Chang Liver Cell Line Research Articles

Chemical constituents from the stem barks of Calophyllum recurvatum P.F. Stevens and Calophyllum andersonii P.F. Stevens, and their in-vitro hepatotoxic activity

Bioactive phenolics can be found in abundance in Calophyllum species. Phytochemical studies are carried out on the stem bark of Calophyllum recurvatum and Calophyllum andersonii, which has led to the isolation and elucidation of phytochemicals, thwaitesixanthone (1), teysmanone A (2), soulattrolide (3), calanone (4), isocalanone (5) and friedelin (6), respectively. The cytotoxic activities of compounds (2), (3), (4) and (5) as well as plant extracts were tested against HeLa Chang liver, HepG2 and HL-7702 cell lines. Phenylpyranocoumarins, teysmanone A (2) and soulattrolide (3) portrayed appreciable cytotoxicity activities at 42.57 ± 1.20 and 34.53 ± 3.41 µg/mL, respectively against HepG2 cell line comparable to the positive control, curcumin. Meanwhile, n-hexane extract from C. recurvatum exhibited cytotoxicity with the IC50 value of 36.43 ± 0.64 and 26.25 ± 4.83 µg/mL against HeLa Chang liver and HepG2 cell lines. All the tested compounds and plant extracts displayed non-cytotoxic properties on HL-7702 cell line.

RP-HPLC-DAD Analysis of Mitragynine Content in Mitragyna speciosa Korth. (Ketum) Leaf Extracts Prepared Using Ultrasound Assisted Extraction Technique and Their Cytotoxicity

Mitragynine and its congeners are one of the major phytoconstituents present in Mitragyna speciosa Korth. (ketum) leaves and a well-known factor that contributes to ketum’s pharmacological activities. This study describes the usage of a green extraction method to yield botanical leaf extracts of ketum. The leaf extracts were assessed for mitragynine content, total phenolic and flavonoid content, and cytotoxicities. The Ultrasound Assisted Extraction (UAE) method showed a varying dry yield of the extracts (0.22–1.92 g) that were obtained with solvents of variable polarities. However, the mitragynine content was consistent among the organic solvent extracts (7.22–9.40%). This method calls for a minimal extraction solvent volume (solid to solvent ratio, 1:30) and a shorter extraction period (20 min). Of the solvents tested, the methanolic extract showed the highest content of total phenolic (419.50 ± 2.50 GAE mg/g) and flavonoids (177.33 ± 3.00 QE mg/g). The extract was nontoxic towards kidney (HEK-293) and Chang liver (HeLa) cell lines. Analysis via UHPLC-ESI-QTOF-MS/MS made it possible to identify mitragynine congeners, such as mitragynine, paynantheine, and speciociliatine, in the leaves extract. In conclusion, the UAE method using methanol as the extraction solvent provides a noncytotoxic ketum botanical extract for future preclinical and clinical studies.

Molecular and Nano-Structural Optimization of Nanoparticulate Mn2+-Hexarhenium Cluster Complexes for Optimal Balance of High T1- and T2-Weighted Contrast Ability with Low Hemoagglutination and Cytotoxicity.

The present work introduces rational design of nanoparticulate Mn(II)-based contrast agents through both variation of the μ3 (inner) ligands within a series of hexarhenium cluster complexes [{Re6(μ3-Q)8}(CN)6]4− (Re6Q8, Q = S2−, Se2− or Te2−) and interfacial decoration of the nanoparticles (NPs) K4−2xMnxRe6Q8 (x = 1.3 − 1.8) by a series of pluronics (F-68, P-123, F-127). The results highlight an impact of the ligand and pluronic for the optimal colloid behavior of the NPs allowing high colloid stability in ambient conditions and efficient phase separation under the centrifugation. It has been revealed that the K4−2xMnxRe6Se8 NPs and those decorated by F-127 are optimal from the viewpoint of magnetic relaxivities r1 and r2 (8.9 and 10.9 mM−1s−1, respectively, at 0.47 T) and low hemoagglutination activity. The insignificant leaching of Mn2+ ions from the NPs correlates with their insignificant effect on the cell viability of both M-HeLa and Chang Liver cell lines. The T1- and T2-weighted contrast ability of F-127–K4−2xMnxRe6Q8 NPs was demonstrated through the measurements of phantoms at whole body 1.5 T scanner.

