Medium Roasting and Brewing Methods Differentially Modulate Global Metabolites, Lipids, Biogenic Amines, Minerals, and Antioxidant Capacity of Hawai'i-Grown Coffee (Coffea arabica).

In the United States, besides the US territory Puerto Rico, Hawai'i is the only state that grows commercial coffee. In Hawai'i, coffee is the second most valuable agricultural commodity. Health benefits associated with moderate coffee consumption, including its antioxidant capacity, have been correlated to its bioactive components. Post-harvest techniques, coffee variety, degree of roasting, and brewing methods significantly impact the metabolites, lipids, minerals, and/or antioxidant capacity of brewed coffees. The goal of our study was to understand the impact of roasting and brewing methods on metabolites, lipids, biogenic amines, minerals, and antioxidant capacity of two Hawai'i-grown coffee (Coffea arabica) varieties, "Kona Typica" and "Yellow Catuai". Our results indicated that both roasting and coffee variety significantly modulated several metabolites, lipids, and biogenic amines of the coffee brews. Furthermore, regardless of coffee variety, the antioxidant capacity of roasted coffee brews was higher in cold brews. Similarly, total minerals were higher in "Kona Typica" cold brews followed by "Yellow Catuai" cold brews. Hawai'i-grown coffees are considered "specialty coffees" since they are grown in unique volcanic soils and tropical microclimates with unique flavors. Our studies indicate that both Hawai'i-grown coffees contain several health-promoting components. However, future studies are warranted to compare Hawai'i-grown coffees with other popular brand coffees and their health benefits in vivo.

Correlations between Coffee Consumption and Metabolic Phenotypes, Plasma Folate, and Vitamin B12: NHANES 2003 to 2006.

Metabolic syndrome (MetS) is prevalent not only among the overweight and obese but also normal weight individuals, and the phenotype is referred to as a metabolically unhealthy phenotype (MUHP). Besides normal weight individuals, overweight/obese individuals are also protected from MetS, and the phenotype is known as a metabolically healthy phenotype (MHP). Epidemiological studies indicate that coffee and micronutrients such as plasma folate or vitamin B12 (vit. B12) are inversely associated with MetS. However, correlations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 remain unknown. Our objective was to investigate the correlation between coffee consumption, metabolic phenotypes, plasma folate, and vit. B12 as well as to understand associations between plasma folate, vit. B12, and metabolic phenotypes. Associations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 were assessed in a cross-sectional study of 2201 participants, 18 years or older, from 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys (NHANES). MUHP was classified as having > three metabolic abnormalities. Coffee consumption was not associated with metabolic phenotypes, but negatively correlated with several metabolic variables, including BMI (p < 0.001). Plasma folate was positively associated with MUHP (p < 0.004), while vit. B12 was inversely associated with MUHP (p < 0.035). Our results suggest the potential protective impact of coffee on individual components of MetS and indicate a positive correlation between coffee consumption and MUHP among overweight individuals. Identifying possible dietary factors may provide practical and low-cost dietary intervention targets, specifically for early intervention. Larger and randomized intervention studies and prospective longitudinal studies are required to further evaluate these associations.

Momordica charantia (bitter melon) modulates adipose tissue inflammasome gene expression and adipose-gut inflammatory cross talk in high-fat diet (HFD)-fed mice.

Systemic and tissue-specific inflammation has a profound influence on regulation of metabolism, and therefore, strategies to reduce inflammation are of special interest in prevention and treatment of obesity and type 2 diabetes (T2D). Antiobesity and antidiabetic properties of Momordica charantia (bitter melon, BM) have been linked to its protective effects on inflammation and gut microbial dysbiosis. We investigated the mechanisms by which freeze-dried BM juice reduces adipose inflammation in mice fed a 60% high-fat diet (HFD) for 16 weeks. Although earlier studies indicated that BM inhibited recruitment of macrophages (Mφ) infiltration in adipose tissue of rodents and reduced NF-kB and IL-1ß secretions, the mechanisms remain unknown. We demonstrate that freeze-dried BM juice inhibits recruitment of Mφ into adipose tissue and its polarization to inflammatory phenotype possibly due to reduction of sphingokinase 1 (SPK1) mRNA in HFD-fed mice. Furthermore, reduction of IL-1ß secretion by freeze-dried BM juice in the adipose tissue of HFD-fed mice is correlated to alleviation of NLRP3 inflammasome components and their downstream signaling targets. We confirm previous observations that BM inhibited inflammation of colon and gut microbial dysbiosis in HFD-fed mice, which in part may be associated with the observed anti-inflammatory effects in adipose tissue if HFD-fed mice. Overall, functional foods such as BM may offer potential dietary interventions that may impact sterile inflammatory diseases such as obesity and T2D.

