Mitigation of X-ray induced DNA damages and expression of DNA-repair genes by antioxidative Potentilla fulgens root extract and its ethyl-acetate fraction in mammalian cells.

Potentilla fulgens is a medicinal plant in North-East India whose root is reported to have anti-diabetic, anticarcinogenic and antioxidant properties. The potential of hydro-alcoholic extract of P. fulgens root (PRE) for providing protection to mammalian cells exposed to ionising radiation was investigated in this study. The methanolic extract of PRE shows an enhanced radical scavenging ability in a concentration dependent manner. PRE-pre-treatment to stimulated human blood lymphocytes (HBLs) reduced the frequency of deletion and exchange aberrations induced by X-irradiation. Similar protection of chromosome aberrations was also observed in mouse bone marrow cells (BMCs) where mice were given PRE extract (1 mg extract/day/mice) ad libitum in the drinking water for 45 days before whole-body X-irradiation. Of the various extracts prepared by partitioning of the methanol extract, the ethyl-acetate (EA) fraction was found to possess better antioxidant, radical scavenging and DNA-damage reduction activities. PRE-pre-treatment also reduced the radiation-induced cell-cycle delay effectively in HBL. In HEK-293 cells, PRE reduced radiation-induced G2-block in cell kinetics. Interestingly, PRE-treatment alone increased the concentration of endogenous glutathione (GSH) in mouse BMC and in stimulated HBL along with the elevated expression of γ-glutamyl-cysteine synthetase heavy/catalytic subunit, a key determinant of GSH synthesis. Studies on expression of two DNA-repair genes revealed that there was a marked increase in the expression of GADD45 and H2AX genes after X-irradiation in stimulated HBL, and such expression was reduced significantly if PRE-treatment was given prior to radiation. The present findings show the ability of PRE to reduce radiation-induced DNA damages probably by free radical scavenging whereas modulation of expression of DNA-repair genes' and endogenous GSH-increment emerge as effective strategies. The present study is the first report on the selected medicinal plant species that suggests it to be a potential natural radioprotector when used as root extract or its EA fraction for mitigating radiation toxicity.

Tropical lichen, Dirinaria consimilis, induces ROS-mediated activation of MAPKs and triggers caspase cascade mediated apoptosis in brain and cervical cancer cells.

Lichens are the symbiotic association between photobiont algae and mycobiont fungi having diverse phytochemicals. However, they are still an underexplored natural resource for biological activities. In the present report, we have evaluated the anti-brain and anti-cervical cancer activity of tropical lichen, Dirinaria consimilis (DCME) through the cell viability assay, cell cycle analysis, annexin V-FLUOS staining, morphological analysis, ROS-induction mechanism, evaluation of antioxidant levels, and western blotting study. The WST-1-based cell viability assay showed the cytotoxic nature of DCME towards U87 (IC50-52.65 ± 1.04 µg/ml) and HeLa (IC50-77.60 ± 2.23 µg/ml) cells. Interestingly, DCME does not showed any toxicity towards non-malignant fibroblast cell line WI-38 (IC50-685.80 ± 19.51 µg/ml). Furthermore, the cell cycle analysis showed sub-G1 arrest (apoptosis), and annexin V-FLUOS staining showed an increase in early apoptosis population dose-dependently. Confocal-based morphological data confirmed the DNA condensation and fragmentation upon treatment. Furthermore, DCME treatment induces ROS and regulates the levels of antioxidant enzymes (SOD, Catalase, GST, and GSH) in both U87 and HeLa cells. Finally, the western blotting data revealed the increase in Bax/Bcl-2 ratio, activation of Bid, Caspase-8, -9 and -3 along with degradation of PARP. Moreover, regulation of MAP kinases and activation of p53 was also observed upon DCME treatment. Herein, we first reported the anticancer activity of D. consimilis against brain and cervical cancer cells. Performed in-depth anticancer study revealed the ROS-mediated regulation of MAP kinases and activation of caspase cascade in U87 and HeLa cells upon DCME treatment.

Identification and characterization of novel microRNAs in disease-resistant and disease-susceptible Penaeus monodon.

