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Evaluation of safety and cognitive enhancing effect of Morus alba leaves extract in healthy older adults
102
Abstracts of Pharma Nutrition 2013 / PharmaNutrition 2 (2014) 75–119
obtain ‘good practices’ for a smarter and faster development, (regulatory) acceptance and implementation of methods to replace, reduce or refine (3R) animal experiments. This will be accomplished by intensifying the collaborations between stakeholders already involved at the start of the 3R assay development process, e.g. companies, regulatory bodies and research institutes. Thereby aiming to reduce the time needed to implement innovative and alternative approaches for animal testing. The project team identified several research areas with promising 3R approaches that would contribute to a reduction of animal experiments in safety assessment in these areas. These approaches have been critically reviewed by an advisory board, consisting of scientists working for international regulatory agencies. The individual research projects in the field of reproductive toxicity, food allergy, carcinogenicity and exposure barriers have commenced and will be presented. During the project, obstacles and drivers of 3R-method acceptance will be identified and communicated to a broader group of stakeholders, ranging from scientific experts and policy makers to the general public. The new approach is expected to contribute to acceleration and stimulation of innovations in life sciences. Keywords: Alternatives to animal experiments; Safety assessment; Regulatory acceptance and implementation; Best practices http://dx.doi.org/10.1016/j.phanu.2013.11.075 [P35] Evaluation of safety and cognitive enhancing effect of Morus alba leaves extract in healthy older adults J. Wattanathorn 1,∗ , T. Tong-un 1 , S. Muchimapura 1 , P. Wannanon 1 , W. Thukhammee 1 , K. Anulukanapakorn 2 , M. Bunjob 2 1 2
Khon Kean University, Thailand Ministry of Public Health, Thailand
Cognitive impairment, one of the most complaints of older adults, is continually increased. Thus, attempts to improve cognitive function of these populations have gained much attention. Since Morus alba leaves showed memory enhancing effect in preclinical study, we aimed to determine the cognitive enhancing effect and possible mechanism of M. alba leaves extract in healthy middle aged and elderly volunteers. Sixty healthy volunteers were randomly assigned to receive either placebo or standardized plant extract at doses of 1050 and 2100 mg once daily for 3 months. After the assessment of biographic information, all subjects were collected venous blood for the determination of hematological and clinical chemistry changes and evaluated the working memory and cognitive function using computerized battery test and the auditory oddball paradigm of event related potential before and after 3-month of intervention. It was found that subjects who consumed the extract both at doses of 1050 and 2100 mg. Day-1 showed the enhanced working memory together with the decreased N100 and P300 latencies without any toxicity. These findings suggested the cognitive enhancing effect of M. alba leaves extract. Therefore, M. alba leaves are the potential cognitive enhancer for older adults. However, the precise underlying mechanisms are required further investigation. Keywords: Morus alba; Mulberry; Cognitive enhancing effect; Working memory http://dx.doi.org/10.1016/j.phanu.2013.11.076
[P36] Musa sapientum extract decreases fatigue and oxidative stress markers in rats S. Muchimapura ∗ , J. Wattanathorn, W. Thukhammee Khon Kean University, Thailand Exercise induced fatigue can enhance oxidative stress giving rise to the deterioration of muscle performance. Most energy supplements used can be deleterious and forbidden. Therefore, the search for approved, safe and effective anti-fatigue agents has drawn attention. Ripen Musa sapientum has been used as tonic herb and rejuvenation. Based on its antioxidant and reputation in traditional folklore, the effect of extract on fatigue and on muscle oxidative stress was investigated. Male Wistar rats, weighing 180–220 g, were orally given M. sapientum extract at doses of 20, 100 and 500 mg/kg for 14 days. Rats were subjected to weightloaded swimming test after single administration and every 7 days and exhausted swimming time was recorded. At the end of experiment, they were determined oxidative stress markers including MDA level and the activities of SOD, CAT and GPx in gastrocnemius, soleus and extensor digitorum longus (EDL). All doses of M. sapientum enhances exhausted swimming time after single administration whereas only medium and high doses enhanced this parameter at 7 days of intervention and no change was observed at 14 day of intervention. The changes of oxidative stress markers failed to show closed association with the anti-fatigue effect. Therefore, the precise underlying mechanism is required further study. Keywords: Musa sapientum; Anti-fatigue; Oxidative stress http://dx.doi.org/10.1016/j.phanu.2013.11.077 [P37] Non-digestible oligosaccharides scGOS/lcFOS combined with TLR9 ligand induces a Th1 and regulatory T response in an in vitro co-culture model S.A. Overbeek 1,∗ , K.A.T. Verheijden 1 , A.D. Garssen 1,2 , L.E.M. Willemsen 1 1 2
Kraneveld 1 , J.
