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Background: Rhizoma Paridis (RP) is a traditional Chinese herb used for the treatment of tumors, detoxification and hemostasia. Studies show the main components of RP are Polyphyllin I (PPI), polyphyllin VI (PPVI), and polyphyllin VII (PPVII). However, the pharmaco-mechanisms of these compounds are not clear. Objective: By used 1H nuclear magnetic resonance (1H-NMR) based metabolomics approach to identify the Anticancer effects of PPI, PPVI and PPVII in HepG2 cells. Methods: 1H nuclear magnetic resonance (1H-NMR) based metabolomics approach was applied to investigate the toxicological effect of PPI, PPVI, PPVII on HepG2 cells. Multivariate statistical analysis was employed to examine the metabolic changes and abnormal metabolic pathways, including Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and orthogonal PLS-DA (OPLS-DA). Results: The results showed that the effects of metabolic phenotypes were affected separately by PPI, PPVI, and PPVII. The metabolic phenotypes were also changed over time. The characteristic metabolites were varied by affecting different polyphylins, which were identified by the reconstructed OPLSDA loading plots. According to the characteristic metabolites, the mainly disturbed metabolic pathways were found, such as alanine, aspartate and glutamate metabolism, pyruvate metabolism, glycine, serine, and threonine metabolism. Conclusion: The current work could allow us to understand the therapeutic effect of RP in metabolism. It also indicated that RP would be a promising candidate for liver cancer treatment.

This study was designed to evaluate the hepatoprotective effect of alcoholic and n-hexane extracts of crayfish Procambarus clarkii against CCl4 (4 mM) induced toxicity in the human hepatoma cell li...

Diabetes mellitus leads to cellular damage and causes apoptosis by oxidative stress. Heartwood extract of Pterocarpus marsupium has been used in Ayurveda to treat various diseases such as leprosy, diabetes, asthma, and bronchitis. In this study, we worked out the mechanism of the antidiabetic potential of methanolic heartwood extract of Pterocarpus marsupium (MPME). First, metabolic profiling of MPME was done using gas chromatography-mass spectrometry (GCMS), ultra-performance liquid chromatography-mass spectroscopy (UPLC-MS), and high-performance thin-layer chromatography (HPTLC) to identify phenols, flavonoids, and terpenoids in MPME. Biological studies were carried out in vitro using the HepG2 cell line. Many antidiabetic compounds were identified including Quercetin. Methanolic extract of MPME (23.43 µg/mL–93.75 µg/mL) was found to be safe and effective in reducing oxyradicals in HepG2 cells. A concentration of 93.75 µg/mL improved glucose uptake efficiently. A significant decrease in oxidative stress, cell damage, and apoptosis was found in MPME-treated HepG2 cells. The study suggests that the heartwood of Pterocarpus marsupium offers good defense in HepG2 cells against oxidative stress and improves glucose uptake. The results show the significant antidiabetic potential of MPME using a HepG2 cell model. The effect seems to occur by reducing oxidative stress and sensitizing the cells towards glucose uptake, hence lowering systemic glucose levels, as well as rescuing ROS generation.

A new fluorescent probe (PAC) based on phenothiazine was designed and synthesized for the detection of hydrazine (N2H4), which uses methyl cyanoacetate as the recognition group and phenothiazine as the fluorescent chromophore. The Stoke shift of probe PAC at the presence of hydrazine reached to 120 nm and the detection limit of probe PAC performed as 6.7 ppb. PAC had AIE properties and provided with the functions of naked-eye recognition. The DFT and TD-DFT calculations exhibited that the probes of PAC performed good responses to hydrazine. In addition, cell imaging showed that the probe PAC effectively recognized the hydrazine in HepG2 cells and stained the cells green.

Chemical investigation of the whole plant of Sauropus hirsutus Beille led to the isolation of eight quinolines and two known flavonoids. Furthermore, five quinolines were new, two were reported in plant for the first time and one was known. Cytotoxicity evaluation against cholangiocarcinoma, KKU-M156, showed that the most active compound was 4-hydroxy-6-methoxy-7,8-methylenedioxyquinaldine (IC50 20.54 ± 6.82 µM) which was a little more active than the cisplatin standard (IC50 24.39 ± 1.14 µM).

