and NF-κB inhibitors decreased TNF-α-induced apoptosis of EPCs, as well as the expression of cleaved caspase-3 and parp. These results suggest that rosiglitazone may mediate the inhibitory effect on EPCs apoptosis under TNF-α stimulation through suppression of ERK/MAPK and NF-κB signal pathways.     

Systemic TNF-α blockade attenuates anxiety and depressive-like behaviors in db/db mice through downregulation of inflammatory signaling in peripheral immune cells

Research studies have indicated that the comorbidity burden of mood disorders and obesity is reasonably high. Insulin signaling has been shown to modulate multiple physiological functions in the brain, indicating its association with neuropsychiatric diseases, including mood disorders. Leptin is a hormone responsible for regulating body weight and insulin homeostasis. Previous studies on db/db mice (a mouse model that carries a spontaneous genetic mutation in leptin receptor Lepr^db) have shown that they exhibit inflammation as well as neurobehavioral traits associated with mood. Therefore, targeting inflammatory pathways such as TNF-α may be an effective strategy in the treatment of obesity-linked mood disorders. The objective of this study was to investigate the effect of long-term administration of etanercept (a TNF-α blocker) on anxiety and depressive-like behaviors in db/db mice. This was performed using light/dark box, forced swim, and open field tests with lean littermate wild type (WT) mice serving as a control group. Using flow cytometry in peripheral blood, we further examined the molecular effects of etanercept on NF-κB p65, TNF-α, IL-17A, and TLR-4 expressing CD4+, CD8+, and CD14+ cells in the peripheral blood. Our data show that peripheral administration of etanercept decreased these cells in db/db mice. Furthermore, our results indicated that peripheral administration of etanercept reduced anxiety and depressive-like behaviors. Therefore, targeting TNF-α signaling might be an effective strategy for modulating obesity-associated depression and anxiety.     

Saikosaponins-b suppresses tumor growth and angiogenesis of hepatocellular carcinoma by regulating VEGF/ERK/HIF-1α signal pathway

OBJECTIVE Angiogenesis therapy has attracted interest as a potential treatment for hepatocellular carcinoma(HCC).In this study,we investigated the anti-proliferative activities and antiangiogenesis effects of saikosaponins(SS)-b on hepatocellular carcinoma(HCC)and its regulation on VEGF/ERK/HIF-1 αsignal pathway.METHODS H22 hepatoma-bearing mice model and HepG-2 cells were used to study the anti-tumor and anti-angiogenesis effects of SS-b in vivo and in vitro.Pathological change of tumor tissue was observed by HE staining,the microvascular changes were detected by immunohistochemical method.The effects of SS-b on angiogenesis were examined by using the chick embryo chorioallantoic membrane(CAM)model.The effects of SS-b on proliferation,migration and invasion were investigated by MTT assay,scratch wound healing assay and transwell assay inhuman umbilical vein endothelial cell(HUVEC)and HepG2 cells in vitro.Vascular endothelial growth factor(VEGF),matrix metalloproteinase-2/9(MMP-2/9),hypoxia-inducible factor-1α(HIF-1α)expression and the phosphorylation of extracellular regulated kinase(ERK)were analyzed using RT-PCR and Westernblot.RESULTS SS-b effectively inhibited the tumor growth of H22 mice in vivo.The inhibitory rate of tumor was 49.1%,50.7%,66.1%in SS-b 5,10 and 20 mg·kg-1group respectively.HE staining results showed that SS-b induced tumor necrosis and nuclear dissolution in H22 mice.Moreover,SS-b also reduced the number of microvessels of tumor tissue in H22 mice significantly and suppressed the angiogenesis of CAM induced by b-FGF.SS-b had an obvious inhibitory effect on cell proliferation,migration and invasion of HUVEC cells and HepG-2 cells.These effects were associated with downregulation of the expression of MMP2/9 and suppression of VEGF/ERK/HIF-1αsignaling in H22 mice and Hep-G2 cells.CONCLUSION Our findings showed that SS-b exerts anti-tumor effects by inhibiting tumor angiogenesis via regulating VEGF/ERK/HIF-1α signal pathway in vivo and in vitro.     

Astragalus polysaccharides suppress ICAM-1 and VCAM-1 expression in TNF-α-treated human vascular endothelial cells by blocking NF-κB activation

Aim:

To investigate the effects Astragalus polysaccharides (APS) on tumor necrosis factor (TNF)-α-induced inflammatory reactions in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanisms.

Methods:

HUVECs were treated with TNF-α for 24 h. The amounts of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined with Western blotting. HUVEC viability and apoptosis were detected using cell viability assay and Hoechst staining, respectively. Reactive oxygen species (ROS) production was measured by DHE staining. Monocyte and HUVEC adhesion assay was used to detect endothelial cell adhesive function. NF-κB activation was detected with immunofluorescence.

Results:

TNF-α (1-80 ng/mL) caused dose- and time-dependent increases of ICAM-1 and VCAM-1 expression in HUVECs, accompanied by significant augmentation of IκB phosphorylation and NF-κB translocation into the nuclei. Pretreatment with APS (10 and 50 μg/mL) significantly attenuated TNFα-induced upregulation of ICAM-1 VCAM-1 and NF-κB translocation. Moreover, APS significantly reduced apoptosis, ROS generation and adhesion function damage in TNF-α-treated HUVECs.

Conclusion:

APS suppresses TNFα-induced adhesion molecule expression by blocking NF-κB signaling and inhibiting ROS generation in HUVECs. The results suggest that APS may be used to treat and prevent endothelial cell injury-related diseases.     

Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells

Aim:

To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis.

Methods:

Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays.

Results:

Ibrolipim 5 and 50 μmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the ibrolipim treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by ibrolipim.

Conclusion:

Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.