The Effect of NeuroAid (MLC901) on Cholestasis-Induced Spatial Memory Impairment with Respect to the Expression of BAX, BCL-2, BAD, PGC-1α and TFAM Genes in the Hippocampus of Male Wistar Rats.

Cholestasis is a bile flow reduction that is induced following Bile Duct Ligation (BDL). Cholestasis impairs memory and induces apoptosis. Apoptosis consists of two pathways: intrinsic and extrinsic. The intrinsic pathway is modulated by BCL-2 (B cell lymphoma-2) family proteins. BCL-2 (a pro-survival BCL-2 protein) has anti-apoptotic effect, while BAD (BCL-2-associated death) and BAX (BCL-2-associated X), the other members of BCL-2 family have pro-apoptotic effect. Furthermore, TFAM (mitochondrial transcriptional factor A) is involved in transcription and maintenance of mitochondrial DNA and PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) is a master regulator of mitochondrial biogenesis. On the other hand, NeuroAid is a Traditional Chinese Medicine with neuroprotective and anti-apoptosis effects. In this study, we evaluated the effect of cholestasis on spatial memory and expression of BCL-2, BAD, BAX, TFAM, and PGC-1α in the hippocampus of rats. Additionally, we assessed the effect of NeuroAid on cholestasis-induced cognitive and genetic alterations. Cholestasis was induced by BDL surgery and NeuroAid was injected intraperitoneal at the dose of 0.4 mg/kg. Furthermore, spatial memory was evaluated using Morris Water Maze (MWM) apparatus. The results showed cholestasis impaired spatial memory, increased the expression of BAD and BAX, decreased the expression of TFAM and PGC-1α, and did not alter the expression of BCL-2. Also, NeuroAid decreased the expression of BAD and BAX and increased the expression of TFAM, PGC-1α, and BCL-2. In conclusion, cholestasis impaired spatial memory and increased the expression of pro-apoptotic genes. Also, cholestasis decreased the expression of TFAM and PGC-1α. Interestingly, NeuroAid restored the effects of cholestasis.

ASMq protects against early burn wound progression in rats by alleviating oxidative stress and secondary mitochondria­associated apoptosis via the Erk/p90RSK/Bad pathway.

Burn wounds present an evolutionary progression, in which the initial wound tissue deepens and expands following thermal injury. Progressive tissue damage in the zone of stasis may worsen burn injury, which is associated with oxidative stress and secondary apoptosis, and worsen the prognosis of patients with burn wounds. The mitochondrial apoptotic pathway is involved in receiving oxidative signals and regulating tissue apoptosis. Previously, Abnormal Savda Munziq (ASMq), a natural compound of traditional Uyghur Medicine, which includes ten types of herb, has been reported to exhibit a number of effects, including anti­inflammatory, antioxidative and anti­apoptotic activities. The present study demonstrated that ASMq protected against early burn wound progression following thermal injury in rats; this effect may be mediated by its ability to attenuate oxidative stress­induced mitochondria­associated apoptosis. The present study may provide a novel therapeutic method to prevent early burn wound progression following burn injury.

Taurine inhibits neuron apoptosis in hippocampus of diabetic rats and high glucose exposed HT-22 cells via the NGF-Akt/Bad pathway.

Type 2 Diabetes causes learning and memory deficits that might be mediated by hippocampus neuron apoptosis. Studies found that taurine might improve cognitive deficits under diabetic condition because of its ability to prevent hippocampus neuron apoptosis. However, the effect and mechanism is not clear. In this study, we explore the effect and mechanism of taurine on inhibiting hippocampus neuron apoptosis. Sixty male Sprague-Dawley rats were randomly divided into control, T2D, taurine treatment (giving 0.5%, 1%, and 2% taurine in drinking water) groups. Streptozotocin was used to establish the diabetes model. HT-22 cell (hippocampus neurons line) was used for in vitro experiments. Morris Water Maze test was used to check the learning and memory ability, TUNEL assay was used to measure apoptosis and nerve growth factor (NGF); Akt/Bad pathway relevant protein was detected by western blot. Taurine improved learning and memory ability and significantly decreased apoptosis of the hippocampus neurons in T2D rats. Moreover, taurine supplement also inhibited high glucose-induced apoptosis in HT-22 cell in vitro. Mechanistically, taurine increased the expression of NGF, phosphorylation of Trka, Akt, and Bad, as well as reduced cytochrome c release from mitochondria to cytosol. However, beneficial effects of taurine were blocked in the presence of anti-NGF antibody or Akt inhibitor. Taurine could inhibit hippocampus neuron apoptosis via NGF-Akt/Bad pathway. These results provide some clues that taurine might be efficient and feasible candidate for improvement of learning and memory ability in T2D rats.

