Aqueous extract of Laurus nobilis leaf accelerates the alcohol metabolism and prevents liver damage in single-ethanol binge rats.

BACKGROUND/OBJECTIVES: Excessive alcohol consumption has harmful health effects, including alcohol hangovers and alcohol-related liver disease. Therefore, methods to accelerate the alcohol metabolism are needed. Laurus nobilis is a spice, flavoring agent, and traditional herbal medicine against various diseases. This study examined whether the standardized aqueous extract of L. nobilis leaves (LN) accelerates the alcohol metabolism and protects against liver damage in single-ethanol binge Sprague-Dawley (SD) rats. MATERIALS/METHODS: LN was administered orally to SD rats 1 h before ethanol administration (3 g/kg body weight [BW]) at 100 and 300 mg/kg BW. Blood samples were collected 0.5, 1, 2, and 4 h after ethanol administration. The livers were excised 1 h after ethanol administration to determine the hepatic enzyme activity. The alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in the liver tissue were measured. RESULTS: LN decreased the serum ethanol and acetaldehyde levels in ethanol-administered rats. LN increased the hepatic ADH and ALDH activities but decreased the alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities in the ethanol-administered rats. In addition, LN inhibited lipid peroxidation and increased the activities of SOD and GPx. CONCLUSIONS: LN modulates the mediators of various etiological effects of excessive alcohol consumption and enhances the alcohol metabolism and antioxidant activity, making it a potential candidate for hangover treatments.

Porcine Placenta Peptide Inhibits UVB-Induced Skin Wrinkle Formation and Dehydration: Insights into MAPK Signaling Pathways from In Vitro and In Vivo Studies.

Excessive exposure to ultraviolet (UV) radiation from sunlight accelerates skin aging, leading to various clinical manifestations such as wrinkles, dryness, and loss of elasticity. This study investigated the protective effects of porcine placenta peptide (PPP) against UVB-induced skin photoaging. Female hairless SKH-1 mice were orally administered PPP for 12 weeks, followed by UVB irradiation. PPP significantly reduced wrinkle formation, improved skin moisture levels, and prevented collagen degradation. Mechanistically, PPP inhibited the expression of matrix metalloproteinases (MMPs) and upregulated collagen production. Moreover, PPP elevated hyaluronic acid levels, contributing to enhanced skin hydration. Additionally, PPP demonstrated antioxidant properties by increasing the expression of the antioxidant enzyme GPx-1, thereby reducing UVB-induced inflammation. Further molecular analysis revealed that PPP suppressed the activation of p38 MAP kinase and JNK signaling pathways, crucial mediators of UV-induced skin damage. These findings highlight the potential of porcine placental peptides as a natural and effective intervention against UVB-induced skin photoaging. The study provides valuable insights into the mechanisms underlying the protective effects of PPP, emphasizing its potential applications in skincare and anti-aging formulations.

Carcass Characteristics, Proximate Composition, Fatty Acid Profile, and Oxidative Stability of Pectoralis major and Flexor cruris medialis Muscle of Broiler Chicken Subjected to with or without Level of Electrical Stunning, Slaughter, and Subsequent Bleeding.

With an emphasis on the global meat market and considering the ritual requirements and quality aspects, four types of slaughtering treatments were compared: (1) NSHS (without electrical stunning, halal neck cut, and subsequent bleeding for 180 s), (2) LSHS (electrically stunned at 250 mA for five seconds, halal neck cut, and subsequent bleeding for 180 s), (3) MSHS (electrically stunned at 500 mA for 10 s, halal neck cut, and subsequent bleeding for 180 s), and (4) HSHS (electrically stunned at 1000 mA for 20 s, halal neck cut, and subsequent bleeding for 180 s). Four hundred 36 day-old Ross 308 broiler chickens (body weights of 1.4 to 1.8 kg) were divided into four random groups of 100 birds each (ten replicated pens of ten birds). This study examined the livability, bleeding out, Pectoralis major and Flexor cruris medialis proximate composition, cholesterol content, fatty acid profile and post-mortem pH, microbial loads, and oxidative stability. The livability and bleeding out were higher in NSHS and LSHS than MSHS and HSHS (p < 0.05). The Pectoralis major and Flexor cruris medialis proximate composition, cholesterol content and fatty acid profile, post-mortem pH, and microbial loads were unaffected by the slaughter treatments (p > 0.05), but the oxidative stability of Pectoralis major differed during the eight-day post-mortem period (p < 0.05). The results suggest that for capturing the global meat market, the meat industry can consider NSHS and LSHS because the ritual requirements are fulfilled, and there is no negative impact on the nutritional aspects.

