Effects of Moringa oleifera on working memory: an experimental study with memory-impaired Wistar rats tested in radial arm maze.

OBJECTIVE: Memory impairment is a serious problem that has a significant negative impact on survival and quality of life. When used for a long time, drugs used to treat memory loss become less effective and have more side effects, making therapy more difficult. Different medicinal plants are now being highlighted because of their valuable applications and low risk of adverse effects. Moringa oleifera is one of these plants that has gained much attention due to its diverse biological functions. The study aimed to determine the effects of Moringa oleifera on working memory in memory-impaired Wistar rats. RESULTS: For this experimental study, 30 male Wistar rats having 150-250 g bodyweight were divided equally into three groups: Group-I/normal memory group (treated with oral normal saline 5 ml/kg body weight), Group-II/memory-impaired group (induced by intraperitoneal ketamine 15 mg/kg body weight), and Group-III/experimental group (treated with oral Moringa oleifera 200 mg/kg bodyweight and intraperitoneal ketamine 15 mg/kg body weight). The experimental group showed significantly fewer working memory errors than the memory-impaired group. The experimental group also provides the lowest variability of WMEs among groups. Thus, the study concludes that M. oleifera can prevent ketamine-induced memory impairment in Wistar rats.

Is there tea complemented with the appealing flavor of microplastics? A pioneering study on plastic pollution in commercially available tea bags in Bangladesh.

Microplastic pollution is a global concern, mainly due to its adverse effects on organisms and ecosystems. However, our knowledge of its impact on humans, in particular, is still very limited. Thus, while we have not gathered definitive information on their consequences, studies that aim to identify the MP's sources constitute subsidies to better understand the various exposure pathways to these pollutants. Thus, we investigated the possible presence of MP-like particles in teabag samples (of different brands) obtained in Dhaka, Bangladesh. Surprisingly, all analyzed samples (five brands) were contaminated with MPs. Fragments and fibers were identified in a higher percentage, and a wide variety of colors was identified, with a predominance of brown, blue, and red colors. Scanning electron microscope images of teabags exhibited net-like structures of fiber particles with a smooth surface. Furthermore, we observed irregularly shaped MPs and rougher surfaces and fragments in the process of detachment from the main fiber, oxidation flakes, and fracture-like. The average size of these pollutants was between 200.6 and 220.7 µm, and the polymer types identified via Fourier-transform infrared spectroscopy (FT-IR) were polytetrafluoroethylene, high-density polyethylene, polycarbonate, nylon, polyvinyl chloride, polytetrafluoroethylene, ethylene-vinyl acetate, cellulose acetate, and acrylonitrile butadiene styrene, the last three being the most frequent in the analyzed samples. Finally, we noticed that MPs from tea bags in Dhaka could cause an average emission of 10.9 million grams of MPs/year. Although the teabags analyzed in our study are not "complemented with the appealing flavor of MPs", it is very likely that tea ingestion in Dhaka is accompanied by the concomitant ingestion of plastic particles making teabags an important route of human exposure to these micropollutants.

An evaluation of pharmacological healing potentialities of Terminalia Arjuna against several ailments on experimental rat models with an in-silico approach.

