Pelargonidin Research Articles

Exploring a new phyto-derived nanoparticle for targeting bacterial protein EF-Tu: an integrated approach to develop antimicrobial drug

ABSTRACT The application of antibiotic medicine to save numerous lives is in jeopardy due to the alarming elevation in antibiotic-resistant organisms as a consequence of improper and imprudent usage of antibiotics. This study investigated the antibacterial efficacy of pelargonidin (PG) by employing a cost-effective nano-formulation-based targeted drug delivery system as an alternative to conventional strategies. The precise targeting of bacteria was made easier by synthesizing nano-particles of phyto-product pelargonidin (NPG) by employing poly-lactide-co-glycolide (PLGA), a biodegradable polymer. The physico-chemical characterization of NPGs was performed via AFM study and the antibacterial efficacy of NPGs tested against Escherichia coli and Staphylococcus aureus was assessed by agar disc diffusion method. Additionally, the docking platform explored in this study enabled the prediction of the ability of PG to occupy the binding pocket of EF-Tu (elongation factor thermo unstable), a vital bacterial protein that operates on a translational level. The overall results implicate that NPG was an effective drug candidate against the gram-negative bacteria E. coli and the gram-positive bacteria S. aureus according to the diameter of the inhibition zone (23 ± 0.82 mm: E. coli and 22.67 ± 1.25 mm: S. aureus). Furthermore, in silico analysis revealed that the NPG-EF-Tu complex had an excellent docking score of −9.13 Kcal/mol, indicating key amino acid residues required for interaction, and anticipating the signaling component/s involved that may be hindered by NPG, thereby leading to a decline of bacterial growth. The core phyto-compound of NPG (pelargonidin) could effectively bind to EF-Tu thereby exercising strong antimicrobial efficacy against both E. coli and S. aureus making it a potential alternative to the usage of commercial antibacterials with a history of drug-resistance.

Pelargonidin ameliorates inflammatory response and cartilage degeneration in osteoarthritis via suppressing the NF-κB pathway

Pelargonidin (PG), a derivative of anthocyanins, has anti-oxidant and anti-inflammatory properties. Herein, the protective effect and the mechanism of PG in counteract the osteoarthritis (OA) progression were needed to further evaluate. In the current study, C57BL/6 mice was induced by destabilization of medial meniscus (DMM) surgery to establish the OA model. Primary chondrocytes were acquired from the knee cartilage of newborn mice. Then, PG was administrated to OA mice and IL-1β-stimulated chondrocytes to evaluate its protective effects, respectively. Results uncovered that no conspicuous cytotoxic effects were observed when chondrocytes were treated with PG at a concentration lower than 40 μM for 24–72 h. Thus, 10 μM, 20 μM, and 40 μM PG were chosen for subsequent experiments in vitro. Then, we observed that 10, 20, and 40 μM PG reduced the levels of IL-6, TNF-α, COX-2 and iNOS in chondrocytes. In line, PG inhibited the IL-1β-induced ECM catabolism in chondrocytes, as evidenced by deepening toluidine blue staining, increased expression of Collagen II, and decreased expressions of ADAMTS5 and MMP13. Moreover, PG also reduced the IL-1β-stimulated p-p65 overexpression and nuclear translocation of p65 in chondrocytes. In vivo, Safranin O/Fast green and HE staining showed that articular cartilage surface morphology was basically smooth and complete after PG treatment for 8 weeks. Similarly, OARSI scores and MMP13 expression were apparently decreased, whereas Aggrecan expression was elevated in PG-treated mice 8 weeks after DMM surgery. In conclusion, PG can effectively ameliorate inflammatory reactions and cartilage degeneration via suppressing the NF-κB pathway, thereby restraining the OA progression.

