Protective Potential of a Botanical-Based Supplement Ingredient against the Impact of Environmental Pollution on Cutaneous and Cardiopulmonary Systems: Preclinical Study.

Air pollution is a growing threat to human health. Airborne pollution effects on respiratory, cardiovascular and skin health are well-established. The main mechanisms of air-pollution-induced health effects involve oxidative stress and inflammation. The present study evaluates the potential of a polyphenol-enriched food supplement ingredient comprising Lippia citriodora, Olea europaea, Rosmarinus officinalis, and Sophora japonica extracts in mitigating the adverse effects of environmental pollution on skin and cardiopulmonary systems. Both in vitro and ex vivo studies were used to assess the blend's effects against pollution-induced damage. In these studies, the botanical blend was found to reduce lipid peroxidation, inflammation (by reducing IL-1α), and metabolic alterations (by regulating MT-1H, AhR, and Nrf2 expression) in human skin explants exposed to a mixture of pollutants. Similar results were also observed in keratinocytes exposed to urban dust. Moreover, the ingredient significantly reduced pollutant-induced ROS production in human endothelial cells and lung fibroblasts, while downregulating the expression of apoptotic genes (bcl-2 and bax) in lung fibroblasts. Additionally, the blend counteracted the effect of urban dust on the heart rate in zebrafish embryos. These results support the potential use of this supplement as an adjuvant method to reduce the impact of environmental pollution on the skin, lungs, and cardiovascular tissues.

In Vitro Determination of the Skin Anti-Aging Potential of Four-Component Plant-Based Ingredient.

The beauty industry is actively searching for solutions to prevent skin aging. Some of the crucial elements protecting cells from the aging process are telomere shortening, telomerase expression, cell senescence, and homeostasis of the redox system. Modification of these factors using natural antioxidants is an appealing way to support healthy skin aging. Therefore, in this study, we sought to investigate the antiaging efficacy of a specific combination of four botanical extracts (pomegranate, sweet orange, Cistanche and Centella asiatica) with proven antioxidant properties. To this end, normal human dermal fibroblasts were used as a cell model and the following studies were performed: cell proliferation was established by means of the MTT assay and the intracellular ROS levels in stress-induced premature senescence fibroblasts; telomere length measurement was performed under standard cell culture conditions using qPCR and under oxidative stress conditions using a variation of the Q-FISH technique; telomerase activity was examined by means of Q-TRAP; and AGE quantification was completed by means of ELISA assay in UV-irradiated fibroblasts. As a result, the botanical blend significantly reversed the H2O2-induced decrease in cell viability and reduced H2O2-induced ROS. Additionally, the presence of the botanical ingredient reduced the telomere shortening rate in both stressed and non-stressed replicating fibroblasts, and under oxidative stress conditions, the fibroblasts presented a higher median and 20th percentile telomere length, as well as a lower percentage of short telomeres (<3 Kbp) compared with untreated fibroblasts. Furthermore, the ingredient transiently increased relative telomerase activity after 24 h and prevented the accumulation of UVR-induced glycated species. The results support the potential use of this four-component plant-based ingredient as an antiaging agent.

New App-Based Dietary and Lifestyle Intervention on Weight Loss and Cardiovascular Health.

Consumer digital technology is rapidly evolving, allowing users to manage their health in a simple, non-invasive manner. However, there are few studies revealing if using digital technology as part of an intervention really has an impact in consumer health compared with traditional strategies. The objective of the current study is to compare two groups (MTB; n = 18, 46.1 ± 10.4 years and MTBAPP; n = 19, 45.3 ± 6.40 years) of overweight, prehypertensive individuals in losing weight and lowering their blood pressure. Both were provided with nutritionist-guided recommendations, a wearable tracking device and a dietary supplement that has previously been proven to help lose body weight and lower blood pressure. In addition, one of the groups (MTBAPP) used a mobile app specifically designed for the intervention. Blood pressure, body composition, triglyceride level, peak expiratory flow, forced expiratory volume in the first second and maximum oxygen volume were measured at different time points. In addition, participants were monitored with an activity bracelet throughout the intervention. As a result, both groups significantly lost body weight, while the group using the app additionally improved blood pressure levels and lowered fat mass. Furthermore, the app users significantly increased the number of daily steps and decreased sedentary time. In conclusion, the addition of a mobile app with daily reminders to follow healthy lifestyle recommendations increased physical activity and overall improved blood pressure and fat mass levels when compared with a group performing the same intervention but in absence of the mobile application.

Anxiolytic Effect and Improved Sleep Quality in Individuals Taking Lippia citriodora Extract.

