Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis and Cell Cycle Arrest.

BACKGROUND: Drug repurposing in oncology promises a high impact on many patients through its ability to provide access to novel, fast-tracked treatments. Previous studies have demonstrated that depression may influence tumor progression. Anti-proliferative activity of certain antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), are reported in the literature. OBJECTIVE: This study was conducted to repurpose selective serotonin reuptake inhibitors (SSRIs) in treating breast cancers, and it merits the pursuit of drug repositioning in oncology. EXPERIMENTAL: Changes in cell morphology were studied using DAPI staining, and the Annexin V/PI method was employed for apoptotic analysis. The expression of specific genes involved in cancer progression was also analyzed via RT-PCR. Caspase-3 activation was observed through fluorometric assay. RESULTS: We have identified that sertraline hydrochloride most effectively inhibited the growth of breast cancer cell cells in vitro. Preliminary mechanistic studies demonstrated that the cytotoxicity of sertraline hydrochloride was possibly through the induction of apoptosis, as inferred from enhanced nuclear fragmentation, flow cytometric data, and caspase-3/7 activation. Gene expression analysis also showed an increased expression of proapoptotic Bax and a slight decrease in oncogene c-myc in the presence of sertraline hydrochloride. CONCLUSION: In conclusion, our data suggest that sertraline hydrochloride, an antidepressant, can potentially be used for the treatment of breast cancer.

Oxadiazole Derivatives of Diclofenac as an Anti-proliferative Agent for B-cell Non-Hodgkin Lymphoma: An In vitro and In Silico Studies.

BACKGROUND: Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies. AIM: The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches. METHODS: Anti-lymphoma potential was evaluated by alamar blue technique. MTT assay employed for cytotoxicity. Gene and protein expression studies was performed by qRT-PCR and ELISA respectively. Docking studies was performed by using MOE program. RESULTS: Among five diclofenac derivatives, (II) showed promising anti-lymphoma effects, where it inhibited the expression of BCL-2, p-38 MAPK and TGF-ß in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells. The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in (II) is involved in the crucial interactions with the binding site residue. CONCLUSION: The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent.

Dysregulation of Type I Interferon (IFN-I) Signaling: A Potential Contributor to Racial Disparity in Hepatocellular Carcinoma (HCC).

African-American (AA)/Black hepatocellular carcinoma (HCC) patients have increased incidence and decreased survival rates compared to non-Hispanic (White) patients, the underlying molecular mechanism of which is not clear. Analysis of existing RNA-sequencing (RNA-seq) data in The Cancer Genome Atlas (TCGA) and in-house RNA-sequencing of 14 White and 18 AA/Black HCC patients revealed statistically significant activation of type I interferon (IFN-I) signaling pathway in AA/Black patients. A four-gene signature of IFN-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors versus White. HCC is a disease of chronic inflammation, and IFN-Is function as pro-inflammatory cytokines. We tested efficacy of ginger extract (GE), a dietary compound known for anti-inflammatory properties, on HCC cell lines derived from White (HepG2), AA/Black (Hep3B and O/20) and Asian (HuH-7) patients. GE exhibited a significantly lower IC50 on Hep3B and O/20 cells than on HepG2 and HuH-7 cells. The GE treatment inhibited the activation of downstream mediators of IFN-I signaling pathways and expression of ISGs in all four HCC cells. Our data suggest that ginger can potentially attenuate IFN-I-mediated signaling pathways in HCC, and cells from AA/Black HCC patients may be more sensitive to ginger. AA/Black HCC patients might benefit from a holistic diet containing ginger.

Effects of ultrasonic processing on the quality properties of fortified yogurt.

