Bioactive Fractions Isolated from Harungana madagascariensis Lam. and Psorospermum aurantiacum Engl. Regulate Collagen and Melanin Biosynthesis Gene Expression in UVB-Irradiated Cells with Additional Anti-Inflammatory Potential.

BACKGROUND: Harungana madagascariensis (HM) and Psorospermum aurantiacum (PA), used traditionally for skin care, have been reported to upregulate the expression of intracellular antioxidant genes, thereby preventing melanoma and protecting fibroblast cell lines from Ultraviolet B (UVB)-induced intracellular oxidative stress. AIMS: This investigation aimed to identify major compounds in bioactive fractions using bioassay- guided fractionation. METHODS: The anti-inflammatory effect of fractions was determined by measuring their inhibitory activity on 15-lipoxygenase and nitric oxide (NO) in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Additionally, the anti-aging efficacy of the fractions was determined by assessing the expression of markers for the aging process, i.e., expression of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), procollagen type-1 (COL1A1), and matrix metalloproteinase- 1 (MMP-1) in UVB-induced photoaging in skin cell-lines. Furthermore, UHPLCMS- based identification of the bioactive compounds from the most prominent fraction was also carried out. RESULTS: Hexane fraction of HM significantly inhibited (p <0.05) the 15-lipoxygenase (IC50 = 46.80 µg/mL) and NO production (IC50 = 66.55 µg/mL), whereas hexane fraction of PA was effective (p <0.05) in inhibiting 15-lipoxygenase activity (IC50 = 27.55 µg/mL). Furthermore, the hexane fraction of HM and methanol fraction of PA were significantly effective (p <0.05) in reverting the UVB-mediated altered expressions of MMP-1, TYR, TRP-1, and COL1A1. Furthermore, hexane fraction of HM revealed the presence of harunganin and betulinic acid, whereas vismion D, vismin, kenganthranol B, and bianthrone 1a were identified from the methanol fraction of PA. CONCLUSION: Overall, the hexane fraction of HM and methanol fraction of PA displayed effective anti-aging activities, with additional anti-inflammatory effects.

Synthesis of Novel Bis-imino and Bis-amino Curcuminoids for Evaluation of Their Anticancer and Antibacterial Activity.

A new set of curcumin analogues with a Schiff base moiety were synthesized from a bis-aldehyde derivative of hydroxybenzylidene cyclohexanone and various alicyclic and aromatic amines. The single crystals of compound 2 (bis-aldehyde), compound 3b (bis-cyclohexylimino derivative), and compound 3c (bis-1-imino piperidyl derivative) were developed. The said bis-imino and bis-amino curcuminoids were tested for anticancer activity against MCF-7 utilizing the conventional MTT assay. These Schiff bases had significantly higher anticancer efficacy than curcumin and methotrexate against MCF-7 cell lines. Compounds 3k, 3b, and 3l have the highest efficacy among all synthesized curcuminoids. The MTT results are in accordance with the binding affinities found by docking the said molecules with HER2 Tyrosine Kinase (HER2-TK). Compound 3b is identified as a promising HER2-TK inhibitor and also shows effective inhibition against Gram-positive bacteria Staphylococcus aureus.

Vitamin-H Channeled Self-Therapeutic P-gp Inhibitor Curcumin-Derived Nanomicelles for Targeting the Tumor Milieu by pH- and Enzyme-Triggered Hierarchical Disassembly.

