Exploring antiviral activity of Betanin and Glycine Betaine against dengue virus type-2 in transfected Hela cells.

Dengue virus (DENV) infection is a worldwide public health concern infecting approximately 400 million individuals and about 40,000 mortalities yearly. Despite this, no licensed or readily available antiviral medication is currently available specifically for DENV infection, and therapy is typically symptomatic. Therefore, the objective of the study was to investigate the antiviral activity of Beta vulgaris L. phytoconstituents against DENV-2 targeting NS3 protein. The antiviral activity of phytochemicals was examined through virtual ligand-based screening, antiviral inhibition and dosage response assays, western blotting analysis and MD simulations. We conducted toxicological, and pharmacokinetic analysis to assess plant-based natural compound's efficacy, safety, and non-toxic doses. Molecular docking and MD simulation results revealed that the nonstructural protein-3 (NS3) might prove as a funamental target for Betanin and Glycine Betaine against Dengue virus. Betanin and Glycine betaine were initially studied for their non-toxic doses in HeLa, CHO, and Vero cells via MTT assay. HeLa cells were transiently transfected with cloned vector pcDNA3.1/Zeo(+)/DENV-2 NS3 along with non-toxic doses (80 µM-10 µM) of selected phytochemicals. The dose-response assay illustrated downregulated expression of DENV-2 NS3 gene after administration of Betanin (IC50 = 4.35 µM) and Glycine Betaine (IC50 = 4.49 µM). Dose response analysis of Betanin (80 µM-10 µM) depicted the significant inhibition of NS3 protein expression as well. These results suggested downregulated expression of DENV-2 NS3 at mRNA and protein level portraying the DENV replication inhibition. Based on our study findings, NS3 protease is depicted as distinctive DENV-2 inhibitor target. We will channel our study further into in vitro characterization employing the mechanistic study to understand the role of host factors in anti-flavi therapeutic.

Protective effects of betanin, a novel acetylcholinesterase inhibitor, against H2O2-induced apoptosis in PC12 cells.

BACKGROUND: Dysfunction of the cholinergic system and increased oxidative stress have a crucial role in cognitive disorders including Alzheimer's disease (AD). Here, we have investigated the protective effects of betanin, a novel acetylcholinesterase (AChE) inhibitor, on hydrogen peroxide (H2O2)-induced cell death in PC12 cells. METHODS AND RESULTS: The protective effects were assessed by measuring cell viability, the amount of reactive oxygen species (ROS) production, AChE activity, cell damage, and apoptosis using resazurin, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), Ellman method, lactate dehydrogenase (LDH) release, propidium iodide (PI) staining and flow cytometry, and Western blot analysis. H2O2 (150 µM) resulted in cell viability reduction and apoptosis induction while, pretreatment with the betanin (10, 20, and 50 µM) and N-Acetyl-L-cysteine (NAC) (2.5 and 5 mM) significantly increased the viability (P < 0.05, P < 0.01 and P < 0.001) and at 5-50 µM betanin decreased ROS amount (P < 0.05, P < 0.01 and P < 0.001). Whereas, pretreatment with the betanin (10, 20, and 50 µM) decreased AChE activity (P < 0.001), also at 20 and 50 µM betanin reduced the release of LDH (P < 0.001), and at 10-50 µM decreased the percentage of apoptotic cells (P < 0.001). Apoptosis biomarkers such as cleaved poly (ADP-ribose) polymerase (PARP) (P < 0.01 and P < 0.001) and cytochrome c (P < 0.05 and P < 0.001) were attenuated after pretreatment of PC12 cells with betanin at 10-20 µM and 10-50 µM respectively. Indeed, survivin (P < 0.001) increased after pretreatment of cells with betanin at 10-20 µM. CONCLUSIONS: Overall, betanin may use the potential to delay or prevent cell death caused by AD through decreasing the activity of AChE as well as attenuating the expression of proteins involved in the apoptosis pathway.

Elucidating the therapeutic mechanism of betanin in Alzheimer's Disease treatment through network pharmacology and bioinformatics analysis.

