Alpinia oxyphylla Miq extract ameliorates cardiac fibrosis associated with D‐galactose induced aging in rats

Cardiac fibrosis is a common pathophysiological process observed during chronic and stress‐induced acceleration of cardiac aging. Fibrosis is a necessary process during wound healing and tissue repair. However, its deposition in organs would proceed to scarring and organ damage. Here Alpinate Oxyphyllae Fructus (AOF), a Chinese medicine extract was used to protect aging heart from collagen accumulation. About 8 weeks old, male SD rats were randomly divided into (i) Control, (ii) D‐galactose induced aging (IA), (iii) IA + AOF 50 (AOF low, AL), (iv) IA + AOF 100 (AOF medium, AM), (v) IA + AOF 150 (AOF high, AH) mg/kg/day, AOF was administered orally. After 8 weeks rats were sacrificed and hearts were collected. Results showed collagen deposition and up‐regulation of matrix metalloproteinases‐MMP‐2 and ‐9 in D‐galactose‐induced aging rats. Furthermore, western blotting and immunostaining were also confirmed the upregulation of TGF‐β1 mediated fibrosis in aging induced rats. However, collagen deposition and fibrosis were significantly decreased by AOF treatments (AM and AH). AOF treatments salvaged the cardiac fibrosis. Hence, AOF might be a potential therapeutic agent in the prevention of cardiac fibrosis associated with aging. The protective effects of AOF might have promising results in anti‐aging treatments.     

Oral administration of alcalase potato protein hydrolysate‐APPH attenuates high fat diet‐induced cardiac complications via TGF‐β/GSN axis in aging rats

Consumption of high fat diet (HFD) is associated with increased cardiovascular risk factors among elderly people. Aging and obesity induced‐cardiac remodeling includes hypertrophy and fibrosis. Gelsolin (GSN) induces cardiac hypertrophy and TGF‐β, a key cytokine, which induces fibrosis. The relationship between TGF‐β and GSN in aging induced cardiac remodeling is still unknown. We evaluated the expressions of TGF‐β and GSN in HFD fed 22 months old aging SD rats, followed by the administration of either probucol or alcalase potato protein hydrolysate (APPH). Western blotting and Masson trichrome staining showed that APPH (45 and 75 mg/kg/day) and probucol (500 mg/kg/day) treatments significantly reduced the aging and HFD‐induced hypertrophy and fibrosis. Echocardiograph showed that the performance of the hearts was improved in APPH, and probucol treated HFD aging rats. Serum from all rats was collected and H9c2 cells were cultured with collected serums separately. The GSN dependent hypertrophy was inhibited with an exogenous TGF‐β in H9c2 cells cultured in HFD+ APPH treated serum. Thus, we propose that along with its role in cardiac fibrosis, TGF‐β also acts as an upstream activator of GSN dependent hypertrophy. Hence, TGF‐β in serum could be a promising therapeutic target for cardiac remodeling in aging and/or obese subjects.     

Adipose‐derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia‐reperfusion in a rat model

Acute kidney injury (AKI) represents a group of complicated syndromes with a high mortality rate. The administration of adipose‐derived mesenchymal stem cells (ADMSCs) has been tested as a possible treatment method for AKI. The long‐term evaluation of AKI induced by ischemia/reperfusion (IR) and the probable renal protection of ADMSCs are limited. In this study we have established a rat AKI model induced by IR and investigated the possible protective effects of ADMSCs. Adult Sprague‐Dawley (SD) rats were divided into three groups (n = 6/each group). The MOCK group was as the normal control. Rats in the IR‐AKI and IR‐AKI+ADMSCs groups were subjected to IR injury by clamping both renal pedicles for 40 minutes. Rats in the MOCK and IR‐AKI groups were injected with PBS via the tail vein as negative treatment controls. Rats in the IR‐AKI+ADMSCs group received ADMSCs therapy (2 × 10⁶ cells were injected into the rats via the tail vein). We found that ADMSC transplantation restored the pathologic morphology induced by IR‐AKI to normal compared with the MOCK group, suggesting the reparative function of ADMSCs in kidney tissues. Compared with IR‐induced AKI alone, ADMSC treatment significantly decreased the number of apoptotic cells, the level of total urinary protein and serum creatinine, the expression of pro‐inflammatory cytokines (IL‐6, TNF‐α, IL‐1β, IFN‐γ, TNF‐α, IFN‐γ, and TGF‐β), and the inflammation‐associated proteins (HGF and SDF1), but increased the expression of the anti‐inflammatory cytokine, IL‐10, and the anti‐apoptotic regulator, Bcl‐2. Our data have indicated that ADMSC transplantation may protect against IR‐induced AKI by anti‐apoptotic and anti‐inflammatory effects.     

