Myricetin and myricitrin indirectly and directly increases uncoupling protein-1 mRNA expression in C3H10T1/2 beige adipocytes.

In thermogenic brown and beige adipocytes, the proton gradient formed by energy derived from nutrients such as lipids and carbohydrates is consumed by uncoupling protein-1 (UCP-1), resulting in thermogenesis without ATP production in the mitochondria. Accordingly, increased UCP-1 expression represents a crucial aspect of dietary management for individuals with overweight and obesity. Myricetin and its glycoside, myricitrin, are food-derived flavonoids that possess various beneficial effects. This is the first study to examine the effects of myricetin and myricitrin on the inflammation-inhibited expression of Ucp-1 using a modified cell-based assay with conditioned medium (CM). The CM derived from lipopolysaccharide (LPS)-activated RAW264.7 macrophages was observed to inhibit the Ucp-1 expression induced by adrenergic stimulation in 10T1/2 adipocytes. Conversely, the CM derived from activated macrophages treated with myricetin or myricitrin reversed this inhibition of Ucp-1 expression. Subsequently, the direct effects of both the compounds on basal and adrenaline-induced expression of Ucp-1 were investigated. In contrast to a previous report, myricetin and myricitrin did not increase the basal Ucp-1 mRNA expression in 10T1/2 adipocytes when treated during the differentiation-promoting period. However, we have found for the first time that both compounds enhanced the adrenergic sensitivity of 10T1/2 adipocytes when treated during the differentiation-inducing period. These results indicate that myricetin and myricitrin have indirect effects on inflammation-induced suppression and direct effects on adrenergic sensitivity, suggesting a novel mechanism that both compounds increase Ucp-1 expression in vivo by both indirect and direct effects, rather than by affecting basal expression.

Treatment with a combination of myricitrin and exercise alleviates myocardial infarction in rats via suppressing Nrf2/HO-1 antioxidant pathway.

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

Myricitrin promotes osteogenesis and prevents ovariectomy bone mass loss via the PI3K/AKT signalling pathway.

This study aimed to explore the effect of myricitrin on osteoblast differentiation in mice immortalised bone marrow mesenchymal stem cells (imBMSCs). Additionally, ovariectomy (OVX) mice were employed to examine the effect of myricitrin on bone trabecular loss in vivo. The effect of myricitrin on the proliferation of imBMSCs was evaluated using a cell counting kit-8 assay. Alizarin red staining, alkaline phosphatase staining were performed to elucidate osteogenesis. Furthermore, qRT-PCR and western blot determined the expression of osteo-specific genes and proteins. To screen for candidate targets, mRNA transcriptome genes were sequenced using bioinformatics analyses. Western blot and molecular docking analysis were used to examine target signalling markers. Moreover, rescue experiments were used to confirm the effect of myricitrin on the osteogenic differentiation of imBMSCs. OVX mice were also used to estimate the delay capability of myricitrin on bone trabecular loss in vivo using western blot, micro-CT, tartaric acid phosphatase (Trap) staining, haematoxylin and eosin staining, Masson staining and immunochemistry. In vitro, myricitrin significantly enhanced osteo-specific genes and protein expression and calcium deposition. Moreover, mRNA transcriptome gene sequencing and molecular docking analysis revealed that this enhancement was accompanied by an upregulation of the PI3K/AKT signalling pathway. Furthermore, copanlisib, a PI3K inhibitor, partially reversed the osteogenesis promotion induced by myricitrin. In vivo, western blot, micro-CT, hematoxylin and eosin staining, Masson staining, Trap staining and immunochemistry revealed that bone trabecular loss rate was significantly alleviated in the myricitrin low- and high-dose groups, with an increased expression of osteopontin, osteoprotegerin, p-PI3K and p-AKT compared to the OVX group. Myricitrin enhances imBMSC osteoblast differentiation and attenuate bone mass loss partly through the upregulation of the PI3K/AKT signalling pathway. Thus, myricitrin has therapeutic potential as an antiosteoporosis drug.

Kinetics of Flavonoid Degradation and Controlled Release from Functionalized Magnetic Nanoparticles.

