Indian Gooseberry and Barley Sprout Complex Prevent Oxidative Stress and Photoaging of the Skin in Ultraviolet B-Irradiated SHK-I Mice.

This study investigated the protective effects of a complex of Indian gooseberry and barley sprout (IB complex) on oxidative stress and skin damage caused by ultraviolet B irradiation in SHK-I hairless mice. The study examined the impact of IB complex on skin hydration, wrinkle formation, and melanogenesis using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and western blot analysis. The IB complex reduced skin hydration loss and wrinkle formation, while also demonstrating enhanced antioxidant activities. The IB complex maintained skin hydration via upregulation of hyaluronic acid and ceramide synthesis, including the regulation of hyaluronic acid synthase, long-chain ceramide formation, dihydroceramide desaturase 1 activity, and type I collagen production. The IB complex prevented wrinkle formation via downregulating JNK and upregulating TGF-ß pathways. Moreover, IB complex blocked melanin production via inhibition of protein kinase A, cAMP response element-binding protein, and microphthalmia-associated transcription factor pathways. These results suggest that IB complex is a potential agent to protect the skin against photodamage caused by exposure to UVB radiation. The research protocols underwent approval from the Institutional Animal Care and Use Committee of Kyung Hee University (KHGASP-21-577), ensuring compliance with ethical standards.

Lactuca sativa L. Extract Enhances Sleep Duration Through Upregulation of Adenosine A1 Receptor and GABAA Receptors Subunits in Pentobarbital-Injected Mice.

We investigated the effects of Lactuca sativa L. extracts (Lactuc) on pentobarbital-induced sleep in mice to elucidate the mechanisms underlying its impact on sleep quality. Mice were randomly assigned to five groups: control, positive control (diazepam 2 mg/kg b.w.), and three groups orally administered with Lactuc (50, 100, and 200 mg/kg b.w.). After 2 weeks of oral administration and intraperitoneal injections, the mice were killed. We found that the Lactuc-administered groups had significantly reduced sleep latency and increased sleep duration compared with the control group. Furthermore, the oral administration of Lactuc induced a significant increase in mRNA expression and protein expression of adenosine A1 receptor in the brains compared with the expressions in the control group. In addition, the Lactuc-administered groups exhibited significantly higher levels of mRNA expressions of GABAA receptors subunits α2, ß2, γ1, and, γ2 in the brain tissue. Therefore, we suggest that Lactuc could be used to develop natural products that effectively improve sleep quality and duration.

Curcuma longa L. extract exhibits anti-inflammatory and cytoprotective functions in the articular cartilage of monoiodoacetate-injected rats.

Background: Osteoarthritis (OA), the most prevalent form of arthritis, is a degenerative joint disease marked by the progressive deterioration of articular cartilage, leading to clinical manifestations such as joint pain. Objective: This study investigated the effects of Curcuma longa L. extract (CL) containing curcumin, demethoxycurcumin, and bisdemethoxycurcumin on monosodium iodoacetate (MIA)-induced OA rats. Design: Sprague-Dawley rats with MIA-induced OA received CL supplementation at doses of 5, 25, and 40 mg/kg body weight. Results: CL extract administration suppressed mineralisation parameters and morphological modifications and decreased arachidonate5-lipoxygenase and leukotriene B4 levels in articular cartilage. Additionally, it decreased serum prostaglandin E2, NO, and glycosaminoglycanlevels as well as the protein expression of phosphorylated inhibitor kappa B-alpha, phosphorylated p65, cyclooxygenase-2, and inducible nitric oxide synthase in the cartilage of MIA-injected rats. Furthermore, it also reduced matrix metalloproteinases and elevated SMAD family member 3 phosphorylation, tissue inhibitor of metalloproteinases, aggrecan, collagen type I, and collagen type II levels in the articular cartilage of MIA-induced OA rats. Conclusions: This study's findings suggest that CL supplementation helps prevent OA development and is an effective therapy for OA.

Low-Molecular-Weight Fish Collagen Peptide (Valine-Glycine-Proline-Hydroxyproline-Glycine-Proline-Alanine-Glycine) Prevents Osteoarthritis Symptoms in Chondrocytes and Monoiodoacetate-Injected Rats.

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.