Protective Effects of Pelargonidin against DMBA-Induced Mammary Tumorigenesis in BALB/c Mice through Reduced Oxidative Stress and Lipid Anomalies

Among luminal types of breast cancers, ER + breast cancer is the most frequently diagnosed cancer globally. ER + breast cancer is commonly treated with SERM drugs that block ER to prevent ER-mediated cancerous growth. Our previous computational screening found pelargonidin (PG) can inhibit ER-signaling with potent bioactivity and satisfactory toxicological features. The present study explored the anti-tumoral prospect of PG against DMBA-induced ER + murine mammary carcinogenesis. The female BALB/c mice were divided into control (A) and DMBA-exposed groups. Following tumor appearance, the DMBA-exposed group was divided into five groups: tumor control, PG-treated (Groups P25, P50, and P100), and tamoxifen-treated (TAM). The results indicated that PG-treatment dose-dependently reduced the mean tumor volume, reinstated body weight loss, and enhanced the percentage survival of tumor-bearing mice. In addition, we recorded a significant reduction in LPO, total cholesterol, and triglycerides and a surge in the activity of antioxidases and phase II detoxifying enzymes in PG-treated animals. PG also dose-dependently increased the serum level of unbound estradiol, an indicator of competitive ER binding by an ER agonist/antagonist. These data suggest that pelargonidin has potent anticancer potential against the animal model of ER + breast cancer that matches the efficiency of tamoxifen with conceivably fewer side effects.

Interaction mechanism of pelargonidin against tyrosinase by multi-spectroscopy and molecular docking.

The interaction mechanism of pelargonidin (PG) with tyrosinase was investigated by multi-spectroscopy and molecular docking. As a result, PG had strong inhibitory activity on tyrosinase with the IC50 value of 41.94 × 10-6 mol·L-1 . The inhibition type of PG against tyrosinase was determined as a mixed-mode. Meanwhile, the fluorescence of tyrosinase was quenched statically by PG, and accompanied by non-radiative energy transfer. The three-dimensional (3-D) fluorescence, ultraviolet-visible spectroscopy (UV-Vis) and circular dichroism spectroscopies (CD) indicated that PG decreased the hydrophobicity of the micro-environment around tryptophan (Trp) and tyrosine (Tyr), which resulted in the conformational change of tyrosinase. In addition, fluorescence and molecular docking analysis indicated that PG bound to tyrosinase via hydrogen bonds (H-bonds) and van der Waals force (vdW force). We herein recommended that PG might be a potential candidate drug for the treatment of melanin-related diseases.

Pelargonidin ameliorates reserpine-induced neuronal mitochondrial dysfunction and apoptotic cascade: a comparative in vivo study

Background Targeting the neuronal mitochondria as a possible intervention to guard against neurodegenerative disorder progression has been investigated in the current work via the administration of pelargonidin (PEL) to rats intoxicated by the mitochondrial toxin reserpine. The main criteria for choosing PEL were its reported antioxidant, anti-apoptotic and anti-inflammatory activities. Methods Male albino Wistar rats were randomized into five experimental groups; normal control, reserpinized to induce mitochondrial failure, standard PARP-1-inhibitor 1,5-isoquinolinediol (DIQ)-treated reserpinized, PEL-treated reserpinized, and GSK-3β inhibitor (AR-A 014418) -treated reserpinized. Results PEL administration reversed the reserpine-induced abnormal behaviors marked by decreased catalepsy time. In addition, PEL restored brain glutathione with a reduction in nitric oxide content as compared to the reserpine-challenged group. Meanwhile, it improved neuronal mitochondrial function by the elevation of complex I activity associated with a low ADP/ATP ratio. Likely through its anti-inflammatory effect, PEL reduced the elevation of serum interleukin-1ß level and inhibited serum lactate dehydrogenase activity. These findings are aligned with the reduced expression of cleaved PARP and cleaved caspase-3 proteins, indicating PEL’s suppressive effect on the intrinsic apoptotic pathway. Those biochemical findings were confirmed through comparable histopathological tissue examination among the experimental groups. Conclusions In conclusion, PEL is a promising candidate for future use in the management of mitochondria-associated neuronal complications via controlling the ongoing inflammatory and degeneration cascades.

Protective effect of chronic administration of pelargonidin on neuronal apoptosis and memory process in amyloid-beta-treated rats.

