Impact of a High-Fat Meal on the Pharmacokinetics of Sotorasib, a KRAS G12C Inhibitor.

Sotorasib is a small molecule drug that specifically and irreversibly inhibits the KRAS p.G12C mutant protein. This analysis investigated the impact of a high-calorie high-fat meal on the pharmacokinetics, safety, and tolerability of sotorasib in both healthy volunteers and patients with KRAS G12C advanced solid tumors. Each subject received a single oral dose of 360 or 960 mg of sotorasib under fasted conditions or with a high-fat meal (fed conditions). The geometric least squares means (GLSM) ratios (fed/fasted) for 360 mg of sotorasib Cmax and AUCinf were 1.03 and 1.38, respectively, in healthy volunteers (N = 14). The GLSM ratios (fed/fasted) for Cmax and AUC0-24h were 1.38 and 1.75, respectively, with 360 mg of sotorasib in cancer patients (N = 2). The GLSM ratios (fed/fasted) for Cmax and AUC0-24h were 0.660 and 1.25, respectively, with 960 mg of sotorasib in cancer patients (N = 8). Sotorasib was well tolerated in fast and fed conditions. The impact of a high-fat meal on sotorasib exposure is less than a 2-fold increase or decrease in Cmax and AUCs.

Possible interactions between selected food processing and medications.

The impact of food processing on drug absorption, metabolism, and subsequent pharmacological activity is a pressing yet insufficiently explored area of research. Overlooking food-processing-drug interactions can significantly disrupt optimal clinical patient management. The challenges extend beyond merely considering the type and timing of food ingestion as to drug uptake; the specific food processing methods applied play a pivotal role. This study delves into both selected thermal and non-thermal food processing techniques, investigating their potential interference with the established pharmacokinetics of medications. Within the realm of thermal processing, conventional methods like deep fat frying, grilling, or barbecuing not only reduce the enteric absorption of drugs but also may give rise to side-products such as acrylamide, aldehydes, oxysterols, and oxyphytosterols. When produced in elevated quantities, these compounds exhibit enterotoxic and pro-inflammatory effects, potentially impacting the metabolism of various medications. Of note, a variety of thermal processing is frequently adopted during the preparation of diverse traditional herbal medicines. Conversely, circumventing high heat through innovative approaches (e.g., high-pressure processing, pulsed electric fields, plasma technology), opens new avenues to improve food quality, efficiency, bioavailability, and sustainability. However, it is crucial to exercise caution to prevent the excessive uptake of active compounds in specific patient categories. The potential interactions between food processing methods and their consequences, whether beneficial or adverse, on drug interactions can pose health hazards in certain cases. Recognizing this knowledge gap underscores the urgency for intensified and targeted scientific inquiry into the multitude of conceivable interactions among food composition, processing methods, and pharmaceutical agents. A thorough investigation into the underlying mechanisms is imperative. The complexity of this field requires substantial scrutiny and collaborative efforts across diverse domains, including medicine, pharmacology, nutrition, food science, food technology, and food engineering.

Analysis of medication administration in relation to food and beverages in inpatients.

Proper medication administration in relation to beverage or food is one of the essential tools to achieve the pharmacotherapy goals. It is not known whether this is also considered in the care of inpatients. The aim of this study was to describe and analyse the current practice of medication administration in relation to food and beverages to patients hospitalized in four hospitals in the Czech Republic. This study was conducted based on the results of the first phase of a prospective observation study focused on the safety of medication administration performed by nurses. All data, including the timing of medication administration in relation to food and the data on beverages used, were obtained by the method of direct observation. The team of observersaccompanied the nurse during medication administration. The appropriateness of the medication administration in relationto food/beverages was assessed according to the summary of product characteristics and the published literature. In total, the administration of 5718 oral medications and 198 insulins were analysed. Unproper food timing wasobserved in 15.7% of oral medication administrations and 26.8% of insulin administrations. The highest number ofunproper food timing occurred in the proton pump inhibitors, antihypertensives, and prokinetics. Tea (63.4%) was the most used beverage. Errors with clinically serious impact have been observed in some groups of drugs. The necessity of a systemic approach in management of medication administration is required including interdisciplinary cooperation.

Physiological, Anatomical and Physicochemical Characteristics of Children Affecting Food-Drug Interaction-Review.