MicroRNAs (miRNAs), known as a translational regulator, are evolutionary conserved, small, and noncoding RNA. They have played a vital role in disease biology through the host-virus-miRNA-interaction. In this study, novel miRNAs of naturally occurring, virus-free disease-resistant and disease-susceptible Penaeus monodon were identified and characterized. In disease-susceptible samples, 45 homologous mature miRNAs and 28 homologous precursor miRNAs were identified. In disease-resistant samples, 52 homologous mature miRNAs and 87 homologous precursor miRNAs were identified. In disease-susceptible samples, 33 novel mature miRNAs and 33 novel precursor miRNAs were identified. In disease-resistant samples, 523 novel mature miRNAs and 141 novel precursor miRNAs were identified. Differential expression study revealed the up-regulated and down-regulated miRNAs in disease-resistant and disease-susceptible P. monodon. Gene ontology pathway of known and novel miRNAs revealed that P. monodon miRNAs might have a potential and specific role in signal transduction, cell-to-cell signaling, innate immune response and defense response to different pathogens.

The natural flavones, acacetin and apigenin, induce Cdk-Cyclin mediated G2/M phase arrest and trigger ROS-mediated apoptosis in glioblastoma cells.

Brain and CNS-related cancers are rare; however, 0.3 million incidences and 0.24 million deaths in 2018 demonstrates the unrelenting associated dangers. Glioblastoma is a brain cancer of star-shaped glial cells. It is almost universally fatal within 2 years of diagnosis despite maximal medical therapies. This study aims to evaluate the in-depth anticancer activity of acacetin and apigenin on glioblastoma cells (U87). In the present report, we have isolated two flavonoids, acacetin and apigenin; and studied the in-depth anticancer activity on U87 cells. Selective cytotoxicity of acacetin and apigenin was observed towards the U87 cells (IC50: 43.73 ± 1.19 and 48.18 ± 1.37 µM, respectively). The flow cytometer-based result revealed the induction of G2/M phase arrest along with the increase in sub G1 population upon compound treatment. Annexin-V-FLUOS and DAPI staining also confirmed the apoptosis-inducing effects of compounds. Flow cytometer and confocal microscopy-based DCFH-DA staining showed ROS-inducing effect of the compounds. The up-regulation of p21 and down-regulation of Cyclin-A1, Cyclin-B1, and Cdk-1 revealed the G2/M phase arrest mechanism of acacetin and apigenin. Furthermore, western blotting result confirmed the activation of intrinsic pathway of apoptosis upon acacetin treatment and activation of both extrinsic and intrinsic pathways of apoptosis upon apigenin treatment through the regulation of Bax, t-Bid, caspase 8, caspase 9, caspase 3, and PARP. The obtained result showed a significant effect (P < 0.05) of acacetin and apigenin on U87 cells. Acacetin and apigenin-induced ROS is responsible for the induction of cell cycle arrest and activation of caspase-cascade pathways in U87 cells.

Development and characterization of white spot disease linked microsatellite DNA markers in Penaeus monodon, and their application to determine the population diversity, cluster and structure.

Pathogens that are introduced suddenly to natural populations can potentially cause quick changes to the genetics and diversity of the host. In the past three decades, white spot syndrome virus (WSSV) has caused damaging epizootics in Penaeus monodon populations. In this study, we developed WSSV resistance- or susceptibility-linked microsatellite DNA markers, and their effectiveness was validated experimentally. WSSV-resistant marker linked retroelements and genes that may have an important role in WSSV-resistance phenomena were partially identified. Allelic data of 1,694 samples from nine distinct geographic locations in India were revealed that populations from Digha and Kochi were highly dispersed, and also showed higher genetic diversity, higher population diversity, and lower prevalence of disease resistance. A very high level of gene flow was observed within all populations and a very high level of genetic variation was present within populations. Two genetically admixture population clusters were estimated in nature. WSSV-resistance has a significant link with genetic diversity, population cluster and population diversity. Microsatellite marker analysis characterized genetic divergence, diversity and structure among wild populations.

In Vitro Mechanistic Study of the Anti-inflammatory Activity of a Quinoline Isolated from Spondias pinnata Bark.