Selenium Nanoparticle Protection of Fibroblast Stress: Activation of ATF4 and Bcl-xL Expression.

BACKGROUND: In recent years, selenium nanostructures have been researched due to their antibacterial properties, low toxicity to mammalian cells, and high biological efficacy. However, the clinical implementation of the use of selenium has received mixed results, and there is much work needed to improve the understanding of the biological mechanisms involved in the observed cellular responses. MATERIALS AND METHODS: In this work, an investigation into the mechanistic pathways of selenium nanoparticles (SeNPs) in biological systems was conducted by studying the changes in gene expression of ATF4, Bcl-xL, BAD2, HSP70, and SOD2 in non-cancerous human dermal fibroblasts (HDF) under oxidative stress, nutrient deprivation stress, and no treatment (control) conditions. RESULTS: This study revealed that SeNP incubation led to reduced internal reactive oxygen species (ROS) generation for all conditions tested, thus, providing a protective environment for HDF. At the stress conditions, the expression of ATF4 and Bcl-xL increased for cells treated with SeNP incubation, leading to attenuation of the cells under stress. These results also hint at reductive stress causing a detrimental impact to cell proliferation under routine cell passaging conditions. CONCLUSION: In summary, this study highlights some possible mechanistic pathways implicated in the action of SeNPs that warrant further investigation (specifically, reducing stress conditions for HDF) and continues to support the promise of SeNPs in a wide range of medical applications.

Ubiquinol promotes retinal ganglion cell survival and blocks the apoptotic pathway in ischemic retinal degeneration.

Coenzyme Q10 (CoQ10) protects retinal ganglion cells (RGCs) in experimental retinal ischemia and glaucoma by scavenging reactive oxygen species. We tested whether a diet supplemented with ubiquinol, the reduced form of CoQ10, promotes RGC survival and blocks the apoptotic pathway in ischemic mouse retina induced by acute high intraocular pressure (IOP) elevation. Ubiquinol (1%) treatment significantly promoted RGC survival at 2 weeks after ischemia/reperfusion. The ubiquinol treatment significantly blocked activation of astroglial and microglial cells in the ischemic retina at 2 weeks. While the ubiquinol treatment significantly decreased active Bax protein expression in the ischemic retina, phosphorylation of Bad at serine 112 and Bcl-xL protein expression were preserved in the ubiquinol-treated ischemic retina at 12 h. Consistently, the ubiquinol treatment prevented apoptotic cell death by blocking caspase-3 cleavage. These results suggest that the ubiquinol enhances RGC survival by modulating the Bax/Bad/Bcl-xL-mediated apoptotic pathway in the ischemic retina. Ubiquinol has therapeutic potential for ameliorating elevated IOP-induced ischemic retinal degeneration.

Expression of Bcl-2 Family Proteins in the Ovarian Follicular Apparatus in the Acute Period after Experimental Hyperthermia.

The expression of apoptosis regulators (proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day 3 after hyperthermia (rectal temperature 43.5°C). Hyperthermia in the catabolic phase leads to different degrees of activation of the molecular "switches" of apoptosis in cells of ovarian follicular epithelium. This was seen from increased intensity of immunohistochemical staining for Bad protein against the background of more pronounced expression of Bcl-2 protein. On day 3 after exposure to hyperthermia, Bcl-2/Bad ratio increased, which reflects antiapoptotic protection of cells and conditions for blockade of mitochondrial pathway of apoptosis in the follicular apparatus of the ovaries during the acute period after hyperthermia.

Melatonin-Aluminum Oxide-Polymethylsiloxane Complex on Apoptosis of Liver Cells in a Model of Obesity and Type 2 Diabetes Mellitus.

We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.

Identification of apoptosis-related genes Bcl2 and Bax from yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to waterborne and dietborne zinc exposure.