Flavonoids are naturally occurring antioxidants that have been shown to protect cell membranes from oxidative stress and have a potential use in photodynamic cancer treatment. However, they degrade at physiological pH values, which is often neglected in drug release studies. Kinetic study of flavonoid oxidation can help to understand the mechanism of degradation and to correctly analyze flavonoid release data. Additionally, the incorporation of flavonoids into magnetic nanocarriers can be utilized to mitigate degradation and overcome their low solubility, while the release can be controlled using magnetic fields (MFs). An approach that combines alternating least squares (ALS) and multilinear regression to consider flavonoid autoxidation in release studies is presented. This approach can be used in general cases to account for the degradation of unstable drugs released from nanoparticles. The oxidation of quercetin, myricetin (MCE), and myricitrin (MCI) was studied in PBS buffer (pH = 7.4) using UV-vis spectrophotometry. ALS was used to determine the kinetic profiles and characteristic spectra, which were used to analyze UV-vis data of release from functionalized magnetic nanoparticles (MNPs). MNPs were selected for their unique magnetic properties, which can be exploited for both targeted drug delivery and control over the drug release. MNPs were prepared and characterized by X-ray diffraction, infrared spectroscopy, scanning electron microscopy, superconducting quantum interference device magnetometer, and electrophoretic mobility measurements. Autoxidation of all three flavonoids follows a two-step first-order kinetic model. MCE showed the fastest degradation, while the oxidation of MCI was the slowest. The flavonoids were successfully loaded into the prepared MNPs, and the drug release was described by the first-order and Korsmeyer-Peppas models. External MFs were utilized to control the release mechanism and the cumulative mass of the flavonoids released.

Toward the bioactive potential of myricitrin in food production: state-of-the-art green extraction and trends in biosynthesis.

Myricitrin is a member of flavonols, natural phenolic compounds extracted from plant resources. It has gained great attention for various biological activities, such as anti-inflammatory, anti-cancer, anti-diabetic, as well as cardio-/neuro-/hepatoprotective activities. These effects have been demonstrated in both in vitro and in vivo models, making myricitrin a favorable candidate for the exploitation of novel functional foods with potential protective or preventive effects against diseases. This review summarized the health benefits of myricitrin and attempted to uncover its action mechanism, expecting to provide a theoretical basis for their application. Despite enormous bioactive potential of myricitrin, low production, high cost, and environmental damage caused by extracting it from plant resources greatly constrain its practical application. Fortunately, innovative, green, and sustainable extraction techniques are emerging to extract myricitrin, which function as alternatives to conventional techniques. Additionally, biosynthesis based on synthetic biology plays an essential role in industrial-scale manufacturing, which has not been reported for myricitrin exclusively. The construction of microbial cell factories is absolutely an appealing and competitive option to produce myricitrin in large-scale manufacturing. Consequently, state-of-the-art green extraction techniques and trends in biosynthesis were reviewed and discussed to endow an innovative perspective for the large-scale production of myricitrin.

Hepatoprotective role of myricitrin isolated from Mimusops elengi Linn. leaves extract on γ-radiation-induced liver damage in rats: Phyto-biochemical investigations.

The hepatoprotective effects of methanol extract of Mimusops elengi Linn. (M. elengi L.) leaves and isolated pure myricitrin (3-, 4-, 5-, 5, 7-five hydroxyflavone-3-O-α-l-rhamnoside) (Myr) were evaluated in male rats exposed to γ-irradiation. The extraction of M. elengi L. leaves was performed using ethyl acetate (EtOAC). Seven groups of rats were used: control group, irradiated (IRR) group (6 Gy of γ-rays in a single dose), vehicle group (oral administration of 0.5% carboxymethyl cellulose for 10 days), EtOAC extract group (100 mg/kg body weight of extract, orally for 10 days), EtOAC + IRR group (administration of extract and exposure to γ-rays on Day 7), Myr group (50 mg/kg body weight Myr, orally for 10 days), and Myr + IRR group (administration of Myr and exposure to γ-rays on Day 7). High-performance liquid chromatography and 1H-nuclear magnetic resonance were used to isolate and characterize the compounds from M. elengi L. leaves. Enzyme-linked immunosorbent assay was used for biochemical analyses. Identified compounds were Myr, myricetin 3-O-galactoside, myricetin 3-O-rahmnopyranoside (1 → 6) glucopyranoside, quercetin, quercitol, gallic acid, α-,ß-amyrin, ursolic acid, and lupeol. Serum aspartate transaminase and alanine transaminase activities were significantly increased, while serum protein and albumin levels were significantly decreased after irradiation. Hepatic levels of tumor necrosis factor-α, prostaglandin 2, inducible nitric oxide synthase, interleukin-6 (IL-6), and IL-12 were increased following irradiation. Improvements were observed in most serological parameters after treatment with extract or pure Myr, with histological analyses confirming decreased liver injury in treated rats. Our study demonstrates that pure Myr has a greater hepatoprotective effect than M. elengi leaf extracts against irradiation-induced hepatic inflammation.