The drug-food interaction has a great interest in nutrition research to minimize unfavorable reactions to nutritional treatment. Failure to supply appropriate nutrition to the child can harm both body development and growth. This review aimed to examine available data on the impact of diet on medication absorption in pediatric populations. Mechanisms underlying food-drug interactions were investigated to explore possible distinctions between adult and pediatric populations and to gain insight into how this may impact the pharmacokinetic profile in a child. Several changes in physiology, anatomy and physicochemical properties among children are likely to result in food-drug interactions that cannot be anticipated based on adult studies. The influence of food on medications results in decreased bioavailability and altered drug elimination. Drugs, on the other hand, can affect dietary intake, digestion, absorption and excretion. Literature shows that differences in gastrointestinal physiology and anatomy between pediatric and adult populations can have a major impact on drug absorption and bioavailability. A higher splanchnic blood flow may result in decreased drug bioavailability due to increased loss in first-pass metabolism. To overcome the overall lack of knowledge on analyzing food-drug interactions among pediatric populations, comprehensive procedures and recommendations must be developed.

The Use of an Antioxidant Enables Accurate Evaluation of the Interaction of Curcumin on Organic Anion-Transporting Polypeptides 4C1 by Preventing Auto-Oxidation.

Flavonoids have garnered attention because of their beneficial bioactivities. However, some flavonoids reportedly interact with drugs via transporters and may induce adverse drug reactions. This study investigated the effects of food ingredients on organic anion-transporting polypeptide (OATP) 4C1, which handles uremic toxins and some drugs, to understand the safety profile of food ingredients in renal drug excretion. Twenty-eight food ingredients, including flavonoids, were screened. We used ascorbic acid (AA) to prevent curcumin oxidative degradation in our method. Twelve compounds, including apigenin, daidzein, fisetin, genistein, isorhamnetin, kaempferol, luteolin, morin, quercetin, curcumin, resveratrol, and ellagic acid, altered OATP4C1-mediated transport. Kaempferol and curcumin strongly inhibited OATP4C1, and the Ki values of kaempferol (AA(-)), curcumin (AA(-)), and curcumin (AA(+)) were 25.1, 52.2, and 23.5 µM, respectively. The kinetic analysis revealed that these compounds affected OATP4C1 transport in a competitive manner. Antioxidant supplementation was determined to benefit transporter interaction studies investigating the effects of curcumin because the concentration-dependent curve evidently shifted in the presence of AA. In this study, we elucidated the food-drug interaction via OATP4C1 and indicated the utility of antioxidant usage. Our findings will provide essential information regarding food-drug interactions for both clinical practice and the commercial development of supplements.

The Effects of Jabara Juice on the Intestinal Permeation of Fexofenadine.

Jabara juice and its component narirutin inhibit the activity of organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1, which are considered to play significant roles in the intestinal absorption of fexofenadine. In this study, we investigated the effects of jabara juice on the intestinal absorption of fexofenadine in mice and the inhibitory effects of jabara juice and narirutin on the permeation of fexofenadine using Caco-2 cell monolayers and LLC-GA5-COL300 cell monolayers. In the in vivo study, the area under the plasma concentration-time curve (AUC) of fexofenadine in mice was increased 1.8-fold by jabara juice. In the permeation study, 5% jabara juice significantly decreased the efflux ratio (ER) of fexofenadine for Caco-2 monolayers. Furthermore, the ERs of fexofenadine and digoxin, which is a typical substrate of P-glycoprotein (P-gp), for LLC-GA5-COL300 cell monolayers were decreased in a concentration-dependent manner by jabara juice extract, suggesting that jabara juice may increase the intestinal absorption of fexofenadine by inhibiting P-gp, rather than by narirutin inhibiting OATPs. The present study showed that jabara juice increases the intestinal absorption of fexofenadine both in vivo and in vitro. The intestinal absorption of fexofenadine may be altered by the co-administration of jabara juice in the clinical setting.

Influence of Food With Different Fat Concentrations on Alectinib Exposure: A Randomized Crossover Pharmacokinetic Trial.

