Deer Velvet and Eleutherococcus senticosus Mixture Regulated Immune Function in C57BL/6N Mice with Immunosuppression Induced by Forced Swimming.

Immunosuppression occurs in response to a variety of external antigens. However, various immune cells and cytokines can activate the immune system. In this study, it was found that fermented deer velvet (FD) and fermented Eleutherococcus senticosus (FE) extract (FDE) mixtures regulated the immunity of animals that underwent induced immunosuppression through forced swimming exercise (FSE). Seven mouse treatment groups were included in the experiment: normal controls, FSE controls, positive controls (FSE+red ginseng 300 mg/kg body weight), FD200 (FSE+FD 200 mg/kg body weight), FE200 (FSE+FE 200 mg/kg body weight), FDE50 (FSE+FDE 50 mg/kg body weight), and FDE200 (FSE+FDE 200 mg/kg body weight). Oral intake of experimental and control substances lasted for 2 weeks. Oral FDE intake increased cell counts for major histocompatibility complex (MHC) I, MHC II, CD4(+) T cells, and CD8(+) T cells compared with controls. Moreover, FDE increased Th1 (interleukin [IL]-2 and interferon gamma) cytokine proliferation, T cell proliferation, IL-12 and IL-15 production, and natural killer cell activity compared with controls. In addition, FDE inhibited Th2 cytokines (IL-4, IL-6, IL-10, and tumor necrosis factor alpha) and nitric oxide production, increased B cell proliferation and leukocyte count, and promoted immunoglobulin A and G serum levels compared with controls. Thus, the finding that FDE increased immune function in an immunosuppression model suggests that FDE has immunomodulatory capacity.

Hypouricemic Effects of Chrysanthemum indicum L. and Cornus officinalis on Hyperuricemia-Induced HepG2 Cells, Renal Cells, and Mice.

Hyperuricemia, abnormally excess accumulation of uric acid, is caused by an imbalance between the production and excretion of uric acid and is a major cause of gout. We compared the effects of extracts from Chrysanthemum indicum L. (Ci) and Cornus officinalis Siebold and Zucc. (Co) on hyperuricemia, both individually and in combination (FSU-CC), using hypoxanthine-treated human liver cancer (HepG2) cells, primary mouse renal proximal tubule cells, and potassium oxonate induced hyperuricemic mice. The Ci contained 7.62 mg/g luteolin and 0 mg/g loganin, Co contained 0 mg/g luteolin and 4.90 mg/g loganin, and FSH-CC contained 3.95 mg/g luteolin and 2.48 mg/g loganin. We found that treatment with Ci, Co, and FSU-CC suppressed the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase while inducing an increase in the expression levels of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) proteins and a decrease in the expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins. Particularly, treatment and supplementation with FSU-CC showed stronger effects than those of supplementation with either Ci or Co alone. We observed that the excretion of creatinine and uric acid in the combination of Ci and Co was higher than that observed in their individual supplementations and was similar to that of the normal group. Therefore, our data suggest that a combination of Ci and Co may potentially be used for the development of effective natural anti-hyperuricemic functional foods.

Standardized Saw Palmetto Extract Directly and Indirectly Affects Testosterone Biosynthesis and Spermatogenesis.

We investigated whether a standardized saw palmetto extract (SP, mixture of supercritical extract and ethanol extract at a ratio of 9.5 to 0.5) can relieve the symptoms of andropause, including metabolic syndrome, and decreases in muscle endurance and spermatogenesis, in old rats. Twenty-four-week-old male Sprague Dawley rats received oral supplementation of SP at 40, 80, and 160 mg/kg body weight (bw) for 4 weeks. We found that SP supplementation reduced body weight gain by decreasing visceral and epididymal fat weights and the levels of serum triglycerides, total cholesterol, and low-density lipoprotein/very low-density lipoprotein cholesterol. In addition, SP supplementation increased muscle endurance, sperm counts, and testosterone biosynthesis through hormonal regulation. In Leydig cells under hydrogen peroxide-induced oxidative stress, SP treatment directly induced testosterone biosynthesis by activating the mRNA expression of the genes encoding 17,20-desmolase and 3ß-hydroxysteroid dehydrogenase 4. In conclusion, our results suggest that supplementation of SP may be useful for alleviating the symptoms of andropause via direct and indirect regulation of testosterone biosynthesis.

Effects of a Mixture of Humulus japonicus on Longitudinal Bone Growth in Hypophysectomized Rats.

Previously, we reported that the administration of a mixture of Humulus japonicus (MH) increased the longitudinal bone growth rate in Sprague Dawley rats. In this study, we investigated the effects of the dietary administration of MH on longitudinal bone growth in growth hormone (GH)-deficient hypophysectomized male and female rats to determine whether the effect of MH was similar to that of GH. We measured the nose-to-anus and nose-to-tail length gain, femur and tibia lengths, growth plate zones, and expression of insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) after the dietary administration of MH or the injection of GH into hypophysectomized rats for 4 weeks. Results demonstrated that the dietary administration of MH had no effect on longitudinal bone growth, whereas the injection of GH increased the nose-to-tail length gain and femur and tibia lengths in hypophysectomized rats. In addition, MH did not affect the growth plate, bone mineralization, and expression of IGF-1 and IGFBP-3. These findings indicate that MH does not exert a GH-like effect and that the effects of MH and GH on longitudinal bone growth involve different pathways.

