Analysis of health-related, skill-related physical strength, and physique by blood pressure levels of Korean seniors.

In Korea, the prevalence rate of hypertension among people aged over 30 is on an upward trend, which increased from 26.2% in 2008 to 28.3% in 2018. This hovers above the global morbidity rate of hypertension. As hypertension is the cause of cerebrovascular or cardiovascular diseases, early treatment and management are critical. Also, while there has been numerous research conducted on exercise intervention, the number of studies done on hypertension and physical fitness falls far below. To identify the relationship between health and physical fitness depending on the blood pressure levels of Korean seniors, the physical fitness test results of the National Fitness Award 100 conducted in 2017 were used, and blood pressure level, physique, and physical fitness data of 17,110 elderly population aged above 65 were analyzed. IBM Statistics SPSS 25.0 was used to process the collected data. Due to the gender difference in blood pressure levels, physique, and physical strength, the analysis was conducted by each gender, and the analysis of variance (ANOVA) was performed to identify the differences in physique and physical strength depending on the blood pressure level. Also, Tukey's HDS test was conducted if such differences were found. All analyzes were tested at the significance level (α) of 0.05. As a result of comparing the physique factors by blood pressure level, only males showed a significant difference between groups in terms of height(p = .019), and higher blood pressure implied greater height. Also, for both genders, those with high blood pressure appeared to have greater body weight(p < .001), body fat percentage(p < .001), BMI(p < .001), waist circumference(p < .001), and waist-to-height ratio(p < .001),. In addition, as the result of comparing health-related physical strength and skill-related physical strength by blood pressure level, males showed a significant difference only in muscular strength(p = .026) and flexibility(p < .001), while females showed a significant difference between groups in terms of cardiovascular endurance(p < .001), muscular strength(p = .025), muscular endurance(p < .001), balance, and motor coordination except for flexibility. Holistically, males only showed a significant difference in muscular strength and flexibility while females appeared to have a significant difference between groups in all categories except flexibility, which can be considered that physical fitness factors influence the blood pressure of females more than males.

The Administration of Panax Ginseng Berry Extract Attenuates High-Fat-Diet-Induced Sarcopenic Obesity in C57BL/6 Mice.

Sarcopenia and obesity are serious health problems that are highly related to several metabolic diseases. Sarcopenic obesity, a combined state of sarcopenia and obesity, results in higher risks of metabolic diseases and even mortality than sarcopenia or obesity alone. Therefore, the development of therapeutic agents for sarcopenic obesity is crucial. C57BL/6 mice were fed with a high-fat diet (HFD) for 9 weeks. Then, mice were administered with Panax ginseng berry extract (GBE) for an additional 4 weeks, with continuous HFD intake. GBE significantly decreased the food efficiency ratio, serum lipid and insulin levels, adipose tissue weights, and adipocyte size. It significantly increased the grip strength, muscle masses, and myofiber cross-sectional area. It deactivated the protein kinase C (PKC) theta and zeta, resulting in activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is known to regulate muscle synthesis and degradation. Furthermore, it inhibited the production of inflammatory cytokines in the muscle tissue. GBE attenuated both obesity and sarcopenia. Thus, GBE is a potential agent to prevent or treat sarcopenic obesity.

Stromal cell-derived DEL-1 inhibits Tfh cell activation and inflammatory arthritis.

The secreted protein developmental endothelial locus 1 (DEL-1) regulates inflammatory cell recruitment and protects against inflammatory pathologies in animal models. Here, we investigated DEL-1 in inflammatory arthritis using collagen-induced arthritis (CIA) and collagen Ab-induced arthritis (CAIA) models. In both models, mice with endothelium-specific overexpression of DEL-1 were protected from arthritis relative to WT controls, whereas arthritis was exacerbated in DEL-1-deficient mice. Compared with WT controls, mice with collagen VI promoter-driven overexpression of DEL-1 in mesenchymal cells were protected against CIA but not CAIA, suggesting a role for DEL-1 in the induction of the arthritogenic Ab response. Indeed, DEL-1 was expressed in perivascular stromal cells of the lymph nodes and inhibited Tfh and germinal center B cell responses. Mechanistically, DEL-1 inhibited DC-dependent induction of Tfh cells by targeting the LFA-1 integrin on T cells. Overall, DEL-1 restrained arthritis through a dual mechanism, one acting locally in the joints and associated with the anti-recruitment function of endothelial cell-derived DEL-1; the other mechanism acting systemically in the lymph nodes and associated with the ability of stromal cell-derived DEL-1 to restrain Tfh responses. DEL-1 may therefore be a promising therapeutic for the treatment of inflammatory arthritis.

