Ganoderma lucidum spores-derived particulate ß-glucan treatment improves antitumor response by regulating myeloid-derived suppressor cells in triple-negative breast cancer.

Granular ß-1,3-glucan extracted from the wall of Ganoderma lucidum spores, named GPG, is a bioregulator. In this study, we investigated the structural, thermal, and other physical properties of GPG. We determined whether GPG ameliorated immunosuppression caused by Gemcitabine (GEM) chemotherapy. Triple-negative breast cancer mice with GPG combined with GEM treatment had reduced tumor burdens. In addition, GEM treatment alone altered the tumor microenvironment(TME), including a reduction in antitumor T cells and a rise in myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs). However, combined GPG treatment reversed the tumor immunosuppressive microenvironment induced by GEM. GPG inhibited bone marrow (BM)-derived MDSC differentiation and reversed MDSC expansion induced by conditioned medium (CM) in GEM-treated E0771 cells through a Dectin-1 pathway. In addition, GPG downgraded PD-L1 and IDO1 expression on MDSC while boosting MHC-II, CD86, TNF-α, and IL-6 expression. In conclusion, this study demonstrated that GPG could alleviate the adverse effects induced by GEM chemotherapy by regulating TME.

A network pharmacology-based method to explore the therapeutic effect of honokiol on diabetes with comorbid depression in mice.

The effective treatment of diabetes with comorbid depression is a big challenge so far. Honokiol, a bioactive compound from the dietary supplement Magnolia officinalis extract, possesses multiple health benefits. The present study aims to propose a network pharmacology-based method to elucidate potential targets of honokiol in treating diabetes with comorbid depression and related mechanisms. The antidepressant-like efficacy of honokiol was evaluated in high-fat diet (HFD) induced diabetic mice using animal behavior testing, immuno-staining and western blotting assay. Through network pharmacology analysis, retinoid X receptor alpha (RXRα) and vitamin D receptor (VDR) were identified as potential targets related to diabetes and depression. The stable binding conformation between honokiol and RXR/VDR was determined by molecular docking simulation. Moreover, hononkiol effectively alleviated depression-like behaviors in HFD diabetic mice, presented anti-diabetic and anti-neuroinflammatory functions, and protected the hippocampal neuroplasticity. Importantly, honokiol could activate RXR/VDR heterodimer in vivo. The beneficial effects of honokiol on HFD mice were significantly suppressed by UVI3003 (a RXR antagonist), while enhanced by calcitriol (a VDR agonist). Additionally, the disruption of autophagy in the hippocampus of HFD mice was ameliorated by honokiol, which was attenuated by UVI3003 but strengthened by calcitriol. Taken together, the data provide new evidence that honokiol exerts the antidepressant-like effect in HFD diabetic mice via activating RXR/VDR heterodimer to restore the balance of autophagy. Our findings indicate that the RXR/VDR-mediated signaling might be a potential target for treating diabetes with comorbid depression.

Pharmacodynamic study of chitosan in combination with salvianolic acid B in the treatment of CC14 -induced liver fibrosis in mice.

Liver fibrosis is a chronic liver lesion caused by excessive deposition of the extracellular matrix after liver damage, resulting in fibrous scarring of liver tissue. The progression of liver fibrosis is partially influenced by the gut microbiota. Chitosan can play a therapeutic role in liver fibrosis by regulating the gut microbiota based on the 'gut-liver axis' theory. Salvianolic acid B can inhibit the development of liver fibrosis by inhibiting the activation of hepatic stellate cells and reducing the production of extracellular matrix. In this study, the therapeutic effect of chitosan in combination with salvianolic acid B on liver fibrosis was investigated in a mouse liver fibrosis model. The results showed that the combination of chitosan and salvianolic acid B was better than the drug alone, improving AST/ALT levels and reducing the expression of α-SAM, COL I, IL-6 and other related genes. It improved the structure of gut microbiota and increased the abundance of beneficial bacteria such as Lactobacillus. The above results could provide new ideas for the clinical treatment of liver fibrosis.

Sodium hyaluronates applied in the face affects the diversity of skin microbiota in healthy people.

