Chemopreventive Effects of Polysaccharides and Flavonoids from Okra Flowers in Azomethane/Dextran Sulfate Sodium-Induced Murine Colitis-Associated Cancer.

Okra flowers are a good source of polysaccharides and flavonoids, with biological activities of anti-inflammatory action and modulation of the gut microbiota. Previously, we reported that flavonoid-rich extracts from okra flowers (AFE) presented effective anti-colorectal cancer (CRC) activity in CRC cells as well as xenograft models, but their role in colitis-associated cancer (CAC) is unidentified. In this study, we aimed to evaluate the effects of AFE and APE (polysaccharides extracted from okra flowers) on the CAC symptoms of azoxymethane (AOM)/dextran sodium sulfate (DSS)-intervened mice. The results showed that APE and AFE exert potent efficacy in inhibiting colitis and colorectal tumorigenesis stimulated by AOM/DSS, characterized by decreased colonic shortening, DAI score, and tumor numbers. Compared with the control group, APE/AFE alleviated the microbiota dysbiosis driven by AOM/DSS. In addition, AFE elicited its anticancer activity through regulation of NFκB/IL-6/Stat3, JAK2/Stat3, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in AOM/DSS mice, which was consistent with a vitro model of CT26 cells, while APE treatment exhibited anticancer activity through regulation of Nrf2/IL-6, MAPKs, PI3K/AKT, and Wnt/ß-catenin signal transductions in the AOM/DSS mouse model. Collectively, our studies revealed, for the first time, that flavonoids and polysaccharides from okra flowers possess the ability to attenuate colitis and colorectal tumorigenesis, with them having great potential to become promising candidates against CRC.

Positive effects of Pycnogenol®-Centellicum® on venous elasticity: an ex-vivo concept study.

BACKGROUND: The aim of this ex-vivo study was to evaluate the efficacy of Pycnogenol®-Centellicum® oral supplementation on vein segments, retrieved from graft harvesting or from vein surgery. The parameters assessed were elasticity and recovery after dynamic tests: 1) an enlargement stress; 2) an elongation stress; and 3) elasticity after torsion. The tests were made in standardized conditions, less than 3 hours after explant, at 22 °C by the same operator with surgical and microsurgical experience. METHODS: Veins of 59 subjects were included in the study: 17 subjects with normal veins with a planned bypass graft and 42 subjects with varicose veins. Of the subjects with normal veins, 8 subjects followed standard management (group 1) and 9 took Pycnogenol®-Centellicum® for 4 weeks before surgery (group 2). In the group with varicose veins, 22 subjects served as controls (group 3) and 20 were supplemented with Pycnogenol®-Centellicum® for 4 weeks before surgery (group 4). No side effects or tolerability problems were observed in the supplementation period before surgery and veins harvesting. The full return to initial shape/sizes after dynamic stress was evaluated in 1 min after removing the stress. RESULTS: In group 1, 4 out of 8 vein segments recovered their size after forced enlargement vs. 7/9 in the Pycnogenol®-Centellicum® group 2 (P<0.05). In the elongation test, 3/8 normal control vein segments recovered their length (group 1) vs. 7/9 in the supplement group (group 2) (P<0.05). In the torsion test, 4/8 (group 1) veins recovered their shape after torsion vs. 9/9 veins in Pycnogenol®-Centellicum®-pretreated segments (group 2) (P<0.05). Only 45.8% of normal, control vein segments (group 1) recovered their shape/size in comparison with 85.2% of normal vein segments in the supplement group (group 2) (P<0.05). In group 3 and 4 (segments of varicose veins), the proportion of vein segments with enlargements, elongation and torsion were significantly lower at the end of the test (P<0.05) in the Pycnogenol®-Centellicum® group 4 with 51.7% of the vein segments recovering their shape in the Pycnogenol®-Centellicum® vs. 16.6% of the vein segments recovering their shape in control segments (P<0.05). Results show that Pycnogenol®-Centellicum® supplementation allows vein segments to better return to their original shape/size after a morphological alteration of shape (in different directions). This could be an expression of an improved wall tone and elasticity of the veins. No vein was teared or damaged during the 59 tests indicating that all stresses were well within the normal wall tensile characteristics of the veins. CONCLUSIONS: In this study, Pycnogenol®-Centellicum® improved vein elasticity in subjects with normal and varicose veins as vein segments were more elastic (able to recover length and shape) and less passively dilated by high pressure or dynamic stresses. This study indicates that the protective effects of Pycnogenol®-Centellicum® may partially stop passive dilatation of veins to varicose veins over time by improving vein elasticity. Pycnogenol®-Centellicum® managed vein segments return more rapidly back to the initial dimensions, shapes and diameters after a dynamic stress.

