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Effects of Dietary Caloric Restriction and Exercise on GLUT 2 in Liver and GLUT-4 and VAMP-2 in Muscle Tissue of Diabetic Rats

  • Jeong, Ilgyu;Oh, Myungjin;Jang, Moonnyeo;Koh, Yunsuk;Biggerstaff, Kyle D.;Nichols, David;Ben-Ezra, Vic
    • Korean Journal of Exercise Nutrition
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    • v.13 no.1
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    • pp.1-7
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    • 2009
  • It has been shown that both caloric restriction and exercise, enhances glucose uptake through translocation of GLUT-4 protein. It remains unclear how exercise and caloric restriction affect the changes in VAMP (vesicle-associated membrane protein) in skeletal muscle and GLUT-2 in liver. This study investigated the effects of exercise training and caloric restriction on the expressions of glucose transport relating proteins in muscle and liver tissues in diabetic rats. Forty male Sprague-Dawley rats (250±10 g; 8 week in age) were assigned equally to four different groups; control (C), exercise only (E), dietary restriction only (D) and dietary restriction and exercise (DE). Daily food consumption was monitored to establish baseline intake. Both C and E groups consumed baseline food intake while D and DE groups were provided with only 60% of baseline total food intake. Forty-eight hours after intraperitoneal injection of STZ (50 mg/kg), diabetes was confirmed (8-hr fasting blood glucose levels ≥300 mg/dl). Rats in the E and DE groups exercised on a motorized treadmill for 30 min/d, 5 days/week for 4 weeks (5 min running at 3 m/min, 0% grade; 8 m/min for the next 5min, and then 15 m/min for 20 min). Rats were sacrificed 48 hrs after the last bout of exercise. Soleus muscle and liver were extracted to analyze for GLUT-4, VAMP-2, and GLUT-2, respectively. All variables were analyzed using the Western Blotting technique. All values were expressed as optical volume measured by optical density. A Two-way ANOVA was used to examine the difference between groups and applied Duncan's test for post-hoc. No significant differences in GLUT-2 expression were found among groups. However, E (280133±13228 arbitrary units{AU}) and DE (268833±14424 AU) groups showed significantly higher (p<.001) levels of GLUT-4 as compared with C (34461±2099 AU) and D groups (27847±703 AU). VAMP-2 protein expression increased (p<.001) in E (184137±7803 AU) and DE (189800±10856 AU) groups as compared to C (74201±8296AU) and D (72967±863 AU) groups. These results suggest that either exercise with or without caloric restriction increases the up-regulation of GLUT-4 and VAMP-2 in skeletal muscle of diabetic rats. However, GLUT-2 protein in liver was not affected by either exercise or exercise with caloric restriction.

The Clinical Investigation Study of Pancreatitis Developed in Burn Patients (화상환자에서 발생한 췌장염의 임상적 고찰)

  • Cho, Gi Yuon;Chun, Jin Woo;Kim, Young Min;Yoon, Jae Chul;Yim, Haejun;Cho, Yong Suk;Kim, Dohern;Hur, Jun;Chun, Wook
    • Journal of the Korean Burn Society
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    • v.22 no.1
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    • pp.10-14
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    • 2019
  • Purpose: To find progression and prognosis of pancreatitis developed in massive burn patients through retrospective analysis. Methods: A retrospective study was conducted on 32 patients with abnormal increase of serum lipase level among 2523 acute burn patients admitted to our burn center from January 1, 2017 to June 30, 2018. Pancreatitis in this study was defined as a serum lipase concentration level that is higher than 180 IU/L which is three times more than the normal level (less than 60 IU/L). In this study, a retrospective analysis was performed on patients with serum lipase level higher than 300 IU/L to better understand causality of burns and pancreatitis. Results: 32 patients (1.27%) had serum lipase level higher than 180 IU/L among 2523 acute burn subjects. And 13 patients (0.52%) of these 32 patients had serum lipase level elevated more than 300 IU/L. The study indicated serum lipase level was increased around 7 days after the injury. It returned to normal level early as after 1 to 2 weeks and late as after 4 to 6 weeks of injury. The serum amylase level was increased as similar modality as to the serum lipase level increase. The serum bilirubin, AST, ALT, LD, and GGT were also observed to be elevated when serum lipase was more than 1000 IU/L. Conclusion: The pancreatitis developed in burn patients are mostly as mild symptom. It could due to the ischemic injury and can easily be treated by a temporary fasting, TPN, and Gabexate intravenous injection.