An effective nanocarrier-mediated drug delivery to cancer cells primarily faces limitations like the presence of successive drug delivery barriers, insufficient circulation time, drug leakage, and decreased tumor penetration capacity. With the aim of addressing this paradox, a self-therapeutic, curcumin-derived copolymer was synthesized by conjugation with PEGylated biotin via enzyme- and acid-labile ester and acetal linkages. This copolymer is a prodrug of curcumin and self-assembles into ∼150-200 nm-sized nanomicelles; it is capable of encapsulating doxorubicin (DOX) and hence can be designated as self-therapeutic. pH- and enzyme-responsive linkages in the polymer skeleton assist in its hierarchical disassembly only in the tumor microenvironment. Further, the conjugation of biotin and poly(ethylene glycol) (PEG) imparts features of tumor specificity and improved circulation times to the nanocarrier. The dynamic light scattering (DLS) analysis supports this claim and demonstrates rapid swelling and disruption of micelles under acidic pH. UV-vis spectroscopy provided evidence of an accelerated acetal degradation at pH 4.0 and 5.0. The in vitro release studies revealed a controlled release of DOX under acidic conditions and curcumin release in response to the enzyme. The value of the combination index calculated on HepG2 cells was found to be <1, and hence, the drug pair curcumin and DOX acts synergistically for tumor regression. To prove the efficiency of acid-labile linkages and the prodrug strategy for effective cancer therapy, curcumin-derived polymers devoid of sensitive linkages were also prepared. The prodrug stimuli-responsive nanomicelles showed enhanced cell cytotoxicity and tumor penetration capability on HepG2 cells as well as drug-resistant MCF-7 cell lines and no effect on normal NIH/3T3 fibroblasts as compared to the nonresponsive micelles. The results were also supported by in vivo evidence on a hepatocellular carcinoma (HCC)-induced nude mice model. An evident decrease in MMP-2, MMP-9, and α-fetoprotein (AFP), the biomarkers specific to tumor progression, was observed along with metastasis upon treatment with the drug-loaded dual-responsive nanomicelles. These observations corroborated with the SGOT and SGPT data as well as the histoarchitecture of the liver tissue in mice.

Melatonin induces Nrf2-HO-1 reprogramming and corrections in hepatic core clock oscillations in Non-alcoholic fatty liver disease.

Melatonin pleiotropically regulates physiological events and has a putative regulatory role in the circadian clock desynchrony-mediated Non-alcoholic fatty liver disease (NAFLD). In this study, we investigated perturbations in the hepatic circadian clock gene, and Nrf2-HO-1 oscillations in conditions of high-fat high fructose (HFHF) diet and/or jet lag (JL)-mediated NAFLD. Melatonin treatment (100 µM) to HepG2 cells led to an improvement in oscillatory pattern of clock genes (Clock, Bmal1, and Per) in oleic acid (OA)-induced circadian desynchrony, while Cry, Nrf2, and HO-1 remain oblivious of melatonin treatment that was also validated by circwave analysis. C57BL/6J mice subjected to HFHF and/or JL, and treated with melatonin showed an improvement in the profile of lipid regulatory genes (CPT-1, PPARa, and SREBP-1c), liver function (AST and ALT) and histomorphology of fatty liver. A detailed scrutiny revealed that hepatic mRNA and protein profiles of Bmal1 (at ZT6) and Clock (at ZT12) underwent corrective changes in oscillations, but moderate corrections were recorded in other components of clock genes (Per1, Per2, and Cry2). Melatonin induced changes in oscillations of anti-oxidant genes (Nrf2, HO-1, and Keap1) subtly contributed in the overall improvement in NAFLD recorded herein. Taken together, melatonin induced reprograming of hepatic core clock and Nrf2-HO-1 genes leads to an improvement in HFHF/JL-induced NAFLD.

HSP60 knockdown exerts differential response in endothelial cells and monocyte derived macrophages during atherogenic transformation.

Ectopic expression of HSP60 in vascular cells is known to activate auto-immune response that is critical to atherogenic initiation. However, the pathogenic relevance of the aberrant HSP60 upregulation in intracellular signaling pathways associated with atherogenic consequences in vascular cells remains unclear. The aim of the present study was to determine the role of endogenous HSP60 in atherogenic transformation of endothelial cells and macrophages. After generating primary evidence of oxidized low density lipoprotein (OxLDL) induced HSP60 upregulation in human umbilical vein endothelial cells (HUVEC), its physiological relevance in high fat high fructose (HFHF) induced early atherogenic remodelling was investigated in C57BL/6J mice. Prominent HSP60 expression was recorded in tunica intima and media of thoracic aorta that showed hypertrophy, lumen dilation, elastin fragmentation and collagen deposition. Further, HSP60 overexpression was found to be prerequisite for its surface localization and secretion in HUVEC. eNOS downregulation and MCP-1, VCAM-1 and ICAM-1 upregulation with subsequent macrophage accumulation provided compelling evidences on HFHF induced endothelial dysfunction and activation that were also observed in OxLDL treated- and HSP60 overexpressing-HUVEC. OxLDL induced concomitant reduction in NO production and monocyte adhesion were prevented by HSP60 knockdown, implying towards HSP60 mediated possible regulation of the said genes. OxLDL induced HSP60 upregulation and secretion was also recorded in THP-1 derived macrophages (TDMs). HSP60 knockdown in TDMs accounted for higher OxLDL accumulation that correlated with altered scavenger receptors (SR-A1, CD36 and SR-B1) expression further culminating in M1 polarization. Collectively, the results highlight HSP60 upregulation as a critical vascular alteration that exerts differential regulatory role in atherogenic transformation of endothelial cells and macrophages.

