• Biomedical Science Letters
• /
• v.23 no.3
• /
• pp.261-271
• /
• 2017

It has been suggested that ginseng is beneficial for ameliorating the aging males' symptoms, such as weight gain, fatigue, erectile dysfunction, and depression, in elderly men with testosterone deficiency. We thus investigated the effects of Korean red ginseng (Panax ginseng C.A. Meyer; Araliaceae) on obesity in a mouse model of testosterone deficiency (castrated C57BL/6J mice). The effects of ginseng extract (GE) and/or testosterone on obesity and adipogenesis in high-fat diet (HFD)-fed castrated C57BL/6J mice and 3T3-L1 adipocytes were examined using in vivo and in vitro approaches. After feeding mice a HFD for 8 weeks, we found that mice also receiving GE and/or testosterone showed decreased body weight, adipose tissue mass, adipocyte size, and hepatic lipid accumulation compared with untreated HFD-fed mice. Expression of adipogenic genes ($PPAR{\gamma}$, $C/EBP{\alpha}$, and aP2) was decreased by GE and/or testosterone in adipose tissues. Consistent with the in vivo data, lipid accumulation and the mRNA expression of adipogenesis genes in 3T3-L1 adipocytes were decreased by GE, ginsenosides, and testosterone. The inhibitory effects of GE (or ginsenosides) were comparable to those of testosterone, and the effects of co-treatment with GE (or ginsenosides) and testosterone were greater than those of testosterone alone in vivo and in vitro. Our results indicate that ginseng may be able to potentiate the inhibitory effects of testosterone on obesity and adipogenesis in HFD-fed castrated mice, providing possible therapeutic implications in men with testosterone deficiency.

• Journal of Ginseng Research
• /
• v.40 no.2
• /
• pp.141-150
• /
• 2016

Background: Adipocyte-macrophage communication plays a critical role regulating white adipose tissue (WAT) inflammatory gene expression. Because WAT inflammation contributes to the development of metabolic diseases, there is significant interest in understanding how exogenous compounds regulate the adipocyte-macrophage crosstalk. An aqueous (AQ) extract of North American (NA) ginseng (Panax quinquefolius) was previously shown to have strong inflammo-regulatory properties in adipocytes. This study examined whether different ginseng extracts influence adipocyte-macrophage crosstalk, as well as WAT inflammatory gene expression. Methods: The effects of AQ and ethanol (EtOH) ginseng extracts ($5{\mu}g/mL$) on adipocyte and macrophage inflammatory gene expression were studied in 3T3-L1 and RAW264.7 cells, respectively, using real-time reverse transcription polymerase chain reaction. Adipose tissue organ culture was also used to examine the effects of ginseng extracts on epididymal WAT (EWAT) and inguinal subcutaneous WAT (SWAT) inflammatory gene expression. Results: The AQ extract caused significant increases in the expression of common inflammatory genes (e.g., Mcp1, Ccl5, Tnf-${\alpha}$, Nos2) in both cell types. Culturing adipocytes in media from macrophages treated with the AQ extract, and vice versa, also induced inflammatory gene expression. Adipocyte Ppar-${\gamma}$ expression was reduced with the AQ extract. The AQ extract strongly induced inflammatory gene expression in EWAT, but not in SWAT. The EtOH extract had no effect on inflammatory gene expression in either both cell types or WAT. Conclusion: These findings provide important new insights into the inflammo-regulatory role of NA ginseng in WAT.

• The Journal of Korean Medicine
• /
• v.28 no.2 s.70
• /
• pp.185-199
• /
• 2007

Objectives : This study was carried out to investigate the inhibitive effect of a combined-herb prescription of Dansam-san (DSS) on formation of foam cells and cytokine. Methods : Experimental formation of foam cells was induced on macrophage RAW 264.7 with ox-LDL. The effect of DSS extract was observed by measuring the changes of CD36, $PPAR-{\Gamma}$, MMP-9, iNOS expression and changes of formation level of foam cells after treating experimentally induced foam cells with DSS extract. Then the antioxidative effect of DSS extract was compared with butylated hydroxyanisole (BHA). Result and Conclusions : Results obtained are as follows: 1. DSS extract showed significant antioxidative effect at 8 mg/ml or more. 2. DSS extract inhibited the formation of foam cells. 3. DSS extract inhibited the creation and revelation of conversion-related material about foam cells. 4. DSS extract prohibited the increase of smooth muscle of vessels.