The current fast-moving, hectic lifestyle has increased the number of individuals worldwide with difficulties in managing stress, which in turn is also affecting their sleep quality. Therefore, the objective of the current study was to assess a natural plant-based dietary supplement comprised of lemon verbena (Lippia citriodora) extract, purified in phenylpropanoids, in alleviating stress and improving quality of sleep. A double-blind, placebo-controlled study was conducted for 8 weeks, followed by a 4-week washout period. Both validated questionnaires and functional tests were performed during the study, whereas questionnaires were used after the washout. As a result, the group taking the lemon verbena extract significantly reduced their perception of stress after 8 weeks, which was corroborated by a significant decrease in cortisol levels. After the washout period, the subjects reported to present even lower stress levels, due to the lasting effect of the ingredient. As for sleep quality, the subjects taking the supplement reported feeling better rested, with a stronger effect observed in women. Sleep tracking using a wearable device revealed that the supplement users improved their times in the deeper stages of sleep, specifically their percentage of time in deep sleep and REM. In conclusion, lemon verbena extract purified in phenylpropanoids is revealed as a natural solution to help individuals to improve their stress and sleep quality.

Antioxidant and reduced skin-ageing effects of a polyphenol-enriched dietary supplement in response to air pollution: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Air pollution exposure is one of the major threats to skin health and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure to air pollutants, especially in urban areas, strategies to protect the skin are needed. Plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants and a dietary approach based on these compounds could provide an efficient protection measure. OBJECTIVE: Here we investigated the efficacy of a commercially available polyphenol-enriched dietary supplement (Zeropollution®) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian subjects exposed to air pollution. Zeropollution is composed of four standardized herbal extracts: Olea europaea leaf, Lippia citriodora, Rosmarinus officinalis, and Sophora japonica. DESIGN: A double-blind randomized, parallel group study was carried out on 100 outdoor workers living in a polluted urban European area (Milan) to assess the efficacy of the dietary supplement. The total antioxidant capacity on saliva (FRAP), the oxidative damage on skin (lipoperoxides content), skin moisturization (corneometer), transepidermal water loss (tewameter), skin radiance and colour (spectrophotometer), skin elasticity (cutometer), skin sebum content (sebumeter), and the skin roughness (image analysis) were measured. RESULTS: Both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical-monitored parameters, in both Caucasian and Asian individuals. Some of the positive effects such as decreased wrinkle depth, increased elasticity and firmness, improved skin moisturization and transepidermal water loss, and reduced dark spots pigmentation were statistically significant as early as 2 weeks of product consumption. CONCLUSIONS: The results of the study indicate reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area. Therefore, the oral intake of this four-plant based supplement could be considered a complementary nutrition strategy to avoid the negative effects of environmental pollution exposure.

Correction: Marhuenda, J., et al. A Randomized, Double-Blind, Placebo Controlled Trial to Determine the Effectiveness a Polyphenolic Extract (Hibiscus sabdariffa and Lippia citriodora) in the Reduction of Body Fat Mass in Healthy Subjects. Foods 2020, 9(1), 55.

The authors wish to make the following correction to this paper [...].

A Randomized, Double-Blind, Placebo Controlled Trial to Determine the Effectiveness a Polyphenolic Extract (Hibiscus sabdariffa and Lippia citriodora) in the Reduction of Body Fat Mass in Healthy Subjects.

: The location and quantity of body fat determine the health risks, limiting people with obesity. Recently, polyphenols have attracted the attention of the scientific community because of their potential use for the reduction of obesity. A proprietary formula comprised of a blend of Lippia citriodora and Hibiscus sabdariffa has been recognized for its high content of polyphenols, powerful antioxidant molecules that may prevent weight gain and could be helpful for the treatment of obesity, as proven previously by in vivo models. The aim of the present study is to determine if the supplementation with Lippia citriodora and Hibiscus sabdariffa is useful for the treatment of obesity and/or weight control in subjects without a controlled diet. The intake of the extract for 84 days reduced body weight, the body mass index, and the fat mass measured with both bioimpedance and densitometry. This decrease in fat mass was observed to a greater extent, being significant, in the fat mass of the trunk (chest and torso).

Differential effects of a combination of Hibiscus sabdariffa and Lippia citriodora polyphenols in overweight/obese subjects: A randomized controlled trial.

