The study on synthesis and vitro hypolipidemic activity of novel berberine derivatives nitric oxide donors.

Berberine was used as the lead compound in the present study to design and synthesize novel berberine derivatives by splicing bromine bridges of different berberine carbon chain lengths coupled nitric oxide donors, and their lipid lowering activities were assessed in a variety of ways. This experiment synthesized 17 new berberine nitric oxide donor derivatives. Compared with berberine hydrochloride, most of the compounds exhibited certain glycerate inhibitory activity, and compounds 6a, 6b, 6d, 12b and 12d showed higher inhibitory activity than berberine, with 6a, 6b and 6d having significant inhibitory activity. In addition, compound 6a linked to furazolidone nitric oxide donor showed better NO release in experiments; In further mechanistic studies, we screened and got two proteins, PCSK9 and ACLY, and docked two proteins with 17 compounds, and found that most of the compounds bound better with ATP citrate lyase (ACLY), among which there may be a strong interaction between compound 6a and ACLY, and the interaction force was better than the target drug Bempedoic Acid, which meaning that 6a may exert hypolipidemic effects by inhibiting ACLY; moreover, we also found that 6a may had the better performance in gastrointestinal absorption, blood-brain barrier permeability, Egan, Muegge class drug principle model calculation and bioavailability.

[Determination of 15 preservative allergens in cosmetics by gas chromatography-tandem mass spectrometry].

Most preservatives are irritating and can easily induce skin sensitivities. Therefore, both domestic and international regulations impose clear restrictions on the use of preservatives in cosmetics. Herein, gas chromatography-tandem mass spectrometry (GC-MS/MS) was employed to simultaneously analyze the levels of 15 preservative allergens in cosmetics. Further, a precise identification approach based on a two-column retention index and mass spectrometry matching degree was developed. Cosmetic samples were extracted via acetonitrile vortex ultrasound extraction and then dehydrated with anhydrous MgSO4. The preservative allergens were separated on two columns, namely, DB-5MS and DB-WAX. Targets were identified using electron impact ionization (EI) source and the multiple reaction monitoring (MRM) mode and characterized using a retention index calibrated by a series of n-alkane standards. Following two tests, the LODs for the 15 preservative allergens on the DB-5MS column were in the range of 0.02-0.2 mg/kg, while those for 12 preservative allergens on the DB-WAX column were in the range of 0.01-20 mg/kg. The preservative allergens on the DB-5MS and DB-WAX columns demonstrated strong correlations, with all correlation coefficients exceeding 0.99. The recoveries for the 15 preservative allergens were in the range of 70.1%-129.8% at low, medium, and high levels, and the relative standard deviations (RSDs) were all below 15% (n=6) when using water, lotion, facial mask, and cream as the representative matrix. Next, 80 batches of genuine samples were tested using the established method. Isopropyl 4-hydroxybenzoate, a prohibited preservative, was detected in two sample batches using the DB-5MS and DB-WAX columns. Additionally, 11 and 10 restricted preservative allergens were identified on the DB-5MS and DB-WAX columns, respectively. The test results indicate that the double-column system approach offers excellent accuracy, effectively preventing false-positive and false-negative results, and can detect the 15 preservative allergens in cosmetics. The use of the retention index for the qualitative detection of these preservative allergens offers valuable options for non-targeted screening and meeting regulatory criteria.

EEBR induces Caspase-1-dependent pyroptosis through the NF-κB/NLRP3 signalling cascade in non-small cell lung cancer.

Lung cancer is a leading cause of cancer-related deaths worldwide. Recent studies have identified pyroptosis, a type of programmed cell death, as a critical process in the development and progression of lung cancer. In this study, we investigated the effect of EEBR, a new compound synthesized by our team, on pyroptosis in non-small cell lung cancer cells (NSCLC) and the underlying molecular mechanisms. Our results demonstrated that EEBR significantly reduced the proliferation and metastasis of NSCLC cells in vitro. Moreover, EEBR-induced pyroptosis in NSCLC cells, as evidenced by cell membrane rupture, the release of cytokines such as interleukin-18 and interleukin-1 beta and the promotion of Gasdermin D cleavage in a Caspase-1-dependent manner. Furthermore, EEBR promoted the nuclear translocation of NF-κB and upregulated the protein level of NLRP3. Subsequent studies revealed that EEBR-induced pyroptosis was suppressed by the inhibition of NF-κB. Finally, EEBR effectively suppressed the growth of lung cancer xenograft tumours by promoting NSCLC pyroptosis in animal models. Taken together, our findings suggest that EEBR induces Caspase-1-dependent pyroptosis through the NF-κB/NLRP3 signalling cascade in NSCLC, highlighting its potential as a candidate drug for NSCLC treatment.