The search for new plant-based anti-inflammatory drugs continues in order to overcome the detrimental side effects of conventional anti-inflammatory agents, both steroidal and nonsteroidal. This study involves the quinoline SPE2, 7-hydroxy-6-methoxyquinolin-2(1 H)-one, isolated from the EtOAc fraction of Spondias pinnata bark. Structure elucidation was done using analytical spectroscopic methods including Fourier transform infrared spectroscopy, high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and single-crystal X-ray crystallography. The anti-inflammatory activity of SPE2 was evaluated in a lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 model. SPE2 effectively suppressed LPS-induced overproduction of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, and reactive oxygen species. Expression levels of NO synthesizing enzyme, cyclooxygenase-2, TNF-α, IL-6 and IL-1ß were also determined to return to normal after SPE2 treatment. Localization of NF-κB was evaluated by confocal microscopy and Western blotting, which showed a dose-dependent reduction of NF-κB inside the nucleus and an increase in cytoplasmic NF-κB with SPE2 treatment. Collectively, the results suggest that SPE2 has anti-inflammatory activity via inhibition of NF-κB activation.

A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation.

Self-Assembly of Novel Thiophene-Based BODIPY RuII Rectangles: Potential Antiproliferative Agents Selective Against Cancer Cells.

Novel Ru (2+2) rectangles were designed and synthesized by self-assembly of a new thiophene-functionalized dipyridyl BODIPY ligand, BDPS, and ruthenium(II) precursors. The complexes exhibited dose-dependent antiproliferative activities against cancer cells, in which some compounds selectively kill cancer cells. The net fluorescence due to BODIPY allowed us to visualize their location inside cancer cells. Moreover, the metalla-rectangles displayed substantial propensity to bind with biomolecules.

Self-Assembled Novel BODIPY-Based Palladium Supramolecules and Their Cellular Localization.

Four new palladium metal supramolecules with triangular/square architectures derived from boron dipyrromethane (BODIPY) ligands were synthesized by self-assembly and fully characterized by 1H and 31P NMR, electrospray ionization mass spectrometry, and single-crystal X-ray diffraction. These supramolecules were more cytotoxic to brain cancer (glioblastoma) cells than to normal lung fibroblasts. Their cytotoxicity to the glioblastoma cells was higher than that of a benchmark metal-based chemotherapy drug, cisplatin. The characteristic green fluorescence of the BODIPY ligands in these supramolecules permitted their intracellular visualization using confocal microscopy, and the compounds were localized in the cytoplasm and on the plasma membrane.

A microalga, Euglena tuba induces apoptosis and suppresses metastasis in human lung and breast carcinoma cells through ROS-mediated regulation of MAPKs.

BACKGROUND: Euglena tuba, a microalga, is known for its excellent antioxidant and iron-chelation activities; however its anticancer efficacies have not been reported yet. This study investigates the antitumor and antimetastatic activities of 70 % methanolic extract of Euglena tuba (ETME) against human lung (A549) and breast cancer (MCF-7) cells in vitro. Moreover, we had examined ETME's role in inducing intracellular ROS with the regulation of antioxidants and MAPK pathway. METHODS: Anticancer activity of ETME was thoroughly studied using flow cytometry, confocal microscopy and western blotting; along with various biochemical assays for analysing ROS-induced regulation of antioxidant enzymes. Inhibition of invasion and migration of malignant cells by ETME were investigated by wound healing and zymographic studies. DNA-Protein interaction with ETME was also studied. RESULTS: ETME inhibited the growth of both A549 (IC50 92.14 µg/ml) and MCF-7 cells (IC50 50.27 µg/ml) by inducing apoptosis, while remained non-toxic against nomral WI-38 cells (IC50 911.43 µg/ml). ETME treatment resulted in increasing Bax/Bcl-2 ratio, BID truncation and activation of caspase cascade. This ultimately leads to PARP degradation and apoptosis through the intrinsic and extrinsic pathway in both A549 and MCF-7 cells. Wound healing and gelatin zymography studies revealed that ETME significantly inhibited the invasion and migration of both A549 and MCF-7 cells dose-dependently through the downregulation of MMP-9. Further investigations showed that ETME selectively induces intracellular ROS, regulated the levels of intracellular antioxidants and suppresses the activation of ERK1/2, JNK, P38 mitogen-activated protein kinase pathways in both type of malignant cells. Further DNA and protein binding studies revealed that ETME strongly interact with DNA as well as protein attributing the possibilities of presence of components which are targeting the macromolecules in cancer cells. Moreover, when the identified compounds from ETME were examined for their cytotoxicities individually, it was found that they lost their specificities towards cancer cells and also attacked normal cells. CONCLUSIONS: Our study suggests that ETME retards the growth of both lung and breast cancer cells, in vitro, through multivariate mechanisms, proving its candidature for the development of better and safer drugs against these cancers.