Glucose-regulated protein 78 (GRP78) is overexpressed in a wide variety of solid tumors, serving as a well-characterized target for tumor imaging or therapy. In this work, we developed a GRP78-responsive radiotracer (DOTA-68Ga)-Gly-Gly-Gly-Ser-Phe-Ser-Ile-Ile-His-Thr-Pro-Ile-Leu-Pro-Leu-Gly-Gly-Cys ([68Ga]SP94) for hepatocellular carcinoma (HCC) micro-PET imaging. DOTA-SP94 was synthesized by solid phase synthesis and then radiolabeled with 68GaCl3 with >99% radiochemical purity. The expression levels of GRP78 in HepG2 cells were confirmed by Western blotting. In vitro and in vivo study of [68Ga]SP94 showed high stability and high uptake in GRP78-overexpressing HepG2 cells and tumor, fast clearance, and low nontarget uptake. Micro-PET images showed excellent tumor accumulation of [68Ga]SP94 in the HepG2-implanted nude mice tumor model. Additionally, the radiotracer uptake in HepG2 tumors can be blocked by unlabeled DOTA-SP94, suggesting that the tracer uptake by HCC was receptor-mediated. We envision that our radiotracer can be used for noninvasive imaging of HCC and is worthy of further clinical investigations.

The study aimed to investigate the bioaccessibility and the stability of purified ethanol extracts (PEE) from Cudrania cochinchinensis roots, and the changes in antioxidant activity and enzyme inhibition activity and cytotoxicity by in vitro digestion. No compounds were lost during the gastrointestinal digestion (GID) process, 15 compounds were tentatively identified using UPLC-TOF-MS/MS technology, including five phenolic and ten flavonoid compounds. After the gastric digestion (GD), the bioaccessibility of phenolic and flavonoid compounds was 55.66% and 52.44%, respectively. After the intestinal digestion (ID), the bioaccessibility of phenolic and flavonoid compounds reduced to 39.70% and 33.36%, respectively. The gastrointestinal digestion (GID) decreased the bioaccessibility of phenolic compounds. All compounds were affected throughout the gastrointestinal digestion (GID), among which the more affected compounds were 4-hydroxybenzoic acid, eriodictyol-7-O-glucoside, resveratrol and 3,6,3’,4’-tetrahydroxyflavone (compared with the peak intensity of the undigested PEE). Furthermore, there was a reduction in the antioxidant activity, inhibition activity against α-glucosidase and tyrosinase, and cytotoxicity toward HepG2 cells of the PEE after GID. There was a significantly positive correlation between the bioactivity and the total phenolic/flavonoid contents. The results showed that in vitro digestion had significant effects on the phenolic content and bioactivity. Although phenolic contents were decreased during GID, C. cochinchinensis roots is still a good source of bioactive compounds for the development of functional foods with health benefits.

Two new triterpenoids, entanolide (1) and methyl 3,4-secotirucalla-23-oxo-4(28),7,24-trien-21-al-3-oate (2), together with nine known compounds (3-11), were isolated from the bark of Entandrophragma angolense. Their structures were elucidated based on spectroscopic analyses, mainly 1 D and 2 D NMR spectral data. Compounds 1-6 and 8 were evaluated for their cytotoxicity against HepG2 cells, and compounds 2-5 exhibited weak activities.

Ruthenium complexes are at the forefront of developments in metal-based anticancer drugs, but many questions remain open regarding their reactivity in biological media, including the role of transferrin (Tf) in their transport and cellular uptake. A well-known anticancer drug, KP1019 ((IndH)[RuIIICl4(Ind)2], where Ind = indazole) and a reference complex, [RuIII(nta)2]3− (nta = nitrilotriacetato(3−)) interacted differently with human apoTf, monoFeTf, or Fe2Tf. These reactions were studied by biolayer interferometry (BLI) measurements of Ru–Fe–Tf binding to recombinant human transferrin receptor 1 (TfR1) in conjunction with UV-vis spectroscopy and particle size analysis. Cellular Ru uptake in human hepatoma (HepG2) cells was measured under the conditions of the BLI assays. The mode of Tf binding and cellular Ru uptake were critically dependent on the nature of Ru complex, availability of Fe(III) binding sites of Tf, and the presence of proteins that competed for metal binding, particularly serum albumin. Cellular uptake of KP1019 was not Tf-mediated and occurred mostly by passive diffusion, which may also be suitable for treatments of inoperable cancers by intratumoral injections. High cellular Ru uptake from a combination of [RuIII(nta)2]3− and Fe2Tf in the absence of significant Ru–Tf binding was likely to be due to trapping of Ru(III) species into the endosome during TfR1-mediated endocytosis of Fe2Tf.

A new triarylindanone, namely selagindanone A (1), and a new isobenzofuranone (2), 3,4-bis(4-hydroxyphenyl)isobenzofuran-1(3H)-one, were isolated from Selaginella tamariscina. Their structures were elucidated by comprehensive spectroscopic and mass spectrometric analyses, including 1 D-, 2 D-NMR and HR-ESI-MS. Compound 1 possesses a unique structural feature of triaryl-substituted in the skeleton of 1-indanone. In addition, compound 2 showed weak cytotoxicity against human hepatocellular carcinoma SMMC-7721 and HepG2 cell lines.