Evaluation of biomolecular interactions and cytotoxic activity of organometallic binuclear Ru(II) complexes of ferrocenyl thiosemicarbazones.

Four new ferrocenyl substituted thiosemicarbazone ligands (L1-L4) and their corresponding binuclear ruthenium(II) arene complexes of the general type [(η6-p cym)(L)Ru(µ-im)Ru(L)(η6-p-cym)]Cl (C1-C4) and [(η6-p cym)(L)Ru(µ-azpy)Ru(L)(η6-p-cym)]Cl2 (C5-C8) (cym = cymene, im = imidazole, azpy = 4,4'-azopyridine) have been synthesized and characterized. The structures of the complexes were established through DFT calculations and geometry optimization. The interactions of the binuclear complexes with DNA were investigated by absorption, emission and viscosity studies which indicated that the complexes bind to DNA via intercalation. Meanwhile, the interaction of complexes with the protein, bovine serum albumin (BSA), has also been studied using fluorescence emission spectroscopy. The experimental results show that the binuclear complexes exhibit good binding propensities to BSA. The complexes can quench the intrinsic fluorescence of BSA remarkably through a static or dynamic quenching process. In addition, the in vitro cytotoxicity of complexes C1-C8 against HeLa cell line was assayed which showed lower IC50 values indicating their higher cytotoxicity and potency in killing the cancer cells at low concentrations.Communicated by Ramaswamy H. Sarma.

Myeloid Differentiation Primary Response 88-Cyclin D1 Signaling in Breast Cancer Cells Regulates Toll-Like Receptor 3-Mediated Cell Proliferation.

Toll-like receptor 3 (TLR3)-mediated apoptotic changes in cancer cells are well-documented, and hence, several synthetic ligands of TLR3 are being used for adjuvant therapy, but there are reports showing a contradictory effect of TLR3 signaling, which include our previous report that had shown cell proliferation following surface localization of TLR 3. However, the underlying mechanism of cell surface localization of TLR3 and subsequent cell proliferation lacks clarity. This study addresses the TLR3 ligand-mediated signaling cascade that regulates a proliferative effect in breast cancer cells (MDA-MB-231 and T47D) challenged with TLR3 ligand in the presence of myeloid differentiation primary response 88 (MyD88) inhibitor. Evidences were obtained using immunoblotting, coimmunoprecipitation, confocal microscopy, immunocytochemistry, ELISA, and flow cytometry. Results had revealed that TLR3 ligand treatment significantly enhanced breast cancer cell proliferation marked by an upregulated expression of cyclinD1, but the same was suppressed by the addition of MyD88 inhibitor. Also, expression of interleukin 1 receptor-associated kinase 1 (IRAK1)-TNF receptor-associated factor 6 (TRAF6)-transforming growth factor beta-activated kinase 1 (TAK1) was altered in the given TLR3-signaling pathway. Inhibition of MyD88 disrupted the downstream adaptor complex and mediated signaling through the TLR3-MyD88-NF-κB (p65)-IL-6-cyclin D1 pathway. TLR3-mediated alternative signaling of the TLR3-MyD88-IRAK1-TRAF6-TAK1-TAB1-NF-κB axis leads to upregulation of IL6 and cyclin D1. This response is hypothesized to be via the MyD88 gateway that culminates in the proliferation of breast cancer cells. Overall, this study provides first comprehensive evidence on the involvement of canonical signaling of TLR3 using MyD88-cyclin D1-mediated breast cancer cell proliferation. The findings elucidated herein will provide valuable insights into understanding the TLR3-mediated adjuvant therapy in cancer.

