ABSTRACT
INTRODUCTION: Eczema and contact dermatitis are relatively common, non-life-threatening disease, but can reduce the patient's quality-of-life when it becomes chronic. This study describes two cases of bee venom acupuncture (BVA) and herbal medicine (San Wu Huangqin decoction; SWH) co-treatment for hand eczema and contact dermatitis, then confirms the effect of the combination therapy in an in vivo model of eczema. CASE PRESENTATION: A 56-year-old female (case 1) and a 33-year-old male (case 2) presented to the clinic with symptoms of itching and erythema (case 1), and scaliness (case 2) on both hands. Both were diagnosed with hand eczema and contact dermatitis based on examination of the erythema and scaliness. They were treated with BVA and SWH for three months. The lesions were healed and had not recurred after 1 and 3 years of follow-up. A mouse study was conducted by repeated application of 2,4-dinitrochlorobenzene (DNCB) to induce eczema-like contact dermatitis in Balb/c mice. In a DNCB-induced eczema-like contact dermatitis model, BVA and SWH co-administration synergistically improved clinical symptoms seen in eczema. Also, they improved histological changes of the skin, suppressed immune cell infiltration, and decreased inflammatory cytokines and immunoglobulin E in the serum. CONCLUSION: This study suggests BVA and SWH could be an alternative treatment for eczema and contact dermatitis.
Subject(s)
Acupuncture Therapy , Bee Venoms , Eczema , Humans , Male , Bee Venoms/therapeutic use , Middle Aged , Acupuncture Therapy/methods , Adult , Animals , Eczema/drug therapy , Eczema/therapy , Female , Mice , Drugs, Chinese Herbal/therapeutic use , Mice, Inbred BALB C , Dermatitis, Contact/drug therapy , Dermatitis, Contact/therapy , Combined Modality Therapy , Hand Dermatoses/drug therapy , Hand Dermatoses/therapy , DinitrochlorobenzeneABSTRACT
The enormous library of natural products and herbal medicine prescriptions presents endless research avenues. However, the lack of research evidence and trials on cancer-induced cachexia limit the therapeutic potential of natural products. Cancer-induced cachexia is a systemic wasting syndrome characterized by continuous body weight loss with skeletal muscle and adipose tissue atrophy. Cancer cachexia is a problem in itself and reduces the quality of life by lessening the treatment efficacy of anticancer drugs. This review summarizes single natural product extracts for cancer-induced cachexia, not compounds derived from natural products and herbal medicine prescriptions. This article also discusses the effect of natural products on cachexia induced by anticancer drugs and the role of AMPK in cancer-induced cachexia. The article included the mice model used in each experiment to encourage researchers to utilize animal models for research on cancer-induced cachexia in the future.
Subject(s)
Antineoplastic Agents , Neoplasms , Mice , Animals , Cachexia/drug therapy , Cachexia/etiology , Cachexia/pathology , Quality of Life , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/pathology , Muscle, Skeletal/pathology , Antineoplastic Agents/pharmacology , Plant Extracts/pharmacology , Muscular Atrophy/pathologyABSTRACT
Panax ginseng C.A. Meyer, a widely used traditional medicine in East Asia, shows many beneficial effects on immune function, male erectile dysfunction, cancer, excessive oxidants, and aging issues. However, its effect on benign prostatic hyperplasia (BPH) and its potential in the treatment of side effects related to finasteride (Fi), an FDA-approved drug for BPH, are less known. This study aimed to verify the therapeutic effects of a water extract of P. ginseng (PGWE) on BPH in testosterone propionate (TP)-induced BPH rats and TP-treated RWPE-1 human epithelial cells, and the inhibitory potential on the Fi-induced side effects is also explored. In the TP-induced BPH rat model, PGWE alleviated the pathological markers of BPH such as weight and epithelial thickness of the prostate, and the serum level of dihydrotestosterone. PGWE downregulated androgen-related BPH factors such as 5α-reductase 2 and androgen receptor. PGWE also showed prostatic cell apoptosis accompanied by increased expression of Bax and decreased expression of Bcl-xL and cleaved-caspase 3, respectively, in addition to increasing mitochondrial dynamics in both in vivo and in vitro BPH models. Notably, reduced sperm count, one of the serious side effects of Fi, in the epididymis of BPH rats was recovered with PGWE treatment, suggesting less toxicity to sperm development by PGWE. PGWE also protected against Fi-induced sperm loss when PGWE was administered in combination with Fi without compromising the therapeutic effects of Fi on BPH. Based on these findings, we propose that PGWE could be an alternative therapeutic agent for BPH.