Herbal remedies have been used in many cultures for decades to treat illnesses. These medicinal plants have been found to contain various phytochemical compounds that can help to cure mild to severe illnesses. The inadequacies of conventional medicines and their unusual side effects sparked a determined search for alternative natural therapeutic agents. Another reason for this hunt could be the availability and fewer side effects of natural products. T. arjuna is widely used in traditional medicine to alleviate various diseases like relieving pain, ameliorating diabetes, mitigating inflammation, and back-pedaling of depression. In this study, the ethanolic extract of T. arjuna possesses a promising effect on the animal model (p < 0.05/p < 0.01) as an antihyperglycemic, analgesic, anti-inflammatory, and antidepressant agent, but in a dose-dependent manner. The lower dose of T. arjuna was found to be capable of reversing the disturbed physiological state at a significant level (p < 0.05). However, a higher dose of T. arjuna exerts better therapeutic effects for those diseases. This animal study aims to evaluate the anti-diabetic, anti-depressant, and anti-inflammatory properties of T. arjuna compared to conventional marketed drugs. We will perform an in-silico study for active constituents of T. arjuna against their proposed targets and look for the molecular cascade on their claimed pharmacological properties. This study shows that different doses of T. arjuna bark extracts give similar therapeutic responses compared with established marketed drugs in managing hyperglycemia, stress-induced depression, and inflammation. Besides, our docking study reveals that flavonoids and triterpenoid active constituents of T. arjuna play an important role in its usefulness. This study, therefore, scientifically confirmed the traditional use of this medicinal plant in the management of several diseased conditions.

Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids.

BACKGROUND: Uterine fibroids are highly prevalent, collagen-rich, mechanically stiff, fibrotic tumors for which new therapeutic options are needed. Increased extracellular matrix (ECM) stiffness activates mechanical signaling and Hippo/YAP promoting fibroid growth, but no prior studies have tested either as a therapeutic target. We tested the hypothesis that injection of a purified form of collagenase Clostridium histolyticum (CCH) that selectively digests type I and type III collagens would alter ECM stiffness, Hippo signaling, and selectively reduce fibroid cell growth. We also used two FDA-approved drugs, verteporfin and nintedanib, to elucidate the role of Hippo/YAP signaling in uterine fibroid and myometrial cells. METHODS: The clinical trial was registered (NCT02889848). Stiffness of samples was measured by rheometry. Protein expression in surgical samples was analyzed via immunofluorescence. Protein and gene expression in uterine fibroid or myometrial cell lines were measured by real time PCR and western blot, and immunofluorescence. RESULTS: Injection of CCH at high doses (0.1-0.2 mg/cm3 ) into fibroids resulted in a 46% reduction in stiffness in injected fibroids compared to controls after 60 days. Levels of the cell proliferation marker proliferative cell nuclear antigen (PCNA) were decreased in fibroids 60 days after injection at high doses of CCH. Key Hippo signaling factors, specifically the transcriptionally inactive phosphorylated YAP (p-YAP), was increased at high CCH doses, supporting the role of YAP in fibroid growth. Furthermore, inhibition of YAP via verteporfin (YAP inhibitor) decreased cell proliferation, gene and protein expression of key factors promoting fibrosis and mechanotransduction in fibroid cells. Additionally, the anti-fibrotic drug, nintedanib, inhibited YAP and showed anti-fibrotic effects. CONCLUSIONS: This is the first report that in vivo injection of collagenase into uterine fibroids led to a reduction in Hippo/YAP signaling and crucial genes and pathways involved in fibroid growth. These results indicate that targeting ECM stiffness and Hippo signaling might be an effective strategy for uterine fibroids.

Traditional Herbal Medicines, Bioactive Metabolites, and Plant Products Against COVID-19: Update on Clinical Trials and Mechanism of Actions.

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.

Effects of metabolic state on the regulation of melanocortin circuits.

Dysfunction in neurophysiological systems that regulate food intake and metabolism are at least partly responsible for obesity and related comorbidities. An important component of this process is the hypothalamic melanocortin system, where an imbalance can result in severe obesity and deficits in glucose metabolism. Exercise offers many health benefits related to cardiovascular improvements, hunger control, and blood glucose homeostasis. However, the molecular mechanism underlying the exercise-induced improvements to the melanocortin system remain undefined. Here, we review the role of the melanocortin system to sense hormonal, nutrient, and neuronal signals of energy status. This information is then relayed onto secondary neurons in order to regulate physiological parameters, which promote proper energy and glucose balance. We also provide an overview on the effects of physical exercise to induce biophysical changes in the melanocortin circuit which may regulate food intake, glucose metabolism and improve overall metabolic health.

