Sipyimigwanjung-tang, a traditional herbal medication, alleviates weight gain in a high-fat diet-induced obese mice model.

Obesity leads to the development of metabolic syndrome and comorbidities. Overweight and obesity continue to be a relentless global issue. Sipyimigwanjung-tang (SGT), a traditional herbal medication, was first mentioned in Dongui Sasang Shinpyun and has been used to treat edema, meteorism, and jaundice, which are common findings associated with obesity. The main physiological feature of obesity is expanded adipose tissue, which causes several impairments in liver metabolism. Therefore, this study aimed to investigate the anti-obesity effects of SGT in the epididymal white adipose tissue (eWAT) and livers of high-fat diet (HFD)-induced obese mice. SGT significantly blocked HFD-induced weight gain in C57BL/6N mice. In addition, SGT effectively reduced the increased weight and adipocyte size in eWAT of HFD-induced obese C57BL/6 N mice. Moreover, SGT significantly decreased the elevated gene expression of Peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and Sterol regulatory element-binding protein 1 in the eWAT of HFD-induced obese mice. Furthermore, SGT significantly decreased lipid accumulation in the livers of HFD-induced obese mice and differentiated 3T3-L1 adipocytes. Hence, the present study provides substantial evidence that SGT has potential therapeutic effects on obesity.

Magnolia officinalis Rehder & E. Wilson ameliorates white adipogenesis by upregulating AMPK and SIRT1 in vitro and in vivo.

Although there is an established link between Magnolia Cortex (MO) and lipid metabolism in previous research, its exploration within the context of obesity has been limited. Therefore, the present study investigated the therapeutic effects of MO on obesity and its mechanism of action in vitro and in vivo. Our chromatography analysis revealed that Honokiol and Magnolol are contained in MO extract. In vitro experiments showed that lipid droplets, adipogenic, and lipogenic genes were notably diminished by increasing sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK) protein expression in MO-treated 3T3-L1 adipocytes. In vivo experiments exhibited that MO administration significantly recovered the adipogenesis, lipogenesis, and fatty acid oxidation genes by increasing the SIRT1 and AMPK expression in white adipose tissue. Furthermore, hepatic steatosis by HFD feeding was ameliorated in MO-administered obese mice. We conclude that MO could be important manager for treating obesity through AMPK and SIRT1 regulation.

Drynaria rhizome water extract alleviates high­fat diet­induced obesity in mice.

Drynaria rhizome is a herbal medicine used for strengthening bones and treating bone diseases in East Asia. Although obesity is considered to benefit bone formation, it has been revealed that visceral fat accumulation can promote osteoporosis. Given the complex relationship between bone metabolism and obesity, bone­strengthening medicines should be evaluated while considering the effects of obesity. The present study investigated the effects of Drynaria rhizome extract (DRE) on high­fat diet (HFD)­induced obese mice. DRE was supplemented with the HFD. Body weight, food intake, the expression levels of lipogenesis transcription factors, including sterol regulatory element binding protein (SREBP)­1, peroxisome proliferator­activated receptor (PPAR)­Î³ and adenosine monophosphate­activated protein kinase (AMPK)­α, and AMPK activation were evaluated. Mice fed DRE and a HFD exhibited reduced body weight without differences in food intake compared with those in the HFD group. Furthermore, DRE; upregulated AMPK­α of epididymal one; down­regulated SREBP­1 and PPAR­Î³, as determined using western blotting and quantitative polymerase chain reaction, respectively. Decreased lipid accumulation were observed in both fat pad and liver of HFD­fed mice, which were suppressed by DRE treatment. These results demonstrated the potential of DRE as a dietary natural product for strengthening bones and managing obesity.

Effects of Magnoliae Flos on Atopic Dermatitis-Like Inflammation Evaluated via Extracellular Signal-regulated Kinase or Signal Transducers and Activators of Transcription 1/3 Signalling Pathways.