The molecular mechanisms underlying anti-inflammatory effects of galangin in different diseases.

When used as an alternative source of drugs to treat inflammation-associated diseases, phytochemicals with anti-inflammatory properties provide beneficial impacts. Galangin is one of the most naturally occurring flavonoids. Galangin has many biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antimicrobial, anti-obesity, antidiabetic, and anti-genotoxic activities. We observed that galangin was well tolerated and positively impacted disease underlying inflammation for the renal, hepatic, central nervous system, cardiovascular, gastrointestinal system, skin, and respiratory disorders, as well as ulcerative colitis, acute pancreatitis, retinopathy, osteoarthritis, osteoporosis, and rheumatoid arthritis. Galangin anti-inflammatory effects are mediated mainly by suppressing p38 mitogen-activated protein kinases, nuclear factor-kappa B, and nod-like receptor protein 3 signals. These effects are confirmed and supported by molecular docking. Clinical translational research is required to accelerate the bench-to-bedside transfer and determine whether galangin can be utilised as a safe, natural source of pharmaceutical anti-inflammatory medication for humans.

Antihyperglycemic Effect of Rhamnus alaternus L. Aqueous Extract in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Traditionally, the aerial parts of Rhamnus alaternus L. have been widely used in Mediterranean countries, including Morocco, to cure diabetes. AIM: This study aimed to evaluate the antidiabetic effect of Rhamnus alaternus aqueous extract in streptozotocin(STZ)-induced diabetic rats. OBJECTIVE: This work aimed to evaluate the antihyperglycemic effect of Rhamnus alaternus aqueous extract (RAAE) in normal and diabetic rats. Then the phytochemical composition, antioxidant capacity, and potential toxicity of RAAE were also assessed. METHODS: The effects of acute (6 h) and subchronic (7 days) oral administration of RAAE (20 mg/kg) on blood glucose levels and lipid profiles were evaluated in normal and diabetic rats. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity, using the DPPH method, were evaluated. Additionally, the toxicity of the aqueous extract (5 mg/kg) was also studied and the LD50 value was determined. RESULTS: RAAE (20 mg/kg) over 7 days of oral administration significantly decreased the blood glucose levels both in normal and diabetic rats. In diabetic rats, this extract also improved oral glucose tolerance. In addition, RAAE possessed significant antioxidant activity. According to preliminary phytochemical research, RAAE contains several chemical compounds, including alkaloids, polyphenols, flavonoids, cyanidins, anthraquinones, and sterols. On the other hand, the quantitative phytochemical study of the aqueous extract revealed a considerable amount of total phenolic compounds (497.93 ± 3.38 mg GAE/1g of RAAE), flavonoids (100.42 ± 0.32 mg RE/ g of RAAE), and tannins (14.32 ± 0.37 mg CE/1g of RAAE). CONCLUSION: We conclude that RAAE exerts a significant antihyperglycemic effect in STZ-induced diabetic rats at a low dose. Indeed, more research is still required to support the use of this plant in the Moroccan population's diabetes care.

A Nutraceutical Compound Containing a Low Dose of Monacolin K, Polymethoxyflavones, Phenolic Acids, Flavonoids, and Hydroxytyrosol Improves HDL Functionality.

