Production of Secondary Metabolites from Cell Cultures of Sageretia thea (Osbeck) M.C. Johnst. Using Balloon-Type Bubble Bioreactors.

Sageretia thea is used in the preparation of herbal medicine in China and Korea; this plant is rich in various bioactive compounds, including phenolics and flavonoids. The objective of the current study was to enhance the production of phenolic compounds in plant cell suspension cultures of Sageretia thea. Optimum callus was induced from cotyledon explants on MS medium containing 2,4-dichlorophenoxyacetic acid (2,4-D; 0.5 mg L-1), naphthalene acetic acid (NAA, 0.5 mg L-1), kinetin (KN; 0.1 mg L-1) and sucrose (30 g L-1). Browning of callus was successfully avoided by using 200 mg L-1 ascorbic acid in the callus cultures. The elicitor effect of methyl jasmonate (MeJA), salicylic acid (SA), and sodium nitroprusside (SNP) was studied in cell suspension cultures, and the addition of 200 µM MeJA was found suitable for elicitation of phenolic accumulation in the cultured cells. Phenolic and flavonoid content and antioxidant activity were determined using 2,2 Diphenyl 1 picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethybenzothiazoline-6-sulphonic acid (ABTS), ferric reducing antioxidant power (FRAP) assays and results showed that cell cultures possessed highest phenolic and flavonoid content as well as highest DPPH, ABTS, and FRAP activities. Cell suspension cultures were established using 5 L capacity balloon-type bubble bioreactors using 2 L of MS medium 30 g L-1 sucrose and 0.5 mg L-1 2,4-D, 0.5 mg L-1 NAA, and 0.1 mg L-1 KN. The optimum yield of 230.81 g of fresh biomass and 16.48 g of dry biomass was evident after four weeks of cultures. High-pressure liquid chromatography (HPLC) analysis showed the cell biomass produced in bioreactors possessed higher concentrations of catechin hydrate, chlorogenic acid, naringenin, and other phenolic compounds.

Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide, causing serious liver complications, including nonalcoholic steatohepatitis. Recent findings suggest that peripheral serotonin (5-hydroxytryptamine, 5HT) regulates energy homeostasis, including hepatic lipid metabolism. More specifically, liver-specific 5HT2A knockout mice exhibit alleviated hepatic lipid accumulation and hepatic steatosis. Here, structural modifications of pimavanserin (CNS drug), a 5HT2A antagonist approved for Parkinson's disease, led us to synthesize new peripherally acting 5HT2A antagonists. Among the synthesized compounds, compound 14a showed good in vitro activity, good liver microsomal stability, 5HT subtype selectivity, and no significant inhibition of CYP and hERG. The in vitro and in vivo blood-brain barrier permeability study proved that 14a acts peripherally. Compound 14a decreased the liver weight and hepatic lipid accumulation in high-fat-diet-induced obesity mice. Our study suggests new therapeutic possibilities for peripheral 5HT2A antagonists in NAFLD.

Restoration of Cellular Proliferation and Characteristics of Human Tenocytes by Vitamin D.

Vitamin D (Vit D) increases calcium absorption in the intestine after binding to the Vit D receptor (VDR). The VDR has also been identified in muscle cells. Vit D supplementation resulted in improved muscle strength. However, there is a paucity of studies of the role of Vit D on tenocytes. We investigated the effects of Vit D on damaged tenocytes. Human tenocytes were treated with dexamethasone (Dex) to induce cell injury. Expression of the tenocyte-related markers tenomodulin (Tnmd), tenascin C (Tnc), scleraxis (Scx), mohawk (Mkx), and collagen (Col) 1 and 3 were measured. Then, tenocytes were cotreated with Vit D. 1-α-Hydroxylase and VDR were explored in tenocytes. With 10 µM Dex, the growth of tenocytes was significantly inhibited, and the gene expression of Tnmd, Tnc, Scx, Mkx, Col 1 and 3 also decreased. When tenocytes were cotreated with Vit D, cell proliferation recovered in a dose-dependent manner, and the expression of TNMD and Col 1 improved. When studying the mechanisms of the effects of Vit D on tenocytes, reactive oxygen species produced by Dex decreased with Vit D, and the phosphorylation of extracellular signal-regulated kinase and p38 was stimulated by Vit D cotreatment. 1-α-Hydroxylase and VDR were found in tenocytes, indicating that the cells have the ability to use an inactive form of Vit D and interact with it. Vit D is known to perform diverse actions and its protective effects on tenocytes suggest its beneficial role in tendon in addition to muscle and bone. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2241-2248, 2019.

