Effects of Soluble Dextrin Fiber from Potato Starch on Body Weight and Associated Gut Dysbiosis Are Evident in Western Diet-Fed Mice but Not in Overweight/Obese Children.

BACKGROUND: The study investigated the impact of starch degradation products (SDexF) as prebiotics on obesity management in mice and overweight/obese children. METHODS: A total of 48 mice on a normal diet (ND) and 48 on a Western diet (WD) were divided into subgroups with or without 5% SDexF supplementation for 28 weeks. In a human study, 100 overweight/obese children were randomly assigned to prebiotic and control groups, consuming fruit and vegetable mousse with or without 10 g of SDexF for 24 weeks. Stool samples were analyzed for microbiota using 16S rRNA gene sequencing, and short-chain fatty acids (SCFA) and amino acids (AA) were assessed. RESULTS: Results showed SDexF slowed weight gain in female mice on both diets but only temporarily in males. It altered bacterial diversity and specific taxa abundances in mouse feces. In humans, SDexF did not influence weight loss or gut microbiota composition, showing minimal changes in individual taxa. The anti-obesity effect observed in mice with WD-induced obesity was not replicated in children undergoing a weight-loss program. CONCLUSIONS: SDexF exhibited sex-specific effects in mice but did not impact weight loss or microbiota composition in overweight/obese children.

L-Arginine supplementation in pregnancy: a systematic review of maternal and fetal outcomes.

BACKGROUND/AIM OF THE STUDY: L-Arginine (L-Arg)/Nitric Oxide (NO) system is involved in the pathophysiology of relevant Obstetric conditions. This review aims at summarizing the effects of L-Arg supplementation in pregnancy looking at safety and efficacy. METHODS: We conducted a systematic review of the literature utilizing PubMed for studies published from inception to September 2022. The search included human and animal studies where L-Arg was supplemented pre-conceptionally or during pregnancy, by either oral or intravenous route. The main perinatal outcomes were focused. RESULTS: Among 1028 publications, 51 studies were eligible for inclusion, 25 were performed in women, and the remnant in animals. Compared to controls/placebo, the supplementation with L-Arg reduced the development of pre-eclampsia (four studies), decreased blood pressure, and reduced the need for antihypertensive drugs in women with Hypertensive Disorders of Pregnancy (HDP, eight studies). In women carrying growth retarded fetuses, L-Arg improved fetoplacental circulation, birth weight and neonatal outcomes (five studies), while in the case of threatened preterm birth, L-Arg reduced uterine contractions (two studies). In several animal species, L-Arg supplementation in pregnancy improved reproductive performance by increasing the litter number and size. Moreover, in pre-eclamptic and metabolic syndrome experimental models, maternal hypertension and fetal growth were improved. CONCLUSION: L-Arg displays biological activities in pregnancies complicated by HDP and growth restriction, both in women and animal models. L-Arg administration is safe and could be a candidate as an intervention beneficial to maternal and fetal outcomes, at least in moderate clinical disorders.

Short-chain fatty acids as a link between diet and cardiometabolic risk: a narrative review.

AIM: Diet has a profound impact on cardiometabolic health outcomes such as obesity, blood glucose, blood lipids and blood pressure. In recent years, the gut microbiota has emerged as one of several potential key players explaining dietary effects on these outcomes. In this review we aim to summarise current knowledge of interaction between diet and gut microbiota focusing on the gut-derived microbial metabolites short-chain fatty acids and their role in modulating cardiometabolic risk. FINDINGS: Many observational and interventional studies in humans have found that diets rich in fibre or supplemented with prebiotic fibres have a favourable effect on the gut microbiota composition, with increased diversity accompanied by enhancement in short-chain fatty acids and bacteria producing them. High-fat diets, particularly diets high in saturated fatty acids, have shown the opposite effect. Several recent studies indicate that the gut microbiota modulates metabolic responses to diet in, e.g., postprandial blood glucose and blood lipid levels. However, the metabolic responses to dietary interventions, seem to vary depending on individual traits such as age, sex, ethnicity, and existing gut microbiota, as well as genetics. Studies mainly in animal models and cell lines have shown possible pathways through which short-chain fatty acids may mediate these dietary effects on metabolic regulation. Human intervention studies appear to support the favourable effect of short-chain fatty acid in animal studies, but the effects may be modest and vary depending on which cofactors were taken into consideration. CONCLUSION: This is an expanding and active field of research that in the near future is likely to broaden our understanding of the role of the gut microbiota and short-chain fatty acids in modulating metabolic responses to diet. Nevertheless, the findings so far seem to support current dietary guidelines encouraging the intake of fibre rich plant-based foods and discouraging the intake of animal foods rich in saturated fatty acids.