Validation of stability-indicating LC method, degradation study, and impact on antioxidant and antifungal activities of Eugenia uniflora leaves extract.

The aim of this study is to demonstrate the stability-indicating capacity of an analytical method for Eugenia uniflora, enhance understanding of the stability of myricitrin, and assess the effect of degradation of spray-dried extract (SDE) on antioxidant and antifungal activities. Validation of the stability-indicating method was carried out through a forced degradation study of SDE and standard myricitrin. The antioxidant and antifungal activities of SDE were evaluated both before and after degradation. The quantification method described was found to be both accurate and precise in measuring myricitrin levels in SDE from E. uniflora, with excellent selectivity that confirmed its stability-indicating capability. The forced degradation study revealed that the marker myricitrin is sensitive to hydrolysis, but generally stable under other stress conditions. By contrast, the standard myricitrin displayed greater susceptibility to degradation under forced degradation conditions. Analysis of the antioxidant activity of SDE before and after degradation showed a negative impact in this activity due to degradation, while no significant effect was observed on antifungal activity. The method described can be a valuable tool in the quality control of E. uniflora, and the findings can assist in determining the optimal conditions and storage of products derived from this species.

Modulatory effect of myricitrin against chromosome instability and cytostasis induced by bleomycin and oxaliplatin in CHO-K1 cells.

Myricitrin (MYR), a flavonol consumed in the leaves and fruits of plants of the Myrtaceae family, presents anti-proliferative, anti-inflammatory, anti-diabetic, and antioxidant properties in humans. However, there are few studies regarding the cyto-genotoxicity and the chemopreventive potential of MYR. Using the in vitro Micronucleus test, the cytostasis, mutagenicity, and modulatory effect of MYR in CHO-K1 cells were assessed. The concentrations of 39 and 78 µg/mL (p < 0.001.) of MYR decrease the cytokinesis-block proliferation index (CBPI) in the short exposure treatment (4 h), while in the extended treatment (24 h), concentrations of 4.8, 9.7, 19.5, 39 and 78 µg/mL (p < 0.001.) decreased the CBPI. MYR associated with oxaliplatin decreased CBPI at all tested concentrations in the pre-(p < 0.001) and post-treatments (p < 0.001), but there was no decrease when associated with bleomycin. As for chromosome instability, MYR did not increase the frequency of micronuclei (MNi), nucleoplasmic bridges (NPBs), or nuclear buds (NBUDs) in the 4 h exposure time, however, in the 24 h treatment, MYR increased the frequency of MNi and NPBs at concentration 19.5 µg/mL (p < 0.001). As for the modulatory effect, MYR associated with bleomycin decreased the frequency of MNi, NPBs, and NBUDs at all concentrations in the pretreatment (MNi and NPBs p < 0.001, NBUDs p < 0.05) and simultaneously (MNi, NPBs and NBUDs p < 0.001). When associated with oxaliplatin, the simultaneous treatment decreased the frequency of MNi (p < 0.001) and NBUDs (p < 0.01) at all concentrations, however, in the post-treatment, MYR increased MNi (p < 0.001) and NPBs p < 0.05) in CHO-K1 cells, when compared to oxaliplatin alone. The results demonstrated that MYR could modulate the mutagenic and cytostatic actions of bleomycin and oxaliplatin, demonstrating distinct behaviors, depending on the mechanism of action of the chemotherapeutic agent.

A Study on the Interactions of Proteinase K with Myricetin and Myricitrin by Multi-Spectroscopy and Molecular Modeling.

Myricetin (MYR) and myricitrin (MYT) are well recognized for their nutraceutical value, such as antioxidant, hypoglycemic, and hypotensive effects. In this work, fluorescence spectroscopy and molecular modeling were adopted to investigate the conformational and stability changes of proteinase K (PK) in the presence of MYR and MYT. The experimental results showed that both MYR and MYT could quench fluorescence emission via a static quenching mechanism. Further investigation demonstrated that both hydrogen bonding and van der Waals forces play significant roles in the binding of complexes, which is consistent with the conclusions of molecular modeling. Synchronous fluorescence spectroscopy, Förster resonance energy transfer, and site-tagged competition experiments were performed to prove that the binding of MYR or MYT to PK could alter its micro-environment and conformation. Molecular docking results revealed that either MYR or MYT spontaneously interacted with PK at a single binding site via hydrogen bonding and hydrophobic interactions, which is consistent with the results of spectroscopic measurements. A 30 ns molecular dynamics simulation was conducted for both PK-MYR and PK-MYT complexes. The calculation results showed that no large structural distortions or interaction changes occurred during the entire simulation time span. The average RMSD changes of PK in PK-MYR and PK-MYT were 2.06 and 2.15 Å, respectively, indicating excellent stability of both complexes. The molecular simulation results suggested that both MYR and MYT could interact with PK spontaneously, which is in agreement with spectroscopic results. This agreement between experimental and theoretical results indicates that the method herein could be feasible and worthwhile for protein-ligand complex studies.