Carbon nanotube embedded cyclodextrin polymer derived injectable nanocarrier: A multiple faceted platform for stimulation of multi-drug resistance reversal.

A combination of cocktail chemotherapy (CCT), photothermal therapy (PTT) and inhibition of angiogenesis was investigated as an effective approach to combat major challenges of multidrug resistance and non-targeted drug delivery encountered in conventional cancer therapy. An injectable nanocarrier was developed through functionalization of carbon nanotubes (CNTs) with rationally modified carbohydrate (ß-Cyclodextrin-CD) derived pH and thermo responsive polymer. Embedding CNT to CD polymer offers a nanocarrier which effectively demonstrated CCT, high NIR triggered photothermal efficiency, anti-angiogenic potential for selective tumor homing as well as enhanced multi-drug resistance (MDR) reversal with minimal toxic effects on normal cells. The simultaneously loading with curcumin and doxorubicin hydrochloride exhibited synergistic effect for triggering antitumor effect in vitro and demonstrated down regulation of growth factors associated with angiogenesis ex-ovo. In-vivo studies ascertained that the nanocarrier synthesized with the rational for MDR reversal can lead to enhanced cancer cell death via multiple approaches.

Carbon monoxide releasing molecule-A1 improves nonalcoholic steatohepatitis via Nrf2 activation mediated improvement in oxidative stress and mitochondrial function.

Nuclear factor-erythroid 2 related factor 2 (Nrf2)-mediated signaling plays a central role in maintaining cellular redox homeostasis of hepatic cells. Carbon monoxide releasing molecule-A1 (CORM-A1) has been reported to stimulate up-regulation and nuclear translocation of Nrf2 in hepatocytes. However, the role of CORM-A1 in improving lipid metabolism, antioxidant signaling and mitochondrial functions in nonalcoholic steatohepatitis (NASH) is unknown. In this study, we report that CORM-A1 prevents hepatic steatosis in high fat high fructose (HFHF) diet fed C57BL/6J mice, used as model of NASH. The beneficial effects of CORM-A1 in HFHF fed mice was associated with improved lipid homeostasis, Nrf2 activation, upregulation of antioxidant responsive (ARE) genes and increased ATP production. As, mitochondria are intracellular source of reactive oxygen species (ROS) and important sites of lipid metabolism, we further investigated the mechanisms of action of CORM-A1-mediated improvement in mitochondrial function in palmitic acid (PA) treated HepG2 cells. Cellular oxidative stress and cell viability were found to be improved in PA + CORM-A1 treated cells via Nrf2 translocation and activation of cytoprotective genes. Furthermore, in PA treated cells, CORM-A1 improved mitochondrial oxidative stress, membrane potential and rescued mitochondrial biogenesis thru upregulation of Drp1, TFAM, PGC-1α and NRF-1 genes. CORM-A1 treatment improved cellular status by lowering glycolytic respiration and maximizing OCR. Improvement in mitochondrial respiration and increment in ATP production in PA + CORM-A1 treated cells further corroborate our findings. In summary, our data demonstrate for the first time that CORM-A1 ameliorates tissue damage in steatotic liver via Nrf2 activation and improved mitochondrial function, thus, suggesting the anti-NASH potential of CORM-A1.

Camptothecin encapsulated into functionalized MCM-41: In vitro release study, cytotoxicity and kinetics.

The application of MCM-41 functionalized by 12-tungstophosphoric acid (TPA) as drug carrier for cancer treatment was studied by loading of camptothecin (CPT). In-vitro controlled release study of CPT in Simulated Body Fluid (pH 7.4, 37 °C) was carried out under stirring as well as static conditions. The systems were also evaluated on cancer cells (HepG2) and the carriers are found to be non-toxic to the cancer cells. In order to see the influence of inorganic moiety on release rate of drug, study was also carried out with CPT loaded unfunctionalized MCM-41. A detailed study on release kinetics and release mechanism using First Order Release Kinetic Model, Higuchi Model, Koresmeyer-Pepps Model and Extended kinetic model was also carried out.

ß-cyclodextrin based dual-responsive multifunctional nanotheranostics for cancer cell targeting and dual drug delivery.