Assessment of Combined Administration of Hypoglycemic Agents and Herbal Extracts (Pyeongwi-san or HyangsaPyongwi-san) on Blood Glucose Levels in Type 2 Diabetes Mellitus: A Retrospective Study (표준 치료를 받고 있는 제2형 당뇨병 환자에서 혈당강하제와 평위산 및 향사평위산 병용 투여가 혈당에 미치는 영향 및 안정성 연구)

  • Woo-nyoung Jung;Seung-hyun Oh;Mee-ryoung Song;Ji-won Noh;Young-min Ahn;Se-young Ahn;Byung-cheol Lee
    • The Journal of Internal Korean Medicine
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    • v.44 no.4
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    • pp.661-674
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    • 2023
  • Abstract: This retrospective study delved into the effects and safety considerations associated with the concomitant usage of hypoglycemic agents and herbal extracts, specifically Pyeongwi-san (PWS) or HyangsaPyongwi-san (HSPWS) in the context of type 2 diabetes mellitus management. Methods: The investigation involved 38 inpatients with type 2 diabetes mellitus who received PWS or HSPWS treatment at Kyung Hee University Korean Medical Hospital from January 2012 to December 2022. By investigating clinical attributes and conducting laboratory assessments, this study aimed to discern the impact of these herbal extracts on blood glucose levels, encompassing fasting blood sugar (FBS) and mean 2-hour postprandial glucose (PP2) levels. Furthermore, the safety profile of the herbal extracts was assessed by comparing liver function indicators, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (GGT), alongside kidney function markers, such as blood urea nitrogen (BUN) and creatinine (Cr). Results: Following the administration of the herbal extracts, no statistically significant alterations in FBS and mean PP2 levels emerged compared to the baseline levels. Notably, the safety evaluation revealed no significant differences in liver and kidney function parameters following herbal extract administration. Conclusion: The results of this research indicate that using PWS or HSPWS alongside hypoglycemic medications could be a beneficial additional method for addressing digestive symptoms in individuals with type 2 diabetes mellitus. Notably, this combination seems to have no negative interactions with other drugs.

Consideration of Predictive Indices for Metabolic Syndrome Diagnosis Using Cardiometabolic Index and Triglyceride-glucose Index: Focusing on Those Subject to Health Checkups in the Busan Area (Cardiometabolic Index, Triglyceride-glucose Index를 이용한 대사증후군 진단 예측지수에 대한 고찰: 부산지역 건강검진대상자 중심으로)