Towards a modern approach to traditional use of Helichrysum italicum in dermatological conditions: In vivo testing supercritical extract on artificially irritated skin.

ETHNOPHARMACOLOGICAL RELEVANCE: Helichrysum italicum has been widely used in traditional medicine to treat allergies, colds, cough, skin, liver and gallbladder disorders, inflammation, infections, and sleeplessness. Furthermore, it possesses considerable wound healing and skin protective properties, documented by several in vivo studies performed on animals. However, there is a lack of experimental evidence supporting its potential as a topical agent tested by human clinical trials. AIM OF THE STUDY: The study aimed to investigate the skin protective activity of cotton gauze and polypropylene non-woven fabric, impregnated with H. italicum extract by the integrated supercritical CO2 extraction-supercritical solvent impregnation process. MATERIALS AND METHODS: The integrated process of supercritical CO2 extraction of H. italicum and the impregnation of cotton gauze and polypropylene non-woven fabric was performed under 350 bar and 40 °C with and without the addition of ethanol as a cosolvent. Impregnated textile materials were tested in vivo for their bioactivity on irritated human skin. Randomized in vivo studies performed involved assays of both safety and efficacy of the impregnated textiles. The effects were evaluated using the in vivo non-invasive biophysical measurements of the following skin parameters: electrical capacitance, transepidermal water loss, melanin index, erythema index, and skin pH. RESULTS: Both cotton gauze and polypropylene non-woven fabric were impregnated with H. italicum extracts under supercritical conditions with considerable values of the impregnation yield (1.97%-4.25%). The addition of ethanol as a cosolvent during the process caused significant changes in the incorporated extracts' impregnation yield and chemical profile. Both impregnated textile materials were safe, evaluated by their testing on the human skin with no cause of any irritation and redness. However, efficacy studies revealed that polypropylene non-woven fabric impregnated with H. italicum extract with ethanol as a cosolvent, possessed significantly greater potential for skin protection than the other investigated samples. CONCLUSIONS: The present study demonstrated the feasibility of the combined supercritical extraction and impregnation process in developing materials for topical application based on H. italicum extract. The results of in vivo studies performed on human volunteers confirmed the suitability of H. italicum active components to be a part of human skin protective preparations because of their ability to maintain the skin unimpaired. Traditionally claimed applications as a medicinal plant capable of regenerating skin have been scientifically proven, in addition to employing green technology in obtaining the impregnated materials with a broad spectrum of utilization.

Efficacy and Variability in Plasma Nitrite Levels during Long-Term Supplementation with Nitrate Containing Beetroot Juice.

Long-term consumption of beetroot juice on efficacy of converting dietary nitrate to plasma nitrate and nitrite was investigated. Adults were randomized to consume either beetroot juice with 380 mg of nitrate (BR) or a beetroot juice placebo (PL) for 12-weeks. Plasma nitrate and nitrite were measured before and 90-minutes after consuming their intervention beverage. Percent change in nitrite across the 90 min was greater in BR (273.2 ± 39.9%) vs. PL (4.9 ± 36.9%). Long-term consumption of nitrate containing beetroot juice increased fasting nitrate and nitrite plasma levels compared to baseline.

Antioxidant potential of family Cucurbitaceae with special emphasis on Cucurbita genus: A key to alleviate oxidative stress-mediated disorders.

Oxidative stress is the imbalance between reactive oxygen species (ROS) production, and accumulation and the ability of a biological system to clear these reactive products. This imbalance leads to cell and tissue damage causing several disorders in human body, such as neurodegeneration, metabolic problems, cardiovascular diseases, and cancer. Cucurbitaceae family consists of about 100 genera and 1,000 species of plants including mostly tropical, annual or perennial, monoecious, and dioecious herbs. The plants from Cucurbita species are rich sources of phytochemicals and act as a rich source of antioxidants. The most important phytochemicals present in the cucurbits are cucurbitacins, saponins, carotenoids, phytosterols, and polyphenols. These bioactive phyto-constituents are responsible for the pharmacological effects including antioxidant, antitumor, antidiabetic, hepatoprotective, antimicrobial, anti-obesity, diuretic, anti-ulcer activity, and antigenotoxic. A wide number of in vitro and in vivo studies have ascribed these health-promoting effects of Cucurbita genus. Results of clinical trials suggest that Cucurbita provides health benefits for diabetic patients, patients with benign prostate hyperplasia, infertile women, postmenopausal women, and stress urinary incontinence in women. The intend of the present review is to focus on the protective role of Cucurbita spp. phytochemicals on oxidative stress-related disorders on the basis of preclinical and human studies. The review will also give insights on the in vitro and in vivo antioxidant potential of the Cucurbitaceae family as a whole.