Unripe Pear Extract Suppresses UVB-Induced Skin Photoaging in Hairless Mice and Keratinocytes.

Our study aimed to investigate whether unripe pear extract (UP) could provide protection against UVB-induced damage to both mouse skin and keratinocytes. We observed that UVB exposure, a common contributor to skin photoaging, led to wrinkle formation, skin dryness, and inflammation in mice. Nevertheless, these effects were mitigated in the groups of UVB-irradiated mice treated with UP. Moreover, UP treatment at 400 µg/mL increased the antioxidant enzyme activities (sodium dodecyl sulfate, 2.22-fold higher; catalase, 2.91-fold higher; GPx, 1.96-fold higher) along with sphingomyelin (1.58-fold higher) and hyaluronic acid (1.31-fold higher) levels in UVB-irradiated keratinocytes. In the keratinocytes irradiated with UVB, UP 400 µg/mL resulted in reduced cytokine production (TNF-α, 33.2%; IL-1ß, 45.3%; IL-6, 33.4%) and the expression of inflammatory pathway-related proteins. The findings indicate that UP has a direct protective effect on UVB-irradiated keratinocytes and is also able to shield against photoaging induced by UVB. Hence, it is suggested that UP could contribute to improved skin health by averting skin photoaging.

Lactobacillus reuteri NCIMB 30242 (LRC) Inhibits Cholesterol Synthesis and Stimulates Cholesterol Excretion in Animal and Cell Models.

In this study, we evaluated the effects of Lactobacillus reuteri NCIMB (LRC™) supplementation on hypercholesterolemia by researching its effects on cellular cholesterol metabolism in hypercholesterolemic rats (KHGASP-22-170) and HepG2 cell line. Rats were separated into six groups after adaptation and were then fed a normal control (NC), a high-cholesterol diet (HC), or a HC supplemented with simvastatin 15 mg/kg body weight (positive control [PC]), LRC 1 × 109 colony-forming units (CFU)/rat/day, LRC 4 × 109 CFU/rat/day, or LRC 1 × 1010 CFU/rat/day (1 × 109, 4 × 109, or 1 × 1010). The rats were dissected to study the effects of LRC on cholesterol metabolism and intestinal excretion at the end of experimental period. We discovered that LRC mainly participated in the restraint of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the uptake of low-density lipoprotein (LDL) cholesterol into tissues, partially in the transport of cholesteryl esters into high density lipoprotein for maturation, and intestinal excretion of cholesterol. These results are supported by the expression of transcription factors and enzymes such as HMG-CoA reductase, SREBP2, CYP7A1, CETP, and LCAT in both messenger RNA (mRNA) and protein levels in serum and hepatic tissue. Furthermore, the LRC treatment in HepG2 significantly reduced the mRNA expression of HMG-CoA reductase, SREBP2, and CEPT and significantly increased the mRNA expression of LDL-receptor, LCAT, and CYP7A1 at all doses. Hence, we suggest that LRC supplementation could alleviate the serum cholesterol level by inhibiting the intracellular cholesterol synthesis, and augmenting excretion of intestinal cholesterol.

Wheat Ceramide Powder Mitigates Ultraviolet B-Induced Oxidative Stress and Photoaging by Inhibiting Collagen Proteolysis and Promoting Collagen Synthesis in Hairless Mice.

The protective effects of wheat ceramide powder (WC-P) on ultraviolet B (UVB)-induced skin oxidative stress and photoaging in hairless mice were investigated in this study. Moreover, the activities of antioxidant enzymes, inflammation, wrinkle formation-related pathway, and moisturizing capacity were evaluated. Mice were randomly divided into six groups (n=8): normal control (non-UVB irradiation), control (UVB irradiation), L-ascorbic acid [positive control, UVB irradiation with dietary supplementation of L-ascorbic acid at 100 mg/kg/body weight (bw)], WC-P5 (UVB irradiation with dietary supplementation of WC-P at 5 mg/kg/bw), WC-P20 (UVB irradiation with dietary supplementation of WC-P at 20 mg/kg/bw), and WC-P40 (UVB irradiation with dietary supplementation of WC-P at 40 mg/kg/bw). AIN-96G diet and water were supplemented ad libitum, and 100 mL of L-ascorbic acid and WC-P dissolved in water were forcefully administered orally to mice. UVB irradiation resulted in dehydration and wrinkle formation in the dorsal skin of mice. However, WC-P supplementation suppressed. Furthermore, WC-P supplementation enhanced the activites of antioxidant enzymes and expression of transforming growth factor-ß receptor I, procollaten C-endopeptideas enhancer protein, hyaluronan synthase, and ceramide synthase 4 and reduced the activation of the inflammation and the c-Jun N-terminal kinase/c-FOS/c-Jun- mediated matrix metalloproteinase pathways. These findings demonstrate that WC-P can protect the skin from UVB-induced oxidative stress, inflammation, and photoaging by inhibiting collagen proteolysis and promoting collagen synthesis, thereby promoting skin health.