BACKGROUND: Alectinib is the keystone treatment in advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). An exposure-response threshold of 435 ng/mL has recently been established, albeit 37% of patients do not reach this threshold. Alectinib is orally administered, and absorption is largely influenced by food. Hence, further investigation into this relationship is needed to optimize its bioavailability. PATIENTS AND METHODS: In this randomized 3-period crossover clinical study in ALK+ NSCLC, alectinib exposure was compared among patients with different diets. Every 7 days, the first alectinib dose was taken with either a continental breakfast, 250-g of low-fat yogurt, or a self-chosen lunch, and the second dose was taken with a self-chosen dinner. Sampling for alectinib exposure (Ctrough) was performed at day 8, just prior to alectinib intake, and the relative difference in Ctrough was compared. RESULTS: In 20 evaluable patients, the mean Ctrough was 14% (95% CI, -23% to -5%; P=.009) and 20% (95% CI, -25% to -14%; P<.001) lower when taken with low-fat yogurt compared with a continental breakfast and a self-chosen lunch, respectively. Administration with a self-chosen lunch did not change exposure compared with a continental breakfast (+7%; 95% CI, -2% to +17%; P=.243). In the low-fat yogurt period, 35% of patients did not reach the threshold versus 5% with the other meals (P<.01). CONCLUSIONS: Patients and physicians should be warned for a detrimental food-drug interaction when alectinib is taken with low-fat yogurt, because it results in a clinically relevant lower alectinib exposure. Intake with a self-chosen lunch did not change drug exposure and could be a safe and patient-friendly alternative.

Co-administration of pazopanib and enteral nutrition with omega-3 fatty acids as a safety issue in a patient treated for metastatic clear cell renal cancer: A case report.

Pazopanib is an oral multitargeting tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs), approved as the first-line treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma (STS) at a fixed dose of 800 mg daily taken fasted. Potential drug-meal interactions and adverse events (AEs) may lack recognition and the related data in literature. We report one case of stomatitis/oral mucositis associated with pazopanib administrated with an oral nutritional supplement enriched with omega-3 fatty acids. The 50-year-old patient with mRCC started pazopanib treatment at standard doses of 800 mg daily as first-line therapy for mRCC, and after a few days, he developed stomatitis. Co-administration of pazopanib with high-fat meals could increase the solubility of highly lipophilic pazopanib, increasing its plasma pazopanib area under the curve (AUC), and maximum concentration (Cmax) above optimal therapeutic level can consequently lead to increased frequency/grade of AEs.

Weak Inhibitory Effects of Anthocyanins on Human Aldehyde Oxidase Activity: An In Vitro Study.

Aldehyde oxidase (AO) plays an important role in the metabolism of antitumor and antiviral drugs, including methotrexate, favipiravir, and acyclovir. The consumption of blueberry fruits or their extracts, which contain large amounts of anthocyanins, has recently increased. The intake of large amounts of anthocyanins occurs through the frequent consumption of blueberries or their functional foods, which may result in unwanted interactions between anthocyanins and medicinal drugs. Therefore, the present study examined the inhibition of AO by anthocyanins, anthocyanidins, and blueberry extracts in human liver cytosol using a HPLC assay. A comparison of the 50% inhibitory concentration (IC50) values of the test compounds showed that anthocyanidins slightly suppressed AO activity, whereas the inhibitory effects of anthocyanins and blueberry extracts were negligible. The inhibitory activities of the anthocyanins tested were approximately 60- to 130-fold weaker than that of the positive control menadione and were almost negligible. Furthermore, they were approximately 2,000-fold less potent than that of raloxifene, a typical AO inhibitor, and, thus, unlikely to interfere with drug metabolism by AO. In addition, since the plasma concentrations of anthocyanins after their administration were generally lower than the IC50 level, the inhibition of AO substrate metabolism by anthocyanins does not appear to be severe.

Curcumin improves the ability of donepezil to ameliorate memory impairment in Drosophila melanogaster: involvement of cholinergic and cnc/Nrf2-redox systems.

One of the well-established models for examining neurodegeneration and neurotoxicity is the Drosophila melanogaster model of aluminum-induced toxicity. Anti-cholinesterase drugs have been combined with other neuroprotective agents to improve Alzheimer's disease management, but there is not much information on the combination of anti-cholinesterases with dietary polyphenols to combat memory impairment. Here, we assess how curcumin influences some of the critical therapeutic effects of donepezil (a cholinesterase inhibitor) in AlCl3-treated Drosophila melanogaster. Harwich strain flies were exposed to 40 mM AlCl3 - alone or in combination with curcumin (1 mg/g) and/or donepezil (12.5 µg/g and 25 µg/g) - for seven days. The flies' behavioral evaluations (memory index and locomotor performance) were analyzed. Thereafter, the flies were processed into homogenates for the quantification of acetylcholinesterase (AChE), catalase, total thiol, and rate of lipid peroxidation, as well as the mRNA levels of acetylcholinesterase (ACE1) and cnc/NRF2. Results showed that AlCl3-treated flies presented impaired memory and increased activities of acetylcholinesterase and lipid peroxidation, while there were decrease in total thiol levels and catalase activity when compared to the control. Also, the expression of ACE1 was significantly increased while that of cnc/NRF2 was significantly decreased. However, combinations of curcumin and donepezil, especially at lower dose of donepezil, significantly improved the memory index and biochemical parameters compared to donepezil alone. Thus, curcumin plus donepezil offers unique therapeutic effects during memory impairment in the D. melanogaster model of neurotoxicity.

