Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.

High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/ß-catenin signaling pathway. However, no studies have yet determined the effects of CGK012 on sepsis. We investigated the potential of CGK012 to attenuate the excessive permeability induced by HMGB1 and enhance survival rates in a mouse model of sepsis with reduced HMGB1 levels following lipopolysaccharide (LPS) treatment. In both LPS-stimulated human endothelial cells and a mouse model exhibiting septic symptoms due to cecal ligation and puncture (CLP), we assessed proinflammatory protein levels and tissue damage biomarkers as indicators of reduced vascular permeability. CGK012 was applied after induction in human endothelial cells exposed to LPS and the CLP-induced mouse model of sepsis. CGK012 effectively mitigated excessive permeability and suppressed HMGB1 release, resulting in improved vascular stability, decreased mortality, and enhanced histological conditions in the mouse model of CLP-induced sepsis. In conclusion, our findings indicate that CGK012 treatment in mice with CLP-induced sepsis diminished HMGB1 release and increased the survival rate, suggesting its potential as a pharmaceutical intervention for sepsis.

Therapeutic effects of hederacolchiside A1 on particulate matter-induced pulmonary injury.

Particulate matter (PM) comprises a hazardous mixture of inorganic and organic particles that carry health risks. Inhaling fine PM particles with a diameter of ≤2.5 µm (PM2.5) can promote significant lung damage. Hederacolchiside A1 (HA1) exhibits notable in vivo antitumor effects against various solid tumors. However, our understanding of its therapeutic potential for individuals with PM2.5-induced lung injuries remains limited. Here, we explored the protective properties of HA1 against lung damage caused by PM2.5 exposure. HA1 was administered to the mice 30 min after intratracheal tail vein injection of PM2.5. Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were assessed in mice exposed to PM2.5. Our data showed that HA1 mitigated lung damage, reduced the W/D weight ratio, and suppressed hyperpermeability caused by PM2.5 exposure. Moreover, HA1 effectively decreased plasma levels of inflammatory cytokines in those exposed to PM2.5, including tumor necrosis factor-α, interleukin-1ß, and nitric oxide, while also lowering the total protein concentration in BALF and successfully alleviating PM2.5-induced lymphocytosis. Furthermore, HA1 significantly decreased the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response (MyD) 88, and autophagy-related proteins LC3 II and Beclin 1 but increased the protein phosphorylation of the mammalian target of rapamycin (mTOR). The anti-inflammatory characteristics of HA1 highlights its potential as a promising therapeutic agent for mitigating PM2.5-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.

Steamed Ginseng Berry Powder Ameliorates Skeletal Muscle Atrophy via Myogenic Effects.

Sarcopenia is an age-related loss of muscle mass and function for which there is no approved pharmacological treatment. We tested direct efficacy by evaluating grip strength improvement in a sarcopenia mouse model rather than drug screening, which inhibits specific molecular mechanisms. Various physiological functions of ginseng berries are beneficial to the human body. The present study aimed to evaluate the efficacy and safety of steamed ginseng berry powder (SGBP). SGBP administration increased myotube diameter and suppressed the mRNA expression of sarcopenia-inducing molecules. SGBP also reduced the levels of inflammatory transcription factors and cytokines that are known to induce sarcopenia. Oral administration of SGBP improved muscle mass and physical performance in a mouse model of sarcopenia. In summary, our data suggest that SGBP is a novel therapeutic candidate for the amelioration of muscle weakness, including sarcopenia.

High-Performance One-Body Electrochemical Torsional Artificial Muscles Built Using Carbon Nanotubes and Ion-Exchange Polymers.

Electrochemical torsional artificial muscles have the potential to replace electric motors in the field of miniaturization. In particular, carbon nanotubes (CNTs) are some of the best materials for electrochemical torsional artificial muscles due to their remarkable mechanical strength and high electrical conductivity. However, previous studies on CNT torsional muscle utilize only half of the whole potential range for torsional actuation because the actuations in the positive and negative voltage ranges offset each other. Here, we used an ion-exchange polymer, poly(sodium 4-styrenesulfonate) (PSS), which leads to the participation of only positive ions in the actuation of CNT muscles so that the whole potential range can be used for torsional actuation. As a result, PSS-coated CNT muscle can provide 1.9 times higher torsional actuation compared to neat CNT torsional muscle. This PSS-coated CNT muscle not only provides high performance but also facilitates a one-body system for electrochemical torsional actuation. From these advantages, we implement a one-body torsional muscle for the realization of the forward motion of a model boat. This high performance and one-body structure for electrochemical torsional muscles can be used for further applications, such as soft robotics and implantable devices.