Cytotoxic effects of Lavandula angustifolia seed extracts on the viability of Huh-7 and Chang liver cells.

Flowering plants are valuable in numerous ways, including food/feed supply for living organisms, fuel production, and medicinal uses. Several plant extracts/products are used to treat variety of serious ailments in human and animals. Lavandula angustifolia is a flowering plant that possesses anti-inflammatory and anti-depressive medicinal properties. Cancer is a deadly disorder affecting millions of people globally. It affects several human organs, including liver, stomach, and lungs. Several researchers are doing efforts to eliminate the disease around the globe. In this study, Chang and Huh-7 liver cell lines were utilized as human normal hepatocyte model and innovation to mimic the liver environment. Cytotoxicity of L. angustifolia seed extracts was investigated at two different concentrations (50% and 100%) against Chang and Huh-7 liver cell lines by colorimetric assay which is used to assess cell metabolic activities. The Chang and Huh-7 liver cell lines were treated with L. angustifolia seeds extracts (50% and 100%) and incubated for 24 and 48 hours under standard conditions (37°C, 5% CO2). The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was employed to quantify cell survival. Seed extracts of L. angustifolia exerted varied cytotoxic effects depending on the concentration and treatment duration. The results indicated that L. angustifolia seed extracts with 100% concentration exhibited the highest cytotoxicity against Huh-7 and Chang liver cell lines. In conclusion, L. angustifolia seed extracts exhibited cytotoxic activity which can be enhanced based on the concentration and treatment duration. The findings of the current study are critical for the development of novel herbal-based therapies for fatal disorders such as liver cancer. However, more investigations are required to reveal cytotoxicity mechanisms of L. angustifolia seed extracts.

Sustainable phyto-fabrication of silver nanoparticles using Gmelina arborea exhibit antimicrobial and biofilm inhibition activity

Increase in bacterial resistance to commonly used antibiotics is a major public health concern generating interest in novel antibacterial treatments. Aim of this scientific endeavor was to find an alternative efficient antibacterial agent from non-conventional plant source for human health applications. We used an eco-friendly approach for phyto-fabrication of silver nanoparticles (AgNPs) by utilizing logging residue from timber trees Gmelina arborea (GA). GC–MS analysis of leaves, barks, flowers, fruits, and roots was conducted to determine the bioactive compounds. Biosynthesis, morphological and structural characterization of GA-AgNPs were undertaken by UV–Vis spectroscopy, scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDX), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometer (XRD). GA-AgNPs were evaluated for antibacterial, antibiofilm, antioxidant, wound healing properties and their toxicity studies were carried out. Results identified the presence of terpenoids, sterols, aliphatic alcohols, aldehydes, and flavonoids in leaves, making leaf extract the ideal choice for phyto-fabrication of silver nanoparticles. The synthesis of GA-AgNPs was confirmed by dark brown colored colloidal solution and spectral absorption peak at 420 nm. Spherical, uniformly dispersed, crystalline GA-AgNPs were 34–40 nm in diameter and stable in solutions at room temperature. Functional groups attributed to the presence of flavonoids, terpenoids, and phenols that acted as reducing and capping agents. Antibacterial potency was confirmed against pathogenic bacteria Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus by disc diffusion assay, MIC and MBC assay, biofilm inhibition assay, electron-microscopy, cell staining and colony counting techniques. The results from zone of inhibition, number of ruptured cells and dead-cell-count analysis confirmed that GA-AgNPs were more effective than GA-extract and their bacteria inhibition activity level increased further when loaded on hydrogel as GA-AgNPs-PF127, making it a novel distinguishing feature. Antioxidant activity was confirmed by the free radical scavenging assays (DPPH and ABTS). Wound healing potential was confirmed by cell scratch assay in human dermal fibroblast cell lines. Cell-proliferation study in human chang liver cell lines and optical microscopic observations confirmed non-toxicity of GA-AgNPs at low doses. Our study concluded that biosynthesized GA-AgNPs had enhanced antibacterial, antibiofilm, antioxidant, and wound healing properties.