Cytochrome P-450-mediated herb and food-drug interactions can be identified in cancer patients through patient self-reporting with a tablet application: results of a prospective observational study.

BACKGROUND: Consumption of herbs, food used as medicine and dietary supplements (HFDSs) is common in cancer patients. Herbs and food-drug interactions (HFDIs) can lead to serious adverse effects and can be prevented. We previously reviewed cytochrome P-450 (CYP)-mediated HFDI for 261 HFDSs and we classified the risk of CYP inhibition and induction on a level of evidence scale from 1 (high evidence, supported by several clinical studies) to 5 (low evidence, only limited preclinical data). PATIENTS AND METHODS: We conducted a prospective, non-interventional study (NCT04128865) to assess whether self-assessment of patients could detect HFDI classified as 'probable' (i.e. level 1, 2 or 3 of the scale) in a population of cancer patients. Patients were invited through a tablet application to report their consumption of herbs, regular CYP-interacting food consumption and dietary supplements, as well as some clinical data and cancer treatments. The patient's completion of the survey could be supervised by a health care professional or not. A prespecified threshold of 5% of HFDIs classified as 'probable' detected with the application was deemed relevant. RESULTS: Between 29 March 2018 and 22 June 2018, 143 patients completed the survey. Ninety-five patients (66%) reported at least one current systemic cancer treatment and were included in the analyses. Seventy-four patients reported an intake of at least one HFDS (77.9%), while 21 patients reported no HFDS (22.1%). Twenty-two HFDIs classified as 'probable' were found in 16 patients (16.8%) with the application, which was significantly superior to the prespecified threshold (P = 0.02). The interactions were reported with food (n = 19, 86%) more frequently than with herbs (n = 3, 14%) or with dietary supplements (no interaction reported). CONCLUSIONS: Self-assessment of HFDS interaction with cancer treatment with an application is feasible and should be considered in daily routine. Prospective interventional studies should be conducted to better assess the clinical benefits of this approach.

Possible Mechanisms of the Interplay between Drugs and Mycotoxins-Is There a Possible Impact?

Mycotoxin contamination is a global food safety issue leading to major public health concerns. Repeated exposure to multiple mycotoxins not only has repercussions on human health but could theoretically also lead to interactions with other xenobiotic substances-such as drugs-in the body by altering their pharmacokinetics and/or pharmacodynamics. The combined effects of chronic drug use and mycotoxin exposure need to be well understood in order to draw valid conclusions and, in due course, to develop guidelines. The aim of this review is to focus on food contaminants, more precisely on mycotoxins, and drugs. First, a description of relevant mycotoxins and their effects on human health and metabolism is presented. The potential for interactions of mycotoxins with drugs using in vitro and in vivo animal experiments is summarized. Predictive software tools for unraveling mycotoxin-drug interactions are proposed and future perspectives on this emerging topic are highlighted with a view to evaluate associated risks and to focus on precision medicine. In vitro and in vivo animal studies have shown that mycotoxins affect CYP450 enzyme activity. An impact from drugs on mycotoxins mediated via CYP450-enzymes is plausible; however, an impact of mycotoxins on drugs is less likely considering the much smaller dose exposure to mycotoxins. Drugs that are CYP450 perpetrators and/or substrates potentially influence the metabolism of mycotoxins, metabolized via these CYP450 enzymes. To date, very little research has been conducted on this matter. The only statistically sound reports describe mycotoxins as victims and drugs as perpetrators in interactions; however, more analysis on mycotoxin-drug interactions needs to be performed.

Synergistic cardioprotective ability of co-administration of Moringa supplemented diets and acarbose in diabetic cardiomyopathy involves attenuation of cholinergic, purinergic, monoaminergic, renin-angiotensin system, and antioxidant pathways.