BACKGROUND: In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, and hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL). AIM: This study aimed to evaluate whether the NC could influence determinants of HDL function. METHODS: Forty-five subjects with low-moderate dyslipidaemia were enrolled and treated for 8 weeks with the NC, followed by 4 weeks of washout. Blood samples were collected at every time point to evaluate changes in lipid profile, endothelial function, oxLDL, and markers of HDL function, such as the anti-oxidant activities of paraoxonase-1, glutathione peroxidase-3 (Gpx3), lipoprotein-phospholipase A2 (Lp-PLA2), and pro-oxidant activity of myeloperoxidase (MPO). RESULTS: Although the concentration of HDL-C did not change, the activity of Lp-PLA2 significantly decreased upon treatment (-11.6%, p<0.001) and returned to baseline level 4 weeks after the end of treatment. In contrast, Gpx3 increased after treatment (+5%, p<0.01) and remained unvaried after 4 weeks. Both MPO activity and concentration significantly decreased after the washout period (-33 and 32%, p<0.001). CONCLUSION: For the first time, it was found that the administration of an NC with beneficial effects on lipid homeostasis also positively impacts HDL function by improving the balance between protective and damaging determinants. Further investigation is required to corroborate our findings.

Effect Of The Flavonoid 6-Aminoflavone In Aspirin Induced Gastric Ulcer In Sprague-Dawely Rats: A Histomorphological Study.

Background: The analgesic drugs are the main cause of gastric ulcer. The objective of this study was to determine the gastroprotective ability of flavonoid, 6-aminoflavone in a rat pyloric ligation model of aspirin associated gastro-ulcerogenesis. Methods: A laboratory based experimental study was conducted in the animal house and research laboratory at Khyber Medical College, Peshawar from July to November 2019. A total of 42 adult male Spargue-Dawely rats were divided into seven groups. Flavonoid, 6-aminoflavone was administered orally in doses of 10, 25 and 100 mg/kg with misoprostol, as standard at 50 µg/kg orally for 4 days. On the last day aspirin was given orally at 200 mg/kg and the pyloric ligation surgery was performed. After 4 hours all animals were killed by cervical dislocation. The gastric tissues were collected for histomorphological study. The obtained data were expressed as mean±SEM. Analysis was carried out by using ANOVA. p value ˂0.05 was considered significant. Results: The animals treated with the different doses of 6-aminoflavone showed a marked protective effect in the histological observations. The 10 mg/kg dose had a mild protective effect as occasional ulcerative changes were observed. However, doses of 25 and 100 mg/kg significantly caused the reduction in the ulcer score. These effects produced were equipotent to the gastroprotective effectiveness inherent in the misoprostol. . Conclusion: These findings conclude that 6-aminoflavone as like other flavonoids has a significant gastroprotective propensity with significant effect produced at doses of 25 and 100 mg/kg and can be used as a part of therapy management for the treatment of gastrointestinal disease particularly ulcerative condition.

Protective Effect of Galangin Methylation Modification Based on Cell Imaging on Inflammatory Lung Injury and Its Molecular Mechanism.

