Effect and mechanisms of Gambi-jung against high-fat diet-induced cardiac apoptosis in mice.

Obesity is associated with an increased risk of cardiovascular disease. Gambi-jung (GBJ), a modified herbal formula of Taeumjowi-tang, induces weight loss in high-fat diet (HFD)-fed obese mice. Meanwhile, concerns have been raised regarding Ephedra sinica Stapf (ES), the primary herb of GBJ, having potential adverse cardiovascular effects. However, there have been no reports on the effects of ES and ephedrine-containing products on obesity-induced cardiac apoptosis. Therefore, to investigated the effect of GBJ and ES on HFD-induced cardiac apoptosis, we utilized Western blot analysis, TUNEL-staining, and histological staining of heart tissues from HFD-fed obese mice. Western blot analysis showed that there were significant changes in the protein levels of anti-apoptotic markers (B-cell lymphoma (BCL) protein 2 (BCL-2), BCL-XL, and X-linked inhibitor of apoptosis protein) and pro-apoptotic markers (Fas, Fas-associated protein with death domain, BCL-2 agonist of cell death, BCL-2 associated X, cytochrome C, and cleaved caspase-9) in the heart of HFD-fed mice. In contrast administration of 250 mg/kg GBJ for 12 weeks significantly reversed the protein levels related to the apoptosis signaling pathway, which was greater than that of ES administration. Furthermore, GBJ-treated mice had markedly decreased number of TUNEL-stained apoptotic cells compared to the HFD group. Moreover, GBJ improved the mitochondrial function by regulating the genes expression of uncoupling protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, optic atrophy protein 1, and fission protein 1. Notably, hematoxylin and eosin histological staining showed no changes in the heart tissues of GBJ- and ES-treated mice, indicating that long-term administration of GBJ and ES did not exert any adverse effects on the cardiac tissue. The present study lays the foundation to support the efficacy of GBJ in protecting cardiac cell apoptosis induced by HFD feeding, as well as to verify the cardiac safety of GBJ administration.

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.

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.

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.

Accelerated Oral Healing by Angelica gigas Nakai from Hot Melt Extrusion Technology: An In Vitro Study.

Background and Objectives: In spite of the oral environment being healing-prone, its dynamic changes may affect wound healing. The purpose of this study was to assess the oral wound healing effect of Angelica gigas Nakai (AG) prepared by hot-melt extrusion. Materials and Methods: Human gingival fibroblast (HGF) cells were treated with AG or AG via hot-melt extrusion (AGH) for 24 h to determine the optimal concentration. For evaluating the anti-inflammatory effect of AG and AGH, a nitric oxide assay was performed under lipopolysaccharide (LPS) stimulation. The wound-healing effects of AG and AGH were evaluated using cell proliferation/migration assays and wound-healing marker expression through qRT-PCR. Results: Both AG and AGH showed no cytotoxicity on HGH cells. Regarding nitric oxide production, AGH significantly decreased LPS-induced nitric oxide production (p < 0.05). AGH showed a significantly positive result in the cell proliferation/cell migration assay compared with that in AG and the control. Regarding wound healing marker expression, AGH showed significantly greater VEGF and COL1α1 expression levels than those in the others (p < 0.05), whereas α-SMA expression was significantly different among the groups. Conclusions: Within the limits of this study, AGH accelerated oral wound healing in vitro.

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.