The characterization of the metabolism of lower chlorinated PCB, such as 4-chlorobiphenyl (PCB3), is challenging because of the complex metabolite mixtures formed in vitro and in vivo. We performed parallel metabolism studies with PCB3 and its hydroxylated metabolites to characterize the metabolism of PCB3 in HepG2 cells using nontarget high-resolution mass spectrometry (Nt-HRMS). Briefly, HepG2 cells were exposed for 24 h to 10 μM PCB3 or its seven hydroxylated metabolites in DMSO or DMSO alone. Six classes of metabolites were identified with Nt-HRMS in the culture medium exposed to PCB3, including monosubstituted metabolites at the 3′-, 4′-, 3-, and 4- (1,2-shift product) positions and disubstituted metabolites at the 3′,4′-position. 3′,4′-Di-OH-3 (4′-chloro-3,4-dihydroxybiphenyl), which can be oxidized to a reactive and toxic PCB3 quinone, was a central metabolite that was rapidly methylated. The resulting hydroxylated-methoxylated metabolites underwent further sulfation and, to a lesser extent, glucuronidation. Metabolomic analyses revealed an altered tryptophan metabolism in HepG2 cells following PCB3 exposure. Some PCB3 metabolites were associated with alterations of endogenous metabolic pathways, including amino acid metabolism, vitamin A (retinol) metabolism, and bile acid biosynthesis. In-depth studies are needed to investigate the toxicities of PCB3 metabolites, especially the 3′,4′-di-OH-3 derivatives identified in this study., Please provide a synopsis

This study was undertaken to evaluate the antioxidative and lipid accumulation inhibitory effects in HepG2 cell of 11 Tunisian plants extracts. Total phenolics contents (TPC), and total flavonoid contents (TFC) of 11 plants extracts were measured, and antioxidative activities was analyzed using DPPH, ABTS, FRAP, ORAC and TBA assay. Inhibitory effect of oxidative stress was evaluated by cell viability and lipid peroxidation level in H2O2-treated HepG2 cells. Lipid accumulation inhibitory effect was determined by Oil-Red-O staining and intracellular triglyceride assay in HepG2 cell. M. communis L. (156.73 mgGAE/g) and N. glauca Graham (108.81 mgNAE/g) were the highest TPC and TFC, respectively, among 11 plants. M. communis L. were the highest antioxidant activity in DPPH and ABTS. FRAP and ORAC results revealed that antioxidant activity in 10 species were higher than the positive control. Among the 11 species, 5 species with the lowest malondialdehyde level were selected and HPLC analysis revealed that plants contain caffeic acid, quercetin, and rutin. 5 plants treatment inhibited lipid peroxidation level and protected HepG2 cells from oxidative stress. Moreover 5 plants significantly inhibited the lipid accumulation and triglyceride content. These results imply scientific evidence for the development of functional foods using 11 plants from Tunisia which has oxidative stress and lipid accumulation reduction effects.

A phytochemical investigation on the roots of Sophora flavescens resulted in the isolation of two undescribed lavandulylated acylphloroglucinols, flavescenols A (1) and B (2), together with biogenetically related analogues (3–6). Their structures were established on the basis of 1D, 2D NMR, and HR-ESI-MS spectroscopic analysis. Since flavescenols represent the first example of lavandulylated acylphloroglucinols, the biogenetical relationship of compounds 1-6 is proposed. In addition, all isolates were evaluated for their antiproliferative activity against HepG2 cell lines and inhibitory effects on LPS-induced NO production in RAW 264.7 cells.

In this work, we describe how stereochemically complex polycyclic compounds can be generated by applying a synthetic sequence comprising an intramolecular Ugi reaction followed by a Pictet-Spengler cyclization on steroid-derived scaffolds. The resulting compounds, which combine a fragment derived from a natural product and a scaffold not found in nature. are both structurally distinct and globally similar to natural products at the same time, and interrogate an alternative region of the chemical space. One of the new compounds showed significant antiproliferative activity on HepG2 cells through a caspase-independent cell-death mechanism, an appealing feature when new antitumor compounds are searched.

Three undescribed sesquineolignans, Ziziphusmps A-C (1-3) were isolated from the seeds of Ziziphus jujuba. their gross structure was identified by comprehensive spectroscopic analyses. The part relative configurations were determined by the NOESY correlation and coupling constant. All isolates were tested for their cytotoxicity against the hepatocellular carcinoma Hep3B and HepG2 cells. The results indicated that none of them exhibited obvious cytotoxicity against two hepatocellular carcinoma cell lines.