OBJECTIVE: A healthy and stable microbiome has many beneficial effects on the host, while an unbalanced or disordered microbiome can lead to various skin diseases. Hyaluronic acid is widely used in the cosmetics and pharmaceutical industries; however, specific reports on its effect on the skin microflora of healthy people have not been published. This study aimed to determine the effect of sodium hyaluronate on the facial microflora of healthy individuals. METHODS: Face of 20 healthy female volunteers between 18 and 24 years was smeared with sodium hyaluronate solution once per day. Cotton swabs were used to retrieve samples on days 0, 14, and 28, and high-throughput sequencing of 16 S rRNA was used to determine the changes in bacterial community composition. RESULTS: Facial application of HA can reduce the abundance of pathogenic bacteria, such as Cutibacterium and S. aureus, and increase the colonization of beneficial bacteria. CONCLUSION: This is the first intuitive report to demonstrate the effect of hyaluronic acid on facial microflora in healthy people. Accordingly, sodium hyaluronate was found to have a positive effect on facial skin health.

Puerarin alleviates depressive-like behaviors in high-fat diet-induced diabetic mice via modulating hippocampal GLP-1R/BDNF/TrkB signaling.

OBJECTIVE: Depression is one of the most common complications in patients with diabetes. Our previous study demonstrated puerarin, a dietary isoflavone, improved glucose homeostasis and ß-cell regeneration in high-fat diet (HFD)-induced diabetic mice. Here, we aim to evaluate the potential effect of puerarin on diabetes-induced depression. METHODS: The co-occurrence of diabetes and depression with related biochemical alterations were confirmed in HFD mice and db/db mice, respectively using behavioral analysis, ELISA and western blotting assay. Furthermore, impacts of puerarin on depression-related symptoms and pathological changes were investigated in HFD mice. RESULTS: The results showed that puerarin effectively alleviated the depression-like behaviors of HFD mice, down-regulated serum levels of corticosterone and IL-1ß, while up-regulated the content of 5-hydroxytryptamine. Simultaneously, puerarin increased the number of hippocampal neurons in HFD mice, and suppressed the apoptosis of neurons to protect the hippocampal neuroplasticity. GLP-1R expression in hippocampus of HFD mice was enhanced by puerarin, which subsequently activated AMPK, CREB and BDNF/TrkB signaling to improve neuroplasticity. Importantly, our data indicated that puerarin had an advantage over fluoxetine or metformin in treating diabetes-induced depression. CONCLUSION: Taken together, puerarin exerts anti-depressant-like effects on HFD diabetic mice, specifically by improving hippocampal neuroplasticity via GLP-1R/BDNF/TrkB signaling. Puerarin as a dietary supplement might be a potential candidate in intervention of diabetes with comorbid depression.

Correction: UCP-2 and UCP-3 Proteins Are Differentially Regulated in Pancreatic Beta-Cells.

[This corrects the article DOI: 10.1371/journal.pone.0001397.].

Inhibition of TAK1 aggravates airway inflammation by increasing RIPK1 activity and promoting macrophage death in a mouse model of toluene diisocyanate-induced asthma / 南方医科大学学报

OBJECTIVE@#To explore the effect of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) on toluene diisocyanate (TDI)-induced allergic airway inflammation in mice.@*METHODS@#Thirty-two mice were randomly divided into AOO group, AOO+5Z-7-Oxozeaenol group, TDI group, and TDI+5Z-7-Oxozeaenol group. Another 32 mice were randomly divided into AOO group, TDI group, TDI +5Z-7-Oxozeaenol group, and TDI +5Z-7-Oxozeaenol + Necrostatin-1 group. TAK1 inhibitor (5Z-7-Oxozeaenol, 5 mg/kg) and/or RIPK1 inhibitor (Necrostatin-1, 5 mg/kg) were used before each challenge. Airway responsiveness, airway inflammation and airway remodeling were assessed after the treatments. We also examined the effect of TDI-human serum albumin (TDI-HSA) conjugate combined with TAK1 inhibitor on the viability of mouse mononuclear macrophages (RAW264.7) using CCK8 assay. The expressions of TAK1, mitogen-activated protein kinase (MAPK) and receptor interacting serine/threonine protease 1 (RIPK1) signal pathway in the treated cells were detected with Western blotting. The effects of RIPK1 inhibitor on the viability of RAW264.7 cells and airway inflammation of the mouse models of TDI-induced asthma were evaluated.@*RESULTS@#TAK1 inhibitor aggravated TDI-induced airway inflammation, airway hyper responsiveness and airway remodeling in the mouse models (P < 0.05). Treatment with TAK1 inhibitor significantly decreased the viability of RAW264.7 cells, which was further decreased by co-treatment with TDI-HSA (P < 0.05). TAK1 inhibitor significantly decreased the level of TAK1 phosphorylation and activation of MAPK signal pathway induced by TDI-HSA (P < 0.05). Co-treatment with TAK1 inhibitor and TDI-HSA obviously increased the level of RIPK1 phosphorylation and caused persistent activation of caspase 8 (P < 0.05). RIPK1 inhibitor significantly inhibited the reduction of cell viability caused by TAK1 inhibitor and TDI-HSA (P < 0.05) and alleviated the aggravation of airway inflammation induced by TAK1 inhibitors in TDI-induced mouse models (P < 0.05).@*CONCLUSION@#Inhibition of TAK1 aggravates TDI-induced airway inflammation and hyperresponsiveness and may increase the death of macrophages by enhancing the activity of RIPK1 and causing persistent activation of caspase 8.