Therapeutic and preventive properties of honey and its bioactive compounds in cancer: an evidence-based review.

Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.

Direct and indirect effects of liraglutide on hypothalamic POMC and NPY/AgRP neurons - Implications for energy balance and glucose control.

OBJECTIVE: The long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, stimulates insulin secretion and efficiently suppresses food intake to reduce body weight. As such, liraglutide is growing in popularity in the treatment of diabetes and chronic weight management. Within the brain, liraglutide has been shown to alter the activity of hypothalamic proopiomelanocortin (POMC) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. Moreover, the acute activities of POMC and NPY neurons have been directly linked to feeding behavior, body weight, and glucose metabolism. Despite the increased usage of liraglutide and other GLP-1 analogues as diabetic and obesity interventions, the cellular mechanisms by which liraglutide alters the activity of metabolically relevant neuronal populations are poorly understood. METHODS: In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify POMC and NPY neurons for patch-clamp electrophysiology experiments. RESULTS: We found that liraglutide directly activated arcuate POMC neurons via TrpC5 channels, sharing a similar mechanistic pathway to the adipose-derived peptide leptin. Liraglutide also indirectly increases excitatory tone to POMC neurons. In contrast, liraglutide inhibited NPY/AgRP neurons through post-synaptic GABAA receptors and enhanced activity of pre-synaptic GABAergic neurons, which required both TrpC5 subunits and K-ATP channels. In support of an additive role of leptin and liraglutide in suppressing food intake, leptin potentiated the acute effects of liraglutide to activate POMC neurons. TrpC5 subunits in POMC neurons were also required for the intact pharmacological effects of liraglutide on food intake and body weight. Thus, the current study adds to recent work from our group and others, which highlight potential mechanisms to amplify the effects of GLP-1 agonists in vivo. Moreover, these data highlight multiple sites of action (both pre- and post-synaptic) for GLP-1 agonists on this circuit. CONCLUSIONS: Taken together, our results identify critical molecular mechanisms linking GLP-1 analogues in arcuate POMC and NPY/AgRP neurons with metabolism.

PgMYB2, a MeJA-Responsive Transcription Factor, Positively Regulates the Dammarenediol Synthase Gene Expression in Panax Ginseng.

The MYB transcription factor family members have been reported to play different roles in plant growth regulation, defense response, and secondary metabolism. However, MYB gene expression has not been reported in Panax ginseng. In this study, we isolated a gene from ginseng adventitious root, PgMYB2, which encodes an R2R3-MYB protein. Subcellular localization revealed that PgMYB2 protein was exclusively detected in the nucleus of Allium cepa epidermis. The highest expression level of PgMYB2 was found in ginseng root and it was significantly induced by plant hormones methyl jasmonate (MeJA). Furthermore, the binding interaction between PgMYB2 protein and the promoter of dammarenediol synthase (DDS) was found in the yeast strain Y1H Gold. Moreover, the electrophoretic mobility shift assay (EMSA) identified the binding site of the interaction and the results of transiently overexpressing PgMYB2 in plants also illustrated that it may positively regulate the expression of PgDDS. Based on the key role of PgDDS gene in ginsenoside synthesis, it is reasonable to believe that this report will be helpful for the future studies on the MYB family in P. ginseng and ultimately improving the ginsenoside production through genetic and metabolic engineering.

Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise.

