The Effects of Methanol Extract of Rue Leaves (Ruta graveolens) on Body Weight, Lipid Profile, Adipokine Levels, TCPTP, and Perilipin-1 Expression in Obesity Model Rats
DOI:
https://doi.org/10.48048/tis.2025.10407Keywords:
Rue leaves, Body weight, Adipokine, Lipid profile, ObesityAbstract
Obesity is one of the non-communicable diseases that becomes a health problem with high prevalence every year. Rue leaves (Ruta graveolens) containing a rutacridone active compound can computationally interact with T cell protein tyrosine phosphatase (TCPTP) and have anti-obesity activity properties. Therefore, this study aimed to investigate the Methanol Extract of Rue Leaves (MERL) on Body Weight (BW), Obesity Index (OI), Subcutaneous Fat Thickness (SFT), lipid profile, Fasting Blood Glucose (FBG), Leptin (LEP) and Adiponectin (ADP) levels, TCPTP and Perilipin-1 expression in obesity model rats (OR). This study was an animal experiment with a pre-posttest control group design, which used 48 male rats of the Sprague-Dawley strain and was randomly divided into 6 groups. The normal Group (N) was male rats + rat standard feed (BR-2). The negative and positive Groups (NC and PC) were obese rats (ORs) + BR-2 + 1 mL of 0.9% NaCl and 0.6 mg/kg BW pure rutacridone, respectively. The treatment groups (T1-T3) were ORs + BR-2 + 80, 100, or 200 mg/kg BW MERL for 30 days. Our results demonstrated that MERL administration significantly reduced BW, OI, SFT, TG, TC, LDL-C, FBG, and LEP levels and significantly increased HDL-C and ADP levels with p ˂ 0.05, compared to the NC group in a dose-dependent manner. Our data also showed low expression of TCPTP and Perilipin-1 in all treatment groups. In conclusion, MERL administration reduces leptin, TG, TC, LDL-C, FBG levels, SFT, BW, and OI while increasing ADP and HDL-C levels in male obese rats.
HIGHLIGHTS
- Methanol extract of Rue leaves (MERL) chemically contains Osthol, Psoralen, Rutin, Scoparone, and Quercetin, which potentially become anti-obesity agents.
- Measuring subcutaneous fat thickness (SFT) using an ultrasound sonography device provides accurate data for determining rat obesity.
- Administration of 100 mg/kg BW/day MERL effectively reduces leptin, triglyceride, total cholesterol, LDL-Cholesterol, fasting blood glucose levels, SFT, body weight, and obesity index while increasing adiponectin and HDL-Cholesterol levels in male obese rats.
GRAPHICAL ABSTRACT
Downloads
References
World Obesity Atlas,Avaliable at: https://data.worldobesity.org/publications/?cat=19, accessed July 2024.
B Masood and M Moorthy. Causes of obesity: A review. Clinical Medicine 2023; 23, 284-291.
GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: A systematic analysis for the Global Burden of Disease Study 2021. The Lancet 2023; 402, 203-234.
International Diabetes Federation. IDF diabetes atlas, Available at: https://www.diabetesatlas.org, accessed July 2024.
AM Giudetti. Editorial: Lipid metabolism in obesity. Frontiers in Physiology 2023; 14, 1268288.
A Jais and JC Bruning. Arcuate nucleus-dependent regulation of metabolism - pathways to obesity and diabetes mellitus. Endocrine Reviews 2023; 43(2), 314-328.
SI Lee, JW Kim, YK Lee, SH Yang, I Lee, JW Suh and SD Kim. Anti-obesity effect of Monascus pilosus mycelial extract in high fat diet-induced obese rats. title of the article. Journal Applied Biological Chemistry 2011; 54(3), 195-205.
KW Baek, JS Kim, JS Park, SJ Kim, YC Ha, OY Jeong and JI Yoo. Validation of dual energy x-ray absorptiometry and nuclear magnetic resonance in the analysis of body composition in mice. Journal of Bone Metabolism 2020; 27(4), 291.
SV Eastwood, T Tillin, A Wright, J Heasman, J Willis, IF Godslanc, N Forouhi, P Whincup, AD Hughes and N Chaturvedi. Estimation of CT-derived abdominal visceral and subcutaneous adipose tissue depots from anthropometry in Europeans, South Asians and African Caribbeans. PLoS One 2013; 8(9), e75085.
