Anti-viral activity of compounds from Agrimonia pilosa and Galla rhois extract mixture.

Hepatitis C virus (HCV) infection is a significant health problem, with a worldwide prevalence of about 170 million. Recently, the development of direct acting antiviral (DAA) as a therapeutic agent for HCV has been rapidly increasing. However, DAA has a side effect and is costly. Therefore, it is still necessary to develop a therapeutic agent to treat HCV infection using products. Agrimonia pilosa (AP) and Galla rhois (RG) are traditional medicines and are known to display therapeutic activity on various diseases. Notably, they have been reported to have an anti-viral effect on HBV and influenza virus infections. It is expected that anti-viral activity will increase when two extracts are mixed. To investigate their anti-viral activity, the expression level of HCV Core 1b and NS5A was measured. Remarkably, AP, RG, and their mixed compound (APRG64) strongly inhibited the expression of viral proteins, which led us to identify their metabolites. A total of 14 metabolites were identified using liquid chromatography mass spectrometry (LC-MS). These metabolites were evaluated for their anti-HCV activity to identify active ingredients. In conclusion, our results unveiled that anti-HCV activity of Agrimonia pilosa and Galla rhois extract mixture could lead to the development of a novel therapy for HCV infection.

Prunus mume leaf extract lowers blood glucose level in diabetic mice.

Context Diabetes is a common metabolic disease with long-term complications. Prunus mume Sieb. et Zucc. (Rosaceae) fruits have shown to ameliorate glucose intolerance. However, the antidiabetic effects of P. mume leaves have not been investigated. Objective This study evaluated the effects of P. mume leaf 70% ethanol extract (PMLE) on alleviating diabetes in vivo and in vitro. Materials and methods PMLE was fractionated into n-hexane, dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (BuOH) and water. Polyphenol and flavonoid contents in PMLE fractions were determined using Folin-Ciocalteu reagent and the aluminium chloride colorimetric method, respectively. We evaluated α-glucosidase inhibition using a microplate reader at 400 nm. Adipocyte differentiation by lipid accumulation was measured using Nile Red staining. Male imprinting control region (ICR) mice were injected with streptozotocin (STZ, 100 mg/kg, i.p.). High-fat diets were provided for three weeks prior to PMLE treatments to induce type 2 diabetes. PMLE (0, 5, 25 or 50 mg/kg) was administrated for four weeks with high-fat diets. Results The EtOAc fraction of PMLE inhibited α-glucosidase activity (IC50 = 68.2 µg/mL) and contained 883.5 ± 14.9 mg/g of polyphenols and 820.1 ± 7.7 mg/g of flavonoids. The 50 mg/kg PMLE supplement reduced 40% of blood glucose level compared to obese/diabetes mice. Obese/diabetic mice treated with 50 mg/kg PMLE showed a lower level of triacylglycerol (320.7 ± 20.73 mg/dL) compared to obese/diabetes mice (494.9 ± 14.80 mg/dL). Conclusion The data demonstrate that P. mume leaves exert antidiabetic effects that may be attributable to high concentrations of polyphenols and flavonoids.

Anticancer potency studies of coordination driven self-assembled arene­Ru-based metalla-bowls.

New tetranuclear cationic metalla-bowls 5­7 with the general formula [Ru4(p-cymene)4(N∩N)2(OO∩OO)2]4+ (N∩N=2,6-bis(N-(4-pyridyl carbamoyl)pyridine, OO∩OO=2,5-dihydroxy-1,4-benzoquinonato (5), OO∩OO=5,8-dioxydo-1,4-naphthaquinonato (6), OO∩OO=hoxonato (7)) were prepared by the reaction of the respective dinuclear ruthenium complexes 2­4 with a bispyridine amide donor ligand 1 in methanol in the presence of AgO3SCF3.These new molecular metalla-bowls were fully characterized by analytical techniques including elemental analysis as well as 1H and 13C NMR and HR-ESI-MS spectroscopy. The structure of metalla-bowl 6 was determined from X-ray crystal diffraction data. A UV/visible study was also carried out for the entire suite of new complexes. As with recent studies of similar arene­Ru complexes, the inhibition of cell growth by metalla-bowls was established against SK-hep-1 (liver cancer), AGS (gastric cancer), and HCT-15 (colorectal cancer) human cancer cell lines. Inhibition of cell growth by 6 was found to be considerably stronger against all cancer cell lines than the anticancer drugs, doxorubicin and cisplatin. In particular, in colorectal cancer cells, expression of the cancer suppressor genes APC and p53 was increased following exposure to 6.