Background: Recently, inflammation has become a major threat to human health. Studies have confirmed that some Chinese traditional medicine ingredients may effectively interfere with the expression of inflammatory mediators through epigenetic modification, showing a great potential of the application. Objective: To investigate the role of the PPAR/DNMT3A pathway in the reversal of galangin-mediated inflammatory lung injury, promote the development of new anti-inflammatory drugs, reduce the side effects of chemical synthetic drugs on the body, and prove the effectiveness and safety of galangin in inhibiting inflammatory response and injury. Methods: 120 rats were randomly divided into 6 groups: (Group 1) LPS group; (Group 2) LPS + galangin group; (Group 3) LPS + galangin + GW9662 group; (Group 4) LPS + galangin + DNMT3A siRNA group; (Group 5) LPS + galangin + siRNA negative group; (Group 6) control group. The model of inflammatory lung injury was established by intrathecal instillation of LPS in the first five groups and NS in the control group. SD survival rate was recorded every 24 hours after modeling, lasting for 168 hours. The lung tissues were taken 168 hours after the establishment of the model. The pathological morphology of lung tissue was observed after the staining under the light microscope, and the lung dry/wet weight ratio was calculated after drying. After NS was perfused into lung tissue, the lavage fluid was collected and the levels of IL-6 and TNF-a were measured by ELISA. The contents of PPAR, DNMT3A, phosphorylated p65, and ERK in monocytes were detected by the WB method, and the binding contents of p65 and AP-1 in the promoter regions of IL-6 and TNF-a genes were detected by the Chip-qPCR method. Results: Intraperitoneal injection of galangin could inhibit the synthesis of alveolar inflammatory factors (TFs) in the SD model of lung injury induced by LPS, reduce the degree of pathological injury of lung tissue, and improve the survival rate of the SD model. GW9662 can completely reverse the protective effect, while DNMT3A interference can only partially block its protective effect. In addition, galangin could significantly inhibit the LPS-induced expression of p65 and AP-1 in alveolar monocytes and their binding content in the promoter region of inflammatory genes by activating PPAR/DNMT3A pathway. GW9662 could completely reverse the inhibitory effect of galangin. DNMT3A interference could restore the binding content of transcription factors at the promoter of the inflammatory gene but had no significant effect on its synthesis. Conclusion: Galangin can interfere with the binding of transcription factors to inflammatory gene promoters through the methylation modification induced by PPAR/DNMT3A pathway, so as to inhibit the synthesis of inflammatory molecules and reverse inflammatory lung injury.

Brightening effect of Ziziphus jujuba (jujube) fruit extract on facial skin: A randomized, double-blind, clinical study.

Ziziphus jujuba Mill. (jujube) is an invaluable medicinal plant in traditional and modern medicine. Jujube syrup is a complex of herbal extracts including Z. jujuba, Berberis vulgaris, Rhus coriaria, Prunus domestica, and Rosa damascene. The purpose of the present study was to formulate and investigate the efficacy and safety of jujube syrup on brightening of facial skin. In this randomized, double-blind, controlled clinical study, 46 participants consumed jujube syrup or placebo (23 in each group) twice a day for 8 weeks. The number of pigments, area of pigmentation, and physician's global assessment score (PGAS) were evaluated at baseline and after 8 weeks. The results showed the amounts of total phenolics and flavonoids were 81.97 ± 0.25 and 4.98 ± 1.04 mg/ml, respectively. The amounts of organic acids (gallic acid and chlorogenic acid) were quantified at 1140 ± 17.65 and 1520 ± 25.77 µg/ml, respectively. The amounts of total phenolic and flavonoids were stable under accelerated conditions. Eight weeks after treatment, the number of pigment counts reduced to 0.545 ± 0.307 compared to the placebo group. Moreover, the pigmented area and its percentages were significantly reduced to 0.556 ± 0.285 and 0.561 ± 0.288 in jujube syrup compared with placebo, respectively. Jujube syrup is efficient and safe for treating hyperpigmentation of the face.

Redox Activity of Flavonoids: Impact on Human Health, Therapeutics, and Chemical Safety.