Multifunctional nanoconjugates possessing an assortment of key functionalities such as magnetism, florescence, cell-targeting, pH and thermo-responsive features were developed for dual drug delivery. The novelty lies in careful conjugation of each of the functionality with magnetic Fe3O4 nanoparticles by virtue of urethane linkages instead of silica in a simple one pot synthesis. Further ß-cyclodextrin (CD) was utilized to carry hydrophobic as well as hydrophilic drug. Superlative release of DOX could be obtained under acidic pH conditions and elevated temperature, which coincides with the tumor microenvironment. Mathematical modelling studies revealed that the drug release kinetics followed diffusion mechanism for both hydrophobic drug and hydrophilic drug. A number of fluorophores onto a single nanoparticle produced a strong fluorescence signal to optically track the nanoconjugates. Enhanced internalization due to folate specificity could be observed by fluorescence imaging. Further their accumulation driven by magnet near tumor site led to magnetic hyperthermia. in vitro studies confirmed the nontoxicity and hemocompatibility of the nanoconjugates. Remarkable cell death was observed with drug-loaded nanoconjugates at very low concentrations in cancer cells. The internalization and cellular uptake of poor bioavailable anticancer agent curcumin were found to be remarkably enhanced on dosing the drug loaded nanoconjugates as compared to free curcumin. Site specific drug delivery due to folate conjugation and subsequent significant suppression in tumor growth was demonstrated by in vivo studies.

Toxicity evaluation of magnetic iron oxide nanoparticles reveals neuronal loss in chicken embryo.

Magnetic iron oxide nanoparticles (IONs) display the ability to cross blood - brain barrier and are envisioned as diagnostic and therapeutic applications, but there are few studies on their potential embryonic toxicity in higher vertebrates. This study investigates interaction of IONs with egg albumen and its subsequent toxicity on chicken embryo. Physicochemical interactions of IONs with egg albumen revealed alterations in friccohesity and secondary structural changes due to weak Vander Waals forces. Toxicity assessment of IONs (10, 25, 50, 100, and 200 µg/ml doses) on chicken embryo accounted for 100% mortality at 200 µg/ml dose due to Fe2+ ions overload. However, lower doses (50 and 100 µg/ml) recorded decrement in whole weights and crown-rump lengths of chicken embryo possibly due to ION-albumen interactions. Histology of brain tissue revealed degeneration of neurons (50-60%) at 10-100 µg/ml dose range of IONs. Toxicity studies of IONs with diverse animal models are needed to set a toxicity benchmark for preventing embryonic toxicity prior to its use in biomedical applications. This is the first study on toxicity assessment of IONs in chicken embryo.

Carbon monoxide releasing molecule A-1 attenuates acetaminophen-mediated hepatotoxicity and improves survival of mice by induction of Nrf2 and related genes.

Acute liver injury is frequently associated with oxidative stress. Here, we investigated the therapeutic potential of carbon monoxide releasing molecule A-1 (CORM A-1) in oxidative stress-mediated liver injury. Overnight-fasted mice were injected with acetaminophen (APAP; 300 mg/kg; intraperitoneally) and were sacrificed at 4 and 12 h. They showed elevated levels of serum transaminases, depleted hepatic glutathione (GSH) and hepatocyte necrosis. Mice injected with CORM A-1 (20 mg/kg) 1 h after APAP administration, had reduced serum transaminases, preserved hepatic GSH and reduced hepatocyte necrosis. Mice that received a lethal dose of APAP (600 mg/kg), died by 10 h; but those co-treated with CORM A-1 showed a 50% survival. Compared to APAP-treated mice, livers from those co-treated with CORM A-1, had upregulation of Nrf2 and ARE genes (HO-1, GCLM and NQO-1). APAP-treated mice had elevated hepatic mRNA levels of inflammatory genes (Nf-κB, TNF-α, IL1-ß and IL-6), an effect blunted in those co-treated with CORM A-1. In tert-butyl hydroperoxide (t-BHP)-treated HepG2 cells, CORM A-1 augmented cell viability, reduced oxidative stress, activated the nuclear factor erythroid 2-related factor 2 (Nrf2) and anti-oxidant response element (ARE) genes. The molecular docking profile of CO in the kelch domain of Keap1 protein suggested that CO released from CORM A-1 mediated Nrf2 activation. Collectively, these data indicate that CORM A-1 reduces oxidative stress by upregulating Nrf2 and related genes, and restoring hepatic GSH, to reduce hepatocyte necrosis and thus minimize liver injury that contributes to an overall improved survival rate.