Silymarin attenuates paraquat‐induced lung injury via Nrf2‐mediated pathway in vivo and in vitro

The present study aims to investigate the impacts and mechanisms of silymarin on paraquat (PQ)‐induced lung injury in vivo and in vitro. In in vivo experiments, a total of 32 male Sprague‐Dawley (SD) rats were randomly divided into four groups. The rats were killed on day 3. Histopathological changes in lung tissue were examined using HE and Masson's trichrome staining. Biomarkers of neutrophil activation, pulmonary oedema, pulmonary fibrosis, lung permeability and oxidative stress were detected. Several proinflammatory mediators and antioxidant related proteins were measured. In in vitro experiments, A549 cells were transfected with Nrf2 special siRNA to investigate the roles of Nrf2. The results show that silymarin administration abated PQ‐induced lung histopathologic changes, decreased inflammatory cell infiltration and lung wet weight/dry weight (W/D) ratio, suppressed myeloperoxidase (MPO) activity and nitric oxide (NO)/inducible nitric oxide synthases (iNOS) expression, downregulated hydroxyproline (HYP) levels, reduced total protein concentration and proinflammatory mediator release, and improved oxidative stress (malondialdehyde, MDA; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GSH‐Px) in lung tissue and serum. Meanwhile, treatment with silymarin upregulated the levels of nuclear factor‐erythroid‐2‐related factor 2 (Nrf2), heme oxygenase‐1 (HO‐1) and NAD(P)H:quinone oxidoreductase‐1(NQO1). However, the addition of Nrf2 siRNA reduced the expression of Nrf2‐mediated antioxidant protein HO‐1 and thus reversed the protective effects of silymarin against oxidative stress and inflammatory response. These results suggest that silymarin may exert protective effects against PQ‐induced lung injury. Its mechanisms were associated with the Nrf2‐mediated pathway. Therefore, silymarin may be a potential therapeutic drug for lung injury.     

Pheretima aspergillum extract attenuates high‐KCl‐induced mitochondrial injury and pro‐fibrotic events in cardiomyoblast cells

Hyperkalemia is often associated with cardiac dysfunction. In this study an earthworm extract (dilong) was prepared from dried Pheretima aspergillum powder and its effect against high‐KCl challenge was determined in H9c2 cardiomyoblast cells. H9c2 cells pre‐treated with dilong (31.25, 62.5, 125, and 250 mg/mL) for 24 hours, where challenged with different doses of KCl treatment for 3 hours to determine the protective mechanisms of dilong against cardiac fibrosis. High‐KCl administration induced mitochondrial injury and elevated the levels of pro‐apoptotic proteins. The mediators of fibrosis such as ERK, uPA, SP1, and CTGF were also found to be upregulated in high‐KCl condition. However, dilong treatment enhanced IGF1R/PI3k/Akt activation which is associated with cell survival. In addition, dilong also reversed high‐KCl induced cardiac fibrosis related events in H9c2 cells and displayed a strong cardio‐protective effect. Therefore, dilong is a potential agent to overcome cardiac events associated with high‐KCl toxicity.     