Time for a Paradigm Shift in Animal Nutrition Metabolic Pathway: Dietary Inclusion of Organic Acids on the Production Parameters, Nutrient Digestibility, and Meat Quality Traits of Swine and Broilers.

Because the application of antibiotic growth promoters (AGP) causes accelerated adverse effects on the animal diet, the scientific community has taken progressive steps to enhance sustainable animal productivity without using AGP in animal nutrition. Organic acids (OAs) are non-antibiotic feed additives and a promising feeding strategy in the swine and broiler industry. Mechanistically, OAs improve productivity through multiple and diverse pathways in: (a) reduction of pathogenic bacteria in the gastro-intestinal tract (GIT) by reducing the gut pH; (b) boosting the digestibility of nutrients by facilitating digestive enzyme secretion and increasing feed retention time in the gut system; and (c) having a positive impact and preventing meat quality deterioration without leaving any chemical residues. Recent studies have reported the effectiveness of using encapsulated OAs and synergistic mechanisms of OAs combinations in swine and broiler productivity. On the other hand, the synergistic mechanisms of OAs and the optimal combination of OAs in the animal diet are not completely understood, and further intensive scientific explorations are needed. Moreover, the ultimate production parameters are not similar owing to the type of OAs, concentration level, growth phase, health status of animals, hygienic standards, and environmental factors. Thus, those factors need to be considered before implementing OAs in feeding practices. In conclusion, the current review evaluates the basics of OAs, mode of action, novel strategies to enhance utilization, influence on growth performances, nutrient digestibility, and meat quality traits of swine and broilers and their potential concerns regarding utilization.

Loratadine, an antihistamine drug, exhibits anti-inflammatory activity through suppression of the NF-kB pathway.

Loratadine is an antihistamine drug that shows promise as an anti-inflammatory drug, but supportive studies are lacking. We elucidated the effects and mechanisms by which loratadine inhibits inflammatory responses. Molecular components were evaluated in macrophages by nitric oxide assay, polymerase chain reaction, luciferase assay, immunoblotting, overexpression strategies and cellular thermal shift assay. At the molecular level, loratadine reduced the levels of nitric oxide, iNOS, IL-1ß, TNF-α, IL-6, and COX-2 in RAW264.7 cells treated with lipopolysaccharide. Loratadine also specifically inhibited the NF-kB pathway, targeting the Syk and Src proteins. Furthermore, loratadine bound Src in the bridge between SH2 and SH3, and bound Syk in the protein tyrosine kinase domain. The NF-kB signaling pathway was assessed along with putative binding sites through a docking approach. The anti-inflammatory effect of loratadine was tested using mouse models of gastritis, hepatitis, colitis, and peritonitis. Stomach tissue histopathology, liver morphology, and colon length in the loratadine group were improved over the group without loratadine treatment. Taken together, loratadine inhibited the inflammatory response through the NF-kB pathway by binding with the Syk and Src proteins.

Production of chitinase from Escherichia fergusonii, chitosanase from Chryseobacterium indologenes, Comamonas koreensis and its application in N-acetylglucosamine production.