Atopic dermatitis is a chronic inflammatory skin  disease. Skin is the largest organ and plays a pivotal role in protecting the body. Not only does the skin act as a physical barrier against the external environment, but it also has its own immune system. Atopic dermatitis is caused by prolonged excessive inflammatory responses that worsen under imbalanced cutaneous immune system skin conditions. Although the prevalence and burden of atopic dermatitis is increasing, the standard therapeutic agents remain unclear due to  the complicated pathophysiology of the condition. The objective of this study is to examine the use of Magnoliae flos, the dried flower bud of Magnolia biondii or  related plants. The effects and underlying mechanism of  action of aqueous extract of the buds of Magnoliae flos (MF) were evaluated. Immortalized human keratinocytes (HaCaT) stimulated with tumour necrosis factor-α and interferon-γ mixture and NC/Nga mice stimulated with 2,4-dinitrochlorobenzene were used as atopic dermatitis models, in vitro and in vivo, respectively. The effects of MF were determined by measuring the suppression of pro-inflammatory signalling pathways, such as extracellular signal-regulated kinase or signal transducers and activators of transcription 1/3 and restoring skin barrier molecules. In conclusion, MF is a potential therapeutic alternative for the treatment of atopic dermatitis through repressing inflammatory pathways.

Apocynin alleviates weight gain and obesity-induced adipose tissue inflammation in high-fat diet-fed C57BL/6 mice.

Obesity involves chronic low-grade inflammation within adipose tissue. Apocynin (APO) is a therapeutic agent for the treatment of inflammatory diseases. Therefore, the present study aimed to investigate whether APO can reduce weight gain and obesity-induced adipose tissue inflammation. C57BL/6 mice were administered APO or orlistat (Orli) as a positive control with a high-fat diet (HFD) for 12 weeks. Lipopolysaccharide-stimulated 3T3-L1 adipocytes were used for the in vitro study. Our results showed a significantly lower white adipose tissue (WAT) mass index in 10 mg/kg APO-treated mice than in 20 mg/kg Orli-treated mice. Moreover, the protein expression of adipose triglyceride lipase, fatty acid synthase, sterol regulatory element-binding transcription factor 1, and peroxisome proliferator-activated receptor γ was reversed in the WAT of 10 mg/kg APO-treated mice. Furthermore, APO reduced the expression of the macrophage marker F4/80, decreased the mRNA levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and increased the mRNA levels of interleukin-10 in WAT. APO decreased the phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p65 in vivo and in vitro. Notably, APO had a stronger effect on the amelioration of adipose tissue inflammation than Orli did. Our findings lay the foundation for research on the use of APO as an agent to ameliorate weight gain and obesity-induced inflammatory diseases.

Magnoliae flos Downregulated Lipopolysaccharide-Induced Inflammatory Responses via NF-κB/ERK-JNK MAPK/STAT3 Pathways.

Background: Magnoliae flos is the dried flower bud of Magnolia biondii and related plants. It has been used as a medicinal herb for the treatment of rhinitis, sinusitis, and sinus headaches. Nevertheless, the effects of Magnoliae flos in microbial infection or sepsis remain unclear. In this study, we investigated the anti-inflammatory effects of Magnoliae flos water extract (MF) in lipopolysaccharide- (LPS-) induced septic mice and LPS-stimulated RAW264.7 macrophages. Results: We found that MF reduced the mortality of LPS-challenged mice. Enzyme immunoassays and reverse transcription polymerase chain reaction analysis revealed that MF administration attenuated mRNA expression and protein production of proinflammatory mediators, including cyclooxygenase 2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. In parallel to these results in mice, pretreatment with MF suppressed the LPS-induced production of proinflammatory mediators in RAW264.7 macrophages. In addition, we found that MF exerted its suppressive effects by inhibiting the activation of the mitogen-activated protein kinase, nuclear factor-κB, and signal transducer and activator of transcription pathways at the protein level. Conclusion: MF could be a potential therapeutic agent for regulating excessive inflammatory responses in sepsis.

Euphorbia hirta Leaf Ethanol Extract Suppresses TNF-α/IFN-γ-Induced Inflammatory Response via Down-Regulating JNK or STAT1/3 Pathways in Human Keratinocytes.