Among several strategies related to cancer therapy targeting the modulation of αβ-tubulin has shown encouraging findings, more specifically when this is achieved by inhibitors located at the colchicine binding site. In this work, we aim to fish new αβ-tubulin modulators through a diverse and rational VS study, and thus, exhibiting the development of two VS pipelines. This allowed us to identify two compounds 5 and 9 that showed IC50 values of 19.69 and 21.97 μM, respectively, towards possible modulation of αβ-tubulin, such as assessed by in vitro assays in C6 glioma and HEPG2 cell lines. We also evaluated possible mechanisms of action of obtained hits towards the colchicine binding site of αβ-tubulin by using docking approaches. In addition, assessment of the stability of the active (5 and 9) and inactive compounds (3 and 13) within the colchicine binding site was carried out by molecular dynamics (MD) simulations, highlighting the solvent effect and revealing the compound 5 as the most stable in the complex. At last, deep analysis of these results provided some valuable insights on the importance of using mixed ligand- and structure-based strategies in VS campaigns, in order to achieve higher chemical diversity and biological effect as well.

Protein tyrosine phosphatase 1B (PTP1B) is a highly validated target for the treatment of type 2 diabetes and obesity. Previous studies have shown that bromophenols from marine red alga Rhodomela confervoides can inhibit PTP1B activity. However, traditional in vitro enzymatic assays may result in false positive activity. Here, we reported a successful application of molecular docking and surface plasmon resonance (SPR) assay for the characterization of small-molecule PTP1B inhibitors with high affinity. First, molecular docking study indicated that six bromophenol compounds preferred to bind PTP1B with open conformation rather than one with closed conformation. Next, SPR study indicated that compound 3 was the most potent and stable PTP1B inhibitor at the nanomolar level. Then Lineweaver-Burk plot data showed that compound 3 was a competitive PTP1B inhibitor. Moreover, compound 3 could improve palmitate-induced insulin resistance in HepG2 cells. Taken together, molecular docking and SPR-based methodology could apply in the development of PTP1B inhibitors with high affinity.

Morchella angusticeps Peck, one of the most popular edible mushrooms, has attracted great attention due to its delicious taste and healthy properties. However, both its biological effects and the possible mechanism of action have not yet been known. We investigated the anti-proliferative activity of the phenolic extract derived from Morchella angusticeps Peck (MPE) against HepG2 human hepatocellular carcinoma cells. Results showed that MPE at non-cytotoxicity doses significantly inhibited the proliferation of HepG2 cells in a dose-dependent manner with inhibitory rates ranging from 18 to 90% (P

Hepatocellular cancer (HCC) is one of the leading causes of mortality worldwide. Unfortunately, a limited choice of anti-cancer drugs is available for treatment, owing to their minimal efficacy and development of acquired resistance. Autophagy, a cellular survival pathway, often exhibits a pleiotropic role in HCC progression. Studies show increased autophagy in established HCC, promoting the survival of HCC cells in the tumour microenvironment. Therefore, novel anti-autophagy drugs hold promise for preventing HCC progression. Here, using a non-biased transcriptomics analysis in HepG2 cells we demonstrate the existence of an autophagy-FOXM1 nexus regulating growth in HepG2 cells. Additionally, we show that suppression of autophagy by an Unc-51 Like Autophagy Activating Kinase 1(ULK1) inhibitor not only attenuates the expression of FOXM1 and its transcriptional targets, but also has a synergistic effect on the inhibition of HepG2 growth when combined with FOXM1 inhibitors. Thus, the autophagic protein, ULK1, is a promising candidate for preventing HCC progression. Collectively, our results provide new insight into the role of autophagy in HCC growth and are a proof-of concept for combinatorial therapy using ULK1 and FOXM1 inhibitors.

Oxidative stress can directly damage lipids, proteins, and DNA, which promotes the progression from steatosis to nonalcoholic fatty liver disease. This study aimed to determine the antioxidative effects of Campanula takesimana Nakai, Ilex integra THUNB., Indigofera pseudotinctoria Matsum., Rubus takesimensis Nakai, and Tsuga sieboldii from Ulleung Island and their ability to inhibit lipid accumulation in HepG2 cells. The total phenolics (TPC) and flavonoid (TFC) contents of extracts of the five plants were determined, and their antioxidative activities were analyzed using DPPH and ABTS radical scavenging ability, Fe2+ reducing capacity (FRAP), oxygen radical absorbance capacity (ORAC), and thiobarbituric acid assays. Lipid accumulation was evaluated by Oil Red O staining and intracellular triglyceride (TG) assays. Rubus takesimensis Nakai had the highest TPC among the five plants. The antioxidant activity of R. Nakai was DPPH (IC50=0.30 mg/mL), ABTS (IC50=0.33 mg/mL), FRAP (318.61 μmol FeSO4/g), and ORAC (1.74 μmol TE/g). The lipid peroxidation inhibitory effect of R. Nakai was reduced to 52.51% at 1 mg/mL. Incubating HepG2 cells with extracts of the five plants reduced lipid and TG accumulation by >50%, and inhibited lipid peroxidation by ~19%. These results provided evidence for the development of functional foods based on these five plants from Ulleung Island, due to their antioxidant activities and ability to reduce lipid accumulation.