The important platform polysaccharide N-acetylglucosamine (GlcNAc) has great potential to be used in the fields of food, cosmetics, agricultural, pharmaceutical, medicine and biotechnology. This GlcNAc is being produced by traditional methods of environment-unfriendly chemical digestion with strong acids. Therefore, researchers have been paying more attention to enzymatic hydrolysis process for the production of GlcNAc. Hence, in this study, we isolated novel chitinase (Escherichia fergusonii) and chitosanase (Chryseobacterium indologenes, Comamonas koreensis) producing strains from Korean native calves feces, and developed the potential of an eco-friendly microbial progression for GlcNAc production from swollen chitin and chitosan by enzymatic degradation. Maximum chitinase (7.24±0.07U/ml) and chitosanase (8.42±0.09, 8.51±0.25U/ml) enzyme activity were reached in submerged fermentation at an optimal pH of 7.0 and 30°C. In this study, sucrose, yeast extract, (NH4)2SO4, and NaCl were found to be the potential enhancers of exo-chitinase activity and glucose, corn flour, yeast extract, soybean flour, (NH4)2SO4, NH4Cl and K2HPO4 were found to be the potential activator for exo-chitosanase activity. Optimum concentrations of the carbon sources for enhanced chitinase activity were 9.91, 3.21, 9.86, 1.66U/ml and chitosanase activity were 1.63, 1.13, 2.28, 3.71, 9.02, 4.93, and 2.14U/ml. These enzymes efficiently hydrolyzed swollen chitin and chitosan to N-acetylglucosamine were characterized by thin layer chromatography and were further confirmed by high-pressure liquid chromatography. From a commercial perspective, we isolated, optimized and characterized exochitinase from Escherichia fergusonii (HANDI 110) and chitosanase from Chryseobacterium indologenes (HANYOO), and Comamonas koreensis (HANWOO) for the large-scale production of GlcNAc facilitating its potential use in industrial applications.

Development and Validation of an Analytical Method Readily Applicable for Quality Control of Tabebuia impetiginosa (Taheebo) Ethanolic Extract.

The dried inner bark of Tabebuia impetiginosa, known as taheebo or red lapacho, has numerous beneficial effects on human health. This study presents the first simple and reliable quantitative method that could serve for the QC of taheebo. The method uses LC-UV spectroscopy to determine the veratric acid (VA; 3,4-dimethoxybenzoic acid) content of taheebo extracts (TEs). Sample preparation entailed the dissolution of TE in methanol (MeOH), facilitated by ultrasonic radiation for 10 min. The optimized conditions included chromatographic separation on an Agilent Eclipse Plus C18 column (4.6 × 150 mm, 5 µm) at 30°C. The mobile phase consisted of 1% acetic acid in water and MeOH, which was eluted under gradient mode at a flow rate of 1.0 mL/min. The detection wavelength was 254 nm. Using these conditions, VA was selectively resolved, and the entire chromatographic analysis time was 27 min. The method was linear in the range of 50-500 µg/mL (r2 = 0.9995), precise (≤3.97% RSD), and accurate (97.10-102.72%). The validated method was applied to three batches of TE samples, yielding an estimated VA content range of 14.92-15.58 mg/g. Thus, the proposed method could serve as an easy and practical method for the QC of TEs or related products containing TEs.

Effect of fermented total mixed rations on the growth performance, carcass and meat quality characteristics of Hanwoo steers.

This study was conducted to assess the effects of fermented total mixed ration (FTMR) on the growth performance, carcass and meat quality traits of Hanwoo steers. The present study evidenced that the FTMR had a strong effect on dry matter intake, body weight, daily gain, slaughter weight and carcass characteristics compared with control animals. The results showed that the dry matter intake (7.17 ± 0.13 kg), average body weight (615.20 ± 112.82 kg), and daily gain (0.56 ± 0.16 kg) were greater in animals receiving FTMR than in control animals (P < 0.05). The meat quality characteristics indicated that cooking loss and the pH values did not vary between control and FTMR treated animals; however, animals in the treated groups (FTMR) had higher meat quality grades, carcass weight (396.13 ± 18.35), fat thickness (13.25 ± 1.75), marbling score (5.63 ± 0.56), meat color (40.06 ± 1.23), crude fat (18.39 ± 1.32) and sensory characteristics (flavor 5.03 ± 0.17; tenderness 4.42 ± 0.33; juiciness 5.10 ± 0.16). Nevertheless, the shear force values decreased significantly in FTMR-treated animals compared with control group steers. Overall, FTMR may not only improve the growth performance, biochemical metabolites, and fatty and acetic acid profiles of steers, but may also enhance the carcass and meat quality characteristics of Hanwoo steers. Regarding economics, our research findings suggest that FTMR-based feeds may enhance Hanwoo steer meat quality at a low cost.