Myricitrin ameliorates cognitive deficits in MCAO cerebral stroke rats via histone acetylation-induced alterations of brain-derived neurotrophic factor.

The present study screened the effect of Myricitrin on cognitive deficits post-cerebral ischemic stroke and the involved mechanism. The rats were submitted to middle cerebral artery occlusion (MCAO) and were treated with sodium butyrate or Myricitrin (15 and 30 mg/kg) for 28 days. The spatial memory was studied by Morris water maze (MWM). After 4 weeks, the rats were euthanized and hippocampus region was utilized for neurochemical and biochemical changes. The extent of histone acetylation was studied by ELISA. Protein levels were analyzed by Western blot analysis. The mRNA levels were analyzed by polymerase chain reaction (PCR). In silico bioinformatics docking studies were done for target confirmation of Myricitrin. The treatment of Myricitrin showed improved memory in MWM compared to rats treated with vehicle, and the effects of Myricitrin were similar to sodium butyrate-treated rats. At a dose of 30 mg/kg Myricitrin, the histone deacetylase content was decreased, the expression levels of BDNF were increased, the levels of acetylated H3 and H4 along with Syn-I in the hippocampus region were over-expressed compared to control vehicle-treated rats. However, at low dose, i.e., 15 mg/kg Myricitrin failed to show alterations in biochemical as well as neurochemical markers. Docking studies suggested the BDNF and Sun-I as potential target proteins of Myricitrin. The cognitive ameliorating effect of Myricitrin post-cerebral ischemia stroke can be attributed to increased expression of BDNF and Syn-I and modulation of histone acetylation.

Nano-based drug delivery systems used as vehicles to enhance polyphenols therapeutic effect for diabetes mellitus treatment.

Diabetes mellitus is one of the biggest health emergencies of the 21st century worldwide, characterized by deficiency in insulin secretion and/or action, leading to hyperglycemia. Despite the currently available antidiabetic therapeutic options, 4.2 million people died in 2019 due to diabetes. Thus, new effective interventions are required. Polyphenols are plant secondary metabolites and have been recognized for their vast number of biological activities, including potential antidiabetic effects. However, the poor bioavailability and high metabolization of polyphenols restrict their biological effects in vivo. Nanotechnology is a promising area of research to improve the therapeutic effect of several compounds. Therefore, this review provides an overview of the literature about the utility of nano-based drug delivery systems as vehicles of polyphenols in diabetes treatment. It was possible to conclude that, in general, nano-based drug delivery systems can potentiate the beneficial antidiabetic properties of polyphenols, when compared with the free compounds, opening a new field of research in diabetology.

Suppression of apoptosis in vascular endothelial cell, the promising way for natural medicines to treat atherosclerosis.

Atherosclerosis, a chronic multifactorial disease, is closely related to the development of cardiovascular diseases and is one of the predominant causes of death worldwide. Normal vascular endothelial cells play an important role in maintaining vascular homeostasis and inhibiting atherosclerosis by regulating vascular tension, preventing thrombosis and regulating inflammation. Currently, accumulating evidence has revealed that endothelial cell apoptosis is the first step of atherosclerosis. Excess apoptosis of endothelial cells induced by risk factors for atherosclerosis is a preliminary event in atherosclerosis development and might be a target for preventing and treating atherosclerosis. Interestingly, accumulating evidence shows that natural medicines have great potential to treat atherosclerosis by inhibiting endothelial cell apoptosis. Therefore, this paper reviewed current studies on the inhibitory effect of natural medicines on endothelial cell apoptosis and summarized the risk factors that may induce endothelial cell apoptosis, including oxidized low-density lipoprotein (ox-LDL), reactive oxygen species (ROS), angiotensin II (Ang II), tumor necrosis factor-α (TNF-α), homocysteine (Hcy) and lipopolysaccharide (LPS). We expect this review to highlight the importance of natural medicines, including extracts and monomers, in the treatment of atherosclerosis by inhibiting endothelial cell apoptosis and provide a foundation for the development of potential antiatherosclerotic drugs from natural medicines.