Objective:Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with impaired cognitive skills and learning and memory dysfunctions. It has been suggested that pelargonidin (PG), as an antioxidant agent, has a neuroprotective effect. PG could prevent damaging effects of amyloid-beta (Aβ) deposition. The aim of this study was to determine the chronic effect of PG on hippocampal neurons and memory processes in a rat model of AD.Materials and Methods:Twenty-eight male adult rats were divided into sham, AD, AD+PG (5 μg, intracerebroventricular), and PG (5 μg, intracerebroventricular) groups. Intracerebroventricular (ICV) injection of Aβ peptides (6 μg) was done using stereotaxic surgery. ICV administration of PG or saline was performed daily for 28 consecutive days. Behavioral analysis was performed using the novel object recognition (NOR) and passive avoidance tests. Neuronal apoptosis was detected using TUNEL assay in the hippocampus. Results:The ICV injection of Aβ reduced step-through latency and discrimination index in behavioral tests (p<0.001). Aβ increased the number of apoptotic neurons (p<0.001). PG treatment decreased the time spent in the dark compartment and neuronal apoptosis in the AD+PG rats (p<0.001). PG increased the discrimination index in the NOR test (p<0.001). Although PG did not change behavioral variables, it decreased cell death in the PG group.Conclusion:PG attenuated neuronal apoptosis and improved cognition and memory deficiency in AD rats. The protective effect of PG against Aβ may be due to its anti-apoptotic property. It is suggested that PG can be useful to treat AD.

“Pelargonidin mediated selective activation of p53 and parp proteins in preventing food additive induced genotoxicity: an in vivo coupled in silico molecular docking study”

Food-additive toxicity has become a major health hazard issue globally. Alloxan (ALX), a food-additive, intaken daily through flour causes diabetes and genotoxicity by inducing chromosomal-aberration and DNA-damage. The use of phytochemicals as a protective measure of health hazards has become quite evident because of their least side effects. Pelargonidin (PG), one such phyto-product, have an anti-genotoxic and anti-diabetic effect. In this study, the possibility of PG to inhibit alloxan-induced chromosomal-aberration and DNA-damage was assessed in mice model in vivo and the experimental outcome was validated theoretically through in silico structure-based molecular docking study. Results of the mitotic-index observed from the PG-pre-treated-alloxan-administered (PG+ALX) mice group revealed a significant reduction in chromosomal-anomaly, DNA-damage, and an upregulation of the p53 and PARP protein expression when compared to the ALX-treated mice group. Additionally, the in silico molecular docking study predicted the biochemical mechanism of actions of pelargonidin by identifying the two important amino acid residues p53 and PARP as the active bio-targets of pelargonidin. Therefore, results of our present in vivo and silico studies implicate that pelargonidin could effectively restrict DNA-damage and chromosomal-aberration by modulating PARP and p53 repair proteins showing its ability for possible protein-drug interaction, an effective therapeutic tool in future drug discovery.

Identifying Active Compounds and Targets of Fritillariae thunbergii against Influenza-Associated Inflammation by Network Pharmacology Analysis and Molecular Docking.

Complications due to influenza are often associated with inflammation with excessive release of cytokines. The bulbs of Fritillariae thunbergii (FT) have been traditionally used to control airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate active compounds, the targets, and underlying mechanisms of FT for the treatment of influenza-induced inflammation, systems biology was employed. Active compounds of FT were identified through the TCMSP database according to oral bioavailability (OB) and drug-likeness (DL) criteria. Other pharmacokinetic parameters, Caco-2 permeability (Caco-2), and drug half-life (HL) were also identified. Biological targets of FT were retrieved from DrugBank and STITCH databases, and target genes associated with influenza, lung, and spleen inflammation were collected from DisGeNET and NCBI databases. Compound-disease-target (C-D-T) networks were constructed and merged using Cytoscape. Target genes retrieved from the C-D-T network were further analyzed with GO enrichment and KEGG pathway analysis. In our network, GO and KEGG results yielded two compounds (beta-sitosterol (BS) and pelargonidin (PG)), targets (PTGS1 (COX-1) and PTGS2 (COX-2)), and pathways (nitric oxide, TNF) were involved in the inhibitory effects of FT on influenza-associated inflammation. We retrieved the binding affinity of each ligand-target, and found that PG and COX-1 showed the strongest binding affinity among four binding results using a molecular docking method. We identified the potential compounds and targets of FT against influenza and suggest that FT is an immunomodulatory therapy for influenza-associated inflammation.

Pelargonidin ameliorates CCl4-induced liver fibrosis by suppressing the ROS-NLRP3-IL-1β axis via activating the Nrf2 pathway.