Glycoside rich fraction from Spondias pinnata bark ameliorate iron overload induced oxidative stress and hepatic damage in Swiss albino mice.

BACKGROUND: Iron in the overloaded condition in liver promotes the overproduction of free radicals that lead to oxidative stress and ultimately hepatic damage. The present study was designed to evaluate the ameliorating potential from iron overloaded hepatotoxicity by the glycosidic fraction from Spondious pinnata bark (SPW1) along with its antioxidant property. METHODS: The fraction was tested for its in vitro antioxidant, free radical scavenging property and iron chelation potential via standard biochemical assays. Iron overload condition was generated by the intraperitoneal administration of iron dextran in mice. The levels of serum enzymes, antioxidant enzymes in liver, markers of hepatic damage, liver iron, and ferritin content were measured in response to the oral treatment of SPW1. Histopathology of the liver sections was performed for visual confirmation of the amelioration potential of SPW1. RESULTS: The fraction exhibited excellent in vitro antioxidant as well as free radical scavenging potential against both reactive oxygen species and reactive nitrogen species. Administration of SPW1 significantly normalized the disturbed levels of antioxidant enzymes, liver iron, lipid peroxidation, liver fibrosis, serum enzyme and ferritin better than standard desirox which were also supported by the morphological study of the liver sections. Phytochemical analysis as well as HPLC study, confirmed that the fraction mainly consisted of glycosidic phenolics and flavonoids that attributed to its biological activities. CONCLUSIONS: The above results suggested that beneficial effects of SPW1 on iron overload induced hepatotoxicity that can be considered as a possible candidate against iron overload diseases.

Identification and characterisation of microsatellite DNA markers in order to recognise the WSSV susceptible populations of marine giant black tiger shrimp, Penaeus monodon.

White spot disease (WSD) which is caused by white spot syndrome virus (WSSV) creates severe epizootics in captured and cultured black tiger shrimp, resulting a huge loss in the economic output of the aquaculture industry worldwide. Performing selective breeding using DNA markers would prove to be a potential cost effective strategy for long term disease control in shrimps. In the present investigation, microsatellite DNA fingerprints were compared between naturally occurring WSSV resistant and susceptible populations of Penaeus monodon. After PCR with a set of shrimp specific primers three reproducible DNA fragments of varying sizes were found, among which 442 bp and 236 bp fragments were present in considerably higher frequencies in the WSSV susceptible shrimp population (p ≤ 0.0001). After WSSV challenge experiment the copy no. of WSSV was determined using real-time PCR, where it was found to be almost 4 × 10(3) fold higher in WSSV susceptible shrimps than in the resistant ones. Thus, these microsatellite DNA markers will be useful to distinguish between WSSV susceptible and resistant brood stocks of P. monodon. Sequencing studies revealed that these DNA markers were novel in P. monodon. Highest WSSV resistance using these DNA markers, was observed in the shrimp populations of Andaman Island and Chennai among the different coastal areas of India, suggesting these places as safe for specific pathogen resistant brood stock shrimp collection. This study will be a very effective platform towards understanding the molecular pathogenesis of WSD for generation of disease free shrimp aquaculture industry.

Amelioration of iron overload-induced liver toxicity by a potent antioxidant and iron chelator, Emblica officinalis Gaertn.