One of the major complications of diabetes mellitus (DM) is diabetic cardiomyopathy (DCM) due to the multifaceted therapy involved. Here, we evaluated the combinatorial effect of Moringa leaf (ML) and seed (MS) supplemented diets plus acarbose (ACA) on cardiac acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), adenosine deaminase (ADA), monoamine oxidase (MAO), arginase, angiotensin-I converting enzyme (ACE), and lactate dehydrogenase (LDH) activities, thiobarbituric acid reactive species (TBARS), and thiols levels. The diets and ACA (25 mg/kg) were administered for 14 days. The fasting blood glucose level (FBGL), cardiac AChE, ATPase, ADA, MAO, arginase, ACE, LDH activities, and TBARS and thiol levels were determined. Relative to the normal rats, the biomarkers were significantly increased in DM rats but were suppressed significantly in the diets plus ACA-treated rats while improving antioxidant status, with the 4% Moringa plus ACA proving outstanding compared to individual ML/MS and ACA. In addition, ML-supplemented diets with/without ACA had better effects compared to MS with/without ACA, respectively. In conclusion, the combination of ML/MS supplemented diets and ACA synergistically modulates the tested biochemicals. However, the effect on blood vessels and the nerves that control the heart, stiffness of left ventricular (LV) hypertrophy, fibrosis, cell signaling abnormalities, related gene expression, clinical trials, and echocardiology studies should be further investigated to affirm this claim. PRACTICAL APPLICATIONS: Moringa oleifera has been a vocal appetite in mitigating cardiovascular disease induced by diabetes, but the formulation of a medicinal diet as an ameliorative route of attention to the pathology is fairly addressed, not talking of its combination with the synthetic antidiabetic drug, such as ACA. Based on this experiment, it is imperative to explore such an idea. This research shows that co-administration of moringa leaf/seed formulated diets plus ACA exhibits a synergistic effect in DCM management. However, further research is needed in this field of experiment.

Effect of chlorogenic acid plus donepezil on critical neurocortical enzyme activities, inflammatory markers, and synaptophysin immunoreactivity in scopolamine-assaulted rats, supported by multiple ligand simultaneous docking.

The effect of chlorogenic acid (a natural phenolic acid ubiquitous in plant foods) on selected therapeutic properties of donepezil (DON) in a scopolamine (SCOP)-induced rat model of amnesia was the focus of this study. Adult albino (Wister strain) rats were allocated into five groups (n = 11) consisting of control, SCOP, SCOP + chlorogenic acid (CGA), SCOP + DON, and SCOP + CGA + DON for 7 days. Post-treatment, the rat brain cerebral cortex homogenate was assayed for cholinesterase and monoamine oxidase activities. Also, the reactive oxygen species, total thiol and nitric oxide contents, alongside catalase, and superoxide dismutase activities were determined. Routine histology for neuronal and glial cells as well as synaptophysin immunoreactivity was also carried out on the cerebral cortex. Thereafter, multiple ligand simultaneous docking was carried out for DON and CGA at the active sites of AChE and BChE. The results revealed that the biochemical parameters, glial cells, and synaptophysin immunoreactivity were significantly impaired in the cerebral cortex of scopolamine-treated rats. However, impaired butyrylcholinesterase and monoamine oxidase activity, together with antioxidant, glial cells, and synaptophysin levels were significantly ameliorated in scopolamine-treated rats administered DON + CGA compared to donepezil alone. The docking of both DON and CGA at the active sites of AChE or BChE showed higher binding energy to both enzymes compared to individual interactions of either DON or CGA. Hence, this study has been able to show that CGA could improve some of the therapeutic effects of DON, which could broaden the therapeutic spectrum of this drug. PRACTICAL APPLICATIONS: This study showed that chlorogenic acid (a major phenolic acid found in plant foods such as coffee) modulated some of the therapeutic properties of donepezil (an anticholinesterase drug used in the treatment of mild-to-moderate Alzheimer's disease). The combinations elicited better anti-butyrylcholinesterase, antimonoamine oxidase, and antioxidant properties, thus presenting this food-drug interaction as potentially able to offer better therapeutic properties.

Core shell stationary phase for a novel separation of some COVID-19 used drugs by UPLC-MS/MS Method: Study of grapefruit consumption impact on their pharmacokinetics in rats.