Comparison of anticancer activities of Korean Red Ginseng-derived fractions.

BACKGROUND: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). METHODS: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. RESULTS: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. CONCLUSION: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

In vitro antioxidative and anti-inflammatory effects of the compound K-rich fraction BIOGF1K, prepared from Panax ginseng.

BACKGROUND: BIOGF1K, a compound K-rich fraction prepared from the root of Panax ginseng, is widely used for cosmetic purposes in Korea. We investigated the functional mechanisms of the anti-inflammatory and antioxidative activities of BIOGF1K by discovering target enzymes through various molecular studies. METHODS: We explored the inhibitory mechanisms of BIOGF1K using lipopolysaccharide-mediated inflammatory responses, reporter gene assays involving overexpression of toll-like receptor adaptor molecules, and immunoblotting analysis. We used the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to measure the antioxidative activity. We cotransfected adaptor molecules, including the myeloid differentiation primary response gene 88 (MyD88) and Toll/interleukin-receptor domain containing adaptor molecule-inducing interferon-ß (TRIF), to measure the activation of nuclear factor (NF)-κB and interferon regulatory factor 3 (IRF3). RESULTS: BIOGF1K suppressed lipopolysaccharide-triggered NO release in macrophages as well as DPPH-induced electron-donating activity. It also blocked lipopolysaccharide-induced mRNA levels of interferon-ß and inducible nitric oxide synthase. Moreover, BIOGF1K diminished the translocation and activation of IRF3 and NF-κB (p50 and p65). This extract inhibited the upregulation of NF-κB-linked luciferase activity provoked by phorbal-12-myristate-13 acetate as well as MyD88, TRIF, and inhibitor of κB (IκBα) kinase (IKKß), and IRF3-mediated luciferase activity induced by TRIF and TANK-binding kinase 1 (TBK1). Finally, BIOGF1K downregulated the NF-κB pathway by blocking IKKß and the IRF3 pathway by inhibiting TBK1, according to reporter gene assays, immunoblotting analysis, and an AKT/IKKß/TBK1 overexpression strategy. CONCLUSION: Overall, our data suggest that the suppression of IKKß and TBK1, which mediate transcriptional regulation of NF-κB and IRF3, respectively, may contribute to the broad-spectrum inhibitory activity of BIOGF1K.

Genome scan linkage analysis identifies a major quantitative trait loci for fatty acid composition in longissimus dorsi muscle in an F2 intercross between Landrace and Korean native pigs.

OBJECTIVE: This study was conducted to locate quantitative trait loci (QTL) influencing fatty acid (FA) composition in a large F2 intercross between Landrace and Korean native pigs. METHODS: Eighteen FA composition traits were measured in more than 960 F2 progeny. All experimental animals were genotyped with 165 microsatellite markers located throughout the pig autosomes. RESULTS: We detected 112 QTLs for the FA composition; Forty seven QTLs reached the genome-wide significant threshold. In particular, we identified a cluster of highly significant QTLs for FA composition on SSC12. QTL for polyunsaturated fatty acid on pig chromosome 12 (F-value = 97.2 under additive and dominance model, nominal p-value 3.6×10-39) accounted for 16.9% of phenotypic variance. In addition, four more QTLs for C18:1, C18:2, C20:4, and monounsaturated fatty acids on the similar position explained more than 10% of phenotypic variance. CONCLUSION: Our findings of a major QTL for FA composition presented here could provide helpful information to locate causative variants to improve meat quality traits in pigs.