OBJECTIVE: Hypothalamic Pro-opiomelanocortin (POMC) and Neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) neurons are critical nodes of a circuit within the brain that sense key metabolic cues as well as regulate metabolism. Importantly, these neurons retain an innate ability to rapidly reorganize synaptic inputs and electrophysiological properties in response to metabolic state. While the cellular properties of these neurons have been investigated in the context of obesity, much less is known about the effects of exercise training. METHODS: In order to further investigate this issue, we utilized neuron-specific transgenic mouse models to identify POMC and NPY/AgRP neurons for patch-clamp electrophysiology experiments. RESULTS: Using whole-cell patch-clamp electrophysiology, we found exercise depolarized and increased firing rate of arcuate POMC neurons. The increased excitability of POMC neurons was concomitant with increased excitatory inputs to these neurons. In agreement with recent work suggesting leptin plays an important role in the synaptic (re)organization of POMC neurons, POMC neurons which express leptin receptors were more sensitive to exercise-induced changes in biophysical properties. Opposite to effects observed in POMC neurons, NPY neurons were shunted toward inhibition following exercise. CONCLUSIONS: Together, these data support a rapid reorganization of synaptic inputs and biophysical properties in response to exercise, which may facilitate adaptations to altered energy balance and glucose metabolism.

Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells.

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability.

The development of chemo-sensitizers is urgently needed to overcome 5-fluorouracil (5-FU) therapeutic resistance and adverse toxicity in colorectal cancer. This work aims to evaluate the synergic effects of 5-FU and Manuka honey (MH), a rich source of bioactive compounds, in enhancing the anticancer effects of this drug on human colon cancer HCT-116 and LoVo cells. Compared to 5-FU alone, MH synergistically enhanced the chemotherapeutic effects of 5-FU, by reducing cell proliferation through the suppression of EGFR, HER2, p-Akt and p-mTOR expression, and promoting apoptosis by the modulation pro-apoptotic (p53, Bax, Cyto c, FasL caspase-3, -8, -9 and cleave-PARP) and anti-apoptotic (Bcl-2) markers. The activations of p-p38MAPK and p-Erk1/2 pathways and ROS production were also involved in this process. Downregulation of transcription factor (NF-κB and Nrf2) and antioxidant enzyme activity (SOD, catalase, glutathione peroxidase and glutathione reductase) and expression (SOD, catalase and HO-1) were more evident after the combined treatment, leading to more cell death by oxidative stress. Moreover, additive effects were also observed by increasing lipid and protein oxidation and arresting cell cycle. All the parameters of mitochondrial respiration and glycolysis function decreased and both cells entered the quiescent stage after the combined treatments. MH also influenced the anti-metastasis effects of 5-FU by decreasing migration ability, suppressing the expression of MMP-2, MMP-9 and increasing N-cadherin and E-cadherin. In conclusion, MH could be a useful preventive or adjuvant agent in the treatment of colorectal cancer with 5-FU.

Characterization of phenolic extracts from Brava extra virgin olive oils and their cytotoxic effects on MCF-7 breast cancer cells.

The aim of the present work was to evaluate the phenolic profile of the 'Brava' extra virgin olive oil and assess its potential as a "natural adjuvant" in combination with chemotherapy treatment. The total phenol content of the phenolic extracts was 764 mg gallic acid equivalents/kg and the total antioxidant capacity was 2309, 1881 and 2088 µM trolox equivalents/kg determined by Diphenyl-1-picrylhydrazyl free radical method, Ferric Reducing Antioxidant Power and Trolox Equivalent Antioxidant Capacity assay, respectively. Secoiridoids comprised 83% of the total phenolic compounds. The main secoiridoid from oleuropein was the main isomer of oleuropein aglycone (74 mg/kg). The main secoiridoid from ligstroside was the main isomer of ligstroside aglycone (214 mg/kg). These phenolic extracts showed a significant decrease in cell viability on MCF-7 breast cancer cells in a dose and time dependent manner. 48 h-treatments with different concentrations of the extracts induced intracellular ROS generation and cell death.

Guava (Psidium guajava L. cv. Red Suprema) Crude Extract Protect Human Dermal Fibroblasts against Cytotoxic Damage Mediated by Oxidative Stress.