Anti-Diabetic Potential of Noni: The Yin and the Yang.

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni's several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni's exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their "natural" origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation "from bench side to bedside". In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni's health benefits.

Reduced immune cell infiltration and increased pro-inflammatory mediators in the brain of Type 2 diabetic mouse model infected with West Nile virus.

BACKGROUND: Diabetes is a significant risk factor for developing West Nile virus (WNV)-associated encephalitis (WNVE) in humans, the leading cause of arboviral encephalitis in the United States. Using a diabetic mouse model (db/db), we recently demonstrated that diabetes enhanced WNV replication and the susceptibility of mice to WNVE. Herein, we have examined immunological events in the brain of wild type (WT) and db/db mice after WNV infection. We hypothesized that WNV-induced migration of protective leukocytes into the brain is attenuated in the presence of diabetes, leading to a high viral load in the brain and severe disease in diabetic mice. METHODS: Nine-week old C57BL/6 WT and db/db mice were infected with WNV. Leukocyte infiltration, expression of cell adhesion molecules (CAM), neuroinflammatory responses, activation of astrocytes, and neuronal death were analyzed using immunohistochemistry, qRT-PCR, flow cytometry, and western blot. RESULTS: We demonstrate that infiltration of CD45+ leukocytes and CD8+T cells was significantly reduced in the brains of db/db mice, which was correlated with attenuated expression of CAM such as E-selectin and ICAM-1. WNV infection in db/db mice was associated with an enhanced inflammatory response in the brain. mRNA and protein levels of key chemokines such as CXCL10, CXCL1, CCL2, CCL5, CCL3, and G-CSF, and cytokines such as IL-1ß, TNF, IL-6, IFNγ, and IL-1α were significantly elevated in the brains of db/db mice compared to WT mice. Elevated levels of cytokines also correlated with increased astrocytes activation and neuronal damage in the brains of db/db mice. CONCLUSION: These data suggest that reduced leukocytes recruitment, in part, due to lower levels of CAM results in failure to clear WNV infection from the brain leading to increased production of inflammatory molecules, which mediates increased neuronal death and mortality in db/db mice. This is the first study to elucidate the expression of CAM and their correlation with the migration of leukocytes, specifically cytotoxic CD8+ T cells, in increasing disease severity in the diabetic mouse model.

Bitter melon reduces head and neck squamous cell carcinoma growth by targeting c-Met signaling.

Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and despite of advances in treatment, the overall survival rate has only modestly improved over the past several years. Thus, there is an urgent need for additional therapeutic modalities. We hypothesized that treatment of HNSCC cells with a dietary product such as bitter melon extract (BME) modulates multiple signaling pathways and regresses HNSCC tumor growth in a preclinical model. We observed a reduced cell proliferation in HNSCC cell lines. The mechanistic studies reveal that treatment of BME in HNSCC cells inhibited c-Met signaling pathway. We also observed that BME treatment in HNSCC reduced phosphoStat3, c-myc and Mcl-1 expression, downstream signaling molecules of c-Met. Furthermore, BME treatment in HNSCC cells modulated the expression of key cell cycle progression molecules leading to halted cell growth. Finally, BME feeding in mice bearing HNSCC xenograft tumor resulted in an inhibition of tumor growth and c-Met expression. Together, our results suggested that BME treatment in HNSCC cells modulates multiple signaling pathways and may have therapeutic potential for treating HNSCC.

Impaired virus clearance, compromised immune response and increased mortality in type 2 diabetic mice infected with West Nile virus.