Antimicrobial activities against periodontopathic bacteria of Pittosporum tobira and its active compound.

The study of medicinal plants for treatment of periodontitis is of great value to establish their efficacy as sources of new antimicrobial drugs. Five hundred and fifty eight Korean local plant extracts were screened for antibacterial activity against representative periodontopathic bacteria such as Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum. Among the various medicinal plants, the alcohol extract of Pittosporum tobira, which significantly exhibited antibacterial effect for all tested strains, showed the highest activity in the antimicrobial assays. NMR analyses revealed that R1-barrigenol, a triterpene sapogenin, was the most effective compound in P. tobira. These results demonstrated that P. tobira possesses antimicrobial properties and would be beneficial for the prevention and treatment of periodontitis.

Anti-varicella zoster virus and related anti-inflammation effects of ethanolic extract of Elaeocarpus sylvestris.

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as "sanduyoung," has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES. AIM OF THE STUDY: In the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES. METHODS: and methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells. RESULTS: To evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1ß, IL-6, and TNF-α. CONCLUSION: E. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection.

Evaluation of the acute, sub-chronic and chronic oral toxicity, genetic toxicity, and safety of a Lomens-P0.

Extracts of Hordeum vulgare and Chrysanthemum zawadskii, two traditional herbal medicines, have long been used to treat women's diseases. Our previous studies have confirmed that these extracts could help relieve the symptoms of premenstrual syndrome by inhibiting prolactin release. A mixture of these natural products was named Lomens-P0. In this study, we conducted three genotoxicity tests (bacterial reverse mutation, mammalian chromosome aberration, and mammalian erythrocyte micronucleus studies) and four oral toxicity tests (single-dose, 2-week repeated-dose, and 13-week repeated-dose studies in rodents, and a single-dose dose-escalation toxicity study in a non-rodent model) to confirm the potential toxicity and safety of Lomens-P0. The results of this series of tests indicated Lomens-P0 did not induce genotoxicity, and the NOAEL for the rodent was 2000 mg/kg BW/day. Similarly, no toxic effects were evident in the single-dose-escalation study in the non-rodent model. In conclusion, we confirmed that Lomens-P0 might have potential utility as a raw material for nutraceuticals and natural medicines. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-021-00090-5.

Preventive Effects against Retinal Degeneration by Centella asiatica Extract (CA-HE50) and Asiaticoside through Apoptosis Suppression by the Nrf2/HO-1 Signaling Pathway.

Age-related macular degeneration (AMD) is caused by the chronic and gradual oxidative degeneration of the retina. Unfortunately, the general purpose of current treatments is to slow AMD progression, as the retina cannot be restored to its pre-AMD condition. We aimed to identify natural products that can be potential treatments that prevent AMD and can delay the development of late-AMD and selected Centella asiatica extract (CA-HE50), which shows excellent efficacy in cytoprotection. In animal experiments using N-methyl-N-nitrosourea (MNU), CA-HE50 dramatically increased the thickness of photoreceptors and the outer nuclear layer (ONL) and the number of nuclei in the ONL (p < 0.05). Using retinal epithelial ARPE-19 cells showed that CA-HE50 inhibited apoptosis through inhibition of the intrinsic apoptosis signaling pathway and cell cycle regulation (p < 0.05). The anti-apoptotic efficacy was confirmed to be due to activation of the Nrf2/HO-1 antioxidation pathway (p < 0.05). These results were also observed with asiaticoside, a functional substance of CA-HE50. In addition, the accumulation of oxidized-N-retinylidene-N-retinylethanolamine (A2E), which induces AMD, was inhibited by CA-HE50, resulting in increased ARPE-19 cell viability (p < 0.05). This study demonstrates that CA-HE50 is worth further research and human application tests, to develop it as a raw material for treatment or dietary supplement for the prevention of AMD.