Discovery of novel amidobenzimidazole derivatives as orally available small molecule modulators of stimulator of interferon genes for cancer immunotherapy.

Stimulator of interferon genes (STING) agonists show promise as immunomodulatory agents for cancer therapy. In this study, we report the discovery of a novel orally available STING agonist, SAP-04, that exhibits potent immunomodulatory effects for cancer therapy. By optimizing the amidobenzimidazole core with various pyridine-based heterocyclic substituents, we identified a monomeric variant that displayed more efficient STING agonistic activity than the corresponding dimer. SAP-04 efficiently induced cytokine secretion related to innate immunity by directly binding of the compound to the STING protein, followed by sequential signal transduction for the STING signaling pathway and type I interferon (IFN) responses. Further pharmacological validation in vitro and in vivo demonstrated the potential utility of SAP-04 as an immunomodulatory agent for cancer therapy in vivo. The in vivo anticancer effect was observed in a 4T1 breast tumor syngeneic mouse model through oral administration of the compound. Our findings suggest a possible strategy for developing synthetically accessible monomeric variants as orally available STING agonists.

Myogenesis Effects of RGX365 to Improve Skeletal Muscle Atrophy.

Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the myogenic effect of RGX365 on mouse myoblast cells (C2C12) and dexamethasone (10 µM)-induced atrophy of differentiated C2C12. RGX365-treated myotube diameters and myosin heavy chain (MyHC) expression levels were analyzed using immunofluorescence. We evaluated the myogenic effects of RGX365 in aging sarcopenic mice. RGX365 increased myoblast differentiation and MyHC expression, and attenuated the muscle atrophy-inducing F-box (Atrogin-1) and muscle RING finger 1 (MuRF1) expression. Notably, one month of oral administration of RGX365 to 23-month-old sarcopenic mice improved muscle fiber size and the expression of skeletal muscle regeneration-associated molecules. In conclusion, rare ginsenosides, agonists of steroid receptors, can ameliorate skeletal muscle atrophy during long-term administration.

Effect of curcumin supplementation on inflammatory status and muscle damage in competitive female soccer players: a placebo-controlled, singleblind, nonrandomized, crossover pilot study.

PURPOSE: Curcumin, a major component of turmeric, has anti-inflammatory and antioxidative properties, which are associated with protective effects against muscle damage. This study examined the effects of dietary curcumin on inflammation and muscle damage in female competitive soccer players. METHODS: A single-blinded, placebo-controlled, nonrandomized, crossover pilot study was conducted. Six competitive female soccer players (20.0 ± 2.0 yearsold) who participated in a 2-week preseason training program were assigned to two conditions: placebo and curcumin. The participants ingested a placebo or curcumin dosage (270 mg/day) during 2 weeks of preseason training, with 1 week of washout. Fasting blood samples were collected under resting conditions before (day 0) and after (day 15) the training period to examine changes in the concentration of interleukin 6 (IL-6), an inflammatory marker, and indices reflective of muscle damage. RESULTS: Curcumin decreased the concentration of IL-6 released (mean decrease, -30.2 ± 28.1%), whereas no decrease was observed in the placebo condition (13.4 ± 17.4%). Changes in plasma IL-6 concentrations were significantly greater in the curcumin condition than in the placebo condition (p < 0.05). However, curcumin supplementation had no significant effects on muscle damage indices. CONCLUSION: The present study shows that curcumin supplementation could attenuate inflammation, as indicated by IL-6 concentrations, in competitive female soccer players during the training period.

Chiral separation and molecular modeling study of decursinol and its derivatives using polysaccharide-based chiral stationary phases.

