PMID: 

J Food Biochem. 2019 Aug 23:e13021. Epub 2019 Aug 23. PMID: 31441956

Abstract Title: 

Momordica charantia reverses type II diabetes in rat.

Abstract: 

Diabetes, a disease with abnormal production or use of insulin, is a growing concern that affects many individuals globally. Although many attempts have been made, there is no satisfactory treatment for diabetes. Recently, scientists have been exploring a promising treatment of diabetes involving herbal medicine. In this line, we show that Momordica charantia, a tendril-bearing vine belonging to the Cucurbitaceae family, permanently normalizes blood glucose levels comparable to healthy rats. Most importantly, M. charantia increases the expression of Insulin and Pdx1 genes while lowers the expression Glut2. Moreover, the number and size of the pancreatic islets have remarkably increased in treated animals. Liver ALT, AST, and ALP enzyme activities fell into normal range in treated animals suggesting the protective effect of M. charantia. These data indicate that M. Charantia improves the pancreas function by activating pancreatic beta cells and protecting liver tissue. PRACTICAL APPLICATIONS: Owing to the effectiveness of Momordica Charantia extracts in management of diabetes in STZ-induced diabetic rats, we have intention to evaluate the powder of Charantia to discover novel drug for treating diabetes. It is expected that the results could be translated in clinical trials.

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PMID: 

Int J Environ Res Public Health. 2019 Sep 4 ;16(18). Epub 2019 Sep 4. PMID: 31487939

Abstract Title: 

The Role ofin Resisting Obesity.

Abstract: 

(), commonly known as bitter gourd, bitter melon, kugua, balsam pear, or karela, is a tropical and sub-tropical vine belonging to the Cucurbitaceae family. It has been used to treat a variety of diseases in the traditional medicine of China, India, and Sri Lanka. Here, we review the anti-obesity effects of various bioactive components ofestablished at the cellular and organismal level. We aim to provide links between various bioactive components ofand their anti-obesity mechanism. An advanced search was conducted on the worldwide accepted scientific databases via electronic search (Google Scholar, Web of Science, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, SciFinder, CNKI) database with the query TS ="Momordica charantia"and"obesity". Information was also obtained from International Plant Names Index, Chinese Pharmacopoeia, Chinese herbal classic books, online databases, PhD and MSc dissertations, etc. First, studies showing the anti-obesity effects ofon the cells and on animals were classified. The major bioactive components that showed anti-obesity activities included proteins, triterpenoids, saponins, phenolics, and conjugated linolenic acids. Their mechanisms included inhibition of fat synthesis, promotion of glucose utilization, and stimulation of auxiliary lipid-lowering activity. Finally, we summarized the risks of excessive consumption ofand the application. Although further research is necessary to explore various issues, this review establishes the therapeutic potential ofand it is highly promising candidate for the development of anti-obesity health products and medicines.

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PMID: 

Free Radic Res. 2017 Jul-Aug;51(7-8):684-692. Epub 2017 Aug 14. PMID: 28750563

Abstract Title: 

High-dose ascorbic acid induces carcinostatic effects through hydrogen peroxide and superoxide anion radical generation-induced cell death and growth arrest in human tongue carcinoma cells.

Abstract: 

High-dose ascorbic acid (AsA) treatment, known as pharmacological AsA, has been shown to exert carcinostatic effects in many types of cancer cells and in vivo tumour models. Although pharmacological AsA has potential as a complementary and alternative medicine for anticancer treatment, its effects on human tongue carcinoma have not yet been elucidated. In this study, we investigated the effect of AsA treatment on human tongue carcinoma HSC-4 cells compared with non-tumourigenic tongue epithelial dysplastic oral keratinocyte (DOK) cells. Our results show that treatment with 1 and 3 mM of AsA for 60 min preferentially inhibits the growth of human tongue carcinoma HSC-4 over DOK cells. Furthermore, AsA-induced effects were accompanied by increased intracellular oxidative stress and were repressed by treatment with a hydrogen peroxide (HO) scavenger catalase and a superoxide anion radical (O) scavenger, tempol. Time-lapse observation and thymidine analog EdU incorporation revealed that AsA treatment induces not only cell death but also suppression of DNA synthesis and cell growth. Moreover, the growth arrest was accompanied by abnormal cellular morphologies whereby cells extended dendrite-like pseudopodia. Taken together, our results demonstrate that AsA treatment can induce carcinostatic effects through induction of cell death, growth arrest, and morphological changes mediated by HOand Ogeneration. These findings suggest that high-dose AsA treatment represents an effective treatment for tongue cancer as well as for other types of cancer cells.