Apoptosis plays a key role in the physiology of multicellular organisms, and has been well studied in mammals, but not in teleosts. Zinc (Zn) has been shown to be an important regulator of apoptosis and apoptosis involves in the regulation of lipid metabolism. Moreover, our recent study indicated that waterborne and dietborne Zn exposure differently influenced lipid metabolism in Pelteobagrus fulvidraco, but further mechanism remained unknown. The hypothesis of the present study is that apoptosis mediated the Zn-induced changes of lipid metabolism of P. fulvidraco subjected to different exposure pathways. To this end, we cloned full-length cDNA sequences of Bcl2 and three Bax subtypes involved in apoptosis in P. fulvidraco, explored their mRNA expressions in responses to different Zn exposure pathways. Bcl2 and three Bax subtypes shared similar domain structure as typical pro- and anti-apoptotic Bcl2 family members. Their mRNAs were widely expressed among various tissues, but at variable levels. Waterborne Zn exposure down-regulated mRNA levels of Baxg and ratios of Baxa/Bcl2, and Baxg/Bcl2, but showed no significant effects on mRNA abundances of Bcl2, Baxa and Baxb, and the ratio of Baxb/Bcl2. In contrast, dietborne Zn exposure up-regulated mRNA levels of Bcl2, Baxa, Baxb and Baxg, but reduced the ratios of Baxa/Bcl2, Baxb/Bcl2, and Baxg/Bcl2. Considering their important roles of these genes in apoptosis induced by Zn, apoptosis may mediate the Zn-induced changes of hepatic lipid metabolism of Pelteobagrus fulvidraco under different Zn exposure pathways. For the first time, we characterized the full-length cDNA sequences of Bcl2 and three Bax subtypes, determined their expression profiles and transcriptional responses to different Zn exposure pathways, which would contribute to our understanding of the molecular basis of apoptosis, and also provide new insights into physiological responses to different Zn exposure pathways.

Achyranthes bidentate saponins protect rat articular chondrocytes against interleukin-1ß-induced inflammation and apoptosis in vitro.

Achyranthes bidentate Blume (Niuxi) is often employed for treatment of arthritis in Traditional Chinese Medicine and possesses anti-inflammatory properties. Phytochemical and pharmacological studies proved the oleanane-type saponins to be the main bioactive principles. In the present study, protective effects of A. bidentata saponins (ABS) on inflammation and apoptosis in interleukine-1ß (IL-1ß)-induced chondrocytes were investigated. Rat chondrocytes were pretreated with ABS at 3 µg/mL, 10 µg/mL, and 30 µg/mL, and subsequently stimulated with IL-1ß (10 ng/mL). Methylthiazolyldiphenyl-tetrazolium bromide assay and annexin V/propidium iodide dual staining demonstrated that ABS could protect IL-1ß-induced chondrocyte injury. ABS suppressed IL-1ß-induced apoptosis by suppressing the activation of caspase-3, inhibiting levels of proapoptotic proteins Bax and Bad, decreasing p53 protein phosphorylation, and promoting the expression of antiapoptotic protein Bcl-xL and proliferating cell nuclear antigen. IL-1ß-induced inflammation and matrix degradation were also alleviated by ABS through the downregulation of the expressions of matrix metalloproteinases 3 and 9 and cyclooxygenase-2. Moreover, ABS inhibited IL-1ß-induced nuclear factor κB activation in rat chondrocytes. We demonstrated, for the first time, the protective effects of ABS on IL-1ß-stimulated chondrocytes and their molecular mechanisms. Thus, it is suggested that ABS might be a potential drug in the treatment of osteoarthritis.

Vitamin B2 Sensitizes Cancer Cells to Vitamin-C-Induced Cell Death via Modulation of Akt and Bad Phosphorylation.

Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits, including anticancer activity. Vitamin B2, another essential dietary nutrient, often coexists with vitamin C in some fruits, vegetables, or dietary supplements. The objective of the present study is to determine whether the combination of vitamin C and B2 can achieve a synergistic anticancer activity. MDA-MB-231, MCF-7, and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that the combination of vitamin C and B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin-C-based cancer chemoprevention and chemotherapy.

Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide.

Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 µM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to ΔΨm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions.

Recombinant Human Keratinocyte Growth Factor Induces Akt Mediated Cell Survival Progression in Emphysematous Mice.