Anti-obesity effect of Lythri herba water extracts in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Lythrum salicaria L., also called purple loosestrife, has traditionally been used as a medicinal plant to treat internal dysfunction, such as gastrointestinal disorders or hemorrhages. It contains numerous phytochemical compounds, including orientin, and has been reported to have anti-diarrheal, anti-inflammatory, antioxidant, and antimicrobial properties. AIM OF THE STUDY: The effects of Lythrum salicaria L. on obesity have not been explored. Therefore, we investigated the anti-obesity effects of Lythri Herba, the aerial part of this plant, in vitro and in vivo. MATERIALS AND METHODS: Using distilled water, Lythri Herba water extracts (LHWE) were prepared by extracting Lythri Herba at 100°Ï¹. The contents of orientin in LHWE were identified using High Performance Liquid Chromatography (HPLC) analysis. To evaluate the anti-obesity effect of LHWE, 3T3-L1 adipocytes and a high-fat diet (HFD)-fed mice were used. Oil-red O staining was performed to examine the anti-adipogenic effects of LHWE in vitro. The histological changes in epididymal white adipose tissue (epiWAT) by LHWE were examined using hematoxylin and eosin staining. Serum leptin levels were measured by enzyme-linked immunosorbent assay. Specific quantification kits measured total cholesterol and triglyceride levels in the serum. The relative fold induction of protein and mRNA was determined using western blot and Quantitative real-time Polymerase Chain Reaction analysis, respectively. RESULTS: HPLC analysis demonstrated the presence of orientin in LHWE. LHWE treatment markedly reduced lipid accumulation in differentiated 3T3-L1 adipocytes. LHWE administration also conferred resistance to HFD-induced weight gain in mice and reduced epiWAT mass. Mechanistically, LHWE significantly decreased lipogenesis by downregulating lipoprotein lipase (LPL), glucose-6-phosphate dehydrogenase, ATP-citrate lyase, fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding transcription factor 1, and carbohydrate response element binding protein expression and increased the expression of genes involved in fatty acid oxidation (FAO), peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase 1 in 3T3-L1 adipocytes and epiWAT. Furthermore, LHWE significantly up-regulated the phosphorylation of AMP-activated protein kinase in 3T3-L1 adipocytes and epiWAT. CONCLUSION: LHWE decreases white adipogenesis in vitro and HFD-induced weight gain in vivo, which is associated with reduced lipogenesis and enhanced FAO.

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.

Clitorin ameliorates western diet-induced hepatic steatosis by regulating lipogenesis and fatty acid oxidation in vivo and in vitro.

Nonalcoholic fatty liver disease (NAFLD) is usually correlated with metabolic diseases, such as obesity, insulin resistance, and hyperglycemia. Herein, we investigated the inhibitory effects and underlying governing mechanism of clitorin in a western diet (WD)-induced hepatic steatosis mouse model, and in oleic acid-stimulated HepG2 cells. Male C57BL/6 mice were fed a normal diet, WD, WD + 10 or 20 mg/kg orlistat, and WD + 10 or 20 mg/kg clitorin. HepG2 cells were treated with 1 mM oleic acid to induce lipid accumulation with or without clitorin. Clitorin significantly alleviated body weight gain and hepatic steatosis features (NAFLD activity score, micro-, and macro-vesicular steatosis) in WD-induced hepatic steatosis mice. Additionally, clitorin significantly decreased protein expressions of sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα) in WD-induced hepatic steatosis mice. Moreover, clitorin significantly diminished the mRNA levels of SREBP1, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and enhanced the mRNA levels of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltranserase-1 (CTP-1), as well as adenosine monophosphate-activated protein kinase (AMPK) in the liver of WD-induced hepatic steatosis mice and oleic acid-stimulated HepG2 cells. Overall, our findings demonstrated that clitorin can be a potentially efficacious candidate for NAFLD management.

Atractylodes chinensis Water Extract Ameliorates Obesity via Promotion of the SIRT1/AMPK Expression in High-Fat Diet-Induced Obese Mice.

Obesity remains a continuing global health concern, as it is associated with an increased risk of many chronic diseases. Atractylodes chinensis Koidz. (Ac) is traditionally used in the treatment of inflammatory diseases, such as arthritis, hepatitis, and gastric ulcers. Despite the diverse pharmacological activities of Ac, scientific evidence for the use of Ac in obesity is still limited. Therefore, the present study aimed to determine the anti-obesity effects of Ac. C57BL/6N mice were divided into five groups as follows: chow diet group (CON), 45% HFD group, HFD + oral administration of orlistat group, and HFD + oral administration of Ac groups. RT-PCR and western blotting were used to examine the expression of molecules relating to obesity progression. Ac-administered mice showed dramatically decreased body weight and weight gain compared to the high-fat diet (HFD)-fed mice. In addition, Ac administration attenuated the protein expression levels of adipogenic transcription factors in the white adipose tissue (WAT) and livers of HFD-fed mice. Furthermore, Ac administration declined the expression levels of lipogenic genes, while enhancing those of the fatty acid oxidation genes in the WAT of HFD-fed mice. Importantly, Ac administration highly upregulated the AMP-activated kinase (AMPK) and sirtuin 1 (SIRT1) expression levels in WAT of the HFD-induced obese mouse model. Our results provide evidence that Ac can effectively ameliorate weight gain and adipose tissue expansion.

Therapeutic effects of Gambi-jung for the treatment of obesity.

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.

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.

