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.

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.

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.

Betanin exhibits significant potential as an antihyperglycemic and attenuating the glycoprotein components in streptozotocin-nicotinamide-induced experimental rats.

This study hypothesized to evaluate the effect of betanin, a chromoalkaloid on plasma and altered tissues glycoprotein components in streptozotocin-nicotinamide-induced diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin (45 mg/kg b.w.) dissolved in 0.1 M citrate buffer (pH 4.5) 15 min after the i.p. administration of nicotinamide (110 mg/kg b.w.). Experimental rats were administered betanin at the dose of 20 mg/kg b.w. and glibenclamide (600 µg/kg b.w.) once a day for 30 days. Diabetic rats revealed significant (p < 0.05) increase in the levels of glucose, HbA1C, hexose, hexosamine, sialic acid and fucose in the plasma; decrease in the levels of plasma insulin, Hb and sialic acid in the liver and kidney; significant (p < 0.05) increase in hexose, hexosamine and fucose in the liver and kidney. Moreover, periodic acid-Schiff staining of tissues revealed positive-stain accumulation in diabetic rats. On co-supplementation of betanin and glibenclamide to diabetic rats for the period of 30 days brought back the levels of plasma and tissues glycoprotein components. Based on the present study, we propose that betanin possesses significant protective effect on glycoprotein components in plasma and tissue of diabetic rats.

Ameliorating effect of betanin, a natural chromoalkaloid by modulating hepatic carbohydrate metabolic enzyme activities and glycogen content in streptozotocin - nicotinamide induced experimental rats.

Betanin, a chromoalkaloid of beetroot, has shown significant biological effects of antioxidants, anti-inflammatory and anticarcinogenic activities. So, we attempted to determine whether betanin (a natural pigment) would be protective against hyperglycemia in streptozotocin (STZ) - nicotinamide (NA) induced diabetic rats. Rats were injected with STZ (40mg/kgb.w.) 15 mins after the administration of NA (110mg/kgb.w.) by intraperitonially (i.p.) 30days for the induction of experimental diabetes mellitus. After 72h diabetic rats were treated with betanin orally at a doses of 10, 20 and 40mg/kg b.w., respectively in a dose dependent manner and glibenclamide (600µg/kgb.w.). The promising character of betanin against diabetic rats was evaluated by performing the various biochemical parameters and histomorphological changes in liver and pancreas. Among the three doses, 20mg/kgb.w. of betanin was able to positively regulate plasma glucose, insulin, glycosylated hemoglobin (HbA1c) and hemoglobin (Hb) levels by significantly increasing the activity of glycolytic enzyme (glucokinase and pyruvate kinase), glucose-6-phosphate dehydrogenase and significantly decreasing the activity of gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-bisphosphatase) thereby increasing the glycogen content in the liver. We put forward that betanin could significantly restore the levels of carbohydrate metabolic key enzymes to near normal in diabetic rat. Immunohistochemical observation of pancreas revealed that betanin treated diabetic rats showed increased insulin immunoreactive ß-cells, which confirmed the biochemical findings. Taken together, present study suggests that betanin modulates the carbohydrate metabolism and has beneficial effects in glucose homeostasis.

Betanin attenuates carbon tetrachloride (CCl4)-induced liver injury in common carp (Cyprinus carpio L.).

This study investigates the protective effect of betanin against liver injury induced by carbon tetrachloride (CCl4) in common carp (Cyprinus carpio L.). The fish were treated with 1, 2, and 4 % betanin in fodder throughout the experiment. After 20 days of treatment, the fish were intraperitoneally injected with 20 % (v/v in peanut oil) CCl4 at a volume of 0.5 mL/kg body weight. The fish were killed 3 days after CCl4 intoxication, and then, histological and biochemical assays were performed. Results showed that CCl4-induced liver CYP2E1 activity, oxidative stress, and injury, as indicated by the depleted glycogen storage, increased serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activities and liver histological damage. Compared with the CCl4 control group, the betanin-treated groups exhibited reduced CYP2E1 activity, decreased malondialdehyde level, increased liver antioxidative capacity (increased glutathione level and superoxide dismutase and catalase activities), increased liver glycogen storage, and reduced serum AST/ALT activities, with significant differences in the 2 and 4 % groups (p < 0.05). Histological assay further confirmed the protective effect of betanin. In conclusion, betanin attenuates CCl4-induced liver damage in common carp. Moreover, the inhibition of CYP2E1 activity and oxidative stress may have significant roles in the protective effect of betanin.

Betanin a betacyanin pigment purified from fruits of Opuntia ficus-indica induces apoptosis in human chronic myeloid leukemia Cell line-K562.

Betalains are water-soluble nitrogenous vacuolar pigments present in flowers and fruits of many caryophyllales with potent antioxidant properties. In the present study the antiproliferative effects of betanin, a principle betacyanin pigment, isolated from the fruits of Opuntia ficus-indica, was evaluated on human chronic myeloid leukemia cell line (K562). The results show dose and time dependent decrease in the proliferation of K562 cells treated with betanin with an IC(50) of 40 microM. Further studies involving scanning and transmission electron microscopy revealed the apoptotic characteristics such as chromatin condensation, cell shrinkage and membrane blebbing. Agarose electrophoresis of genomic DNA of cells treated with betanin showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 40 microM betanin showed 28.4% of cells in sub G0/G1 phase. Betanin treatment to the cells also induced the release of cytochrome c into the cytosol, poly (ADP) ribose polymerase (PARP) cleavage, down regulation Bcl-2, and reduction in the membrane potentials. Confocal microscopic studies on the cells treated with betanin suggest the entry of betanin into the cells. These studies thus demonstrate that betanin induces apoptosis in K562 cells through the intrinsic pathway and is mediated by the release of cytochrome c from mitochondria into the cytosol, and PARP cleavage. The antiproliferative effects of betanin add further value to the nutritional characteristics of the fruits of O. ficus-indica.