Active Property-Structure Integrated Reconfiguration of Individual Resonant Nanoparticles.

Property-structure reconfigurable nanoparticles (NPs) provide additional flexibility for effectively and flexibly manipulating light at the nanoscale. This has facilitated the development of various multifunctional and high-performance nanophotonic devices. Resonant NPs based on dielectric active materials, especially phase change materials, are particularly promising for achieving reconfigurability. However, the on-demand control of the properties, especially the morphology, in individual dielectric resonant NP remains a significant challenge. In this study, we present an all-optical approach for one-step fabrication of Ge2Sb2Te5 (GST) hemispherical NPs, integrated active reversible phase-state switching, and morphology reshaping. Reversible optical switching is demonstrated, attributed to reversible phase-state changes, along with unidirectional modifications to their scattering intensity resulting from morphology reshaping. This novel technology allows the precise adjustment of each structural pixel without affecting the overall functionality of the switchable nanophotonic device. It is highly suitable for applications in single-pixel-addressable active optical devices, structural color displays, and information storage, among others.

A turn-on fluorescent probe for detecting and bioimaging of HOCl in inflammatory and liver disease models.

Hypochlorous acid (HOCl) is a common reactive oxygen species (ROS) associated with the development of liver, tumor, inflammatory, and other diseases. In this work, the turn-on fluorescent probe named (WZ-HOCl) with a naphthalimide structure was designed and synthesized to detect endogenous HOCl in disease models. WZ-HOCl can achieve a fast response to HOCl with good linearity in the range of 0-45 µM (LOD = 147 nM). The application of WZ-HOCl in bioimaging was investigated by constructing a series of cellular disease models, and the results showed that WZ-HOCl could sensitively detect endogenous HOCl in inflammatory and liver disease models. It can also be used to differentiate between hepatocytes and hepatoma cells. WZ-HOCl will provide new methods and ideas for fluorescent probes in detecting drug-induced liver injury, alcoholic and non-alcoholic steatohepatitis, and some inflammation-related diseases.

A Lipid Droplet-Specific NIR Fluorescent Probe with a Large Stokes Shift for In Vivo Visualization of Polarity in Contrast-Induced Acute Kidney Injury.

The research on lipid droplets (LDs) has attracted great attention in the field of biomedical science in recent years. LD malfunction is found to be associated with the development of acute kidney injury (AKI). To monitor this biological process and explain related pathological behavior, the development of excellent LD fluorescent probes with a polarity-sensitive character would provide a desirable strategy. Herein, we designed a new polarity-susceptible fluorescent probe named LD-B with LD targetability, which exhibits very weak fluorescence in highly polar solvents based on the twisted intramolecular charge transfer effect but enhanced fluorescence in low polar environments, enabling us to visualize polarity alteration. The probe LD-B also possesses the merits of intense near-infrared (NIR) emission, good photostability, large Stokes shift, low toxicity, faster metabolic rate, and wash-free ability; thereby, it would contribute to efficient LD fluorescence visualization application. Using LD-B via confocal laser scanning fluorescence imaging and a small-animal imaging system in vivo, we first manifested a prominent rise of LD polarity in contrast-induced AKI (CI-AKI), not only at the cellular level but also in animals in vivo. Furthermore, the in vivo studies suggest that LD-B could accumulate in the kidney. In addition, the normal cell lines (including kidney cells) exhibiting a greater polarity of LDs than the cancer cells have been demonstrated systemically. Altogether, our work presents an effective approach for the medical diagnosis of LDs related to CI-AKI and identification of potential therapeutic markers.

Tetrahydroberberrubine prevents peritoneal adhesion by suppressing inflammation and extracellular matrix accumulation.