Temperature-sensitive emission of dialkylaminostyrylhetarene dyes and their incorporation into phospholipid aggregates: Applicability for thermal sensing and cellular uptake behavior

A series of dialkylaminostyrylhetarene dyes constructed from electron-rich and electron-deficient moieties of various structures connected via vinylene π-bridges are introduced as temperature-sensitive luminophores. The temperature dependent emission of the dyes in the acidified dichloromethane solutions derives from temperature-induced shift of the equilibrium between neutral and protonated forms of the dyes. The heating-induced blue shift and intensification of emission of neutral form of the dyes make them a promising basis for development of nanoparticles exhibiting temperature-sensitivity in aqueous solutions at pH typical of biological liquids. Hydrophobicity-driven incorporation of the water insoluble dyes into L-α-phosphatidylcholine(PC)-based bilayers allows to obtain water dispersible dye-PC aggregates, and to follow their emission in the aqueous solutions. Structure of the dyes has strong impact on the efficacy of the dyes incorporation into the PC-based bilayers, temperature sensitivity of emission of the dye-PC aggregates and its reversibility under the heating/cooling cycles. This enables structural optimization of the dyes in order to obtain the dye-PC species demonstrating maximal temperature dependence and reversibility of their luminescence in aqueous solutions. The selected leader exhibits low cytotoxicity exemplified for M−HeLa and Chang Liver cell lines, while the efficient cell internalization of the dye, manifested in the staining of the cell cytoplasm, opens further opportunities for biosensing applications.

In vitro anti-diabetic effect and cytotoxicity of South African Ipomoea oblongata

Ipomoea oblongata is a popular plant known for its diverse therapeutic uses in South African folk medicine but currently has limited empirical evidence to support some of these uses. In the current study, we evaluated the in vitro anti-diabetic and cytotoxic effects of the root extracts of Ipomoea oblongata. Methanol and water extracts were tested for anti-diabetic activity using glucose uptake/utilisation response in muscle (C2C12) and Chang liver cell lines. Water extract demonstrated a noteworthy (182%) anti-diabetic activity in muscle cell lines which was similar to the effect exerted by insulin (192%, positive control). No noteworthy glucose uptake/utilisation occurred with the Chang liver cell lines. Generally, Ipomoea oblongata extracts were relatively safe based on the response in the MTT assay against muscle (C2C12) and Chang liver cell lines. The noteworthy in vitro anti-diabetic effect and absence of cytotoxic effect against both cell lines provide preliminary empirical evidence that supports the utilisation of Ipomoea oblongata as a popular herbal medicine in folk medicine.

Ethanolic extract of Nymphaea lotus L. (Nymphaeaceae) leaves exhibits in vitro antioxidant, in vivo anti-inflammatory and cytotoxic activities on Jurkat and MCF-7 cancer cell lines

