PMID: 

Food Res Int. 2020 Jan ;127:108722. Epub 2019 Oct 8. PMID: 31882094

Abstract Title: 

The prebiotic properties of Hibiscus sabdariffa extract contribute to the beneficial effects in diet-induced obesity in mice.

Abstract: 

The metabolic syndrome has been associated with an alteration of intestinal microbiota, which can be considered as a target for the management of these patients. Phenolic extracts from Hibiscus sabdariffa have shown beneficial effects on obesity and its related complications. However, their effects on gut microbiota have not been investigated yet. This study evaluates the effects of a chemically characterized polyphenolic extract of H. sabdariffa (HSE) in an experimental model of diet-induced obesity (DIO) in mice. HSE was administered daily by oral gave for 42 days. HSE reduced weight increase in high fat diet (HFD)-fed mice, and improved glucose tolerance, insulin sensitivity and normalized LDL/HDL cholesterol ratio. It also enhanced the inflammatory state in the liver, reducing the expression of different adipokines and proinflammatory mediators, andreinforced gut integrity by increasing the expression of mucins and proteins involved in the maintenance of mucosal barrier. Moreover, HSE had a prebiotic effect, ameliorating the changes in the gut microbiota induced by the HFD. Thus, HSE improved the Firmicutes/Bacteroidetes ratio, which may contribute to the beneficial effects. Consequently, HSE could be considered for the development of a complementary treatment for the metabolic syndrome due to its beneficial properties.

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PMID: 

Res Pharm Sci. 2018 Jun ;13(3):205-212. PMID: 29853930

Abstract Title: 

Anxiolytic effects ofin a mouce model of anxiety.

Abstract: 

is commonly used in Iranian folk medicine for treatment of many disorders. Since there scientific data to prove the anxiolytic properties of this plant in Iran are scarce, we aimed to evaluate the sedative and anxiolytic activity of the leaf extract and essence ofin an animal model of anxiety. The extract and the essence used were obtained after maceration and hydro-distillation of the leaves of, respectively. We evaluated the anti-anxiety profile and sedative activity of diazepam (1 mg/kg i.p. as the standard), hydroethanolic extract (200 and 400 mg/kg i.p.) and the essence (10, 15, and 50 mg/kg i.p.) of leaves ofusing elevated plus-maze and locomotor activity. We also used flumazenil, to find out if the possible effects are mediated through gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. The results showed that the essence ofat a dose of 15 mg/kg is the most effective anxiolytic dose. Interestingly, flumazenil reversed this action of the essence as well as that of diazepam. The extract even at a dose of 400 mg/kg did not show significant anxiolytic effect. In locomotor activity studies, the essence caused sedation to a lesser extent than diazepam. The results suggest that the essence of this plant could be a better candidate for further analysis and fractionation. As the anxiolytic effect of the essence is reversed by flumazenil, it is possible that the GABA receptor could be involved in mediating these effects.

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PMID: 

Int J Mol Sci. 2019 Jul 20 ;20(14). Epub 2019 Jul 20. PMID: 31330819

Abstract Title: 

Elucidation of the Molecular Mechanism Underlying(Lim.)-Induced Relaxation and Anti-Depression.

Abstract: 

ethanolic extract (VEE) and verbascoside (Vs), a phenypropanoid glycoside, have been demonstrated to exert relaxant and anxiolytic properties. However, the molecular mechanisms behind their effects are still unclear. In this work, we studied the effects and action mechanisms of VEE and Vsand, on human neurotypic SH-SY5Y cells.TST was conducted on mice treated orally with VEE (25, 50 and 100 mg/Kg), Vs (2.5 and 5 mg/Kg), Bupropion (20 mg/Kg) and Milli-Q water. Higher dose of VEE-treated mice showed an increase of immobility time compared to control groups, indicating an induction of relaxation. This effect was found to be induced by regulation of genes playing key roles in calcium homeostasis (calcium channels), cyclic AMP (cAMP) production and energy metabolism. On the other hand, low doses of VEE and Vs showed an antidepressant-like effect and was confirmed by serotonin, noradrenalin, dopamine and BDNF expressions. Finally, VEE and Vsenhancedcell viability, mitochondrial activity and calcium uptakeconfirmingfindings. Our results showed induction of relaxation and antidepressant-like effects depending on the administered dose of VEE and Vs, through modulation of cAMP and calcium.

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PMID: 

Nutrients. 2019 Dec 4 ;11(12). Epub 2019 Dec 4. PMID: 31817196

Abstract Title: 

The Potential Synergistic Modulation of AMPK byCompounds as a Target in Metabolic Disorders.