Exacerbated cardiac fibrosis induced by β‐adrenergic activation in old mice due to decreased AMPK activity

Senescent hearts exhibit defective responses to β‐adrenergic receptor (β‐AR) over‐activation upon stress, leading to more severe pathological cardiac remodelling. However, the underlying mechanisms remain unclear. Here, we investigated the role of adenosine monophosphate‐activated protein kinase (AMPK) in protecting against ageing‐associated cardiac remodelling in mice upon β‐AR over‐activation. 10‐week‐old (young) and 18‐month‐old (old) mice were subcutaneously injected with the β‐AR agonist isoproterenol (ISO; 5 mg/kg). More extensive cardiac fibrosis was found in old mice upon ISO exposure than in young mice. Meanwhile, ISO treatment decreased AMPK activity and increased β‐arrestin 1, but not β‐arrestin 2, expression, and the effects of ISO on AMPK and β‐arrestin 1 were greater in old mice than in young mice. Similarly, young AMPKα2‐knockout (KO) mice showed more extensive cardiac fibrosis upon ISO exposure than that was observed in age‐matched wild‐type (WT) littermates. The extent of cardiac fibrosis in WT old mice was similar to that in young KO mice. Additionally, AMPK activities were decreased and β‐arrestin 1 expression increased in KO mice. In contrast, the AMPK activator metformin decreased β‐arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure. In conclusion, more severe cardiac fibrosis is induced by ISO in old mice than in young mice. A decrease in AMPK activity, which further increases β‐arrestin 1 expression, is the central mechanism underlying the ageing‐related cardiac fibrosis induced by ISO. The AMPK activator metformin is a promising therapeutic agent for treating ageing‐related cardiac remodelling upon β‐AR over‐activation.     

Attenuation of the LPS‐induced,ERK‐mediated upregulation of fibrosis‐related factors FGF‐2, uPA,MMP‐2, and MMP‐9 by Carthamus tinctorius L in cardiomyoblasts

Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. LPS was previously found to dramatically upregulate expression of fibrosis‐related factors FGF‐2, uPA, MMP‐2, and MMP‐9 in primary cardiac fibroblasts. MMPs are capable of denaturing and degrading fibrillar collagens and other components of the extracellular matrix (ECM). Studies have shown that dysregulation of expression of MMPs is associated with development of myocardial extracellular matrix remodeling and cardiac fibrosis, which contribute to progression of heart failure. In this study, H9c2 cells and cardiac fibroblasts were divided into five treatment groups: control, LPS (1 μg/mL) and three concentrations of FC_EtOH (Carthami Flos ethanolic extract) (31.25, 62.5, and 125 μg/mL). Phosphorylation of ERK‐1/2 was observed to be rapidly induced upon treatment with LPS. In contrast, it was significantly suppressed by the administration of FC_EtOH (125 μg/mL). Effects of FC_EtOH on LPS‐induced MMP‐2 and MMP‐9 expression in H9c2 cells occurred directly through ERK1/2 were determined. H9c2 cells were therefore pretreated with EGF‐R to activate ERK pathway. Both protein levels of MMP‐2 and MMP‐9 and immunefluorescent signals of MMP‐9 were significantly enhanced by EGFR. In contrast, MMP‐2 and MMP‐9 were significantly reduced after FC_EtOH administration. Based on these findings, the authors concluded that FC_EtOH elicits a protective effect against LPS‐induced cardio‐fibrosis through the ERK1/2 pathway. Carthamus tinctorius L may potentially serve as a cardio‐protective agent against LPS‐ induced cardiac fibrosis. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 754–763, 2017.     

l‐Arginine Attenuates Cardiac Dysfunction,But Further Down‐Regulates α‐Myosin Heavy Chain Expression in Isoproterenol‐Induced Cardiomyopathy