Betanin, a natural compound with anti-inflammatory and antioxidant properties, has shown promise in mitigating Alzheimer's disease (AD) by reducing amyloid plaque production. Employing network pharmacology, this study aimed to elucidate betanin's therapeutic mechanism in AD treatment. Through integrated analyses utilizing SwissTargetPrediction, STITCH, BindingDB, Therapeutic Target Database (TTD), and OMIM databases, potential protein targets of betanin in AD were predicted. Gene ontology analysis facilitated the identification of 49 putative AD targets. Subsequent gene enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis revealed associations between these targets and AD. Network pharmacology techniques and molecular docking aided in prioritizing essential genes, with APP, CASP7, ITPR1, CASP8, CASP3, ITPR3, and NF-KB1 emerging as top candidates. The results provide novel insights into betanin's therapeutic efficacy, shedding light on its potential clinical application in AD treatment. By targeting key genes implicated in AD pathology, betanin demonstrates promise as a valuable addition to existing therapeutic strategies. This holistic approach emphasizes the relevance of network pharmacology and bioinformatics analysis in understanding natural chemical disease therapy processes.

The synergistic effects of betanin and radiotherapy in a prostate cancer cell line: an in vitro study.

BACKGROUND: Prostate cancer is among the most common cancers in men with an increasing incidence rate. Radiation therapy (RT) is a therapeutic strategy for the management of prostate cancer after surgery; nonetheless, it has different side effects on neighboring healthy cells/tissues. Moreover, radioresistance has been an increasing phenomenon in the recent years. Therefore, there is an urgent need for the introduction of a safe and effective radiosensitizing agent. Accordingly, the recent trend in the development of novel drugs is accompanied by a push toward natural compounds. Our study evaluated the effects of betanin combined with RT as a potential radiosensitizing agent in the PC-3 cell line. METHODS AND RESULTS: MTT assay was utilized to determine the growth inhibitory impact of betanin. The possible synergistic effect was evaluated with CompuSyn software upon Trypan blue exclusion test. Apoptosis-related gene expression was evaluated via Real-time PCR and the protein expression of P21 was determined using western blotting. A synergistic anticancer effect with an optimal combination index of 0.61 was achieved by treating PC-3 cells with betanin and RT. The results pointed out that betanin synergistically triggered RT-mediated apoptosis and cell cycle arrest through modulating gene and protein expression in comparison with each of the monotherapies. CONCLUSION: These findings shed light on the synergistic antitumor effect of betanin and RT in prostate cancer, indicating the potential use of betanin as a radiosensitizer agent.

Exploring the possible mitoprotective and neuroprotective potency of thymoquinone, betanin, and vitamin D against cytarabine-induced mitochondrial impairment and neurotoxicity in rats' brain.

It has been suggested that cytarabine (Ara-C) induces toxicity via mitochondrial dysfunction and oxidative stress. Therefore, we hypothesized that mitochondrial protective agents and antioxidants can reduce cytarabine-induced neurotoxicity. For this purpose, 48 male Wistar rats were assigned into eight equal groups include control group, Ara-C (70 mg/kg, i.p.) group, Ara-C plus betanin (25 mg/kg, i.p.) group, Ara-C plus vitamin D (500 U/kg, i.p.) group, Ara-C plus thymoquinone (0.5 mg/kg, i.p.) group, betanin group, vitamin group, and thymoquinone group. The activity of acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), the concentrations of antioxidants (reduced glutathione and oxidized glutathione), oxidative stress (malondialdehyde) biomarkers, mitochondrial toxicity parameters as well as histopathological alteration in brain tissues were measured. Our results demonstrated that Ara-C exposure significantly declines the brain enzymes activity (AChE and BChE), levels of antioxidant biomarkers (GSH), and mitochondrial functions, but markedly elevate the levels of oxidative stress biomarkers (MDA) and mitochondrial toxicity. Almost all of the previously mentioned parameters (especially mitochondrial toxicity) were retrieved by betanin, vitamin D, and thymoquinone compared to Ara-C group. These findings conclusively indicate that betanin, vitamin D, and thymoquinone administration provide adequate protection against Ara-C-induced neurotoxicity through modulations of oxidative, antioxidant activities, and mitochondrial protective (mitoprotective) effects.