Clinical Practice Guideline for the Diagnosis and Treatment of Pediatric Obesity: Recommendations from the Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology Hepatology and Nutrition.

The Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition newly developed the first Korean Guideline on the Diagnosis and Treatment of Obesity in Children and Adolescents to deliver an evidence-based systematic approach to childhood obesity in South Korea. The following areas were systematically reviewed, especially on the basis of all available references published in South Korea and worldwide, and new guidelines were established in each area with the strength of recommendations based on the levels of evidence: 1) definition and diagnosis of overweight and obesity in children and adolescents; 2) principles of treatment of pediatric obesity; 3) behavioral interventions for children and adolescents with obesity, including diet, exercise, lifestyle, and mental health; 4) pharmacotherapy; and 5) bariatric surgery.

Clinical practice guideline for the diagnosis and treatment of pediatric obesity: recommendations from the Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology Hepatology and Nutrition.

The Committee on Pediatric Obesity of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition newly developed the first Korean Guideline on the Diagnosis and Treatment of Obesity in Children and Adolescents to deliver an evidence-based systematic approach to childhood obesity in South Korea. The following areas were systematically reviewed, especially on the basis of all available references published in South Korea and worldwide, and new guidelines were established in each area with the strength of recommendations based on the levels of evidence: (1) definition and diagnosis of overweight and obesity in children and adolescents; (2) principles of treatment of pediatric obesity; (3) behavioral interventions for children and adolescents with obesity, including diet, exercise, lifestyle, and mental health; (4) pharmacotherapy; and (5) bariatric surgery.

Protective effect of Cornus walteri Wangerin leaf against UVB irradiation induced photoaging in human reconstituted skin.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus walteri Wangerin has been used in oriental traditional medicine for the treatment of antidiarrheal and inflammation. AIM OF THE STUDY: The efficacy of Cornus walteri Wangerin on skin anti-photoaging was investigated. MATERIALS AND METHODS: Hydrolyzed Cornus walteri Wangerin leaf was tested for the anti-photoaging effects against ultraviolet B (UVB)-induced matrix metalloproteinase (MMP)-1, pro-inflammatory cytokines using human reconstituted skin (KeraSkin™-FT) and also tested for elastase activity in vitro. The MMP-1 and pro-inflammatory cytokine levels of the extract were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The extract of hydrolyzed Cornus walteri Wangerin leaf (CWE) had the elastase inhibitory activity (IC50: 0.457mg/mL). CWE inhibited MMP-1 expression up to 61% in comparison with the control group which was not treated using CWE, but exposed to UVB. CWE also showed an inhibitory effect on releasing pro-inflammatory cytokines (IL-6 and IL-8) in KeraSkin™-FT (30% and 57% inhibition at dose of 50µg/mL, respectively). CONCLUSION: CWE is a promising anti-photoaging agent for the treatment of UVB-induced skin.

Transduced PEP-1-FK506BP ameliorates atopic dermatitis in NC/Nga mice.

Immunophilin, FK506-binding protein 12 (FK506BP), is a receptor protein for the immunosuppressive drug FK506 by the FK506BP/FK506 complex. However, the precise function of FK506BP in inflammatory diseases remains unclear. Therefore, we examined the protective effects of FK506BP on atopic dermatitis (AD) in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-induced HaCaT cells and 2,4-dinitrofluorobenzene-induced AD-like dermatitis in Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice using a cell-permeable PEP-1-FK506BP. Transduced PEP-1-FK506BP significantly inhibited the expression of cytokines, as well as the activation of NF-κB and mitogen-activated protein kinase (MAPK) in TNF-α/IFN-γ-induced HaCaT cells. Furthermore, topical application of PEP-1-FK506BP to NC/Nga mice markedly inhibited AD-like dermatitis as determined by a histological examination and assessment of serum IgE levels, as well as cytokines and chemokines. These results indicate that PEP-1-FK506BP inhibits NF-κB and MAPK activation in cells and AD-like skin lesions by reducing the expression levels of cytokines and chemokines, thus suggesting that PEP-1-FK506BP may be a potential therapeutic agent for AD.