A Combination of Soybean and Haematococcus Extract Alleviates Ultraviolet B-Induced Photoaging.

Soybean-derived isoflavones have been investigated for their preventative effects against UV-induced symptoms of skin damage including wrinkle formation and inflammation. Haematococcus pluvialis is a freshwater species of Chlorophyta that contains high concentrations of the natural carotenoid pigment astaxanthin. Astaxanthin is known to be involved in retinoic acid receptor (RAR) signaling and previously been associated with the inhibition of activator protein (AP)-1 dependent transcription. Based on previous studies, we hypothesized that a combination of soy extract (SE) and Haematococcus extract (HE) may prevent UVB-induced photoaging through specific signaling pathways, as measured by UVB-induced wrinkling on hairless mice skin and expression changes in human dermal fibroblasts (HDFs). The 1:2 ratio of SE and HE mixture (SHM) showed the optimal benefit in vivo. SHM was found to inhibit wrinkle formation via the downregulation of matrix metalloproteinase (MMP)-1 mRNA and protein expression. SHM also inhibited mitogen-activated protein kinase (MAPK) phosphorylation and the transactivation of AP-1 which plays an important role in regulating MMP expression. These results highlight the potential for SHM to be developed as a therapeutic agent to prevent UVB-induced skin wrinkling.

Type I saikosaponins a and d inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells.

Many osteopenic disorders, including a postmenopausal osteoporosis and lytic bone metastasis in breast and prostate cancers, are linked with a hyperosteoclast activity due to increased receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblastic/stromal cells. Therefore, inhibition of RANKL-induced osteoclastogenesis and osteoclast-induced bone resorption is an important approach in controlling pathophysiology of these skeletal diseases. We found that, of seven type I, II, and III saikosaponins isolated from Bupleurum falcatum, saikosaponins A and D, type I saikosaponins with an allyl oxide linkage between position 13 and 28 and two carbohydrate chains that are directly attached to the hydroxyl groups in position 3, exhibited the most potent inhibition on RANKL-induced osteoclast formation at noncytotoxic concentrations. The stereochemistry of the hydroxyl group at C16 did not affect their activity. Saikosaponins A and D inhibited the formation of resorptive pits by reducing the secreted levels of matrix metalloproteinase- (MMP-) 2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Additionally, saikosaponins A and D inhibited mRNA expression of parathyroid hormone-related protein as well as cell viability and invasion in metastatic human breast cancer cells. Thus, saikosaponins A and D can serve as a beneficial agent for the prevention and treatment of osteoporosis and cancer-induced bone loss.

Sweet bee venom pharmacopuncture for chemotherapy-induced peripheral neuropathy.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is sensory and motor nerve damage to the peripheral nervous system caused by chemotherapeutic agents. It often causes pain and other varying degrees of neuropathic symptoms accompanied by functional limitations and reduced quality of life. Currently, there is no standard treatment protocol for the treatment of CIPN. OBJECTIVE: In need of more research to develop new therapeutic options focusing on their safety, efficacy, and long-term sustained clinical effects, a pilot study of sweet bee venom pharmacopuncture (SBVP) for CIPN was conducted to build up preliminary efficacy data in the process of preparing for a future larger scale randomized controlled SBVP trial for CIPN. METHODS: We conducted a prospective case series by analyzing the clinical observations made of CIPN patients treated with SBVP. A total of 11 eligible consecutive CIPN patients who visited East-West Cancer Center from June 1, 2010, to February 28, 2011, were treated with total of six SBVP treatments given within the 3-week period. The outcomes were measured using World Health Organization Common Toxicity Criteria for Peripheral neuropathy (WHO grading system), Patient Neurotoxicity Questionnaire (PNQ), Visual Analogue System (VAS), and Health-Related Quality of Life (HRQOL) collected at the baseline, post-second, fourth, and the final treatment. Patients were followed 3 weeks into no intervention to determine the sustained effects of pharmacopuncture. RESULTS: Both of the WHO CIPN grade and PNQ scores have shown a decrease in the level of neuropathy. VAS pain level has also shown a great decrease and improvement in patients' quality of life have also been detected though modest. Changes in WHO grade, VAS and Total HRQOL scores between the baseline and after the last treatment session were significant. Changes in WHO grade, Total PNQ, PNQ-sensory, VAS, Total HRQOL, and HRQOL-functional scores between the baseline and the 3-week follow-up were significant. CONCLUSION: The positive result of the study supports the potential value of conducting a fully powered trial to explore further efficacy of SBVP for CIPN. However a single positive result within this pilot study must be interpreted with caution.

A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus.