The cost-effectiveness of presently used therapies is a problem in overall redox-based management, which is posing a significant financial burden on communities across the world. As a result, sophisticated treatment models that provide notions of predictive diagnoses followed by targeted preventive therapies adapted to individual patient profiles are gaining global acclaim as being beneficial to patients, the healthcare sector, and society as a whole. In this context, natural flavonoids were considered due to their multifaceted antioxidant, anti-inflammatory, and anticancer effects as well as their low toxicity and ease of availability. The aim of this review is to focus on the capacity of flavonoids to modulate the responsiveness of various diseases and ailments associated with redox toxicity. The review will also focus on the flavonoids' pathway-based redox activity and the advancement of redox-based therapies as well as flavonoids' antioxidant characteristics and their influence on human health, therapeutics, and chemical safety. Research findings indicated that flavonoids significantly exhibit various redox-based therapeutic responses against several diseases such as inflammatory, neurodegenerative, cardiovascular, and hepatic diseases and various types of cancer by activating the Nrf2/Keap1 transcription system, suppressing the nuclear factor κB (NF-κB)/IκB kinase inflammatory pathway, abrogating the function of the Hsp90/Hsf1 complex, inhibiting the PTEN/PI3K/Akt pathway, and preventing mitochondrial dysfunction. Some flavonoids, especially genistein, apigenin, amentoflavone, baicalein, quercetin, licochalcone A, and biochanin A, play a potential role in redox regulation. Conclusions of this review on the antioxidant aspects of flavonoids highlight the medicinal and folk values of these compounds against oxidative stress and various diseases and ailments. In short, treatment with flavonoids could be a novel therapeutic invention in clinical trials, as we hope.

Flavonoid-statin interactions causing myopathy and the possible significance of OATP transport, CYP450 metabolism and mevalonate synthesis.

3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, statins, are a primary treatment for hyperlipidemic cardiovascular diseases which are a leading global cause of death. Statin therapy is life saving and discontinuation due to adverse events such as myotoxicity may lead to unfavourable outcomes. There is no known mechanism for statin-induced myotoxicity although it is theorized that it is due to inhibition of downstream products of the HMG-CoA pathway. It is known that drug-drug interactions with conventional medicines exacerbate the risk of statin-induced myotoxicity, though little attention has been paid to herb-drug interactions with complementary medicines. Flavonoids are a class of phytochemicals which can be purchased as high dose supplements. There is evidence that flavonoids can raise statin plasma levels, increasing the risk of statin-induced myopathy. This could be due to pharmacokinetic interactions involving hepatic cytochrome 450 (CYP450) metabolism and organic anion transporter (OATP) absorption. There is also the potential for flavonoids to directly and indirectly inhibit HMG-CoA reductase which could contraindicate statin-therapy. This review aims to discuss what is currently known about the potential for high dose flavonoids to interact with the hepatic CYP450 metabolism, OATP uptake of statins or their ability to interact with HMG-CoA reductase. Flavonoids of particular interest will be covered and the difficulties of examining herbal products will be discussed throughout.

Is There a Difference in the Clinical Efficacy of Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disorders? Review of Available Evidence.

Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders (CVD). Among venoactive drugs, diosmin is a naturally occurring flavonoid glycoside that can be isolated from various plant sources; it can also be obtained after conversion of hesperidin extracted from citrus rinds. Micronized purified flavonoid fraction (MPFF) is a preparation that contains mainly diosmin and a small fraction of hesperidin. We performed a state-of-the-art literature review to collect and analyze well-conducted randomized clinical studies comparing diosmin - also called non-micronized or hemisynthetic diosmin - 600 mg a day and MPFF, 1000 mg a day. Three clinical studies met the criteria and were included for this literature review. These clinical studies showed a significant decrease of CVD symptom intensity (up to approximately 50%) and global patient satisfaction after one-to-six-month treatment with diosmin or MPFF, without statistical differences between these two forms of diosmin. Both treatments were well tolerated with few mild adverse drug reactions reported. Overall, based on this literature review, there is no clinical benefit to increase the dose of diosmin beyond 600 mg per day, to use the micronized form, or to add hesperidin, since clinical efficacy on venous symptomatology is achieved with 600 mg per day of pure non-micronized diosmin. This challenges the status of diosmin - 600 mg a day - in guidelines for the management of CVD, which is currently categorized 2C (weak recommendations for use and poor quality of evidence), while the most widely used and assessed preparation MPFF is rated 1B (strong recommendation for use and moderate quality of evidence).

Effects of Hormone Therapy and Flavonoids Capable on Reversal of Menopausal Immune Senescence.