Apoptotic potential of C-phycoerythrin from Phormidium sp. A27DM and Halomicronema sp. A32DM on human lung carcinoma cells.

Phycobilisomes present in cyanobacteria are photosynthetic macromolecular protein complexes that are categorized into three types - phycoerythrins (high energy), phycocyanin (intermediate energy) and allophycocyanin (low energy). Structurally, they consist of α and ß protein subunits and open chain tetrapyrrole prosthetic group (bilin chromophore), known for its antioxidant properties and therapeutic potential against a variety of physiological ailments. Phycoerythrins (C-PE) were purified from cyanobacterial strains Phormidium sp. A27DM and Halomicronema sp. A32DM and their respective apoptotic potentials were assessed on A549 human lung carcinoma cells. Both strains of cyanobacteria were cultured and the C-PE from each strain was extracted, quantified and characterized. C-PE accounted for a dose dependent decrement in cell viability, mitochondrial membrane potential and an increment in lactate dehydrogenase release. Higher doses of C-PE (of both strains) accounted for loss of cell viability and nuclear pycnosis. These findings were further substantiated with flow cytometry that revealed a cell arrest at G0/G1 phase and a high percentage of cells undergoing apoptosis following C-PE treatment. These results confirm the efficacy of C-PE from Phormidium sp. or Halomicronema sp. in triggering apoptotic cell death. This study is the first to report on apoptotic property of C-PE against A549 human lung carcinoma cells and warrants further studies to establish its anti-cancer potential.

Sunflower oil mediated biomimetic synthesis and cytotoxicity of monodisperse hexagonal silver nanoparticles.

In this work, sunflower oil was utilized for the biomimetic synthesis of silver (Ag) nanoparticles (NPs), leading to highly mono-dispersed hexagonal-shaped silver nanoparticles (NPs) at various concentrations. It was found that the biomolecules of the oil not only have the capability to reduce silver ions, due to its extended phenolic system, but also appear to recognize and affect the Ag nanocrystal growth on the (110) face, leading to hexagonal growth of the NPs of 50 nm size. Initially, some spherical AgNPs of less than 10nm diameter were observed; however, over a longer period of time, a majority of hexagonal-shaped nanocrystals were formed. The one step synthesis can be extended for other metals. The as prepared sunflower oil capped AgNPs being completely free of toxic chemicals can be directly utilized for in vitro studies and offer a more rational approach for cellular applications. The NP solution exhibited dose-dependent cytotoxicity in human lung carcinoma cells and physiologically relevant cell model (3T3L1 cells).

Synthesis and cytotoxicity evaluation of novel acylated starch nanoparticles.

Starch nanoparticles (StNPs) were acylated under ambient conditions to obtain various nanosized derivatives formed stable suspension in water and soluble in organic solvents. The degree of substitution (DS) was determined using (1)H NMR technique. The cytotoxicity potential of the derivatised StNPs was evaluated in mouse embryonic fibroblast (3T3L1) cells and A549 tumor cell line using MTT cell viability assay. Other parameters that determine the oxidative stress viz., reactive oxygen species (ROS) generation, intracellular reduced glutathione (GSH), superoxide generation and acridine orange/ethidium bromide staining were also investigated. The present study led to the conclusion that cytotoxic activity of acylated starch nanoparticles was dependent on their dosage, DS and type of substitution. The non-toxic nature in non-cancerous cells reveals that the nanoparticles (NPs) can be used for cancer therapy and drug delivery. The nanoparticles also offered reasonable binding propensity with CT-DNA.

Protective role of standardized Feronia limonia stem bark methanolic extract against carbon tetrachloride induced hepatotoxicity.