  • Hyun An;Hyun-Seo Yoon;Chung-Mu Park
    • Journal of radiological science and technology
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    • v.46 no.5
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    • pp.367-377
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    • 2023
  • This study investigates the utility of the Triglyceride-glucose(TyG) index and Cardiometabolic Index(CMI) as predictors for diagnosing metabolic syndrome. The study involved 1970 males, 1459 females, totaling 3429 participants who underwent health checkups at P Hospital in Busan between January 2023 and June 2023. Metabolic syndrome diagnosis was based on the presence of 3 or more risk factors out of the 5 criteria outlined by the American Heart Association/National Heart, Lung, and Blood Institute(AHA/NHLBI), and participants with 2 or fewer risk factors were categorized as normal. Statistical analyses included independent sample t-tests, chi-square tests, Pearson's correlation analysis, Receiver Operating Characteristic(ROC) curve analysis, and logistic regression analysis, using the Statistical Package for the Social Sciences(SPSS) program. Significance was established at p<0.05. The comparison revealed that the metabolic syndrome group exhibited attributes such as advanced age, male gender, elevated systolic and diastolic blood pressures, high blood sugar, elevated triglycerides, reduced LDL-C, elevated HDL-C, higher Cardiometabolic Index, Triglyceride-glucose index, and components linked to abdominal obesity. Pearson correlation analysis showed strong positive correlations between waist circumference/height ratio, waist circumference, Cardiometabolic Index, and triglycerides. Weak positive correlations were observed between LDL-C, body mass index, and Cardiometabolic index, while a strong negative correlation was found between Cardiometabolic Index and HDL-C. ROC analysis indicated that the Cardiometabolic Index(CMI), Triglyceride-glucose(TyG) index, and waist circumference demonstrated the highest Area Under the Curve(AUC) values, indicating their efficacy in diagnosing metabolic syndrome. Optimal cut-off values were determined as >1.34, >8.86, and >84.5 for the Cardiometabolic Index, Triglyceride-glucose index, and waist circumference, respectively. Logistic regression analysis revealed significant differences for age(p=0.037), waist circumference(p<0.001), systolic blood pressure(p<0.001), triglycerides(p<0.001), LDL-C(p=0.028), fasting blood sugar(p<0.001), Cardiometabolic Index(p<0.001), and Triglyceride-glucose index (p<0.001). The odds ratios for these variables were 1.015, 1.179, 1.090, 3.03, and 69.16, respectively. In conclusion, the Cardiometabolic Index and Triglyceride-glucose index are robust predictive indicators closely associated with metabolic syndrome diagnosis, and waist circumference is identified as an excellent predictor. Integrating these variables into clinical practice holds the potential for enhancing early diagnosis and prevention of metabolic syndrome.

Effect of sweet pumpkin powder on lipid metabolism in leptin-deficient mice (Leptin 유전자 결핍 동물모델에서 단호박분말 투여가 지방대사변화에 미치는 영향)

  • Inae Jeong;Taesang Son;Sang-myeong Jun;Hyun-Jung Chung;Ok-Kyung Kim
    • Journal of Nutrition and Health
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    • v.56 no.5
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    • pp.469-482
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    • 2023
  • Purpose: Obesity has emerged as a critical global public health concern as it is associated with and increases susceptibility to various diseases. This condition is characterized by the excessive enlargement of adipose tissue, primarily stemming from an inequity between energy intake and expenditure. The purpose of this study was to investigate the potential of sweet pumpkin powder in mitigating obesity and metabolic disorders in leptin-deficient obese (ob/ob) mice and to compare the effects of raw sweet pumpkin powder (HNSP01) and heat-treated sweet pumpkin powder (HNSP02). Methods: Leptin-deficient obese mice were fed a diet containing 10% HNSP01 and another containing 10% HNSP02 for 6 weeks. Results: The supplementation of ob/ob mice with HNSP01 and HNSP02 resulted in decreased body weight gain, reduced adipose tissue weight, and a smaller size of lipid droplets in the adipose tissue and liver. Furthermore, the ob/ob-HNSP01 and ob/ob-HNSP02 supplemented groups exhibited lower levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and insulin, as well as a reduced atherogenic index in comparison with the control group. Molecular analysis also demonstrated that the intake of HNSP01 and HNSP02 resulted in a diminished activation of factors associated with fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase, while concurrently enhancing factors associated with lipolysis, including adipose triglyceride lipase and hormone-sensitive lipase, in the adipose tissue. Conclusion: Taken together, these findings collectively demonstrate the potential of sweet pumpkin powder as a functional food ingredient with therapeutic properties against obesity and its associated metabolic disorders, such as insulin resistance and dyslipidemia.