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PMID: 

Cell Biol Int. 2017 Oct ;41(10):1127-1145. Epub 2017 Aug 24. PMID: 28755485

Abstract Title: 

Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs).

Abstract: 

Colorectal cancer is one of the global causes of cancer deaths. Cancer stem cells (CSCs) inside the tumour niche responsible for metastasis and relapses, and hence need to be targeted for cancer therapeutics. Although dietary fibre and lifestyle changes have been recommended as measures for colorectal cancer prevention, no such recommendations are available for using water soluble vitamins as prophylaxis measure for colorectal cancers. High dose of Vitamin C has been proven to selectively kill colon cancer cells having BRAF and KRAS mutations by inducing oxidative stress. In this study, we show for the first time the opposing effects of the low and high dose of Vitamin C and vitamin B3 on colon CSCs isolated from HT-29 and HCT-15 colorectal carcinoma cell lines. At small doses, both of these vitamins exerted a cell proliferative effect only on CSCs, while there was no change in the proliferation status of non-stem cancer cells and wild-type (WT) populations. On the other hand, the death effects induced by high doses of Vitamin C and B3 were of the order of 50-60% and∼30% on CSCs from HT-29 and HCT15, respectively. Interestingly, the control fibroblast cell line (NIH3T3) was highly refractory all the tested concentrations of Vitamin C and B3, except for the highest dose – 10,000 μg of Vitamin C that induced only 15% of cell death. Hence, these results indicate the future scope of use of therapeutic doses of Vitamin C and B3 especially in patients with advanced colorectal cancer.

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PMID: 

Sci Rep. 2017 12 7 ;7(1):17188. Epub 2017 Dec 7. PMID: 29215048

Abstract Title: 

High Dose Parenteral Ascorbate Inhibited Pancreatic Cancer Growth and Metastasis: Mechanisms and a Phase I/IIa study.

Abstract: 

Pancreatic cancer is among the most lethal cancers with poorly tolerated treatments. There is increasing interest in using high-dose intravenous ascorbate (IVC) in treating this disease partially because of its low toxicity. IVC bypasses bioavailability barriers of oral ingestion, provides pharmacological concentrations in tissues, and exhibits selective cytotoxic effects in cancer cells through peroxide formation. Here, we further revealed its anti-pancreatic cancer mechanisms and conducted a phase I/IIa study to investigate pharmacokinetic interaction between IVC and gemcitabine. Pharmacological ascorbate induced cell death in pancreatic cancer cells with diverse mutational backgrounds. Pharmacological ascorbate depleted cellular NAD+ preferentially in cancer cells versus normal cells, leading to depletion of ATP and robustly increasedα-tubulin acetylation in cancer cells. While ATP depletion led to cell death, over-acetylated tubulin led to inhibition of motility and mitosis. Collagen was increased, and cancer cell epithelial-mesenchymal transition (EMT) was inhibited, accompanied with inhibition in metastasis. IVC was safe inpatients and showed the possibility to prolong patient survival. There was no interference to gemcitabine pharmacokinetics by IVC administration. Taken together, these data revealed a multi-targeting mechanism of pharmacological ascorbate's anti-cancer action, with minimal toxicity, and provided guidance to design larger definitive trials testing efficacy of IVC in treating advanced pancreatic cancer.