Hepatoprotective effect of Centella asiatica 50% ethanol extract against acetaminophen-induced acute liver injury in BALB/c mice.

N-acetyl-p-aminophenol (acetaminophen, APAP) is a well-known component of analgesic and antipyretic monotherapy products. However, exceeding the recommended dose can lead to serious injury to the liver. We conducted this study to determine the potential of Centella asiatica as a natural substance to protect against APAP-induced liver injury. When acute hepatotoxicity was induced in mice by APAP overdose, their liver weight decreased significantly (p < 0.05). However, mice treated with C. asiatica 50% ethanol extract (CA-HE50, 200 mg/kg) for a week before induction of hepatotoxicity by APAP had similar liver weights to those of mice in which hepatotoxicity was not induced. In particular, levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, which are biomarkers of liver injury, were significantly increased by APAP and dose-dependently decreased by CA-HE50 (p < 0.05). Glutathione and malondialdehyde, indicators of oxidative stress, were significantly changed by APAP and CA-HE50 (p < 0.05). In addition, hepatic necrosis and expression of genes encoding pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1ß, and IL-4) induced by APAP were inhibited by CA-HE50, and these results were dose-dependent. Through our in vivo studies, we found that CA-HE50 can help prevent APAP-induced hepatic tissue injury in BALB/c mice. Furthermore, CA-HE50 was effective at protecting RAW 264.7 cells from lipopolysaccharide-induced cytotoxicity and inhibiting the release of nitric oxide from these cells; in particular, asiaticoside was found to be a key component of CA-HE50 responsible for these effects. Therefore, we suggest that CA-HE50 has potential applications in functional health foods and drugs.

A Comparative Study of the Hepatoprotective Effect of Centella asiatica Extract (CA-HE50) on Lipopolysaccharide/d-galactosamine-Induced Acute Liver Injury in C57BL/6 Mice.

Acute liver failure (ALF) refers to the sudden loss of liver function and is accompanied by several complications. In a previous study, we revealed the protective effect of Centella asiatica 50% ethanol extract (CA-HE50) on acetaminophen-induced liver injury. In the present study, we investigate the hepatoprotective effect of CA-HE50 in a lipopolysaccharide/galactosamine (LPS-D-Gal)-induced ALF animal model and compare it to existing therapeutic silymarin, Lentinus edodes mycelia (LEM) extracts, ursodeoxycholic acid (UDCA) and dimethyl diphenyl bicarboxylate (DDB). Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased in the CA-HE50, silymarin, LEM, UDCA and DDB groups compared to the vehicle control group. In particular, AST and ALT levels of the 200 mg/kg CA-HE50 group were significantly decreased compared to positive control groups. Lactate dehydrogenase (LDH) levels were significantly decreased in the CA-HE50, silymarin, LEM, UDCA and DDB groups compared to the vehicle control group and LDH levels of the 200 mg/kg CA-HE50 group were similar to those of the positive control groups. Superoxide dismutase (SOD) activity was significantly increased in the 100 mg/kg CA-HE50, LEM and UDCA groups compared to the vehicle control group and, in particular, the 100 mg/kg CA-HE50 group increased significantly compared to positive control groups. In addition, the histopathological lesion score was significantly decreased in the CA-HE50 and positive control groups compared with the vehicle control group and the histopathological lesion score of the 200 mg/kg CA-HE50 group was similar to that of the positive control groups. These results show that CA-HE50 has antioxidant and hepatoprotective effects at a level similar to that of silymarin, LEM, UDCA and DDB, which are known to have hepatoprotective effects; further, CA-HE50 has potential as a prophylactic and therapeutic agent in ALF.

Anti-obesity effects of galla rhois via genetic regulation of adipogenesis.