BACKGROUND AND OBJECTIVES: Non-small-cell lung cancer (NSCLC) represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus(HAP) has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. METHODS: The study involved six patients treated at the East- West Cancer Center (EWCC) from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT) scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS) and progression-free survival (PFS). RESULTS: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD), and the other three showed progressive disease (PD). The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. CONCLUSION: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

Anti-inflammatory effects of BT-201, an n-butanol extract of Panax notoginseng, observed in vitro and in a collagen-induced arthritis model.

BACKGROUND & AIMS: Although there has been some success with protein-based anti-tumor necrosis factor alpha (TNF-alpha) therapeutics, the problems associated with protein-based drugs demand alternative approaches. We screened various herbal extracts for their ability to inhibit TNF-alpha secretions and found that BT-201, an n-butanol extract of Panax notoginseng (Burk.) F. H. Chen (P. notoginseng) has such an ability. METHODS: The purpose of this study has been to evaluate the anti-inflammatory and anti-rheumatic effects of BT-201. The anti-inflammatory effects were evaluated by measuring the effects of BT-201 on the production of TNF-alpha, interleukin (IL)-1beta, inducible nitric oxide (iNO), and matrix metalloproteinase-13 (MMP-13), in vitro. The anti-rheumatic effects were evaluated by treating mice with collagen-induced arthritis (CIA) using a daily oral administration of BT-201 at 15 mg/kg/day. In addition, the effects on NF-kappaB and mitogen-activated protein kinase (MAPK) pathways were evaluated by Western blotting using phospho-specific antibodies. RESULTS: BT-201 significantly inhibited all the inflammatory parameters evaluated in vitro and delayed the onset and progression of CIA. BT-201 inhibited the activation of NF-kappaB, ERK, p38, and JNK pathways. CONCLUSIONS: Our results demonstrated that BT-201 can modulate various aspects of inflammation in vitro and that it has disease-modifying, anti-rheumatic effects in vivo, suggesting that it can be a potential alternative to the current anti-TNF-alpha therapeutics for rheumatoid arthritis and other inflammatory disease.

Intestinal bacteria activate estrogenic effect of main constituents puerarin and daidzin of Pueraria thunbergiana.

To understand the relationship between the metabolites and estrogenic activity of the main isoflavones puerarin and daidzin of the rhizome of Pueraria thunbergiana (PT, family Leguminosae), PT and its isoflavones were transformed by human intestinal bacteria and their estrogenic effects were investigated. All human fecal specimens hydrolyzed puerarin and daidzin to daidzein, but their hydrolyzing activities varied depending on the individuals. All intestinal bacteria isolated from human also hydrolyzed daidzin to daidzein, but a few bacteria transformed puerarin to daidzein. When the estrogenic effect of PT, puerarin and daidzin was compared with those of their metabolites, the metabolites more potently increased proliferation of MCF-7 cells than PT, puerarin and daidzin. The metabolite daidzein also potently increased estrogen-response c-fos mRNA and PR protein expressions. These findings suggest that intestinal bacteria, which can hydrolyze puerarin and/or daidzin, may activate a potent estrogenic activity of PT.

Estrogenic effect of main components kakkalide and tectoridin of Puerariae Flos and their metabolites.

To understand the relationship between the metabolism and estrogenic activity of kakkalide and tectoridin, main isoflavones in the flower of Pueraria thunbergiana (family Leguminosae), these isoflavones and their metabolites by human intestinal microflora as well as their estrogenic effects were investigated. All human fecal specimens metabolized kakkalide and tectoridin. All isolated kakkalide-hydrolyzing intestinal bacteria also hydrolyzed kakkalide and tectoridin to irisolidone and tectorigenin, respectively. When the estrogenic effects of kakkalide and tectoridin were compared with those of their metabolites irisolidone and tectorigenin, the metabolites more potently increased proliferation of MCF-7 cells than kakkalide and tectoridin. These metabolites also potently induced estrogen-response c-fos and pS2 mRNA expression. These results suggest that kakkalide and tectoridin may be metabolized mainly to irisolidone and tectorigenin, respectively, by intestinal microflora in the intestines, and which may be subsequently absorbed into the blood where they can express their estrogenic effect.

In vitro inhibitory effect of flavonoids on growth, infection and vacuolation of Helicobacter pylori.