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PMID: 

Vet Comp Oncol. 2018 Dec ;16(4):616-621. Epub 2018 Sep 6. PMID: 30188000

Abstract Title: 

Anticancer effects of high-dose ascorbate on canine melanoma cell lines.

Abstract: 

The use of the well-known powerful antioxidant ascorbate has recently become more widespread in human medicine. Intravenous administration of high-dose ascorbate has been demonstrated to exert anticancer effects. It has resulted in effective cell death in vitro and inhibition of tumour growth in vivo. The aim of the current study was to evaluate the effects of high-dose ascorbate on canine melanoma in vitro. Four canine melanoma cell lines, UCDK9M1, UCDK9M3, UCDK9M4 and UCDK9M5 were treated with ascorbate for 2 hours at a range of millimolar concentrations (0-20 mM) to investigate the resulting effects on cell viability. All four canine melanoma cell lines exhibited reduced viability in a dose-dependent manner. Further investigation demonstrated that high-dose ascorbate induced apoptosis via the activation of Bax. These findings suggest that high-dose ascorbate has an anticancer effect on canine melanoma cell lines in vitro. With regard to clinical application, further in vivo investigation should be conducted.

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PMID: 

Adv Clin Exp Med. 2019 01 ;28(1):19-24. PMID: 30156389

Abstract Title: 

Vitamin C may exert variable effects on viability and proliferation of HeLa cells exhibiting high and low chromosomal instability.

Abstract: 

BACKGROUND: Chromosomal instability (CIN), defined as abnormality in chromosome structure or number, is the hallmark of malignancies. The role of vitamin C in cancer treatment is controversial and its effect on CIN is still an open field of research. In this work, we tried to study the effect of high-dose L-ascorbic acid (L-AA) on CIN-induced (CINhi = CIN high) and non-CIN-induced (CINlo = CIN low) cervical cancer cells.OBJECTIVES: The aim of this study was to explore the effect of high-dose L-AA on CIN in the cervical cancer cell line (HeLa) cells.MATERIAL AND METHODS: The HeLa cells (CINhi and CINlo) were treated with 2 doses (5 mM and 8 mM) of L-AA for 24 h and 48 h. They were then analyzed by micronucleus (MN) scoring, cell ploidy and flow cytometry, the latter regardingγH2AX expression. Cell viability was assessed by the methylthiazol tetrazolium (MTT) and Annexin V assays.RESULTS: Treatment of CINhi cells with L-AA led to a decrease in MN score (colchicine – 71.5±4.95, 67.5 ±0.71; L-AA (5 mM) – 49 ±7.07, 46.5 ±4.95; L-AA (8 mM) – 42 ±9.89, 41 ±1.41, at 24 h and 48 h, respectively; p

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PMID: 

Phytother Res. 2019 Aug ;33(8):2094-2101. Epub 2019 Jun 21. PMID: 31225673

Abstract Title: 

Three-arm, placebo-controlled, randomized clinical trial evaluating the metabolic effect of a combined nutraceutical containing a bergamot standardized flavonoid extract in dyslipidemic overweight subjects.

Abstract: 

Our double-blind, placebo-controlled, parallel-group, dose-escalation, clinical trial aimed to test the effect of a combined nutraceutical containing bergamot extract (120-mg flavonoids), phytosterols, vitamin C, and chlorogenic acid from dry artichoke extract on 90 overweight dyslipidemic subjects. Participants were randomly allocated to treatment with two pills of either active treatment or placebo, or a combination of both (a pill per treatment). After 8 weeks, all active-treated groups experienced a significant improvement in triglycerides (TG) versus placebo and in low-density lipoprotein cholesterol (LDL-C) versus baseline and placebo treatments. In the high-dose-treated group, also total cholesterol (TC), nonhigh-density lipoprotein cholesterol (non-HDL-C), γ-glutamil transpeptidasi, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α) significantly decreased. At 24-week follow-up, TG levels maintained lower than baseline in all groups. All patients allocated to either low-dose or high-dose active treatment experienced a significant decrease in TG, LDL-C, and homeostatin model assessment of insulin resistance. In subjects taking high-dose active treatment, adiponectin significantly increased, whereas TC, non-HDL-C, insulin (fasting plasma insulin), leptin, leptin/adiponectin ratio, hs-CRP, and TNF-αwere significantly reduced. The tested nutraceutical showed to improve lipid and glucose metabolism, adipokines pattern, and systemic inflammation in dyslipidemic overweight subjects.