In the present study, we investigated the effects of Galla Rhois (GR) on obesity and gene expression. We prepared a GR extract and various solvent fractions and evaluated the degree to which they inhibited adipocyte differentiation and adipogenesis in vitro. Among them, the GR ethyl acetate fraction (GE) had the lowest EC50 for adipocyte differentiation and adipogenesis and thus was selected for in vivo experiments. We induced obesity in C57BL/6 mice by providing them a high-fat diet (HFD). Then, GE (10-40 mg/kg) or orlistat (positive control, 4 mg/kg) was orally administered daily for six weeks. Mean body weights and weight gain were significantly lower in the GE40 group (40 mg/kg of GE) compared with the HFD group (p < 0.05). The most significant changes in serum glucose, total cholesterol, and triglyceride levels were confirmed in the GE40 group (p < 0.05). Epididymal fat was weighed and stained for body fat measurement, and significant differences were recorded from GE10 to GE40 (p < 0.05). Finally, 3T3-L1 pre-adipocytes were treated with GE, and cDNA from these cells was used for microarray analysis and qRT-PCR. Microarray analysis revealed 13 genes up-regulated and 21 genes down-regulated by GE. From the qRT-PCR analysis, we found that GE altered the mRNA expression of eosinophil peroxidase, glucose-dependent insulinotropic polypeptide receptor, and apolipoprotein B. Based on this study, we suggest that GR could be developed as an anti-obesity therapeutic agent.

Lomens-P0 (mixed extracts of Hordeum vulgare and Chrysanthemum zawadskii) regulate the expression of factors affecting premenstrual syndrome symptoms.

BACKGROUND/OBJECTIVES: Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms. MATERIALS/METHODS: Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS: Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1ß, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS: The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

Steamed Ginger May Enhance Insulin Secretion through KATP Channel Closure in Pancreatic ß-Cells Potentially by Increasing 1-Dehydro-6-Gingerdione Content.

Ginger (Zingiber officinale Roscoe) and its active compounds (gingerols, shogaols and paradols) have been reported as having beneficial functions for several diseases, including diabetes. In this study, we revealed that the steaming process could enhance the anti-diabetic potential of ginger. To confirm the anti-diabetic effect of steamed ginger extract (GG03), we assessed pancreatic islets impaired by alloxan in zebrafish and demonstrated anti-hyperglycemic efficacy in a mouse model. The EC50 values of ginger extract (GE) and GG03 showed that the efficacy of GG03 was greater than that of GE. In addition, LC50 values demonstrated that GG03 had lower toxicity than GE, and the comparison of the Therapeutic Index (TI) proved that GG03 is a safer functional food. Furthermore, our data showed that GG03 significantly lowered hyperglycemia in a diabetic mouse model. HPLC was performed to confirm the change in the composition of steamed ginger. Interestingly, GG03 showed a 375% increase in 1-dehydro-6-gingerdione (GD) compared with GE. GD has not yet been studied much pharmacologically. Thus, we identified the protective effects of GD in the damaged pancreatic islets of diabetic zebrafish. We further assessed whether the anti-diabetic mechanism of action of GG03 and GD involves insulin secretion. Our results suggest that GG03 and GD might stimulate insulin secretion by the closure of KATP channels in pancreatic ß-cells.

Antihyperglycemic and Antilipidemic Effects of the Ethanol Extract Mixture of Ligularia fischeri and Momordica charantia in Type II Diabetes-Mimicking Mice.