Potential impacts of diabetes mellitus and anti-diabetes agents on expressions of sodium-glucose transporters (SGLTs) in mice.

PURPOSE: Sodium-glucose transporters (SGLTs) are important targets for therapeutic intervention of type 2 diabetes. This study aims to evaluate the physiological influences of diabetes mellitus and the potential impacts of metformin and fluoxetine on SGLTs expressions. METHODS: Alterations of SGLT1 and SGLT2 were measured in organs involved in glucose homeostasis (kidney, intestine, liver and pancreas) of streptozotocin (STZ) and high-fat diet (HFD) induced diabetic mice by western blotting and real-time PCR (RT-PCR) respectively. RESULTS: In kidney, duodenal segments of intestine, liver, and pancreas of HFD diabetic mice, expressions of SGLT2 were all elevated compared to control mice. The level of SGLT1 was significantly increased in intestine, but was decreased in pancreas. SGLT1 expression in kidney was unaffected, and SGLT1 was undetectable in hepatocytes. Similar results were obtained in STZ diabetic mice. More importantly, here we noticed metformin decreased levels of SGLT2 in kidney, intestine, and pancreas of HFD mice markedly. Expressions of SGLT1 in intestine and pancreas were reduced by metformin as well. In contrast, fluoxetine increased abundances of SGLT2 and SGLT1 in kidney of HFD mice, but decreased SGLT1 expression in intestine. CONCLUSIONS: The present study provided evidence that expressions of SGLT1 and SGLT2 were significantly modulated by diabetes mellitus as well as by metformin and fluoxetine, which indicated the efficacy of SGLT2 inhibitors might be impacted by these factors.

Parkinson's disease a futile entangle of Mankind's credence on an herbal remedy: A review.

Parkinson's disease (PD) is a disease of the human nervous system with an onset, in the sixth and seventh decades of the human life. Chiefly perceived as progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) with the ensued loss of dopamine in the striatum and the presence of Lewy bodies, consisting of α-synuclein agglomeration. In which the neuronal bridge between substantia nigra and striatum plays an advent role in the motor system. Dilapidation of these neurons results in dopamine depletion which in-turn makes hay to PD. Eventually, the etiology and pathogenesis of PD were still on a hike of dilemma. Traditional Chinese medicine (TCM), including Chinese herbal remedies, acupuncture, and manipulative therapies, is commonly used as an adjunctive therapy in different diseases, particularly neurological diseases, in Asian countries. Additionally, TCM might improve the prognoses and the quality of life of patients with PD because it induces less adverse drug reactions. The present review describes research on the various neuroprotective components and herbal extracts from herbal medicines in the context of addressing the effects of PD.

Puerarin ameliorates hyperglycemia in HFD diabetic mice by promoting ß-cell neogenesis via GLP-1R signaling activation.

BACKGROUND: Diabetes is characterized by ß-cell loss and dysfunction. A strategy for diabetes treatment is to promote new ß-cell formation. Puerarin is an isoflavone from the root of Pueraria lobata (Willd.) Ohwi. Our previous study demonstrated puerarin could ameliorate hyperglycemia in diabetic mice. However, related mechanisms and potential roles of puerarin in ß-cell neogenesis have not been elucidated. PURPOSE: The present study aims to investigate whether anti-diabetic effect of puerarin is dependent on promoting ß-cell neogenesis via GLP-1R signaling activation. METHODS: A high-fat diet (HFD) induced diabetic mouse model was applied to investigate effects of puerarin in vivo, exendin-4 (GLP-1R agonist) and metformin were used as positive controls. Moreover, related mechanisms and GLP-1R downstream signal transduction were explored in isolated cultured mouse pancreatic ductal cells. RESULTS: Puerarin improved glucose homeostasis in HFD diabetic mice significantly. Markers of new ß-cell formation (insulin, PDX1 and Ngn3) were observed in pancreatic ducts of HFD mice treated by puerarin. Of note, efficacy of puerarin in vivo was suppressed by GLP-1R antagonist exendin9-39, but enhanced by exendin-4 respectively. In cultured mouse pancreatic ductal cells, puerarin induced expressions of insulin and PDX1, upregulated GLP-1R expression and activated ß-catenin and STAT3 subsequently. Expressions of insulin and PDX1 in ductal cells could be blocked by exendin9-39, or ß-catenin inhibitor ICG001, or JAK2 inhibitor AG490. CONCLUSION: These data clarified puerarin ameliorated hyperglycemia of HFD mice via a novel mechanism involved promoting ß-cell neogenesis. Our finding highlights the potential value of puerarin developing as an anti-diabetic agent.