In view of previously reported increased capacity for nitric oxide production, we suggested that l ‐arginine (ARG), the nitric oxide synthase (NOS) substrate, supplementation would improve cardiac function in isoproterenol (ISO)‐induced heart failure. Male Wistar rats were treated with ISO for 8 days (5 mg/kg/day, i.p.) or vehicle. ARG was given to control (ARG) and ISO‐treated (ISO+ARG) rats in water (0.4 g/kg/day). ISO administration was associated with 40% mortality, ventricular hypertrophy, decreased heart rate, left ventricular dysfunction, fibrosis and ECG signs of ischaemia. RT‐PCR showed increased mRNA levels of cardiac hypertrophy marker atrial natriuretic peptide, but not BNP, decreased expression of myosin heavy chain isoform MYH6 and unaltered expression of pathological MYH7. ISO increased the protein levels of endothelial nitric oxide synthase, but at the same time it markedly up‐regulated mRNA and protein levels of gp91phox, a catalytical subunit of superoxide‐producing NADPH oxidase. Fibrosis was markedly increased by ISO. ARG treatment moderately ameliorated left ventricular dysfunction, but was without effect on cardiac hypertrophy and fibrosis. Combination of ISO and ARG led to a decrease in cav‐1 expression, a further increase in MYH7 expression and a down‐regulation of MYH6 that inversely correlated with gp91phox mRNA levels. Although ARG, at least partially, improved ISO‐impaired basal left ventricular systolic function, it failed to reduce cardiac hypertrophy, fibrosis, oxidative stress and mortality. The protection of contractile performance might be related to increased capacity for nitric oxide production and the up‐regulation of MYH7 which may compensate for the marked down‐regulation of the major MYH6 isoform.     

Naringenin attenuates CCl4‐induced hepatic inflammation by the activation of an Nrf2‐mediated pathway in rats

The possible protective effects of naringenin, a naturally occurring citrus flavonone, on carbon tetrachloride (CCl₄)‐induced liver injury in rats and the mechanism underlying its effects were investigated. Forty rats were divided into five groups. Rats in Groups I and II served as the normal and injured liver groups, respectively; Group III rats were treated with the standard drug silymarin as a positive control; and rats in Groups IV and V (naringenin‐treated groups) were administrated 50 mg/kg, p.o., naringenin for 7 days. Liver samples were collected to evaluate mRNA and protein expression, histological changes and oxidative stress. Naringenin inhibited lipid peroxidation and reduced serum levels of hepatic enzymes induced by CCl₄. In addition, naringenin increased the liver content of reduced glutathione and the activity of anti‐oxidant enzymes in rats treated with CCl₄. Naringenin attenuated liver inflammation by downregulating CCl₄‐induced activation of tumour necrosis factor (TNF)‐α, inducible nitric oxide synthase (iNOS) and cyclo‐oxygenase (COX‐2) at both the protein and mRNA levels. Naringenin treatment significantly increased NF‐E2‐related factor 2 (Nrf2) and heme oxygenase (HO‐1) expression in injured livers. In rats treated with CCl₄ alone, decreases were seen in nuclear Nrf2 expression and in the mRNA levels of its target genes (e.g. HO‐1, NQO1 and glutathione S‐transferase alpha 3 (GST‐a3)). Together, the results suggest that naringenin can protect the liver against oxidative stress, presumably by activating the nuclear translocation of Nrf2 as well as attenuating the TNF‐α pathway to elicit an anti‐inflammatory response in liver tissue.     

Naringenin prevents ischaemic stroke damage via anti‐apoptotic and anti‐oxidant effects

Apoptosis and oxidative stress are considered to be the major factors associated with the development and progression of many ischaemic cerebrovascular diseases. Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to exhibit anti‐oxidant, anti‐carcinogenic and anti‐apoptotic effects. This study aimed to investigate the anti‐apoptotic and anti‐oxidant effects of naringenin on ischaemic stroke. In vitro, cortical neuron cells isolated from the brains of neonatal Sprague–Dawley rats were randomly divided into control, oxygen and glucose deprivation/reperfusion (OGD/Rep), NAR‐L, NAR‐M and NAR‐H groups. MTT and RT‐PCR were used for cell proliferation and apoptosis‐related proteins analyses. The effects of NAR on the Nrf2 signalling pathway were investigated using transfection approaches. Differences in mitochondrial dysfunction were analyzed by flow cytometry. In vivo, middle cerebral artery occlusion (MCAO) model was prepared and neurological defects and the brain wet/dry (W/D) ratio were assessed and recorded; apoptosis was measured based on the TUNEL assay. Additionally, biochemical indices were detected both in vitro and in vivo. NAR promoted cortical neuron cell proliferation, inhibited apoptosis and oxidative stress, and regulated the localization of Nrf2 protein (P<.05). Furthermore, silencing and overexpression of Nrf2 affected cortical neuron cell proliferation and apoptosis (P<.05). In vivo, NAR could alleviate cerebral oedema, improve neurological defects, and reduce apoptosis and oxidative stress (P<.05). These findings demonstrated that NAR could reduce apoptosis and oxidative stress and that Nrf2 signalling pathway is involved in this regulatory process. NAR has health‐promoting properties because of its anti‐apoptotic and anti‐oxidant effects in cases of ischaemic stroke.     