Effects of Combining Caffeine and Sodium Bicarbonate on Exercise Performance: A Review with Suggestions for Future Research.

This paper aimed to: (a) critically review studies that explored the isolated and combined effects of caffeine and sodium bicarbonate ingestion on exercise performance; (b) discuss some of the possible reasons for the discrepancy in findings; and, (c) provide suggestions for future studies. Out of the eight studies that examined this topic, only one study found that the combined ingestion of both supplements provided additive effects. In other studies, the following findings were observed: (a) only caffeine was ergogenic; (b) isolated and combined ingestion of both supplements was comparably ergogenic; (c) neither isolated nor combined ingestion of caffeine and sodium bicarbonate provided a performance-enhancing effect; and, (d) caffeine and caffeine plus sodium bicarbonate improved performance compared to sodium bicarbonate (but not as compared to placebo). Even though studies used currently recommended protocols of caffeine supplementation and exercise tasks for which the isolated ergogenic effects of caffeine and sodium bicarbonate are already established, the response to sodium bicarbonate supplementation was very variable, which might largely explain the discrepancies in the findings. The protocols of sodium bicarbonate ingestion generally resulted in high incidence and severity of side-effects, which might have had a negative effect on exercise performance. Future studies that optimize protocols of sodium bicarbonate supplementation are needed to fully explore if combining caffeine and sodium bicarbonate indeed provides any additive effects on exercise performance.

Anti-trichomonad activities of different compounds from foods, marine products, and medicinal plants: a review.

Human trichomoniasis, caused by the pathogenic parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease that contributes to reproductive morbidity in affected women and possibly to prostate cancer in men. Tritrichomonas foetus strains cause the disease trichomoniasis in farm animals (cattle, bulls, pigs) and diarrhea in domestic animals (cats and dogs). Because some T. vaginalis strains have become resistant to the widely used drug metronidazole, there is a need to develop alternative treatments, based on safe natural products that have the potential to replace and/or enhance the activity of lower doses of metronidazole. To help meet this need, this overview collates and interprets worldwide reported studies on the efficacy of structurally different classes of food, marine, and medicinal plant extracts and some of their bioactive pure compounds against T. vaginalis and T. foetus in vitro and in infected mice and women. Active food extracts include potato peels and their glycoalkaloids α-chaconine and α-solanine, caffeic and chlorogenic acids, and quercetin; the tomato glycoalkaloid α-tomatine; theaflavin-rich black tea extracts and bioactive theaflavins; plant essential oils and their compounds (+)-α-bisabolol and eugenol; the grape skin compound resveratrol; the kidney bean lectin, marine extracts from algae, seaweeds, and fungi and compounds that are derived from fungi; medicinal extracts and about 30 isolated pure compounds. Also covered are the inactivation of drug-resistant T. vaginalis and T. foetus strains by sensitized light; anti-trichomonad effects in mice and women; beneficial effects of probiotics in women; and mechanisms that govern cell death. The summarized findings will hopefully stimulate additional research, including molecular-mechanism-guided inactivations and human clinical studies, that will help ameliorate adverse effects of pathogenic protozoa.

Potential of Moringa oleifera to Improve Glucose Control for the Prevention of Diabetes and Related Metabolic Alterations: A Systematic Review of Animal and Human Studies.

Moringa oleifera (MO) is a multipurpose plant consumed as food and known for its medicinal uses, among others. Leaves, seeds and pods are the main parts used as food or food supplements. Nutritionally rich and with a high polyphenol content in the form of phenolic acids, flavonoids and glucosinolates, MO has been shown to exert numerous in vitro activities and in vivo effects, including hypoglycemic activity. A systematic search was carried out in the PubMed database and reference lists on the effects of MO on glucose metabolism. Thirty-three animal studies and eight human studies were included. Water and organic solvent extracts of leaves and, secondly, seeds, have been extensively assayed in animal models, showing the hypoglycemic effect, both under acute conditions and in long-term administrations and also prevention of other metabolic changes and complications associated to the hyperglycemic status. In humans, clinical trials are scarce, with variable designs and testing mainly dry leaf powder alone or mixed with other foods or MO aqueous preparations. Although the reported results are encouraging, especially those from postprandial studies, more human studies are certainly needed with more stringent inclusion criteria and a sufficient number of diabetic or prediabetic subjects. Moreover, trying to quantify the bioactive substances administered with the experimental material tested would facilitate comparison between studies.