• Nutrition Research and Practice
• /
• v.8 no.1
• /
• pp.33-39
• /
• 2014

Obesity occurs when a person's calorie intake exceeds the amount of energy burns, which may lead to pathologic growth of adipocytes and the accumulation of fat in the tissues. In this study, the effect and mechanism of pear pomace extracts on 3T3-L1 adipocyte differentiation and apoptosis of mature adipocytes were investigated. The effects of pear pomace extract on cell viability and the anti-adipogenic and proapoptotic effects were investigated via MTT assay, Oil red O staining, western blot analysis and apoptosis assay. 3T3-L1 preadipocytes were stimulated with DMEM containing 10% FBS, 0.5 mM 3-isobutyl-1-methylxanthine (IBMX), $5{\mu}g/ml$ insulin and $1{\mu}M$ dexamethasone for differentiation to adipocytes. 3T3-L1 cells were cultured with PBS or water extract of pear pomace. Water extract of pear pomace effectively inhibited lipid accumulations and expressions of PPAR-${\gamma}$ and $C/EBP{\alpha}$ in 3T3-L1 cells. It also increased expression of p-AMPK and decreased the expression of SREBP-1c and FAS in 3T3-L1 cells. The induction of apoptosis was observed in 3T3-L1 cells treated with pear pomace. These results indicate that pear pomace water extract inhibits adipogenesis and induces apoptosis of adipocytes and thus can be used as a potential therapeutic substance as part of prevention or treatment strategy for obesity.

• BMB Reports
• /
• v.53 no.4
• /
• pp.212-217
• /
• 2020

Activation of peroxisome proliferator-activated receptor γ (PPARγ) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and over-expressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPARγ. In this study, we investigated the effects of induction of HO-1 by PPARγ on TPA-induced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-κB /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ₂, a natural PPARγ ligand. 15d-PGJ₂ induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ₂. These results suggest that 15d-PGJ₂ inhibits TPA-induced MMP-9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPARγ/HO-1 signaling-pathway inhibition may be beneficial for prevention and treatment of breast cancer.

• The Journal of Pediatrics of Korean Medicine
• /
• v.24 no.3
• /
• pp.92-105
• /
• 2010

Objectives: The purpose of this study is to investigate the effects of Daecheongryong-tang (DCRT) on the adipogenesis in 3T3-L1 preadipocytes. Methods: 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 2 days in the absence or presence of DCRT ranging 0.25 and 2%. The effect of DCRT on adipogenesis was examined by Oil red O staining, and the protein, RNA, and RT-PCR were measured. Results: Our results showed that DCRT decreased the TG content by ORO staining. To elucidate the mechanism of the effects of DCRT on lowering TG content in 3T3-L1 adipocytes, we examined the DCRT modulate expressions of transcription factors to induce adipogenesis and adipogenic genes which is related to the regulation of accumulation of lipids. As a result, the expression of SREBP1, C/$EBP{\beta}$, C/$EBP{\delta}$, C/$EBP{\alpha}$, and $PPAR{\gamma}$ genes, which induce the adipose differentiation and adipose-specific aP2, adipsin, LPL, CD36, TGF-${\beta}$ and adiponectin genes which regulates fat formations, were decreased. In addition, DCRT reduced the expression of iNOS and IL-6 in 3T3-L1 adipocytes, resulting in inflammation. Conclusions: DCRT could regulate transcript factor related to induction of adipose differentiation, inhibit the accumulation of lipids and expression of the adipogenic genes.

• Journal of Pharmacopuncture
• /
• v.20 no.3
• /
• pp.158-172
• /
• 2017

Nigella sativa (N. sativa, family Ranunculaceae) is a medicinal plant that has been widely used for centuries throughout the world as a natural remedy. A wide range of chemical compounds found in N. sativa expresses its vast therapeutic effects. Thymoquinone (TQ) is the main component (up to 50%) in the essential oil of N. sativa. Also, pinene (up to 15%), p-cymene (40%), thymohydroquinone (THQ), thymol (THY), and dithymoquinone (DTQ) are other pharmacologically active compounds of its oil. Other terpenoid compounds, such as carvacrol, carvone, 4-terpineol, limonenes, and citronellol, are also found in small quantities in its oil. The main pharmacological characteristics of this plant are immune system stimulatory, anti-inflammatory, hypotensive, hepatoprotective, antioxidant, anti-cancer, hypoglycemic, anti-tussive, milk production, uricosuric, choleretic, anti-fertility, and spasmolytic properties. In this regard, we have searched the scientific databases PubMed, Web of Science, and Google Scholar with keywords of N. sativa, anti-cancer, apoptotic effect, antitumor, antioxidant, and malignancy over the period from 2000 to 2017. The effectiveness of N. sativa against cancer in the blood system, kidneys, lungs, prostate, liver, and breast and on many malignant cell lines has been shown in many studies, but the molecular mechanisms behind that anti-cancer role are still not clearly understood. From among the many effects of N. sativa, including its anti-proliferative effect, cell cycle arrest, apoptosis induction, ROS generation, anti-metastasis/anti-angiogenesis effects, Akt pathway control, modulation of multiple molecular targets, including p53, p73, STAT-3, PTEN, and $PPAR-{\gamma}$, and activation of caspases, the main suggestive anti-cancer mechanisms of N. sativa are its free radical scavenger activity and the preservation of various anti-oxidant enzyme activities, such as glutathione peroxidase, catalase, and glutathione-S-transferase. In this review, we highlight the molecular mechanisms of apoptosis and the anti-cancer effects of N. sativa, with a focus on its molecular targets in apoptosis pathways.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.31 no.2
• /
• pp.49-67
• /
• 2018