Peritoneal adhesion is a common abdominal surgical complication that induces abdominal haemorrhage, intestinal obstruction, infertility, and so forth. The high morbidity and recurrence rate of this disease indicate the need for novel therapeutic approaches. Here, we revealed the protective roles of tetrahydroberberrubine (THBru), a novel derivative of berberine (BBR), in preventing peritoneal adhesion and identified its underlying mechanism in vivo and in vitro. Abrasive surgery was used to create a peritoneal adhesion rat model. We found that THBru administration markedly ameliorated peritoneal adhesion, as indicated by a lowered adhesion score and ameliorated caecal tissue damage. By comparison, THBru exhibited more potent anti-adhesion effects than BBR at the same dose. Mechanistically, THBru inhibited inflammation and extracellular matrix (ECM) accumulation in the microenvironment of adhesion tissue. THBru suppressed the expression of inflammatory cytokines including interleukin-1ß (IL-1ß), IL-6, transforming growth factor ß (TGF-ß), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1), by regulating the transforming growth factor beta-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling pathways. However, THBru promoted the activation of MMP-3 by directly blocking the TIMP-1 activation core and subsequently decreased collagen deposition. Taken together, this study identifies THBru as an effective anti-adhesion agent that regulates diverse mechanisms, thereby outlining its potential therapeutic implications for the treatment of peritoneal adhesion.

Leakage Dynamics of Glass Bottles on Container Closure Integrity Testing: Influence of Different Laser-Drilled Microhole Geometries.

Container closure integrity testing (CCIT) is a critical step in ensuring package integrity and providing feedback on package designs. In practical applications, CCIT methods, namely physical and probabilistic methods, must be appropriately selected and validated to ensure their suitability for the intended use. However, the industry still lacks practical recommendations regarding the choice of CCIT methods and artificial leaks to set the acceptance criteria. The main reason is the lack of correlation between testing methods. Artificially introduced leak microholes are the only way to determine the sensitivity of a CCIT method and to implement the method correlation. However, the type of artificial leakage is a key factor because in most studies, leakage is described and valued using a single parameter, such as size. This can significantly affect the credibility of the relevant test results, especially in the case of microbial invasion, where the difference in test conditions and samples will severely affect the probability of microbial invasion. Therefore, it is vital to conduct a systematic study on the influence of leakage conditions on CCIT methods. In this study, the influence of the shapes of artificial leaks on the two kinds of testing methods was systematically studied based on a laser-drilled microhole-a highly potential and non-exogenous artificial leak manufacturing method that can fabricate different leakage geometries. The reason for the influence of the shape of an artificial leak on the CCIT is that the deterministic method takes defects as an idealized model and ignores the influence of the leak shape, wall thickness, and other factors on leakage and pollution risks. However, these factors seriously affect the dynamic process of leakage and microbial invasion. The pressure decay method is used to test the leakage flow rate of conical and straight holes. Microbial challenge tests are then used to verify the impact of leakage shapes on the pollution risk. The results of the tests indicated that the probability of microbial invasion in the conical holes is much higher than that in straight holes with the same flow test results and that the wall thickness can also affect microbial invasion. Thus, it can be proven that the risk of leakage and invasion or the sensitivity of different methods cannot only be compared through the leak diameter. Numerous influencing factors, including leakage geometry (e.g., shape and thickness), must be considered in practical applications.

Tetrahydroberberrubine retards heart aging in mice by promoting PHB2-mediated mitophagy.

Heart aging is characterized by left ventricular hypertrophy and diastolic dysfunction, which in turn induces a variety of cardiovascular diseases. There is still no therapeutic drug to ameliorate cardiac abnormities in heart aging. In this study we investigated the protective effects of berberine (BBR) and its derivative tetrahydroberberrubine (THBru) against heart aging process. Heart aging was induced in mice by injection of D-galactose (D-gal, 120 mg · kg-1 · d-1, sc.) for 12 weeks. Meanwhile the mice were orally treated with berberine (50 mg · kg-1 · d-1) or THBru (25, 50 mg · kg-1 · d-1) for 12 weeks. We showed that BBR and THBru treatment significantly mitigated diastolic dysfunction and cardiac remodeling in D-gal-induced aging mice. Furthermore, treatment with BBR (40 µM) and THBru (20, 40 µM) inhibited D-gal-induced senescence in primary neonatal mouse cardiomyocytes in vitro. Overall, THBru exhibited higher efficacy than BBR at the same dose. We found that the levels of mitophagy were significantly decreased during the aging process in vivo and in vitro, THBru and BBR promoted mitophagy with different potencies. We demonstrated that the mitophagy-inducing effects of THBru resulted from increased mRNA stability of prohibitin 2 (PHB2), a pivotal factor during mitophagy, thereby upregulating PHB2 protein expression. Knockdown of PHB2 effectively reversed the antisenescence effects of THBru in D-gal-treated cardiomyocytes. On the contrary, overexpression of PHB2 promoted mitophagy and retarded cardiomyocyte senescence, as THBru did. In conclusion, this study identifies THBru as a potent antiaging medicine that induces PHB2-mediated mitophagy and suggests its clinical application prospects.