Apoptotic mechanisms of myricitrin isolated from Madhuca longifolia leaves in HL-60 leukemia cells.

Myricitrin, a naturally occurring flavonoid in Madhuca longifolia, possesses several medicinal properties. Even though our earlier work revealed its role against the proliferation of acute myelogenous leukemia cells (HL-60), its molecular mechanisms have not yet been revealed. The current study aims to explore the molecular mechanisms of myricitrin (isolated from an ethnomedicinal drug Madhuca longifolia) to induce apoptosis in HL-60 cells. Treatment with IC-50 dose of myricitrin (353 µM) caused cellular shrinkage and cell wall damage in HL-60 cells compared to untreated control cells. Myricitrin treatment reduced the mitochondrial membrane potential (22.95%), increased DNA fragmentation (90.4%), inhibited the cell survival proteins (RAS, B-RAF, & BCL-2) and also induced pro-apoptotic proteins (p38, pro-caspase-3, pro-caspase-9 and caspase-3) in the HL-60 cells. The present study provides scientific evidence for the apoptosis caused by myricitrin in HL-60 leukemia cells. Hence, the phytochemical myricitrin could be considered as a potential candidate to develop an anticancer drug after checking its efficacy through suitable pre-clinical and clinical studies.

Myricitrin, a Glycosyloxyflavone in Myrica esculenta Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation.

The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from Myrica esculenta bark, against diabetic nephropathy. Myr exhibited a significant hypoglycemic effect in high fat-fed and a single low-dose streptozotocin-induced type 2 diabetic (T2D) rats. Myr was found to improve glucose uptake by the skeletal muscle via activating IRS-1/PI3K/Akt/GLUT4 signaling in vitro and in vivo. Myr significantly attenuated high glucose (HG)-induced toxicity in NRK cells and in the kidneys of T2D rats. In this study, hyperglycemia caused nephrotoxicity via endorsing oxidative stress and inflammation resulting in the induction of apoptosis, fibrosis, and inflammatory damages. Myr was found to attenuate oxidative stress via scavenging/neutralizing oxidative radicals and improving endogenous redox defense through Nrf-2 activation in both in vitro and in vivo systems. Myr was also found to attenuate diabetes-triggered renal inflammation via suppressing NF-κB activation. Myr inhibited hyperglycemia-induced apoptosis and fibrosis in renal cells evidenced by the changes in the expressions of the apoptotic and fibrotic factors. The molecular docking predicted the interactions between Myr and different signal proteins. An in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) study predicted the drug-likeness character of Myr. Results suggested the possibility of Myr to be a potential therapeutic agent for diabetic nephropathy in the future.

Myricitrin regulates proliferation, apoptosis and inflammation of chondrocytes treated with IL-1ß.

Osteoarthritis (OA) is a clinical disease which seriously affects the quality of life of sufferers. Although the pathogenesis of OA has not been fully unraveled, it is may be due to increased levels of pro-inflammatory cytokines, activation of inflammation-related signaling pathways, and degradation of extracellular matrix. Osteoarthritis is characterized by chronic joint pain, swelling, stiffness, limited movement or joint deformity, all of which seriously affect the quality of life and health of the affected individuals. Myroside (Myr) is a polyphenolic hydroxyflavone glycoside extracted from the fruits, bark and leaves of myroside and other natural plants. It has many pharmacological properties, especially anti-inflammatory effects. In the present study, primary chondrocytes of IL-1ß rats were used to simulate pathological environment of chondrocytes in OA, and to explore the effect of Myr on chondrocytes. It was found that Myr improved the viability and proliferation of chondrocytes, and also inhibited apoptosis in these cells. Moreover, Myr reduced the expressions of inflammatory factors, and inhibited inflammatory reactions in chondrocytes. These findings provide good experimental basis for the clinical application of Myr in the prevention and treatment of progressive degeneration of cartilage in OA.

Myricitrin Ameliorates Hyperglycemia, Glucose Intolerance, Hepatic Steatosis, and Inflammation in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic ß-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes-fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.

Phytochemicals with Added Value from Morella and Myrica Species.