This study evaluated the effect of ultrasonic processing on functional yogurts fortified with banana-resistant starch (BRS) and green papaya powder (GPP). Ultrasonication technology (80% amplitude, 8 min at 20 kHz frequency) was utilized as an alternative to conventional thermal treatment (85 °C, 30 min) to improve functional yogurts' physical and textural properties. A total of 6 set-type yogurt groups were prepared by ultrasonication (UT) and conventional treatment (CT). Based on the textural studies and correlation (Pearson's) plots, fortified and UT samples were more stiff, firm, sticky, adhesive, and viscous (least elastic) compared to the CT samples. All of the tested yogurts maintained a remarkable number of viable colony counts (≥7.23 log CFU/mL) during the storage. Ultrasonication significantly (p < 0.05) changed the L, a*, and b* color values. The ultrasonic processing reduced whey syneresis and improved the water-holding capacity in fresh and stored yogurts. Further, it retained the fatty acid profile of fortified yogurts. However, ultrasonication negatively affected, i.e., reduced the total polyphenol content and antioxidant activity of yogurts as compared to the conventionally (thermal) treated counterparts. Overall, ultrasound technology can be a potential alternative to thermal treatment for the improved quality and safety of fortified yogurts.

Characterization of Green and Yellow Papaya (Carica papaya) for Anti-Diabetic Activity in Liver and Myoblast Cells and Wound-Healing Activity in Fibroblast Cells.

Obesity and diabetes, often characterized as "metabolic syndrome", have been recognized as two of the most important public health issues worldwide. The objective of the present research was to evaluate green and yellow papaya for anti-oxidation and anti-diabetic properties. Leaves, skin, pulp, and seed samples from papayas were freeze-dried and then extracted in water or 80% methanol. The extracts were used to determine total polyphenolic content and anti-oxidation activities, and to determine biological activities, including glucose uptake, Glut-2 expression, triglyceride reduction, and wound-healing activity. Our data demonstrated that methanol and water extracts of green and yellow papaya have similar concentrations of polyphenols in skin (10-20 mg/g dry powder), leaf (25-30 mg/g dry powder), and pulp (1-3 mg/g dry powder) fractions. However, both methanol and water extracts of seeds from yellow papaya have substantially higher concentrations of polyphenols compared to green papaya. Both water and methanol extracts of yellow papaya exhibited higher anti-oxidation activity compared to green papaya in skin (50-60%), pulp (200-300%), and seeds (10-800%). Old leaves also showed greater anti-oxidation activity (30-40%) compared to new leaves. Pulp extracts from both yellow and green papaya stimulated greater glucose uptake, but only pulp from green papaya stimulated glucose uptake in muscle cells. Similarly, pulp extract stimulated glucose transporter Glut-2 expression in liver cells. The skin, pulp, and seeds of green or yellow papaya showed triglyceride-lowering activity in liver cells by 60-80%, but samples taken from yellow papaya had a more potent effect. Seeds from both green and yellow papaya significantly stimulated the migration of fibroblasts in the wounded area by 2-2.5-fold compared to the untreated control. Consistent with these data, seeds from both green and yellow papaya also significantly stimulated collagen synthesis in fibroblast cells by almost 3-fold. In conclusion, our data indicate that different parts of papaya produce stimulatory effects on glucose uptake, Glut-2 expression, TG reduction, and wound-healing activities. This study concludes that different parts of the papaya can be beneficial for preventing diabetes and diabetes-related wound healing.

Immature ginger reduces triglyceride accumulation by downregulating Acyl CoA carboxylase and phosphoenolpyruvate carboxykinase-1 genes in 3T3-L1 adipocytes.