The extract of the Momordica charantia fruit (MCE) is recognized as an alternative treatment for diabetes. The extract of Ligularia fischeri leaves (LFE) is traditionally used as a folk medicine for treating inflammatory diseases in Korea as well. In this study, we investigated the synergistic effect of MCE combined with LFE on antihyperglycemic and antihyperlipidemic potentials. Based on the α-glucosidase inhibitory effect and promotion of adipocyte differentiation in the 3T3-L1 cell line, the MLM was prepared with MCE:LFE (8:2 weight:weight). MLM showed the synergistic effects in the promotion of the glucose uptake rate, suppression of dipeptidyl peptidase-4 (DPP-4) mRNA expression, upregulation of an insulin receptor substrate and glucose transporter type-4 expression, and an increase in insulin-associated signaling in C2C12 cells. In addition, the efficacy of peroxisome proliferator-activated receptor-γ agonism and glucose uptake rate by MLM supplementation was significantly enhanced in vitro. Then, the antihyperglycemic and antihyperlipidemic effects of MCE, LFE, and MLM at the dose of 50, 100, and 200 mg/kg/day (n = 6 per each group) were determined in streptozotocin (STZ)-insulted mice fed an atherogenic diet (ATH) for 4 weeks. In addition, MLM (50, 100, and 200 mg/kg/day, n = 5 per each group) was supplemented in ATH-fed db/db mice for 10 weeks. Compared with MCE or LFE alone, MLM supplementation led to a more significant reduction of glucose levels in both STZ/ATH and db/db/ATH mice as well as lowered lipid profiles in STZ/ATH mice. In addition, the stimulation of islet of Langerhans regeneration was more pronounced by MLM supplementation in both mice models. In conclusion, antihyperglycemic and antihyperlipidemic effects were strengthened by the combined extracts of L. fischeri and M. charantia (MLM) in diabetes-mimicking mice.

Effects of Zanthoxylum piperitum ethanol extract on osteoarthritis inflammation and pain.

Degenerative arthritis, also known as osteoarthritis (OA), is the most common type of arthritis, which is caused by degenerative damage of the cartilage, which primarily protects the joints, leading to inflammation and pain. The objective of this study was to investigate the in vivo and in vitro effects of treatment with ZPE-LR (90% EtOH extract of Zanthoxylum piperitum) on pain severity and inflammation. When using an in vivo OA model MIA (monosodiumidoacetate-induced arthritis) rats, ZPE-LR (100 mg/kg) oral-administratio significantly inhibited MIA-induced change in loaded weight ratio on the left foot, and articular cartilage thickness. To confirm the positive effects on pain relief, acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. Pain related KCNJ6 mRNA expression as well as K + current was increased after ZPE-LR treatment in BV-2 cells. To confirm the positive effects on inflammation, TPA (12-O-tetradecanoylphorbol-13-acetate) induced inflammation measured by mouse ear thickness and biopsy punch weight and TPA-induced iNOS, COX-2 mRNA and protein expression were remarkably suppressed by 50 and 100 mg/kg ZPE-LR oral-administration. In addition, TPA-induced iNOS, COX-2 mRNA level and protein expression were reduced. Acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. We examined in vitro ZPE-LR effects in LPS-induced RAW 264.7 cells. LPS-induced p65 translocation to the nucleus was prohibited by ZPE-LR 100 µg/ml oral administration. Moreover, ROS generation by LPS was significantly inhibited by ZPE-LR 50 and 100 µg/ml treatment. To investigate new ZPE-LR activating mechanisms, the gene fishing method (not a typical term, should probably use PCR based genetic screening) was used. LPS-induced HPRT1 (hypoxanthine phosphoribosyltransferase 1) was decreased by ZPE-LR. However, RPL8 (Ribosomal protein L8) which showed no change in mRNA expression due to LPS, did show increased mRNA levels after ZPE-LR treatment. Our data elucidate mechanisms underlying ZPE-LR and suggest ZPE-LR may be a potential therapeutic agent to modulate osteoarthritis inflammation and pain.

Anti-inflammatory effects of Saururus chinensis aerial parts in murine macrophages via induction of heme oxygenase-1.