Genistein protects against doxorubicin‐induced cardiotoxicity through Nrf‐2/HO‐1 signaling in mice model

Doxorubicin (DOX)‐induced cardiomyopathy is a lethal disease. DOX‐induced cardiotoxic effects are attributed towards increased redox status and apoptotic signaling. In this study, we show that genistein offers protection against DOX‐induced cardio toxicity in the mice model. DOX‐mediated increase in serum cardiac troponin and redox markers (ROS, LPO, 4‐hydroxynonenal‐protein adducts [HNE] levels) was significantly reduced by genistein treatment. Significantly increased TNF‐α, IL‐6, IL‐8 expressions during DOX‐induced inflammatory responses were down regulated by genistein treatment. Further, we found that genistein regulated antioxidant response through increased Nrf‐2, HO‐1, NQO1 protein expressions. In addition, DOX downregulated survival proteins (p‐Akt, Bcl‐2) with concomitant upregulation in Erk (1/2), Bax and cleaved caspase‐3 expressions. The apoptotic activation was significantly downregulated by genistein treatment through suppression of apoptosis. Altogether, these findings show that genistein protects against DOX‐induced cardiotoxic effects through activation of Nrf‐2/HO‐1 signaling.     

The effect of streptozotocin‐induced diabetes on cardiac β‐adrenoceptor subtypes in the rat

1 The present study investigates the effect of short‐term experimental diabetes of 14‐days duration on the β‐adrenoceptor subtypes of the rat heart. 2 β‐adrenoceptor‐mediated functional responses to submaximal doses of isoprenaline were enhanced in Langendorff‐perfused hearts from diabetic rats, manifested as greater changes in tension, heart rate and rates of tension development (+dT/dt) and decline (–dT/dt). 3 Radioligand binding data demonstrated that total cardiac β‐adrenoceptor density and affinity for [³H]‐dihydroalprenolol was unchanged by diabetes, although a decrease in β₁‐adrenoceptor density and increase in β₂‐adrenoceptor density was observed. 4 In conclusion, hearts from 14‐day streptozotocin‐induced diabetic rats demonstrate a number of alterations within the β‐adrenoceptor system. However, the enhanced β‐adrenoceptor‐mediated responses to isoprenaline were not caused by an overall increase in density of β‐adrenoceptors, but were accompanied by changes in the ratio of the β‐adrenoceptor subtypes.     

Telmisartan attenuates peritoneal fibrosis via peroxisome proliferator‐activated receptor‐γ activation in rats

Peritoneal dialysis (PD) is an effective treatment for patients with end‐stage renal diseases, but long‐term continuous PD causes peritoneal fibrosis (PF). This study aims to evaluate the anti‐fibrotic effect of telmisartan on a rat model of PF and to investigate the underlying mechanisms. Five‐sixths kidney nephrectomy and PD were used to establish the PF rat model. Glucose (2.5%) was used to establish an in vitro model in rat peritoneal mesothelial cells (PMC). Haematoxylin–eosin staining was used to examine the structural alterations. Masson's trichrome staining was used to observe the tissue fibrosis in peritoneal membrane of rats. Real‐time polymerase chain reaction was used to measure messenger RNA expressions of profibrotic factors. Western blotting was used to determine protein expressions of profibrotic factors, peroxisome proliferator‐activated receptor‐γ, and mitogen‐activated protein kinases (MAPK). Results demonstrated that administration of telmisartan dose‐dependently attenuated the thickening of the peritoneal membrane and the fibrosis induced by long‐term PD fluid exposure in rats. In addition, telmisartan treatment inhibited the upregulation of profibrotic factors induced by PD in the peritoneum of rats and by high‐concentration glucose in PMC. Telmisartan was also effective in inhibiting PD and high‐concentration, glucose‐induced phosphorylation of MAPK in the peritoneum and PMC. Furthermore, peroxisome proliferator‐activated receptor‐γ (PPARγ) inhibitor GW9662 blocked these protective effects of telmisartan in PMC. The results suggest that telmisartan is effective in attenuating PD‐induced PF, and this effect may be associated with the inhibition of profibrotic factor expression and MAPK phosphorylation via PPARγ activation.     