ABSTRACT
BACKGROUND: Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources. PURPOSE: In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis. METHODS: To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells. RESULTS: In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity. CONCLUSION: These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.
Subject(s)
Glycyrrhiza uralensis , Prostatic Hyperplasia , Testosterone Propionate , Animals , Apoptosis , Cholestenone 5 alpha-Reductase , Humans , Male , Plant Extracts , Rats , Rats, Sprague-Dawley , Seeds , TestosteroneABSTRACT
Benign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3. To investigate the effect of EA on BPH, we used EA, a phytochemical abundant in fruits and vegetables, to treat testosterone propionate (TP)-induced BPH rats and RWPE-1 human prostate epithelial cells. The EA treatment reduced prostate weight, prostate epithelial thickness, and serum DHT levels in the TP-induced BPH rat model. In addition, EA improved testicular injury by increasing antioxidant enzymes in testis of the BPH rats. EA reduced the protein levels of AR, 5AR2, and PSA. It also induced apoptosis by regulating Bax, Bcl_xL, cytochrome c, caspase 9, and caspase 3 with increasing mitochondrial dynamics. Furthermore, EA reduced the expression of IL-6, TNF-α, and NF-κB, as well as phosphorylation of STAT3 and IκBα. These findings were also confirmed in TP-treated RWPE-1 cells. Overall, our data provide evidence of the role of EA in improving BPH through inhibition of AR and the STAT3 pathway.
Subject(s)
Prostatic Hyperplasia , Testosterone Propionate , Androgens/pharmacology , Animals , Ellagic Acid/adverse effects , Humans , Hyperplasia/pathology , Male , Plant Extracts/pharmacology , Prostate/metabolism , Prostatic Hyperplasia/chemically induced , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism , Rats , Rats, Sprague-Dawley , STAT3 Transcription Factor/metabolism , Testosterone Propionate/adverse effectsABSTRACT
BACKGROUND: Obesity has become a serious global health problem due to its increasing prevalence. Because of several limitations or adverse events associated with conventional western medicine therapies, there has been an increase in demand for alternative therapies such as traditional East Asian medicine (TEAM). This study aims to provide comprehensive evidence-based information assessing the clinical efficacy and safety of TEAM treatment for obesity as the basis for reliable clinical strategies for patients with obesity. METHODS: Electronic searches of the PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure, OASIS, and Korea Citation Index will be performed. Methodological quality will be assessed using the "risk of bias" tool. The primary outcome for efficacy will be weight loss. The secondary outcomes will be response rate, body mass index, waist circumference, and blood pressure. We will also evaluate the rates of adverse events and mortality for safety assessment. First, we will conduct a conventional pairwise meta-analysis. Next, we will conduct network meta-analysis using the frequentist approach. We shall verify the assumption of network meta-analysis and provide network geometry, P-score, net league table, and intervention-based forest plot. A subgroup analysis will be conducted to ascertain the factors that affect treatment, such as dosage, treatment duration, and severity of obesity. RESULTS: The results of this study will provide high-quality systematic reviews that can assist decision making in obesity management. Our network meta-analysis results can provide direct and indirect comparison evidence on comparative efficacy and safety. CONCLUSION: This study will provide fundamental data for prospective research on the application of TEAM in patients with obesity. PROTOCOL REGISTRY NUMBER OF ONLINE REGISTRY: This study protocol was registered in open Science framework (OSF) (Registration DOI: 10.17605/OSF.IO/ETWDS). URL OF THE ONLINE REGISTRY: https://osf.io/etwds.