Background: Obesity is the underlying risk factor for major metabolism complications, including non-alcoholic-fatty liver disease, atherosclerosis, and cardiovascular disease. The adipose tissue is a vital endocrine organ that plays a role in the synthesis and storage of lipid and, therefore, is a contributory factor to the development and progression of obesity. A growing interest in nutraceuticals suggests that natural products can alleviate the risk factors and may be effective in mitigating obesity. Aim: The objective of this study was to examine the underlying mechanisms of immature ginger on adipocyte differentiation and lipogenesis in a 3T3-L1 cellular model. Methods: Ginger samples, extracted in 80% methanol, were dried and resuspended in DMSO at 50 µg/mL as stock solution. For analysis, the extracted samples were further diluted in media. Effects on adipogenesis were evaluated by determining lipid droplet and triglyceride accumulation, whereas effects on lipogenesis were determined by measuring triglyceride contents and fatty acid profile. The expression of key regulatory genes involved in adipogenesis and lipogenesis was also determined. Results: Our data indicate that the intracellular lipid accumulation decreased significantly by 15 or 25% on treatment with 25 or 50 µg/mL of ginger extract. Consistent with these data, significantly reduced triglyceride levels by 30 or 50% were observed on 25 or 50 µg/mL treatment with ginger extracts, respectively. In addition, ginger treatment significantly inhibited the differentiation-induced de novo lipogenesis and Δ9 desaturase activity. Furthermore, ginger treatment reduced adipogenesis genes, C/ebpß and C/ebpδ, expression by 47 or 64%, respectively, but significantly increased Pparγ expression by 60% and adiponectin by 75%. Ginger extracts had no effect on Fas genes but reduced lipogenesis genes, acyl CoA carboxylase (Acc) expression by two-fold, and phosphoenolpyruvate carboxy kinase 1 (Pepck1) expression by 50%. Conclusion: Our findings suggest immature ginger can potentially inhibit lipogenesis pathways by limiting the channeling of glucose carbon in fatty acid synthesis by inhibiting the expression of ACC and glycerol production via inhibiting the expression of PEPCK, which consequently inhibits triglyceride formation.

A study of the association between virulence factors and antifungal susceptibility profile of Candida species recovered from cases of vulvovaginal candidiasis.

Background: The incidence of mycotic infections, especially of Candida, has gradually increased over the past few years. In clinical practice, azoles are the most frequently used antifungal agents and the growing incidence of systemic candidiasis and resistance to antifungals have become a matter of concern worldwide. Virulence factors in Candida spp. may be critical for predicting the response of antifungal drugs. Objectives: This study aimed to identify the relationship between virulence factors and the antifungal susceptibility of Candida. Methodology: This cross-sectional study was conducted on a sample of 55 Candida strains isolated from vulvovaginal samples of patients in the reproductive age group, presenting with signs and symptoms of vulvovaginitis in a large tertiary care hospital in central India. Results: A majority of the Candida were sensitive to three tested drugs (89% to amphotericin B, 76.4% to fluconazole, and 89.1% to voriconazole). Resistance to fluconazole was highest at 16.4%. No significant relationships were identified between antifungal sensitivity of the three azoles with biofilm formation, phospholipase, or proteinase synthesis. Conclusions: High level of antifungal resistance to the three antifungals, especially to voriconazole, is worrisome; however, none of the virulence markers have a significant association with antifungal sensitivity of Candida species. This finding rules out the effect of the virulence of the pathogen on drug response.

A challenging case of suspected solanine toxicity in an eleven-year-old Saudi boy.

Potatoes are commonly consumed food item that contributes key nutrients to the diet including vitamin C, potassium, and dietary fiber. Despite their nutritional value, potato tuber may harm human health by virtue of their toxic glycoalkaloids (solanine). Acute solanine poisoning can happen from ingesting green or sprouted potatoes. The toxicity of Gas in humans causes mainly gastrointestinal disturbances such as vomiting, diarrhea, and abdominal pain. However, at higher doses, the toxicity of Gas in humans produces more severe symptoms, including fever, rapid pulse, low blood pressure, rapid respiration, and neurological disorders. Though potatoes are widely consumed, their toxicity is relatively rare. We came across a suspected case of poisoning by raw potato ingestion in an 11 years old Saudi boy who suffered cardiovascular complications, and was managed conservatively in pediatric ICU. The diagnosis was made based on history and clinical presentation. The patient recovered completely and was discharged with counseling.

Isolation and characterization of anti-inflammatory and anti-proliferative compound, for B-cell Non-Hodgkin lymphoma, from Nyctanthes arbor-tristis Linn.