Practical Considerations of Hypotheses and Evidence in Cannabis Pharmacotherapy: Refining Expectations of Clinical Endocannabinoid Deficiency.

An Industry founded on the promotion of presumed health and wellness benefits of cannabis use continues to grow in the United States, despite the lack of substantial evidence in support of the many claims being made. Several hypotheses exist regarding the role of endocannabinoids in human health and the pertinence of phytocannabinoids as pharmacotherapies for addressing their dysregulation. An opinion is offered regarding the tenuous nature of these assumptions and questions are raised regarding how best to interpret the complex metabolic interplay of the still vaguely defined endocannabinoid system.

Pharmacodynamic interactions of antiepileptic drugs: From bench to clinical practice.

BACKGROUND: Approximately 50% of patients do not achieve seizure control with antiepileptic drug (AED) monotherapy, and polytherapy, with more than one AED, is often required. To date, no evidence-based criteria on how to combine AEDs exist. OBJECTIVE: This narrative review aimed to provide critical findings of the available literature about the role of pharmacodynamic AEDs' interactions in patients whose epilepsies were treated with polytherapy. METHODS: Electronic databases, Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE), were systematically searched to identify relevant studies on pharmacodynamic AEDs' interactions in patients with epilepsy. RESULTS AND CONCLUSION: Most data on AED combinations are coming from animal models and preclinical studies. Combining AEDs with different mechanisms of actions seems to have greater effectiveness and lower risk of adverse event development. Conversely, the combination of AEDs may cause pharmacodynamic synergistic effects that may result in not only increased efficacy but also more adverse effects. Despite some AED associations that have been proven to be effective in specific epilepsy/seizure type (e.g., phenobarbital+/phenytoin for tonic seizures and ethosiximide + valproate for absences; lamotrigine + valproate for various epilepsy/seizure types), no clear and definitive evidence exists about AED combinations in humans. Examples of pharmacodynamic interactions that possibly explain the synergistic effects on efficacy or adverse effects include the combination between vigabatrin or pregabalin and sodium channel blockers (supra-additive antiseizure effect) and lacosamide combined with other sodium channel blockers (infra-additive antiseizure effect and neurotoxicity synergistic). The pharmacodynamic lamotrigine-valproate interaction is also supported by synergistic adverse events. Therefore, well-designed double-blind prospective studies recruiting a sufficient number of patients possibly with a crossover design and carefully ascertain the role of pharmacokinetic interactions and variations of AEDs' levels in the blood are needed.

Culinary herbs and spices: what can human studies tell us about their role in the prevention of chronic non-communicable diseases?

Culinary herbs and spices (CHS) are known primarily as flavour enhancers, and it is now well established that they possess bioactive properties that indicate that these foods may have a role to play in the prevention of non-communicable chronic diseases (CNCDs). Human studies are now beginning to provide insights into the significance of the potential health benefits of CHS in a dietary context, particularly concerning their antioxidant and anti-inflammatory properties and their impact on glucose homeostasis, appetite and the consumption of low/reduced fat, salt and sugar foods. However, these studies have also identified a number of factors that are very pertinent to furthering understanding of how CHS can be used for the maintenance of health and the prevention of CNCDs. The challenge for the next phase of studies will be how to incorporate, successfully, these factors into study methodology for investigating the preventative benefits of these foods. © 2019 Society of Chemical Industry.

Selenium, selenoprotein P, and Alzheimer's disease: is there a link?

The essential trace element, selenium (Se), is crucial to the brain but it may be potentially neurotoxic, depending on dosage and speciation; Se has been discussed for decades in relation to Alzheimer's disease (AD). Selenoprotein P (SELENOP) is a secreted heparin-binding glycoprotein which serves as the main Se transport protein in mammals. In vivo studies showed that this protein might have additional functions such as a contribution to redox regulation. The current review focuses on recent research on the possible role of SELENOP in AD pathology, based on model and human studies. The review also briefly summarizes results of epidemiological studies on Se supplementation in relation to brain diseases, including PREADViSE, EVA, and AIBL. Although mainly positive effects of Se are assessed in this review, possible detrimental effects of Se supplementation or exposure, including potential neurotoxicity, are also mentioned. In relation to AD, various roles of SELENOP are discussed, i.e. as the means of Se delivery to neurons, as an antioxidant, in cytoskeleton assembly, in interaction with redox-active metals (copper, iron, and mercury) and with misfolded proteins (amyloid-beta and hyperphosphorylated tau-protein).