Plant-based bioactive substances have long been used to treat inflammatory ailments, owing to their low toxicity and cost-effectiveness. To enhance plant treatment by eliminating undesirable isomers, optimizing the chiral separation techniques in pharmaceutical and clinical studies is important. This study reported a simple and effective method for chiral separation of decursinol and its derivatives, which are pyranocoumarin compounds with anti-cancer and anti-inflammatory properties. Baseline separation (Rs >1.5) was achieved using five different polysaccharide-based chiral stationary phases (CSPs) that differed in chiral origin, chiral selector chemistry, and preparation technique. To separate all six enantiomers simultaneously, n-hexane and three alcohol modifiers (ethanol, isopropanol, and n-butanol) were used as mobile phases in the normal-phase mode. The chiral separation ability of each column with various mobile phase compositions was compared and discussed. As a result, amylose-based CSPs with linear alcohol modifiers demonstrated superior resolution. Three cases of elution order reversal caused by modifications of CSPs and alcohol modifiers were observed and thoroughly analyzed. To elucidate the chiral recognition mechanism and enantiomeric elution order (EEO) reversal phenomenon, detailed molecular docking simulations were conducted. The R- and S-enantiomers of decursinol, epoxide, and CGK012 exhibited binding energies of -6.6, -6.3, -6.2, -6.3, -7.3, and -7.5 kcal/mol, respectively. The magnitude of the difference in binding energies was consistent with the elution order and enantioselectivity (α) of the analytes. The molecular simulation results demonstrated that hydrogen bonds, π-π interactions, and hydrophobic interactions have a significant impact on chiral recognition mechanisms. Overall, this study presented a novel and logical approach of optimizing chiral separation techniques in the pharmaceutical and clinical industries. Our findings could be further applied for screening and optimizing enantiomeric separation.

Ginsenosides for therapeutically targeting inflammation through modulation of oxidative stress.

Ginsenosides are steroid glycosides derived from ginseng plants such as Panax ginseng, Panax quinquefolium, and Panax notoginseng. Advances in recent studies have identified numerous physiological functions of each type of ginsenoside, i.e., immunomodulatory, antioxidative, and anti-inflammatory functions, in the context of inflammatory diseases. Accumulating evidence has revealed the molecular mechanisms by which the single or combined ginsenoside(s) exhibit anti-inflammatory effects, although it remains largely unclear. It is well known that excessive production of reactive oxygen species (ROS) is associated with pathological inflammation and cell death in a variety of cells, and that inhibition of ROS generation ameliorates the local and systemic inflammatory responses. The mechanisms by which ginsenosides attenuate inflammation are largely unknown; however, targeting ROS is suggested as one of the crucial mechanisms for the ginsenosides to control the pathological inflammation in the immune and non-immune cells. This review will summarize the latest progress in ginsenoside studies, particularly in the context of antioxidant mechanisms for its anti-inflammatory effects. A better understanding of the distinct types and the combined action of ginsenosides will pave the way for developing potential preventive and therapeutic modalities in treating various inflammation-related diseases.

Antiplatelet Aggregation Properties of Cirsilineol: A Novel Inhibitor of Blood Coagulation Factor Xa.

A small natural substance called cirsilineol (CSL), which was discovered in the plant Artemisia vestita, is lethal to many cancer cells and has antioxidant, anticancer, and antibacterial properties. Here, we investigated the underlying mechanisms of the antithrombotic action of CSL. We demonstrated that CSL has antithrombotic efficacy comparable to rivaroxaban, a direct blood coagulation factor Xa (FXa) inhibitor employed as a positive control, in inhibiting the enzymatic activity of FXa and the platelet aggregation induced by adenosine diphosphate (ADP) and U46619, a thromboxane A2 analog. The expression of P-selectin, the phosphorylation of myristoylated alanine-rich C kinase substrate by U46619 or ADP, and the activation of PAC-1 in platelets were inhibited by CSL. Nitric oxide production was increased by CSL in ADP- or U46619-treated human umbilical vein endothelial cells (HUVECs), although excessive endothelin-1 secretion was suppressed. CSL demonstrated strong anticoagulant and antithrombotic effects in a mouse model of arterial and pulmonary thrombosis. Our findings suggest that CSL is a potential pharmacological candidate for a novel class of anti-FXa and antiplatelet medications.

Therapeutic Effects of Cornuside on Particulate Matter-Induced Lung Injury.

Particulate matter (PM) is a mixture comprising both organic and inorganic particles, both of which are hazardous to health. The inhalation of airborne PM with a diameter of ≤2.5 µm (PM2.5) can cause considerable lung damage. Cornuside (CN), a natural bisiridoid glucoside derived from the fruit of Cornus officinalis Sieb, exerts protective properties against tissue damage via controlling the immunological response and reducing inflammation. However, information regarding the therapeutic potential of CN in patients with PM2.5-induced lung injury is limited. Thus, herein, we examined the protective properties of CN against PM2.5-induced lung damage. Mice were categorized into eight groups (n = 10): a mock control group, a CN control group (0.8 mg/kg mouse body weight), four PM2.5+CN groups (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight), and a PM2.5+CN group (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight). The mice were administered with CN 30 min following intratracheal tail vein injection of PM2.5. In mice exposed to PM2.5, different parameters including changes in lung tissue wet/dry (W/D) lung weight ratio, total protein/total cell ratio, lymphocyte counts, inflammatory cytokine levels in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were examined. Our findings revealed that CN reduced lung damage, the W/D weight ratio, and hyperpermeability caused by PM2.5. Moreover, CN reduced the plasma levels of inflammatory cytokines produced because of PM2.5 exposure, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and nitric oxide, as well as the total protein concentration in the BALF, and successfully attenuated PM2.5-associated lymphocytosis. In addition, CN substantially reduced the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1, and increased protein phosphorylation of the mammalian target of rapamycin (mTOR). Thus, the anti-inflammatory property of CN renders it a potential therapeutic agent for treating PM2.5-induced lung injury by controlling the TLR4-MyD88 and mTOR-autophagy pathways.

Hederacolchiside A1 Suppresses Autophagy by Inhibiting Cathepsin C and Reduces the Growth of Colon Cancer.

While autophagy degrades non-functional or unnecessary cellular components, producing materials for synthesizing cellular components, it can also provide energy for tumor development. Hederacolchiside A1 (HA1) derived from anemone raddeana has anticancer effects on several carcinomas by inducing apoptosis or exhibiting cytotoxicity, but the relationship with autophagy has not been studied. We investigated the association between HA1 and autophagy and evaluated its anticancer effect on colon cancer. HA1 induced accumulation of the autophagy-related markers LC3B and SQSTM1, with distinct vacuolar formation, unlike other autophagy inhibitors; the effects were similar to those of chloroquine. In addition, HA1 decreased the expression and proteolytic activity of lysosomal protein cathepsin C, reduced the growth of colon cancer cells in vitro, and inhibited tumor growth in vivo. It also reduced the expression of Ki-67 and cathepsin C in mouse tissues and reduced the growth of spheroids and organoids composed of cancer cells. Taken together, these results imply that HA1 regulates cell growth and autophagy and has potential as a promising therapeutic agent in colon cancer.

The Safety and Efficacy of 1-Monoeicosapentaenoin Isolated from the Trebouxiophyceae Micractinium on Anti-Wrinkle: A Split-Face Randomized, Double-Blind Placebo-Controlled Clinical Study.

The skin aging process is governed by intrinsic and extrinsic factors causing skin wrinkles, sagging, and loosening. The 1-monoeicosapentaenoin (1-MEST) is a component isolated from Micractinium, a genus of microalgae (Chlorophyta, Trebouxiophyceae). However, the anti-wrinkle effects of 1-MEST are not yet known. This study aimed to evaluate the anti-wrinkle effects of 1-MEST in vitro and in clinical trials. The cytotoxicity of 1-MEST was investigated in vitro using the MTS assay in human epidermal keratinocytes (HEKs). Expression of matrix metalloproteinase (MMP)-1 and MMP-9 was determined by ELISA in HEKs irradiated with UVB after treatment with 1-MEST. A split-face randomized, double-blind, placebo-controlled study was conducted to evaluate the safety and efficacy of 1-MEST. The study evaluated wrinkle parameters and visual assessment, self-efficacy and usability questionnaires, and adverse events. The study showed that the 1-MEST was not cytotoxic in HEKs, suppressed MMP-1 secretion and MMP-9 protein expression in HEKs irradiated with UVB. The wrinkle parameters and mean visual assessment score were significantly decreased in the test group after 12 weeks and differed from the control group. There were no significant differences in efficacy and usability. Adverse effects were also not observed. The 1-MEST showed anti-wrinkle properties to slow down or prevent skin aging.

Eccentric exercise improves myocardial oxygen supply/demand balance with decelerating aortic diastolic pressure decay: The acute and chronic studies.

Both eccentric (ECC) and concentric (CON) exercises improve energy expenditure and blood lipid profile. Although ECC exercise has a more beneficial effect on these factors than CON exercise, its benefits on vital organs are still unclear. This study investigated the mode-of-action-dependent effects on myocardial perfusion index. Seventeen healthy men (age: 26 ± 5 years) were randomly enrolled in CON (n = 9) and ECC (n = 8) groups. Transient exercise and regular training (three-day a week for 4-week) included bicep curl comprising 5-set of 10-repetition, each using 75% one-repetition maximum concentric loading. The ECC group performed one-repetition of ECC for 3-s and CON for 1-s, while the CON group performed one-repetition of CON for 3-s and ECC for 1-s. All participants were assessed for subendocardial viability ratio (SEVR, myocardial perfusion index) and aortic diastolic pressure decay. Before study, these were found to be same for both groups. Transient (ΔSEVR: 20.3 ± 13.3%, p = 0.01; Δdecay: -0.07 ± 0.02 s-1, p < .001) and regular (ΔSEVR: 18.5 ± 12.8%, p = .001; Δdecay: -0.06 ± 0.05 s-1, p = .004) ECC (but not CON) exercises significantly increased SEVR and decelerated decay. Increased SEVR with ECC exercise was associated with decelerated decay (transient ECC: r2 = 0.56, 95% confidence interval [CI] = -0.95 to -0.10, p = .03; regular ECC: r2 = 0.53, 95% CI = -0.95 to -0.05, p = .04). These findings suggest that ECC exercise improves myocardial perfusion and diastolic pressure contour is involved in physiological mechanisms.

Ameliorative Effect of Ginsenoside Rg6 in Periodontal Tissue Inflammation and Recovering Damaged Alveolar Bone.

Periodontal disease is a chronic disease with a high prevalence, and in order to secure natural materials to prevent oral diseases, new materials that protect periodontal tissue from inflammation are being sought. Genes were identified using real-time quantitative polymerase chain reaction (RT-qPCR), and proteins were confirmed using Western blot. Dichlorodihydrofluorescein diacetate (DCF-DA) analysis was used, and the antibacterial effects were confirmed through Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) analysis. To confirm this effect in vivo, Sprague-Dawley rats, in which periodontitis was induced using ligation or Lipopolysaccharide of Porphyromonas gingivalis (PG-LPS), were used. In vitro experiments using human periodontal ligament (HPDL) cells stimulated with PG-LPS showed that Ginsenoside Rg6 (G-Rg6) had anti-inflammatory, antibacterial, antioxidant, and osteoblast differentiation properties. In vivo, G-Rg6 was effective in Sprague-Dawley rats in which periodontitis was induced using ligation or PG-LPS. Therefore, Ginsenoside Rg6 shows potential effectiveness in alleviating periodontitis.

Effects of acute cycling with electrical muscle stimulation of lower limbs on arterial stiffness / 体力科学

Endurance exercises, such as cycling or running, are useful for reducing arterial stiffness. However, individuals with a low physical fitness level, or patients suffering from leg diseases with pain, are unable to perform such moderate-intensity lower-limb exercises for long periods of time. The aim of this study was to evaluate the effects of acute cycling with Electrical muscle stimulation (EMS) on the brachial to ankle pulse wave velocity (ba-PWV). Ten healthy adult men performed 3 sessions, as follows of 20 min: cycling at 50% VO2max (C), cycling at an intensity of 50%VO2max subtracted from VO2 during EMS (LC), and cycling at the intensity of the LC trial while also being combined with EMS (LC+E). The ba-PWV was measured before and after each exercise. In addition, the femoral artery blood flow (BF) was measured in eight healthy adult men before and after exercise using an ultrasound imaging system. In the C and LC+E trials, the ba-PWV significantly decreased immediately after the exercise session, whereas the ba-PWV did not significantly change following the LC trial in any session. Compared with the baseline, the femoral artery BF values significantly increased after all trials. In the C and LC+E trials, the femoral artery BF was significantly greater than that in the LC trial. Acute endurance low-intensity cycling with EMS results in a reduction in the arterial stiffness which is similar to that with moderate-intensity exercise.

A Coiled Carbon Nanotube Yarn-Integrated Surface Electromyography System To Monitor Isotonic and Isometric Movements.

A surface electromyogram (sEMG) electrode collects electrical currents generated by neuromuscular activity by a noninvasive technique on the skin. It is particularly attractive for wearable systems for various human activities and health care monitoring. However, it remains challenging to discriminate EMG signals from isotonic (concentric/eccentric) and isometric movements. By applying nanotechnology, we provide a coiled carbon nanotube (CNT) yarn-integrated sEMG device to overcome sEMG-based motion recognition. When the arm was contracted at different angles, the sEMG-derived root mean square amplitude signals were constant regardless of the angle of the moving arm. However, the coiled CNT yarn-derived open circuit voltage (OCV) signals proportionally increased when the arm's angle increased, and presented negative and positive values depending on the moving direction of the arm. Moreover, isometric contraction is characterized by the onset of EMG signals without an OCV signal, and isotonic contraction is determined by both EMG signals and OCV signals. Taken together, the integration of EMG and coiled CNT yarn electrodes provides complementary information, including the strength, direction, and degree of muscle movement. Therefore, we suggest that our system has high potential as a wearable system to monitor human motions in industrial and human system applications.

Effects of Dietary Vitamin D Deficiency on Markers of Skeletal Muscle Mitochondrial Biogenesis and Dynamics.

We examined the effects of dietary vitamin D deficiency on markers of mitochondrial biogenesis and dynamics in rat soleus muscle. Male Wistar rats were fed a chow with no vitamin D (No-D; 0 IU/kg) or a moderate dose (Mod-D; 2,000 IU/kg) of vitamin D chow for 8 wk. Compared to the Mod-D group, at 8 wk the No-D group showed significantly lower serum 25(OH)D levels. Although vitamin D deficiency had no effect on body composition, the No-D rats showed significantly decreased levels of PGC-1α, a marker of skeletal muscle mitochondrial biogenesis, and DRP1, a marker of skeletal muscle mitochondrial fission. The change in the PGC-1α protein expression and the serum 25(OH)D concentrations were significantly correlated. The change in DRP1 protein expression and the serum 25(OH)D concentrations tended to be correlated. There was no significant between-group difference in markers of mitochondrial fusion (MFN2 and OPA1) and mitophagy (PARKIN) in soleus muscle, and no relationship with serum 25(OH)D concentrations. Collectively our findings suggest that dietary vitamin D deficiency decreased PGC-1α and DRP1 protein expression in rat soleus muscle.

Inhibitory Activities of Rare Ginsenoside Rg4 on Cecal Ligation and Puncture-Induced Sepsis.

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.

Effect of Taurine on the Regulation of Glucose Uptake in the Skeletal Muscle.

Diabetes is so common in Japan as to be called a national disease. Taurine, a free amino acid found abundantly in mammalian tissues that is also a key ingredient of many "energy drinks," has been shown to be effective in improving the hyperglycemic state caused by diabetes. Taurine administration is associated with increased insulin secretion from the pancreas, higher levels of insulin signaling-related factors, and higher expression of the glucose transporter, GLUT4. Skeletal muscle is the main target organ of insulin: Via cell surface GLUT4 molecules, myocytes take up blood glucose, enabling skeletal muscle contraction. The enhancing effect of taurine on blood glucose uptake in skeletal muscle has not been fully studied, and little is known about its mechanism. This review article summarizes what is known about the effects of taurine on insulin secretion from the pancreas and especially blood glucose uptake in skeletal muscle.