Objectives: This study was conducted to assess the effects of Hwanggimacmundong-tang extract (HM) on obese rats with estrogen deficiency. Methods: The experiments were performed with ovariectomized rats as estrogen-deficient obesity model. Rats were grouped NC (Normal Control Group; sham operation group), OC (Obesity Control Group; estrogen-deficient group), HML (20 mg/kg/day), HMH (100 mg/kg/day). HM was administered orally for six weeks. Body weights and serum lipid level were measured, and real-time PCR was performed to estimate the effect of HM on gene expression in liver. Results: HM decreased the total cholesterol and triglyceride in serum. And HM increased leptin, CPT1 gene expression in liver tissue of obese rats with estrogen deficiency. However HM decreased $PPAR{\gamma}$, $PGC-1{\alpha}$, HMGCR, CYP8B1, LPL, ACAT1, ACAT2, ApoB, ACOX gene expression in liver tissue of obese rats with estrogen deficiency. Conclusions: It is concluded that HM reduced total cholesterol and triglyceride in serum, and regulate gene expression related to lipid metabolism. These results indicate Hwanggimacmundong-tang that might have potential for treatment of obesity and complications during the menopause caused by estrogen-deficiency.

• Journal of Sasang Constitutional Medicine
• /
• v.29 no.2
• /
• pp.136-153
• /
• 2017

Objectives This experimental study was designed to investigate the effect of Phaseolus angularis shell on metabolic syndrome. Methods Each 5 C57BL/6J mice were randomly assigned to normal diet group, high-fat diet(HFD) control group, high-fat diet plus 15.6 mg/kg/day of Orlistat(HFD-Orlistat) group, high-fat diet plus 100mg/kg/day of Phaseolus angularis shell extract(HFD-PAS_E) group. Weight, the blood chemical and hematologic parameter was med. The mRNA expression was assayed through Reverse transcriptase polymerase chain reaction(RT-PCR). Results In HFD-PAS_E group, the body weight gain, weight of liver, and the level of LDL-Cholesterol were significantly decreased and the level of HDL-Cholesterol were significantly increased. The size of adipocyte in HFD-PAS_E group was smaller than HFD group's. In HFD-PAS_E group, the expression of leptin, PPAR-${\gamma}$, AP2/FABP4 mRNA in liver adipocyte tissue was decreased, the expression of Adiponectin, UCP-2 mRNA in liver adipocyte tissue was increased and the expression of Leptin, C/EBP-a, AP2/FABP4 mRNA in epididymal adipocyte tissue was decreased. Conclusion These results suggest that Phaseolus angularis shell has inhibitory effects on metabolic syndrome by reducing the body weight and the levels of lipid contents in high-fat-diet induced obese mice.

• Animal cells and systems
• /
• v.16 no.2
• /
• pp.87-94
• /
• 2012

Nur77 is a member of the nuclear receptor 4A (NR4A) subgroup, which has been implicated in energy metabolism. Although Nur77 is found in adipose tissue, where TR4 plays a key role in lipid homeostasis, the role of Nur77 in adipogenesis is still controversial. Although the Nur77 responsive element (AAAGGTCA) is partially overlapped with TR4-binding sites (AGGTCA $n$ AGGTCA: $n$=0-6), the regulatory role of Nur77 in TR4 function associated with adipocyte biology remains unclear. Here, we found that Nur77 inhibits adipogenesis and TR4 transcriptional activity. Treatment with a Nur77 agonist, 1,1-bis(3'-indolyl)-1-($p$-anisyl)-methane, during 3T3-L1 adipocyte differentiation reduced adipogenesis. In reporter gene analysis, Nur77 specifically suppressed TR4 transcription activity but had little effect on $PPAR{\gamma}$ transcription activity. Consistently, Nur77 also suppressed TR4-induced promoter activity of the TR4 target gene PEPCK, which is known to be important for glyceroneogenesis in adipose tissue. Furthermore, Nur77 suppressed TR4 binding to TR4 response elements without direct interaction with TR4, suggesting that Nur77 may inhibit TR4 transcription activity via binding competition for TR4-binding sites. Furthermore, DIM-C-$pPhOCH_3$ substantially suppressed TR4-induced PEPCK expression in 3T3-L1 adipocytes. Together, our data demonstrate that Nur77 plays an inhibitory role in TR4-induced PEPCK expression in 3T3-L1 adipocytes.