Proteins that interact with calgranulin B in the human colon cancer cell line HCT-116.

Calgranulin B is released from immune cells and can be internalized into colon cancer cells to prevent proliferation. The present study aimed to identify proteins that interact with calgranulin B to suppress the proliferation of colon cancer cells, and to obtain information on the underlying anti-tumor mechanism(s) of calgranulin B. Calgranulin B expression was induced in colon cancer cell line HCT-116 by infection with calgranulin B-FLAG expressing lentivirus, and it led to a significant suppression of cell proliferation. Proteins that interacted with calgranulin B were obtained by immunoprecipitation using whole homogenate of lentivirus-infected HCT-116 cells which expressing calgranulin B-FLAG, and identified using liquid chromatography-mass spectrometry/mass spectrometry analysis. A total of 454 proteins were identified that potentially interact with calgranulin B, and most identified proteins were associated with RNA processing, post-transcriptional modifications and the EIF2 signaling pathway. Direct interaction of calgranulin B with flotillin-1, dynein intermediate chain 1, and CD59 glycoprotein has been confirmed, and the molecules N-myc proto-oncogene protein, rapamycin-insensitive companion of mTOR, and myc proto-oncogene protein were shown to regulate calgranulin B-interacting proteins. Our results provide new insight and useful information to explain the possible mechanism(s) underlying the role of calgranulin B as an anti-tumor effector in colon cancer cells.

In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components.

BACKGROUND: Although Korean Red Ginseng (KRG) has been traditionally used for a long time, its anti-inflammatory role and underlying molecular and cellular mechanisms have been poorly understood. In this study, the anti-inflammatory roles of KRG-derived components, namely, water extract (KRG-WE), saponin fraction (KRG-SF), and nonsaponin fraction (KRG-NSF), were investigated. METHODS: To check saponin levels in the test fractions, KRG-WE, KRG-NSF, and KRG-SF were analyzed using high-performance liquid chromatography. The anti-inflammatory roles and underlying cellular and molecular mechanisms of these components were investigated using a macrophage-like cell line (RAW264.7 cells) and an acute gastritis model in mice. RESULTS: Of the tested fractions, KGR-SF (but not KRG-NSF and KRG-WE) markedly inhibited the viability of RAW264.7 cells, and splenocytes at more than 500 µg/mL significantly suppressed NO production at 100 µg/mL, diminished mRNA expression of inflammatory genes such as inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interferon-ß at 200 µg/mL, and completely blocked phagocytic uptake by RAW264.7 cells. All three fractions suppressed luciferase activity triggered by interferon regulatory factor 3 (IRF3), but not that triggered by activator protein-1 and nuclear factor-kappa B. Phospho-IRF3 and phospho-TBK1 were simultaneously decreased in KRG-SF. Interestingly, all these fractions, when orally administered, clearly ameliorated the symptoms of gastric ulcer in HCl/ethanol-induced gastritis mice. CONCLUSION: These results suggest that KRG-WE, KRG-NSF, and KRG-SF might have anti-inflammatory properties, mostly because of the suppression of the IRF3 pathway.

Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells.

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

A direct protein kinase B-targeted anti-inflammatory activity of cordycepin from artificially cultured fruit body of Cordyceps militaris.