Liver fibrosis is a histological change that often occurs due to hepatic stellate cell (HSC) activation and excessive formation of an extracellular matrix in the liver. Pelargonidin (PEL) is a natural anthocyanidin existing in blueberries, berries, strawberries, and red radishes and has been demonstrated to possess health beneficial effects. Herein, we investigated the effect of PEL on liver fibrosis induced by CCl4 and hepatic stellate cells induced by transforming growth factor-β (TGF-β). We found that PEL administration prevented liver injury and liver fibrosis induced by CCl4 in a dose-dependent manner. Further data revealed that PEL increased liver nuclear factor E2-related factor 2 (Nrf2) and reduced liver oxidative stress and the expression levels of NLRP3, caspase-1 and IL-1β. In TGF-β-challenged HSCs (LX-2 cells), PEL effectively inhibited the LX-2 cell activation. In addition, the anti-fibrosis effects of PEL in LX-2 cells were abolished by Nrf2 knockdown. In summary, our study demonstrated that PEL ameliorated CCl4-induced liver fibrosis and HSC activation induced by TGF-β. The possible molecular mechanisms of PEL in liver fibrosis may be attributed to its suppression of ROS-NLRP3-IL-1β signaling by Nrf2 activation.

Suppressive effects of pelargonidin on lipopolysaccharide-induced inflammatory responses

Pelargonidin (PEL) is a well-known red pigment found in plants, and has been reported as having important biological activities that are potentially beneficial for human health. Here, we tested the possible use of PEL in the treatment of lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The anti-inflammatory activities of PEL were determined by measuring permeability, neutrophils adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and mice. We found that PEL inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of neutrophils to human endothelial cells. PEL also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore, PEL suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with PEL resulted in reduced LPS-induced lethal endotoxemia. These results suggest that PEL possesses anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

Pelargonidin Protects Against Renal Injury in a Mouse Model of Sepsis.

Pelargonidin (PEL) is a well-known red pigment found in plants, and it has been reported to have important biological activities that are potentially beneficial for human health. This study was initiated to determine whether PEL could modulate renal functional damage in a mouse model of sepsis, and to elucidate the underlying mechanisms. The potential of PEL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase (GSH-Px) activity, catalase activity, and superoxide dismutase (SOD) activity. Treatment with PEL resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, PEL inhibited nuclear factor-κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. PEL treatment also reduced the plasma levels of interleukin-6 and tumor necrosis factor-α reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of SOD, GSH-Px, and catalase in kidney tissues. These results suggested that PEL protects mice against sepsis-triggered renal injury.

Inhibitory Effect of Pelargonidin on Secretory Group IIA Phospholipase A2

The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) has been shown to be elevated in various inflammatory diseases, and lipopolysaccharide (LPS) up-regulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Pelargonidin (PEL) is a well-known red pigment found in plants, and has been reported as having important biological activities that are potentially beneficial for human health. Here, PEL was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mouse. Post treatment of cells or mouse with PEL inhibited LPS-induced expression and activity of sPLA2-IIA. Therefore, these results suggest that PEL inhibited LPS mediated expression of sPLA2-IIA.

Protective Effects of Pelargonidin on Lipopolysaccharide-induced Hepatic Failure

Pelargonidin (PEL) is a well-known red pigment found in plants and has important biological activities that are potentially beneficial for human health. The aim of this study was to investigate the effect of PEL on lipopolysaccharide (LPS)-induced liver failure in mice, and to elucidate its underlying molecular mechanisms. Liver failure was induced by LPS (15 mg/kg, i.p) in mice, and 12 h later, they were treated intravenously with PEL. Administration of LPS significantly increased mortality, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and inflammatory cytokines, and expression of toll-like receptor 4 (TLR4) protein; PEL treatment effectively countered these effects of LPS. Further, LPS treatment markedly increased the expression of myeloid differentiation primary response gene 88 (MyD88), phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), and expressions of nuclear proteins, such as nuclear factor (NF)-κB and phosphorylated c-Jun. Additionally, LPS increased the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. All these effects of LPS were attenuated by PEL. In addition, the LPS-mediated increase in the level of serum interferon (IFN)-β expression of the TLR-associated activator of IFN (TRIF) protein, and phosphorylation of IFN regulator factor 3 (IRF3) were reduced by PEL. Our results suggest that PEL attenuates LPS-induced liver damage by inhibition of the TLR-mediated inflammatory pathway and could be used to treat liver diseases.