ETHNOPHARMACOLOGICAL RELEVANCE: Nyctanthes arbor-tristis Linn. is native to Indo-Pak sub-continent and has high medicinal values in Ayureda. This plant has been used traditionally for the treatment of sciatica, rheumatism, chronic fever, diabetes, snakebite, dysentery, cachexia and cancer. Studies have shown many pharmacological properties such as anti-cancer efficacy against Dalton's ascetic lymphoma, cytotoxicity against T-cell leukemia, anti-inflammatory, anti-diabetic and anti-oxidant effects. AIM OF THE STUDY: Aim of the study was to explore the anti-inflammatory and anti-proliferative potential of N. arbor-tristis. MATERIAL AND METHODS: Ethanol extract of fresh and uncrushed aerial parts of N. arbor-tristis was used in the present study. A new compound nyctanthesin A was isolated following a bioactivity-guided fractionation and chromatographic separations. Its chemical structure was elucidated through spectral studies including 1D, 2D-NMR experiments and HREIMS. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) generation from phagocytes were detected by chemiluminescence technique and Griess method, respectively. TNF-α and TGF-ß production was quantified by ELISA. Anti-lymphoma and cytotoxic activities were assessed by alamar blue and MTT assays, respectively. The transcription and protein expression level of Bcl-2, COX-2, p38 MAPK, PDL-1, NF-κB, c-Myc and PNF-κB was performed by qRT-PCR and protein blot assays, respectively. RESULTS: Petroleum ether insoluble fraction of the ethanol extract of fresh and uncrushed aerial parts of N. arbor-tristis revealed anti-inflammatory potential by inhibiting ROS. A previously undescribed compound nyctanthesin A was isolated from this fraction and characterized by UV, IR, NMR and HREIMS. It showed significant anti-inflammatory property by inhibiting ROS, NO and TNF-α production. The strong anti-proliferative effects on B- cell lymphoma cells, DOHH2 and Raji, revealed its anti-lymphoma potential along with non-toxic profile against BJ and NIH-3T3 fibroblast cells of normal origin. The qRT-PCR results showed marked inhibition of Bcl-2, COX-2, p38 MAPK, PDL-1, c-Myc, NF-κB, and PNF-κB at transcription level in DOHH2 cells with comparatively lesser but significant effects in Raji cells, where the expression of Bcl-2 gene was not affected. The protein expression of PNF-κB in DOHH2 cells was inhibited by 66% (P < 0.05) and COX-2 in both cell lines was inhibited by 50% (P < 0.05) at 60 µg/mL. A moderate non-significant inhibition of TGF-ß (∼20%) was observed in both cell lines at 100 µg/mL CONCLUSIONS: Scientific evidences reported here validate the anti-inflammatory and anti-cancer potential of the plant.

Nutritional Composition and Bioactive Components in Quinoa (Chenopodium quinoa Willd.) Greens: A Review.

Quinoa (Chenopodium quinoa Willd.) is a nutrient-rich grain native to South America and eaten worldwide as a healthy food, sometimes even referred to as a "superfood". Like quinoa grains, quinoa greens (green leaves, sprouts, and microgreens) are also rich in nutrients and have health promoting properties such as being antimicrobial, anticancer, antidiabetic, antioxidant, antiobesity, and cardio-beneficial. Quinoa greens are gluten-free and provide an excellent source of protein, amino acids, essential minerals, and omega-3 fatty acids. Quinoa greens represent a promising value-added vegetable that could resolve malnutrition problems and contribute to food and nutritional security. The greens can be grown year-round (in the field, high tunnel, and greenhouse) and have short growth durations. In addition, quinoa is salt-, drought-, and cold-tolerant and requires little fertilizer and water to grow. Nevertheless, consumption of quinoa greens as leafy vegetables is uncommon. To date, only a few researchers have investigated the nutritional properties, phytochemical composition, and human health benefits of quinoa greens. We undertook a comprehensive review of the literature on quinoa greens to explore their nutritional and functional significance to human health and to bring awareness to their use in human diets.

Phytochemical profile and anti-oxidation activity changes during ginger (Zingiber officinale) harvest: Baby ginger attenuates lipid accumulation and ameliorates glucose uptake in HepG2 cells.