Menopause, probably the most important natural change in a woman's life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1ß, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.

Idiopathic myalgic pain (fibromyalgia): supportive management and prevention with Pycnogenol®.

BACKGROUND: The aim of this registry study was the prospective evaluation of the efficacy of Pycnogenol® in idiopathic fibromyalgia (FM), over 4 weeks in comparison with the standard management (SM). METHODS: A SM and a Pycnogenol®+SM group were formed. Pycnogenol® supplementation was used at the dose of 150 mg/day (4 weeks). The study considered the most important/frequent symptoms of FM. RESULTS: Fifty patients with idiopathic fibromyalgia were included: 26 in the Pycnogenol® group and 24 served as controls. The two groups were comparable at inclusion. No other disease or condition was present. All subjects were otherwise healthy women (BMI<26), not using any drug. All subjects had an elevated level of oxidative stress (OS) at inclusion. All routine blood tests - and all inflammatory and rheumatic tests - were within the normal range at inclusion and at the end of the study. No safety or tolerability problems were observed. The percentage of patients using NSAIDs (non-steroidal anti-inflammatory drugs) as rescue medications in the observation period was significantly higher in the SM management group (P<0.05) in comparison with the supplement group. The percentage of patients using corticosteroids as rescue medication was significantly higher in the SM group (P<0.05). The percentage of subjects with the symptoms/complaints decreased significantly, considering each symptom, with Pycnogenol® after 4 weeks in comparison with the SM (P<0.05). CONCLUSIONS: Pycnogenol® supplementation appears to control and reduce the intensity of common symptoms and complaints - especially pain-related - associated with FM. Pycnogenol® could be a 'soft', safe supplementation and prevention method to manage the symptoms of most of these patients, even for longer periods, reducing the need for drugs.

Mutational spectra induced by flavonoid extracts from pepper tree (Schinus terebinthifolius, Raddi) stem bark.

Flavonoids are a diverse family of plant compounds that are involved in pigmentation, protection, and endogenous regulation. Flavonoids also have medicinal applications, suggesting that they may exert chemoprotective effects. However, some studies have shown, that some plant flavonoids have oxidative and toxic effects, including those produced by Schinus terebinthifolius. In Brazil, extracts of this plant are widely used for medical purposes. In this study, we analyzed the mutagenic potential of two flavonoid-enriched fractions from Brazilian pepper tree stem bark using Escherichia coli CC strains deficient and proficient in enzymes involved in the DNA repair of oxidative lesions. The highest mutagenic response was detected in the CC104mutMmutY strain but CC104mutY showed a higher mutation frequency than CC104mutM. The spectrum of mutations induced in plasmid DNA is composed of mutations typically caused by oxidative lesions. However, a new type of lesion must be occurred to explain the cytotoxicity, higher mutation rates in the CC104mutY strain, and the rare A:T → T:A and G:C → C:G transversions found in this work.

Flavonoids as therapeutic candidates for emotional disorders such as anxiety and depression.

Emotional disorders such as anxiety and depression are widespread psychological diseases that affect up to 20% of the world's population. There are many approaches to the discovery of novel agents for the treatment of depressive- and anxiety-like symptoms. However, the efficacy of existing drugs for emotional disorders is only exerted after a few weeks of treatment and have serious side effects. Due to this, new strategies to find suitable and safe options are being sought by many researchers. Among them, a lot of interest has been attracted by plant-derived natural compounds due to their wide range of beneficial effects for new agent development. Flavonoids are natural polyphenol-like compounds found commonly in plants, fruits, vegetables, and medicinal herbs. A diverse range of flavonoids have been studied to investigate their potential therapeutic activities for the treatment of brain-associated disorders, including anxiety and depression. The main aim of this review is to understand the associations between the various flavonoids and the emotional disorders and discuss the therapeutic effects of these natural compounds that were demonstrated during the conduction of recent studies. The current work shows advances in the latest research of some flavonoids as a potential candidate for the treatment of emotional disorders. We summarize their behavioral, molecular, physiological, and neurochemical effects in various in vitro and in vivo models. Therefore, in the present work, the latest studies were collected on the most important flavonoid compounds and their underlying mechanisms of action in emotion-related disorders were discussed.