OBJECTIVE: This study evaluates hepatoprotective potential of Feronia limonia stem bark (FSB) extracts and fractions using experimental models. MATERIALS AND METHODS: Activity levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and cell viability were evaluated in HepG2 cells treated with carbon tetrachloride (CCl4) in presence or absence of FL extracts or fractions. Also, plasma markers of hepatic damage, hepatic antioxidants, lipid peroxidation and histopathological alterations were assessed in rats treated with CCl4 alone or in combination with 200 or 400 mg/kg bodyweight (BW) of FSB-7 or 25 mg/kg BW of silymarin. RESULTS: In vitro co-supplementation of FSB extracts or fractions recorded varying degree of hepatoprotective potentials. Also, pre-supplementation of FSB methanolic extract (FSB-7) followed by CCl4 treatment significantly prevented hepatic damage and depletion of cellular antioxidants. Also, CCl4+ FSB-7 group showed minimal distortion in the histoarchitecture of liver and results were comparable to that of CCl4+ silymarin treated rats. CONCLUSION: This inventory is the first scientific report on hepatoprotective potential of FSB methanolic extract.

Hepatoprotective potential of Tecomella undulata stem bark is partially due to the presence of betulinic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: Tecomella undulata (TU;` Family Bignoniaceae) is used in Indian Ayurvedic system of medicine for treating various diseases including hepatic ailments. It is also incorporated in various marketed hepatoprotective polyherbal formulations. AIM: The present study was aimed at evaluating possible hepatoprotective role of isolated compounds from TU stem bark (TSB) using in vitro and in vivo experimental models. METHODS: In vitro cytotoxicity and hepatoprotective potential of various extract, fractions and isolated compounds from TU stem bark were evaluated using HepG2 cells. Rats were pre-treated with TU methanolic extract (TSB-7) or betulinic acid (MS-2) or silymarin for 7 days followed by a single dose of CCl(4) (0.5 ml/kg, i.p.). Plasma markers of hepatic damage, hepatic antioxidants and indices of lipid peroxidation along with microscopic evaluation of liver were assessed in control and treatment groups. RESULTS: TSB-2 and MS-1 accounted for significant cell death whereas; TSB-1, TBS-7, TSB-9, TSB-10 and, MS-2 did not register significant cytotoxicity. Further, non-cytotoxic components exhibited ascending grade of hepatoprotection in vitro (TSB-10

Cardio protective effect of Coriandrum sativum L. on isoproterenol induced myocardial necrosis in rats.

The preventive effect of Coriandrum sativum L. (CS) on cardiac damage was evaluated by Isoproterenol (IP) induced cardiotoxicity model in male Wistar rats. Rats were pretreated with methanolic extract of CS seeds at a dose of 100, 200 or 300 mg/kg orally for 30 days and they were subsequently administered (s.c.) with IP (85 mg/kg body weight) for the last two days. IP treated rats showed increased LPO, decreased levels of endogenous antioxidants and ATPases in the cardiac tissue together with increased plasma lipids and markers of cardiac damage. TTC staining showed increased infarct areas while HXE staining showed myofibrillar hypertrophy and disruption. CS (200 and 300 mg/kg body weight) pretreatment significantly prevented or resisted all these changes. Our results show that methanolic extract of CS is able to prevent myocardial infarction by inhibiting myofibrillar damage. It is also concluded that, the rich polyphenolic content of CS extract is responsible for preventing oxidative damage by effectively scavenging the IP generated ROS.

Protective role of Brassica olerecea and Eugenia jambolana extracts against H2O2 induced cytotoxicity in H9C2 cells.

This study assesses the efficacy of anthocyanin rich Brassica olerecea leaves (ARCE) and flavonoid rich Eugenia jambolana seed (EJSE) extracts as possible cardioprotective agents against hydrogen peroxide (H(2)O(2)) induced cytotoxicity in H9C2 cells. Presence of ARCE or EJSE resulted in a superior cell viability and cell integrity as revealed by cell viability and lactate dehydrogenase release assays and acridine orange and ethidium bromide staining of control and H(2)O(2) treated H9C2 cells. These extracts were also able to reduce the impact of H(2)O(2) induced lipid peroxidation and depletion of intracellular glutathione. Also, there was an increase in mitochondrial membrane potential and reduced generation of intracellular reactive oxygen species following ARCE or EJSE treatments. These results suggest that ARCE and EJSE are capable of cardioprotective activity due to the high number of anthocyanins and flavonoids in them that are instrumental in lowering intracellular oxidative stress, preventing depletion of cellular antioxidants and improving cell viability.