Flavonoids, which are main constituents of herbal medicines, have been reported to inhibit the growth of Helicobacter pylori (HP). Therefore, to evaluate the anti-HP activity of some flavonoids (flavanols, flavones, flavonols and isoflavonoids), their effects on the growth and vacuolation of HP as well as the infective properties of HP against HeLa cells were investigated. Catechins, quercetin and naringenin weakly inhibited the growth of HP, but all tested compounds did not inhibit HP infection into KATO III cells and HP urease activity. Quercetin and naringenin inhibited HP VacA vacuolation in HeLa cells with IC (50) values of 0.046 and 0.36 mM, respectively. Quercetin also inhibited procaspase-3 activation to caspase-3 in HeLa cells induced by HP VacA toxin, which may induce cell death via the proteolytic activation of a cascade of caspases. However, quercetin did not affect Bax and Bcl-2 protein levels. Based on these findings, quercetin may improve gastric cell death by inhibiting apoptotic signaling by HP VacA toxin. Abbreviations. HP: Helicobacter pyloriBSA:bovine serum albumin ESL:enhanced chemiluminescence MIC:minimum inhibitory concentration MTT:methylthiazolyldiphenyl-tetrazolium bromide PBS:phosphate-buffered saline VacA:Vacuolating cytotoxin.

5-Hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone: a pancreatic lipase inhibitor isolated from Alpinia officinarum.

A pancreatic lipase inhibitor, 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone (HPH), from the rhizome of Alpinia officinarum (AO) was isolated and its antihyperlipidemic activity was measured. HPH inhibited a pancreatic lipase with an IC(50) value of 1.5 mg/ml (triolein as a substrate). HPH significantly lowered the serum TG level in corn oil feeding-induced triglyceridemic mice, and reduced serum triglyceride (TG) and cholesterol in Triton WR-1339-induced hyperlipidemic mice. However, HPH did not show hypolipidemic activity in high cholesterol diet-induced hyperlipidemic mice. Based on these findings, we propose that PL inhibitors may be effective as hypolipidemic agents.

3-Methylethergalangin isolated from Alpinia officinarum inhibits pancreatic lipase.

The pancreatic lipase inhibitory activity of the rhizome of Alpinia officinarum (AO) and its antihyperlipidemic activity were measured. When the water extract of AO was fractionated stepwise with organic solvents, the ethyl acetate fraction exhibited the most potent inhibition. 3-Methylethergalangin was isolated from that fraction as an inhibitor of pancreatic lipase with an IC(50) value of 1.3 mg/ml (triolein as a substrate). AO and its ethyl acetate fraction significantly inhibited the serum TG level in corn oil feeding-induced triglyceridemic mice, and serum triglyceride (TG) and cholesterol in Triton WR-1339-induced hyperlipidemic mice. However, this compound and the AO ethyl acetate fraction did not show hypolipidemic activity in high cholesterol diet-induced hyperlipidemic mice. The results suggest that the hypolipidemic activity of AO and 3-methylethergalangin is due to the inhibition of pancreatic lipase.

Daio-Orengedokuto inhibits HMG-CoA reductase and pancreatic lipase.

To evaluate the antihyperlipidemic activities of Orengedokuto (OT) and Daio-Orengedokuto (DOT), the inhibitory effects of these polyprescriptions on HMG-CoA reductase and pancreatic lipase and on the rat hyperlipidemic model induced by Triton WR-1339 were measured. OT potently inhibited HMG-CoA reductase but did not inhibit lipase. Among their ingredients, Coptidis Rhizoma was the most potent inhibitor, followed by Rhei Rhizoma. The HMG-CoA reductase-inhibitory activity of 80% EtOH extract was superior to that of water extract. However, DOT potently inhibited HMG CoA-reductase as well as pancreatic lipase. In the rat hyperlipidemic model induced by Triton WR-1339, OT and DOT decreased serum total cholesterol and low-density lipoprotein cholesterol levels. DOT also decreased serum triglyceride levels, but OT did not decrease it. These results suggest that the antihyperlipidemic activity of DOT may originate from the inhibition of pancreatic lipase as well as HMG-CoA reductase.

Agonist recognition sites in the cytosolic tails of vanilloid receptor 1.

Vanilloid receptor 1 (VR1), a ligand-gated ion channel activated by vanilloids, acid, and heat, is a molecular detector that integrates multiple modes of pain. Although the function and the biophysical properties of the channel are now known, the regions of VR1 that recognize ligands are largely unknown. By the stepwise deletion of VR1 and by chimera construction using its capsaicin-insensitive homologue, VRL1, we localized key amino acids, Arg-114 and Glu-761, in the N- and C-cytosolic tails, respectively, that determine ligand binding. Point mutations of the two key residues resulted in a loss of sensitivity to capsaicin and a concomitant loss of specific binding to [(3)H]resiniferatoxin, a potent vanilloid. Furthermore, changes in the charges of the two amino acids blocked capsaicin-sensitive currents and ligand binding without affecting current responses to heat. Thus, these two regions in the cytoplasmic tails of VR1 provide structural elements for its hydrophilic interaction with vanilloids and might constitute a long-suspected binding pocket.