We determined the phenolic content and anti-oxidation properties of ginger at different harvesting time and tested its effects on lipid droplet formation and glucose uptake in HepG2 cells. Ginger samples at different stages of maturity were harvested every two weeks starting from mid-October for 16 weeks. Our data indicate that ginger has the highest phenolic contents and superior anti-oxidation activity when harvested early (immature baby ginger); however, the concentration of phenolic contents and its anti-oxidation activity were progressively reduced up to 50% as ginger matures. Furthermore, the data indicate that baby ginger extract inhibits lipid accumulation and triglyceride content in oleic acid-induced HepG2 cells up to 20% in a dose-dependent manner. Baby ginger exhibited significant inhibition of α-amylase enzyme activity by 29.5% and ameliorated glucose uptake in HepG2 cell at similar level. Our results suggest that harvesting ginger at an appropriate (early) time may be beneficial for optimizing its biological active contents and qualitative properties. The data also suggest that a regular use of ginger can potentially lower incidences of obesity and diabetes.

Engineering of fluorescent or photoactive Trojan probes for detection and eradication of ß-Amyloids.

Trojan horse technology institutes a potentially promising strategy to bring together a diagnostic or cell-based drug design and a delivery platform. It provides the opportunity to re-engineer a novel multimodal, neurovascular detection probe, or medicine to fuse with blood-brain barrier (BBB) molecular Trojan horse. In Alzheimer's disease (AD) this could allow the targeted delivery of detection or therapeutic probes across the BBB to the sites of plaques and tangles development to image or decrease amyloid load, enhance perivascular Aß clearance, and improve cerebral blood flow, owing principally to the significantly improved cerebral permeation. A Trojan horse can also be equipped with photosensitizers, nanoparticles, quantum dots, or fluorescent molecules to function as multiple targeting theranostic compounds that could be activated following changes in disease-specific processes of the diseased tissue such as pH and protease activity, or exogenous stimuli such as, light. This concept review theorizes the use of receptor-mediated transport-based platforms to transform such novel ideas to engineer systemic and smart Trojan detection or therapeutic probes to advance the neurodegenerative field.

Nutraceuticals and Nutrition Supplements: Challenges and Opportunities.

The term "nutraceuticals" is derived from "nutrition" and "pharmaceuticals" and is used fornutrition products that are also used as medicine [1] [...].

Naringenin protects AlCl3/D-galactose induced neurotoxicity in rat model of AD via attenuation of acetylcholinesterase levels and inhibition of oxidative stress.

Currently prescribed medications for the treatment of Alzheimer's disease (AD) that are based on acetylcholinesterase inhibition only offer symptomatic relief but do not provide protection against neurodegeneration. There appear to be an intense need for the development of therapeutic strategies that not only improve brain functions but also prevent neurodegeneration. The oxidative stress is one of the main causative factors of AD. Various antioxidants are being investigated to prevent neurodegeneration in AD. The objective of this study was to investigate the neuroprotective effects of naringenin (NAR) against AlCl3+D-gal induced AD-like symptoms in an animal model. Rats were orally pre-treated with NAR (50 mg/kg) for two weeks and then exposed to AlCl3+D-gal (150 mg/kg + 300 mg/kg) intraperitoneally for one week to develop AD-like symptoms. The standard drug, donepezil (DPZ) was used as a stimulator of cholinergic activity. Our results showed that NAR pre-treatment significantly protected AD-like behavioral disturbances in rats. In DPZ group, rats showed improved cognitive and cholinergic functions but the neuropsychiatric functions were not completely improved and showed marked histopathological alterations. However, NAR not only prevented AlCl3+D-gal induced AD-like symptoms but also significantly prevented neuropsychiatric dysfunctions in rats. Results of present study suggest that NAR may play a role in enhancing neuroprotective and cognition functions and it can potentially be considered as a neuroprotective compound for therapeutic management of AD in the future.

Phytochemical profile and antioxidation activity of annona fruit and its effect on lymphoma cell proliferation.

Cancers of the lymphatic system are broadly classified into Hodgkin and non-Hodgkin types. Although lymphomas can be effectively treated with chemotherapy, this approach is associated with the risk of adverse side effects. High intake of certain vegetables and fruits is associated with a reduced risk of cancer development. We hypothesized that Annona fruit, which is rich in fibers and phytochemicals that are known to possess anticancer properties, can be effective in inhibiting lymphoma growth. The Annona fruit's fractions were extracted with water, methanol, or chloroform and then assayed for total phenolic, flavonoids, and tannins content; antioxidation activities; and inhibition of in vitro cell proliferation using the Ramos-1 lymphoma cells. The methanol fractions contained the highest phenolics, flavonoids, and tannins content, and antioxidation activity. However, the methanol extracts of skin, pulp, and seeds had a moderate whereas the chloroform extracts of pulp and seeds had strong effects on Ramos-1 cell proliferation. Our findings suggest that Annona fruits may be effective in the prevention or treatment of lymphoma.

Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from Myrtus communis on Inflammatory Response in Mouse Macrophages.

(1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Myrthus communis Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Furthermore, the effects of the compound were analyzed via phosphorylation and translocation of the transcription factor NF kappa B, which is a key regulator of iNOS activation. The effect of MCA-1 on the inducible nitric oxide synthase (iNOS) enzyme was also examined using in silico docking studies. The anticancer potential for MCA-1 was evaluated with an MTT cytotoxic assay. (3) Results: In stimulated macrophages, MCA-1 inhibited superoxide production by 48%, hydrogen peroxide by 53%, and nitric oxide (NO) with an IC50 of <1 µg/mL. MCA-1 also showed a very strong binding pattern within the active site of the inducible nitric oxide synthase enzyme. Furthermore, 25 µg/mL of MCA-1 inhibited inducible nitric oxide synthase expression and abolished transcription factor (NFκB) phosphorylation and translocation to the nucleus. Cytotoxicity analyses of MCA-1 on 3T3 mouse fibroblasts, CC1 liver cell line, J774.2, macrophages and MDBK bovine kidney epithelial cell, yielded IC50 values of 6.53 ± 1.2, 4.6 ± 0.7, 5 ± 0.8, and 4.6 ± 0.7, µg/mL, respectively. (4) Conclusion: Our results suggest that MCA-1, a major phloroglucinol-type compound, shows strong anti-inflammatory activity and has a potential to be a leading therapeutic agent in the future.

Prevention of cadmium-induced neurotoxicity in rats by essential nutrients present in nuts.

Cadmium, a heavy metal with no physiological function in the human body, is considered a bio-hazard. It is also considered to be a potent neurotoxin. The primary sources of cadmium exposure are diet and cigarette smoke. It has been postulated that nutritional deficiencies can increase the risk of cadmium toxicity. Nuts provide essential nutrients which are necessary for the maintenance of brain health in humans. The present study was designed to investigate the possible protective effects of almond and walnut supplementation on cadmium-induced neurotoxicity. Cadmium was orally administered at a dose of 50 mg/kg weekly with or without the supplementation of almond and walnut in rats. Intensities of depression­ and anxiety-related behaviors were assessed by the forced swim test and light/dark transition test, respectively. Memory function was also evaluated by the elevated plus maze, Morris water maze and novel object recognition task. After four weeks of treatment it was observed that cadmium administration significantly induced depressogenic and anxiogenic behaviors. Memory function was also impaired by cadmium administration. Cadmium-treated rats exhibited reduced noradrenalin, dopamine and serotonin levels in the brain, whereas the levels of their respective metabolites were significantly increased. The dietary supplementation of almond and walnut at a dose of 400 mg/kg/day significantly attenuated cadmium-induced depression, anxiety and memory impairments. Neurochemical aberrations also normalized following supplementation with these nuts in rats. The present study demonstrates that long-term supplementation with almond and walnut provides essential nutrients which may overcome nutritional deficiencies and thereby reduce heavy-metal intoxication.

Polyphenol-Enriched Plum Extract Enhances Myotubule Formation and Anabolism while Attenuating Colon Cancer-induced Cellular Damage in C2C12 Cells.