Comparison of microwave assisted extraction with hot reflux extraction in acquirement and degradation of anthocyanin from powdered blueberry

Abstract: Acquirement and degradation kinetics of anthocyanin from powdered blueberry were studied to analyze the degradation reason and improve the yield of anthocyanin under microwave assisted extraction (MAE) conditions. Hot reflux extraction (HRE) method was employed as a reference with MAE to discriminate the influences of the microwave irradiation under the same extraction temperature at 30°C-70°C. Ethanol was selected as extraction solvent. Microwave volumetric heating improves the diffusion and solubility of anthocyanin within powdered blueberry particles in the pre-heating period. The kinetic coefficients, in terms of delivery kinetic and diffusion kinetic, are lower in MAE than that in HRE. Four anthocyanins including delphinidin, cyanidin, malvidin and pelaronidin were detected in the anthocyanin extracts from blueberry. Delphinidin, cyaniding, and pelargonidin contents significantly decrease, but malvidin was unchanged in MAE. Anthocyanin yield increases with elevating extraction temperatures, but anthocyanin degradation occurred at 41.2°C. The acquirement amount of anthocyanin is lower than its degradation amount when microwave extraction temperature is higher than 53.6°C. The self-aggregation of anthocyanin molecules and degradation results in the reduction of anthocyanin yield extracted from blueberry powder. In MAE, microwave volumetric heating results in the rapidly elevated temperature in pre-heating stage and generation of internal pressure to improve the acquirement of anthocyanin and the non-thermal effect from microwave field may weak the effect of temperature to decline the degradation of anthocyanin to monomer. The non-thermal microwave irradiation has pronounced effects compared to the effects of temperature on the structure changes of anthocyanin molecules at extraction temperature below 50°C. In HRE, convection mode of heat transfer in extraction system form the non-uniform distribution of temperature in the extraction vials to decrease the acquirement yield of anthocyanin from the blueberry powder. The research results provide valuable data to optimize extraction temperature for high extraction yield and bioactivity of anthocyanin in microwave extraction process. Keywords: blueberry, microwave, anthocyanin, degradation, extraction, temperature, kinetic DOI: 10.3965/j.ijabe.20160906.2724 Citation: Sun Y, Xue H K, Liu C H, Liu C, Su X L, Zheng X Z. Comparison of microwave assisted extraction with hot reflux extraction in acquirement and degradation of anthocyanin from powdered blueberry. Int J Agric & Biol Eng, 2016; 9(6): 186－199.

Suppressive effects of pelargonidin on PolyPhosphate-mediated vascular inflammatory responses.

Previous reports suggest that human endothelial cells-derived PolyPhosphate (PolyP) is one of the pro-inflammatory mediators. As a well-known red pigment and found in plants, Pelargonidin (PEL) has been known to have several biological activates which are beneficial for human health. This study was undertaken to investigate whether PEL can modulate PolyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of PEL were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in PolyP-activated HUVECs and mice. In addition, the beneficial effects of PEL on survival rate in PolyP-injected mice. We found that PEL inhibits PolyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, PolyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by PEL in HUVECs. These anti-inflammatory functions of PEL were confirmed in PolyP injected mice. These results suggest that PEL have therapeutic potential for various systemic inflammatory diseases.

Anti-inflammatory effects of pelargonidin on TGFBIp-induced responses.

Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types in response to TGF-β. TGFBIp is released by human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. Pelargonidin (PEL) is a well-known red pigment found in plants, and has been reported as having important biological activities that are potentially beneficial for human health. This study was undertaken to investigate whether PEL can modulate TGFBIp-mediated inflammatory responses in HUVECs and in mice. The anti-inflammatory activities of PEL were determined by measuring permeability, leukocyte adhesion and migration, and activation of proinflammatory proteins in TGFBIp-activated HUVECs and mice. In addition, the beneficial effects of PEL on survival rate in a mouse sepsis model were tested. We found that PEL inhibited TGFBIp-induced barrier disruption, expression of cell adhesion molecules and adhesion/transendothelial migration of neutrophils to human endothelial cells. PEL also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggest that PEL possesses anti-inflammatory properties that result in inhibition of hyperpermeability, expression of cell adhesion molecules, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

Anti-septic effects of pelargonidin on HMGB1-induced responses in vitro and in vivo.