S Cornacchia, LL Tegalo, A Maldera, E Pierpaoli, U Tupputi, G Ricatti, L Eusebi, S Salerno and G Guglielmi. Radiation protection in non-ionizing and ionizing body composition assessment procedures. Quantitative Imaging in Medicine and Surgery 2020; 10(8), 1723.
Y Wang, X Ge, H Ma, S Qi, G Zhang and Y Yao. Deep learning in medical ultrasound image analysis: A review. IEEE Access 2021; 9, 54310-54324.
P Gonzalez-Muniesa, MA Mártinez-González, FB Hu, JP Després, Y Matsuzawa, RJF Loos, LA Moreno, GA Bray and JA Martinez. Obesity. Nature Reviews Disease Primers 2017; 3, 17034.
GA Bray, G Frühbeck, DH Ryan and JPH Wilding. Management of obesity. The Lancet 2016; 387(10031), 1947-1956.
N Kishore, D Marques, Mahmud, MV Kiang, I Rodriquez, AJD Fuller, P Ebner, C Sorensen, F Racy, J Lemery, L Maas, J Leaning, RA Irizarry, S Balsari, CO Buckee and D Phil. Mortality in Puerto Rico after Hurricane Maria. The New England Journal of Medicine 2018; 379(2), 162-170.
Y Fitrianingrum, D Indarto, R Kusumawati and YH Suselo. Actinodaphnine and rutacridone as new T-cell protein tyrosine phosphatase inhibitors for drug development of obesity. IOP Conference Series: Materials Science and Engineering 2019; 546(6), 062007.
H Ali, A Ahmed and AQ Abdulwahab. Potential of some therapeutic effect of Ruta graveolens plant and their bioactivities: A review. Medical Journal of Ahl al-Bayt University 2024; 3(1), 174-189.
A Hosseini, BM Razavi, M Banach and H Hosseinzadeh. Quercetin and metabolic syndrome: A review. Phytotherapy Research 2021; 35(10), 5352-5364.
Y Zhao, B Chen, J Shen, L Wan, Y Zhu, T Yi and Z Xiao. The beneficial effects of quercetin, curcumin, and resveratrol in obesity. Oxidative Medicine and Cellular Longevity 2017; 2017(1), 1459497.
E Valizadeh, A Ostadrahimi, D Fazli, H Khodaei and H Akbari. Efficacy of a traditional herbal mixture as an anti-obesity supplement in obese individuals: A randomized controlled trial. Journal of Nutritional Sciences and Dietetics 2017; 3(4), 1-8.
I Sundari, D Indarto and P Dirgahayu. Dual extracts of star fruit leaves and Toddalia accuelata leaves as antiobesity in rats. Jurnal Aisyah: Jurnal Ilmu Kesehatan 2022; 7(1), 93-100.
MN Ilyas, NB Simbak, AB Atif and MKR Adzim. Sample size calculation for animal studies using degree of freedom (E); an easy and statistically defined approach for metabolomics and genetic research. Current Trends in Biomedical Engineering & Biosciences 2017; 43, 207-213.
RD Marin, S Crespo-Gracia, AM Wilson and P Sapieha. RELi protocol: Optimization for protein extraction from white, brown and beige adipose tissues. MethodsX 2019; 6, 918-928.
LR Vaquero, GA Rivera, JA Mendiola, AADV Martinez, E Ibanez and M Bueno. Utilizing green solvents in compressed fluids technologies for extracting bioactive compounds from Ruta graveolens L. Industrial Crops and Products 2024; 216, 118717.
I Munawar, SSU Hassan, M Abbas, M Abbas, M Saeed, MA Ghaffari and H Ahmad. Phytochemical evaluation and lipid profile significance of Ruta graveolens through obesity-induced animal model. Bioscience Research 2023; 20(2), 557-564.
P Gupta, J Mehla and YK Gupta. Antiobesity effect of Safoof Mohazzil, a polyherbal formulation, in cafetaria diet induced obesity in rats. Indian Journal of Experiment Biology 2012; 50(11), 776-784.