BACKGROUND: Cordyceps militaris is one of well-known medicinal mushrooms with anti-inflammatory, anti-cancer, anti-diabetic, and anti-obesity activities. OBJECTIVE: The objective of the following study is to isolate chemical components from the ethanol extract (Cm-EE) from Cordyceps militaris and to evaluate their anti-inflammatory activities. MATERIALS AND METHODS: Column chromatographic separation was performed and anti-inflammatory roles of these compounds were also examined by using NO production and protein kinase B (AKT) activity assays. RESULTS: From Cm-EE, 13 constituents, including trehalose (1), cordycepin (2), 6-hydroxyethyladenosine (3), nicotinic amide (4), butyric acid (5), ß-dimorphecolic acid (6), α-dimorphecolic acid (7), palmitic acid (8), linoleic acid (9), cordycepeptide A (10), 4-(2-hydroxy-3-((9E,12E)-octadeca-9,12-dienoyloxy)propoxy)-2-(trimethylammonio)butanoate (11), 4-(2-hydroxy-3-(palmitoyloxy)propoxy)-2-(trimethylammonio)butanoate (12), and linoleic acid methyl ester (13) were isolated. Of these components, compound 2 displayed a significant inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW264.7 cells. Furthermore, this compound strongly and directly suppressed the kinase activity of AKT, an essential signalling enzyme in LPS-induced NO production, by interacting with its ATP binding site. CONCLUSION: C. militaris could have anti-inflammatory activity mediated by cordycepin-induced suppression of AKT.

Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies.

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor (NF)-κB, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana.

Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

Anti-inflammatory activity of AP-SF, a ginsenoside-enriched fraction, from Korean ginseng.

BACKGROUND: Korean ginseng is an ethnopharmacologically valuable herbal plant with various biological properties including anticancer, antiatherosclerosis, antidiabetic, and anti-inflammatory activities. Since there is currently no drug or therapeutic remedy derived from Korean ginseng, we developed a ginsenoside-enriched fraction (AP-SF) for prevention of various inflammatory symptoms. METHODS: The anti-inflammatory efficacy of AP-SF was tested under in vitro inflammatory conditions including nitric oxide (NO) production and inflammatory gene expression. The molecular events of inflammatory responses were explored by immunoblot analysis. RESULTS: AP-SF led to a significant suppression of NO production compared with a conventional Korean ginseng saponin fraction, induced by both lipopolysaccharide and zymosan A. Interestingly, AP-SF strongly downregulated the mRNA levels of genes for inducible NO synthase, tumor necrosis factor-α, and cyclooxygenase) without affecting cell viability. In agreement with these observations, AP-SF blocked the nuclear translocation of c-Jun at 2 h and also reduced phosphorylation of p38, c-Jun N-terminal kinase, and TAK-1, all of which are important for c-Jun translocation. CONCLUSION: Our results suggest that AP-SF inhibits activation of c-Jun-dependent inflammatory events. Thus, AP-SF may be useful as a novel anti-inflammatory remedy.

AP-1-Targeting Anti-Inflammatory Activity of the Methanolic Extract of Persicaria chinensis.

In traditional Chinese medicine, Persicaria chinensis L. has been prescribed to cure numerous inflammatory disorders. We previously analyzed the bioactivity of the methanol extract of this plant (Pc-ME) against LPS-induced NO and PGE2 in RAW264.7 macrophages and found that it prevented HCl/EtOH-induced gastric ulcers in mice. The purpose of the current study was to explore the molecular mechanism by which Pc-ME inhibits activator protein- (AP-) 1 activation pathway and mediates its hepatoprotective activity. To investigate the putative therapeutic properties of Pc-ME against AP-1-mediated inflammation and hepatotoxicity, lipopolysaccharide- (LPS-) stimulated RAW264.7 and U937 cells, a monocyte-like human cell line, and an LPS/D-galactosamine- (D-GalN-) induced acute hepatitis mouse model were employed. The expression of LPS-induced proinflammatory cytokines including interleukin- (IL-) 1ß, IL-6, and tumor necrosis factor-α (TNF-α) was significantly diminished by Pc-ME. Moreover, Pc-ME reduced AP-1 activation and mitogen-activated protein kinase (MAPK) phosphorylation in both LPS-stimulated RAW264.7 cells and differentiated U937 cells. Additionally, we highlighted the hepatoprotective and curative effects of Pc-ME pretreated orally in a mouse model of LPS/D-GalN-intoxicated acute liver injury by demonstrating the significant reduction in elevated serum AST and ALT levels and histological damage. Therefore, these results strongly suggest that Pc-ME could function as an antihepatitis remedy suppressing MAPK/AP-1-mediated inflammatory events.