Eleven triterpenoids, including a new tirucallane-type triterpenoid and a new natural product, were isolated from Picrasma quassioides. Their structures were elucidated by extensive spectroscopic analysis. All isolates were evaluated for their cytotoxic activities against Hep3B and HepG2 cell lines. Compounds 1 and 4 showed moderate cytotoxic activities toward the HepG2 cell at 50 μM, and 1 and 4 displayed equivalent effect to the positive control on Hep3B cell.

Context Cyclocarya paliurus (CP) (Batal.) Iljinsk (Cyclocaryaceae), a plant native to China, is the sole species in the genus Cyclocarya. Its leaves have been widely used as a remedy for hyperlipidaemia in traditional folk medicine. However, the mechanism underlying CP-induced lipolysis, especially in the liver, has not been entirely elucidated. Objective This study investigates the effect of CP ethanol extract (CPE) on hepatic steatosis and the underlying molecular mechanisms involved. Materials and methods The effect of CPE at concentrations of 0, 6.25, 12.5, 25, 50, and 100 μg/mL on the viability of HepG2 cells was examined using the cell counting kit-8 (CCK-8) assay after incubation for 24 h. CPE-induced changes in intracellular lipid content were assessed by measuring the absorbance of oil red O staining at 520 nm, and the possible underlying mechanisms were further studied using quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, western blotting, immunofluorescence studies and transmission electron microscopy. Results The half-maximal inhibitory concentration (IC50) of CPE in HepG2 cells was 97.27 μg/mL. Treatment with 50 μg/mL CPE increased lipid clearance, which was associated with increased autophagy in HepG2 cells. CPE-induced autophagy involved downregulation of phosphorylation level of mammalian target of rapamycin (0.87 ± 0.08 vs. 1.31 ± 0.10). Fluorescent double staining and electron microscopy images showed lipid deposits within autolysosomes, thereby confirming the abovementioned findings. Discussion and conclusions CPE can induce hepatic fat clearance through the autophagy-lysosome pathway known as lipophagy. CPE has potential as a functional food.

Four new 4-alkyl-dihydroxyfuran coumarins, Mesuaferols D–F and iso-Mesuaferol F (1–4) were isolated from the flowering buds of Mesua ferrea. The chemical structures of these compounds were confirmed by the extensive analyses of NMR, UV, IR and HR-ESI-MS methods, the absolute configurations were established on the basis of the Mosher’s method, electron circular dichroism (ECD) measurement and theoretical calculation methods. The inhibitory activities of the isolates were evaluated on MDA-MB-231, MCF-7 and HepG2 cancer cell lines. All compounds exhibited potent activity against MCF-7 with IC50 as 26.68 μM, 37.75 μM, 20.53 μM and 33.43 μM respectively, while almost all compounds showed moderate cytotoxic activities against MDA-MB-231 and HepG2 cell lines. The results of prediction potential targets and molecule docking revealed that Mesuaferol D showed the most binding potential against mTOR.

Protein 4'-phosphopantetheinylation is an essential post-translational modification (PTM) in prokaryotes and eukaryotes. So far, only five protein substrates of this specific PTM have been discovered in mammalian cells. These proteins are known to perform important functions, including fatty acid biosynthesis and folate metabolism, as well as β-alanine activation. To explore existing and new substrates of 4'-phosphopantetheinylation in mammalian proteomes, we designed and synthesized a series of new pantetheine analogue probes, enabling effective metabolic labelling of 4'-phosphopantetheinylated proteins in HepG2 cells. In combination with a quantitative chemical proteomic platform, we enriched and identified all the currently known 4'-phosphopantetheinylated proteins with high confidence, and unambiguously determined their exact sites of modification. More encouragingly, we discovered, using targeted chemical proteomics, a potential 4'-phosphopantetheinylation site in the protein of mitochondrial dehydrogenase/reductase SDR family member 2 (DHRS2).