Silymarin Prevents High-Fat Diet-Induced Muscle Atrophy by Regulating Protein Degradation and Synthesis in Mice.

Silymarin is found in Silybum marianum. We investigated the effect of silymarin on muscle atrophy in obese mice. The experimental mice were divided into three groups: CON, normal diet; HFD, 60% high-fat diet (HF); and SILY: 50 mg silymarin +60% HF. It was confirmed that increases in body weight and fat mass in the SILY group were significantly inhibited. Moreover, the muscle mass in SILY mice was significantly higher than that in the HFD group. The grip strength in HFD group was significantly reduced, whereas in the SILY group it was higher than that in HFD group. In HFD mice, the mRNA levels of protein degradation factors (muscle ring-finger protein 1 [MuRF-1] and Atrogin-1) were increased and protein synthesis factors (phosphoinositide 3-kinase [PI3K] and Akt) were decreased. However, silymarin was found to elevate the degradation factors as compared with HFD group, whereas it reduced the synthesis factors. The results suggest that silymarin could prevent not only obesity but also muscle atrophy.

Krill Oil Attenuates Inflammation in Monosodium Iodoacetate-Induced Osteoarthritic Rats, SW982 Synovial Cell Line, and Primary Chondrocytes.

The aim of this study was to investigate the effects of krill oil (FJH-KO) in monoiodoacetate (MIA)-induced osteoarthritis in rat models, and H2O2- or lipopolysaccharide (LPS)-treated primary chondrocytes and the SW982 synovial cell line. We found that 150 mg/kg b.w. FJH-KO supplementation increased running speed, stride, and foot pressure in MIA-induced osteoarthritic rats. In the H2O2-treated SW982 synovial cell line and primary chondrocytes, FJH-KO treatment prevented cell death and suppressed matrix degradation by increasing the levels of anabolic factors of cartilage tissue, including aggrecan, collagen type Ⅰ, collagen type Ⅱ, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-3, and decreasing those of catabolic factors of cartilage tissue, including phosphorylation of Smad, MMP-3, and MMP-13. In addition, FJH-KO treatment suppressed the activation of inflammation and apoptosis pathways in the LPS-treated SW982 synovial cell line and primary chondrocytes. We suggest that FJH-KO supplementation may help prevent osteoarthritis progression because of its direct effects on inflammation and apoptosis of chondrocytes.

Dual Skin-Whitening and Anti-wrinkle Function of Low-Molecular-Weight Fish Collagen.

In this study, we investigated the protective effects of low-molecular-weight fish collagen from tilapia against melanogenesis in melanocytes, ultraviolet B (UVB)-irradiated Hs27 skin fibroblasts, and hairless mice. We observed collagen production-related pathways in UVB-irradiated Hs27 skin fibroblasts and hairless mice, and the melanogenesis-related pathways in melanocyte and UVB-irradiated hairless mice. The collagen production-related pathways were activated in the UVB-irradiated Hs27 skin fibroblasts and hairless mice. In addition, UVB exposure stimulated the melanogenesis-related pathways in melanocytes and hairless mice. However, treatment with low-molecular-weight fish collagen significantly increased the messenger RNA expressions of collagen production-related factors and significantly decreased the production of cytokines. Furthermore, treatment with low-molecular-weight fish collagen suppressed melanogenesis by inhibiting glutathione synthesis and downregulating melanocyte-inducing transcription factor expression through the suppression of cyclic AMP/protein kinase A/cAMP-responsive binding protein signaling and nitric oxide production. Low-molecular-weight fish collagen exerts protective effects against UVB-induced photoaging, through anti-inflammatory, antioxidant, and anti-melanogenesis activities and could be used for developing effective natural anti-photoaging products.