Ultrafast Temporal-Spatial Dynamics of Phase Transition in N-Doped Ge2Sb2Te5 Film Induced by Femtosecond Laser Pulse Irradiation.

Element-doped phase change material (PCM) could improve the performances, e.g., better thermal stability, higher electrical resistance, and faster crystallization speed; thus, the influence of the doping element needs to be further investigated. In this paper, a femtosecond laser, which could realize the ultrafast phase transition rate of PCM between amorphization and crystallization, was used to explore the properties of nitrogen-doped Ge2Sb2Te5 (GST), and a bond effect was proposed. The pure GST and different nitrogen contents of doped GST films were investigated by femtosecond laser pulse excitation through a pump-probe shadowgraph imaging technique. The results showed that the element-doped films could change photon absorption because of the increase in free carriers. This caused the faster rate of reflectivity to change in the irradiated area by the laser beam as the more nitrogen doped. When the nitrogen content increased, the crystallization evolution became harder because it enhanced the bond effect, which suppressed crystalline grain growth and improved the thermal stability. Based on the analysis in the paper, the desired performances of PCMs, e.g., ultrafast dynamics, crystallization evolution, and thermal stability, could be controlled according to the demands by modifying the bond effect.

Ultrafast Dynamics of Different Phase States Ge2Sb2Te5 Film Induced by a Femtosecond Laser Pulse Irradiation.

A femtosecond laser could realize a high transition rate of the phase change material (PCM), and the properties of the amorphous and the crystalline Ge2Sb2Te5 (GST) induced by a femtosecond laser were studied, which was one of the candidates among the PCMs. However, the characteristics of the intermediate phase states in reversible phase transitions were also important and helpful to explore the mechanisms of the phase transitions. In this paper, the ultrafast dynamics of amorphous, crystalline face-centered-cubic (FCC), and hexagonal-close-packed (HCP) states were investigated using a femtosecond laser pulse excitation through a reflective-type pump-probe technique, obtained by annealing at certain temperatures, and verified using X-ray diffraction (XRD) and the Raman spectrum. It was found that as the annealing temperature increased, the electron of the GST films could be excited more easily, while the ablation threshold decreased. Due to annealing, the structure of bonding was changed for different phase states, which resulted in the decrease in the band gap of the films. In addition, it was hard for the intermediate state films to transit to the amorphous structure state via the femtosecond laser, and the crystallization would be enhanced, while the crystalline HCP structures of GST could be directly and easily changed to the amorphous state by a pulse, which resulted from the non-thermal phase change caused by the excited electron.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) modulates the proliferation and apoptosis of acute lymphoblastic leukemia cells by sponging miR-486-5p.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 gene (PVT1) is related to the progress of various cancers. Here, we illuminated the role of PVT1 in acute lymphoblastic leukemia (ALL) cell proliferation and apoptosis. PVT1 was upregulated in plasma samples from patients with ALL and ALL cell lines. PVT1 silencing repressed cell viability and enhanced cell apoptosis in Jurkat and SUP-B15 cells. PVT1 targeted microRNA-486-5p (miR-486-5p) and negatively modulated miR-486-5p expression. Upregulation of miR-486-5p decreased cell viability and increased ALL cell apoptosis. Mastermind Like Transcriptional Coactivator 3 (MAML3) was a downstream molecule of miR-486-5p and miR-486-5p mimic transfection weakened its expression in ALL cells. Rescue experiments proved that reintroduction of PVT1 counteracted the impacts of miR-486-5p in ALL cell proliferation and apoptosis. In vivo, PVT1 silencing repressed the tumor growth of SUP-B15 cells and reduced the expression of MAML3. Altogether, silencing of PVT1 inhibited ALL cell growth and induced cell apoptosis through sponging miR-486-5p.

A Review of the Synthesis of Nitric Oxide Donor and Donor Derivatives with Pharmacological Activities.