M Noori, M Jafari, H Azimi and M Node-Farahani. Effects of Ruta graveolens total and flavonoids extracts on rat blood glucose, cholesterol, triglycerides and urea comparing synthetic drugs. Nusantara Bioscience 2019; 11, 23-29.
AG Manzoni, DF Passos, JLG da Silva, VM Bernardes, JM Bremm, MH Jantsch, JS de Oliveira, TR Mann, CM de Andrade and DBR Leal. Rutin and curcumin reduce inflammation, triglyceride levels and ADA activity in serum and immune cells in a model of hyperlipidemia. Blood Cells, Molecules and Diseases 2019; 76, 13-21.
AR Althaher, M Alwahsh, A Hasan, D Al-Majali, MW Awadallah and T Al-Qirim. Anti-hyperlipidemic effect of Ruta chalepensis ethanolic extract in triton WR-1339-induced hyperlipidemia in rats. Applied Sciences 2024; 14(19), 9017.
C Gur, S Ozkanlar, S Gedikli, E Sengul, V Gelen and A Kara. The effects of quercetin administration on heart tissue and serum parameters in the rats with experimental obesity. Eurasian Journal of Molecular and Biochemical Sciences 2022; 1(1), 16-21.
C Velmurugan, I Sakthivel and V Subramaniyan. Evaluation of anti-diabetic and wound healing potential of Ethiopia plant ‘Ruta graveolens’ in diabetic induced rat. Natural Volatiles & Essential Oils 2022; 9(1), 1571-1582.
Z Peng, X Gong, Y Yang, L Huang, Q Zhang, P Zhang, R Wan and B Zhang. Hepatoprotective effect of quercetin against LPS/d-GalN induced acute liver injury in mice by inhibiting the IKK/NF-κB and MAPK signal pathways. International Immunopharmacology 2017; 52, 281-289.
A Abdullah, A Atia and N Alrawaiq. The effect of administration of an equal dose of different classes of dietary chemicals on NQO1 expressional level in mice liver. Pharmacophore 2017; 8(5), 1-9.
MS Ganjayani, RS Karunakaran, S Gandham and B Meriga. Quercetin‑3‑O‑rutinoside from Moringa oleifera downregulates adipogenesis and lipid accumulation and improves glucose uptake by activation of AMPK/glut‑4 in 3T3‑L1 cells. Revista Brasileira de Farmacognosia 2023; 33(2), 334-343.
SY Seo, WS Ju, K Kim, J Kim, JO Yu, JS Ryu, JS Kim, HA Lee, DB Koo and YK Choo. Quercetin induces mitochondrial apoptosis and downregulates ganglioside GD3 expression in melanoma cells. International Journal of Molecular Sciences 2024; 25(10), 5146.
Y Wang, S Liu, T Jia, Y Feng, X Xu and D Zhang. T cell protein tyrosine phosphatase in glucose metabolism. Frontiers in Cell and Developmental Biology 2021; 9, 682947.
X Bai, X Zhao, K Liu, X Yang, Q He, Y Gao, W Li and W Han. Settings order article reprints open accessarticle mulberry leaf compounds and gut microbiota in alzheimer’s disease and diabetes: A study using network pharmacology, molecular dynamics simulation, and cellular assays. International Journal of Molecular Sciences 2024; 25(7), 4062.
C Bailly. Ruta angustifolia pers. (narrow-leaved fringed rue): Pharmacological properties and phytochemical profile. Plants 2023; 12(4), 827.
A Ran, C Shi, Y Tang, Z Cui, Y Li, Z Chen, M Xiao and L Xu. Chitosan/rutin multifunctional hydrogel with tunable adhesion, anti-inflammatory and antibacterial properties for skin wound healing. Carbohydrate Polymers 2024; 343, 122492.
S Kusumaningrum. 2025, Effects of Methanol Extract of Rue Leaves (Ruta graveolens) on Leptin Resistance, Fat Metabolism, and Weight Loss in Obese Male Rats. Ph.D. Dissertation. Universitas Sebelas Maret, Surakarta, Indonesia.
Published
Issue
Section
License
Copyright (c) 2025 Walailak University

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.