Photobiomodulation for traumatic brain injury and stroke.

There is a notable lack of therapeutic alternatives for what is fast becoming a global epidemic of traumatic brain injury (TBI). Photobiomodulation (PBM) employs red or near-infrared (NIR) light (600-1100nm) to stimulate healing, protect tissue from dying, increase mitochondrial function, improve blood flow, and tissue oxygenation. PBM can also act to reduce swelling, increase antioxidants, decrease inflammation, protect against apoptosis, and modulate microglial activation state. All these mechanisms of action strongly suggest that PBM delivered to the head should be beneficial in cases of both acute and chronic TBI. Most reports have used NIR light either from lasers or from light-emitting diodes (LEDs). Many studies in small animal models of acute TBI have found positive effects on neurological function, learning and memory, and reduced inflammation and cell death in the brain. There is evidence that PBM can help the brain repair itself by stimulating neurogenesis, upregulating BDNF synthesis, and encouraging synaptogenesis. In healthy human volunteers (including students and healthy elderly women), PBM has been shown to increase regional cerebral blood flow, tissue oxygenation, and improve memory, mood, and cognitive function. Clinical studies have been conducted in patients suffering from the chronic effects of TBI. There have been reports showing improvement in executive function, working memory, and sleep. Functional magnetic resonance imaging has shown modulation of activation in intrinsic brain networks likely to be damaged in TBI (default mode network and salience network).

Protective effects of tea, red wine and cocoa in diabetes. Evidences from human studies.

Prevention of diabetes through the diet has recently received an increasing interest, and polyphenolic compounds, such as flavanols, have become important potential chemopreventive natural agents due to their proved benefits on health, with low toxicity and cost. Tea, red wine and cocoa are good sources of flavanols and these highly consumed foods might contribute to prevent diabetes. In this regard, there is increasing evidence for a protective effect of tea, red wine and cocoa consumption against this disorder. This review summarizes the available epidemiological and interventional human studies providing evidence for and against this effect. Overall observational data suggest a benefit, but results are still equivocal and likely confounded by lifestyle and background dietary factors. The weight of data indicate favourable effects on diabetes risk factors for tea, red wine and cocoa intake, and a number of plausible mechanisms have been elucidated in human studies. However, despite the growing evidence it remains uncertain whether tea, red wine and cocoa consumption should be recommended to the general population or to patients as a strategy to reduce the risk of diabetes.

Therapeutic efficacy of rose oil: A comprehensive review of clinical evidence.

OBJECTIVE: Rose oil is obtained from the petals of difference Rosa species especially Rosa centifolia L. and Rosa damascena Mill. Various pharmacological properties have been attributed to rose oil. The aim of the present study was to review the rose oil therapeutic effects which had been clinically evaluated in trial studies. MATERIALS AND METHODS: Google scholar, PubMed, Cochrane Library, and Scopus were searched for human studies which have evaluated the therapeutic effects of rose oil and published in English language until August 2015. RESULTS: Thirteen clinical trials (772 participants) were included in this review. Rose oil was administered via inhalation or used topically. Most of the studies (five trials) evaluated the analgesic effect of rose oil. Five studies evaluated the physiological relaxation effect of rose oil. Anti-depressant, psychological relaxation, improving sexual dysfunction, and anti-anxiety effects were the other clinical properties reported for rose oil. CONCLUSION: Numerous studies on the pharmacological properties of rose oil have been done in animals, but studies in humans are few. In this study, it was observed that rose oil had physiological and psychological relaxation, analgesic and anti-anxiety effects. To obtain conclusive results on the efficacy and safety of rose oil, further clinical trials with larger sample size and better designation are required.

Modulation of Ras/ERK and Phosphoinositide Signaling by Long-Chain n-3 PUFA in Breast Cancer and Their Potential Complementary Role in Combination with Targeted Drugs.

