Anti-apoptotic effects of diosgenin on ovariectomized hearts.

BACKGROUND: The anti-apoptotic effects of diosgenin, a steroid saponin, on hearts in female with estrogen deficiency have been less studied. This study aimed to evaluate the anti-apoptotic effects of diosgenin on cardiac widely dispersed apoptosis in a bilateral ovariectomized animal model. METHODS: A total of 60 female Wistar rats, aged 6-7 months, were divided into the sham-operated group (Sham), bilateral ovariectomized rats for 2 months, and ovariectomized rats administered with 0, 10, 50, or 100 mg/kg diosgenin daily (OVX, OVX 10, OVX 50, and OVX 100, respectively) in the second month. The excised hearts were analyzed by H&E staining, TUNEL(+) assays and Western Blot. RESULT: Cardiac TUNEL(+) apoptotic cells, the levels of Fas ligand, Fas death receptors, Fas-associated death domain, active caspase-8, and active caspase-3 (FasL/Fas-mediated pathways) as well as the levels of Bax, Bad, Bax/Bcl2, Bad/p-Bad, cytosolic Cytochrome c, active caspase-9, and active caspase-3 (mitochondria-initiated pathway) were increased in OVX compared with Sham group but those were decreased in OVX 50 compared with OVX. CONCLUSION: Diosgenin appeared to prevent or suppress ovariectomy-induced cardiac FasL/Fas-mediated and mitochondria-initiated apoptosis. These findings might provide one of the possible therapeutic approaches of diosgenin for potentially preventing cardiac apoptosis in women after bilateral ovariectomy or women with estrogen deficiency.

Small Molecule Compound Nerolidol attenuates Hypertension induced hypertrophy in spontaneously hypertensive rats through modulation of Mel-18-IGF-IIR signalling.

BACKGROUND: Cardiovascular diseases are caused by multitudes of stress factors like hypertension and their outcomes are associated with high mortality and morbidity worldwide. Nerolidol, a naturally occurring sesquiterpene found in several plant species, embodies various pharmacological benefits against numerous health disorders. However, their effects on hypertension induced cardiac complications are not completely understood. PURPOSE: The present study is to elucidate the efficacy of nerolidol against hypertension related cardiac hypertrophy in spontaneously hypertensive rats (SHRs). STUDY DESIGN: For preliminary in vitro studies, H9c2 cardiomyoblasts cells were challenged with 200 nM Angiotensin-II (AngII) for 12 h and were then treated with nerolidol for 24 h. The hypertrophic effect in H9c2 cells were analyzed by actin staining and the modulations in hypertrophic protein markers and mediators were determined by Western blotting analysis. For in vivo experiments, sixteen week-old male Wistar Kyoto (WKY) and SHRs were segregated into five groups (n = 9): Control WKY, hypertensive SHRs, SHRs with low dose (75 mg/kg b.w/day) nerolidol, SHRs with high dose (150 mg/kg b.w/day) nerolidol and SHR rats treated with an anti-hypertensive drug captopril (50 mg/kg b.w/day). Nerolidol treatment was given orally for 8 weeks and were analysed through Echocardiography. After euthanasia, hematoxylin and eosin staining, Immunohistochemical analysis and Western blotting was performed on left ventricle tissue. RESULTS: Western blotting analysis revealed that nerolidol significantly attenuates AngII induced expression of hypertrophic markers ANP and BNP in H9c2 cardiomyoblasts. In addition, actin staining further ascertained the potential of nerolidol to ameliorate AngII induced cardiac hypertrophy. Moreover, nerolidol administration suppressed the hypertrophic signalling mediators like calcineurin, GATA4, Mel-18, HSF-2 and IGFIIR in a dose-dependent fashion. In silico studies also ascertained the role of Mel-18 in the ameliorative effects of nerolidol. Further, these intriguing in vitro results were further confirmed in in vivo SHR model. Oral neraolidol in SHRs efficiently reduced blood pressure and ameliorated hypertension induced cardiac hypertrophic effects by effectively reducing the levels of proteins involved in cardiac MeL-18-HSF2-IGF-IIR signalling. CONCLUSION: Collectively, the data reveals that the cardioprotective effect of nerolidol against hypertension induced hypertrophy involves reduction in blood pressure and regulation of the cardiac Mel-18-IGFIIR signalling cascade.

A novel dipeptide from potato protein hydrolysate augments the effects of exercise training against high-fat diet-induced damages in senescence-accelerated mouse-prone 8 by boosting pAMPK / SIRT1/ PGC-1α/ pFOXO3 pathway.