Plant-polyphenols have shown the capacity to ameliorate obesity-induced metabolic disturbances, both in cell and animal models, where most therapeutic approaches have failed. On the basis of previous research, a dietary supplement containing 500 mg of a combination of polyphenolic extracts from Lippia citriodora L. and Hibiscus sabdariffa L. (LC-HS), in the context of an equilibrated isocaloric diet, was evaluated in a double blind, placebo-controlled and randomized trial in 56 obese/overweight subjects for two months. Compared to controls, the consumption of the LC-HS polyphenols showed significant improvements in body weight, abdominal circumference of overweight subjects (-6.79 ± 0.80 cm in overweight LC-HS group vs -1.85 ± 0.83 cm in controls, p < 0.001) and body fat % (-1.33 ± 0.15% in overweight LC-HS group vs -0.66 ± 0.17% in controls, p < 0.05). Heart rate and systolic blood pressure also presented significant improvements in overweight LC-HS participants. However, changes were more modest in obese subjects. Further, LC-HS extract significantly reduced lipid content and increased AMPK activity in a hypertrophied adipocyte cell model. Therefore, consumption of 500 mg/day of LC-HS extracts enriched in polyphenols for two months in the context of an isocaloric diet by overweight subjects decreased symptoms associated to obesity-related diseases. Modulation of fat metabolism in adipose tissue, probably mediated by AMPK activation, is proposed as a molecular target to be explored in future research.

Metabolaid® Combination of Lemon Verbena and Hibiscus Flower Extract Prevents High-Fat Diet-Induced Obesity through AMP-Activated Protein Kinase Activation.

Lemon verbena (Lippia citriodora) has been used as a food spice, cosmetic, and in traditional medicine formulations to treat asthma and diabetes in South America and Southern Europe. Hibiscus flower (Hibiscus sabdariffa L.) is used in traditional Chinese medicine in the form of a tea to treat hypertension and inflammation. In the present study, we examined the synergistic effects of a formula of Metabolaid® (MetA), a combination of lemon verbena and hibiscus-flower extracts, on obesity and its complications in high-fat-diet (HFD)-induced obese mice. The results showed that MetA decreased body weight, white adipose tissue (WAT), and liver weight. Additionally, serum and hepatic lipid profiles, glucose levels, glucose tolerance, and cold-induced thermogenesis were significantly improved. Appetite-regulating hormones adiponectin and leptin were significantly increased and decreased, respectively, while the inflammatory-related factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated by MetA. Adipogenesis-activating gene expression was decreased, while increased thermogenesis-inducing genes were upregulated in the WAT, correlating with increased phosphorylation of AMPK and fatty-acid oxidation in the liver. Taken together, these results suggest that MetA decreased obesity and its complications in HFD mice. Therefore, this formula may be a candidate for the prevention and treatment of obesity and its complications.

Correction: Hibiscus and lemon verbena polyphenols modulate appetite-related biomarkers in overweight subjects: a randomized controlled trial.

Correction for 'Hibiscus and lemon verbena polyphenols modulate appetite-related biomarkers in overweight subjects: a randomized controlled trial' by Marina Boix-Castejón et al., Food Funct., 2018, 9, 3173-3184.

Hibiscus and lemon verbena polyphenols modulate appetite-related biomarkers in overweight subjects: a randomized controlled trial.

TRIAL DESIGN: Plant-derived polyphenols have shown potential to alleviate obesity-related pathologies by a multi-targeted mechanism in animal models and human intervention studies. A dietary supplement based on a combination of Lippia citriodora (LC) and Hibiscus sabdariffa (HS) polyphenolic extracts was assayed in a double blind and placebo-controlled intervention study with 54 overweight subjects. METHODS: Blood pressure, body weight, height, triceps, biceps and abdominal skinfold thickness, and arm and abdominal circumferences were taken at the baseline, 30 and 60 days of the intervention period. The validated Visual Analogue Scale used to record hunger and satiety-related sensations was passed at the beginning and at 15, 30, 45 and 60 days of the intervention. Subjective health status was assessed through the validated SF-36 questionnaire at the beginning and end of the study. Finally, plasma from fasting blood samples was obtained at the beginning, 30 and 60 days of the study. RESULTS: The results showed an improvement of anthropometric measurements, decreased blood pressure and heart rate and a more positive perception in the overall health status. We also observed that plant polyphenols increased anorexigenic hormones (glucagon-like peptide-1) and decreased orexigenic hormones (ghrelin). CONCLUSIONS: Based on previous evidence we postulate that AMP-activated protein kinase may have a role in such effects through its capability to modulate energy homeostasis, total daily energy expenditure and lipid management. Although further research may be required, we propose that this polyphenolic combination may be used for weight management by increasing long-term weight loss maintenance through the modulation of appetite biomarkers. This may help to avoid the undesired weight regain typical of calorie restriction diets.