Projected supportive effects of PycnogenolⓇ in patients suffering from multi-dimensional health impairments after a SARS-CoV2 infection.

Corona virus disease 2019 (COVID-19) is triggered by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV2) and has rapidly developed into a worldwide pandemic. Unlike other SARS viruses, SARS-CoV2 does not solely impact the respiratory system, but additionally leads to inflammation of endothelial cells, microvascular injuries and coagulopathies, thereby affecting multiple organs. Recent reports of patients who were infected with SARS-CoV2 suggest persistent health problems even months after the initial infection. The French maritime pine bark extract PycnogenolⓇ has demonstrated anti-inflammatory, vascular and endothelium-protective effects in over 90 human clinical studies. It is proposed that PycnogenolⓇ may be beneficial in supporting recovery and mitigating symptoms and long-term consequences resulting from a SARS-CoV2 infection in COVID-19 patients.

Antioxidative and anti-inflammatory activities of Polygonum minus: a review of literature.

Inflammation and oxidative stress are involved in the pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension and ischemic heart disease. Natural products play an important role as nutritional supplements with potential health benefits in cardiovascular diseases. Polygonum minus (PM) is an aromatic plant that is widely used as a flavoring agent in cooking and has been recognized as a plant with various medicinal properties including antioxidative and anti-inflammatory actions. Phytoconstituents found in PM such as phenolic and flavonoid compounds contribute to the plant's antioxidative and anti-inflammatory effects. We conducted this review to systematically identify articles related to the antioxidative and anti-inflammatory activities of PM. A computerized database search was conducted on Ovid MEDLINE, PubMed, Scopus, and ACS publication, from 1946 until May 2020, and the following keywords were used: 'Kesum OR Polygonum minus OR Persicaria minor' AND 'inflammat* OR oxida* OR antioxida*'. A total of 125 articles were obtained. Another eight additional articles were identified through Google Scholar and review articles. Altogether, 17 articles were used for data extraction, comprising 16 articles on antioxidant and one article on anti-inflammatory activity of PM. These studies consist of 14 in vitro studies, one in vivo animal study, one combined in vitro and in vivo study and one combined in vitro and ex vivo study. All the studies reported that PM exhibits antioxidative and anti-inflammatory activities which are most likely attributed to its high phenolic and flavonoid content.

Baicalin induces Mrgprb2-dependent pseudo-allergy in mice.

Baicalin, a component of traditional Chinese medicine, is one of the main compounds present in Scutellaria baicalensis Georgi. Pseudo-allergy induced by the injection of these medicines is a frequent adverse drug reaction. Therefore, elucidation of the anaphylactoid reaction of baicalin and its underlying mechanisms are important. Mast cells are primary effectors of allergic reactions, including pseudo-allergy. Studies have shown that Mrgprx2 in human mast cells is a specific receptor that is crucial for pseudo-allergic drug reactions, Mrgprb3 is the rat ortholog of human Mrgprx2, which in mice is designated as Mrgprb2. Here, we aimed to investigate baicalin-induced pseudo-allergy and the association of Mrgprb3 and Mrgprb2 with this effect. We examined the allergenic effect of baicalin on RBL-2H3 cells and Mrgprb3-knockdown RBL-2H3 cells. Mrgprb2-expressing HEK293 cells and Mrgprb2-knockout mice were used to evaluate the role of Mrgprb2 in baicalin-induced allergy. Baicalin was found to dose-dependently induce pseudo-allergy both in vitro and in vivo. RBL-2H3 cells were activated by baicalin, whereas in Mrgprb3-knockout RBL-2H3 cells, baicalin showed a negligible effect on cell activation. Furthermore, baicalin activated the Mrgprb2-expressing HEK293 cells. Our data showed that baicalin did not induce allergy in Mpgprb2-knockout mice. We conclude that baicalin induces pseudo-allergy via Mrgprb2 in mice.