Clinicoepidemiological data suggest that type 2 diabetes is associated with increased risk of West Nile virus encephalitis (WNVE). However, no experimental studies have elucidated the role of diabetes in WNV neuropathogenesis. Herein, we employed the db/db mouse model to understand WNV immunopathogenesis in diabetics. Nine-week old C57BL/6 WT and db/db mice were inoculated with WNV and mortality, virus burden in the periphery and brain, and antiviral defense responses were analyzed. db/db mice were highly susceptible to WNV disease, exhibited increased tissue tropism and mortality than the wild-type mice, and were unable to clear the infection. Increased and sustained WNV replication was observed in the serum, peripheral tissues and brain of db/db mice, and heightened virus replication in the periphery was correlated with enhanced neuroinvasion and replication of WNV in the brain. WNV infection in db/db mice was associated with enhanced inflammatory response and compromised antiviral immune response characterized by delayed induction of IFN-α, and significantly reduced concentrations of WNV-specific IgM and IgG antibodies. The compromised immune response in db/db mice correlated with increased viremia. These data suggest that delayed immune response coupled with failure to clear the virus leads to increased mortality in db/db mice. In conclusion, this study provides unique mechanistic insight into the immunopathogenesis of WNVE observed in diabetics and can be used to develop therapeutics for the management of WNVE among diabetic patients.

Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FoxO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice.

Renewed interest in alternative medicine among diabetic individuals prompted us to investigate anti-diabetic effects of Morinda citrifolia (noni) in high-fat diet (HFD)-fed mice. Type 2 diabetes is associated with increased glucose production due to the inability of insulin to suppress hepatic gluconeogenesis and promote glycolysis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Based on microarray analysis data, we tested the hypothesis that fermented noni fruit juice (fNJ) improves glucose metabolism via FoxO1 phosphorylation. C57BL/6 male mice were fed a HFD and fNJ for 12 weeks. Body weights and food intake were monitored daily. FoxO1 expression was analysed by real-time PCR and Western blotting. Specificity of fNJ-associated FoxO1 regulation of gluconeogenesis was confirmed by small interfering RNA (siRNA) studies using human hepatoma cells, HepG2. Supplementation with fNJ inhibited weight gain and improved glucose and insulin tolerance and fasting glucose in HFD-fed mice. Hypoglycaemic properties of fNJ were associated with the inhibition of hepatic FoxO1 mRNA expression, with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion of the proteins. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose-6-phosphatase (G6P), were significantly inhibited in mice fed a HFD+fNJ. HepG2 cells demonstrated more than 80 % inhibition of PEPCK and G6P mRNA expression in cells treated with FoxO1 siRNA and fNJ. These data suggest that fNJ improves glucose metabolism via FoxO1 regulation in HFD-fed mice.

Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.

Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle and modulate cyclin D1, cyclin E, and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression and induced PARP cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high-grade prostatic intraepithelial neoplasia in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed approximately 51% reduction of proliferating cell nuclear antigen expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell-cycle progression and proliferation.

Strategies to improve palatability and increase consumption intentions for Momordica charantia (bitter melon): a vegetable commonly used for diabetes management.

BACKGROUND: Although beneficial to health, dietary phytonutrients are bitter, acid and/or astringent in taste and therefore reduce consumer choice and acceptance during food selection. Momordica charantia, commonly known as bitter melon has been traditionally used in Ayurvedic and Chinese medicine to treat diabetes and its complications. The aim of this study was to develop bitter melon-containing recipes and test their palatability and acceptability in healthy individuals for future clinical studies. METHODS: A cross-sectional sensory evaluation of bitter melon-containing ethnic recipes was conducted among 50 healthy individuals. The primary endpoints assessed in this analysis were current consumption information and future intentions to consume bitter melon, before and after provision of attribute- and health-specific information. A convenience sample of 50, self-reported non-diabetic adults were recruited from the University of Hawaii. Sensory evaluations were compared using two-way ANOVA, while differences in stage of change (SOC) before and after receiving health information were analyzed by Chi-square (χ2) analyses. RESULTS: Our studies indicate that tomato-based recipes were acceptable to most of the participants and readily acceptable, as compared with recipes containing spices such as curry powder. Health information did not have a significant effect on willingness to consume bitter melon, but positively affected the classification of SOC. CONCLUSIONS: This study suggests that incorporating bitter foods in commonly consumed food dishes can mask bitter taste of bitter melon. Furthermore, providing positive health information can elicit a change in the intent to consume bitter melon-containing dishes despite mixed palatability results.

Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation.

BACKGROUND: The rising epidemic of obesity is associated with cognitive decline and is considered as one of the major risk factors for neurodegenerative diseases. Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases. Increased metabolic flux to the brain during overnutrition and obesity can orchestrate stress response, blood-brain barrier (BBB) disruption, recruitment of inflammatory immune cells from peripheral blood and microglial cells activation leading to neuroinflammation. The lack of an effective treatment for obesity-associated brain dysfunction may have far-reaching public health ramifications, urgently necessitating the identification of appropriate preventive and therapeutic strategies. The objective of our study was to investigate the neuroprotective effects of Momordica charantia (bitter melon) on high-fat diet (HFD)-associated BBB disruption, stress and neuroinflammatory cytokines. METHODS: C57BL/6 female mice were fed HFD with and without bitter melon (BM) for 16 weeks. BBB disruption was analyzed using Evans blue dye. Phosphate-buffered saline (PBS) perfused brains were analyzed for neuroinflammatory markers such as interleukin-22 (IL-22), IL-17R, IL-16, NF-κB1, and glial cells activation markers such as Iba1, CD11b, GFAP and S100ß. Additionally, antioxidant enzymes, ER-stress proteins, and stress-resistant transcription factors, sirtuin 1 (Sirt1) and forkhead box class O transcription factor (FoxO) were analyzed using microarray, quantitative real-time RT-PCR, western immunoblotting and enzymatic assays. Systemic inflammation was analyzed using cytokine antibody array. RESULTS: BM ameliorated HFD-associated changes in BBB permeability as evident by reduced leakage of Evans blue dye. HFD-induced glial cells activation and expression of neuroinflammatory markers such as NF-κB1, IL-16, IL-22 as well as IL-17R were normalized in the brains of mice supplemented with BM. Similarly, HFD-induced brain oxidative stress was significantly reduced by BM supplementation with a concomitant reduction in FoxO, normalization of Sirt1 protein expression and up-regulation of Sirt3 mRNA expression. Furthermore, plasma antioxidant enzymes and pro-inflammatory cytokines were also normalized in mice fed HFD with BM as compared to HFD-fed mice. CONCLUSIONS: Functional foods such as BM offer a unique therapeutic strategy to improve obesity-associated peripheral inflammation and neuroinflammation.

Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes.

BACKGROUND: Escalating trends of obesity and associated type 2 diabetes (T2D) has prompted an increase in the use of alternative and complementary functional foods. Momordica charantia or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. However, its effects on human adipocytes remain unknown. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation transcription factors in primary human differentiating preadipocytes and adipocytes. METHODS: Commercially available cryopreserved primary human preadipocytes were treated with and without BMJ during and after differentiation. Cytotoxicity, lipid accumulation, and adipogenic genes mRNA expression was measured by commercial enzymatic assay kits and semi-quantitative RT-PCR (RT-PCR). RESULTS: Preadipocytes treated with varying concentrations of BMJ during differentiation demonstrated significant reduction in lipid content with a concomitant reduction in mRNA expression of adipocyte transcription factors such as, peroxisome proliferator-associated receptor gamma (PPARgamma) and sterol regulatory element-binding protein 1c (SREBP-1c) and adipocytokine, resistin. Similarly, adipocytes treated with BMJ for 48 h demonstrated reduced lipid content, perilipin mRNA expression, and increased lipolysis as measured by the release of glycerol. CONCLUSION: Our data suggests that BMJ is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to reduce adipogenesis in humans.

Bitter melon: antagonist to cancer.

The incidence of cancer is increasing worldwide, in spite of substantial progress in the development of anti-cancer therapies. One approach to control cancer could be its prevention by diet, which inhibits one or more neoplastic events and reduces cancer risk. Dietary compounds offer great potential in the fight against cancer by inhibiting the carcinogenesis process through the regulation of cell homeostasis and cell-death machineries. For centuries, Ayurveda (Indian traditional medicine) has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat diabetes and associated complications. It is noteworthy to mention that bitter melon extract has no-to-low side effects in animals as well as in humans. The anti-tumor activity of bitter melon has recently begun to emerge. This review focuses on recent advancements in cancer chemopreventive and anti-cancer efficacy of bitter melon and its active constituents. Several groups of investigators have reported that treatment of bitter-melon-related products in a number of cancer cell lines induces cell cycle arrest and apoptosis without affecting normal cell growth. Therefore, the effect of bitter melon should be beneficial for health, and use of the non-modified dietary product is cost effective.

Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis.

Breast cancer is one of the most common cancers among women in the United States. Although there are effective drugs for treating advanced stages of breast cancers, women eventually develop resistance. One of the approaches to control breast cancer is prevention through diet, which inhibits one or more neoplastic events and reduces cancer risk. In this study, we have used human breast cancer cells, MCF-7 and MDA-MB-231, and primary human mammary epithelial cells as an in vitro model to assess the efficacy of bitter melon (Momordica charantia) extract (BME) as an anticancer agent. BME treatment of breast cancer cells resulted in a significant decrease in cell proliferation and induced apoptotic cell death. Apoptosis of breast cancer cells was accompanied by increased poly(ADP-ribose) polymerase cleavage and caspase activation. Subsequent studies showed that BME treatment of breast cancer cells inhibited survivin and claspin expression. Fluorescence-activated cell sorting analysis suggested that MCF-7 cells treated with BME accumulated during the G2-M phase of the cell cycle. Further studies revealed that BME treatment enhanced p53, p21, and pChk1/2 and inhibited cyclin B1 and cyclin D1 expression, suggesting an additional mechanism involving cell cycle regulation. Together, these results show that BME modulates signal transduction pathways for inhibition of breast cancer cell growth and can be used as a dietary supplement for prevention of breast cancer.

Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions.

Aqueous extracts or juice from unripened fruit of Momordica charantia (bitter melon) has traditionally been used in the treatment of diabetes and its complications. Insulin resistance is characterized by significant down-regulation of hepatic insulin signalling as documented by attenuated phosphorylation of insulin receptor (IR), IR substrates 1 and 2, phosphoinositide-3 kinase, protein kinase B, and over-expression of phosphotyrosine phosphatase 1B. We recently demonstrated that bitter melon juice (BMJ) is a potent inhibitor of apoB secretion and TAG synthesis and secretion in human hepatoma cells, HepG2, that may be involved in plasma lipid- and VLDL-lowering effects observed in animal studies. The aim of this study was to evaluate the effects of BMJ on plasma apoB levels and hepatic insulin signalling cascade in mice fed high-fat diet (HFD). Female C57BL/6 mice (4-6 weeks old) were randomized into three groups receiving regular rodent chow, HFD and HFD+BMJ. The data indicate that BMJ not only improves glucose and insulin tolerance but also lowers plasma apoB-100 and apoB-48 in HFD-fed mice as well as modulates the phosphorylation status of IR and its downstream signalling molecules. Investigating the biochemical and molecular mechanisms involved in amelioration of diabetic dyslipidaemia by BMJ may lead to identification of new molecular targets for dietary/alternative therapies.

Can Sir(2) regulate cancer?

Sirtuin activators, including small molecules such as polyphenols and resveratrol, are much desired due to their potential to ameliorate metabolic disorder and delay or prevent aging. In contrast, recent studies demonstrate that targeted silencing of sirtuin 1 (SIRT1) expression or activity by the deleted in breast cancer 1 (DBC1) may be beneficial by promoting p53-induced apoptosis in cancer cells, and by sensitizing cancerous cells to radiation therapy. Negative SIRT1 regulation also alleviates gene-repression associated with fragile X mental retardation syndrome. The targeted activation or inhibition of SIRT1 activity therefore emerges as a critical point of regulation in disease pathogenesis.

Respected Sir(2): magic target for diabetes.

The endless quest for the 'fountain of youth' has led to the discovery of a family of molecules known as sirtuins in humans, or silent mating type information regulator 2 (Sir2) in yeast, which are associated with longevity in yeast, nematodes, drosophila and rodents. Although sirtuins have yet to be proven to delay aging and promote longevity in humans, they promise 'healthy aging', an ideal of modern society. This review emphasizes the role of various sirtuins in maintaining glucose homeostasis, the therapeutic potential of sirtuin modulators in the prevention and treatment of diabetes, and the emerging associations of SIRT genetic polymorphisms with human longevity.