BackgroundNymphaea lotus L. (N. lotus) is an aquatic plant with anecdotal reports suggesting its use in the traditional management of cancer. However, there is a paucity of data on the antioxidant, anti-inflammatory and cytotoxic properties of N. lotus in relation to its phytochemical and elemental contents. This study aimed at determining the antioxidant, anti-inflammatory and cytotoxic properties of the hydro-ethanolic extract of N. lotus leaves (NLE), and its phenolic, flavonoid and elemental constituents.MethodsThe antioxidant property of NLE was determined using total phenolic and flavonoid, DPPH radical scavenging, lipid peroxidation and reducing power assays. The anti-inflammatory activity of NLE (100–250-500 mg/kg), diclofenac and hydrocortisone (positive controls) were determined by paw oedema and skin prick tests in Sprague Dawley rats. Also, the erythrocyte sedimentation rate (ESR) was determined by Westergren method. The macro/micro-elements content was determined by the XRF method. The cytotoxic property of NLE was determined by the MTT assay, on two cancer cell lines (MCF-7 and Jurkat) and compared to a normal cell line (Chang liver). Inhibitory concentrations were determined as IC50 values (±SEM).ResultsThe extract had appreciable levels of phenolic and flavonoids compounds and was two-fold more potent in scavenging DPPH radicals than Butylated hydroxytoluene (BHT). However, NLE was three- and six-fold less potent than ascorbic acid and BHT, respectively, in reducing Fe3+ to Fe2+. The extract was six-fold more potent than gallic acid in inhibiting lipid peroxidation. The extract caused a dose-dependent decrease in rat paw oedema sizes, comparable to diclofenac, and a significant decrease in wheel diameters and ESR. The elemental analysis revealed relevant concentrations of Mg2+, P2+, S2+, K2+, Mn+, Fe+, Cu+, Zn+ and Cd+. The extract exhibited cytotoxic activity on both MCF-7 (IC50 = 155.00 μg/ml) and Jurkat (IC50 = 87.29 μg/ml), with higher selectivity for Jurkat cell line. Interestingly, the extract showed low cytotoxicity to the normal Chang liver cell line (IC50 = 204.20 μg/ml).ConclusionN. lotus leaves extract exhibited high antioxidant, anti-inflammatory and cancer-cell-specific cytotoxic properties. These aforementioned activities could be attributed to its phenolic, flavonoid and elemental constituents.Graphical abstract

Antihyperglycemic, Antioxidant and Hepatoprotective Properties of Smilax wightii A.DC. : an Endemic Plant of Western Ghats

Phytotherapy is an inevitable companion of human civilization. Smilax wightii is an ethnomedicinal plant in Smilacaceae, with unexplored scientifically therapeutic potential. The antihyperglycemic, antioxidant and hepatoprotective capabilities of the methanolic extract of leaf, stem, rhizome and root of S. wightii were inspected in the present study. Hyperglycemia is a manifestation of the prevalent metabolic disorder, Type 2 Diabetes mellitus. Inhibitors of α –glucosidase and α – amylase could be efficiently employed in diabetes mellitus therapy as hypoglycemic agents. In the α –glucosidase and α – amylase inhibitory assays, root and rhizome extracts recorded better antihyperglycemic activity. DPPH radical scavenging activity and total antioxidant capacity were the parameters employed to determine the antioxidant activity. Hepatoprotectivity determines the capability of samples to safeguard the hepatocytes from damage. Novel hepatoprotective agents are in demand since the incidence of liver impairment is on a high among global population. The rhizome extract showed comparatively superior hepatoprotectivity followed by the leaf, stem and root extracts. Rhizome, at 100μg/ml guaranteed a cell viability percentage of 77.43 in the Chang liver cell line treated with Carbon tetrachloride. So the root and rhizome of S. wightii are the therapeutically significant plant parts with hypoglycemic, free radical scavenging and hepatoprotective potentialities.

Supraamphiphilic Systems Based on Metallosurfactant and Calix[4]resorcinol: Self-Assembly and Drug Delivery Potential.