Subject(s)
Acupuncture Therapy , Medicine, East Asian Traditional , Obesity/therapy , Complementary Therapies , Herbal Medicine , Humans , Meta-Analysis as Topic , Network Meta-Analysis , Prospective Studies , Treatment OutcomeABSTRACT
In this study, we investigated the pharmacological effect of a water extract of Raphani Semen (RSWE) on alcoholic fatty liver disease (AFLD) using ethanol-induced AFLD mice (the NIAAA model) and palmitic acid (PA)-induced steatosis HepG2 cells. An RSWE supplement improved serum and hepatic triglyceride (TG) levels of AFLD mice, as well as their liver histological structure. To explore the molecular action of RSWE in the improvement of AFLD, we investigated the effect of RSWE on four major pathways for lipid homeostasis in the liver: free fatty acid transport, lipogenesis, lipolysis, and ß-oxidation. Importantly, RSWE decreased the mRNA expression of de novo lipogenesis-related genes, such as Srebf1, Cebpa, Pparg, and Lpin1, as well as the protein levels of these factors, in the liver of AFLD mice. That these actions of RSWE affect lipogenesis was confirmed using PA-induced steatosis HepG2 cells. Overall, our findings suggest that RSWE has the potential for improvement of AFLD by inhibiting de novo lipogenesis.
Subject(s)
Fatty Liver, Alcoholic/drug therapy , Lipogenesis/drug effects , Plant Extracts/pharmacology , Raphanus/chemistry , Seeds/chemistry , Animals , Ethanol/adverse effects , Fatty Acids, Nonesterified/metabolism , Fatty Liver, Alcoholic/metabolism , Hep G2 Cells , Humans , Lipid Metabolism/drug effects , Lipolysis/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Oxidation-Reduction/drug effects , Palmitic Acid/adverse effects , Phosphatidate Phosphatase/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , Triglycerides/bloodABSTRACT
Lung cancer is the largest cause of cancer-induced deaths. Non-small cell lung cancer (NSCLC) is the most frequently observed subtype of lung cancer. Although recent studies have provided many therapeutic options, there is still a need for effective and safe treatments. This paper reports the combined effects of cinnamaldehyde (CNM), a flavonoid from cinnamon, together with hyperthermia, a therapeutic option for cancer treatment, on the A549 NSCLC cell line. A hyperthermia treatment of 43 °C potentiated the cytotoxicity of CNM in A549 cells. This was attributed to an increase in the apoptosis markers and suppression of the survival/protective factors, as confirmed by Western blot assays. Flow cytometry supported this result because the apoptotic profile, cell health profile, and cell cycle profile were regulated by CNM and hyperthermia combination therapy. The changes in reactive oxygen species (ROS) and its downstream target pathway, mitogen-activated protein kinases (MAPK), were evaluated. The CNM and hyperthermia combination increased the generation of ROS and MAPK phosphorylation. N-acetylcysteine (NAC), a ROS inhibitor, abolished the apoptotic events caused by CNM and hyperthermia co-treatment, suggesting that the cytotoxic effect was dependent of ROS signaling. Therefore, we suggest CNM and hyperthermia combination as an effective therapeutic option for the NSCLC treatment.
Subject(s)
Acrolein/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/metabolism , Hyperthermia, Induced/methods , JNK Mitogen-Activated Protein Kinases/metabolism , Lung Neoplasms/metabolism , Reactive Oxygen Species/metabolism , A549 Cells , Acetylcysteine/pharmacology , Acrolein/pharmacology , Carcinoma, Non-Small-Cell Lung/therapy , Cell Cycle/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Combined Modality Therapy , Drug Screening Assays, Antitumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , Lung Neoplasms/therapy , MAP Kinase Signaling System/drug effects , Phosphorylation/drug effectsABSTRACT
Secoisolariciresinol diglucoside (SDG) is the main phytoestrogen component of flaxseed known as an antioxidant. Current study focused on the effect of SDG in white adipose tissue (WAT) browning. Browning of WAT is considered as a promising treatment strategy for metabolic diseases. To demonstrate the effect of SDG as an inducer of browning, brown adipocyte markers were investigated in inguinal WAT (iWAT) of high fat diet-fed obese mice and genetically obese db/db mice after SDG administration. SDG increased thermogenic factors such as uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha and PR domain containing 16 in iWAT and brown adipose tissue (BAT) of mice. Similar results were shown in beige-induced 3T3-L1 adipocytes and primary cultured brown adipocytes. Furthermore, SDG increased factors of mitochondrial biogenesis and activation. We also observed SDG-induced alteration of AMP-activated protein kinase α (AMPKα). As AMPKα is closely related in the regulation of adipogenesis and thermogenesis, we then evaluated the effect of SDG in AMPKα-inhibited conditions. Genetic or chemical inhibition of AMPKα demonstrated that the role of SDG on browning and thermogenesis was dependent on AMPKα signaling. In conclusion, our data suggest SDG as a potential candidate for improvement of obesity and other metabolic disorders.