INTRODUCTION: Emphysema has been associated with decreased VEGF and VEGFR-2 expression and the presence of high numbers of apoptotic alveolar cells. Keratinocyte growth factor stimulates VEGF synthesis which in turn confers normal lung structure maintenance via the Akt pathway. In this study the potential role of rHuKGF in the improvement of deregulated Akt mediated cell survival pathway in emphysematous mice was investigated. METHODS: Three experimental groups, i.e., emphysema, treatment and control groups, were prepared. Lungs of mice were treated on 3 occasions by oropharyngeal instillation of 10mg rHuKGF per kg body weight after induction of emphysema with porcine pancreatic elastase. Subsequently, lung tissues from mice were collected for histopathology and molecular biology studies. RESULTS AND DISCUSSION: Histopathology photomicrographs and destructive index analysis have shown that elastase-induced airspace enlargement and loss of alveoli recovered in the treatment group. rHuKGF stimulates VEGF production which in turn induces the Akt mediated cell survival pathway in emphysematous lungs. mRNA expression of VEGF, VEGFR, PI3K and Akt was significantly increased while Pten, Caspase-9 and Bad was notably decreased in treatment group when compared with emphysema group, being comparable with the control group. Moreover, VEGF protein expression was in accordance with that found for mRNA. CONCLUSION: Therapeutic rHuKGF supplementation improves the deregulated Akt pathway in emphysema, resulting in alveolar cell survival through activation of the endogenous VEGF-dependent cell survival pathway. Hence rHuKGF may prove to be a potential drug in the treatment of emphysema.

Apoptosis in MCF-7 breast cancer cells induced by S-alkenylmercaptocysteine (CySSR) species derived from Allium tissues in combination with sodium selenite.

S-Allylmercaptocysteine (CySSA) from garlic is known to exhibit anti-cancer effects. Apoptosis induction by CySSA was contrasted with S-1-propenylmercaptocysteine (CySSPe) (the major onion analog) in the presence of Na2SeO3 (Se) in breast cancer cells MCF-7. The dose of CySSA or CySSPe alone required to reduce viable cells by 50% was >400µM, and this was reduced to 62µM and 91µM for CySSA+Se and CySSPe+Se, respectively, at molar ratios of 39:1. Synergism of the mixtures was confirmed by isobologram analysis and the treatments evoked enhanced thiol efflux from MCF-7 cells. Apoptosis was confirmed by Annexin-V and propidium iodide staining. Cell cycle arrest occurred at the G2/M and sub-G1 interphases. Both CySSR+Se mixtures reduced the levels of Akt. CySSPe+Se elevated GSK-3 protein levels, whereas CySSA+Se did not. CySSR+Se mixtures enhanced phospho-c-Jun levels, with CySSA+Se more potent than CySSPe+Se. Corresponding increases in phospho-p53, Bax and Bad levels were observed, indicating apoptosis occurred via the mitochondrial pathway. Lack of caspases 6/7 activation implicated a caspase-independent pathway for apoptosis. Reduction of imported CySSR and export of thiols by MCF-7 cells facilitates the reduction of selenite to yield H2Se, a cytotoxic agent. This appears to be the first report of an anti-cancer effect of CySSPe.

Genistein suppresses the isoproterenol-treated H9c2 cardiomyoblast cell apoptosis associated with P-38, Erk1/2, JNK, and NFκB signaling protein activation.

Heart disease (HD) is associated with estrogen and therefore gender and menopausal status. In addition, clinical evidence shows that increased serum norepinephrine is found in patients with HD. Therefore, this study aimed to investigate the cardio-protective effect of genistein, a selective estrogen receptor modulator (SERM) from soy bean extract, in H9c2 cardiomyoblast cells treated with isoproterenol (ISO), a norepinephrine analog. In this in vitro model, image data and results from western blotting shown that ISO treatment was capable of inducing cellular apoptosis, especially the mitochondrial dependent pathway. Treatment of genistein could suppress the expression of mitochondrial pro-apoptotic proteins including Bad, caspase-8, caspase-9, and caspase-3 in H9c2 treated with ISO. By contrast, several survival proteins were expressed in H9c2 treated with genistein, such as phosphor (p)-Akt, p-Bad, and p-Erk1/2. Furthermore, we confirmed that the protective role of genistein was partially mediated through the expression of Erk1/2, Akt, and NF κ B proteins by adding several pathway inhibitors. These in vitro data suggest that genistein may be a safe and natural SERM alternative to hormone therapy in cardio-protection.

Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata.

Antrodia camphorata is a Chinese herb indigenous to Taiwan. Previous reports demonstrated that it could induce apoptosis in some cancer cells. The purpose of this study was to investigate the apoptotic effect of the crude extract of A. camphorata in cervical cancer cells. Two human cervical cancer cell lines, HeLa and C-33A, were treated with extract of A. camphorata (10-1000 µg/mL). We found that A. camphorata extract was cytotoxic to both cervical cancer cells in a dose- and time-dependent manner as examined by MTT assay. Treatment with A. camphorata extract at 400 µg/mL induced a 2.3- and 4.4-fold increase in oligonucleosome formation from the cleaved chromosomal DNA in HeLa and C-33A cells, respectively. A. camphorata extract also activated caspase-3, -8, and -9 activities and increased the cytosolic level of cytochrome c in both cell lines as the dosage increased. Furthermore, A. camphorata extract increased expressions of Bak, Bad and Bim, while decreasing expressions of Bcl-2 and Bcl-xL of the Bcl-2 family proteins in HeLa and C-33A cells. The expression of IAP proteins, XIAP and survivin, was also decreased in both cervical cancer cells after treatment with A. camphorata. Our in vitro study suggests that A. camphorata is cytotoxic to cervical cancer cells through both extrinsic and intrinsic apoptotic mechanisms. It could be used as a novel phytotherapeutic agent or auxiliary therapy in the treatment of cervical cancer.

Cadmium induced pathophysiology: prophylactic role of edible jute (Corchorus olitorius) leaves with special emphasis on oxidative stress and mitochondrial involvement.

The present study was undertaken to evaluate the protective effect of aqueous extract of Corchorus olitorius leaves (AECO) against CdCl2 intoxication. In vitro bioassay on isolated mice hepatocytes confirmed dose dependent cytoprotective effect of AECO. The CdCl2 (30 µM) exhibited a significantly increased levels of lipid peroxidation, protein carbonylation along with the reduction of antioxidant enzymes and reduced glutathione levels in hepatocytes. AECO (200 and 400 µg/ml) + CdCl2 (30 µM) could significantly restore the aforementioned oxidation parameters in hepatocytes. Beside this, AECO could significantly reduce Cd-induced increase in Bad/Bcl-2 ratio and the over-expression of NF-κB, caspase 3 and caspase 9. In in vivo assay, CdCl2 (4 mg/kg body weight, for 6 days) treated rats exhibited a significantly increased intracellular Cd accumulation, oxidative stress and DNA fragmentation in the organs. In addition, the haematological parameters were significantly altered in the CdCl2 treated rats. Simultaneous administration of AECO (50 and 100 mg/kg body weight), could significantly restore the biochemical, antioxidant and haematological parameters near to the normal status. Histological studies of the organs supported the protective role of jute leaves. Presence of substantial quantity of phenolic compounds and flavonoids in extract may be responsible for overall protective effect.

MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells.

MicroRNAs (miRNAs) play an essential role in regulating gene expression in normal and malignant cells. Expression of the microRNA-200 (miR-200) family has been correlated with malignancy in cancers. However, whether miR-200a/b plays a role in curcumin-mediated treatment of hepatocellular carcinoma (HCC) is unknown. We performed miRNA array analyses in two different HCC cell lines (HepG2 and HepJ5). The expression patterns of miR-200 family members were assessed with real-time PCR. We overexpressed miR-200 family members using a lentiviral system and selected stably transduced clones with antibiotics. The anticancer effects of curcumin on J5-200a, J5-200b, and J5-control cells were assessed by MTT assay, flow cytometry cell cycle analysis, and TUNEL assay. We found that HepG2 cells, which were more resistant to curcumin treatment than HepJ5 cells, expressed higher levels of miR-200a/b. The MTT assay revealed that the overexpression of miR-200a/b in HepJ5 cells conferred enhanced resistance to curcumin treatment compared with the control cells. By cell cycle analysis and TUNEL assay, we found that apoptosis was increased dramatically in J5-control cells compared with J5-200a and J5-200b cells after curcumin treatment. Finally, we evaluated the levels of Bcl-2, Bax, and Bad, and found a decrease of Bcl-2 levels and increase of Bad levels in the J5-control cells treated with curcumin. The expression levels of miR-200a/b might determine the therapeutic efficacy of curcumin on HCC cells.