Resveratrol therapeutics combines both antimicrobial and immunomodulatory properties against respiratory infection by nontypeable Haemophilus influenzae.

The respiratory pathogen nontypeable Haemophilus influenzae (NTHi) is an important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) that requires efficient treatments. A previous screening for host genes differentially expressed upon NTHi infection identified sirtuin-1, which encodes a NAD-dependent deacetylase protective against emphysema and is activated by resveratrol. This polyphenol concomitantly reduces NTHi viability, therefore highlighting its therapeutic potential against NTHi infection at the COPD airway. In this study, resveratrol antimicrobial effect on NTHi was shown to be bacteriostatic and did not induce resistance development in vitro. Analysis of modulatory properties on the NTHi-host airway epithelial interplay showed that resveratrol modulates bacterial invasion but not subcellular location, reduces inflammation without targeting phosphodiesterase 4B gene expression, and dampens ß defensin-2 gene expression in infected cells. Moreover, resveratrol therapeutics against NTHi was evaluated in vivo on mouse respiratory and zebrafish septicemia infection model systems, showing to decrease NTHi viability in a dose-dependent manner and reduce airway inflammation upon infection, and to have a significant bacterial clearing effect without signs of host toxicity, respectively. This study presents resveratrol as a therapeutic of particular translational significance due to the attractiveness of targeting both infection and overactive inflammation at the COPD airway.

Skin photoprotective and antiageing effects of a combination of rosemary (Rosmarinus officinalis) and grapefruit (Citrus paradisi) polyphenols.

BACKGROUND: Plant polyphenols have been found to be effective in preventing ultraviolet radiation (UVR)-induced skin alterations. A dietary approach based of these compounds could be a safe and effective method to provide a continuous adjunctive photoprotection measure. In a previous study, a combination of rosemary (Rosmarinus officinalis) and grapefruit (Citrus paradisi) extracts has exhibited potential photoprotective effects both in skin cell model and in a human pilot trial. OBJECTIVE: We investigated the efficacy of a combination of rosemary (R. officinalis) and grapefruit (C. paradisi) in decreasing the individual susceptibility to UVR exposure (redness and lipoperoxides) and in improving skin wrinkledness and elasticity. DESIGN: A randomised, parallel group study was carried out on 90 subjects. Furthermore, a pilot, randomised, crossover study was carried out on five subjects. Female subjects having skin phototype from I to III and showing mild to moderate chrono- or photoageing clinical signs were enrolled in both studies. Skin redness (a* value of CIELab colour space) after UVB exposure to 1 minimal erythemal dose (MED) was assessed in the pilot study, while MED, lipoperoxides (malondialdehyde) skin content, wrinkle depth (image analysis), and skin elasticity (suction and elongation method) were measured in the main study. RESULTS: Treated subjects showed a decrease of the UVB- and UVA-induced skin alterations (decreased skin redness and lipoperoxides) and an improvement of skin wrinkledness and elasticity. No differences were found between the 100 and 250 mg extracts doses, indicating a plateau effect starting from 100 mg extracts dose. Some of the positive effects were noted as short as 2 weeks of product consumption. CONCLUSIONS: The long-term oral intake of Nutroxsun™ can be considered to be a complementary nutrition strategy to avoid the negative effects of sun exposure. The putative mechanism for these effects is most likely to take place through the inhibition of UVR-induced reactive oxygen species and the concomitant inflammatory markers (lipoperoxides and cytokines) together with their direct action on intracellular signalling pathways.

A randomized, double-blinded, placebo-controlled study of the effect of a combination of lemon verbena extract and fish oil omega-3 fatty acid on joint management.

OBJECTIVES: The aim of this study was to test the efficacy of an antioxidant/anti-inflammatory supplement containing standardized lemon verbena (Aloysia triphylla, Lippia citriodora) extract and fish oil omega-3 fatty acid in a human pilot trial as an alternative treatment for joint management. METHODS AND DESIGN: First, antioxidant activity of the supplement was determined through an oxygen radical absorbance capacity (ORAC) assay. In a randomized, double-blinded placebo-controlled trial, 45 subjects with pain discomfort received the nutritional supplement or placebo for 9 weeks. Western Ontario MacMaster (WOMAC) and Lequesne's questionnaires, which are disease-specific measurements validated to measure joint dysfunction and pain, were administered and evaluated once per week in the placebo and intervention groups. OUTCOME MEASURES: Pain and stiffness symptoms, and joint function were determined once per week through recording their respective WOMAC and Lequesne's scores in the placebo and intervention groups. Statistically significant differences were determined at every measurement point between the two groups. RESULTS: Lemon verbena extract showed strong antioxidant properties as measured by the ORAC assay. The nutritional supplement containing standardized lemon verbena extract (14% verbascoside, w/w) and fish oil omega-3 fatty acid reduced symptoms of pain and stiffness significantly, and improved physical function as shown by WOMAC and Lequesne's scores after 9 weeks of treatment. WOMAC and Lequesne's total scores decreased 53% and 78%, respectively, at the end of the study compared to initial conditions. Onset of the effect was observed at the third and fourth weeks, when statistically significant differences were detected, compared to placebo. CONCLUSIONS: This pilot study reveals that supplementation with lemon verbena combined with omega-3 fatty acids may be considered for further investigation as a complementary and alternative treatment for improving joint status in subjects with joint discomfort.