A sensitive and selective UPLC-MS/MS method was developed for the synchronized determination of four drugs used in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, azithromycin, apixaban, dexamethasone, and favipiravir in rat plasma. using a Poroshell 120 EC-C18 column (50 mm × 4.6 mm, 2.7 m) with a high-resolution ESI tandem mass spectrometer detection with multiple reaction monitoring. We used an Agilent Poroshell column, which is characterized by a stationary phase based on non-porous core particles. With a remarkable improvement in the number of theoretical plates and low column backpressure. In addition, the developed method was employed in studying the potential food-drug interaction of grapefruit juice (GFJ) with the selected drugs which affects their pharmacokinetics in rats. The LC-MS/MS operated in positive and negative ionization mode using two internal standards: moxifloxacin and chlorthalidone, respectively. Liquid- liquid extraction of the cited drugs from rat plasma was accomplished using diethyl ether: dichloromethane (70:30, v/v). The analytes were separated using methanol: 0.1 % formic acid in water (95: 5, v/v) as a mobile phase in isocratic mode of elution pumped at a flow rate of 0.3 mL/min. A detailed validation of the bio-analytical method was performed in accordance with US-FDA and EMA guidelines. Concerning the in vivo pharmacokinetic study, the statistical significance between the results of the test groups receiving GFJ along with the cited drugs and the control group was assessed demonstrating that GFJ increased the plasma concentration of azithromycin, apixaban, and dexamethasone. Accordingly, this food-drug interaction requires cautious ingestion of GFJ in patients using (SARS-CoV-2) medications as it can produce negative effects in the safety of the drug therapy. A potential drug-drug interaction is also suggested between those medications requiring a suitable dose adjustment.

Comparison of the inhibitory properties of the fruit component naringenin and its glycosides against OATP1A2 genetic variants.

Non-synonymous genetic variants of organic anion-transporting polypeptide (OATP) 1A2 with altered transport activity have been identified. Naringin and narirutin, which are found in grapefruit, and their aglycon naringenin inhibit OATP1A2. However, their inhibitory effects on OATP1A2 variants have not been investigated, nor has the influence of their molecular structure, such as the number of sugar moieties, on their inhibitory potency. This study aimed to investigate the inhibitory effects of naringenin, its monosaccharide glycoside prunin, and its disaccharide glycosides naringin and narirutin on fexofenadine (FEX) uptake by OATP1A2 variants (Ile13Thr, Asn128Tyr, Ala187Thr, and Thr668Ser). Naringin, narirutin, and prunin inhibited FEX (0.3 µM) uptake by all of the examined OATP1A2 variants in a concentration-dependent manner. Compared with those for the wild type, the inhibition constants (Ki) of naringin, narirutin, and prunin for the Ala187Thr variant were significantly increased by 3.36-fold, 7.55-fold, and 10.6-fold, respectively. Naringenin inhibited all of the OATP1A2 variants, except Ala187Thr, concentration-dependently. The order of inhibitory potency was as follows for all variants: aglycone > monosaccharide glycoside > disaccharide glycosides. These results suggest that the Ala187Thr variant is less vulnerable to inhibition by naringenin and its glycosides. Moreover, greater glycosylation of naringenin reduces its inhibitory potency against OATP1A2.

Can gallic acid potentiate the antihyperglycemic effect of acarbose and metformin? Evidence from streptozotocin-induced diabetic rat model.

This study investigated the influence of dietary phenolic acid- Gallic acid (GA) on the antihyperglycemic properties of acarbose (ACA) and metformin (MET). Streptozotocin-induced diabetic rats were treated (p.o) with ACA, MET, GA and their combinations for 14 days. The effects of the treatments on blood glucose and insulin levels, pancreas α-amylase and intestinal α-glucosidase activities, as well as thiobarbituric acid reactive species (TBARS), thiol and reactive oxygen species (ROS) levels, including antioxidant enzyme activities were investigated. A significant increase in blood glucose, insulin, ROS and TBARS levels, and impaired antioxidant status, as well as elevation in the activities of α-amylase and α-glucosidase observed in diabetic rats were ameliorated in the treatment groups. Hpwever, GA had varying effects on the antidiabetic properties of the drugs. Nevertheless, GA showed more potentiating effects on the antidiabetic effect of MET and these effects were better observed at the lower dose of GA.

Dietary Habits and Musculoskeletal Pain in Statin and Red Yeast Rice Users: A Pilot Study.