In liver, the major site of iron storage, iron overload is associated with oxidative damage of protein, lipid, and DNA and causes protein oxidation, lipid peroxidation, and rupture of hepatocytes, leading to cell death. Serum ferritin and liver iron content are the main forecasters of moderate to severe iron overload in the liver. The sequels of excess iron deposition in the liver are fibrosis and enhanced levels of serum enzymes and bilirubin markers. Emblica officinalis (EO) fruit extract was found efficient in lessening intraperitoneally injected iron dextran-induced liver toxicity in Swiss albino mice. Mice administered with different doses of 70% methanol extract of EO (50, 100, and 200 mg kg(-1) body weight) showed significant decrease in liver iron, serum ferritin, and serum enzyme levels, along with the decrease in lipid peroxidation, protein oxidation, and collagen content. The activity was further supported by its considerable iron chelation with half-maximal inhibitory concentration of 70.24 ± 2.74 µg ml(-1) and the protection on ferrous ion-mediated DNA breakdown with 50% protection ([P]50) of 1.04 ± 0.01 µg ml(-1). Simultaneously, the extract effectively induced the antioxidant enzyme levels and also exhibited the potential activity of reductive release of ferritin iron. These findings suggest that the EO extract may be used as a potent drug for the treatment of pathological sequences arisen in the iron overload-induced liver damage.

Protective effect of Clerodendrum colebrookianum leaves against iron-induced oxidative stress and hepatotoxicity in Swiss albino mice.

Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases.

Nerium indicum leaf alleviates iron-induced oxidative stress and hepatic injury in mice.

CONTEXT: Nerium indicum Mill. (Apocynaceae) was reported for its efficient in vitro antioxidant and iron-chelating properties. OBJECTIVE: This study demonstrates the effect of 70% methanol extract of N. indicum leaf (NIME) towards in vitro DNA protection and ameliorating iron-overload-induced liver damage in mice. MATERIALS AND METHODS: Phytochemical and HPLC analyses were carried out to standardize the extract and the effect of Fe(2+)-mediated pUC18 DNA cessation was studied. Thirty-six Swiss Albino mice were divided into six groups of blank, negative control (iron overload only), and iron-overloaded mice receiving 50, 100, and 200 mg/kg b.w. doses of NIME and desirox (20 mg/kg b.w.). The biochemical markers of hepatic damage, various liver and serum parameters, and reductive release of ferritin iron were studied. RESULTS AND DISCUSSION: The presence of different phytocomponents was revealed from phytochemical and HPLC analyses. A substantial supercoiled DNA protection, with [P]50 of 70.33 ± 0.32 µg, was observed. NIME (200 mg/kg b.w.) significantly normalized the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin by 126.27, 125.25, 188.48, and 45.47%, respectively. NIME (200 mg/kg b.w.) was shown to alleviate the reduced levels of superoxide dismutase, catalase, glutathione-S-transferase, and non-enzymatic-reduced glutathione, by 48.95, 35.9, 35.42, and 13.22%, respectively. NIME also lowered raised levels of lipid peroxidation, protein carbonyl, hydroxyproline, and liver iron by 32.28, 64.58, 136.81, and 83.55%, respectively. CONCLUSION: These findings suggest that the active substances present in NIME may be capable of lessening iron overload-induced toxicity, and possibly be a useful drug for iron-overloaded diseases.

Assessment of the phytochemical constituents and antioxidant activity of a bloom forming microalgae Euglena tuba.

BACKGROUND: Unstable generation of free radicals in the body are responsible for many degenerative diseases. A bloom forming algae Euglena tuba growing abundantly in the aquatic habitats of Cachar district in the state of Assam in North-East India was analysed for its phytochemical contents, antioxidant activity as well as free radical scavenging potentials. RESULTS: Based on the ability of the extract in ABTS•+ radical cation inhibition and Fe3+ reducing power, the obtained results revealed the prominent antioxidant activity of the algae, with high correlation coefficient of its TEAC values to the respective phenolic and flavonoid contents. The extract had shown its scavenging activity for different free radicals and 41.89 ± 0.41 µg/ml, 5.83 ± 0.07 µg/ml, 278.46 ± 15.02 µg/ml and 223.25 ± 4.19 µg/ml were determined as the IC50 values for hydroxyl, superoxide, nitric oxide and hypochlorous acid respectively, which are lower than that of the corresponding reference standards. The phytochemical analysis also revealed that the phenolics, flavonoids, alkaloids, tannins and carbohydrates are present in adequate amount in the extract which was confirmed by HPLC analysis. CONCLUSIONS: The results showed that 70% methanol extract of the algae possesses excellent antioxidant and free radical scavenging properties.