Betanin inhibits PI3K/AKT/mTOR/S6 signaling pathway, cell growth and death in osteosarcoma MG-63 cells.

It is possible to develop new chemopreventive compounds so that cancer cells can be targeted in an exclusive manner. Bioactive natural compounds have demonstrated to be efficient chemotherapeutic agents, safe and cost-effective. Majority of anti-cancer medications are derived from natural sources, particularly of plant origins. Betanin (betanidin-5-O-ß-glucoside) is the most common betacyanin with antioxidant, anti inflammatory and anticancer properties. The present study therefore investigated the effect of betanin onosteosarcoma MG-63 cells. The mechanistic pathway of inflammatory responses, cell proliferation and apoptosis were investigated. The MG-63 cells were treated with betanin for 24 h. Betanin actions on the appearance of cell arrangements, morphological changes, ROS induced Δψm , cell migration, cell adhesion and proliferative mechanistic marker expression of PI3K/AKT/mTOR/S6were analyzed. Betanin inhibited MG-63 cells at IC50 concentrations between 9.08 and 54.49 µM and induced apoptosis by triggering the ROS mechanism. Betanin inhibited proliferation and migration of MG-63 cells and induced DNA fragmentation. Betanin also modified the key mediator expression levels of PI3K/AKT/mTOR/S6 signaling pathways. Betanin can potentially be utilized in bone carcinoma therapeutics to inhibit, reverse or delay osteosarcoma.

Isolation of High-Purity Betanin from Red Beet and Elucidation of Its Antioxidant Activity against Peroxynitrite: An in vitro Study.

Reactive oxygen species and reactive nitrogen species (RNS) are damaging for many biomolecules. Peroxynitrite (ONOO-) is the most toxic molecular species among RNS. Betalains are known to possess ONOO- scavenging ability. Betanin, a betalain isolated from red beet, possesses antioxidant, anti-inflammatory, and antitumor activities; however, detailed studies of this isolated pigment have not been conducted, owing to its instability under physiological conditions. This study aimed to isolate highly purified betanin from red beetroots using an improved purification method involving deproteinization and citric acid co-precipitation and evaluated its antioxidant activities. The purified betanin thus obtained had a significantly lower isobetanin content than the commercially available betanin dyes. The antioxidant activity of purified betanin examined in the 2,2-diphenyl-1-picrylhydrazyl assay, the direct ONOO- reaction, ONOO--dependent DNA damage, and lipid peroxidation reactions revealed that betanin possessed higher antioxidant capacity than general antioxidants such as ascorbic acid and quercetin. Furthermore, betanin showed indirect and direct cytoprotective effects against H2O2 and ONOO- cytotoxicity, respectively, in cultured mouse fibroblasts. To the best of our knowledge, this is the first study to demonstrate the cytoprotective effects of betanin against ONOO- toxicity. The highly purified betanin obtained in this study will aid in further exploring its physiological functions.

Anti-Amyloid ß Aggregation Activity and Cell Viability Effect of Betacyanins from Red Pitahaya (Hylocereus polyrhizus) for Alzheimer's Disease.

Betacyanin-rich extract from red beet (Beta vulgaris) was recently reported to inhibit amyloid ß (Aß) aggregation, a main pathological event in Alzheimer's disease. However, the anti-Aß aggregation effect of individual betacyanin isolates has not been reported before. This study investigated the anti-Aß aggregation activity and cytotoxicity of betacyanins from red pitahaya or red dragon fruit (Hylocereus polyrhizus). Betacyanin fraction (IC50 = 16.02 ± 1.15 µg/mL) and individual betacyanin isolates exhibited anti-Aß aggregation activity in a concentration-dependent manner using a thioflavin T fluorescence assay. The highest to lowest IC50 was in the order of betanin (426.30 ± 29.55 µM), phyllocactin (175.22 ± 1.52 µM), and hylocerenin (131.73 ± 5.58 µM), following a trend of increase in functional groups of carboxyl, hydroxyl, and/or carbonyl. Further, the betacyanin fraction of 135.78 µg/mL and below, which were concentrations with an anti-Aß aggregation effect, were validated as non-neurotoxic based on an in vitro cytotoxicity assay using human neuroblastoma (SH-SY5Y) cells. These findings highlight the potential neuroprotective activity of betacyanins for Alzheimer's disease.

Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats.

BACKGROUND: Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats' livers. METHODS: STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR. RESULTS: Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P < 0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P < 0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P < 0.015) except for the catalase (P = 0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P < 0.05) and decrease MDA levels (P < 0.001) compared to diabetic control group. CONCLUSIONS: Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.

Inhibition of scopolamine-induced memory and mitochondrial impairment by betanin.

Mitochondrial dysfunction and oxidative stress are identified to contribute to the mechanisms responsible for the pathogenesis of Alzheimer's disease (AD). Scopolamine (SCO) as a potent drug for inducing memory and learning impairment is associated with mitochondrial dysfunction and oxidative stress. In AD clinical trials molecules with antioxidant properties have shown modest benefit. Betanin as a multifunctional molecule with powerful antioxidative properties may be effective in the treatment of neurodegenerative. Hence, this study was designed to investigate the possible therapeutic effect of betanin against SCO-induced AD on Wistar rats. SCO (1 mg/kg) was administrated intraperitoneally to induce the AD in Wistar rats. The rats were treated with betanin doses (25 mg/kg and 50 mg/kg) intraperitoneally for 9 consecutive days. At the end of the 9th day, the animals were subjected to behavioral examination such as novel object recognition and passive avoidance tests and killed to study the mitochondrial and histological parameters. The results showed attenuation of SCO-induced memory and learning impairment by betanin at 50 mg/kg dose. Also, mitochondrial toxicity parameters such as mitochondrial membrane potential collapse, mitochondrial swelling, decreased activity of succinate dehydrogenase, and reactive oxygen species (ROS) production were reversed by betanin (50 mg/kg) compared to the SCO group. In addition, the ameliorative effect of betanin against SCO was demonstrated in histopathological results of hippocampus. The present investigation established that the betanin ameliorates the SCO-induced memory impairments, tissue injuries, and mitochondrial dysfunction by reducing mitochondrial ROS, which may be due to the potent antioxidant action of betanin.

Betanin alleviates inflammation and ameliorates apoptosis on human oral squamous cancer cells SCC131 and SCC4 through the NF-κB/PI3K/Akt signaling pathway.

Oral squamous cell carcinoma (OSCC) is the prime kind of human malignancy with a great mortality ratio and a deprived prognosis due to its high level of relapse and metastasis. Recently reported is that betanin exerts a preventive role and cytotoxic activity on numerous cancer cells. Betanin comprises the betalain group, which is a highly bioavailable antioxidant. However, the precise molecular actions of betanin in the OSCC cells are yet to be elucidated. It may be the first report on the antiproliferative and apoptotic molecular mechanisms of betanin on OSCC. The current study intended to explore the betanin activity and its underlying mechanisms on SCC131 and SCC4 cells. The cytotoxicity assay, intracellular ROS, MMP, cell apoptosis, and inflammatory mediators of betanin activity on SCC131 and SCC4 cells were evaluated by MTT assay, DCFH-DA, Rh-123, AO/EB, DAPI, PI, analysis of western blot and RT-PCR. The upshots indicated that betanin restrains the SCC131 cells proliferation, MMP and inflammation, whereas induces apoptosis via the enhanced ROS level of SCC131 and SCC4 cells in a dose-dependent mode. Also, betanin-treated OSCC cells reduce inflammatory and apoptotic signaling pathways. The above-mentioned results exposed that betanin can inhibit cell viability, MMP, inflammation and enhanced apoptosis via the expression of NF-κB/PI3K/Akt pathways. Thus, our current findings provided an innovative vision into the protective effect against OSCC.

Ameliorative effect of betanin on experimental cisplatin-induced liver injury; the novel impact of miRNA-34a on the SIRT1/PGC-1α signaling pathway.