Anti-Inflammatory and Antioxidant Effects of Carpesium cernuum L. Methanolic Extract in LPS-Stimulated RAW 264.7 Macrophages.

A hypernomic reaction or an abnormal inflammatory process could cause a series of diseases, such as cardiovascular disease, neurodegeneration, and cancer. Additionally, oxidative stress has been identified to induce severe tissue injury and inflammation. Carpesium cernuum L. (C. cernuum) is a Chinese folk medicine used for its anti-inflammatory, analgesic, and detoxifying properties. However, the underlying molecular mechanism of C. cernuum in inflammatory and oxidative stress conditions remains largely unknown. The aim of this study was to examine the effects of a methanolic extract of C. cernuum (CLME) on lipopolysaccharide- (LPS-) induced RAW 264.7 mouse macrophages and a sepsis mouse model. The data presented in this study indicated that CLME inhibited LPS-induced production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells. CLME treatment also reduced reactive oxygen species (ROS) generation and enhanced the expression of heme oxygenase-1 (HO-1) protein in a dose-dependent manner in the LPS-stimulated RAW 264.7 cells. Moreover, CLME treatment abolished the nuclear translocation of nuclear factor-κB (NF-κB), enhanced the activation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), and reduced the expression of extracellular signal-related kinase (ERK) and ERK kinase (MEK) phosphorylation in LPS-stimulated RAW 264.7 cells. These outcomes implied that CLME could be a potential antioxidant and anti-inflammatory agent.

The Antiobesity Effects of Buginawa in 3T3-L1 Preadipocytes and in a Mouse Model of High-Fat Diet-Induced Obesity.

There has been a remarkable interest in finding lipid inhibitors from natural products to replace synthetic compounds, and a variety of oriental medicinal herbs are reported to have biological activity with regard to lipid inhibition. Buginawa (Bugi) is a novel combined formula that contains twelve medicinal herbs with potential for weight loss induction. We hypothesized that Bugi may have antiobesity effects in 3T3-L1 preadipocytes and in a high-fat diet- (HFD-) induced mouse model. In this study, 3T3-L1 cells were treated with varied concentrations of Bugi (62.5, 125, or 250 µg/mL). Bugi treatment inhibited adipocyte differentiation by suppressing adipogenic transcription genes, including peroxisome proliferator-activated receptor γ protein (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1), and CCAAT/enhancer-binding protein ß (C/EBPß). Mice were fed a normal diet or an HFD for 11 weeks, and Bugi was simultaneously administered at 50 or 100 mg/kg. Bugi administration significantly reduced body weight gain and white adipose tissue (WAT) weight and effectively inhibited lipid droplet accumulation in epididymal white adipose tissue (eWAT) and liver tissue. Further, Bugi treatment suppressed mRNA levels of PPARγ, C/EBPα, and SREBP1 in eWAT and liver tissue. Our findings demonstrate that Bugi could be an effective candidate for preventing obesity and related metabolic disorders.

The anti-obesity effects of Tongbi-san in a high-fat diet-induced obese mouse model.

BACKGROUND: Recently, it has been noted that natural herbal medications may be effective in treating obesity. Tongbi-san (TBS) is a traditional medicine usually used for dysuria (i.e., painful urination), containing three herbs, Cyperus rotundus L., Citrus unshiu Markovich, and Poria cocos. In this study, we aimed to examine whether TBS can inhibit high-fat diet (HFD)-induced adipogenesis in the liver and epididymal adipose tissue of obese mice. METHODS: Male C57BL/6 N mice were fed a normal diet, an HFD, an HFD plus orlistat 10 or 20 mg/kg, or an HFD plus TBS 50 or 100 mg/kg for 11 weeks. Body weight was checked weekly and histological tissue examinations were investigated. An expression of genes involved in adipogenesis was also assessed. RESULTS: Oral administration of TBS significantly reduced body weight and decreased epididymal and visceral white adipose tissue (WAT) weight. In addition, we found that TBS enhanced the expression of the adenosine monophosphate-activated protein kinase (AMPK) and inhibited the expression of transcription factors, such as CCAAT/enhancer-binding proteins (C/EBPs), sterol regulatory element-binding protein 1 (SREBP1), and peroxisome proliferator-activated receptor γ (PPARγ) in the liver and epididymal WAT as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). CONCLUSION: These findings demonstrate that the anti-obesity effects of TBS may be linked to the activation of AMPK.