Metallic amphiphiles are used as building blocks in the construction of nanoscale superstructures, where the hydrophobic effects induce the self-assembly of the nanoparticles of interest. However, the influence of synergizing multiple chemical interactions on an effective design of these structures mostly remains an open question. In this regard, supraamphiphilic systems based on flexible surfactant molecules and rigid macrocycles are being actively developed, but there are few works on the interaction between metallosurfactants and macrocycles. In the present work, the self-assembly and biological properties of a metallosurfactant with calixarene were studied for the first time. The metallosurfactant, a complex between lanthanum nitrate and two 4-aza-1-hexadecylazoniabicyclo[2.2.2]octane bromide units, and calix[4]resorcinol containing sulfonate groups on the upper rim were used to form a novel supraamphiphilic composition. The system formed was studied using a variety of physicochemical methods, including spectrophotometry, NMR, XRF, and dynamic and electrophoretic light scattering. It was found that the most optimal tetraanionic calix[4]resorcinol to dicationic metallosurfactant molar ratio, leading to mixed aggregation upon ion pair complexation, is 2:3. The mixed aggregates formed in the pentamolar concentration range were able to encapsulate hydrophilic substrates, including the anticancer drug cisplatin, the pure form of which is more cytotoxic toward healthy cells than toward diseased cells. Interestingly, the drug loaded into the macrocycle-metallosurfactant particles was less cytotoxic to a healthy Chang liver cell line and more cytotoxic to tumor M-HeLa cells. This selectivity depends on the amount of cisplatin added. The more drug is added to the macrocycle-metallosurfactant composition, the greater the biological activity against cancer cells. Taking into account that the appearance of resistance of cancer cells to drugs, especially to cisplatin, is one of the most important problems in treatment, the results of this work envisage the potential application of a mixed macrocycle-metallosurfactant system for the design of therapeutic cisplatin compositions.

“Double” Pyrimidine Derivatives: Synthesis and Primary Assessment of Hepatoprotective Properties In Vitro

“Double” derivatives of the drug Xymedon (1,2-dihydro-4,6-dimethyl-1-N-(hydroxyethyl)pyrimidone-2), hereafter referred to as pyrimidine (I), in which the pyrimidine (I) molecules are joined by an alkyl(xylylenyl)dionate bridge have been synthesized. Primary data on the hepatoprotective activity of five “double” pyrimidine (I) derivatives with different numbers of methylene groups and a meta-xylylene fragment in the ester bridge have been obtained on normal human hepatocytes of the Chang Liver cell line. The cytotoxicity and the cytoprotective properties of the new compounds against the background of exposure to d-galactosamine at a concentration of 150 mmol/L have been determined, their effect on the cell cycle compared with that of the initial pyrimidine (I) has been studied, and the dependence of the biological properties of the derivatives on their structure has been established.

Long Non-Coding RNA NRAD1 and LINC00152 are Highly Expressed and Associated with Prognosis in Patients with Hepatocellular Carcinoma.

BackgroundHepatocellular carcinoma (HCC) is prevalent throughout the world. The aim of this study is to explore new long non-coding RNAs (lncRNAs) associated with hepatocellular carcinoma and detect their expression levels in hepatocellular carcinoma cell lines and tissues. These results will provide new clues on further function and biomarker studies of HCC-related lncRNAs.Patients and MethodsAll patients were diagnosed as HCC between 30th, March, 2015 and 30th, July, 2018. LncRNA human gene expression microarray was applied to the profiling of lncRNAs in four cancerous tissues and the paired paracancerous tissues.ResultsWe retrospectively reviewed 63 patients with primary HCC who underwent a curative liver resection at the Department of Hepatology, Qingdao Sixth People’s Hospital. The expression level of lncRNA NRAD1 and LINC00152 was detected by real-time PCR. Prognostic factors were evaluated using Kaplan–Meier curves and Cox proportional hazards models. By microarray profiling of lncRNAs, 256 lncRNAs were found to be differentially expressed, including 162 upregulated and 94 downregulated (P<0.05, fold change>2). Two candidate lncRNAs were determined as the targets in this study, which were NRAD1 (upregulated by 6.35 fold), LINC00152 (upregulated by 4.53 fold). NRAD1 and LINC00152 were downregulated in the normal liver cell lines Chang liver, HL7702, THLE-2, THLE-3, FL62891 and AML12, which were significantly lower than HCC cell lines SMMC-7721, Hep3B, HuH7, MHCC-97H, HCC-LM and SK-Hep-1 (P<0.05). Overexpression of lncRNA NRAD1 and LINC00152 was associated with decreasing OS rates, respectively (P=0.0263 and P=0.0285). Meanwhile, overexpression of NRAD1 and LINC00152 was associated with decreasing PFS rates, respectively (P=0.0174 and P=0.0041). After adjusting for competing risk factors, we identified that microvascular invasion (P=0.014), tumor size (P=0.026), lncRNA NRAD1 (P=0.001) and LINC00152P9 (P=0.036) expression levels were independent prognostic factors associated with prognosis of patients with HCC.ConclusionWe found lncRNA NRAD1 and LINC00152 expressed significantly higher in HCC tissues compared with non-tumorous tissues. Overexpression of lncRNA NRAD1 and LINC00152 were independent risk factors associated with the prognosis of patients with HCC.