Antifibrosis effects of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf in a rat model of bleomycin‐induced pulmonary fibrosis

Objective The aim of this study was to investigate the prophylactic effect and some mechanisms of action of triterpene acids of loquat (TAL) on bleomycin A5‐induced pulmonary fibrosis rats. Methods A model of pulmonary fibrosis was induced by injecting rats with a single dose of bleomycin A5 (5 mg/kg) into the trachea. From the second day, rats in the preventive groups were treated with TAL (50, 150 or 450 mg/kg) or dexamethasone (1.2 mg/kg). On the 28th day after medication, the rats were killed and haematoxylin‐eosin or masson staining was used to evaluate the degree of pulmonary fibrosis. Tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) levels in alveolar macrophage culture supernatant were detected by ELISA. The mRNA expression of TNF‐α and TGF‐β1 in alveolar macrophage was observed by RT‐PCR. Key findings Lung histopathological examination showed TAL could ameliorate the structure of the lung and alleviate fibrogenesis. At the same time, TAL (150 or 450 mg/kg dose group) could reduce the expression of TNF‐α and TGF‐β1 in alveolar macrophage of rats with pulmonary fibrosis at either the protein or mRNA level. Conclusions TAL had a positive prophylactic effect on lung fibrosis, which might have been related to its reduction on TNF‐α or TGF‐β1 expression in the alveolar macrophage of pulmonary fibrosis rats.     

Cellular apoptosis and cardiac dysfunction in STZ‐induced diabetic rats attenuated by anthocyanins via activation of IGFI‐R/PI3K/Akt survival signaling

Anthocyanins are known cyto‐protective agents against various stress conditions. In this study cardio‐protective effect of anthocyanins from black rice against diabetic mellitus (DM) was evaluated using a streptozotocin (STZ)‐induced DM rat model. Five‐week‐old male Wistar rats were administered with STZ (55 mg kg^?1, IP) to induce DM; rats in the treatment group received 250 mg oral anthocyanin/kg/day during the 4‐week treatment period. DM and the control rats received normal saline through oral gavage. The results reveal that STZ‐induced DM elevates myocardial apoptosis and associated proapoptotic proteins but down‐regulates the proteins of IGF1R mediated survival signaling mechanism. Furthermore, the functional parameters such as the ejection‐fraction and fraction‐shortening in the DM rat hearts declined considerably. However, the rats treated with anthocyanins significantly reduced apoptosis and the associated proapoptotic proteins and further increased the survival signals to restore the cardiac functions in DM rats. Anthocyanin supplementation enhances cardiomyocyte survival and restores cardiac function.     

β‐LAPachone ameliorates doxorubicin‐induced cardiotoxicity via regulating autophagy and Nrf2 signalling pathways in mice