A Mixture of Humulus japonicus Increases Longitudinal Bone Growth Rate in Sprague Dawley Rats.

The aim of this study was to investigate the effects of administration of a mixture of Humulus japonicus (MH) on longitudinal bone growth in normal Sprague Dawley (SD) rats. We measured the femur and tibia length, growth plate area, proliferation of chondrocytes, and expression of insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3), and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) phosphorylation after dietary administration of MH in SD rats for four weeks. The nose-tail length gain and length of femur and tibia increased significantly in the group that received MH for a period of four weeks. We performed H&E staining and Bromodeoxyuridine/5-Bromo-2'-Deoxyuridine (BrdU) staining to examine the effect of dietary administration of MH on the growth plate and the proliferation of chondrocytes and found that MH stimulated the proliferation of chondrocytes and contributed to increased growth plate height during the process of longitudinal bone growth. In addition, serum levels of IGF-1 and IGFBP-3 and expression of IGF-1 and IGFBP-3 mRNAs in the liver and bone were increased, and phosphorylation of JAK2/STAT5 in the liver was increased in the MH groups. Based on these results, we suggest that the effect of MH on longitudinal bone growth is mediated by increased JAK2/STAT5-induced IGF-1 production.

Policosanol Attenuates Cholesterol Synthesis via AMPK Activation in Hypercholesterolemic Rats.

This study was carried out to investigate the effects of policosanol on high-fat and high-cholesterol diet-induced hypercholesterolemic rats to provide strong evidence in support of its hypocholesterolemic effect. The hypercholesterolemic rats showed elevations in liver weight, total triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol in serum; however, policosanol supplementation reduced these markers significantly. In addition, we found that policosanol supplementation stimulated an increase in fecal cholesterol and bile acid contents and deactivated 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase by AMP-activated protein kinase (AMPK) phosphorylation during high-fat and high-cholesterol-containing diet-induced development of hypercholesterolemia. Policosanol supplementation decreased ApoB levels and increased LDL-receptor expression, but it did not affect the hepatic ACAT2 level in livers from hypercholesterolemic rats. Moreover, supplementation with policosanol significantly decreased aortic wall thickness and levels of P-selectin and soluble vascular cell adhesion molecule (sVCAM-1) in serum. In conclusion, we suggest that policosanol supplementation induces antihypercholesterolemia by inhibiting cholesterol biosynthesis, LDL cholesterol uptake, and cholesterol excretion.

Prunus yedoensis bark inhibits lipopolysaccharide-induced inflammatory cytokine synthesis by IκBα degradation and MAPK activation in macrophages.

The bark of Prunus yedoensis is used in antitussive medicines and in oral herbal formulations for inflammatory skin disorders. In the present study, we explored whether P. yedoensis bark extract (PYE) and its solvent partitioned fractions could modulate lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 in vivo and in vitro. In addition, we examined the effect of PYE extract and its fractions on LPS-induced NF-κB and mitogen-activated protein kinase (MAPK) signaling in mouse peritoneal macrophages. Oral treatment of PYE decreased serum levels of TNF-α and IL-6 in LPS injected mice. PYE inhibited LPS-induced TNF-α and IL-6 in macrophages at the transcriptional level and also suppressed LPS-induced IκBα degradation and MAPK activation in vitro. Among the fractions, the chloroform fraction, which contains genistein, naringenin, sakuranetin, prunetin, and amygdalin, showed inhibitory effects at much lower concentrations than the water and ethyl acetate fractions. Taken together, our results indicate that PYE was able to inhibit LPS-induced expression of TNF-α and IL-6, the latter of which was more prominent. The effects of PYE on inflammatory cytokine synthesis may involve modulation of NF-κB and MAPK activation.

Effect of cinnamon water extract on monocyte-to-macrophage differentiation and scavenger receptor activity.

BACKGROUND: Water soluble cinnamon extract has been shown to increase insulin sensitivity and modulate macrophage activation, a desirable trait for the management of obesity or atherosclerosis. Our present study investigated whether cinnamon water extract (CWE) may influence the differentiation of monocytes into macrophages and the activity of macrophage scavenger receptors, commonly observed in atherosclerotic lesions. METHODS: We investigated the effect of CWE on the expression of various surface markers and the uptake of acetylated low density lipoprotein (LDL) in phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. The protein levels of PMA or macrophage-colony stimulating factor (M-CSF)-stimulated type 1 macrophage scavenger receptor (SRA) were analyzed. Finally, the role of extracellar signal-related kinase (ERK) 1/2 in SRA synthesis and the effect of CWE on PMA-stimulated ERK1/2 were determined. RESULTS: CWE inhibited the differentiation of monocyte by decreasing the expression of CD11b, CD36 and SRA and the uptake of acetyl LDL. CWE suppressed the upregulation of SRA by M-CSF and modulated ERK1/2 activity, which was required for PMA-induced SRA synthesis. CONCLUSIONS: Our results demonstrate that CWE was able to interfere with monocyte differentiation and macrophage scavenger activity, indicating its potential in preventing the development of atherosclerotic lesions.