Soft nanocarriers for new poorly soluble conjugate of pteridine and benzimidazole: Synthesis and cytotoxic activity against tumor cells

New conjugated derivative of pteridine and benzimidazole, 7-(benzimidazol-2-yl)-6-(2,4-dichlorophenyl)-2-thioxo-2,3-dihydropteridin-4(1H)-one (BP) possessing antitumor activity was obtained and thoroughly characterized; its spectrophotometry control in solution was developed. To improve the solubility of the hydrophobic antitumor agent BP in aqueous solutions, amphiphilic systems (micellar solutions and modified liposomes) were fabricated, with their composition optimized. Stable 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based liposomes modified with cationic surfactants, namely cetyltrimetylammonium bromide and 1-methyl-3-hexadecylimidazolium bromide (IA-16), were obtained. It was shown that the use of cationic surfactants for the formation of hybrid drug carriers and varying of the surfactant/lipid molar ratios can be the key factor for obtaining the optimized particles with high efficiency of encapsulation, favorable loading efficacy and prolonged release of the drug. The most beneficial parameters in terms of stability and loading/release efficacy were obtained for IA-16/DPPC hybrid liposomes with the surfactant/lipid molar ratio of 1:50. Free BP demonstrated cytotoxicity toward M-Hela tumor cells, along with the nearly the same toxic effect toward normal Chang liver cells. Importantly, double effect occurred upon the encapsulation of BP into hybrid cationic liposomes, i.e. a sharp decrease in viability of diseased cells and increase of viability of normal cells. Therefore, liposomal BP formulation can be recommended as therapeutics with improved stability and high selective cytotoxicity toward M-Hela tumor cells at the level of commercial drug doxorubicin, in combination with much less toxicity (by 37 times) toward the normal Chang liver cell line.

The Roles Of Angiogenesis And Cancer Stem Cells In Sorafenib Drug Resistance In Hepatocellular Carcinoma.

BackgroundAn increasing number of studies support cancer stem cells as the reason for chemoresistance to sorafenib therapy in hepatocellular carcinoma (HCC), but the mechanism is still unclear. In this study, the mechanism of sorafenib resistance in cancer stem cells was examined by in vitro experiments and xenograft mouse model.MethodsThe expression of cancer stem cell markers in the Chang liver cell line and PLC/PRF/5 and HepG2 hepatoma cell lines were compared by immunoblot assay before and after sorafenib treatment in vitro. As a xenograft mouse model, subcutaneous injection of hepatoma cells followed by sorafenib therapy was performed in NU/NU mice. The effects of sorafenib therapy on tumor growth and cancer stem cell markers were studied. Angiogenesis associated with cancer stem cells was studied by immunoblot and immunohistochemistry assay.ResultsThe expression of cancer stem cell markers was higher in PLC/PRF/5 and HepG2 cells than Chang liver cells, indicating that these hepatoma cells had more stemness-related characteristics. The cancer stem cell markers were upregulated in the hepatoma cell lines following sorafenib treatment in vitro. In the xenograft model, tumors from PLC/PRF/5 and HepG2 cells with high E-cadherin expression were more resistance to sorafenib therapy. However, the expression of cancer stem cell markers was not significantly different after sorafenib therapy in these tumors. Furthermore, we found that sorafenib therapy induced angiogenesis within tumors from high E-cadherin expressing hepatoma cells.ConclusionThe mechanism of chemoresistance in sorafenib therapy in HCC may be the tumor angiogenesis associated with high E-cadherin expression in cancer stem cells.