Alpinate Oxyphyllae extracts enhance the longevity and homing of mesenchymal stem cells and augment their protection against senescence in H9c2 cells.

Adipose-derived mesenchymal stem cells (ADMSCs) are easily accessible and are attractive mesenchymal stem cells for use in regenerative medicine; however their application is frequently restricted due to various challenges present in the environment they are administered. Therefore ADMSCs are preferably preconditioned with various stimulating factors to overcome the barriers developed in any pathological conditions. Here we used ADMSCs from rat adipose based on the abundance of positive markers and preconditioned the cells with extracts from Alpinate Oxyphyllae Fructus (AOF), a traditional Chinese herb used for antiaging, associated various health benefits. The preconditioned stem cells were tested for their potential to drive H9c2 from doxorubicin (Dox)-induced aging. The AOF-treated stem cells enriched stemness in ADMSCs with respect to their stem cells' positive marker, and enhanced their longevity mechanism and elevated the stem cell homing-associated C-X-C chemokine receptor type 7 (CXCR7). The AOF preconditioned stem cells, when cocultured with H9c2 cells, showed effective protection to Dox-induced senescence and stem cell homing to damaged H9c2 cells. The presence of AOF provided greater protective effects in the Dox environment. In addition, AOF-pretreated ADMSCs showed enhanced migration than those treated with AOF in Dox environment. Therefore, our results show that administration of AOF preconditioned stem cells is potentially an effective strategy in the management of aging-associated cardiac disorders.

Total C-21 steroidal glycosides, isolated from the root tuber of Cynanchum auriculatum Royle ex Wight, attenuate hydrogen peroxide-induced oxidative injury and inflammation in L02 cells.

Oxidative stress plays an important role in the pathology of liver disorders. Total C­21 steroidal glycosides (TCSGs), isolated from the root tuber of Cynanchum auriculatum Royle ex Wight, have been reported to exert numerous effects, including liver protective and antioxidant effects. In order to investigate the potential mechanisms underlying the protective effects of TCSGs on liver function, the present study used the human normal liver cell line, L02, to evaluate the effects of TCSGs on hydrogen peroxide (H2O2)­induced oxidative injury and inflammatory responses. The L02 cells were pretreated with various concentrations of TCSGs, followed by exposure to 1.5 mM H2O2. Cell viability was determined by a 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide (MTT) assay. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and nitric oxide (NO) were measured using colorimetric assays. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH­Px) and the production of malondialdehyde (MDA) were also determined. Intracellular reactive oxygen species (ROS) levels were detected using a fluorescent probe. H2O2­induced oxidative toxicity was attenuated following treatment with TCSGs, as indicated by the increase in cell viability, the decreased levels of ALT, AST, LDH, NO, MDA and ROS, and the increased activities of SOD, CAT and GSH­Px. To further explore the possible mechanisms of action of TCSGs, the nuclear factor erythroid 2­related factor 2 (Nrf2) and nuclear factor­κB (NF)­κB pathways were examined. The results revealed that treatment with TCSGs markedly induced Nrf2 nuclear translocation and upregulated the expression of heme oxygenase­1 (HO­1) in the L02 cells damaged by H2O2. In addition, pretreatment with TCSGs inhibited the NF­κB signaling pathway by blocking the degradation of the inhibitor of nuclear factor κBα (IκBα), thereby reducing the expression and nuclear translocation of NF­κB, as well as reducing the expression of tumor necrosis factor­α (TNF­α), interleukin-6 (IL­6), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX­2). On the whole, the findings of this study demonstrate that TCSGs can protect L02 cells against H2O2­induced oxidative toxicity and inflammatory injury by increasing the expression of Nrf2 and HO­1, mediated by the NF­κB signaling pathway.