(1) Background: Diet and statins are commonly used to treat high cholesterol (CHOL) levels. (2) Aim: To compare adherence to Mediterranean diet (Med-D), orthorexia nervosa (ON), and musculoskeletal pain in individuals in treatment with statins metabolized by CYP3A4, not metabolized by CYP3A4 or red yeast rice (RYR, containing monacolin K: MON-K). (3) Methods: starting from 80 individuals, after the exclusion of those with other causes of possible pain, 56 individuals were selected and divided into three groups according to the type of statin (CYP3A4, NO-CYP3A4 and MON-K). Adherence to the Med-D was evaluated with the MEDScore and a sub-score was calculated for fruit and vegetables consumption (MEDScore-FV). ON and musculoskeletal pain were assessed with the ORTO-15 and with the Nordic Musculoskeletal questionnaires, respectively. A retrospective analysis of CHOL decrease after treatment was conducted. (4) Results: CHOL levels were lower in CYP3A4 and NO-CYP3A4 after treatment (182.4 ± 6.3 and 177.0 ± 7.8 mg/dL, respectively), compared with MON-K (204.2 ± 7.1 mg/dL, p < 0.05). MON-K and CYP3A4 groups had a high prevalence of reported knee pain (33.3% and 18.8%, respectively) than NO-CYP3A4 group (0%, p < 0.05). A high percentage of individuals in MON-K take supplements and nutraceuticals (87.5%), whereas MEDScore-FV was higher in CYP3A4 (9.4 ± 0.2) compared to NO-CYP3A4 (7.6 ± 0.5, p < 0.05). (5) Conclusions: This study suggests that individuals receiving treatment with statins and RYR should be monitored from the perspective of plant foods' consumption and nutraceutical use, to prevent musculoskeletal pain.

Potential cytochrome P450-mediated pharmacokinetic interactions between herbs, food, and dietary supplements and cancer treatments.

Herbs, food and dietary supplements (HFDS), can interact significantly with anticancer drug treatments via cytochrome p450 isoforms (CYP) CYP3A4, CYP2D6, CYP1A2, and CYP2C8. The objective of this review was to assess the influence of HFDS compounds on these cytochromes. Interactions with CYP activities were searched for 189 herbs and food products, 72 dietary supplements in Web of Knowledge® databases. Analyses were made from 140 of 3125 clinical trials and 236 of 3374 in vitro, animal model studies or case reports. 18 trials were found to report direct interactions between 9 HFDS with 8 anticancer drugs. 21 HFDS were found to interact with CYP3A4, a major metabolic pathway for many anticancer drugs. All 261 HFDS were classified for their interaction with the main cytochromes P450 involved in the metabolism of anticancer drugs. We provided an easy-to-use colour-coded table to easily match potential interactions between 261 HFDS and 117 anticancer drugs.

Uptake Pathway of Apple-derived Nanoparticle by Intestinal Cells to Deliver its Cargo.

PURPOSE: Food-derived nanoparticles exert cytoprotective effects on intestinal cells by delivering their cargo, which includes macromolecules such as microRNAs and proteins, as well as low-molecular weight compounds. We previously reported that apple-derived nanoparticles (APNPs) downregulate the expression of human intestinal transporter OATP2B1/SLCO2B1 mRNA. To verify the involvement of the cargo of APNPs in affecting the expression of transporters, we characterized the uptake mechanism of APNPs in intestinal cells. METHODS: The uptake of fluorescent PKH26-labeled APNPs (PKH-APNPs) into Caco-2, LS180, and HT-29MTX cells was evaluated by confocal microscopy and flow cytometry. RESULTS: The uptake of PKH-APNPs was prevented in the presence of clathrin-dependent endocytosis inhibitors, chlorpromazine and Pitstop2. Furthermore, PKH-APNPs were incorporated by the HT29-MTX cells, despite the disturbance of the mucus layer. Additionally, the decrease in SLCO2B1 mRNA by APNPs was reversed by Pitstop 2 in Caco-2 cells, indicating that APNPs decrease SLCO2B1 by being incorporated via clathrin-dependent endocytosis. CONCLUSIONS: We demonstrated that clathrin-dependent endocytosis was mainly involved in the uptake of APNPs by intestinal cells, and that the cargo in the APNPs downregulate the mRNA expression of SLCO2B1. Therefore, APNPs could be a useful tool to deliver large molecules such as microRNAs to intestinal cells.