Abstract: 

(LC) represents a complex plant-derived source of polyphenols and iridoids that has shown beneficial properties against obesity-related metabolic disorders. The complete extract and its major compound, verbascoside, have shown AMPK-activating capacity in cell and animal models. In this work, we aimed to elucidate the contribution of the different compounds present in the LC extract on the AMPK activation capacity of the whole extract. Semipreparative reversed-phase high-performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (RP-HPLC-ESI-TOF-MS) was used to identify the major compounds with bioassay-guided fractionation in an adipocyte cell model for the measurement of AMPK activity. Twenty-two compounds were identified and purified almost to homogeneity in 16 fractions, and three compounds, namely verbascoside, luteolin-7-diglucuronide and loganic acid, showed the highest AMPK-activating capacity. The synergy study using the checkerboard and fractional inhibitory concentration index (FICI) methods exhibited synergistic behavior between loganic acid and luteolin-7-diglucuronide. Molecular docking experiments revealed that these three compounds might act as direct agonists of AMPK, binding to the AMP binding sites of the gamma subunit and/or the different sites of the interaction zones between the gamma and beta subunits. Although our findings conclude that the bioactivity of the extract is mainly due to verbascoside, the synergy found between loganic acid and luteolin-7-diglucuronide deserves further research aimed to develop optimized combinations of polyphenols as a new nutritional strategy against obesity-related metabolic disorders.

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PMID: 

Drug Des Devel Ther. 2019 ;13:4291-4303. Epub 2019 Dec 18. PMID: 31908415

Abstract Title: 

The Role of the Reactive Oxygen Species Scavenger Agent, Astaxanthin, in the Protection of Cisplatin-Treated Patients Against Hearing Loss.

Abstract: 

Emerging evidence of significant hearing loss occurring shortly after cisplatin administration in cancer patients has stimulated research into the causes and treatment of this side effect. Although the aetiology of cisplatin-induced hearing loss (CIHL) remains unknown, an increasing body of research suggests that it is associated with excessive generation of intracellular reactive oxygen species (ROS) in the cochlea. Astaxanthin, a xanthophyll carotenoid, has powerful anti-oxidant, anti-inflammatory, and anti-apoptotic properties based on its unique cell membrane function, diverse biological activities, and ability to permeate the blood-brain barrier. In this review, we summarize the role of ROS in CIHL and the effect of astaxanthin on inhibiting ROS production. We focus on investigating the mechanism of action of astaxanthin in suppressing excessive production of ROS.

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PMID: 

Pharmacol Res. 2020 Feb 11:104689. Epub 2020 Feb 11. PMID: 32057895

Abstract Title: 

Astaxanthin anticancer effects are mediated through multiple molecular mechanisms: a systematic review.

Abstract: 

During the latest decades, the interest on the effectiveness of natural compounds and their impact on human health constantly increased, especially on those demonstrating to be effective on cancer. Molecules coming from nature are currently used in chemotherapy like Taxol, Vincristine or Vinblastine, and several other natural substances have been showed to be active in reducing cancer cell progression and migration. Among them, astaxanthin, a xanthophyll red colored carotenoid, displayed different biological activities including, antinflammatory, antioxidant, proapoptotic, and anticancer effects. It can induce apoptosis through downregulation of antiapoptotic protein (Bcl-2, p-Bad, and survivin) expression and upregulation of proapoptotic ones (Bax/Bad and PARP). Thanks to these mechanisms, it can exert anticancer effects towards colorectal cancer, melanoma, or gastric carcinoma cell lines. Moreover, it possesses antiproliferative activity in many experimental models and enhances the effectiveness of conventional chemotherapic drugs on tumor cells underling its potential future use. This review provides an overview of the current knowledge on the anticancer potential of astaxanthin by modulating several molecular targets. While it has been clearly demonstrated its multitarget activity in the prevention and regression of malignant cells in in vitro or in preclinical investigations, further clinical studies are needed to assess its real potential as anticancer in humans.

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PMID: 

Antioxidants (Basel). 2020 Jan 3 ;9(1). Epub 2020 Jan 3. PMID: 31947843

Abstract Title: 

Anthocyanins fromL. Inhibit Oxidative Stress-Mediated Apoptosis by Activating the Nrf2/HO-1 Signaling Pathway.

Abstract: 

L. is distributed widely throughout Eastern and Southern Asia and considered as the national flower of South Korea. The extraction of several plant parts ofL. is currently used as a natural remedy for several diseases, including breast and lung cancer, microbial infection, and chronic inflammation. However, the effect of the anthocyanin extract ofL. petals (PS) in oxidative stress conditions has not been studied. In this study, we evaluated the cytoprotective effect of PS against HO-induced oxidative stress in HaCaT keratinocytes. In this study, we found that PS significantly inhibited HO-induced apoptosis of HaCaT keratinocytes. We also revealed that PS mediated-cytoprotective effect was associated with the increased expression of heme oxygenase-1 (HO-1) arising from the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PS also decreased HO-induced excessive intracellular ROS generation and restored HO-induced mitochondrial depolarization through the downregulation of mitochondrial ROS production. Furthermore, HO-induced Bax and caspase-3 expression was markedly abolished in the presence of PS. The inhibition of HO-1 by zinc protoporphyrin significantly attenuated the cytoprotective effect of PS in HO-treated HaCaT keratinocytes along with ROS generation, indicating that HO-1 crucially affects PS-mediated cytoprotective properties. Collectively, our results suggested that, under HO-mediated oxidative stress conditions, PS sustained a normal level of mitochondrial membrane potential and ROS generation in HaCaT keratinocytes by activating the Nrf2/HO-1 axis, exerting cytoprotective effects against oxidative stress.