New 2,6-diaminopyridines containing a sterically hindered benzylphosphonate moiety in the aromatic core as potential antioxidant and anti-cancer drugs

A series of 2,6-diaminopyridines was synthesized for the first time, containing phosphoryl sterically hindered phenolic fragments in the aromatic core. The antioxidant activity of these compounds was investigated, 2,6-diaminopyridine derivatives were shown to exhibit higher activity in comparison with their structural analogues. For dialkyl/diphenyl [(3,5-di-tert-butyl-4-hydroxyphenyl) (2,6-diaminopyridin-3-yl) methyl] phosphonates, their structural analogues based on meta-phenylenediamine, phosphorus-containing sterically hindered phenols and the corresponding cyclohexadienones cytotoxicity against tumor lines of epithelioid carcinoma of the cervix uteri (M-Hela) and breast adenocarcinoma (MCF-7) has been studied in vitro, as well as on normal human Chang liver cell lines. Diphenyl [(3,5-di-tert-butyl-4-hydroxyphenyl) (2,6-diaminopyridin-3-yl) methyl] phosphonate was shown to be the most active against the epithelioid line M-Hela - IC50 comprises 7.4 μM. It was shown that apoptosis induced by the lead compound proceeds along the internal pathway of caspase-9 activation. It was established that all studied compounds do not possess hemolytic activity.

Screening and identifying hepatotoxic components in Polygoni multiflori radix and Polygoni multiflori radix praeparata

Objective: In this study, the hepatotoxic components of Polygoni multiflori Radix and Polygoni multiflori Radix Praeparata (known as Heshouwu [HSW] and Zhiheshouwu [ZHSW] in China, respectively) were screened, isolated, and identified. Materials and Methods: The ethanol extracts of HSW and ZHSW were separated into 80 fractions according to their polarity in the preparation liquid phase. Chang liver cell line was used to screen the toxic components of HSW and ZHSW in vitro. The obtained toxic mixture was further collected, isolated, and identified to confirm the hepatotoxic compounds of HSW and ZHSW. Results: The identifid hepatotoxic compounds include 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, emodin, physcion-8-O-β-d-glucoside, physcion, and citreorosein, the fist two among them were the main components of HSW and ZHSW. After processing of HSW, the contents of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside and emodin in ZHSW were signifiantly decreased. Conclusions: The traditional processing with herb has signifiant effects on the components, especially the toxic components, in the extract of HSW and is an effective method to reduce its toxicity.

Synthesis and anti-cancer activities of glycosides and glycoconjugates of diterpenoid isosteviol.

A series of glycosides and glycoconjugates of diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with various monosaccharide residues were synthesized and their cytotoxicity against some human cancer and normal cell lines was assayed. Most of the synthesized compounds demonstrated moderate to significant cytotoxicity against human cancer cell lines M-HeLa and MCF-7. Three lead compounds exhibited selective cytotoxic activities against M-HeLa (IC50 = 10.0-15.1 μM) that were three times better than the cytotoxicity of the anti-cancer drug Tamoxifen (IC50 = 28.0 μM). Moreover, the lead compounds were not cytotoxic with respect to the normal human cell line Chang liver (IC50 > 100 μM), whereas Tamoxifen inhibited the viability of normal human Chang liver cells with an IC50 value of 46.0 μM. It was determined that the cytotoxicity of the lead compounds was due to induction of apoptosis proceeding along the mitochondrial pathway. The cytotoxic activity of the synthesized compounds substantially depended on the nature of the monosaccharide residue and its position, that is, whether the monosaccharide residue was attached directly to the isosteviol skeleton or was moved away from it by means of a polymethylene linker.

Toxicity Assessment of Wild Mushrooms from the Western Ghats, India: An in Vitro and Sub-Acute in Vivo Study.

