سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Sun, Xiaojing, Yuan, Yanxiang, Xin, Xianhao, Sun, Ping, Sun, Yunqi, Xie, Mi, Wang, Yuefei, Huang, Shan, Li, Bin. (1404). Ethanol extract of Garcinia kola seeds alleviates HGHFD/STZ-induced nonalcoholic fatty liver disease in diabetic rats by modulating oxidative stress, inflammation, and lipid accumulation. , 28(5), 662-670. doi: 10.22038/ijbms.2025.82786.17889
Xiaojing Sun; Yanxiang Yuan; Xianhao Xin; Ping Sun; Yunqi Sun; Mi Xie; Yuefei Wang; Shan Huang; Bin Li. "Ethanol extract of Garcinia kola seeds alleviates HGHFD/STZ-induced nonalcoholic fatty liver disease in diabetic rats by modulating oxidative stress, inflammation, and lipid accumulation". , 28, 5, 1404, 662-670. doi: 10.22038/ijbms.2025.82786.17889
Sun, Xiaojing, Yuan, Yanxiang, Xin, Xianhao, Sun, Ping, Sun, Yunqi, Xie, Mi, Wang, Yuefei, Huang, