Kefir peptides exhibit antidepressant-like activity in mice through the BDNF/TrkB pathway.

Depression is a prevalent, stress-related mental disorder that can lead to serious psychiatric diseases with morbidity and high mortality. Although some functional fermented dairy drinks have promising anxiolytic and antidepressant effects, the mechanism is still not clear. To determine the antidepressant-like effect and the potential molecule mechanism of kefir peptides (KP), various behavioral tests, including the elevated plus maze test, open field test, forced swimming test, and tail suspension test, were used. Administration of 150 mg/kg KP in mice reduced the duration of immobility in the forced swimming test and tail suspension test, elevated the time spent in the open arm and center zone in the elevated plus maze test, and increased the total distance traveled, average speed, and time spent in the center zone in the open field test compared with the mock group. These results indicated that KP dramatically ameliorated the depression-like behaviors. Kefir peptides were further isolated and identified using high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, from which 3 peptides were identified and designated KFP-1, KFP-3, and KFP-5. Among these peptides, administration of KFP-3 (15 AA residues) remarkably decreased immobility time in the forced swimming test and increased mobility time in the tail suspension test. Therefore, KFP-3 may be the major active peptide with antidepressant activity in KP. Overexpression of brain-derived neurotrophic factor, phosphorylated tropomyosin receptor kinase B, and phosphorylated ERK1/2 protein levels could be detected in the hippocampus under KP administration. Therefore, we suggest that KP improves depressive-like behaviors by activating the brain-derived neurotrophic factor-phosphorylated tropomyosin receptor kinase B signaling pathway. Kefir peptides may serve as a new type of antidepressant dairy product and may provide potent antidepressant effects for clinical use.

The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses.

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.

A Novel Relative High-Density Lipoprotein Index to Predict the Structural Changes in High-Density Lipoprotein and Its Ability to Inhibit Endothelial-Mesenchymal Transition.

Therapeutic elevation of high-density lipoprotein (HDL) is thought to minimize atherogenesis in subjects with dyslipidemia. However, this is not the case in clinical practice. The function of HDL is not determined by its concentration in the plasma but by its specific structural components. We previously identified an index for the prediction of HDL functionality, relative HDL (rHDL) index, and preliminarily explored that dysfunctional HDL (rHDL index value > 2) failed to rescue the damage to endothelial progenitor cells (EPCs). To confirm the effectiveness of the rHDL index for predicting HDL functions, here we evaluated the effects of HDL from patients with different rHDL index values on the endothelial-mesenchymal transition (EndoMT) of EPCs. We also analyzed the lipid species in HDL with different rHDL index values and investigated the structural differences that affect HDL functions. The results indicate that HDL from healthy adults and subjects with an rHDL index value < 2 protected transforming growth factor (TGF)-ß1-stimulated EndoMT by modulating Smad2/3 and Snail activation. HDL from subjects with an rHDL index value > 2 failed to restore the functionality of TGF-ß1-treated EPCs. Lipidomic analysis demonstrated that HDL with different rHDL index values may differ in the composition of triglycerides, phosphatidylcholine, and phosphatidylinositol. In conclusion, we confirmed the applicability of the rHDL index value to predict HDL function and found structural differences that may affect the function of HDL, which warrants further in-depth studies.

Effects of Melatonin on Lipid Metabolism and Circulating Irisin in Sprague-Dawley Rats with Diet-Induced Obesity.

Melatonin, a pivotal photoperiodic signal transducer, may work as a brown-fat inducer that regulates energy balance. Our study aimed to investigate the effects of melatonin treatment on the body fat accumulation, lipid profiles, and circulating irisin of rats with high-fat diet-induced obesity (DIO). Methods: 30 male Sprague-Dawley rats were divided into five groups and treated for 8 weeks: vehicle control (VC), positive control (PC), MEL10 (10 mg melatonin/kg body weight (BW)), MEL20 (20 mg/kg BW), and MEL50 (50 mg/kg BW). The vehicle control group was fed a control diet, and the other groups were fed a high-fat and high-calorie diet for 8 weeks to induce obesity before the melatonin treatment began. Melatonin reduced weight gain without affecting the food intake, reduced the serum total cholesterol level, enhanced the fecal cholesterol excretion, and increased the circulating irisin level. Melatonin downregulated the fibronectin type III domain containing 5 (FNDC5) and lipoprotein lipase (LPL) mRNA expressions of inguinal white adipose tissue (iWAT) and induced the browning of iWAT in both the MEL10 and MEL20 groups. Conclusion: Chronic continuous melatonin administration in drinking water reduced weight gain and the serum total cholesterol levels. Additionally, it enhanced the circulating irisin, which promoted brite/beige adipocyte recruitment together with cholesterol excretion and contributed to an anti-obesity effect.

Combination Therapy of Acarbose and Cyclosporine a Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.

Moderate to severe psoriasis, an immune-mediated inflammatory disease, adversely affects patients' lives. Cyclosporin A (CsA), an effective immunomodulator, is used to treat psoriasis. CsA is ineffective at low doses and toxic at high doses. Acarbose (Acar), a common antidiabetic drug with anti-inflammatory and immunomodulatory effects, reduces imiquimod (IMQ)-induced psoriasis severity. Combinations of systemic drugs are generally more efficacious and safer than higher doses of single drugs. We observed that mice treated with a combination of Acar (250 mg/kg) and low-dose CsA (10 or 20 mg/kg) exhibited significantly milder IMQ-induced psoriasis-like dermatitis and smoother back skin than those treated with Acar (250 mg/kg), low-dose CsA (10 or 20 mg/kg), or IMQ alone. The combination therapy significantly reduced serum and skin levels of Th17-related cytokines (interleukin (IL)-17A, IL-22, and IL-23) and the Th1-related cytokine tumor necrosis factor-α (TNF-α) compared with Acar, low-dose CsA, and IMQ alone. Additionally, the combination therapy significantly reduced the percentages of IL-17- and IL-22-producing CD4+ T-cells (Th17 and Th22 cells, respectively) and increased that of Treg cells. Our data suggested that Acar and low-dose CsA in combination alleviates psoriatic skin lesions by inhibiting inflammation. The findings provide new insights into the effects of immunomodulatory drugs in psoriasis treatment.

Sinensetin induces apoptosis and autophagy in the treatment of human T-cell lymphoma.

The present study was carried out to explore the effect of sinensetin in human T-cell lymphoma Jurkat cells and to reveal the underlying molecular mechanisms. We found that sinensetin significantly impeded Jurkat cell proliferation in a dose-dependent and time-dependent manner. Additionally, sinensetin treatment triggered apoptosis and autophagy in Jurkat cells. The apoptosis induction was related to a loss of mitochondrial membrane potential and to increased caspase-3/-8/-9 and poly(ADP-ribose) polymerase (PARP) cleavage. Sinensetin also induced autophagy, as evidenced by the formation of acidic vacuoles, the upregulation of LC3-II and beclin-1, and the downregulation of p62. In addition, the inhibition of autophagy by 3-methyladenine significantly enhanced the apoptosis rate and improved the sensitivity of the Jurkat cells to sinensetin. Moreover, sinensetin induced cell death, apoptosis, and autophagy through the activation of the reactive oxygen species/ c-Jun N-terminal kinase signaling pathway and the inhibition of the Akt/mTOR signaling pathways. In summary, our results revealed that sinensetin induced apoptosis and autophagy in human T-cell lymphoma Jurkat cells by activating reactive oxygen species/ c-Jun N-terminal kinase and blocking the Akt/mTOR signaling pathways. Thus, sinensetin might be a potential candidate in the development of antitumor drugs targeting T-cell leukemia.

Tea Seed Oil Prevents Obesity, Reduces Physical Fatigue, and Improves Exercise Performance in High-Fat-Diet-Induced Obese Ovariectomized Mice.

Menopause is associated with changes in body composition (a decline in lean body mass and an increase in total fat mass), leading to an increased risk of metabolic syndrome, nonalcoholic fatty liver disease, and heart disease. A healthy diet to control body weight is an effective strategy for preventing and treating menopause-related metabolic syndromes. In the present study, we investigated the effect of long-term feeding of edible oils (soybean oil (SO), tea seed oil (TO), and lard oil (LO)) on female ovariectomized (OVX) mice. SO, TO, and LO comprise mainly polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA), respectively. However, there have been quite limited studies to investigate the effects of different fatty acids (PUFA, MUFA, and SFA) on physiological adaption and metabolic homeostasis in a menopausal population. In this study, 7-week-old female Institute of Cancer Research (ICR) mice underwent either bilateral laparotomy (sham group, n = 8) or bilateral oophorectomy (OVX groups, n = 24). The OVX mice given a high-fat diet (HFD) were randomly divided into three groups: OVX+SO, OVX+TO, and OVX+LO. An HFD rich in SO, TO, or LO was given to the OVX mice for 12 weeks. Our findings revealed that the body weight and relative tissues of UFP (uterus fatty peripheral) and total fat (TF) were significantly decreased in the OVX+TO group compared with those in the OVX+SO and OVX+LO groups. However, no significant difference in body weight or in the relative tissues of UFP and TF was noted among the OVX+SO and OVX+LO groups. Furthermore, mice given an HFD rich in TO exhibited significantly decreased accumulation of liver lipid droplets and adipocyte sizes of UFP and brown adipose tissue (BAT) compared with those given an HFD rich in SO or LO. Moreover, replacing SO or LO with TO significantly increased oral glucose tolerance. Additionally, TO improved endurance performance and exhibited antifatigue activity by lowering ammonia, blood urea nitrogen, and creatine kinase levels. Thus, tea seed oil (TO) rich in MUFA could prevent obesity, reduce physical fatigue, and improve exercise performance compared with either SO (PUFA)- or LO(SFA)-rich diets in this HFD-induced obese OVX mice model.

Effects of dextrose prolotherapy on contusion-induced muscle injuries in mice.

Current treatment options for muscle injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscles. In this study, the effects of dextrose prolotherapy on inflammation and regeneration of skeletal muscles after a contusion injury were investigated. Mice were separated into five groups, including a normal control (NC), post-injury with no treatment (mass-drop injury, MDI), post-injury with 10% dextrose (MDI + 10% dextrose), post-injury with 20% dextrose (MDI + 20% dextrose), and post-injury with 30% dextrose (MDI + 30% dextrose). The gastrocnemius muscles of the mice were subjected to an MDI, and muscle samples were collected at 7 days post-injury. Results showed the serum creatine kinase (CK), blood urea nitrogen (BUN), creatinine (CREA), and low-density lipoprotein (LDH) of the MDI-alone group were significantly higher than those of the normal control group (p<0.05). However, levels of serum CK, BUN, CREA, and lactate dehydrogenase (LDH) significantly decreased with different concentrations of dextrose. In addition, dextrose suppressed the macrophage response (F4/80 protein decreased) and promoted muscle satellite cell regeneration (desmin protein increased). In conclusion, dextrose prolotherapy can effectively help repair muscles; therefore, it may be one of the methods for clinically treating muscle injuries.

A Soft Coral-Derived Compound, 11-Dehydrosinulariolide, Induces G2/M Cell Cycle Arrest and Apoptosis in Small Cell Lung Cancer.

11-Dehydrosinulariolide, an active compound that is isolated from the cultured soft coral Sinularia flexibilis, has been suggested to show anti-tumor biological characteristics according to previous studies. However, its potential effect on small cell lung cancer (SCLC) remains unknown. The present study investigates the underlying mechanism for the treatment of SCLC in vitro and in vivo. Cell viability was examined using the methyl-thiazol-diphenyl-tetrazolium (MTT) assay. Flow cytometry was applied to evaluate cell cycle distribution and apoptosis. The expression of proteins related to the cell cycle and apoptosis was analyzed by Western blot analysis. Additionally, an in vivo study was performed to determine the anti-SCLC effect on an H1688 subcutaneous tumor in a BALB/c nude mouse model. 11-Dehydrosinulariolide inhibited cell growth, triggered G2/M arrest and induced H1688 cell apoptosis in a dose- and time-dependent manner. Additionally, 11-dehydrosinulariolide caused the accumulation of p53 and Bax, accompanied by the activation of DNA damage-inducing kinases, including ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2). Moreover, 11-dehydrosinulariolide increased the activity of caspase-3 and -7, suggesting that caspases are involved in 11-dehydrosinulariolide-induced apoptosis. 11-Dehydrosinulariolide also increased the level of tumor suppressor phosphatase and tensin homolog (PTEN) and inhibited the expression of phosphorylated Akt. In the in vivo study, the intraperitoneal injection of 11-dehydrosinulariolide at a dosage of 10 mg/kg significantly inhibited tumor growth compared with the control treatment. Together, the data indicate that 11-dehydrosinulariolide induces G (2)/M cell cycle arrest and apoptosis through various cellular processes, including the upregulation of p53 and Bax, activation of ATM and Chk2, activation of caspase-3 and -7, and accumulation of PTEN, leading to inhibition of the Akt pathway. These findings suggest that 11-dehydrosinulariolide might serve as a promising chemotherapy drug in the treatment of SCLC.

Effects of Ganoderma lucidum and 'Essence of Chicken' on Physical Fatigue Recovery and Exercise Performance Improvement.

A fast-paced lifestyle, pressure from the environment and a heavy work load often cause extreme tiredness in modern life. Different kinds of nutritional supplements in the form of functional foods or traditional Chinese medicine, such as 'essence of chicken' and Ganoderma lucidum have been claimed to benefit physical performance and promote health. Previous studies have revealed that 'essence of chicken' or G. lucidum have a wide spectrum of biological activities. In this study, we combined these two ingredients together (designated as CEG) to evaluate their synergistic effects on physiological adaption on exercise fatigue and physical activities. The ICR strain mice were allocated as 0, 833, 1666, and 4165 mg/kg dose groups and administrated by oral gavage consecutively for 4 weeks. Physical activities including grip strength and aerobic endurance were evaluated. Various fatigue-associated biochemical variables such as lactate, BUN or CK were also evaluated. The levels of liver and muscle glycogen were measured as an indicator of energy storage at the end of the experiment. Safety assessments for supplementation were also evaluated. CEG supplementation significantly increased the endurance and grip strength and demonstrated beneficial effects on lactate production and clearance rate after an acute exercise challenge. The CEG supplementation significantly mitigated the BUN and CK indexes after extended exercise and elevated the glycogen content in the liver and muscle tissues. According to body composition, biochemical and histopathological data, daily administration of CEG for over 28 days (subacute toxicity) also demonstrated reasonable safety results for supplementation. Combined G. lucidum and 'essence of chicken' can significantly increase the exercise performance and improve fatigue recovery. It may also provide a viable alternative nutritional supplement for health promotion.

Rhododendron oldhamii leaf extract improves fatty liver syndrome by increasing lipid oxidation and decreasing the lipogenesis pathway in mice.

Some members of Rhododendron genus are traditionally used as medicinal plants for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases. To the best of our knowledge, there is no report on the protective effects of R. oldhamii leaf extract on non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. In this study, the effects of R. oldhamii leaf extract on inhibiting the free fatty acid (FFA)-induced accumulation of fat in HepG2 cells and on improving fatty liver syndrome in mice with high fat diet (HFD)-induced NAFLD were investigated. For the in vitro assay, HepG2 cells were treated with FFAs (oleate/palmitate = 2:1) with or without treatment with R. oldhamii leaf ethyl acetate (EtOAc) fraction to observe lipid accumulation using Nile red and oil red O stains. For the in vivo assay, C57BL/6 mice were randomly assigned to three groups (n = 5), including the normal diet group, the HFD group and the HFD+EtOAc group. After 11 weeks, body weight, serum biochemical indices and the mRNA expressions of the liver tissue, as well as the outward appearance, weight and histopathological analysis of liver and adipose tissues were evaluated. Among the fractions derived from R. oldhamii leaf, the EtOAc fraction exhibited a strong fat-accumulation inhibitory activity. Following reverse-phase high-performance liquid chromatography (HPLC), four specific phytochemicals, including (2R, 3R)-astilbin (AS), hyposide (HY), guaijaverin (GU) and quercitrin (QU), were isolated and identified from the EtOAc fraction of R. oldhamii leaf extract. Among them, AS and HY showed excellent fat-accumulation inhibitory activity. Thus, the EtOAc fraction of R. oldhamii leaf and its derived phytochemicals have great potential in preventing FFA-induced fat accumulation. In addition, the EtOAc fraction of R. oldhamii leaf significantly improved fatty liver syndrome and reduced total cholesterol (TC) and triglyceride (TG) in HFD-induced NAFLD mice at a dosage of 200 mg/kg BW. These results demonstrated that the methanolic extracts from R. oldhamii leaf have excellent inhibitory activities against fat accumulation and anti-NAFLD activities and thus have great potential as a natural health product.

Proteomics Analysis to Identify and Characterize the Biomarkers and Physical Activities of Non-Frail and Frail Older Adults.

Globally, the proportion of older adults is increasing. Older people face chronic conditions such as sarcopenia and functional decline, which are often associated with disability and frailty. Proteomics assay of potential serum biomarkers of frailty in older adults. Older adults were divided into non-frail and frail groups (n = 6 each; 3 males in each group) in accordance with the Chinese-Canadian Study of Health and Aging Clinical Frailty Scale. Adults were measured for grip power and the 6-min walk test for physical activity, and venous blood was sampled after adults fasted for 8 h. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used for proteomics assay. The groups were compared for levels of biomarkers by t test and Pearson correlation analysis. Non-frail and frail subjects had mean age 77.5±0.4 and 77.7±1.6 years, mean height 160.5±1.3 and 156.6±2.9 cm and mean weight 62.5±1.2 and 62.8±2.9 kg, respectively. Physical activity level was lower for frail than non-frail subjects (grip power: 13.8±0.4 vs 26.1±1.2 kg; 6-min walk test: 215.2±17.2 vs 438.3±17.2 m). Among 226 proteins detected, for 31, serum levels were significantly higher for frail than non-frail subjects; serum levels of Ig kappa chain V-III region WOL, COX7A2, and albumin were lower. The serum levels of ANGT, KG and AT were 2.05-, 1.76- and 2.22-fold lower (all p < 0.05; Figure 1A, 2A and 3A) for non-frail than frail subjects and were highly correlated with grip power (Figure 1B, 2B and 3B). Our study found that ANGT, KG and AT levels are known to increase with aging, so degenerated vascular function might be associated with frailty. In total, 226 proteins were revealed proteomics assay; levels of angiotensinogen (ANGT), kininogen-1 (KG) and antithrombin III (AT) were higher in frail than non-frail subjects (11.26±2.21 vs 5.09±0.74; 18.42±1.36 vs 11.64±1.36; 22.23±1.64 vs 9.52±0.95, respectively, p < 0.05). These 3 factors were highly correlated with grip power (p < 0.05), with higher correlations between grip power and serum levels of ANGT (r = -0.89), KG (r = -0.90), and AT (r = -0.84). In conclusion, this is the first study to demonstrate a serum proteomic profile characteristic of frailty in older adults. Serum ANGT, KG and AT levels could be potential biomarkers for monitoring the development and progression of frailty in older adults.

Characterization of the serum and liver proteomes in gut-microbiota-lacking mice.

Current nutrition research is focusing on health promotion, disease prevention, and performance improvement for individuals and communities around the world. The humans with required nutritional ingredients depend on both how well the individual is provided with balanced foods and what state of gut microbiota the host has. Studying the mutually beneficial relationships between gut microbiome and host is an increasing attention in biomedical science. The purpose of this study is to understand the role of gut microbiota and to study interactions between gut microbiota and host. In this study, we used a shotgun proteomic approach to reveal the serum and liver proteomes in gut-microbiota-lacking mice. For serum, 15 and 8 proteins were uniquely detected in specific-pathogen-free (SPF) and germ-free (GF) mice, respectively, as well as the 3 and 20 proteins were significantly increased and decreased, respectively, in GF mice compared to SPF mice. Among the proteins of the serum, major urinary protein 1 (MUP-1) of GF mice was significantly decreased compared to SPF mice. In addition, MUP-1 expression is primarily regulated by testosterone. Lacking in gut flora has been implicated in many adverse effects, and now we have found its pathogenic root maybe gut bacteria can regulate the sex-hormone testosterone levels. In the liver, 8 and 22 proteins were uniquely detected in GF mice and SPF mice, respectively, as well as the 14 and 30 proteins were significantly increased and decreased, respectively, in GF mice compared to SPF mice. Furthermore, ingenuity pathway analysis (IPA) indicated that gut microbiota influence the host in cancer, organismal injury and abnormalities, respiratory disease; cell cycle, cellular movement and tissue development; cardiovascular disease, reproductive system disease; and lipid metabolism, molecular transport and small molecule biochemistry. Our findings provide more detailed information of the role of gut microbiota and will be useful to help study gut bacteria and disease prevention.

Effect of Coriolus versicolor Mycelia Extract on Exercise Performance and Physical Fatigue in Mice.

In this study, Coriolus versicolor mycelia (CVM) was evaluated the ergogenic and anti-fatigue activities. Male ICR mice were divided into four groups (n = 8/group) to receive vehicle or CVM by oral gavage for 4 weeks at 0, 615, 1230 or 3075 mg/kg/day, which were respectively designated the vehicle, CVM-1X, CVM-2X and CVM-5X groups. Forelimb grip strength, endurance swimming time, and levels of physical fatigue-associated parameters serum lactate, ammonia, glucose and creatine kinase (CK) after physical challenge were performed to evaluate exercise performance and anti-fatigue activity. Results revealed that the forelimb grip strength of mice in group CVM-1X, CVM-2X and CVM-5X were significantly increased by 1.20-, 1.18- and 1.23-fold, respectively, compared to the vehicle group. After the 15 minute swimming exercise, the levels of serum lactate of CVM-1X, CVM-2X and CVM-5X groups were significantly lower than the vehicle control group by 29%, 23% and 31%, respectively. The levels of ammonia in CVM-1X, CVM-2X and CVM-5X groups were significantly lowered by 22%, 25% and 41%, respectively, compared to the vehicle control group. In addition, the levels of serum CK in CVM-2X and CVM-5X groups were significantly lowered by 13% and 11%, respectively, compared to the vehicle control group. Accordingly, the supplementation with CVM has beneficial effects on performance improvement and anti-fatigue activity, and thus has great potential as a source for natural health products.

Effect of Exercise Training on Skeletal Muscle SIRT1 and PGC-1α Expression Levels in Rats of Different Age.

The protein deacetylase sirtuin 1 (SIRT1) and activate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) pathway drives the muscular fiber-type switching, and can directly regulate the biophysiological functions of skeletal muscle. To investigate whether 12-week swimming exercise training modulates the SIRT1/PGC-1α pathway associated proteins expression in rats of different age. Male 3-month-old (3M), 12-month-old (12M) and 18-month-old (18M) Sprague-Dawley rats were used and assigned to sedentary control (C) or 12-week swimming exercise training (E) and divided into six groups: 3MC (n = 8), 12MC (n = 6), 18MC (n = 8), 3ME (n = 8), 12ME (n = 5) and 18ME (n = 6). Body weight, muscle weight, epididymal fat mass and muscle morphology were performed at the end of the experiment. The protein levels of SIRT1, PGC-1α, AMPK and FOXO3a in the gastrocnemius and soleus muscles were examined. The SIRT1, PGC-1α and AMPK levels in the gastrocnemius and soleus muscles were up-regulated in the three exercise training groups than three control groups. The FOXO3a level in the 12ME group significantly increased in the gastrocnemius muscles than 12MC group, but significantly decreased in the soleus muscles. In 3-, 12- and 18-month-old rats with and without exercise, there was a significant main effect of exercise on PGC-1α, AMPK and FOXO3a in the gastrocnemius muscles, and SIRT1, PGC-1α and AMPK in the soleus muscles. Our result suggests that swimming training can regulate the SIRT1/PGC-1α, AMPK and FOXO3a proteins expression of the soleus muscles in aged rats.

Beneficial effects of cocoa, coffee, green tea, and garcinia complex supplement on diet induced obesity in rats.

BACKGROUND: Cocoa, coffee, green tea and garcinia contain large amounts of polyphenols. Polyphenols are well-known phytochemicals and found in plants, and have modulated physiological and molecular pathways that are involved in energy metabolism, adiposity, and obesity. METHODS: To evaluate the obesity-lowering effect of a combined extract (comprising cocoa, coffee, green tea and garcinia; CCGG) in high-energy diet (HED)-induced obese rats. Male Sprague Dawley rats (8 weeks old) were randomly divided into four groups (n = 12 per group): normal diet with vehicle treatment (Control), and HED to receive vehicle or CCGG by oral gavage at 129, 258, or 517 mg/kg/day for 4 weeks, designated the HED, 0.5X, 1X and 1X groups, respectively. RESULTS: HED induced macrovesicular fat in the liver and the formation of adipose tissues, and significantly increased the levels of serum free fatty acids (FFA), triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and LDL-C/HDL-C, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and ketone bodies in serum, and hepatic TG and TC levels, and decreased the levels of high density lipoprotein cholesterol (HDL-C) in serum and lipase activity in fat tissues. Treatment with CCGG could significantly decrease the levels of FFA, TG, TC, LDL-C, and LDL-C/HDL-C, AST, ALT, and ketone bodies in serum, and hepatic TG and TC contents, and increase the levels of HDL-C in serum and lipase activity in fat tissues compared to the HED group. Liver histopathology also showed that CCGG could significantly reduce the incidence of liver lesions. CONCLUSION: These results suggested that CCGG stimulated lipid metabolism in HED-induced obese rats, which is attributable to fat mobilization from adipose tissue.

Effects of Resveratrol Supplementation and Exercise Training on Exercise Performance in Middle-Aged Mice.

Resveratrol (RES) has antioxidative, anti-inflammatory, anticancer, antidiabetic, antiasthmatic, antalgic, and anti-fatigue activities. Exercise training (ET) improves frailty resulting from aging. This study evaluated the effects of a combination of RES supplementation and ET on the exercise performance of aged mice. C57BL/6J mice (16 months old) were randomly divided into four groups: an older control group (OC group), supplementation with RES group (RES group), ET group (ET group), and a combination of ET and RES supplementation group (ET+RES group). Other 10-week-old mice were used as a young control group (Y-Ctrl group). In this study, exercise performance was evaluated using forelimb grip strength and exhaustive swimming time, as well as levels of plasma lactate, ammonia, glucose, and creatine kinase after an acute swimming exercise. Our results showed that the forelimb grip strength of mice in the ET+RES group was significantly higher than those in the OC, RES, and ET groups (by 1.3-, 1.2-, and 1.1-fold, respectively, p < 0.05), and exhibited no difference with the Y-Ctrl group. The endurance swimming test showed that swimming times of the ET and ET+RES groups were significantly longer than those of the OC and RES groups. Moreover, plasma lactate and ammonia levels of the ET + RES group after acute swimming exercise were significantly lower compared to the OC group (p < 0.05). Thus, it was suggested that by combining RES supplementation with ET for 4 weeks, the muscle strength and endurance performance of aged mice were significantly improved compared to the single intervention with either RES or ET alone. This combination might help shorten the extent of deterioration accompanying the aging process.

Antioxidative phytochemicals from Rhododendron oldhamii Maxim. leaf extracts reduce serum uric acid levels in potassium oxonate-induced hyperuricemic mice.

BACKGROUND: Some of the genus Rhododendron was used in traditional medicine for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases and many species of the genus Rhododendron contain a large number of phenolic compounds and antioxidant properties that could be developed into pharmaceutical products. METHODS: In this study, the antioxidative phytochemicals of Rhododendron oldhamii Maxim. leaves were detected by an online HPLC-DPPH method. In addition, the anti-hyperuricemic effect of the active phytochemicals from R. oldhamii leaf extracts was investigated using potassium oxonate (PO)-induced acute hyperuricemia. RESULTS: Six phytochemicals, including (2R, 3R)-epicatechin (1), (2R, 3R)-taxifolin (2), (2R, 3R)-astilbin (3), hyposide (4), guaijaverin (5), and quercitrin (6), were isolated using the developed screening method. Of these, compounds 3, 4, 5, and 6 were found to be major bioactive phytochemicals, and their contents were determined to be 130.8 ± 10.9, 105.5 ± 8.5, 104.1 ± 4.7, and 108.6 ± 4.0 mg per gram of EtOAc fraction, respectively. In addition, the four major bioactive phytochemicals at the same dosage (100 mmol/kg) were administered to the abdominal cavity of potassium oxonate (PO)-induced hyperuricemic mice, and the serum uric acid level was measured after 3 h of administration. H&E staining showed that PO-induced kidney injury caused renal tubular epithelium nuclear condensation in the cortex areas or the appearance of numerous hyaline casts in the medulla areas; treatment with 100 mmol/kg of EtOAc fraction, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin significantly reduced kidney injury. In addition, the serum uric acid level was significantly suppressed by 54.1, 35.1, 56.3, 56.3, and 53.2 %, respectively, by the administrations of 100 mmol/kg EtOAc fraction and the derived major phytochemicals, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin, compared to the PO group. The administration of 10 mg/kg benzbromarone, a well-known uricosuric agent, significantly reduced the serum uric acid level by 45.5 % compared to the PO group. CONCLUSION: The in vivo decrease in uric acid was consistent with free radical scavenging activity, indicating that the major phytochemicals of R. oldhamii leave extracts and the derived phytochemicals possess potent hypouricemic effects, and they could be potential candidates for new hypouricemic agents.

Lactoferrin protects against chemical-induced rat liver fibrosis by inhibiting stellate cell activation.

Liver diseases, which can be caused by alcohol abuse, chemical intoxication, viral hepatitis infection, and autoimmune disorders, are a significant health issue because they can develop into liver fibrosis and cirrhosis. Lactoferrin (LF), a siderophilic protein with 2 iron-binding sites, has been demonstrated to possess a multitude of biological functions, including antiinflammation, anticancer, and antimicrobial effects, as well as immunomodulatory-enhancing functions. In the current study, we induced hepatotoxicity in rats with dimethylnitrosamine (DMN) to establish a situation that would enable us to evaluate the hepatoprotective effects of LF against hepatic injury. Our results showed that DMN-induced hepatic pathological damage significantly decreased the body weight and liver index, increased the mRNA and protein levels of collagen α-1(I) (ColIα-1) and α-smooth muscle actin, and increased the hydroxyproline content. However, treatment with LF significantly increased body weight and liver index, decreased the mRNA and protein levels of ColIα-1 and α-smooth muscle actin, and suppressed the hydroxyproline content when compared with the DMN-treated group. Liver histopathology also showed that low-dose LF (100mg/kg of body weight) or high-dose LF (300 mg/kg of body weight) could significantly reduce the incidences of liver lesions induced by DMN. These results suggest that the LF exhibits potent hepatoprotection against DMN-induced liver damage in rats and that the hepatoprotective effects of LF may be due to the inhibition of collagen production and to stellate cell activation.

Natural sweetener glycyrrhizin protects against precocious puberty by modulating the gut microbiome.

AIMS: Precocious puberty (PP) may lead to many adverse outcomes. Recent evidence suggests that PP is a gut-brain disease. On the other hand, the use of glycyrrhizin, a natural sweetener, has become popular in the past decade. Glycyrrhizin possesses various health benefits, but its impact on PP has yet to be investigated. We aimed to explore the protective effects of glycyrrhizin against PP in both humans (observational) and animals (interventional). MATERIALS AND METHODS: In the human cohort, we investigated the association between glycyrrhizin consumption and risk of PP. In the animal experiment, we observed puberty onset after feeding danazol-induced PP rats with glycyrrizin. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. We also performed a fecal microbiota transplantation to confirm to causal relationship between glycyrrhizin and PP risk. KEY FINDINGS: Glycyrrhizin exhibited a protective effect against PP in children (OR 0.60, 95%CI: 0.39-0.89, p = 0.013), primarily driven by its significance in girls, while no significant effect was observed in boys. This effect was consistent with findings in rodents. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the hypothalamic-pituitary-gonadal axis and prevented PP progression. A fecal microbiota transplantation indicated that the causal correlation between glycyrrhizin intake and PP is mediated by the gut microbiome alterations. SIGNIFICANCE: Our findings suggest that glycyrrhizin can protect against PP by altering the gut microbiome. Long term use of glycyrrhizin is safe and tolerable. Therefore, glycyrrhizin can serve as a safe and affordable complementary therapy for PP.