Utrecht University, The Netherlands Danone research, The Netherlands
Background: Non-digestible oligosaccharides stimulate the growth and activity of microbiota in the gut and may modulate immune responses in the intestine. Short chain galacto- and long chain fructooligosaccharides (scGOS/lcFOS), resembling oligosaccharides present in human milk, have been reported to reduce the development of allergy. In this study the human intestine was mimicked by using an in vitro transwell co-culture model to investigate the effect of scGOS/lcFOS on immune modulation. Methods: HT-29 cells (human colon adenocarcinoma cell line) were cultured on transwell filters and were used just after reaching confluency. PBMCs were added to the basolateral compartment and stimulated with anti-CD3 and anti-CD28. The HT-29 cells were apically exposed to scGOS/lcFOS in the presence or absence of TLR9 ligand CpG. Moreover, the effect of scGOS/lcFOS with or without CpG in modulating the immune response in the presence or absence of HT-29 was evaluated. Production of IFN␥, IL-13, IL-10, TNF-␣ and galectin-9 in the basolateral compartment was measured after 24 h of co-culture. Results: Apically added TLR9 ligand CpG enhanced IFN␥, IL10 and galectin-9 and reduced IL-13 secretion in the presence of HT-29 cells. This effect was more pronounced in the presence of scGOS/lcFOS; the apical addition of the non-digestible
Abstracts of Pharma Nutrition 2013 / PharmaNutrition 2 (2014) 75–119
obtain ‘good practices’ for a smarter and faster development, (regulatory) acceptance and implementation of methods to replace, reduce or refine (3R) animal experiments. This will be accomplished by intensifying the collaborations between stakeholders already involved at the start of the 3R assay development process, e.g. companies, regulatory bodies and research institutes. Thereby aiming to reduce the time needed to implement innovative and alternative approaches for animal testing. The project team identified several research areas with promising 3R approaches that would contribute to a reduction of animal experiments in safety assessment in these areas. These approaches have been critically reviewed by an advisory board, consisting of scientists working for international regulatory agencies. The individual research projects in the field of reproductive toxicity, food allergy, carcinogenicity and exposure barriers have commenced and will be presented. During the project, obstacles and drivers of 3R-method acceptance will be identified and communicated to a broader group of stakeholders, ranging from scientific experts and policy makers to the general public. The new approach is expected to contribute to acceleration and stimulation of innovations in life sciences. Keywords: Alternatives to animal experiments; Safety assessment; Regulatory acceptance and implementation; Best practices http://dx.doi.org/10.1016/j.phanu.2013.11.075 [P35] Evaluation of safety and cognitive enhancing effect of Morus alba leaves extract in healthy older adults J. Wattanathorn 1,∗ , T. Tong-un 1 , S. Muchimapura 1 , P. Wannanon 1 , W. Thukhammee 1 , K. Anulukanapakorn 2 , M. Bunjob 2 1 2
Khon Kean University, Thailand Ministry of Public Health, Thailand
Cognitive impairment, one of the most complaints of older adults, is continually increased. Thus, attempts to improve cognitive function of these populations have gained much attention. Since Morus alba leaves showed memory enhancing effect in preclinical study, we aimed to determine the cognitive enhancing effect and possible mechanism of M. alba leaves extract in healthy middle aged and elderly volunteers. Sixty healthy volunteers were randomly assigned to receive either placebo or standardized plant extract at doses of 1050 and 2100 mg once daily for 3 months. After the assessment of biographic information, all subjects were collected venous blood for the determination of hematological and clinical chemistry changes and evaluated the working