Skin inflammation may cause allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis. Euphorbia hirta (E. hirta) is a member of the Euphorbiaceae family and is well-known for its anti-asthma effects. E. hirta has traditionally been used to treat respiratory ailments, dysentery, jaundice, and digestive problems. However, its effects on skin inflammation remain unclear. Here, we determined the effects of 70% ethanol extract of E. hirta leaves (ELE) in vitro using human keratinocyte HaCaT cells, which constitute most epidermal skin cells. We determined the inhibitory effects of ELE on the inflammation caused by tumor necrosis factor (TNF)-α/interferon (IFN)-γ in keratinocytes using ELISA, immunoblotting, and qRT-PCR assay. ELE was found to reduce the production and mRNA expression of pro-inflammatory cytokines such as TNF-α or interleukin-6 and the expression of various proteins, including signal transducers, activators of transcription 1/3, and mitogen-activated protein kinase. Expression levels of these proteins were found to be upregulated in the TNF-α/IFN-γ-stimulated condition and downregulated by ELE treatment. These results indicate that ELE protects HaCaT cells against TNF-α/IFN-γ-induced skin inflammation.

Peucedanum japonicum Thunberg alleviates atopic dermatitis-like inflammation via STAT/MAPK signaling pathways in vivo and in vitro.

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disorder that exhibits clinical relapse. The disruption of the skin barrier increases the symptoms of AD, which is accompanied by a reduction in skin integrity. As an immune barrier, the skin plays a crucial role in regulating the inflammatory responses in AD. In this study, we used murine atopic dermatitis model using 2,4-dinitrochlorobenzen (DNCB), which is one of haptens to disrupt the skin barrier and generate the inflammation. As the small molecule, DNCB is easily penetrate the epidermis and binds to tissue proteins provoking immune responses. We evaluated the effects of an aqueous extract of Peucedanum japonicum Thunberg (PJT) in an experimental model of AD by measuring the mRNA and protein expression of cytokines and their related biomarkers. We examined the dorsal skin lesions, transepidermal water loss (TEWL), scratching behavior, expression of molecules related to skin barrier integrity, and histological changes in a murine model of DNCB- induced AD. We found out the down-regulatory effects of PJT on the AD-like symptoms or inflammatory dorsal lesions. For in vitro study, we used a mixture of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in human keratinocytes. The protein and mRNA expressions of skin barrier molecules and inflammatory markers were measured with western blotting and qRT-PCR assays, respectively. As a result, PJT alleviated the AD-like symptoms, and suppressed the inflammation caused by a TNF-α and IFN-γ in human keratinocytes. The regulatory effects of PJT appeared to be mediated via the mitogen-activated protein kinase (MAPK) and signal transducers and activators of transcription (STAT) signaling pathways both in vivo and in vitro. Altogether, the results indicated that PJT could serve as a promising therapeutic candidate for suppressing AD by inhibiting inflammation and improving the integrity of the skin barrier.

Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by an impaired skin barrier and intense itchiness, which decreases the individual's quality of life. No fully effective therapeutic agents have prevailed for AD due to an insufficient grasp of the complex etiology. Ellagic acid (EA), a natural compound, has anti-inflammatory properties in chronic diseases. The effects of EA on AD have not yet been explored. The present study investigated the effects of EA on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and house dust mite-induced AD-like skin lesions in NC/Nga mice. Treatment with EA suppressed inflammatory responses in keratinocytes by regulating critical inflammatory signaling pathways, such as mitogen-activated protein kinases and signal transducers and activators of transcription. In vivo studies using a DfE-induced AD mouse model showed the effects of EA administration through ameliorated skin lesions via decremented histological inflammatory reactions. These results suggest that EA could be a potential therapeutic alternative for the treatment of AD by inhibiting inflammatory signaling pathways.

Pharmacological Properties of a Traditional Korean Formula Bojungchiseup-tang on 3T3-L1 Preadipocytes and High-Fat Diet-Induced Obesity Mouse Model.