Subject(s)
AMP-Activated Protein Kinases/drug effects , Adipose Tissue, Brown/drug effects , Adipose Tissue, White/drug effects , Butylene Glycols/pharmacology , Glucosides/pharmacology , Phytoestrogens/pharmacology , Signal Transduction/drug effects , Thermogenesis/drug effects , 3T3-L1 Cells , Adipocytes, Brown/drug effects , Animals , Diet, High-Fat , Glucose Tolerance Test , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Organelle BiogenesisABSTRACT
Brown adipocytes, which contain abundant mitochondria, use stored energy as fuel during a process named nonshivering thermogenesis. Thus, the pharmacological activation of thermogenesis in brown adipose tissue (BAT) has become a promising target for treating obesity. We investigated the effect of fruit of Hovenial dulcis Thunb. (FHD), a frequently used herbal treatment for liver diseases, on thermogenesis and its mechanism using primary cultured brown adipocytes and BAT of high-fat-diet (HFD)-induced obese mice. Thermogenesis-related factors including UCP1 and PGC1α increased with FHD treatment. FHD also increased mitochondrial biogenesis and activation factors such as nuclear respiratory factor (NRF)1 and oxidative phosphorylation (OXPHOS) complex. Furthermore, FHD increased the intercellular nicotinamide adenine dinucleotide (NAD+) level and sirtuin 1 (SIRT1) activity, which may be responsible for the activation of the thermogenic reaction. Overall, our results suggest that FHD can be a novel option for obesity treatment due to its thermogenic action through mitochondrial biogenesis and activation.
Subject(s)
Adipocytes, Brown/drug effects , Mitochondria/metabolism , Obesity/drug therapy , Plant Extracts/administration & dosage , Rhamnaceae/chemistry , Thermogenesis/drug effects , Adipocytes, Brown/metabolism , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Animals , Diet, High-Fat/adverse effects , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Mitochondria/drug effects , Obesity/etiology , Obesity/genetics , Obesity/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolism , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolismABSTRACT
BACKGROUNDS: Ephedrae Herba is widely used to treat obesity. There is a concern for adverse events (AEs) using it and we need to develop strategies to attenuate it without its effectiveness for weight-reducing potential. We investigated the effects of a combination of Ephedra Herba with Zhizichi decoction and Phellodendri Cortex (Anmyungambi (AMGB) decoction) in reducing the incidence of Ephedra Herba-related AEs. METHODS: We performed a retrospective chart review from a clinical case series of patients visiting the Jaonmi Korean Medicine Clinic (Seoul, Korea). The inclusion criteria was patients who were prescribed AMGB decoction, (containing Ephedrae Herba, Phellodendri Cortex, and Zhizichi decoction [Gardeniae Fructus, and Glycine Semen Preparata] in different proportions) for weight reduction. Exclusion of Phellodendri Cortex in the original AMGB preparation was allowed; conventional medications, acupuncture, and dietary supplements were not allowed. The primary outcome was absolute weight loss at the end of treatment. RESULTS: Twenty-seven patients (6 men and 21 women), aged 18-75 years (mean age, 42.6 ± 11.1 years) and the average treatment duration was 39.4 days. Absolute weight loss at the end of treatment was 4.49 ± 2.40 kg. Fifteen patients lost more than 5% weight (55.6%). Treatment >45 days resulted in significantly greater weight loss compared to treatment <30 days (p < 0.001). Not severe AEs were reported in 16 patients including constipation, fatigue, etc. CONCLUSION: A combination of Ephedra Herba with Zhizichi decoction and Phellodendri Cortex may be a safe and effective treatment for weight reduction in obese and overweight patients.