Depression, Health-Related Habits, Eating Habits, and Nutrient Intake of Male Youth Before and After the Outbreak of the COVID-19 Pandemic -Analysis of the 2018 and 2020 Korea National Health and Nutrition Examination Survey- (코로나19 전후 남자청년의 우울, 건강 관련 습관, 식습관 및 영양소 섭취량의 변화 -2018년, 2020년 국민건강영양조사 자료 분석-)

  • Kyung-Ae Park
    • Journal of the Korean Dietetic Association
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    • v.29 no.4
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    • pp.211-229
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    • 2023
  • This study analyzed the differences in the general characteristics, mental and health-related factors, eating habits, and nutrient intake of Korean male youths before and after the outbreak of the coronavirus disease 2019 (COVID-19). The data of a total of 1,231 subjects, from among the participants in the 2018 and 2020 Korea National Health and Nutrition Examination Survey (KNHANES), were analyzed. The 2020 group had fewer married members than the 2018 group. The subjects in the 2020 group weighed more (P<0.05), had a higher waist circumference (P<0.01), and showed greater weight gain (P<0.05) than the 2018 group subjects. The aerobic physical activity of the 2020 group was lower (P<0.01) compared to the 2018 group. The members of the 2020 group had higher depression scores (P<0.01), suicidal tendencies (P<0.01), and need for counseling for mental problems (P<0.05) than those of the 2018 group. The prevalence of high fasting blood sugar levels and diabetes was higher in the 2020 group compared to the 2018 group. The frequency of breakfast (P<0.01) and dining out (P<0.001) and the proportion of breakfast (P<0.01) and dinner (P<0.05) taken with the family or non-family members was lower in the 2020 group than in the 2018 group. The rate of dietary supplement intake of the 2020 group was higher than that of the 2018 group (P<0.01). There were significant differences in the protein (P<0.05), riboflavin (P<0.01), and carbohydrate (P<0.01) intakes between the two groups. These results suggest that male youths had a higher waist circumference and high levels of depression, and showed a decrease in frequency of breakfast intake and dining out after the out break COVID-19 pandemic. Therefore, nutrition and health promotion programs are urgently needed to improve mental health, other health-related factors and nutritional status of male adults that are associated with the COVID-19 pandemic.

CRISPR/Cas9-mediated knockout of the Vanin-1 gene in the Leghorn Male Hepatoma cell line and its effects on lipid metabolism

  • Lu Xu;Zhongliang Wang;Shihao Liu;Zhiheng Wei;Jianfeng Yu;Jun Li;Jie Li;Wen Yao;Zhiliang Gu
    • Animal Bioscience
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    • v.37 no.3
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    • pp.437-450
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    • 2024
  • Objective: Vanin-1 (VNN1) is a pantetheinase that catalyses the hydrolysis of pantetheine to produce pantothenic acid and cysteamine. Our previous studies have shown that the VNN1 is specifically expressed in chicken liver which negatively regulated by microRNA-122. However, the functions of the VNN1 in lipid metabolism in chicken liver haven't been elucidated. Methods: First, we detected the VNN1 mRNA expression in 4-week chickens which were fasted 24 hours. Next, knocked out VNN1 via CRISPR/Cas9 system in the chicken Leghorn Male Hepatoma cell line. Detected the lipid deposition via oil red staining and analysis the content of triglycerides (TG), low-density lipoprotein-C (LDL-C), and high-density lipoprotein-C (HDL-C) after VNN1 knockout in Leghorn Male Hepatoma cell line. Then we captured various differentially expressed genes (DEGs) between VNN1-modified LMH cells and original LMH cells by RNA-seq. Results: Firstly, fasting-induced expression of VNN1. Meanwhile, we successfully used the CRISPR/Cas9 system to achieve targeted mutations of the VNN1 in the chicken LMH cell line. Moreover, the expression level of VNN1 mRNA in LMH-KO-VNN1 cells decreased compared with that in the wild-type LMH cells (p<0.0001). Compared with control, lipid deposition was decreased after knockout VNN1 via oil red staining, meanwhile, the contents of TG and LDL-C were significantly reduced, and the content of HDL-C was increased in LMH-KO-VNN1 cells. Transcriptome sequencing showed that there were 1,335 DEGs between LMH-KO-VNN1 cells and original LMH cells. Of these DEGs, 431 were upregulated, and 904 were downregulated. Gene ontology analyses of all DEGs showed that the lipid metabolism-related pathways, such as fatty acid biosynthesis and long-chain fatty acid biosynthesis, were enriched. KEGG pathway analyses showed that "lipid metabolism pathway", "energy metabolism", and "carbohydrate metabolism" were enriched. A total of 76 DEGs were involved in these pathways, of which 29 genes were upregulated (such as cytochrome P450 family 7 subfamily A member 1, ELOVL fatty acid elongase 2, and apolipoprotein A4) and 47 genes were downregulated (such as phosphoenolpyruvate carboxykinase 1) by VNN1 knockout in the LMH cells. Conclusion: These results suggest that VNN1 plays an important role in coordinating lipid metabolism in the chicken liver.