We analyzed guava fruits (Psidium guajava L. cv. Red Suprema) from Cuba to determine their chemical composition, total antioxidant capacity, as well as their protective effect against oxidative damage using an in vitro model of human dermal fibroblasts. The guava fruit is a natural source of bioactive compounds, such as polyphenols, vitamin C, folates and beta carotenes with proven health benefits. Human dermal fibroblasts were pre-incubated with different concentrations of guava crude extract and then subjected to oxidative stress using the AAPH stressor. The number of apoptotic and dead cells, as well as the markers of oxidative damage such as lipid and protein oxidation significantly decreased when cells were pre-incubated with guava crude extract and then exposed to the stressor. The activity of antioxidant enzymes also improved when cells were pre-incubated with guava crude extract in comparison to cells subjected to stress without prior pre-incubation with the guava extract. The results obtained in this study highlight the health benefits of guava regarding oxidative stress, proving it to be an important source of bioactive compounds associated with important biological properties.

Strawberry extracts efficiently counteract inflammatory stress induced by the endotoxin lipopolysaccharide in Human Dermal Fibroblast.

A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to counteract this inflammatory state. The aim of the present work was to evaluate the effects of strawberry extracts on inflammation evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring reactive oxygen species production, apoptosis rate, antioxidant enzymes activity, mitochondria functionality and also investigating the molecular pathway involved in inflammatory and antioxidant response. The results demonstrated that strawberry pre-treatment reduced intracellular reactive oxygen species levels, apoptotic rate, improved antioxidant defences and mitochondria functionality in lipopolysaccharide -treated cells. Strawberry exerted these protective activities through the inhibition of the NF-kB signalling pathway and the stimulation of the Nrf2 pathway, with a mechanism AMPK-dependent. These results confirm the health benefits of strawberry in the prevention of inflammation and oxidative stress condition in lipopolysaccharide-treated cells.

The protective effect of acerola (Malpighia emarginata) against oxidative damage in human dermal fibroblasts through the improvement of antioxidant enzyme activity and mitochondrial functionality.

Acerola fruits (Malpighia emarginata DC.) from the central region of Cuba were analyzed to determine their chemical composition and protective capacity against oxidative damage using an in vitro human dermal fibroblast (HDFa) model. The chemical composition analyses showed a high content of vitamin C, total polyphenols, ß-carotene and folates in the acerola fruit. From the HPLC-DAD/ESI-MSn analyses, two anthocyanins (cyanidin 3-O-rhamnoside and pelargonidin 3-O-rhamnoside), three hydroxycinnamoyl derivatives (caffeoyl hexoside, dihydrocaffeoylquinic acid and coumaroyl hexoside) and fifteen flavonols (mostly glycosylated forms of quercetin and kaempferol) were detected. HDFa were pre-incubated with an acerola crude extract (ACExt) and subsequently subjected to oxidative stress induced by AAPH. Apoptosis, intracellular ROS and the biomarkers of lipid and protein oxidation significantly increased after inducing stress, while the activities of the antioxidant enzyme catalase and superoxide dismutase and mitochondrial functionality were markedly affected. However, ACExt was able to protect against oxidative damage through decreasing apoptosis, intracellular ROS levels and lipid and protein damage, besides improving antioxidant enzyme activities and mitochondrial functionality. The obtained results support acerola fruits as relevant sources of functional compounds with promising effects on human health.

The healthy effects of strawberry bioactive compounds on molecular pathways related to chronic diseases.

It is generally accepted that a fruit and vegetable-enriched diet is favorable for human health. The consumption of strawberries, in particular, has been related to the maintenance of well-being and the prevention of several chronic diseases, owing to the high contents of antioxidants and phytochemicals present in the fruit. Several biological effects have been explained through the total antioxidant capacity exerted by these bioactive compounds, but recently more intricate mechanisms have begun to be examined. In this context, it has been reported that strawberry phenolics are able to exert anti-inflammatory, anticarcinogenic, antiproliferative, and antiatherosclerotic activities, acting on specific molecular pathways related to antioxidant defenses, metabolism, survival, and proliferation. The overall aim of this work is to discuss and update the cellular and molecular mechanisms recently proposed to clarify the effects of strawberry phenolics on human health, with particular attention to the most common chronic diseases, such as metabolic syndrome, cardiovascular disease, and cancer.