The anticancer agent, cisplatin (CIS), is associated with hepatotoxic effects related to activation of oxidative stress and inflammation pathways. CIS-induced oxidative DNA damage reduces sirtuin 1 (SIRT1) activity, which in turn, modulates the activity of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). Moreover, microRNA-34a (miRNA-34a) was shown to hinder both SIRT1 and nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Thus, targeting such a pathway can alleviate CIS-induced hepatotoxicity. Betanin (BET) is a natural red glycoside food dye obtained from beets, which is reported to exhibit antioxidant function. However, its role in CIS-induced liver injury and the molecular mechanism has not been fully elucidated. Thus, the aim of this study was to investigate the ameliorative effect of BET on CIS-induced acute hepatotoxicity through the SIRT1/PGC-1α signaling pathway and illustrate the impact of miRNA-34a. Seventy-two rats were divided into six equal groups: (1) Control, (2) BET, (3) CIS, (4) CIS/BET, (5) CIS/EX527, and (6) CIS/BET/EX527. CIS-induced liver injury was evidenced by deregulated BAX and BCL2 levels, decreased levels of AMP-activated protein kinase and PGC-1α expression, and decreased SIRT1 activity. Consequently, reduced levels of Nrf2 and the expression of associated heme oxygenase-1 and glutamate-cysteine ligase modifier subunit were observed. Intriguingly, BET succeeded in reducing the CIS-induced liver injury through reducing miRNA-34a expression and enhancing the SIRT1/PGC-1α pathway. These findings coincide with the molecular docking results and the histopathological picture. In conclusion, the current research provided novel findings of the BET ameliorative effect on CIS-induced liver injury through modulating miRNA-34a expression and the SIRT1/PGC-1α signaling cascade.

Betanin Prevents Experimental Abdominal Aortic Aneurysm Progression by Modulating the TLR4/NF-κB and Nrf2/HO-1 Pathways.

Betanin, a bioactive ingredient mostly isolated from beetroots, exhibits a protective effect against cardiovascular diseases. However, its effects on abdominal aortic aneurysm (AAA) have not been elucidated. In this study, an AAA model was constructed by infusion of porcine pancreatic elastase in C57BL/6 mice. Mice were then administered with betanin or saline intragastrically once daily for 14 d. Our results showed that treatment with betanin remarkably limited AAA enlargement and mitigated the infiltration of inflammatory cells in the adventitia. The increased expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) was also significantly alleviated following betanin treatment. Furthermore, betanin suppressed the activation of toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) signaling in the aortic wall, and downregulated the levels of tissue-reactive oxygen species as well as circulating 8-isoprostane by stimulating the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Taken together, these data suggest that betanin may attenuate AAA progression and may be used as a therapeutic drug against AAA.

Betanin Attenuates Oxidative Stress Induced by 6-OHDA in PC12 Cells via SAPK/JNK and PI3 K Pathways.

Parkinson's disease is a neurodegenerative disorder which accompanied with cognitive decline, chorei form moves and behavioral difficulties. Oxidative stress which promote the apoptotic cell death are responsible for neurodegeneration in Parkinson. The purpose of this study is to evaluate the protective effects of betanin against toxicity and oxidative damage induced by 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Parkinson's cell damage. PC12 cells pretreated with betanin (1-200 µM) for 24 h, and exposed to either 6-OHDA (100 µM) or H2O2 (150 µM) for 24 h. Cell survival and intracellular reactive oxygen species (ROS) production analyzed by resazurin and DCF-DA assay. The anti-apoptotic effects of betanin in PC12 cells were studied using flow cytometry of PI stained cells. Also, western blot analysis of survivin, Cyt c, Phospho SAPK/JNK, SAPK/JNK, Phospho-PI3 kinase P85, PI3 kinase P85 was performed for detection of apoptosis. Betanin (1-200 µM) significantly decreased the 6-OHDA and H2O2 cytotoxicity also attenuated the ROS level. Cell apoptosis significantly increased after 6-OHDA (100 µM) treatment, compared to the control. However, pretreatment with betanin (20 and 50 µM), protected against apoptosis. Western blot analysis of PC12 cells showed that 100 µM 6-OHDA could increase the proteins involved in apoptosis signaling and betanin (20 and 50 µM), could decrease the apoptosis. The results show that betanin has antioxidant and anti-apoptotic effects and may have the ability to prevent or delay the progress of neural death in Parkinson's disease.