ABSTRACT
BACKGROUND: Gomisin A (G.A), a lignan compound extracted from the fruits of Schisandra chinensis, is known to exert anti-tumor effects on hepatocarcinoma and colorectal cancer cells. Suppression of proliferation and metastatic abilities of cancer cells are some effective cancer treatment methods. PURPOSE: The objective of this study is to investigate the effects of G.A on metastatic melanoma, and the mechanism by which it affects metastatic melanoma. STUDY DESIGN: The anti-proliferative and anti-metastatic effects of G.A were observed in in vitro and in vivo. METHODS: WST assay and flow cytometry were conducted to investigate the effect of G.A on proliferation, cell cycle arrest, and apoptosis in metastatic melanoma cell lines. Migration and invasion abilities of G.A-treated melanoma cells were observed by wound healing and invasion assays. RESULTS: G.A (25-100 µM) decreased the viability of melanoma cells by inducing cell cycle arrest and apoptosis. These anti-proliferative effects of G.A were found to be mediated by AMPK, ERK, and JNK activation. G.A (5-20 µM) decreased the migration and invasion of melanoma cells by suppressing epithelial-mesenchymal transition (EMT). Consequently, G.A (2-50 mg/kg) inhibited lung metastasis by suppressing EMT and inducing cell cycle arrest and apoptosis in melanoma cells. CONCLUSION: These results conclude that G.A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cyclooctanes/pharmacology , Dioxoles/pharmacology , Lignans/pharmacology , Melanoma/drug therapy , Melanoma/pathology , AMP-Activated Protein Kinases/antagonists & inhibitors , AMP-Activated Protein Kinases/metabolism , Animals , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Epithelial-Mesenchymal Transition/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , MAP Kinase Kinase 4/metabolism , Melanoma/metabolism , Mice, Inbred C57BL , Xenograft Model Antitumor AssaysABSTRACT
The alteration of white adipose tissue (WAT) "browning", a change of white into beige fat, has been considered as a new therapeutic strategy to treat obesity. In this study, we investigated the browning effect of black raspberry (Rubus coreanus Miquel) using in vitro and in vivo models. Black raspberry water extract (BRWE) treatment inhibited lipid accumulation in human mesenchymal stem cells (hMSCs) and zebrafish. To evaluate the thermogenic activity, BRWE was orally administered for 2 weeks, and then, the mice were placed in a 4 °C environment. As a result, BRWE treatment increased rectal temperature and inguinal WAT (iWAT) thermogenesis by inducing the expression of beige fat specific markers such as PR domain zinc-finger protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and t-box protein 1 (TBX1) in cold-exposed mice. Furthermore, ellagic acid (EA), a constituent of BRWE, markedly promoted beige specific markers: UCP1, PGC1α, TBX1, and nuclear respiratory factor 1 in beige differentiation media (DM)-induced 3T3-L1 adipocytes. Our findings indicate that BRWE can promote beige differentiation/activation, and EA is the active compound responsible for such effect. Thus, we suggest the nature-derived agents BRWE and EA as potential agents for obesity treatment.