Differential effects of oleuropein, a biophenol from Olea europaea, on anionic and zwiterionic phospholipid model membranes.

Oleuropein (Ole) is the major phenolic constituent of the olive leaf (Olea europaea) and it is also present in olive oil and fruit. In the last years several compounds from olive tree, oleuropein among them, have shown a variety of biological activities such as antimicrobial or antioxidant. A phospholipid model membrane system was used to study whether the Ole biological effects could be membrane related. Ole showed a significant partition level in phospholipid membranes, i.e. 80%, at lipid-saturating conditions. Moreover, fluorescence quenching experiments indicated a shallow location for Ole in membranes. Ole promoted weak effects on zwiterionic phospholipids such as phosphatidylcholine or phosphatidylethanolamine. In contrast, differential scanning microcalorimetry, light scattering and fluorescence anisotropy pH titration studies revealed strong effects on anionic phospholipids such as phosphatidylglycerol at physiological pH and salt conditions. These effects consisted on perturbations at the phospholipid membrane surface, which might involve specific molecular interactions between Ole and the negatively charged phosphate group and therefore modify the phospholipid/water interface properties. It is proposed that Ole induces lipid structures similar to the gel-fluid intermediate phase (IP) described for PG membranes, in a similar way than low ionic strength does. These effects on phosphatidylglycerol may account for the antimicrobial activity of Ole.

The olive leaf extract exhibits antiviral activity against viral haemorrhagic septicaemia rhabdovirus (VHSV).

A commercial plant extract derived from olive tree leaf (Olea europaea) (LExt) and its major compound, oleuropein (Ole), inhibited the in vitro infectivity of the viral haemorrhagic septicaemia virus (VHSV), a salmonid rhabdovirus. Incubation of virus with LExt or Ole before infection reduced the viral infectivity to 10 and 30%, respectively. Furthermore, LExt drastically decreased VHSV titers and viral protein accumulation (virucidal effect) in a dose dependent manner when added to cell monolayers 36 h post-infection. On the other hand, both the LExt and Ole were able to inhibit cell-to-cell membrane fusion induced by VHSV in uninfected cells, suggesting interactions with viral envelope. Therefore, we propose that O. europaea could be used as a potential source of promising natural antivirals, which have demonstrated to lack impact on health and environment. In addition, Ole could be used to design other related antiviral agents.

The relationship between the antioxidant and the antibacterial properties of galloylated catechins and the structure of phospholipid model membranes.

The effects of four catechins, (+)-catechin (C), (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), on the physical properties of phospholipid model membranes and the correlation to their antioxidant and antibacterial capacities have been studied by using differential scanning calorimetry (DSC), fluorescence spectroscopy, infrared spectroscopy (IR), AAPH-induced oxidation, and leakage experiments. DSC data revealed that galloylated catechins, especially ECG, affected the physical properties of both the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers dramatically. Galloylated catechins showed higher phospholipid/water partition coefficients than their homologues and were immersed in the phospholipid palisade intercalating within the hydrocarbon chains, ECG being at the deepest position. In contrast, nongalloylated catechins presented a shallow location close to the phospholipid/water interface. ECG also exhibited the highest antioxidant capacity against lipid peroxidation, which correlated with its strong effect on DPH fluorescence anisotropy (as observed by the increase of the lipid order of fluid PC bilayers) and with the presence of highly cooperative transitions as seen by DSC. We propose that the high antioxidant capacity of some galloylated catechins such as ECG could be partially due to the formation of membrane structures showing resistance to detergent solubilization and in which the phospholipids have tightly packed acyl chains and highly hydrated phosphate groups. Significantly, PE was found to be essential to the promotion of carboxyfluorescein leakage from bacterial model membranes by galloylated catechins, indicating that their bactericidal activity, at least at the membrane level, could be due to the specific effect of these catechins on PE.