Preventing muscle wasting in certain chronic diseases including cancer is an ongoing challenge. Studies have shown that polyphenols derived from fruits and vegetables shows promise in reducing muscle loss in cellular and animal models of muscle wasting. We hypothesized that polyphenols derived from plums (Prunus domestica) could have anabolic and anti-catabolic benefits on skeletal muscle. The effects of a polyphenol-enriched plum extract (PE60) were evaluated in vitro on C2C12 and Colon-26 cancer cells. Data were analyzed using a one-way ANOVA and we found that treatment of myocytes with plum extract increased the cell size by ~3-fold (p < 0.05) and stimulated myoblast differentiation by ~2-fold (p < 0.05). Plum extract induced total protein synthesis by ~50% (p < 0.05), reduced serum deprivation-induced total protein degradation by ~30% (p < 0.05), and increased expression of Insulin-Like Growth Factor-1 (IGF-1) by ~2-fold (p < 0.05). Plum extract also reduced tumor necrosis factor α (TNFα)-induced nuclear factor κB (NFκB) activation by 80% (p < 0.05) in A549/NF-κB-luc cells. In addition, plum extract inhibited the growth of Colon-26 cancer cells, and attenuated cytotoxicity in C2C12 myoblasts induced by soluble factors released from Colon-26 cells. In conclusion, our data suggests that plum extract may have pluripotent health benefits on muscle, due to its demonstrated ability to promote myogenesis, stimulate muscle protein synthesis, and inhibit protein degradation. It also appears to protect muscle cell from tumor-induced cytotoxicity.

A natural flavonoid lawsonaringenin induces cell cycle arrest and apoptosis in HT-29 colorectal cancer cells by targeting multiple signalling pathways.

Colorectal cancer is the third most common malignancy in the world having a high mortality rate. Flavonoids possess many biological activities including anti-cancer activity. lawsonaringenin (LSG) is a flavonoid isolated from leaves of Lawsonia alba Lam. The objective of this study was to demonstrate the anti-cancer potential of LSG in colorectal cancer for the first time. The HT-29 cells were treated with LSG or 5-fluoruracil, as a positive control, to determine its effect on cell cytotoxicity by a MTT cell proliferation assay, and cell cycle progression and apoptosis using flowcytometry. We also determined the mechanisms underlying LSG-mediated growth inhibition of HT-29 cells by by investigating the expression of key oncogenes and apoptosis genes using q-RT PCR and immunocytochemical analysis. The cell cytotoxicity data showed that the IC50 value of LSG was significantly less than the IC50 value of 5-FU (50 µM). The anti-proliferative effect of LSG was mediated by arresting cells in the S phase of the cell cycle which then led to the induction of apoptosis the q-RT PCR and immunocytochemical analysis showed that LSG reduced the expression of ß-catenin (non-phosphorylated) and its downstream signalling target c-Myc, whereas it increased the phosphorylation of ß-catenin. Furthermore, LSG also downregulated the expression of oncogene K-Ras and anti-apoptotic proteins, Bcl-2, and Bcl-xL. In conclusion, our data demonstrates that LSG exerted its anti-tumor activity by arresting the cell cycle in S phase, and by downregulating the expression of oncogenes including ß-catenin, c-Myc, K-Ras and anti-apoptosis proteins Bcl-2 and Bcl-xL. This study suggests a potential use of natural flavonoid, lawsonaringenin, to attenuate colorectal cancer growth; however, further pre-clinical/clinical studies are required to establish its role as a therapeutic agent.

Dietary Supplementation of Almond Prevents Oxidative Stress by Advocating Antioxidants and Attenuates Impaired Aversive Memory in Male Rats.

Scopolamine, an anti-muscarinic agent, has been shown to induce amnesia and oxidative stress similar to that observed in the older age. The present study was designed to determine the relationship between the oxidative status and memory improvement in scopolamine injected rats pre-administered with almonds. Rats (n = 8) in the almond group were administered orally with 400 mg/kg almond suspension for 28 days daily before the intraperitoneal injection of scopolamine (0.5 mg/kg). Passive avoidance task (PAT) was used to assess memory function at the end of treatment. The present study revealed that scopolamine injection significantly impaired the memory function in rats pre-treated with saline which was accompanied by increased oxidative stress as evident by increased brain malondialdehyde (MDA) levels and reduced activities of antioxidant enzymes as compared to healthy controls. Pre-treatment with almond significantly ameliorated scopolamine-induced oxidative stress and memory dysfunction. These findings suggest that dietary supplementation with almonds may have a beneficial effect in reducing the risk of oxidative stress-induced memory loss and delaying or preventing the onset of age-related memory impairment.