Saururus chinensis (Lour.) Baill. is a perennial plant distributed throughout Northeast Asia and its roots have been widely used as a traditional medicine for hepatitis, asthma, pneumonia, and gonorrhea. This study was designed to investigate the anti-inflammatory activity of an extract of S. chinensis of the aerial parts (rather than the root), and the signaling pathway responsible for this effect in lipopolysaccharide-stimulated murine macrophages. The subfraction 4 (SCF4) from the n-hexane layer of the ethanol extract of the aerial parts of S. chinensis exhibited the highest nitrite-inhibitory activity. SCF4 significantly inhibited the production of nitrite and the expression of pro-inflammatory mediators via heme oxygenase-1 upregulation. SCF4 caused significant phosphorylation of p38 MAPK and Akt, which subsequently induced the nuclear translocation of p-p65 nuclear factor-κB and Nrf2. SCF4 also suppressed the phosphorylation of signal transducers and activators of transcription 1 (p-STAT1). The heme oxygenase-1 inhibitor zinc protoporphyrin attenuated the inhibitory effect of SCF4 on lipopolysaccharide-stimulated nitrite production and expression of inflammatory mediators, tumor necrosis factor alpha, and p-STAT1. We identified sauchinone as the active compound in S. chinensis extract and SCF4. Sauchinone was shown to significantly inhibit nitrite production and inflammatory mediators expression via heme oxygenase-1 upregulation. These results suggest that S. chinensis extract, SCF4, and its active compound, sauchinone, could be used as an anti-inflammatory agent.

Antitumor and biological investigation of doubly cyclometalated ruthenium(II) organometallics derived from benzimidazolyl derivatives.

In this study, we report the synthesis, anticancer and biological properties of three doubly cyclometalated phenylbenzimidazole derived ruthenium(ii) organometallics () and their corresponding three organic ligands. The structures of were fully characterized by various analytical techniques, and the meso stereoisomer of the doubly cyclometalated ruthenacycle was unambiguously confirmed by single crystal X-ray diffraction. The anticancer effects of the newly synthesized compounds were tested against selected human cancer cell lines AGS (gastric carcinoma), SK-hep-1 (hepatocellular carcinoma), and HCT-15 (colorectal carcinoma). The growth inhibitory effects of ruthenacycles on cancer cells were found to be considerably more effective against the abovementioned cancer cells than the reference drug oxaliplatin. Compound exhibited a more specific effect on the AGS cells. Gene-fishing and ELISA array were performed to analyze the target genes and cytokine secretion by . As a result, a significant reduction was observed in RPS21 by . Moreover, increased the secretion of cytokines such as IFNγ in macrophages and reduced the release of cytokines such as rantes and IGF-1. These results show that could be a very good anticancer drug through the regulation of the RPS21 gene and cytokines.

Inhibitory effects of norlignans isolated from Anemarrhena asphodeloides on degranulation of rat basophilic leukemia- 2H3Cells.

Anemarrhena asphodeloides is known to suppress inflammation and lower various fevers. To determine the active component of A. asphodeloides, ethanol (EtOH) extract of A. asphodeloides rhizomes was fractionized. The compounds isolated from the dichloromethane (CH2Cl2) soluble fraction were identified as 4'-O-methylnyasol (1), nyasol (2), 3″-methoxynyasol (3), 3″-hydroxy-4″-methoxy-4″-dehydroxynyasol (4), 4-hydroxybenzaldehyde (5), and 4-hydroxyacetophenone (6). The four norlignans (1-4) potently inhibited the release of ß-hexosaminidase from immunoglobulin E (IgE)/dinitrophenol-conjugated bovine serum albumin (DNP-BSA)-treated rat basophilic leukemia (RBL)-2H3 and A23187 plus phorbol 12-myristate 13-acetate co-treated isolated rat primary mast cells, as markers of degranulation and histamine release. The intraperitoneal treatment with the EtOH extract significantly suppressed the fetal reaction, and serum histamine release induced by compound 48/80 in mice. These results suggest that the four active norlignan compounds and the EtOH extract of A. asphodeloides may have potential to be developed as medicines for the treatment of allergies by inhibiting the activation of mast cells.

Anti-obesity effect of Crinum asiaticum var. japonicum Baker extract in high-fat diet-induced and monogenic obese mice.