The global obesity epidemic has nearly doubled since 1980, and this increasing prevalence is threatening public health. It has been reported that natural products could contain potential functional ingredients that may assist in preventing obesity. Bojungchiseub-tang (BJT), mentioned in the Donguibogam as an herbal medication for the treatment of edema, a symptom of obesity, consists of eleven medicinal herbs. However, the pharmacological activity of BJT has not been investigated. The present study was designed to investigate the putative effect of BJT on the adipogenesis of 3T3-L1 cells and the weight gain of high-fat diet (HFD-) fed C57BL/6 mice. Oil Red O staining was conducted to examine the amount of lipids in 3T3-L1 adipocytes. Male C57BL/6 mice were divided into three groups: standard diet group (control, CON), 45% HFD group (HFD), and HFD supplemented with 10% of BJT (BJT). The expression levels of genes and proteins related to adipogenesis in cells, WAT, and liver were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. We found that BJT treatment significantly decreased the protein and mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) in a dose-dependent manner in differentiated 3T3-L1 cells. Similar to the results of the in vitro experiment, BJT suppressed HFD-induced weight gain in an obese mouse model. In addition, BJT effectively reduced the HFD-induced epididymal adipose tissue weight/body weight index. BJT also downregulated the mRNA levels of PPARγ, C/EBPα, and SREBP1 in the epididymal adipose and liver tissue of HFD-fed obese mice. These findings suggest that BJT induces weight loss by affecting adipogenic transcription factors.

Astilbe Chinensis ethanol extract suppresses inflammation in macrophages via NF-κB pathway.

BACKGROUND: Macrophages play a crucial role in inflammation. Astilbe chinensis is one of perennial herbs belonging to the genus Astilbe. Plants in the genus have been used for pain, headaches, arthralgia, and chronic bronchitis. However, the effect of A.chinensis on inflammation remains unclear. To study the anti-inflammatory action of A.chinensis ethanol extract (ACE), we investigated the effect of ACE on the production of pro-inflammatory mediators and cytokines in macrophages. METHODS: We evaluated the effectiveness of ACE in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and thioglycollate (TG)-elicited peritoneal macrophages from male C57BL/6 mice. We measured the levels of pro-inflammatory mediators and cytokines, and examined the anti-inflammatory actions of ACE on nuclear factor κB (NF-κB) pathway in the macrophages. Western blot analysis and immunofluorescence microscopy were used to determine protein level and translocation, respectively. RESULTS: ACE suppressed the output of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in stimulated macrophages via inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. ACE suppressed mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α). We examined the efficacies of ACE on NF-κB activation by measuring the expressions including IκB kinase (IKK), inhibitor of κB (IκB), and nuclear p65 proteins. In addition, the inhibition of NF-κB p65's translocation was determined with immunofluorescence assay. CONCLUSION: Our findings manifested that ACE inhibited LPS or TG-induced inflammation by blocking the NF-κB signaling pathway in macrophages. It indicated that ACE is a potential therapeutic mean for inflammation and related diseases.

Rice Hull Extract (RHE) Suppresses Adiposity in High-Fat Diet-Induced Obese Mice and Inhibits Differentiation of 3T3-L1 Preadipocytes.

Obesity is one of major health challenges in the industrial world. Although rice hull has been reported to show various bioactivities, no studies have evaluated its anti-obesity effect. We hope to demonstrate the anti-obesity effect of rice hull extract (RHE) and the underlying mechanism in high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Serum lipid profiles were determined by enzymatic methods. Histological analysis of liver and epididymis fat tissues was carried out with hematoxylin and eosin stain. The mRNA expression of adipogenic markers was analyzed with qRT-PCR and western blotting. Oral administration of RHE reduced body weight gain and fat accumulation in HFD-fed mice. RHE also reduced lipid accumulation by inhibiting the mRNA expression of adipogenic-related genes in HFD-fed obese mice and differentiated preadipocytes. The downregulation of adipogenesis by RHE was mediated through the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, RHE induced the phosphorylation of c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinases (ERK) in liver and epididymis adipose tissues of HFD-fed obese mice. Taken together, these findings indicate that RHE could inhibit the differentiation of adipose cell and prevent HFD-induced obesity, suggesting its potential in the prevention of obesity and metabolic syndrome and related-disorders.

Anti-Atopic Dermatitis Effect of Seaweed Fulvescens Extract via Inhibiting the STAT1 Pathway.