Genista sessilifolia DC. extracts induce apoptosis across a range of cancer cell lines.

OBJECTIVES: Restorative properties of medicinal plants such as Genista sessilifolia DC. have often been suggested to occur, in epidemiological studies. However, full characterization of effective principles responsible for this action has never previously been performed. Here, we have characterized G. sessilifolia's anti-cancer effects and identified the chemical components involved in this anti-tumour action. MATERIALS AND METHODS: Cell cycle, apoptosis, necrosis, differentiation analyses, high-performance liquid chromatography, western blotting, RNA extraction, real-time PCR and primers have all been observed/used in the study. RESULTS: We report that G. sessilifolia methanol extract has anti-cancer activity on solid and haematological cancer cells. G. sessilifolia extract's anti-proliferative action is closely bound to induction of apoptosis, whereas differentiation is only weakly modulated. Analysis of G. sessilifolia extract, by high-performance liquid chromatography, identifies fraction 18-22 as the pertinent component for induction of apoptosis, whereas fractions 11-13 and 27-30 both seem to contribute to differentiation. G. sessilifolia extract induces apoptosis mediated by caspase activation and p21, Rb, p53, Bcl2-associated agonist of cell death (BAD), tumour necrosis factor receptor super-family, member 10 (TRAIL) overexpression and death receptor 5 (DR5). Accordingly, fraction 18-22 inducing apoptosis was able to induce TRAIL. CONCLUSIONS: Our results indicate that G. sessilifolia extract and its fraction 18-22 containing genistin and isoprunetin, were able to induce anti-cancer effects supporting the hypothesis of a pro-apoptotic intrinsic content of this natural medicinal plant.

Alpinate oxyphyllae fructus (Alpinia Oxyphylla Miq) extracts inhibit angiotensin-II induced cardiac apoptosis in H9c2 cardiomyoblast cells.

Angiotensin II (Ang II) is a risk factor for cardiovascular disease. We used a traditional Chinese medicine, alpinate oxyphyllae fructus (AOF), to evaluate its effect on Ang II-induced cardiac apoptosis and mitochondrial dysfunction. Ang II-treated H9c2 cells were administered AOF of 20-100 µg/mL concentrations. Ang II significantly increased TUNEL-positive nuclei in the H9c2 cells, effect was inhibited by AOF administration in both pre-treated and post-treated H9c2 cells. Caspases 9 and 3 activities were increased by Ang II and downregulated by AOF administration, especially in pre-treatment. AOF treatment reversed Ang II-induced mitochondria membrane potential instability in H9c2 cells as observed by JC-1 stain assay. Furthermore, pro-apoptotic proteins Bad and cytochrome c increased and decreased respectively under AOF administration. The levels of p-Bad anti-apoptotic protein were significantly increased after AOF treatment. This study indicates that mitochondrial dependent apoptosis induced by Ang II.

Selected nutraceutic screening by therapeutic effects on doxorubicin-induced chronic kidney disease.

SCOPE: The number of patients with chronic kidney disease (CKD) are increasing. Interventions such as controlling hypertension and specific pharmacologic options are recommended. Some nutraceutics may have benefits in this regard. METHODS AND RESULTS: Naringenin (a flavanon), catechin (a flavanol), and quercetin (a flavonol) and rutin (a flavonol rutinoside) were tried on CKD in a Sprague Dawley rat model. Results indicated quercetin to be the most effective therapeutic candidate with respect to renal edema, hypertension, serum creatinine, hematocrit, cardiopathy, aorta calcification, glomerular amyloidosis, erythrocyte depletion in bone marrow, collagen deposition, expressions of TNF-α, cleaved caspase-3, IκBα, PPARα, and serum insulin. But quercetin was only partially effective in restoring glomerular filtration rate, albuminuria, serum cholesterol, triglyceride, blood urea nitrogen (BUN), uric acid, malondialdehyde, superoxide dismutase; urinary BUN and urinary creatinine. As for signaling, quercetin was completely effective in alleviating the cleaved caspase-3, being only partially effective in suppressing Bax and Bad, restoring Bcl-2, and rescuing DNA damage. CONCLUSION: The CKD status cannot to be ameliorated by naringenin, rutin, and catechin. Comparatively, quercetin may be a better therapeutic candidate.