This study determined the anti-obesity effect of Crinum asiaticum var. japonicum Baker extract (CAE) on adipocytes and obese mice. The inhibitory effects of CAE on adipocyte differentiation and adipogenesis were determined using differentiation induction medium in 3T3-L1 cells. To get an insight into underlying molecular actions of CAE, we investigated the changes in the expression levels of genes involved in lipogenesis by CAE treatment using qRT-PCR. CAE strongly suppressed adipocyte differentiation through downregulation of PPARγ, C/EBPα, C/EBP ß, and aP2. CAE treatment could also suppress the expression levels of ACC, FAS, LPL and HMGCR gene in 3T3-L1 cells. Male C57BL/6 strain and C57BL/6J-ob/ob strain mice were fed with HFD containing 60% fat and normal diet in the presence or absence of 25, 50, and 100mg/kg CAE for 7 weeks. CAE supplementation could highly suppress the body weight gain and epididymal fat accumulation without changes in food uptake in both obese models. Increases in total cholesterol, LDL-cholesterol and triglyceride were highly suppressed in the presence of CAE. In summary, CAE has an anti-obesity effect and this anti-obesity potential might be associated with downregulation of genes involved in adipocyte differentiation and lipogenesis.

Antiallergic Activity of Ethanol Extracts of Arctium lappa L. Undried Roots and Its Active Compound, Oleamide, in Regulating FcεRI-Mediated and MAPK Signaling in RBL-2H3 Cells.

The antiallergic potential of Arctium lappa L. was investigated in Sprague-Dawley rats, ICR mice, and RBL-2H3 cells. Ethanol extract (90%) of A. lappa (ALE, 100 µg/mL) inhibited the degranulation rate by 52.9%, determined by the level of ß-hexosaminidase. ALE suppressed passive cutaneous anaphylaxis (PCA) in rats and attenuated anaphylaxis and histamine release in mice. To identify the active compound of ALE, we subsequently fractionated and determined the level of ß-hexosaminidase in all subfractions. Oleamide was identified as an active compound of ALE, which attenuated the secretion of histamine and the production of tumor necrosis factor (TNF)-α and interleukin-4 (IL-4) in cells treated with compound 48/80 or A23187/phorbol myristate acetate (PMA). Oleamide suppressed FcεRI-tyrosine kinase Lyn-mediated pathway, c-Jun N-terminal kinases (JNK/SAPK), and p38 mitogen-activated protein kinases (p38-MAPKs). These results showed that ALE and oleamide attenuated allergic reactions and should serve as a platform to search for compounds with antiallergic activity.

Cynanchum wilfordii Radix attenuates liver fat accumulation and damage by suppressing hepatic cyclooxygenase-2 and mitogen-activated protein kinase in mice fed with a high-fat and high-fructose diet.

Excessive consumption of fat and fructose augments the pathological progression of nonalcoholic fatty liver disease through hepatic fibrosis, inflammation, and hepatic de novo lipogenesis. We hypothesized that supplementation with Cynanchum wilfordii extract (CWE) decreases fat accumulation in the liver by suppressing cyclooxygenase-2 (COX-2), the nuclear translocation of nuclear factor κB (NF-κB), and p38 mitogen-activated protein kinase (MAPK). The beneficial effect of CWE was evaluated in a murine model of nonalcoholic fatty liver disease. Mice were fed either a normal diet or an atherogenic diet with fructose (ATHFR) in the presence or absence of CWE (50, 100, or 200 mg/kg; n=6/group). Treatment with ATHFR induced a hepatosplenomegaly-like condition (increased liver and spleen weight); this pathological change was attenuated in the presence of CWE. The ATHFR group exhibited impaired liver function, as evidenced by increased blood levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, fat accumulation in the liver, and lipid profiles. Supplementation of CWE (100 and 200 mg/kg, P<.05) ameliorated these impaired liver functions. Atherogenic diet with fructose increased the protein levels of COX-2 and p38 MAPK, as well as the nuclear translocation of NF-κB. These signaling pathways, which are associated with the inflammatory response, were markedly suppressed after CWE treatment (100 and 200 mg/kg). In summary, CWE supplementation reduced high-fat and high-fructose diet-induced fat accumulation and damage in the liver by suppressing COX-2, NF-κB, and p38 MAPK.