A Retrospective Review about Korean Medicine Treatment for Obesity and Change of Body Composition on Climacteric Women in a Korean Medicine Hospital (일개 한방병원에 내원한 갱년기 여성의 한의 비만 치료와 체성분 변화에 대한 후향적 분석)

  • Hye-Won An;Ji-Yeon Kim;Ji-Yeon Lee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.37 no.1
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    • pp.75-88
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    • 2024
  • Objectives: This study aimed to identify the current use of Korean medicine for obesity and its effect for women in climacteric period. Methods: We studied women aged 45-55 who visited Daejeon Korean medicine Hospital of Daejeon University to lose body weight from January 1, 2021 to December 31, 2022 via an analysis of the medical records. The treatment duration was continuous for more than 2 weeks, and a body composition was measured by Inbody 770 at 2 to 4 weeks after the first visit. Results: 28 patients were finally selected and their average age was 49.32±3.38 years. Based on the body mass index (BMI) classification, 19 were in the 1st obesity group, 5 in the 2nd obesity group, 3 in the overweight group and 1 in the normal group. Patients usually complained comcomitant symptoms, and the symptoms of menopausal disorder was the most frequent. The average treatment duration was 3.68±0.67 weeks and the average treatment frequency was 3.93±0.98 times. All patients took herbal medicines Gambi-tang and 23 took modified fasting therapy including Gamro-su. 14 were treated by whole body far-infrared therapy and 6 were gotten partial obesity treatment. Among patients treated for accompanying symptoms, menopausal disorders were the most common (35.71%), and herbal medicine such as Gamisoyou-san, Hominis Placenta Pharmacopuncture, moxibustion, and cupping were used. After treatment, on average, body composition changed significantly; body weight 3.28±1.82 kg, BMI 1.36±1.04 kg/m2, body fat 1.70±1.67 kg, skeletal muscle mass 0.81±0.91 kg, abdominal circumference 2.04±2.6 cm, and visceral fat area 8.91±12.83 cm2. Conclusions: We analyzed general characteristics, BMI distribution, types of Korean medicine treatment and change of body composition. This study could be used as reference to provide practical data of treatment for obese women in climacteric period.

NK cell-activating receptor NKp46 does not participate in the development of obesity-induced inflammation and insulin resistance