β‐LAPachone (B‐LAP) is a naphthoquinone that possesses antioxidant properties. In the present investigation, the protective effect of B‐LAP against doxorubicin (DOX)‐induced cardiotoxicity was examined in mice. Thirty‐five mice were divided into 5 groups: control group, B‐LAP (5 mg/kg) group, DOX (15 mg/kg) group, DOX+B‐LAP (2.5 mg/kg) group and DOX+B‐LAP (5 mg/kg) group. B‐LAP was administered orally for 14 days of experimental period. A single dose of DOX (15 mg/kg) was injected intraperitoneally on day 3. Cardiac function, histoarchitecture, indices of oxidative stress and circulating markers of cardiac injury were examined. B‐LAP (5 mg/kg) decreased serum levels of lactate dehydrogenase (LDH), creatine kinase MB (CK‐MB) and cardiac troponin I (cTnI), and ameliorated cardiac histopathological alterations. In addition to increasing cellular NAD⁺/NADH ratio, B‐LAP up‐regulated the cardiac levels of SIRT1, beclin‐1, p‐LKB1 and p‐AMPK, and reduced the cardiac levels of p‐mTOR, interleukin (IL)‐1β, TNF (tumour necrosis factor)‐α and caspase‐3. B‐LAP also elevated the nuclear accumulation of Nrf2 and simultaneously up‐regulated the protein levels of haem oxygenase (HO‐1) and glutathione S‐transferase (GST) in the hearts of DOX mice. While B‐LAP reduced malondialdehyde concentrations in heart of DOX‐treated mice, it further promoted the activities of cardiac superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT).In accordance with increased cell survival, B‐LAP significantly improved the cardiac function of DOX mice. Collectively, these findings underline the protective potential of B‐LAP against DOX‐induced cardiotoxicity by regulating autophagy and AMPK/Nrf2 signalling pathway in mice.     

Chronic moderate alcohol consumption relieves high‐fat high‐cholesterol diet‐induced liver fibrosis in a rat model

Nonalcoholic fatty liver disease is a worldwide health issue and chronic alcohol consumption may have different effects on this disease. This study explored the role of chronic moderate alcohol consumption on high‐fat high‐cholesterol (HFHC) diet‐induced liver fibrosis in a rodent model. Male Sprague–Dawley rats were divided into five groups: standard chow group, standard chow plus Er Guo Tou (EGT, a Chinese spirit made from fermented cereals) group, HFHC group, HFHC plus EGT group, and HFHC plus pure ethanol (EtOH) group. Rats were fed standard chow or HFHC chow for 12 weeks. EGT or pure ethanol was administrated at a daily dose of 4 g/kg body weight via intra‐gastric gavage from week 4. At the end of week 12, hematoxylin and eosin staining, Sirius red and immunohistochemistry of liver sections were examined. The hepatic expression of F4/80, TNF‐α, IL‐1β, IL‐6, CXCL1, CXCL2, α‐SMA, Collagen, TGF‐β, MMP2, MMP9, and TIMP1 was calculated. Both moderate EGT and pure ethanol did not increase plasma endotoxin in the portal vein comparing with the FHFC group. EGT and pure ethanol did not improve hepatic inflammation, but ameliorated liver fibrosis in histology. Moderate EGT and pure ethanol ameliorated HFHC diet‐induced activation of Kupffer cells and hepatic stellate cells. In conclusion, chronic moderate EGT and pure ethanol could ameliorate HFHC diet‐induced liver fibrosis.     

Catecholamine‐induced myocardial fibrosis and oxidative stress is attenuated by Terminalia arjuna (Roxb.)

Objectives Myocardial fibrosis and oxidative stress accompany a number of cardiac disorders such as hypertrophic cardiomyopathy, hypertensive heart disease and cardiac failure. Stem bark of Terminalia arjuna has been advocated for cardiac ailments. The present study evaluated the effects of T. arjuna bark extract on myocardial fibrosis and oxidative stress induced by chronic beta‐adrenoceptor stimulation. Methods Aqueous extract of T. arjuna bark was evaluated at 63, 125 and 250 mg/kg given orally for antifibrotic and antioxidant effects in rats given the selective β‐adrenoceptor agonist isoprenaline (5 mg/kg s.c.) for 28 days. Captopril (50 mg/kg per day, given orally), an inhibitor of angiotensin‐converting enzyme used as a standard cardioprotective drug, was used as a positive control. Key findings Isoprenaline caused fibrosis, increased oxidative stress and cardiac hypertrophy (increased heart weight: body weight ratio and cardiomyocyte diameter). The T. arjuna bark extract and captopril significantly prevented the isoprenaline‐induced increase in oxidative stress and decline in endogenous antioxidant level. Both also prevented fibrosis but not the increase in heart weight: body weight ratio. Conclusions T. arjuna protects against myocardial changes induced by chronic beta‐adrenoceptor stimulation.