Subject(s)
Adipocytes, Beige/drug effects , Adipocytes, White/drug effects , Adipogenesis/drug effects , Adipose Tissue, Beige/drug effects , Adipose Tissue, White/drug effects , Anti-Obesity Agents/pharmacology , Plant Extracts/pharmacology , Thermogenesis/drug effects , 3T3-L1 Cells , Adipocytes, Beige/metabolism , Adipocytes, White/metabolism , Adipose Tissue, Beige/metabolism , Adipose Tissue, White/metabolism , Animals , Anti-Obesity Agents/isolation & purification , Cold Temperature , Gene Expression Regulation , Humans , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred C57BL , Plant Extracts/isolation & purification , Rubus/chemistry , Signal Transduction , ZebrafishABSTRACT
Obesity is a global health threat. Herein, we evaluated the underlying mechanism of anti-obese features of bitter orange (Citrus aurantium Linné, CA). Eight-week-administration of CA in high fat diet-induced obese C57BL/6 mice resulted in a significant decrease of body weight, adipose tissue weight and serum cholesterol. In further in vitro studies, we observed decreased lipid droplets in CA-treated 3T3-L1 adipocytes. Suppressed peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha indicated CA-inhibited adipogenesis. Moreover, CA-treated primary cultured brown adipocytes displayed increased differentiation associated with elevation of thermogenic factors including uncoupling protein 1 and PPARγ coactivator 1 alpha as well. The effects of CA in both adipocytes were abolished in AMP-activated protein kinase alpha (AMPKα)-suppressed environments, suggesting the anti-adipogenic and pro-thermogenic actions of CA were dependent on AMPKα pathway. In conclusion, our results suggest CA as a potential anti-obese agent which regulates adipogenesis and thermogenesis via AMPKα.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adipogenesis/drug effects , Adipose Tissue/drug effects , Anti-Obesity Agents/pharmacology , Citrus , Diet, High-Fat , Obesity/drug therapy , Plant Extracts/pharmacology , Thermogenesis/drug effects , 3T3-L1 Cells , Adipocytes, Brown/drug effects , Adipocytes, Brown/enzymology , Adipocytes, White/drug effects , Adipocytes, White/enzymology , Adipose Tissue/enzymology , Adipose Tissue/physiopathology , Animals , Anti-Obesity Agents/isolation & purification , Citrus/chemistry , Disease Models, Animal , Enzyme Activation , Male , Mice , Mice, Inbred C57BL , Obesity/enzymology , Obesity/physiopathology , Plant Extracts/isolation & purification , Signal TransductionABSTRACT
Benign prostatic hyperplasia (BPH) is a common disease in elderly men which can be characterized by an abnormal enlargement of the prostate associated with lower urinary symptoms. Current medications available for BPH treatment display several adverse effects; thus, the search for effective treatments with less side effects is still ongoing. In this study, we investigated the effect of Aconiti Lateralis Radix Preparata (dried root of Aconitum carmichaelii Debx.; AL), which is an herb used to treat extremely cold symptoms in traditional Korean medicine, on BPH using a testosterone propionate- (TP-) induced BPH rat model. Eight-week inguinal injection of TP induced BPH in rats, the prostate of which was displaying an abnormal proliferation. The pathological proliferation of the prostate was ameliorated by AL treatment of 4 weeks. Pathohistological changes in the prostate including epithelial thickness and lumen area were restored in AL-treated rats. Furthermore, 5α-reductase (5AR) and androgen receptor (AR), the two main factors in the pathogenesis of BPH, were decreased. In addition, the ratio of BAX and Bcl-2, an indicator of apoptosis, was increased by AL as well. Similar results were observed in AL-treated LNCaP prostate cancer cells. AL treatment suppressed the expression of the 5AR-AR axis and increased the ratio of BAX and Bcl-2. Apoptosis in the testis is considered a crucial side effect of finasteride, a 5AR inhibitor used to treat BPH. Our results showed that AL treatment did not display such effects, while finasteride treatment resulted in loss of spermatogenic cells within the prostate. Overall, these results suggest AL as a potentially safe nature-derived therapeutic agent for BPH treatment.
ABSTRACT
Activation of brown adipose tissue (BAT) has been proposed as a promising target against obesity due to its increased capacity for thermogenesis. In this study, we explored the effect of ß -Lapachone ( ß L), a compound obtained from the bark of the lapacho tree, against obesity. In vivo administration of ß L into either high fat diet (HFD)-induced obese C57BL6 mice and genetically obese Lepr -∕- mice prevented body weight gain, which was associated with tissue weight loss of white adipose tissue (WAT). In addition, ß L elevated thermogenic proteins including uncoupling protein 1 (UCP1) and mitochondrial count in BAT and human adipose tissue-derived mesenchymal stem cells (hAMSCs). ß L also induced AMP-activated protein kinase (AMPK) phosphorylation, subsequent upregulation of acetyl-CoA carboxylase (ACC) and UCP1, and these effects were diminished by AMPK inhibitor compound C, suggesting that AMPK underlies the effects of ß L. Mitogen-activated protein kinase pathways participated in the thermogenesis of ß L, specifically p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) were activated by ß L treatment in hAMSCs. Additionally, inhibitors of p38/JNK/ERK1/2 abrogated the activity of ß L. Taken together, ß L exerts anti-obese effects by inducing thermogenesis mediated by AMPK signaling pathway, suggesting that ß L may have a potential therapeutic implication of obesity. Taken together, ß L exerts anti-obese effects by not only inducing thermogenesis on brown adipocytes but also inducing the browning of white adipocytes. The anti-obese effect of ß L is mediated by AMPK signaling pathway, suggesting that ß L may have potential therapeutic implication of obesity.