Background: Poisoning by different kinds of toxic mushrooms is unfortunately becoming an increasingly important medical problem, evident from the growing number of reports worldwide since the 1950s. Mycetism being a health concern, deserves scientific attention. In this perspective, the present study aims to assess the potential effects of ingesting the selected wild mushrooms from regions of the Western Ghats, India.Methods: The preliminary cytotoxicity of the selected mushrooms was studied in vitro on the intestinal NCM460 and the Chang's liver cell lines on the basis of cell viability. Further, the hepatotoxicity was assessed by measuring biologically relevant endpoints such as membrane integrity, mitochondrial stress and oxidative status. A 28 day sub-acute toxicity study was carried out by orally administering the mushroom extracts to mice at 250 and 500 mg/kg body weight. The hematological and serum analysis as well as histological examinations were carried out to evaluate their in vivo toxicity. GC-MS analysis of the mushrooms facilitated the identification of their volatile chemical profile.Result: The in vitro intestinal cytotoxicity exhibited by these wild mushrooms in comparison to the edible mushroom indicated their potential gastrointestinal toxicity. The pathological findings in small intestine on exposure to Chlorophyllum molybdites and Agaricus endoxanthus also validates the speculations about their intestinal toxicity. The toxic insult to the hepatocytes due to Amanita angustilamellata, Entoloma crassum, and Clarkeinda trachodes was predictive of the observed in vivo hepatotoxicity which was also accompanied by renal toxicity at the higher dose of 500 mg/kg bwt.Conclusion: The potential toxicity exhibited by these representative mushrooms from the wild warrants caution about their consumption. The present work could also have broader implications for global mycetism.

NH4Cl affects the expression of Wnt/β-catenin pathway in hepatocytes.

We intended to explore whether NH4Cl influences the viability and regulates the expression of Wnt/β-catenin pathway in hepatocytes. The Chang liver cell line was used and cultured with different concentrations of NH4Cl (2.5, 5, 10, 20, 40, and 50 mmol/L) for 12, 24, and 48 h. The viability of hepatocytes was detected by MTT assay. The mRNA and protein expression level was analyzed with qRT-PCR and Western blotting, respectively. NH4Cl concentration significantly affects the viability of hepatocytes. With the increase of NH4Cl concentration, the viability of hepatocytes was decreased, accordingly. The mRNA and protein expression of Wnt1, β-catenin, and cyclin D was significantly increased after treatment with low concentrations of NH4Cl as compared with the control group, whereas their expression levels were decreased after treatment with high concentrations of NH4Cl. The mRNA and protein expression of Wnt1, β-catenin, and cyclin D was also significantly increased after treatment with NH4Cl for a short period as compared with the control group, whereas their expression levels were decreased after treatment with NH4Cl for a long period. In addition, we found NH4Cl treatment significantly reversed the results after RNA silencing of Wnt1 in hepatocytes. NH4Cl influences the viability of hepatocytes and affects the expression of Wnt/β-catenin pathway in hepatocytes.

Optimization of Biosynthesis of Silver Oxide Nanoparticles and Its Anticancer Activity

Silver oxide nanoparticle can be synthesized by chemical and biological methods. Biological synthesis has emerged as an exciting, ecofriendly approach. However, the process tends to be slow when we consider its industrial applicability. The development of reliable method for rapid synthesis of nanoparticles is one of the significant zones of interests in current nanotechnological research. In this paper, optimization of physiochemical parameters for rapid silver oxide nanoparticle synthesis using Bacillus thuringiensis SSV1 culture supernatant has been elucidated. Spherical-shaped silver oxide nanoparticles with an average particle size of 30[Formula: see text]nm were obtained. The cytotoxic effect of silver oxide nanoparticles was studied against HepG2 and Chang liver cell lines by MTT assay. These nanoparticles showed dose-dependent response on HepG2 (IC[Formula: see text]g/mL) and Chang liver cells (IC[Formula: see text]g/mL).