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PMID: 

Pathophysiology. 2019 Sep 19. Epub 2019 Sep 19. PMID: 31564389

Abstract Title: 

Vitamin C suppresses ovarian pathophysiology in experimental polycystic ovarian syndrome.

Abstract: 

BACKGROUND: Polycystic ovary syndrome (PCOS), also known as the Stein-Leventhal syndrome is one of the most common causes of anovulation, infertility and hyperandrogenism in women, affecting between 5-10 % of women of reproductive age (12-35 years) worldwide. Despite substantial effort to define the cause of PCOS, its pathophysiology remains poorly understood. Consequently, determining the mechanisms of PCOS and the possible treatment is the major goal of medical research in endocrine and reproductive physiology.AIM: To investigate the mechanism of ovarian metabolic changes in dehydroepiandrosterone (DHEA)-induced polycystic ovary in Wistar rats treated with vitamin C.METHODS: Twenty-eight immature female Wistar rats weighing (16-21 g) were randomly divided into four groups (n = 7/group): group I served as control and was given water, group II were injected with DHEA (6 mg/100 g in 0.2 ml corn oil subcutaneously to induce PCOS condition), group III received 150 mg/kg BW of Vitamin C orally, group IV were co-administered with 6 mg/kg BW DHEA in 0.2 ml of corn oil subcutaneously and 150 mg/kg BW of Vitamin C orally. All treatments lasted for 15 days. Twenty-four hours after the last administration, the rats were sacrificed by cervical dislocation. Blood samples and ovaries were collected for reproductive hormonal analysis, biochemical and histopathological analysis. The expressions of mRNA androgen receptor gene in the ovary were determined by real-time reverse transcriptase polymerase chain reaction. All data were analysed using one-way ANOVA.RESULTS: There was a significant decrease (p 

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PMID: 

Onco Targets Ther. 2019 ;12:7405-7413. Epub 2019 Sep 10. PMID: 31571901

Abstract Title: 

High-dose vitamin C suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition.

Abstract: 

Purpose: Vitamin C (VC) is a kind of essential nutrient in the body regarded as a canonical antioxidant during the past hundred years. However, the anti-cancer effect of VC is controversial. Our study is trying to clarify the relationship between VC dosage and breast cancer metastasis.Methods: Human breast cancer cell lines Bcap37 and MDA-MB-453 were treated with VC at three different concentrations (low-dose, 0.01 mM; medium-dose, 0.1 mM; high-dose, 2 mM). Wound healing assays were conducted for migration assay; transwell tests were performed to detect the ability of cell invasion. The protein levels were evaluated by Western blot analysis or immunohistochemistry. Tumor xenografts in nude mice were builtto test the effects of VC on breast cancer cell proliferation and metastasis.Results: 0.01 and 0.1 mM VC promoted cell migration and invasion when compared with the control group, but 2 mM VC significantly suppressed cell migration and invasion of breast cancer cell lines. High-dose VC increased E-cadherin and reduced Vimentin, indicating that high-dose VC suppressed epithelial-mesenchymal transition (EMT) in breast cancer cells. Besides, high-dose VC inhibited cell invasion promoted by TGF-β1 in breast cancer cells. Meanwhile, high-dose VC reversed the suppression of E-cadherin and enhancement of Vimentin induced by TGF-β1 in breast cancer cells. Furthermore, high-dose VC significantly inhibited breast cancer metastasis in vivo.Conclusion: High-dose VC inhibits cell migration and invasion of breast cancer cell lines through suppressing EMT. Thus, it may be considered as an anticancer drug candidate for breast cancer patients.

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