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Application of 5-fluorouracil (5-FU) in cholangiocarcinoma (CCA) is limited by adverse side effects and chemoresistance. Therefore, the combination therapy of 5-FU with other substances, especially natural products may provide a new strategy for CCA treatment. The aim of this study was to evaluate the combination effects of 5-FU and two ethanolic extracts of Thai noni juice (TNJ) products on CCA cell lines and nude mice xenografts. The results of antiproliferative assay showed the combination treatment of 5-FU and each TNJ ethanolic extract exerted more cytotoxicity on CCA cells than either single agent treatment. Synergistic effects of drug combinations can enable the dose reduction of 5-FU. The mechanism underlying a combination treatment was apoptosis induction through an activation of p53 and Bax proteins. In the nude mouse xenograft model, combination treatments of 5-FU with each TNJ ethanolic extract suppressed the growth of CCA cells implanted mice more than single agent treatments with no effects on mouse body weight, kidney, and spleen. Moreover, low doses of TNJ ethanolic extracts reduced the hepatotoxicity of 5-FU in nude mice. Taken together, these data suggested that the ethanolic extracts of TNJ products can enhance the anti-CCA effect and reduce toxicity of 5-FU. © 2021. The Author(s).

PURPOSE: To report the unsafe herb-drug interactions between a commercial product of noni juice and phenytoin in a human case. CASE REPORT: A 49-year-old-male has been treated with phenytoin for epilepsy for more than ten years. In spite of his medication adherence, persistent sub-therapeutic phenytoin levels, which were sometimes from low to undetectable, with the result of having poor seizure control were noted as the noni fruit juice was co-administered daily. The possible mechanism is speculated to be due to noni juiceinduced cytochrome P-450 2C9 metabolism of phenytoin. Owing to many beneficial effects of noni juice, the patient was unwilling to accept our advice to quit taking it. Clobazam treatment was added, and with gradually reducing the amount of juice drunk over six months, the patient's epilepsy has been well controlled. Now only auras along with sometimes minor partial seizures occur, but no major attack has been reported for more than one year. CONCLUSION: Phenytoin had been commonly used for seizure control worldwide and nearly half of patients with epilepsy had received complementary and alternative medicine in Taiwan. Thus, this report is significantly important for clinicians to be aware of the interaction between antiepileptic drugs and some herbs like noni juice. Moreover, as far as we know, this is a rare human case that is reported to disclose this unfavorable herb-drug interaction.

INTRODUCTION: This survey aims to identify herb-chemotherapeutic drug combinations in a defined group of cancer patients and to explore possible clinical consequences of these combinations. METHODS: Herb-chemotherapeutic drug combinations were identified among adult cancer patients, and clinical consequences of the combinations were explored by literature searches in medical databases on possible mutual effects on similar cytochrome P-450 metabolising enzymes (CYPs) and/or the P-glycoprotein (P-gp) transporter. RESULTS: Among 42 cancer patients using herbal remedies concurrently with chemotherapy, 136 two-agent herb-drug combinations were registered and 47 different potential herb-drug interactions were identified on the level of CYP metabolism and P-gp transport in vitro. Garlic, ginger, green tea and noni juice were the herbal remedies most frequently used in such combinations. For 48 % of the herbal remedies identified no literature data exist on their interaction potentials. Clinical studies were available for four herbal remedies only. Minor clinical potential for CYP interactions in humans was indicated for green tea and Echinacea. P-gp interactions were only investigated for garlic, which showed a significant interaction potential both in vivo and in vitro. CONCLUSION: The large number of in vitro potential herb-drug interactions identified urge for more clinical pharmacokinetic interaction studies in humans.

BACKGROUND AND OBJECTIVES: The use of additional medicines by patients with chronic medical illness like diabetes mellitus is on the increase. We investigated the effect of fruit juice of Morinda citrifolia on blood glucose of diabetic rats alone or when combined with insulin. METHODS: Twenty adult male Sprague Dawley rats with body weights 140-210 g were used for the experiments. They were randomly allocated into groups of five, with five rats in each group. The first group, (Group A) served as control and received standard rat chow and water, throughout the duration of the study. Group B received noni juice treatment, after induction of diabetes, for 4 weeks. Group C rats received fixed dose insulin treatment (Humilin 70/30) in two divided doses, at a dose of 0.6 units/Kg body weight/day, following induction of diabetes, for 4 weeks. The Group D rats received fixed dose insulin as well as noni juice, following induction of diabetes for 4 weeks. We monitored blood glucose level by measuring fasting blood sugar weekly. The result of the experiments show that after an initial hyperglycemia, following alloxan induced diabetes, treatment with noni juice restored reduced blood sugar but euglycaemia was not achieved (Group B). RESULTS: At the end of 4 weeks of experimentation. The mean fasting blood sugar level of 8.0 +/- 0.8 mmol/L following combination therapy, in which insulin treatment was combined with noni juice for 4 weeks, was lower than when either noni juice 15.4 +/- 1.5 mmol/L or insulin was used alone (P < 0.05). 12.9 +/- 1.6 mmol/L. CONCLUSION: In this study, a synergistic action with insulin was demonstrated by fruit juice of Morinda citrifolia.

The use of complementary and alternative medicine (CAM) in the United States is growing at a remarkable speed. Herbal products and dietary supplements are CAM therapies that have grown faster than any other CAM treatments. Little information is available about herbs and dietary supplement use in the stage 5 chronic kidney disease population. These products contain a myriad of pharmacologically active compounds that, when used by people with kidney disease, may be hazardous. Members of the renal dietitian listserv were queried about herbs and dietary supplements reportedly used by dialysis patients. Up-to-date information on the use, safety, efficacy, adverse effects, and recommended dosages in the nondialysis population are presented for 24 products. In the dialysis population, Noni juice should be avoided because of its high potassium content. In addition, bulk-forming laxatives such as flaxseed should be used with caution because of the need for increased fluid intake. Dialysis practitioners should include specific questions about herbs and dietary supplement use in medical and nutrition histories, and they should increase their knowledge about these products to advise patients appropriately. A list of reliable sources of information for the health care provider on herbs and dietary supplements is also presented.

Cigarette smoke-induced oxidative stress leads to dyslipidemia and systemic inflammation. Morinda citrifolia (noni) fruit juice has been found previously to have a significant antioxidant activity. One hundred thirty-two adult heavy smokers completed a randomized, double blind, placebo-controlled clinical trial designed to investigate the effect of noni juice on serum cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), high-sensitivity C-reactive protein (hs-CRP), and homocysteine. Volunteers drank noni juice or a fruit juice placebo daily for one month. Drinking 29.5 mL to 188 mL of noni juice per day significantly reduced cholesterol levels, triglycerides, and hs-CRP. Decreases in LDL and homocysteine, as well increases in HDL, were also observed among noni juice drinkers. The placebo, which was devoid of iridoid glycosides, did not significantly influence blood lipid profiles or hs-CRP. Noni juice was able to mitigate cigarette smoke-induced dyslipidemia, an activity associated with the presence of iridoids.