Abstract Four new sesquiterpenoids, artemyrianins A–D (1–4), and three new norlignans, artemyrianins E–G (5–7), together with five known compounds (8–12), were isolated from the aerial parts of Artemisia myriantha (Asteraceae). The new compounds were established by spectroscopic data analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2 μM. Graphic Abstract

Naturally occurring anacardic acid based benzamides were reported to show anti-inflammatory and anticancer activities, where we synthesized and characterized by NMR and HRMS analysis and also tested a series of anacardic acid based benzamides and evaluated against the proliferation of human liver cancer cells (HepG2). Among the tested compounds, 6j-m showed good inhibitory activity against HepG2 cells with IC50 values ranging from 78.2-91.9 μM. In conclusion, we herein reported the newer series of an academic acid benzamides for the first time.

Using different chromatographic methods, four new compounds were isolated from the aerial parts of Suaeda monoica (Chenopodiaceae) along with 2-hydroxy-1-naphthoic acid (SCM-3). The structures of the new compounds were established as 6′-hydroxy-10′-geranilanyl naphtha-1-oate (SMC-1), 4,4,8β,10β-Tetramethyl-9β-isobutanyl decalin-13-ol-13-O-β-D-xylopyranoside (SCM-2), 6′-(2-hydroxynaphthalen-3-yl) hexanoic acid (SCM-4) and 1′-(2-Methoxy-3-naphthyl)-4′-(2′'-methylbenzoyl)-n-butane (SMC-5) by IR, EIMS and NMR (1 & 2D) analyses. All compounds (50 μg/mL) were tested for cell proliferative potential on cultured human liver cell HepG2 cells by MTT assay. The results revealed a marked cell proliferative potential of all compounds (1.42–1.48 fold) as compared to untreated control. The results of molecular docking and binding with specific proteins such as PTEN (Phosphatase and Tensin homolog) and p53 also justify the cell proliferative potential of the isolated compounds. Glide program with Schrodinger suit 2018 was used to evaluate the binding between SMC compounds and proteins (PTEN and p53). The binding affinity of all compounds was in order of 104–105 M−1 towards both PTEN and p53. All the SMC compounds have been found to bind at the active site of PTEN, thereby may prevent the binding of phosphatidylinositiol 3,4,5-triphosphate (PI3P). In the locked position, PTEN would not be able to hydrolyze PI3P and hence the PI3P regulated signaling pathway remains active. Similarly, SMC molecules were found to interact with the amino acid residues (Ser99, Thr170, Gly199, and Asp224) which are critically involved in the formation of tetrameric p53. The blockage of p53 to attain its active conformation thus may prevent the recruitment of p53 on DNA and hence may promote cell proliferation. Keywords: Suaeda monoica, Cell-proliferation, Molecular docking, β-Naphthol, Caproic acid, Chenopodiaceae, HepG2 cells

The overexpression of sialic acids and sialyltransferases (STs) during malignant transformation and progression could result in the aberrant sialylation of cancer cells. Therefore, interfering the sialic acid synthesis might be an effective pathway in cancer therapy. In this study, we assessed that the antitumor inhibitors of 20(S)-ginsenosides Rg3, 20(R)-ginsenosides Rg3, 20(S)-ginsenosides Rh2, and 20(R)-ginsenosides Rh2 could block the sialoglycans in liver cancer cells HepG2. The results showed that these four compounds could inhibit the expressions of the total and free sialic acid at different levels in HepG2, respectively; also, it showed dose dependence. In addition, the results of the enzyme-linked immunosorbent assay showed that the above four compounds can inhibit the expression of STs significantly. We also found that these compounds could mediate the block of sialylation of α2,3- and α2,6-linked sialic acids in HepG2 cells by flow cytometry. Meanwhile, the results of the molecular docking investigation showed that these compounds showed strong interaction with ST6GalI and ST3GalI. These results verified that the ginsenosides have a powerful inhibiting aberrant sialylation, and it laid a theoretical foundation for further research on the investigation of ginsenosides as the target inhibitors on STs.

Fetal growth restriction (FGR) is associated with decreased nutrient availability and reduced insulin-like growth factor (IGF)-I bioavailability via increased IGF binding protein (IGFBP)-1 phosphorylation. While protein kinase C (PKC) is implicated in IGFBP-1 hyperphosphorylation in nutrient deprivation, the mechanisms remain unclear. I hypothesized that the interaction of PKCα with protein kinase CK2β and activation of PKCα under leucine deprivation (L0) mediate fetal hepatic IGFBP-1 hyperphosphorylation. Parallel Reaction Monitoring Mass Spectrometry (PRM-MS) followed by PKCα knockdown demonstrated the PKCα isoform interacts with IGFBP-1 and CK2β under L0. Pharmacological PKCα activation with phorbol 12-myristate 13-acetate (PMA) increased whereas inhibition with bisindolylmaleimide II (Bis II) decreased IGFBP-1 phosphorylation (Ser101/119/169, Ser98+101 and Ser169+174), respectively. Furthermore, PMA mimicked L0-induced PKCα translocation and IGFBP-1 expression. PKCα expression was increased in baboon fetal liver in FGR, providing biological relevance in vivo. In summary, I report a novel nutrient-sensitive mechanism for PKCα in mediating IGFBP-1 hyperphosphorylation in FGR.