memory and cognitive function using computerized battery test and the auditory oddball paradigm of event related potential before and after 3-month of intervention. It was found that subjects who consumed the extract both at doses of 1050 and 2100 mg. Day-1 showed the enhanced working memory together with the decreased N100 and P300 latencies without any toxicity. These findings suggested the cognitive enhancing effect of M. alba leaves extract. Therefore, M. alba leaves are the potential cognitive enhancer for older adults. However, the precise underlying mechanisms are required further investigation. Keywords: Morus alba; Mulberry; Cognitive enhancing effect; Working memory http://dx.doi.org/10.1016/j.phanu.2013.11.076
[P36] Musa sapientum extract decreases fatigue and oxidative stress markers in rats S. Muchimapura ∗ , J. Wattanathorn, W. Thukhammee Khon Kean University, Thailand Exercise induced fatigue can enhance oxidative stress giving rise to the deterioration of muscle performance. Most energy supplements used can be deleterious and forbidden. Therefore, the search for approved, safe and effective anti-fatigue agents has drawn attention. Ripen Musa sapientum has been used as tonic herb and rejuvenation. Based on its antioxidant and reputation in traditional folklore, the effect of extract on fatigue and on muscle oxidative stress was investigated. Male Wistar rats, weighing 180–220 g, were orally given M. sapientum extract at doses of 20, 100 and 500 mg/kg for 14 days. Rats were subjected to weightloaded swimming test after single administration and every 7 days and exhausted swimming time was recorded. At the end of experiment, they were determined oxidative stress markers including MDA level and the activities of SOD, CAT and GPx in gastrocnemius, soleus and extensor digitorum longus (EDL). All doses of M. sapientum enhances exhausted swimming time after single administration whereas only medium and high doses enhanced this parameter at 7 days of intervention and no change was observed at 14 day of intervention. The changes of oxidative stress markers failed to show closed association with the anti-fatigue effect. Therefore, the precise underlying mechanism is required further study. Keywords: Musa sapientum; Anti-fatigue; Oxidative stress http://dx.doi.org/10.1016/j.phanu.2013.11.077 [P37] Non-digestible oligosaccharides scGOS/lcFOS combined with TLR9 ligand induces a Th1 and regulatory T response in an in vitro co-culture model S.A. Overbeek 1,∗ , K.A.T. Verheijden 1 , A.D. Garssen 1,2 , L.E.M. Willemsen 1 1 2
Kraneveld 1 , J.
Utrecht University, The Netherlands Danone research, The Netherlands
Background: Non-digestible oligosaccharides stimulate the growth and activity of microbiota in the gut and may modulate immune responses in the intestine. Short chain galacto- and long chain fructooligosaccharides (scGOS/lcFOS), resembling oligosaccharides present in human milk, have been reported to reduce the development of allergy. In this study the human intestine was mimicked by using an in vitro transwell co-culture model to investigate the effect of scGOS/lcFOS on immune modulation. Methods: HT-29 cells (human colon adenocarcinoma cell line) were cultured on transwell filters and were used just after reaching confluency. PBMCs were added to the basolateral compartment and stimulated with anti-CD3 and anti-CD28. The HT-29 cells were apically exposed to scGOS/lcFOS in the presence or absence of TLR9 ligand CpG. Moreover, the effect of scGOS/lcFOS with or without CpG in modulating the immune response in the presence or absence of HT-29 was evaluated. Production of IFN␥, IL-13, IL-10, TNF-␣ and galectin-9 in the basolateral compartment was measured after 24 h of co-culture. Results: Apically added TLR9 ligand CpG enhanced IFN␥, IL10 and galectin-9 and reduced IL-13 secretion in the presence of HT-29 cells. This effect was more pronounced in the presence of scGOS/lcFOS; the apical addition of the non-digestible