Impact of betanin against paracetamol and diclofenac induced hepato-renal damage in rats.

Context: Paracetamol (PAR) and diclofenac (DF) are the most popular consumed analgesics and anti-inflammatory medications.Objective: This study aimed to explore the protective effect of betanin (Bet) against PAR or DF induced hepato-renal damage in rats.Methods: Rats were randomly divided into five groups: Normal control (NC) group rats were given saline only. PAR group rats received PAR (400 mg/kg). PAR/Bet treated group rats administered PAR (400 mg/kg) plus Bet (25 mg/kg). DF group rats received DF (10 mg/kg). DF/Bet treated group rats administered DF (10 mg/kg) plus Bet (25 mg/kg). All drugs were given by gavage for 28 consecutive days.Results: PAR and DF administration in high dose and long-time induced liver and kidney injury, disrupted serum lipid profile, enhanced serum levels of inflammatory and oxidative stress markers, triggered DNA fragmentation and caused drastic changes in the histopathological pictures of the two organs. Bet supplementation succeeded to ameliorate most of the biochemical changes and protected DNA from damage as obtained from comet assay. Histological features in H&E taken to different groups also mirrors this findings.Conclusion: Bet exerted a potential anti-inflammatory and antioxidant effect against hepato-renal damage induced by PAR or DF overconsumption.

The protective effect of betanin and copper on heart and lung in end­organ ischemia reperfusion injury.

OBJECTIVES: Betanin and copper sulphate have been previously indicated as beneficial agents for ischemia/reperfusion (I/R) as antioxidant compounds in various models. We investigated whether betanin and copper have any protective effects on the heart and lung against I/R injury in rats. METHODS: Spraque-Dawley rats were assigned in groups: Sham (laparotomy only), control (I/R only), betanin treatment (100 mg/kg of betanin administered intraperitoneally (i.p.) 60 minutes before I/R) and copper sulfate treatment group (0.1 mg/kg/day copper sulfate i.p. for 7 days before I/R). Ischemia was induced by clamping the aorta between the left renal artery and aortic bifurcation for 45 minutes. After 48-hour reperfusion, the rats were sacrificed and heart/lung tissues were harvested. Malondialdehyde (MDA), myeloperoxidase (MPO), interleukin 6 (IL-6) levels were determined. Apoptosis was determined via TUNEL assay. RESULTS: MDA, MPO, IL-6 levels and apoptotic cells were significantly increased in the I/R group. In both treatment groups, MDA and MPO levels were decreased. IL-6 was significantly decreased in response to betanin administration in the heart, but not in the lung; copper had no effect in either area. The numbers of apoptotic cells were significantly decreased in both treatment groups. CONCLUSION: Betanin and copper may have protective effects on I/R injury in the heart and lung in rats (Fig. 6, Ref. 39).

The effect of Betanin parenteral pretreatment on Jejunal and pulmonary tissue histological architecture and inflammatory response after Jejunal ischemia-reperfusion injury.