The authors would like to acknowledge the Academy of Finland funding; No. 327248 (ValueBiomat) and 327865 (Bioeconomy). This work was a part of the Academy of Finland's Flagship Programme under Projects No. 318890 and 318891 (Competence Center for Materials Bioeconomy, FinnCERES). The authors would also like to thank Ms. Marja Kärkkäinen for providing TEMPO-CNF and the Biohybrid Materials Research Group (Aalto University) for providing the HepG2 cells. Plant-based hydrogels have attracted great attention in biomedical fields since they are biocompatible and based on natural, sustainable, cost-effective, and widely accessible sources. Here, we introduced new viscoelastic bio-inks composed of quince seed mucilage and cellulose nanofibrils (QSM/CNF) easily extruded into 3D lattice structures through direct ink writing in ambient conditions. The QSM/CNF inks enabled precise control on printing fidelity where CNF endowed objects with shape stability after freeze-drying and with suitable porosity, water uptake capacity, and mechanical strength. The compressive and elastic moduli of samples produced at the highest CNF content were both increased by ~100% (from 5.1 ± 0.2 kPa and 32 ± 1 kPa to 10.7 ± 0.5 and 64 ± 2 kPa, respectively). These values ideally matched those reported for soft tissues; accordingly, the cell compatibility of the printed samples was evaluated against HepG2 cells (human liver cancer). The results confirmed the 3D hydrogels as being non-cytotoxic and suitable to support attachment, survival, and proliferation of the cells. All in all, the newly developed inks allowed sustainable 3D bio-hydrogels fitting the requirements as scaffolds for soft tissue engineering.

Black elderberry (Sambucus Nigar) with high polyphenol content has been reported to have a hypolipidemic effect, but its underlying mechanisms have not been well characterized. In the present study, we investigated the effects of polyphenol-rich black elderberry (BEE) on oxidative stress and hepatic lipid metabolism. The total antioxidant activity of BEE was evaluated. The expression of genes for lipid metabolism was measured in 50 or 100 μg/mL of BEE-treated HepG2 cells. The mRNA and protein levels of genes for cholesterol metabolisms, i.e., sterol regulatory element-binding protein 2, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and low-density lipoprotein receptor, were decreased by BEE. There was marked induction of genes for high-density lipoprotein metabolism, i.e., scavenger receptor class B type 1and ATP-binding cassette (ABC) transporter A1 in BEE-treated cells. The expression of canalicular efflux transporter for hepatic cholesterol and bile acids, such as ABCG5/G8 and ABCB11, was significantly increased by BEE treatment. There was no alteration of the lipogenic genes, whereas BEE significantly decreased the expression of genes for fatty acid oxidation. BEE significantly altered the expression of histone deacetylase and sirtuins. These data suggest that the hypocholesterolemic effects of BEE may be attributed to the alteration of genes for hepatic cholesterol synthesis and flux.

One new siaresinolic acid saponin (1)and three new rotundic acid saponins (2-4) were isolated from the roots of Ilex centrochinensis. Their structures were confirmed by detailed analysis of standard spectroscopic data (IR, MS, 1D and 2D NMR). Compounds (1-4) exhibited anti-inflammatory activity by inhibiting nitric oxide production in a lipopolysaccharide-induced RAW264.7 cell inflammatory model. However, they showed no significant lipid-lowering activity against the production of triglycerides in the lipid-accumulation model of HepG2 cells induced by oleic acid.

Contrary to the major vitamin E congener α-tocopherol, which carries a saturated sidechain, and α-tocotrienol, with a threefold unsaturated sidechain, little is known about the intracellular fate of α-tocomonoenol, a minor vitamin E derivative with a single double bond in C11′-position of the sidechain. We hypothesized that, due to structural similarities, the uptake and metabolism of α-tocomonoenol will resemble that of α-tocopherol. Cytotoxicity, cellular uptake of α-tocomonoenol, α-tocopherol and α-tocotrienol and conversion into the short-chain metabolites αCEHC and αCMBHC were studied in HepG2 cells. α-Tocomonoenol did not show significant effects on cell viability and its uptake was similar to that observed for α-tocopherol and significantly lower than for α-tocotrienol. α-Tocomonoenol was mainly metabolized to αCMBHC in liver cells, but to a lower extent than α-tocotrienol, while α-tocopherol was not metabolized in quantifiable amounts at all. In summary, the similarities in the cytotoxicity, uptake and metabolism of α-tocomonoenol and α-tocopherol suggest that this minor vitamin E congener deserves more attention in future research with regard to its potential vitamin E activity.