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PMID: 

Foods. 2020 Jan 6 ;9(1). Epub 2020 Jan 6. PMID: 31935957

Abstract Title: 

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

Abstract: 

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

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PMID: 

Phytother Res. 2020 Feb ;34(2):329-339. Epub 2020 Jan 14. PMID: 31943427

Abstract Title: 

The efficacy of sour tea (Hibiscus sabdariffa L.) on selected cardiovascular disease risk factors: A systematic review and meta-analysis of randomized clinical trials.

Abstract: 

This study sought to summarize clinical evidence of sour tea (Hibiscus sabdariffa L.) administration on cardiovascular disease risk factors. PubMed, Scopus, Institute for Scientific Information Web of Science, and Google Scholar were systematically searched from inception to June 2019 to identify randomized clinical trials, which assessed the effect of sour tea consumption on lipid profiles, fasting plasma glucose, and blood pressure in adult populations. Mean and standard deviation for each parameter were extracted to calculate effect size. Cochrane Collaboration tools were used to evaluate risk of bias assessment. A total of seven randomized clinical trials consisting 362 participants were included in the meta-analysis. Pooled effect size demonstrated that sour tea consumption significantly reduces fasting plasma glucose (-3.67 mg/dl, 95% confidence interval, CI [-7.07, -0.27]; I= 37%), systolic blood pressure (-4.71 mmHg, 95% CI [-7.87, -1.55]; I= 53%), and diastolic blood pressure (-4.08 mmHg, 95% CI [-6.48, -1.67]; I= 14%). Although no significant effect was observed on triacylglycerol, total cholesterol, and high-density lipoprotein cholesterol following sour tea consumption, a trend toward a significant reduction was found in low-density lipoprotein cholesterol serum concentrations (p = 0.08). This systematic review and meta-analysis suggests that sour tea consumption could have beneficial effect in controlling glycemic status and blood pressure among adult population.

PMID: 

J Ethnopharmacol. 2020 Feb 6 ;253:112647. Epub 2020 Feb 6. PMID: 32035878

Abstract Title: 

Anti-hyperglycaemic activity of H. rosa-sinensis leaves is partly mediated by inhibition of carbohydrate digestion and absorption, and enhancement of insulin secretion.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Hibiscus rosa-sinensis (HRS) is a tropical flowery plant, widely distributed in Asian region and an important traditional medicine used in many diseases including cough, diarrhoea and diabetes.AIM OF THIS STUDY: Hibiscus rosa-sinensis (HRS) leaves have been reported to possess anti-hyperglycaemic activity, but little is known concerning the underlying mechanism. This study investigated effects of ethanol extract of HRS on insulin release and glucose homeostasis in a type 2 diabetic rat model.MATERIALS & METHODS: Effects of ethanol extract of grinded H. rosa-sinensis (HRS) leaves on insulin release, membrane potential and intracellular calcium were determined using rat clonalβ-cells (BRIN-BD11 cells) and isolated mouse pancreatic islets. Effects on DPP-IV enzyme activity were investigated in vitro. Acute effects of HRS on glucose tolerance, gut perfusion in situ, sucrose content, intestinal disaccharidase activity and gut motility were measured. Streptozotocin inducedtype 2 diabetic rats treated for 28 days with ethanol extract of HRS leaf (250 and 500 mg/kg) were used to assess glucose homeostasis.RESULTS: HRS, significantly increased insulin release from clonal rat BRIN-BD11 cells and this action was confirmed using isolated mouse pancreas islets with stimulatory effects equivalent to GLP-1. HRS induced membrane depolarization and increased intracellular Cain BRIN BD11 cells and significantly inhibited DPP-IV enzyme activity in vitro. HRS administration in vivo improved glucose tolerance in type 2 diabetic rats, inhibited both glucose absorption during gut perfusion and postprandial hyperglycaemia and it reversibly increased unabsorbed sucrose passage through the gut following sucrose ingestion. HRS decreased intestinal disaccharidase activity and increased gastrointestinal motility in non-diabetic rats. In a chronic 28-day study with type 2 diabetic rats, HRS, at 250 or 500 mg/kg, significantly decreased serum glucose, cholesterol, triglycerides and increased circulating insulin, HDL cholesterol and hepatic glycogen without increasing body weight.CONCLUSION: These data suggest the antihyperglycaemic activity of HRS is mediated by inhibiting carbohydrate digestion and absorption, while significantly enhancing insulin secretion in a dose dependent manner. This suggests that HRS has potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes.

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