Assessment of WSSV prevalence and distribution of disease-resistant shrimp among the wild population of Penaeus monodon along the west coast of India.

Shrimp aquaculture is threatened by many diseases, among which white spot disease (WSD) caused by white spot syndrome virus (WSSV) is the leading one. Information related to the geographical distribution and seasonal prevalence of WSD is necessary to obtain a clear understanding of the disease biology in shrimp. Identification of WSD-resistant individual shrimp with DNA markers is also an important technique to develop better WSD-free shrimp health management. The present study aim is to estimate the occurrence of WSSV in Penaeus monodon qualitatively and quantitatively during three different seasons during the years 2011 to 2013 along the west coast of India. Additionally, the disease resistance prevalence using previously developed 71 bp microsatellite and 457 bp RAPD-SCAR DNA markers is also investigated. Samples were collected throughout the year from four locations along the west coast of India: Kochi, Kerala; Mangalore, Karnataka; Vasco-da-Gama, Goa; and Veraval, Gujarat. The results depicted that the average WSSV prevalence, as determined by the nested PCR method and taken cumulatively over the four locations, was the lowest (0%) during the post-monsoon season and the highest (31.6%) during the monsoon season. The WSD prevalence was observed to increase when the latitude was decreased along the west coast of India (from Veraval to Kochi). Out of the three different seasons, the average WSSV copy number was the highest (approximately 10(3) copies µg(-1) shrimp genomic DNA) during the monsoon season. The disease-resistant prevalence, as determined using the developed DNA markers, was found to be the highest in Vasco-da-Gama (59.5%) and the lowest in Kochi (40.9%). The present study suggests better options for the efficient collection of disease-free and disease-resistant brood stocks, which would be a more cost-effective and safer approach toward disease prevention over conventional trends of seed generation from unselected wild brood stock.

Spondias pinnata stem bark extract lessens iron overloaded liver toxicity due to hemosiderosis in Swiss albino mice.

The present study was designed to evaluate the ameliorating effect of 70% methanol extract of Spondias pinnata (SPME) on iron overload induced liver injury. Iron overload was induced by intraperitoneal administration of iron-dextran into mice and resulting liver damage was manifested by significant rise in serum enzyme markers (ALT, AST, ALP and bilirubin) and reduction in liver antioxidants (SOD, CAT, GST and GSH). Hepatic iron, serum ferritin, lipid peroxidation, protein carbonyl and hydroxyproline contents were measured in response to the oral administration of SPME of different doses (50, 100 and 200 mg/kg body weight). In order to determine the efficiency as iron chelating drug, the release of iron from ferritin by SPME was further studied. Enhanced levels of antioxidant enzymes were detected in SPME treated mice. SPME produced a dose dependent inhibition of lipid peroxidation, protein oxidation, liver fibrosis; and levels of serum enzyme markers and ferritin were also reduced dose dependently. The liver iron content was also found to be less in SPME treated group compared to control group. The reductive release of ferritin iron was augmented significantly after dose dependent addition of SPME. The ameliorating effect of SPME on damaged liver was furthermore supported by the histopathological studies that showed improved histological appearances. In conclusion, the present results demonstrate the hepatoprotective efficiency of SPME in iron intoxicated mice, and hence possibly useful as iron chelating drug for iron overload diseases.

Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

Hepatoprotective Potential of Caesalpinia crista against Iron-Overload-Induced Liver Toxicity in Mice.

The present study was carried out to evaluate the ameliorating effect of Caesalpinia crista Linn. (CCME) extract on iron-overload-induced liver injury. Iron overload was induced by intraperitoneal administration of iron dextran into mice. CCME attenuated the percentage increase in liver iron and serum ferritin levels when compared to control group. CCME also showed a dose-dependent inhibition of lipid peroxidation, protein oxidation, and liver fibrosis. The serum enzyme markers were found to be less, whereas enhanced levels of liver antioxidant enzymes were detected in CCME-treated group. In presence of CCME, the reductive release of ferritin iron was increased significantly. Furthermore, CCME exhibited DPPH radical scavenging and protection against Fe(2+)-mediated oxidative DNA damage. The current study confirmed the hepatoprotective effect of CCME against the model hepatotoxicant iron overload and the activity is likely related to its potent antioxidant and iron-chelating property.