Seven undescribed dammarane-type saponins, gypenosides LXXXI-LXXXVII, together with four known compounds, were isolated from the whole herb of Gynostemma pentaphyllum. The chemical structures of these undescribed compounds were elucidated on the basis of physical and spectroscopic analysis and comparison with literature data. All the isolates were evaluated for their proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory activities in HepG2 cells. Among them, gypenosides LXXXII-LXXXVII, gynosaponin II, IV and VI suppressed the expression of PCSK9 in LPDS-induced HepG2 cells at 20 μM; gypenosides LXXXII, LXXXV and LXXXVII showed inhibitory activities against PCSK9 at 10 μM; notably, gypenoside LXXXII still exhibited inhibitory activity against PCSK9 at 5 μM.

Four series of cajanonic acid A (CAA) derivatives have been designed and synthesized. The newly prepared compounds have been screened for glucose consumption activity in HepG2 cell lines and PPARγ antagonistic activity in HEK293 cell lines. Compound 26g bearing a tetrahydroisoquinolinone scaffold showed the most potent PPARγ antagonistic and hypoglycemic activities. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 26g was a potent hypoglycemic agent. In addition, the possible binding modes for compound 26g in the PPARγ protein have been investigated in this study.

Background：Flaxseed peptide (FPs) showed serum cholesterol-lowering activity in SD rats fed a high-cholesterol diet, but the cholesterol-lowering amino acid sequences and mechanism of FPs were still unclear. Methods: FPs were separated via ultrafiltration, and the amino acid sequences of the selected fractions were determined via high-performance liquid chromatography- Electrospray Ionisation - Orbitrap- Mass spectrometry (HPLC-ESI-Orbitrap MS). These peptides then were synthesized by solid-phase synthesis (SPPS). IPPF with the highest CMSR was determined to exist in flaxseed protein by specific antibodies. The effects of IPPF on intestinal cholesterol absorption and hepatic cholesterol metabolism were investigated in Caco-2 cells and HepG2 cells.Results：1 kDa FP5 fraction had the highest cholesterol micelle solubility inhibition rate (CMSR) 72.39% compared with the other ultrafiltration fractions. Then Eleven peptides were identified from FP5. Ile-Pro-Pro-Phe (IPPF), with the highest CMSR 93.47%, was selected to research the cholesterol-lowering mechanism in Caco-2 and HepG2 cells. IPPF significantly reduces the amount of cholesterol transported in Caco2 cells and the amount of total cholesterol in HepG2 cells. IPPF significantly modulated the protein levels of NCP1L1 and ABCG5/8 in Caco2 cells and significantly reduced the mRNA levels of Srebp-2 and Hmgcr in HepG2 cells. Conclusion: IPPF inhibits cholesterol intestinal absorption through modulating the expression of cholesterol transporters in Caco-2 cells and reduces hepatic cholesterol synthesis through inhibiting the SREBP2-regulated mevalonate (HMGCR) pathway in HepG2 cells. IPPF is a new food-derived inhibitor of intestinal cholesterol absorption and hepatic cholesterol synthesis without side effects and provides a nutritional therapy component for hypercholesterolemia.

Acetochlor is one of the most widely used chiral herbicides in the world, and it is usually produced and used as racemic form (Rac). The potential effects of acetochlor in human body are mainly induced by its residue in agriculture food. The direct target exposed is the liver in human body. However, the potential toxic and mechanism threat to human liver cells caused by chiral acetochlor has been rarely reported. The purpose of this study is to explore the potential mechanism of the toxicity caused by chiral acetochlor in HepG2 cells. The results revealed that acetochlor and its enantiomers could inhibit cell activity and cause DNA damage in HepG2 cells. The toxicity of Rac was higher than that of the two enantiomers, mainly derived from S configuration. The mechanism is through inducing decreased membrane potential (△Ψ), up-regulated Bax/BcL-2 expression, caused a cascade reaction, activated casepase-3 and casepase-9 and cleaved PARP, which maybe lead to cell death through apoptotic-signaling pathway in the end. These results illuminate that the genotoxic and cytotoxic risks of chiral acetochlor are major coming from S configuration. It provides a theoretical basis for the production of single pesticide to reduce the effects of human health.