• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.162-167
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• 2009

Adipocytes undergo adipocyte stress in the excessive presence of lipid. Adipocyte stress accompanies the typical signs of endoplasmic reticulum (ER) stress: unfolded protein response and overexpression of molecular chaperones. Apoptotic induction in adipocytes is known as a good strategy for treating obesity. The drug "tunicamycin" was tested for its therapeutic potential in inducing apoptosis on differentiating adipocytes of 3T3-L1. When the 3T3-L1 cells, stimulated for adipogenesis, were treated with tunicamycin, they showed typical ER stress symptoms. Despite progression in ER stress, however, the differentiated 3T3-L1 hardly proceeded to apoptosis based on the CHOP protein expression and FACS analysis. This is very different from C2C12, the myogenic counterpart of 3T3-L1, which showed significant apoptosis along with ER stress. This study also characterizes a potential mechanism whereby adipocyte may avoid apoptosis to sustain the pathological state of obesity. The level of GRP94 expression significantly upholds in 3T3-L1 under tunicamycin treatment compared to preadipocytes and C2C-12. When GRP94 expression was inhibited by siRNA, 3T3-L1 showed a higher level of CHOP expression compared to C2C12 cells. In conclusion, adipocytes exert an anti-apoptotic mechanism under ER stress caused by tunicamycin; thus, apoptotic induction in adipocyte is not a viable anti-obesity option. The unusual level of GRP94 may serve as a key role whereby adipocytes reach to the obesity level circumventing the apoptosis.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.2
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• pp.43-45
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• 2016

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. Serotonin is among those traditional pharmacological targets for anti-obesity treatment because central 5-HT functions as an anorexigenic neurotransmitter in the brain. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Fat specific Tph1 knock-out (Tph1 FKO) mice exhibit similar phenotypes as mice with pharmacological inhibition of 5-HT synthesis, suggesting the localized effects of 5-HT in adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure in BAT and Htr2a KO mice exhibit the decreased lipid accumulation in WAT. These data suggest the clinical significance of the peripheral serotonergic system as a new therapeutic target for anti-obesity treatment.

• Journal of Pharmacopuncture
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• v.26 no.1
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• pp.10-17
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• 2023

Objectives: Murraya paniculata (family-Rutaceae), popularly known as orange jasmine, is the most important evergreen plant. The Rutaceae family is economically significant due to its diverse edible fruits and essential oils. Methods: Murraya paniculata extracts (MPE) of leaf have been shown to include phenolic compounds, highly oxygenated flavonoids, flavanones, sesquiterpenoids, polymethoxy glycosides, and coumarins. Cyclocitral, methyl salicylate, trans-nerolidol, cubenol, isogermacrene, -cadinol, and cubeb-11-ene are all abundant in MPE. The usages of various parts of this plant, such as bark, leaves and flower, as a remedy for a variety of ailments as widely recorded in the traditional literature. The plant has anti-diabetic, anti-obesity, antibacterial, anti-implantation, anti-oxidative, cytotoxic, anti-diarrheal, antidepressant and anti-anxiety properties and many others. Results: The goal of the review is to reignite interest in this potential plant, encouraging researchers to continue their research in order to uncover novel therapeutic compounds for the treatment and management of a range of infections. The current review provided a comprehensive overview of this traditional unique plant. Conclusion: The review paves a way for exploring its active chemical elements with substantial pharmacological values further for potential benefits of mankind.

• Journal of Applied Biological Chemistry
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• v.63 no.4
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• pp.339-345
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• 2020

Euchrestaflavanone A (EFA) is a flavonoid found in the root bark of Cudrania tricuspidata. C. tricuspidata extract, widely used throughout Asia in traditional medicine, has been investigated phytochemically and biologically and is known to have anti-obesity, anti-inflammatory, and anti-tumor effects. It has been reported that C. tricuspidata extract also possesses anti-platelet effects; however, the mechanism of its anti-platelet and anti-thrombotic activities is yet to be elucidated. In this study, we investigated the effects of EFA on the modulation of platelet function using collagen-induced human platelets. Our results showed that EFA markedly inhibited platelet aggregation. Furthermore, it downregulated glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production, and clot retraction, but upregulated the cyclic adenosine monophosphate-dependent pathway. Taken together, EFA possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.12-19
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• 2024

Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management. These compounds primarily function by activating the Akt/mTOR signaling pathway, upregulating myogenin and MyoD to induce muscle hypertrophy, downregulating atrophic factors (atrogin1, muscle ring-finger protein-1, myostatin, and mitochondrial reactive oxygen species production), and suppressing the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cachexia. Ginsenoside compounds are also used for obesity management, and their anti-obesity effects are attributed to peroxisome proliferator activated receptor gamma (PPARγ) inhibition, AMPK activation, glucose transporter type 4 (GLUT4) translocation, and increased phosphorylations of insulin resistance (IR), insulin receptor substrate-1 (IRS-1), and Akt. This review was undertaken to provide an overview of the use of ginseng-related compounds for the management of SM-related disorders.