The pathological effects of obesity are often severe in aging condition. Although exercise training is found to be advantageous, the intensity of exercise performed is limited in aging condition. Therefore in this study we assessed the effect of a combined treatment regimen with a short-peptide IF isolated from alcalase potato-protein hydrolysates and a moderate exercise training for 15 weeks in a 6 month old HFD induced obese senescence accelerated mouse-prone 8 (SAMP8) mice model. Animals were divided into 6 groups (n=6) (C:Control+BSA); (HF:HFD+BSA); (EX:Control+ BSA+Exercise); (HF+IF:HFD+ IF); (HF+EX:HFD+Exercise); (HF+EX+IF:HFD+Exercise+IF). A moderate incremental swimming exercise training was provided for 6 weeks and after 3 weeks of exercise, IF was orally administered (1 mg/kg body Weight). The results show that combined administration of IF and exercise provides a better protection to aging animals by reducing body weight and regulated tissue damage. IF intake and exercise training provided protection against cardiac hypertrophy and maintains the tissue homeostasis in the heart and liver sections. Interestingly, IF and exercise training showed an effective upregulation in pAMPK/ SIRT1/ PGC-1α/ pFOXO3 mechanism of cellular longevity. Therefore, exercise training with IF intake is a possible strategy for anti-obesity benefits and superior cardiac and hepatic protection in aging condition.

Protein hydrolysate from potato confers hepatic-protection in hamsters against high fat diet induced apoptosis and fibrosis by suppressing Caspase-3 and MMP2/9 and by enhancing Akt-survival pathway.

BACKGROUND: A potato protein hydrolysate, APPH is a potential anti-obesity diet ingredient. Since, obesity leads to deterioration of liver function and associated liver diseases, in this study the effect of APPH on high fat diet (HFD) associated liver damages was investigated. METHODS: Six week old male hamsters were randomly separated to six groups (n = 8) as control, HFD (HFD fed obese), L-APPH (HFD + 15 mg/kg/day of APPH), M-APPH (HFD + 30 mg/kg/day), H-APPH (HFD + 75 mg/kg/day of APPH) and PB (HFD + 500 mg/kg/day of probucol). HFD fed hamsters were administered with APPH 50 days through oral gavage. The animals were euthanized and the number of apoptotic nuclei in liver tissue was determined by TUNEL staining and the extent of interstitial fibrosis was determined by Masson's trichrome staining. Modulation in the molecular events associated with apoptosis and fibrosis were elucidated from the western blotting analysis of the total protein extracts. RESULTS: Hamsters fed with high fat diet showed symptoms of liver damage as measured from serum markers like alanine aminotransferase and aspartate aminotransferase levels. However a 50 day long supplementation of APPH effectively ameliorated the effects of HFD. HFD also modulated the expression of survival and apoptosis proteins in the hamster liver. Further the HFD groups showed elevated levels of fibrosis markers in liver. The increase in fibrosis and apoptosis was correlated with the increase in the levels of phosphorylated extracellular signal-regulated kinases (pERK1/2) revealing a potential role of ERK in the HFD mediated liver damage. However APPH treatment reduced the effect of HFD on the apoptosis and fibrosis markers considerably and provided hepato-protection. CONCLUSION: APPH can therefore be considered as an efficient therapeutic agent to ameliorate high fat diet related liver damages.

Hepato-protective effects of Glossogyne tenuifolia in Streptozotocin-nicotinamide-induced diabetic rats on high fat diet.

BACKGROUND: Glossogyne tenuifolia (GT) is a traditional herbal tea in Penghu Island, Taiwan. Its extract is traditionally been used as an antipyretic, hepatoprotective and anti-inflammatory remedy in folk medicine among local residents. The present study investigated whether GT could improve streptozotocin-induced acute liver injury of type 2 diabetes mellitus. METHODS: Male Wistar rats aged eight weeks were induced to be hyperglycemic by the subcutaneous injection of streptozotocin-nicotinamide (STZ-NA) and a combination of a high-fat diet (HFD) (N group). The animals were given GT extracts at a low dose (50 mg/kg) (L group) or a high dose (150 mg/kg) (H group) or an anti-diabetic drug (acarbose) (P group) in drinking water for 4 weeks. RESULTS: The results revealed that STZ-NA increased hepatomegaly, hepatocyte cross-sectional area, hypertrophy-related pathways (IL6/STAT3-MEK5-ERK5, NFATc3, p38 and JNK MAPK), proapoptotic molecules (cytochrome C, cleaved caspase-3), and fibrosis-related pathways (FGF-2, pERK1/2). These pathway components were then expressed at lower levels in the L and H group when compared with the N group. The liver-protective effect of GT in STZ-NA-induced diabetic rats with hyperlipidemia was through an enhancement in the activation of the compensatory PI3K-Akt and Bcl2 survival-related pathway. CONCLUSION: The results demonstrate that the hot water extracts of GT efficiently ameliorates the STZ-NA-induced diabetes associated liver damage in rat models.

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.

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.

Potential phytoestrogen alternatives exert cardio-protective mechanisms via estrogen receptors.

The 17 beta-estradiol (E2) is a sex hormone that is most abundant and most active estrogen in premenopausal women. The importance of E2 in providing cardioprotection and reducing the occurrence of heart disease in women of reproductive age has been well recognized. There are three subtype of estrogen receptors (ERs), including ERα, ERß and GPR30 have been identified and accumulating evidence reveal their roles on E2-mediated genomic and nongenomic pathway in cardiomyocytes against various cardiac insults. In this review, we focus on the estrogen and ERs mediated signaling pathways in cardiomyocytes that determines cardio-protection against various stresses and further discuss the clinical implication of ERs and phytoestrogens. Further we provide some insights on phytoeostrogens which may play as alternatives in estrogen replacement therapies.