A certain nucleosomal protein-high mobility group box-1 (HMGB1)-has recently been established as a late mediator of sepsis, with a relatively wide therapeutic window for pharmacological intervention. Pelargonidin (PEL) is a well-known red pigment found in plants; it has important biological activities that are potentially beneficial for human health. In the present study, we investigated whether PEL can modulate HMGB1-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of PEL were determined by measuring permeability, leukocyte adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice, as well as the beneficial effects of PEL on survival rate in the mouse sepsis model. The data showed that PEL had effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1 and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. Furthermore, PEL inhibited the HMGB1-mediated production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), as well as the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Collectively, these results indicate that PEL could be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.

Impact of Anthocyanidins on Mitoxantrone-Induced Cytotoxicity and Genotoxicity: An In Vitro and In Vivo Analysis.

Hypothesis. Anthocyanins possess well-known biological effects and suppress DNA damage induced by therapeutic topoisomerase poisons. Our study focusses on the modulatory effects of anthocyanidins—malvidin (MAL) and pelargonidin (PEL)—on topoisomerase II poison mitoxantrone (MXT)-induced cytotoxicity and genotoxicity in in vitro and in vivo conditions. Study design. HepG2 cells were treated with MXT (1-10 µM), MAL (10-100 µM,) and PEL (5-640 µM) to determine cell viability. Further, experiments on cytotoxicity and apoptosis induction by single agents or combinations were performed. In vitro and in vivo antigenotoxic effect of MAL/PEL against MXT was evaluated in human lymphocytes and mouse bone marrow cells. Methods. Cytotoxicity of test agents and apoptosis induction in HepG2 cells was assessed by MTT assay, trypan blue dye exclusion assay and Hoechst 33258 staining. Antigenotoxic effects of MAL/PEL against MXT were assessed in co-treated human lymphocytes and bone marrow from mice that received MXT intraperitoneally 30 minutes post MAL/PEL oral administration Results. Dose-dependent cytotoxicity was observed with all 3 test agents in HepG2 cells. Highest test concentration of 100 µM MAL, 640 µM PEL, and 10 µM MXT decreased HepG2 cell viability by 80%, 30%, and 90%, respectively. The combination of 1 µM MXT + 80 µM MAL reduced cell viability better than single agents. MAL/PEL treatment significantly reduced MXT-induced genotoxicity in human lymphocytes and micronuclei formation in mice. Conclusion. Combination of MAL/PEL with lower doses of MXT, especially MAL+MXT increases the cytotoxicity in cancer cells. In addition, MXT treatment with MAL/PEL reduced MXT-induced genotoxicity and protected normal cells during chemotherapy.

Nanopharmaceutical approach using pelargonidin towards enhancement of efficacy for prevention of alloxan-induced DNA damage in L6 cells via activation of PARP and p53.

Alloxan is an environmental food contaminant that causes DNA damage in living cells and induces hyperglycemia. Pelargonidin (PG), an active ingredient found in extract of various fruits and vegetables, has been nanoencapsulated (NPG) with poly-lactide-co-glycolide (PLGA) and tested for efficacy in prevention of alloxan (ALX)-induced DNA damage in L6 cells in vitro. Glucose uptake, reactive oxygen species (ROS) generation, glucose transporter 4, glucokinase levels and mechanism of activation of DNA repair proteins (PARP and p53) have been studied in ALX-induced L6 cells. Drug-DNA interaction has been analyzed using calf thymus DNA as target through circular dichroism and melting temperature profile. NPGs were physico-chemically characterized by standard protocols using dynamic light scattering and transmission electron microscopy. Pre-treatment with both PG and/or NPG was effective in reducing ALX-induced oxidative stress and showed favourable effects for protection against DNA damage by activating DNA repair cascades. Results suggested ∼10-fold increase in efficacy of NPG than PG in prevention of alloxan-induced oxidative stress and DNA damage.

Pelargonidin induces apoptosis and cell cycle arrest via a mitochondria mediated intrinsic apoptotic pathway in HT29 cells

Pelargonidin (PE) is an anticancer anthocyanidin that is abundant in berries.