Seaweed fulvescens (SF) is a green alga rich in chlorophyll with unique flavor and taste. It is also called Maesaengi which has antioxidant and other physiological activities. In the present study, we evaluated the therapeutic effects of SF in a mouse model of Dermatophagoides farinae body-induced atopic dermatitis (AD) and in tumor necrosis factor-α and interferon-γ-stimulated HaCaT keratinocytes. SF treatment (200 mg/mouse) inhibited the development of AD symptoms, compared to that in the control group, as evidenced from the improved dorsal skin lesion, reduced thickness and infiltration of inflammatory cells and smaller lymph nodes, and reduced levels of proinflammatory cytokines. In HaCaT keratinocytes, SF (10, 25, and 50 µg/mL) suppressed the production of proinflammatory cytokines in a dose-dependent manner. In addition, SF reduced the phosphorylation of signal transducer and activator of transcription 1, which is one of the major signaling molecules involved in cellular inflammation. These results suggested that SF could be a potential therapeutic alternative for the treatment of AD.

Clinical experience with (18)F-fluorodeoxyglucose positron emission tomography and (123)I-metaiodobenzylguanine scintigraphy in pediatric neuroblastoma: complementary roles in follow-up of patients.

PURPOSE: To evaluate the potential utility of (123)I-metaiodobenzylguanine ((123)I-MIBG) scintigraphy and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) for the detection of primary and metastatic lesions in pediatric neuroblastoma (NBL) patients, and to determine whether (18)F-FDG PET is as beneficial as (123)I-MIBG imaging. METHODS: We selected 8 NBL patients with significant residual mass after operation and who had paired (123)I-MIBG and (18)F-FDG PET images that were obtained during the follow-up. We retrospectively reviewed the clinical charts and the findings of 45 paired scans. RESULTS: Both scans correlated relatively well with the disease status as determined by standard imaging modalities during follow-up; the overall concordance rates were 32/45 (71.1%) for primary tumor sites and 33/45 (73.3%) for bone-bone marrow (BM) metastatic sites. In detecting primary tumor sites, (123)I-MIBG might be superior to (18)F-FDG PET. The sensitivity of (123)I-MIBG and (18)F-FDG PET were 96.7% and 70.9%, respectively, and their specificity were 85.7% and 92.8%, respectively. (18)F-FDG PET failed to detect 9 true NBL lesions in 45 follow-up scans (false negative rate, 29%) with positive (123)I-MIBG. For bone-BM metastatic sites, the sensitivity of (123)I-MIBG and (18)F-FDG PET were 72.7% and 81.8%, respectively, and the specificity were 79.1% and 100%, respectively. (123)I-MIBG scan showed higher false positivity (20.8%) than (18)F-FDG PET (0%). CONCLUSION: (123)I-MIBG is superior for delineating primary tumor sites, and (18)F-FDG PET could aid in discriminating inconclusive findings on bony metastatic NBL. Both scans can be complementarily used to clearly determine discrepancies or inconclusive findings on primary or bone-BM metastatic NBL during follow-up.

Intima-media thickness and pulse wave velocity in hypertensive adolescents.

Increased intima-media thickness (IMT) and pulse wave velocity (PWV) are noninvasive markers of early arterial wall alteration and are more widely used in adult clinical research. We investigated whether IMT and PWV are useful predictors of cardiovascular risk in hypertensive adolescents. Fifteen hypertensive adolescents (13-18 yr old, systolic BP > or = 140 mmHg, diastolic BP > or = 90 mmHg) and seventeen normotensive subjects were included. Height, weight, obesity index, body mass index (BMI), and fat distribution were obtained from each group. Serum lipid, insulin, vitamine B12, folate, renin, aldosterone, angiotensin-converting enzyme (ACE), and homocysteine levels were compared. The carotid IMT and PWV were measured. Arterial wall compliance and distensibility were calculated with the equation. High systolic blood pressure significantly correlated with height, weight, BMI, obesity index, arm circumference, fat mass, and fat distribution. Hypertensive adolescents had significantly greater cIMT (carotid intima-media thickness) and lower elastic properties such as cross-sectional compliance and distensibility of the carotid artery. The carotid IMT significantly correlated with brachial-ankle PWV. In conclusion, the measurement of carotid IMT and brachial-ankle PWV might be useful to predict the development of atherosclerosis in hypertensive adolescents.