Terrestrial plants, due to their sessile nature, are highly exposed to environmental pressure and therefore need to produce very effective molecules that enable them to survive all the threats. Myrica and Morella (Myricaceae) are taxonomically close genera, which include species of trees or shrubs with edible fruits that exhibit relevant uses in traditional medicine. For instance, in Chinese or Japanese folk medicine, they are used to treat diarrhea, digestive problems, headache, burns, and skin diseases. A wide array of compounds isolated from different parts of Myrica and/or Morella species possess several biological activities, like anticancer, antidiabetic, anti-obesity, and cardio-/neuro-/hepatoprotective activities, both in vitro and in vivo, with myricanol, myricitrin, quercitrin, and betulin being the most promising. There are still many other compounds isolated from both genera whose biological activities have not been evaluated, which represents an excellent opportunity to discover new applications for those compounds and valorize Morella/Myrica species.

Enhanced Protection of Biological Membranes during Lipid Peroxidation: Study of the Interactions between Flavonoid Loaded Mesoporous Silica Nanoparticles and Model Cell Membranes.

Flavonoids, polyphenols with anti-oxidative activity have high potential as novel therapeutics for neurodegenerative disease, but their applicability is rendered by their poor water solubility and chemical instability under physiological conditions. In this study, this is overcome by delivering flavonoids to model cell membranes (unsaturated DOPC) using prepared and characterized biodegradable mesoporous silica nanoparticles, MSNs. Quercetin, myricetin and myricitrin have been investigated in order to determine the relationship between flavonoid structure and protective activity towards oxidative stress, i.e., lipid peroxidation induced by the addition of hydrogen peroxide and/or Cu2+ ions. Among investigated flavonoids, quercetin showed the most enhanced and prolonged protective anti-oxidative activity. The nanomechanical (Young modulus) measurement of the MSNs treated DOPC membranes during lipid peroxidation confirmed attenuated membrane damage. By applying a combination of experimental techniques (atomic force microscopy-AFM, force spectroscopy, electrophoretic light scattering-ES and dynamic light scattering-DLS), this work generated detailed knowledge about the effects of flavonoid loaded MSNs on the elasticity of model membranes, especially under oxidative stress conditions. Results from this study will pave the way towards the development of innovative and improved markers for oxidative stress-associated neurological disorders. In addition, the obtained could be extended to designing effective delivery systems of other high potential bioactive molecules with an aim to improve human health in general.

Study on the Material Basis of Neuroprotection of Myrica rubra Bark.

Background: Increasing attention has been given to the search for neuroprotective ingredients from natural plants. Myrica rubra bark (MRB) has been used in traditional oriental medicine for over thousand years and has potential neuroprotection. Methods and Results: Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to identify the compounds in MRB extract, and the MTT assay was performed to evaluate the neuroprotection of six major compounds from MRB against glutamate-induced damage in PC12 cells. The result displayed nineteen compounds were identified, and myricitrin and myricanol 11-sulfate were shown to have neuroprotection, which prevented cell apoptosis through alleviating oxidative stress by reducing the levels of reactive oxygen species and methane dicarboxylic aldehyde, as well as by enhancing the activities of superoxide dismutase. Conclusions: Several active compounds from MRB may offer neuroprotection and have the potential for the development of new drugs against central nervous system diseases.

Isolation of Myricitrin and 3,5-di-O-Methyl Gossypetin from Syzygium samarangense and Evaluation of their Involvement in Protecting Keratinocytes against Oxidative Stress via Activation of the Nrf-2 Pathway.

The wax apple (Syzygium samarangense) is traditionally employed as an antibacterial and immunostimulant drug in traditional medicine. This plant is rich in different flavonoids and tannins. In this study, we isolated two compounds from S. samarangense leaves: myricitrin and 3,5-di-O-methyl gossypetin. Then, we investigated the mechanisms of action of the two compounds against oxidative stress (induced by sodium arsenite) and inflammation (induced by UV light) on human keratinocytes. We could clearly demonstrate that the pre-treatment of cells with both compounds was able to mitigate the negative effects induced by oxidative stress, as no alteration in reactive oxygen species (ROS) production, glutathione (GSH) level, or protein oxidation was observed. Additionally, both compounds were able to modulate mitogen-activated protein kinase (MAPK) signaling pathways to counteract oxidative stress activation. Finally, we showed that 3,5-di-O-methyl gossypetin exerted its antioxidant activity through the nuclear transcription factor-2 (Nrf-2) pathway, stimulating the expression of antioxidant proteins, such as HO-1 and Mn-SOD-3.