Autophagy Flux Contributes to Regulation of Components of Eclipta prostrata L. on Cigarette Smoking-Induced Injury of Bronchial Epithelial Cells.

Excessive autophagy plays a crucial role in cigarette smoking extract (CSE)-induced inflammation response and oxidative damage of respiratory epithelial cells. The components from Eclipta prostrata L. (CCE) have been shown to be beneficial for CSE-induced epithelial cells injury. However, whether its protection on CSE-stress injury is related to its regulation on autophagy remains still unclear. In this study, CCE, containing mainly wedelolactone of 45.88% and demethylwedelolactone of 23.74%, could improve significantly 10%CSE-induced cell viability of normal human bronchial epithelial (NHBE) cells using CCK-8 kit. We revealed that CCE could remarkably increase autophagic factors Beclin-1, Atg5, ATF4 proteins expression levels and the transformation of LC3-I to LC3-II. Additionally, CCE up-regulated significantly p-p16 and p-p21 phosphorylation levels whereas down-regulated p-p53 in NHBE cells. The changes of typical autolysosom and representative autophagosome in the presence of CCE or/and autophagy inhibitor chloroquine (CQ) were also observed by transmission electron microscopy. These data demonstrated that CCE reduced CSE-induced autophagy flux activation in NHBE cells. The blockade of CCE on autophagy flux contributes to its protection against CSE-induced NHBE cells damage, and CCE is promising to be combination therapeutic molecules to excessive autophagic damage in respiratory diseases.

Salidroside, A Natural Antioxidant, Improves ß-Cell Survival and Function via Activating AMPK Pathway.

Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces ß-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on ß-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased ß-cell mass and ß-cell replication of diabetic mice. Mechanism study in Min6 cells revealed that, under diabetic stimuli, salidroside suppressed reactive oxygen species production and restore mitochondrial membrane potential (ΔΨm) via reducing NOX2 expression and inhibiting JNK-caspase 3 apoptotic cascade subsequently to protect ß-cell survival. Simultaneously, diabetes associated oxidative stress also activated FOXO1 and triggered nuclear exclusion of PDX1 which resulted in ß-cell dysfunction. This deleterious result was reversed by salidroside by activating AMPK-AKT to inhibit FOXO1 and recover PDX1 nuclear localization. The efficacy of salidroside in improving ß-cell survival and function was further confirmed in isolated cultured mouse islets. Moreover, the protective effects of salidroside on ß-cells against diabetic stimuli can be abolished by an AMPK inhibitor compound C, which indicated functions of salidroside on ß-cells were AMPK activation dependent. Conclusion: These results confirmed beneficial metabolic effects of salidroside and identified a novel role for salidroside in preventing ß-cell failure via AMPK activation. Our finding highlights the potential value of Rhodiola rosea as a dietary supplement for diabetes control.

Inhibition of Cardiac Hypertrophy Effects in D-Galactose-Induced Senescent Hearts by Alpinate Oxyphyllae Fructus Treatment.

Aging is a complex physiological phenomenon accelerated by ROS accumulation, with multisystem decline and increasing vulnerability to degenerative diseases and death. Cardiac hypertrophy is a key pathophysiological component that accompanies the aging process. Alpinate Oxyphyllae Fructus (Alpinia oxyphylla MIQ, AOF) is a traditional Chinese medicine, which provides cardioprotective activity against aging, hypertension, and cerebrovascular disorders. In this study, we found the protective effect of AOF against cardiac hypertrophy in D-galactose-induced aging rat model. The results showed that treating rats with D-galactose resulted in pathological hypertrophy as evident from the morphology change, increased left ventricular weight/whole heart weight, and expression of hypertrophy-related markers (MYH7 and BNP). Both concentric and eccentric cardiac hypertrophy signaling proteins were upregulated in aging rat model. However, these pathological changes were significantly improved in AOF treated group (AM and AH) in a dose-dependent manner. AOF negatively modulated D-galactose-induced cardiac hypertrophy signaling mechanism to attenuate ventricular hypertrophy. These enhanced cardioprotective activities following oral administration of AOF reflect the potential use of AOF for antiaging treatments.

Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine.