  • Gracia Nathalie;Beatriz Dal Santo Francisco Bonamichi;Jieun Kim;Jiwon Jeong;Haneul Kang;Emirrio Reinaldie Hartland;Eveline Eveline;Jongsoon Lee
    • Molecules and Cells
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    • v.47 no.3
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    • pp.100007.1-100007.11
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    • 2024
  • Recent evidence establishes a pivotal role for obesity-induced inflammation in precipitating insulin resistance and type-2 diabetes. Central to this process is the proinflammatory M1 adipose-tissue macrophages (ATMs) in epididymal white adipose tissue (eWAT). Notably, natural killer (NK) cells are a crucial regulator of ATMs since their cytokines induce ATM recruitment and M1 polarization. The importance of NK cells is shown by the strong increase in NK-cell numbers in eWAT, and by studies showing that removing and expanding NK cells respectively improve and worsen obesity-induced insulin resistance. It has been suggested that NK cells are activated by unknown ligands on obesity-stressed adipocytes that bind to NKp46 (encoded by Ncr1), which is an activating NK-cell receptor. This was supported by a study showing that NKp46-knockout mice have improved obesity-induced inflammation/insulin resistance. We therefore planned to use the NKp46-knockout mice to further elucidate the molecular mechanism by which NKp46 mediates eWAT NK-cell activation in obesity. We confirmed that obesity increased eWAT NKp46+ NK-cell numbers and NKp46 expression in wild-type mice and that NKp46-knockout ablated these responses. Unexpectedly, however, NKp46-knockout mice demonstrated insulin resistance similar to wild-type mice, as shown by fasting blood glucose/insulin levels and glucose/insulin tolerance tests. Obesityinduced increases in eWAT ATM numbers and proinflammatory gene expression were also similar. Thus, contrary to previously published results, NKp46 does not regulate obesity-induced insulin resistance. It is therefore unclear whether NKp46 participates in the development of obesity-induced inflammation and insulin resistance. This should be considered when elucidating the obesity-mediated molecular mechanisms that activate NK cells.

The Herbal Formula C-DM3 Improves the Changes of Diabetes-Related Biomarkers in High-Fat Diet-Induced Obese Mice through Regulation of the IRS1/PI3K/AKT and AMPK Signaling Pathways in the Liver and Pancreas (고지방식이를 통해 비만이 유발된 마우스에서 C-DM3 복합추출물의 항비만 및 항당뇨 효능 연구)

  • Yoon Yong Choi;Chenzi Lyu;Tong Zhang;Haifeng Shao;Xianglong Meng;Chu Duc Thanh;Jong-Seong Kang;Hyo Won Jung;Yong-Ki Park
    • Journal of Korean Medicine for Obesity Research
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    • v.24 no.1
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    • pp.25-40
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    • 2024
  • Objectives: In the present study, we investigated the effects of clean-diabetes mellitus 3 (C-DM3), a herbal formula with Trichosanthis Radix, Coptidis Rhizoma, Crataegi Fructus, and Cinnamomi Cortex, on the pathological and serological symptoms of diabetes and its related molecular mechanisms in diet-induced obese mice. Methods: We prepared an obese mouse model using a high-fat diet for 8 weeks and then administered the C-DM3 extract for 4 weeks. The changes of pathological and serological biomarkers for diabetes assessment were measured in the mice and histological changes were observed in the liver and pancreas tissues. We also identified the main compounds in the C-DM3 extract using high pressure liquid chromatography (HPLC) and analyzed the molecular mechanism of the disease condition by network pharmacological analysis. Results: In the in vivo, the administration of C-DM extract to obese mice significantly reduced body weight gain, fatty liver symptoms, and muscle loss, and decreased the levels of fasting blood glucose, insulin, aspertate aminotransferase, triglycerides, and low-density lipoprotein-cholesterol. In addition, C-DM extract significantly increased the phosphorylation of insulin receptor substrate 1, protein kinase b (AKT), phosphoinositide 3-kinase (PI3K), adenosine monophosphate-activated protein kinase, and glucose transporter 4 in all pancreatic and liver tissues, with inhibition of histopathological changes in obese mice. HPLC analysis identified hyperoside, berberine, epiberberine, columbamin, coptisine, coumarin, jatrorrhizine, and citric acid as the main compounds. In the network pharmacological analysis, the molecular targets of C-DM3 extract on obesity and diabetes were shown as the insulin, AKT, PI3K, and mitogen-activated protein kinase pathways with the regulation of inflammatory molecules interleukin 6 (IL-6), jun proto-oncogene, and IL-1β, which matched our in vivo targets. Conclusions: Based on these results, C-DM3 extract is expected to be effective in improving obesity and preventing diabetic progression.