Effects of Bonito Elastin HC on Skin Dryness, Wrinkles, and Pigmentation In Vitro and In Vivo.

We investigated the effects of bonito fish (Katsuwonus pelamis) elastin HC (KE) on skin dryness, wrinkles, and pigmentation in vitro and in vivo. In vitro, we evaluated the expression of mRNA genes and proteins related to skin dryness, wrinkles, and pigmentation. HaCaT and HS27 cells were exposed to ultraviolet B radiation (UVB) (50 mJ/cm2), and B16F10 cells were stimulated with 3-isobutyl-1-methylxanthine (IBMX, 250 µg/mL) for 72 h to induce melanin synthesis. All cells were treated with KE (50-400 µg/mL) for 24 h. We found that KE increased the expression of long-chain base 1, dihydroceramide desaturase 1, elastin, hyaluronan synthase 2, and ceramide synthase 4 mRNA or protein as well as hyaluronic acid and sphingomyelin levels in UVB-irradiated HaCaT cells. Moreover, KE regulated factors related to collagen production, wrinkles, and melanin production in UVB-irradiated HS27 cells and IBMX-stimulated B16F10 cells. In vivo, we evaluated skin hydration and the expression of mRNA genes and proteins in the skin, and conducted morphological observations in SKH-I hairless mice (5-week-old male). The mice were exposed stepwise to UVB and given KE (10, 20, and 30 mg/kg b.w.) for 8 weeks. We found that skin hydration and protein or mRNA expression related to skin moisturization were increased in the KE group. Moreover, KE intake increased factors related to collagen production, wrinkles, and melanin production in UVB-irradiated SKH-I hairless mice. These results suggest that KE may have efficacy for the development of treatments for improving skin health.

Artichoke Extract Directly Suppresses Inflammation and Apoptosis in Hepatocytes During the Development of Non-Alcoholic Fatty Liver Disease.

We evaluated the effect of artichoke leaf extract (ALE) on the livers of mice with non-alcoholic fatty liver disease (NAFLD) induced by high-fat/high-fructose diet and H2O2-treated HepG2 cells, as well as the mechanism underlying its hepatoprotective effects. Supplementation with ALE suppressed the NAFLD-induced increases in serum lipids, bilirubin, gamma-glutamyl transferase, aspartate transaminase (AST), and alanine aminotransferase. In addition, we observed that supplementation with ALE attenuated the increases in antioxidant enzyme activity, mRNA levels of proinflammatory cytokines, and apoptosis signaling pathways caused by a high-fat/high-fructose diet. We found that ALE treatment suppressed inflammation and apoptosis caused by H2O2-induced oxidative stress in HepG2 cells. These findings suggest that ALE supplementation directly suppresses inflammation and apoptosis in hepatocytes during the development of NAFLD. Based on these results, we suggest that supplementation with ALE may be useful for preventing the progression of liver diseases, including hepatic steatosis and non-alcoholic steatohepatitis.

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.

Combination of Bifidobacterium longum and Galacto-Oligosaccharide Protects the Skin from Photoaging.

Overexposure to ultraviolet B (UVB) irradiation induces photoaging that is characterized by the formation of wrinkles and loss of skin elasticity. To understand the mechanism of action of probiotics and prebiotics in skin protection against photoaging, we investigated the effects of dietary supplementation with the probiotic, Bifidobacterium longum, and prebiotic, galacto-oligosaccharide, on UVB-induced photoaging in hairless mice. We measured short chain fatty acid (SCFA) levels, antioxidant enzyme activity, and inflammatory signaling protein levels to elucidate the possible mechanisms underlying the effects of the dietary supplements B. longum and galacto-oligosaccharide. We observed that dietary supplementation with B. longum and galacto-oligosaccharide, individually and in combination, exerted protective effects against UVB-induced photoaging, showing anti-inflammatory and antioxidative effects. In particular, supplementation with the combination of B. longum and galacto-oligosaccharide showed stronger protective effects than supplementation with the probiotic or prebiotic alone. In addition, the serum levels of SCFAs and acetate were increased following dietary supplementation with B. longum and galacto-oligosaccharide, especially in combination. Therefore, we suggest that the combination of B. longum and galacto-oligosaccharide may potentially be used as a functional food to protect UVB-induced photoaging.