PURPOSE: Hepatocellular carcinoma (HCC) cases are closely associated with chronic inflammation and fibrosis which is known as hepatic inflammation-fibrosis-cancer (IFC) axis. The aim of this study is to elucidate the development characteristics of the rat HCC model based on IFC axis. METHODS: The diethylnitrosamine (DEN)-induced rat HCC, which presents a stepwise histopathological progression that is similar to human HCC, was used to analyze the features of the different stages (inflammation, fibrosis, cancer). Rats were injected DEN at a dose of 30 mg/kg body weight twice a week for 11 weeks and the animals were observed until week 20. Time series sera and organ samples from the DEN animal model were collected to evaluate the dynamic changes. RESULTS: It was found that serum biochemical indicators (AST, ALT, ALP, TP, T-BIL, IL-6, TNF-α) from DEN-treated group were higher than that from control group. Fibrosis-related index in serum and live tissue were increased, respectively, from week 4 after DEN treatment. The expression of TGF-ß1 and α-SMA in DEN-treated group was higher than that in control group. JAK2/STAT3 signaling was significantly up-regulated in DEN-treated group compared to that in control group. The histological examination confirmed that the hepatocarcinogenesis model was successfully established, and 100% of the animals in the DEN-exposed group developed liver tumors at 20 weeks. According to the pathological changes, the model characterized resulted in three stages: the inflammation stage (week 2-6), the fibrosis stage (week 8-12), and the HCC stage (week 14-20). CONCLUSIONS: The results suggested that the HCC development was associated with IFC axis. The serial progression of hepatocarcinogenesis was according to the sequence of hepatic inflammation, fibrosis and then hepatic tumor.

Alpinate Oxyphyllae Fructus Inhibits IGFII-Related Signaling Pathway to Attenuate Ang II-Induced Pathological Hypertrophy in H9c2 Cardiomyoblasts.

Angiotensin II (Ang II) is a very important cardiovascular disease inducer and may cause cardiac pathological hypertrophy and remodeling. We evaluated a Chinese traditional medicine, alpinate oxyphyllae fructus (AOF), for therapeutic efficacy for treating Ang II-induced cardiac hypertrophy. AOF has been used to treat patients with various symptoms accompanying hypertension and cerebrovascular disorders in Korea. We investigated its protective effect against Ang II-induced cytoskeletal change and hypertrophy in H9c2 cells. The results showed that treating cells with Ang II resulted in pathological hypertrophy, such as increased expression of transcription factors NFAT-3/p-NFAT-3, hypertrophic response genes (atrial natriuretic peptide [ANP] and b-type natriuretic peptide [BNP]), and Gαq down-stream effectors (PLCß3 and calcineurin). Pretreatment with AOF (60-100 µg/mL) led to significantly reduced hypertrophy. We also found that AOF pretreatment significantly suppressed the cardiac remodeling proteins, metalloproteinase (MMP9 and MMP2), and tissue plasminogen activator (tPA), induced by Ang II challenge. In conclusion, we provide evidence that AOF protects against Ang II-induced pathological hypertrophy by specifically inhibiting the insulin-like growth factor (IGF) II/IIR-related signaling pathway in H9c2 cells. AOF might be a candidate for cardiac hypertrophy and ventricular remodeling prevention in chronic cardiovascular diseases.

Gualou Xiebai decoction inhibits cardiac dysfunction and inflammation in cardiac fibrosis rats.

BACKGROUND: Gualou Xiebai Decoction (GXD) is a well-known traditional Chinese recipe. It has been used to treat cardiovascular disorders for nearly two thousand years. But there is a lack of reports on cardiac fibrosis and underlying mechanism. METHODS: Myocardial infarction was performed by ligation of left anterior descending coronary artery (LAD) in male Wistar rats. Rats with myocardial infarction were treated with GXD (1.14 g/kg, 4.53 g/kg) daily for 4 weeks. Cardiac function was evaluated by echocardiography. Hemodynamic parameters and infarct size were measured in each group. Myocardial enzymes were examined by biochemical tests. Inflammatory cytokines were assessed by ELISA, and interrelated proteins were detected by western blot. RESULTS: Cardiac function was significantly improved in GXD-treatment rats after myocardial infarction (MI), which was accompanied with decreased infarct size. Administration of GXD to myocardial fibrosis rats significantly ameliorated the activities of AST, LDH and CK-MB in serum. The increase in inflammatory factors (TNF-α, IL-1ß) were markedly reduced upon GXD treatment. Furthermore, the inflammatory mediators (NF-κB p65, TNF-α, MCP-1) were down-regulated by GXD in the myocardial fibrosis rats. CONCLUSIONS: Treatment with GXD improved cardiac function induced by myocardial fibrosis by inhibiting expression of inflammatory mediators associated with NF-κB.