• International Journal of Industrial Entomology and Biomaterials
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• v.21 no.2
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• pp.169-174
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• 2010

Hydrolysate silk fibroin (HSF) is a fibrous protein composed of parallel $\beta$-structures and is made from pure silk elements including 18 amino acids, with glycine, alanine, and serine comprising of over 80% of the amino acids. Numerous studies have documented a range of effects of HSF, including moisturizing, antioxidant activity, nervous system disorders, and many more. We investigated whether HSF has anti-obesity effects in vitro. The effects of HSF inhibition on lipid accumulation and acceleration of lipid degradation in 3T3-L1 cells were studied. Treatment of 3T3-L1 cells with HSF caused significant inhibition of cell viability, an increase in glycerol release, and a decreased in adipocyte differentiation. Moreover HSF stimulated downregulated of adipogenic enzyme expressions (PPAR${\gamma}$ and C/EBP${\alpha}$) and up-regulated of fatty oxidation enzyme expressions (CPT-1 and UCP-2). Based on these results, hydrolysate silk fibroin can be suggested as a potential therapeutic substance as part of a prevention or treatment strategy for obesity.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.23-34
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• 2003

Objective : In 2001, the rate of obesity in Korea reached 30.6%. There are many therapeutic ways to reduce body weight, such as low and very low calorie diet, exercise therapy, behavior modification therapy, etc. However, in many cases the patients feel stress under obesity treatment because of starvation. This study was aimed to evaluate the anti-starvation stress effect of Coicis Semen on mice. Methods : First, the mice were divided into 6 groups : Normal (group with no starvation), Control (administrated normal saline 6 times before starting 36 hours starvation), and Samples A, B, C, and D (administrated 0.25, 0.5, 1.0, 3.0 g/kg Coicis Semen respectively 6 times before starting 36 hours starvation). Then the plasma corticosterone level and rectal temperature were measured. The norepinephrine, dopamine, DOPAC (dihydroxy-phenylacetic acid), 5-HT (5-hydroxytryptamine) and 5- HIAA (5-hydroxy-indole-acetic acid) in the hypothalamus were measured by the HPLC method. Result : I. The rectal temperature in Sample group D showed a significant difference (P<0.05) compared with the Control group. 2. The DOPAC in Sample groups A, C and D showed the significant difference (P<0.05) compared with the Control group. Conclusion : It might be recognized that Coicis Semen has an anti-starvation stress effect.

• Journal of the Korea Convergence Society
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• v.10 no.3
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• pp.127-133
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• 2019

The ami of our study was on the anti-obesity effect of ethanol extract from Trichosanthes kirilowii Maxim root (TKM) in murine adipocytes, 3T3-L1 cells. This study focused on anti-adipogenic activity through inhibition of cell differentiation in 3T3-L1 cells treated TKM. 100 ug/ml of non-cytotoxic TEM remarkablely inhibited content of triglycerol and suppressed expressions of $C/EBP{\alpha}$, $PPAR{\gamma}a$ and SREBP-1c related with lipogenic transcription factors in theres 3T3-L1 cells compared to (-)control cells. As phosphorylations of AMPK and ACC were incerased, HSL and CPT-1 mRNA expression increased upon TKM treatment, which involved in inhibition of fatty acid synthase expression. In conclusion, these results indicate that TKM can inhibit mRNA and protein expression of lipogenic genes in 3T3-L1 adipocytes. Our study suggests that TKM has potential anti-obesity effects and is a convergence therapeutic functional agent with anti-adipogenic activity via hypolipogenesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.2
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• pp.75-80
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• 2020

In this study, we investigated the dose-dependent effects of mixtures of Atractylodes macrocephala (AM) and Amomum villosum (AV) water extracts in a ratio of 3:1 on high fat diet (HFD)-induced obesity model. Oral administration of various concentrations with mixtures of AM and AV extracts in a ratio of 3:1 for 6 weeks inhibited HFD-induced increases of body, liver and epididymal fat weights in a dose-dependent fashions. Those effects may be mediated by decreased expressions of lipogenesis-related genes such as acetyl coA carboxylase (ACC) and fatty acid synthase (FAS) in liver. Also, increase of insulin and decrease of adiponectin in serum by HFD supply were inhibited by three different dosages of mixtures of AM and AV extracts in a ratio of 3:1. HFD supply induced increases of serum total cholesterol, triglyceride and LDL cholesterol. However, hyperlipidemia was significantly decreased in dose-dependent manners by treatment with mixtures of AM and AV extracts. Based on the results of the present study, hypolipidemic and anti-obesity effects by mixtures of AM and AV extracts were found in HFD-induced obesity model. Further clinical investigation is needed to develop anti-obesity therapeutic or preventive agents by using mixtures of AM and AV extracts.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.107-116
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• 2019

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.