Endogenous nitric oxide (NO) is an important effector molecule and signal transduction molecule, which participates in the regulation of multiple functions in organisms, involving various a variety of physiological and pathological processes, especially playing a very important role in the cardiovascular, immune, and nervous systems. NO is a gaseous substance with a short half-life in the body and is unstable in aqueous solutions. Therefore, many researchers focus on the release and activity of NO donors and their derivatives. However, NO donors can release free NO or NO analogues under physiological conditions to meet the human need. NO donors can be coupled with the corresponding active basic nucleus, so that they have the biological activity derived from both the basic nucleus and the NO donors, thus performing better bioactivity. This paper reviewed the routes of synthesis and advance activities of NO donor derivatives.

Kanglexin delays heart aging by promoting mitophagy.

Heart aging is characterized by structural and diastolic dysfunction of the heart. However, there is still no effective drug to prevent and treat the abnormal changes in cardiac function caused by aging. Here, we present the preventive effects of emodin and its derivative Kanglexin (KLX) against heart aging. We found that the diastolic dysfunction and cardiac remodeling in mice with D-galactose (D-gal)-induced aging were markedly mitigated by KLX and emodin. In addition, the senescence of neonatal mouse cardiomyocytes induced by D-gal was also reversed by KLX and emodin treatment. However, KLX exhibited better anti-heart aging effects than emodin at the same dose. Dysregulated mitophagy was observed in aging hearts and in senescent neonatal mouse cardiomyocytes, and KLX produced a greater increase in mitophagy than emodin. The mitophagy-promoting effects of KLX and emodin were ascribed to their abilities to enhance the protein stability of Parkin, a key modulator in mitophagy, with different potencies. Molecular docking and SPR analysis demonstrated that KLX has a higher affinity for the ubiquitin-like (UBL) domain of Parkin than emodin. The UBL domain might contribute to the stabilizing effects of KLX on Parkin. In conclusion, this study identifies KLX and emodin as effective anti-heart aging drugs that activate Parkin-mediated mitophagy and outlines their putative therapeutic importance.

Synthesis and evaluation of antitumor activities of 4-selenopyrimidine derivatives.

Pyrimidine antimetabolic agents are the essential drugs in treatment of various tumors. Novel synthesis and biological evaluation of the pyrimidine derivatives incorporating selenium element and amino acid carrier as potential antitumor agents have not been tried and studied. Based on the biological significance of pyrimidine structure, these two additional elemental fragments maybe enhance the antitumor effect and reduce toxic side effects of pyrimidine agents. The aim of this paper is to synthesis a series of 4-selenopyrimidine derivatives in order to find more potent lead compounds against cancer. In this study, 12 new 4-selenopyrimidine derivatives that are unstable in acidic solutions but very stable in alkaline and neutral solutions avoiding light were synthesized, and the antitumor activities on HepG2 cell lines of these compounds were evaluated by MTT assay. The results have shown that these compounds could reduce the proliferation of HepG2 cells in a dose-dependent fashion, and the inhibitory activity of compounds a6 was greater than that of positive control 5-fluorouracil (5-FU), the IC50 for a6 was 3.63 µM. In the comprehensive analysis of the structure-activity relationship, we could draw the antitumor effect of selenouracil derivatives is stronger than those of selenothymine derivatives. These results suggest that the substituent groups of selenium element and amino acid on the pyrimidine derivatives are vital for their antitumor activities on HepG2 cells.

Fabrication of Ge2Sb2Te5 crystal micro/nanostructures through single-shot Gaussian-shape femtosecond laser pulse irradiation.

Femtosecond (fs) laser-thin film interaction is one of the most practical methods for fabricating functional nanostructures. However, the details of the interaction mechanism remain unclear. In this study, we demonstrate an abnormal ablation effect on nanofilms by using a tightly focused single fs laser pulse. After the irradiation of a single Gaussian-shaped femtosecond laser pulse, a molten micro/nanopatch at the irradiated central high-power zone is isolated from the surrounding film. The confined localized threshold effect is proposed as the main mechanism for the phase isolation. With this effect, the high refractive index dielectric Ge2Sb2Te5 crystal nanostructures can be fabricated by directed dewetting of the isolated molten micro/nanopatch on Si substrates. After the laser irradiation, the central isolated liquid through an amorphous GST film is transformed into a crystalline state after resolidification. The isolated central micro/nanopatch size can be controlled by the focused spot size and pulse energy, so that the morphologies (size, geometrical morphology, and distribution) of GST nanostructures can be flexibly modulated. Furthermore, separated solid and liquid phase states detected using spatial-temporal-resolved microscopy validates the crucial role of the confined-localized threshold effect in the dewetting effect based on the separated liquid phase.