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.

Emblica officinalis and Hordeum vulgare L. Mixture Regulates Lipolytic Activity in Differentiated 3T3-L1 Cells.

In this study, we investigated the lipolytic effects of an Emblica officinalis (Indian gooseberry [IG]) and Hordeum vulgare L. (barley sprout [BP]) mixture on differentiated 3T3-L1 cells. On the ninth day of differentiation, Oil red O staining and Western blotting were performed; additionally, glycerol release and triglyceride (TG), fatty acid (FA), and cyclic adenosine monophosphate (cAMP) levels were measured. Compared to the differentiation-induced control (C) group, the IG and BP mixture inhibited intracellular TG and FA levels by 61.7% and 48.9%, respectively, at a concentration of 200 µg/mL. Moreover, the mixture increased glycerol release and cAMP levels by more than twofold more than those in the C group. Western blotting was performed to confirm the protein expression involved in lipolysis, and the IG and BP mixture was found to significantly increase the protein activities of AMP-activated protein kinase, protein kinase A, and hormone-sensitive lipase compared to those of the C group. Furthermore, the mixture significantly inhibited the protein activities of phosphodiesterase 3B, adipose TG lipase, and perilipin compared to those of the C group at a concentration of 200 µg/mL. We found that the IG and BP mixture activates the cAMP pathway and regulates lipolytic enzymes, which are necessary for lipolysis. In conclusion, our findings suggest that the IG and BP mixture can be potentially developed as a new material for targeting mechanisms underlying lipolysis.

Ethanolic Extract of Vaccinium corymbosum Alleviates Muscle Fatigue in Mice.

The aim of this study was to evaluate the effects of ethanol extracts of Vaccinium corymbosum (VCE) on exercise-induced fatigue in mice. Mice were randomly divided into three groups; nonexercise control group (CON), exercise control group (Ex-CON), and exercise and VCE supplementation group (Ex-VCE). Compared with Ex-CON, Ex-VCE showed increased endurance exercise capacity on day 21. In Ex-VCE mice, the accumulation of lactate was inhibited and the consumption of fatty acids was enhanced, indicating the delay of muscle fatigue. In addition, VCE supplementation elevated mRNA expression levels of mitochondrial biogenesis-associated genes such as peroxisome proliferator-activated receptor-1γ coactivator 1α (PGC-1α), nuclear respiratory factor (NRF), and mitochondrial transcription factor A (Tfam) and fatty acid ß-oxidation-associated genes such as carnitine palmitoyltransferase-1 (CPT-1), ß-hydroxyacyl coenzyme A dehydrogenase (ß-HAD), and peroxisome proliferator-activated receptor-δ (PPAR-δ). These results suggest that VCE can potentially prevent muscle fatigue by enhancing mitochondrial biogenesis and fatty acid ß-oxidation.

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.

Immunomodulatory Effect of a Salvia plebeia R. Aqueous Extract in Forced Swimming Exercise-induced Mice.

This study investigated the immunomodulatory effect of Salvia plebeia R. aqueous extract (FIE-SP, SPW) in forced swimming exercise-induced mice and the immunostimulatory effects on Raw264.7 cells. Mice were randomly assigned to four groups: the control group (CON), the forced swimming test group (FST), and two FIE-SP groups (low and high dose of FIE-SP). Compared with the control group, the FIE-SP groups showed significantly increased ratios of T lymphocyte surface markers CD4+/CD8+ and major histocompatibility complex (MHC)I/MHCII, as well as increased concentrations of immunoglobulin (Ig)A and IgG. FIE-SP groups significantly increased Th1 cytokines and decreased Th2 cytokines compared with negative control exercise-induced mice. Conversely, the immunostimulatory effects of FIE-SP significantly increased phagocytic activities, nitric oxide (NO) production, and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß in Raw264.7 cells. Furthermore, FIE-SP increased natural killer (NK) cell activities and cytokines (IL-12) in splenocytes compared with the CON group. These results indicated that FIE-SP supplementation could prevent imbalanced immune states and produce immunostimulatory effects to support innate immunity.