The effects of three alternative treatment strategies after 8 weeks of proton pump inhibitor therapy for GERD in children.

OBJECTIVES: The purpose of this 24-week treatment study was to evaluate the effects of three treatment strategies after 8 weeks of lansoprazole therapy for gastroesophageal reflux disease in children. DESIGN: Open-labelled, uncontrolled, prospective study. SETTING: Samsung Medical Center, Seoul, Korea. METHODS: 37 erosive reflux disease (ERD) and 20 non-erosive reflux disease (NERD) patients were divided into three groups by symptom assessment at 8 weeks: (1) observation without treatment in the 'symptoms-resolved' group, (2) 'on-demand' treatment for an additional 16 weeks in the 'symptoms-attenuated' group and (3) continuous treatment in the 'symptoms-persistent' group. RESULTS: For ERD, six (100%) out of six patients in the 'symptoms-resolved' group remained improved at weeks 16 and 24. Sixteen (72.7%) out of 22 patients in the 'symptoms-attenuated' group had improvement of symptoms at 16 weeks, and 18 (81.8%) patients at 24 weeks. Six (66.7%) out of nine patients in the 'symptoms-persistent' group remained improved at weeks 16 and 24. For NERD, seven (100%) out of seven patients in the 'symptoms-resolved' group remained improved at weeks 16 and 24. Eight (80.0%) out of 10 patients in the 'symptoms-attenuated' group remained improved at week 16, and 10 (100.0%) patients at week 24. None out of three patients in the 'symptoms-persistent' group remained improved at weeks 16 and 24. CONCLUSIONS: The selection of each alternative for long-term management according to the results of the assessment of symptoms at week 8 was useful and well tolerated. 'On-demand' therapy was equally effective. The 16-week therapy had the same efficacy as the 24-week therapy with regard to long-term lansoprazole treatment.

Hypocholesterolemic effect of sonication-killed Bifidobacterium longum isolated from healthy adult Koreans in high cholesterol fed rats.

We have previously reported that live Bifidobacterium longum SPM1207, a strain isolated from healthy adult Koreans, significantly reduced serum cholesterol in broth and rat. We here examined the effect of oral administration of sonication-killed B. longum SPM1207 on serum cholesterol in rats in order to investigate whether this killed strain could be utilized as a potent probiotics for human and animals. Dietary treatments consisted of 3 treatment groups of 24 rats each randomly assigned to either normal diet, high cholesterol diet and saline (HCS), or high cholesterol diet and sonication-killed B. longum SPM1207 (HCKB) for 3 weeks. Although HDL-cholesterol levels in the serum were not significantly (p > 0.05) different between HCKB rats and HCS rats, total and LDL-cholesterol levels in the serum were significantly (p < 0.05) less increased in HCKB (total: 177.71 mg/dL, LDL-: 60.50 mg/dL) rats when compared to HCS (total: 237.17 mg/dL, LDL-: 71.50 mg/dL) rats. AI was significantly (p < 0.05) lower in HCKB (4.95 mg/dL) rats when compared to HCS (9.22 mg/dL) rats. Body weight increase and relative liver weight were significantly (p < 0.05) lower in HCKB rats when compared to HCS rats. Over the time, high cholesterol diet caused dry feces accompanied by decreased fecal water content (66.00 to 61.94%) but sonication-killed B. longum SPM1207 administration increased fecal water content (71.58 to 74.25%). The results in the current study provide evidence that the sonication-killed cells of B. logum SPM1207 isolated from healthy adult Koreans have a greater potential to be used as a cholesterol-lowering agent. Furthermore, the current study suggest that this killed specific strain may play role in part in blocking the body weight increase and relieving or eliminating constipation.

Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation among nursing home residents.

BACKGROUND: Constipation is a significant problem in the elderly, specifically nursing home and/or extended-care facility residents are reported to suffer from constipation. Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as diarrhea and constipation effect. The objective of this study was to investigate the efficacy of this LAB supplement in the management of nursing home residents. METHODS: Nineteen subjects (8M, 11F; mean age 77.1 +/- 10.1) suffering with chronic constipation were assigned to receive LAB (3.0 x 10(11) CFU/g) twice (to be taken 30 minutes after breakfast and dinner) a day for 2 weeks in November 2008. Subjects draw up a questionnaire on defecation habits (frequency of defecation, amount and state of stool), and we collected fecal samples from the subjects both before entering and after ending the trial, to investigate LAB levels and inhibition of harmful enzyme activities. Results were tested with SAS and Student's t-test. RESULTS: Analysis of questionnaire showed that there was an increase in the frequency of defecation and amount of stool excreted in defecation habit after LAB treatment, but there were no significant changes. And it also affects the intestinal environment, through significantly increase (p < 0.05) fecal LAB levels. In addition, tryptophanase and urease among harmful enzyme activities of intestinal microflora were significantly decreased (p < 0.05) after LAB treatment. CONCLUSION: LAB, when added to the standard treatment regimen for nursing home residents with chronic constipation, increased defecation habit such as frequency of defecation, amount and state of stool. So, it may be used as functional probiotics to improve human health by helping to prevent constipation.

Anti-inflammatory effects of YeongyoSeungma-tang.

ETHNOPHARMACOLOGICAL RELEVANCE: YeongyoSeungma-tang which includes Fructus Forsythia, has been used in oriental traditional medicine for treatment of early smallpox and atopic dermatitis. AIM OF THE STUDY: YeongyoSeungma-tang was carried out to investigate for anti-inflammatory effects. MATERIALS AND METHODS: YeongyoSeungma-tang was tested for anti-inflammatory effects against lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E(2) (PGE(2)), and tumor necrosis factor alpha (TNF-alpha) releases as well as nuclear factor kappa B (NF-kappaB) expression using RAW264.7 macrophage cells. RESULTS: YeongyoSeungma-tang significantly inhibited generation of NO (42% and 59% inhibition at doses of 5 microg/mL and 10 microg/mL, respectively), PGE(2) (46% and 80% inhibition at doses of 5 microg/mL and 10 microg/mL, respectively) and TNF-alpha (6% and 23% inhibition at doses of 5 microg/mL and 10 microg/mL, respectively) on LPS-stimulated RAW 264.7 cells in a concentration-dependent manner. Consistently in these observations, the expression of inducible NO synthase (iNOS) enzyme was also inhibited by YeongyoSeungma-tang. However, YeongyoSeungma-tang did not show any influence on the expression of cyclooxygenase-2. The cream containing 0.075% YeongyoSeungma-tang showed good skin moisturizing effect without any irritation. CONCLUSION: The present study may support the fact that YeongyoSeungma-tang can have the good possibility as an anti-inflammatory agent for troubled skins.

Deoxypodophyllotoxin (DPT) inhibits eosinophil recruitment into the airway and Th2 cytokine expression in an OVA-induced lung inflammation.

The effect of deoxypodophyllotoxin (DPT) isolated from Anthriscus sylvestris Hoffm. was evaluated in an IN VIVO animal model for antiasthmatic activity. DPT (1.0 to 5 mg/kg) was given orally to ovalbumin (OVA)/alum-induced asthmatic mice. DPT reduced the number of infiltrated eosinophils in bronchoalveolar lavage (BAL) fluid in a dose-dependent manner. Dexamethasone (5 mg/kg), which was used as a positive control, also strongly inhibited the number of infiltrated eosinophils. The effect of DPT on a transcript profile in a murine asthma model was determined by RT-PCR, which showed that DPT decreased the mRNA levels of the Th2 cytokines. Northern blot analysis showed that DPT also reduced both the eotaxin and arginase I mRNA levels in a dose-dependent manner.