Effects of kava alkaloid, pipermethystine, and kavalactones on oxidative stress and cytochrome P450 in F-344 rats.

Kava-containing products remain popular in the United States and continue to be sold in health food stores and ethnic markets regardless of the fact that it was banned in Western countries such as Germany, France, Switzerland, Australia, and Canada, following reports of alleged hepatotoxicity. It is therefore critical to establish efficacy and verify adverse effects and/or herb-drug interactions for kava-kava (Piper methysticum). We have previously demonstrated that kava alkaloid, pipermethystine (PM), abundant in leaves and stem peelings, induces mitochondrial toxicity in human hepatoma cells, HepG2, as compared with the bioactive components, kavalactones (KL), abundant in the rhizome. The current study compared short-term toxic effects of PM in Fischer-344 (F-344) rats to acetone-water extracts of kava rhizome (KRE). Treatment of F-344 rats with PM (10 mg/kg) and KRE (100 mg/kg) for 2 weeks failed to elicit any significant changes in liver function tests or cause severe hepatic toxicity as measured by lipid peroxidation and apoptosis markers such as malondialdehyde, Bax, and Bcl-2. However, PM-treated rats demonstrated a significant increase in hepatic glutathione, cytosolic superoxide dismutase (Cu/ZnSOD), tumor necrosis factor alpha mRNA expression, and cytochrome P450 (CYP) 2E1 and 1A2, suggesting adaptation to oxidative stress and possible drug-drug interactions.

Lipid lowering effects of Momordica charantia (Bitter Melon) in HIV-1-protease inhibitor-treated human hepatoma cells, HepG2.

1. Hyperlipidemic effects of HIV-1-protease inhibitors (PI) are associated with increased hepatic production of triglyceride (TG)-rich lipoproteins, rather than lipoprotein clearance. PI are known to increase apolipoprotein B (apoB) secretion, apoC-III mRNA expression and decrease apoA-1 secretion. Nutritional therapy remains an important strategy to manage PI-associated hyperlipidemia. 2. This study investigated the in vitro efficacy of Asian vegetable, Momordica charantia or bitter melon (BM) to ameliorate PI-associated apoB and lipid abnormalities in HepG2 cells. 3. Our study demonstrates that bitter melon juice (BMJ) significantly reduced apoB secretion and apoC-III mRNA expression and normalized apoA-I expression in PI-treated HepG2 cells. BMJ also significantly reduced cellular TG and microsomal TG transfer protein, suggesting that lipid bioavailability and lipidation of apoB assembly may play a role in decreased apoB secretion. 4. Identifying molecular targets of BM may offer alternative dietary strategies to decrease PI-associated hyperlipidemia and improve quality of life among HIV-1-infected patients.

Microsomal triglyceride transfer protein gene expression and ApoB secretion are inhibited by bitter melon in HepG2 cells.

Momordica charantia or bitter melon is traditionally used as an antidiabetic agent in Asia, Africa, and South America. Recent studies indicate that bitter melon can also lower plasma lipids and VLDL in diabetic animal models as well as animals fed a high-fat diet, suggesting an effect on lipoprotein metabolism. The aim of this study was to delineate the cellular and molecular mechanisms involved in the lipid-lowering properties of bitter melon and regulation of apolipoprotein B (apoB). Human hepatoma cells, HepG2, treated with bitter melon juice (BMJ) for 24 h reduced apoB secretion with and without the addition of lipids (P < 0.05). However, BMJ did not increase apoB secretion in cells treated with N-acetyl-leucyl-leucyl-norleucinal, indicating a lack of effect on the proteasomal degradation pathway. BMJ reduced the secretion of new triglycerides (P < 0.05) and decreased microsomal triglyceride transfer protein (MTP) mRNA expression, suggesting that lipid bioavailability and lipidation of lipoprotein assembly are likely involved in decreased apoB secretion. Interestingly, BMJ increased the nuclear translocation of the mature form of sterol regulatory element-binding protein-1c (SREBP-1c, P < 0.05), involved in MTP secretion. Our data suggest that BMJ is a potent inhibitor of apoB secretion and TG synthesis and secretion that may be involved in the plasma lipid- and VLDL-lowering effects observed in animal studies.