Supplementary management with Pycnogenol® in patients with lupus vasculitis in remission phases: a pilot, concept registry study.

BACKGROUND: The aim of this pilot study was the supplementary management of minimal, residual symptoms of systemic Lupus (SLE) with vasculitis (LV) in remission phases, using a natural, anti-inflammatory, antioxidant agent (Pycnogenol®) extracted from French maritime pine bark. Pycnogenol® has a significant clinical anti-inflammatory activity; it is a standardized supplement with a high-safety profile. METHODS: Subjects with Lupus vasculitis were included in the study. The standard management (SM) was used in all subjects for 8 weeks; one group added Pycnogenol® (150 mg/day) to SM. RESULTS: The two groups completing 8 weeks were comparable at baseline with 12 subjects managed with SM and 14 subjects supplemented with Pycnogenol®. No side effects due to Pycnogenol® were observed; Pycnogenol® was associated with an optimal tolerability. The proportion of patients with photosensitivity, oral ulcers, renal-associated hematuria (minimal), leukopenia, lymphopenia, thrombocytopenia, positive anti-DNA and positive antiphospolipids tests were significantly lower in the Pycnogenol® group (P<0.05) at 8 weeks in comparison with controls. No difference in activity between SM and supplementation was observed for rash, serositis, anemia, neurological symptoms (all mild at inclusion) and anti-Smith. Considering additional clinical parameters such as the need for corticosteroids, peripheral ischemia, oxidative stress, the effects of Pycnogenol® appeared to be superior to SM alone (P<0.05). The decrease in oxidative stress was significantly higher with Pycnogenol® (P<0.05) compared to SM. This is particularly interesting as it has not been observed before in LV. Considering microvascular parameters, the number of subjects with 'cold' hypoperfused thermographic areas was significantly lower in the supplement group (P<0.05) and distal flux (laser Doppler) was higher with the supplement (P<0.05) at 8 weeks. CONCLUSIONS: This pilot registry indicates that Pycnogenol® can be safely used in subjects with LV with mild symptoms (in remission) possibly avoiding some drug treatments that may cause side effects. A larger study in progress is evaluating the effects of Pycnogenol® on recurrent symptoms in subjects in remission.

The effect of icariin for infertile women with thin endometrium: A protocol for systematic review.

BACKGROUND: Thin endometrium, defined as <7 mm of the endometrial thickness around ovulation period, had been identified as a negative factor on pregnancy rate of infertile women. It was considered to be the toughest part in treatment of infertility, because there was a lack of significant effect, although many drugs had been already used. Icariin was one of the major bioactive pharmaceutical constituent extracted from the Chinese herb "Ying Yang Huo," in the genus of Epimedium, and some randomized controlled trials reported its application for thin endometrium. There is no systematic review focusing on the effective of icariin in treating infertile women with thin endometrium, so our review aims to explore it. METHODS: The bibliographic database and electronic library will be systematically searched online, such as MEDLINE, EMBASE, Web of Science, Clinicaltrails.org., China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, and Cochrane Library. And the reference listed for potential literatures of included studies will be scanned additionally. Related randomized controlled trials (RCTs) will be collected and selected before January 4, 2020. Trials will be screened by independent reviewers, and the literature will be search in English or Chinese, with the search terms as "Icariin," "Epimedium," "infertile women," "female infertility," "endometrium," "pregnancy rate." The software for Systematic review and Meta-analysis is RevMan 5.3. The protocol and the systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. RESULT AND CONCLUSION: The efficacy of icariin to treat thin endometrium will be evaluated, and the conclusion will be published to help clinicians determine treatment strategy for infertile women with thin endometirum by providing medical evidence. REGISTRATION INFORMATION: PROSPERO CRD42019148977.