Intestinal ischemic-reperfusion (IR) injury has detrimental effects on both local and distant organs in the body. Betanin is known for its antioxidant properties, and it is found mostly in vegetables. Therefore, the aim of the present study was to test the hypothesis that betanin administration prior intestinal IR, may be beneficial in protecting jejunal mucosa and lung parenchyma against IR damage. Male specific pathogen-free Charles River Wistar rats were used (n = 42). Betanin (50 mg/kg) was administered intraperitoneally 30 min before ischemia of the superior mesenteric artery lasting 1 h, followed by 1, 4 and 24 h of reperfusion. Immunohistochemical as well as histomorphometrical analysis indicated a protective effect of betanin pretreatment on jejunal tissue. Regarding morphometrical analysis betanin significantly (p < 0.01) augments intestinal villus height after 24 of reperfusion comparing to early stages. Betanin application reduced number of mast cells population in early reperfusion periods (p < 0.05). The protective effect of betanin on lung parenchyma, was detected in late reperfusion period (24 h) with improvement of histopathological injury index and morphometric analysis (p < 0.001 for both). The improvement of histopathological injury index (p < 0.001) and morphometric analysis (p < 0.001) during the late reperfusion period, suggests a protective effect of betanin on lung parenchyma. Moreover, suppression of the inflammatory response was mirrored by the reduction of myeloperoxidase (MPO) positive cells within lung parenchyma after 1 and 4 h of reperfusion (p < 0.001). Especially, during the first 4 h of reperfusion after betanin administration, a reduction of 74% of the polymorphonuclear neutrophils infiltration (MPO positive cell population) and of a nearly 46% of active MCs was observed. Upon morphometric examination, the lung histological architecture after 24 h of reperfusion appeared to be almost 100% better following betanin treatment, with 25% thinner interalveolar septa and 20% larger alveolar surface for respiratory gas exchange. The results suggest that betanin pretreatment protects the jejunal mucosa and the lung parenchyma, as well as reduces the inflammatory cell density after intestinal IR injury.

Protective effects of betanin against paracetamol and diclofenac induced neurotoxicity and endocrine disruption in rats.

Context: Overconsumption of paracetamol (PAR) and diclofenac (DF) have been reported to induce neurotoxicity and endocrine disruption. Objective: The current study was designed to explore the protective potential of betanin against PAR and DF inducing neurotoxicity and endocrine disruption in a rat model. Material and Methods: Forty rats were equally divided into five groups: group I served as control, group II received PAR (400 mg/kg), group III received PAR plus betanin (25 mg/kg), group IV received DF (10 mg/kg) and group V received DF plus betanin orally for 28 consecutive days. Thyroid axis hormones, sex hormone, neurotransmitters, paraoxonase-1, hemeoxygenase-1 and nuclear factor-2 were measured by ELISA. While, the oxidative stress markers were colorimetrically estimated. Moreover, DNA damage and histopathological picture of the brains were investigated. Results: A marked reduction in thyroid axis hormones, brain neurotransmitters and serum testosterone as well as enhanced oxidative stress and brain DNA damage accompanied by drastic changes in the brain histopathological picture were recorded in the challenged PAR and DF groups. Betanin supplementation ameliorated most of the biochemical and histopathological changes induced by PAR or DF. Conclusion: The study suggests betanin of potential protective effects against neurotoxicity and endocrine disruption induced by PAR and DF overconsumption.

Biofilm inhibiting activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms.

AIMS: To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. METHODS AND RESULTS: The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml-1 ) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml-1 ) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability. CONCLUSION: Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections.

Betanin, a Natural Food Additive: Stability, Bioavailability, Antioxidant and Preservative Ability Assessments.

Betanin is the only betalain approved for use in food and pharmaceutical products as a natural red colorant. However, the antioxidant power and health-promoting properties of this pigment have been disregarded, perhaps due to the difficulty in obtaining a stable chemical compound, which impairs its absorption and metabolism evaluation. Herein, betanin was purified by semi-preparative HPLC-LC/MS and identified by LC-ESI(+)-MS/MS as the pseudomolecular ion m/z 551.16. Betanin showed significant stability up to -30 °C and mild stability at chilling temperature. The stability and antioxidant ability of this compound were assessed during a human digestion simulation and ex vivo colon fermentation. Half of the betanin amount was recovered in the small intestine digestive fluid and no traces were found after colon fermentation. Betanin high antioxidant ability was retained even after simulated small intestine digestion. Betanin, besides displaying an inherent colorant capacity, was equally effective as a natural antioxidant displaying peroxy-radical scavenger ability in pork meat. Betanin should be considered a multi-functional molecule able to confer an attractive color to frozen or refrigerated foods, but with the capacity to avoid lipid oxidation, thereby preserving food quality. Long-term supplementation by beetroot, a rich source of betanin, should be stimulated to protect organisms against oxidative stress.