Subject(s)
AMP-Activated Protein Kinases/physiology , Adipocytes/metabolism , Adipose Tissue, Brown/metabolism , Naphthoquinones/administration & dosage , Naphthoquinones/pharmacology , Obesity/drug therapy , Obesity/metabolism , Phytotherapy , Signal Transduction/physiology , Tabebuia/chemistry , Thermogenesis/drug effects , Animals , Anti-Obesity Agents , Cells, Cultured , Diet, High-Fat/adverse effects , Humans , Male , Mice, Inbred C57BL , Mitochondria/pathology , Naphthoquinones/isolation & purification , Obesity/etiology , Phosphorylation , Thermogenesis/genetics , Thermogenesis/physiology , Uncoupling Protein 1/metabolism , Weight Gain/drug effectsABSTRACT
BACKGROUND: Although rubrofusarin-6-ß-gentiobioside (RFG), which is a component of Cassiae tora seed, could likely regulate hyperlipidemia, its anti-obesity effect and related mechanism have not been elucidated. PURPOSE: The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG. STUDY DESIGN: In in vitro experiments, we confirmed the anti-adipogenic effect of RFG using 3T3-L1 cells and human adipose mesenchymal stem cells (hAMSCs). To confirm the anti-obesity effect, High-Fat Diet (HFD)-induced obese mice were selected as a model. METHODS: We investigated anti-adipogenic effects of RFG using MTS assay, Oil Red O Staining, real-time RT-PCR, western blot analysis, and immunofluorescence staining. The anti-obesity effect of RFG was confirmed in HFD-induced mice model using hematoxylin and eosin staining and serum analysis. RESULTS: RFG inhibited lipid accumulation in 3T3-L1 cells and hAMSCs by reducing expression of mammalian targets of rapamycin (mTOR), peroxisome proliferator-activated receptor (PPAR)γ, and CCAAT-enhancer binding protein (C/EBP)α. RFG phosphorylated AMP-activated protein kinase (AMPK) in a liver kinase B (LKB) 1-independent manner. Moreover, the anti-adipogenic effect of RFG was blocked by AMPK inhibitor. These results suggest that RFG inhibits lipid accumulation via AMPK signaling. Furthermore, RFG reduced the body weight, size of epididymal white adipose tissue (eWAT), and fatty liver in the mice. RFG also suppressed levels of adipogenic factors PPARγ, C/EBPα, FAS, LPL, and aP2) by activating AMPK in the eWAT and liver. CONCLUSION: RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.