A potential complementary role of the dietary long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFA) in combination with innovative mono-targeted therapies has recently been proposed. These compounds are thought to act pleiotropically to prevent the development and progression of a variety of cancers, including breast cancer. We hereinafter critically analyze the reports investigating the ability of LCn-3 PUFA to modulate the Ras/ERK and the phosphoinositide survival signaling pathways often aberrantly activated in breast cancer and representing the main targets of innovative therapies. The in vitro or in vivo animal and human interventional studies published up to January 2017 investigating the effects of LCn-3 PUFA on these pathways in normal and cancerous breast cells or tissues were identified through a systematic search of literature in the PubMed database. We found that, in most cases, both the in vitro and in vivo studies demonstrated the ability of LCn-3 PUFA to inhibit the activation of these pro-survival pathways. Altogether, the analyzed results strongly suggest a potential role of LCn-3 PUFA as complementary agents in combination with mono-targeted therapies. Moreover, the results indicate the need for further in vitro and human interventional studies designed to unequivocally prove the potential adjuvant role of these fatty acids.

Chyawanprash: A review of therapeutic benefits as in authoritative texts and documented clinical literature.

ETHNOPHARMACOLOGICAL RELEVANCE: Chyawanprash (CP), a traditional immune booster recipe, has a long history of ethnic origin, development, household preparation and usage. There are even mythological stories about the origin of this recipe including its nomenclature. In the last six decades, CP, because of entrepreneurial actions of some research Vaidyas (traditional doctors) has grown to industrial production and marketing in packed forms to a large number of consumers/patients like any food or health care product. Currently, CP has acquired a large accepted user base in India and in a few countries out-side India. AIM OF THE STUDY: Authoritative texts, recognized by the Drugs and Cosmetics Act of India, describe CP as an immunity enhancer and strength giver meant for improving lung functions in diseases with compromised immunity. This review focuses on published clinical efficacy and safety studies of CP for correlation with health benefits as documented in the authoritative texts, and also briefs on its recipes and processes. MATERIALS AND METHODS: Authoritative texts were searched for recipes, processes, and other technical details of CP. Labels of marketing CP products (Indian) were studied for the health claims. Electronic search for studies of CP on efficacy and safety data were performed in PubMed/MEDLINE and DHARA (Digital Helpline for Ayurveda Research Articles), and Ayurvedic books were also searched for clinical studies. RESULTS: The documented clinical studies from electronic databases and Ayurvedic books evidenced that individuals who consume CP regularly for a definite period of time showed improvement in overall health status and immunity. However, most of the clinical studies in this review are of smaller sample size and short duration. Further, limitation to access and review significant data on traditional products like CP in electronic databases was noted. CONCLUSIONS: Randomized controlled trials of high quality with larger sample size and longer follow-up are needed to have significant evidence on the clinical use of CP as immunity booster. Additional studies involving measurement of current biomarkers of immunity pre- and post-consumption of the product as well as benefits accruing with the use of CP as an adjuvant are suggested.

Polyphenols and DNA Damage: A Mixed Blessing.

Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds. A variety of assays are in use to study genetic damage endpoints. Human trials, of which there are rather few, tend to show decreases in endogenous DNA damage and protection against DNA damage induced ex vivo in blood cells. Most animal experiments have investigated the effects of polyphenols (often at high doses) in combination with known DNA-damaging agents, and generally they show protection. High concentrations can themselves induce DNA damage, as demonstrated in numerous cell culture experiments; low concentrations, on the other hand, tend to decrease DNA damage.

Quantitation and pharmacokinetic modeling of therapeutic antibody quality attributes in human studies.

A thorough understanding of drug metabolism and disposition can aid in the assessment of efficacy and safety. However, analytical methods used in pharmacokinetics (PK) studies of protein therapeutics are usually based on ELISA, and therefore can provide a limited perspective on the quality of the drug in concentration measurements. Individual post-translational modifications (PTMs) of protein therapeutics are rarely considered for PK analysis, partly because it is technically difficult to recover and quantify individual protein variants from biological fluids. Meanwhile, PTMs may be directly linked to variations in drug efficacy and safety, and therefore understanding of clearance and metabolism of biopharmaceutical protein variants during clinical studies is an important consideration. To address such challenges, we developed an affinity-purification procedure followed by peptide mapping with mass spectrometric detection, which can profile multiple quality attributes of therapeutic antibodies recovered from patient sera. The obtained data enable quantitative modeling, which allows for simulation of the PK of different individual PTMs or attribute levels in vivo and thus facilitate the assessment of quality attributes impact in vivo. Such information can contribute to the product quality attribute risk assessment during manufacturing process development and inform appropriate process control strategy.