Strawberry-Based Cosmetic Formulations Protect Human Dermal Fibroblasts against UVA-Induced Damage.

Extreme exposure of skin to Ultraviolet A (UVA)-radiation may induce a dysregulated production of reactive oxygen species (ROS) which can interact with cellular biomolecules leading to oxidative stress, inflammation, DNA damage, and alteration of cellular molecular pathways, responsible for skin photoaging, hyperplasia, erythema, and cancer. For these reasons, the use of dietary natural bioactive compounds with remarkable antioxidant activity could be a strategic tool to counteract these UVA-radiation-caused deleterious effects. Thus, the purpose of the present work was to test the efficacy of strawberry (50 µg/mL)-based formulations supplemented with Coenzyme Q10 (100 µg/mL) and sun protection factor 10 in human dermal fibroblasts irradiated with UVA-radiation. The apoptosis rate, the amount of intracellular reactive oxygen species (ROS) production, the expression of proteins involved in antioxidant and inflammatory response, and mitochondrial functionality were evaluated. The results showed that the synergic topical use of strawberry and Coenzyme Q10 provided a significant (p < 0.05) photoprotective effect, reducing cell death and ROS, increasing antioxidant defense, lowering inflammatory markers, and improving mitochondrial functionality. The obtained results suggest the use of strawberry-based formulations as an innovative, natural, and useful tool for the prevention of UVA exposure-induced skin diseases in order to decrease or substitute the amount of synthetic sunscreen agents.

Lipid Accumulation in HepG2 Cells Is Attenuated by Strawberry Extract through AMPK Activation.

Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2). For such purpose, the lipid profile and the expression of proteins metabolically related to AMPK were determined on cells lysates. The results demonstrated that strawberry methanolic extract decreased total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides levels (up to 0.50-, 0.30-, and 0.40-fold, respectively) while it stimulated the p-AMPK/AMPK expression (up to 3.06-fold), compared to the control. AMPK stimulation led to the phosphorylation and consequent inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively. Strawberry treatment also entailed a 4.34-, 2.37-, and 2.47-fold overexpression of LDL receptor, sirtuin 1 (Sirt1), and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), respectively, compared to control. The observed results were counteracted by treatment with compound C, an AMPK pharmacological inhibitor, confirming that multiple effects of strawberries on lipid metabolism are mediated by the activation of this protein.

Strawberry (cv. Romina) Methanolic Extract and Anthocyanin-Enriched Fraction Improve Lipid Profile and Antioxidant Status in HepG2 Cells.

Dyslipidemia and oxidation of low density lipoproteins (LDL) are recognized as critical factors in the development of atherosclerosis. Healthy dietary patterns, with abundant fruit and vegetable consumption, may prevent the onset of these risk factors due to the presence of phytochemical compounds. Strawberries are known for their high content of polyphenols; among them, flavonoids are the major constituents, and it is presumed that they are responsible for the biological activity of the fruit. Nevertheless, there are only a few studies that actually evaluate the effects of different fractions isolated from strawberries. In order to assess the effects of two different strawberry extracts (whole methanolic extract/anthocyanin-enriched fraction) on the lipid profile and antioxidant status in human hepatocellular carcinoma (HepG2) cells, the triglycerides and LDL-cholesterol content, lipid peroxidation, intracellular reactive oxygen species (ROS) content and antioxidant enzymes' activity on cell lysates were determined. Results demonstrated that both strawberry extracts not only improved the lipid metabolism by decreasing triglycerides and LDL-cholesterol contents, but also improved the redox state of HepG2 cells by modulating thiobarbituric acid-reactive substances production, antioxidant enzyme activity and ROS generation. The observed effects were more pronounced for the anthocyanin-enriched fraction.