Subject(s)
Anti-Obesity Agents/pharmacology , Chromones/pharmacology , Glucosides/pharmacology , Lipid Metabolism/drug effects , Weight Gain/drug effects , 3T3-L1 Cells , AMP-Activated Protein Kinases/metabolism , Adipocytes/drug effects , Adipogenesis/drug effects , Adipogenesis/physiology , Animals , Body Weight/drug effects , Diet, High-Fat/adverse effects , Humans , Male , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Mice , Mice, Obese , Obesity/drug therapy , Obesity/etiology , TOR Serine-Threonine Kinases/metabolismABSTRACT
BACKGROUND: Platycodi Radix (root of Platycodon grandiflorum) and its active compound platycodin D (PD) has been previously shown to possess anti-obesity properties, but the underlying mechanisms remain poorly understood. PURPOSE: The present study was aimed to evaluate the anti-obese effect of PD and reveal its mechanism of action. STUDY DESIGN/METHODS: Genetically obese db/db mice were orally treated with PD for 4 weeks, and body weight gain, adipose tissue weight, serum parameters were measured. Then, assays on adipogenic factors, thermogenic factors, and AMP-activated protein kinase (AMPK) pathway were performed in PD-treated 3T3-L1 murine adipocytes, human adipose-derived mesenchymal stem cells (hAMSCs), and primary cultured brown adipocytes. RESULTS: PD treatment attenuated body weight gain, suppressed white adipose tissue weight and improved obesity-related serum parameters in db/db mice. Two major adipogenic factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) were decreased by PD treatment in WAT of db/db mice, 3T3-L1 adipocytes and hAMSCs. In BAT of db/db mice and primary cultured brown adipocytes, PD treatment elevated the expressions of uncoupled protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator 1 α (PCG1α), the key regulators of BAT-associated thermogenesis. In addition, PD activated AMPKα both in vivo and in vitro. However, when AMPK was inhibited by compound C, PD treatment failed to suppress adipogenic factors and increase thermogenic factors. CONCLUSIONS: PD improved obesity in db/db mice by AMPK-associated decrease of adipogenic markers including PPARγ and C/EBPα. PD increased thermogenic factors such as UCP1 and PGC1α in db/db mice and primary cultured brown adipocytes. AMPK inhibition nullified the effects of PD, suggesting its anti-adipogenic and thermogenic actions were dependent on AMPK pathway activation.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adipocytes, Brown/drug effects , Adipogenesis/drug effects , Obesity/drug therapy , Saponins/pharmacology , Thermogenesis/drug effects , Triterpenes/pharmacology , 3T3-L1 Cells , Adipose Tissue, Brown/cytology , Adipose Tissue, White/cytology , Animals , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Humans , Male , Mesenchymal Stem Cells/drug effects , Mice , Mice, Knockout , PPAR gamma/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Platycodon/chemistry , Uncoupling Protein 1/metabolismABSTRACT
Obesity has become a major health threat in developed countries. However, current medications for obesity are limited because of their adverse effects. Interest in natural products for the treatment of obesity is thus rapidly growing. Korean medicine is characterized by the wide use of herbal formulas. However, the combination rule of herbal formulas in Korean medicine lacks experimental evidence. According to Shennong's Classic of Materia Medica, the earliest book of herbal medicine, Bupleuri Radix (BR) and Scutellariae Radix (SR) possess the Sangsoo relationship, which means they have synergistic features when used together. Therefore these two are frequently used together in prescriptions such as Sosiho-Tang. In this study, we used the network pharmacological method to predict the interaction between these two herbs and then investigated the effects of BR, SR, and their combination on obesity in 3T3-L1 adipocytes. BR, SR, and BR-SR mixture significantly decreased lipid accumulation and the expressions of two major adipogenic factors, peroxisome proliferator-activated receptor-gamma (PPARγ) and CCAAT/enhancer-binding protein-alpha (C/EBPα), and their downstream genes, Adipoq, aP2, and Lipin1 in 3T3-L1 cells. In addition, the BR-SR mixture had synergistic effects compared with BR or SR on inhibition of adipogenic-gene expressions. BR and SR also inhibited the protein expressions of PPARγ and C/EBPα. Furthermore, the two extracts successfully activated AMP-activated protein kinase alpha (AMPK α), the key regulator of energy metabolism. When compared to those of BR or SR, the BR-SR mixture showed higher inhibition rates of PPARγ and C/EBPα, along with higher activation rate of AMPK. These results indicate a new potential antiobese pharmacotherapy and also provide scientific evidence supporting the usage of herbal combinations instead of mixtures in Korean medicine.
ABSTRACT
Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1[Formula: see text] (HIF-1[Formula: see text]). In addition, the release of prostaglandin E2 and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1[Formula: see text] expressions in the tumor necrosis factor-[Formula: see text] stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of I[Formula: see text]B and the translocation of the nuclear factor-[Formula: see text]B (NF-[Formula: see text]B). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-[Formula: see text]B transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.