Design, synthesis and biological evaluation of 2-indolinone derivatives as PAK1 inhibitors in MDA-MB-231 cells.

P21-activated kinase 1 (PAK1) plays a vital role in the proliferation, survival and migration of cancer cells, which has emerged as a promising drug target for cancer therapy. In this study, a series of 2-indolinone derivatives were designed and synthesized through a structure-based strategy. A potent PAK1 inhibitor (ZMF-005) was discovered, which presented an IC50 value of 0.22 µM against PAK1 with potent antiproliferative activity. Furthermore, we predicted the binding mode of ZMF-005 and PAK1 by molecule docking and dynamic (MD) simulation. In addition, ZMF-005 was documented to induce significant apoptosis and suppress migration in MDA-MB-231 cells. Collectively, these findings revealed that ZMF-005 is a novel potent PAK1 inhibitor for breast cancer treatment.

Controllable formation of laser-induced periodic surface structures on ZnO film by temporally shaped femtosecond laser scanning.

We achieved the controllable formation of laser-induced periodic surface structures (LIPSSs) on ZnO films deposited on fused silica induced by modulated temporally shaped femtosecond (fs) laser pulses (800 nm, 50 fs, 1 kHz) through the laser scanning technique. Two-dimensional (2D) high spatial frequency LIPSSs (HSFLs) with a period from 100 to 200 nm could be flexibly modulated based on the preprocessed nanostructures with appropriate fs laser irradiation conditions (fluence, scanning speed, and pulse delay). The finite-difference time-domain (FDTD) method combined with the Drude model was employed to calculate the redistributions of electric fields, which suggested the origin of HSFL formation.

Ginsenosides, potent inhibitors of sialyltransferase.

The overexpression of sialic acids and sialyltransferases (STs) during malignant transformation and progression could result in the aberrant sialylation of cancer cells. Therefore, interfering the sialic acid synthesis might be an effective pathway in cancer therapy. In this study, we assessed that the antitumor inhibitors of 20(S)-ginsenosides Rg3, 20(R)-ginsenosides Rg3, 20(S)-ginsenosides Rh2, and 20(R)-ginsenosides Rh2 could block the sialoglycans in liver cancer cells HepG2. The results showed that these four compounds could inhibit the expressions of the total and free sialic acid at different levels in HepG2, respectively; also, it showed dose dependence. In addition, the results of the enzyme-linked immunosorbent assay showed that the above four compounds can inhibit the expression of STs significantly. We also found that these compounds could mediate the block of sialylation of α2,3- and α2,6-linked sialic acids in HepG2 cells by flow cytometry. Meanwhile, the results of the molecular docking investigation showed that these compounds showed strong interaction with ST6GalI and ST3GalI. These results verified that the ginsenosides have a powerful inhibiting aberrant sialylation, and it laid a theoretical foundation for further research on the investigation of ginsenosides as the target inhibitors on STs.

Kanglexin protects against cardiac fibrosis and dysfunction in mice by TGF-ß1/ERK1/2 noncanonical pathway.

Cardiac fibrosis is a common pathological manifestation accompanied by various heart diseases, and antifibrotic therapy is an effective strategy to prevent diverse pathological processes of the cardiovascular system. We currently report the pharmacological evaluation of a novel anthraquinone compound (1,8-dihydroxy-6-methyl-9,10-anthraquinone-3-oxy ethyl succinate) named Kanglexin (KLX), as a potent cardioprotective agent with antifibrosis activity. Our results demonstrated that the administration of KLX by intragastric gavage alleviated cardiac dysfunction, hypertrophy, and fibrosis induced by transverse aortic constriction (TAC) surgical operation. Meanwhile, KLX administration relieved endothelial to mesenchymal transition of TAC mice. In TGF ß1-treated primary cultured adult mouse cardiac fibroblasts (CFs) and human umbilical vein endothelial cells (HUVECs), KLX inhibited cell proliferation and collagen secretion. Also, KLX suppressed the transformation of fibroblasts to myofibroblasts in CFs. Further studies revealed that KLX-mediated cardiac protection was due to the inhibitory role of TGF-ß1/ERK1/2 noncanonical pathway. In summary, our study indicates that KLX attenuated cardiac fibrosis and dysfunction of TAC mice, providing a potentially effective therapeutic strategy for heart pathological remodeling.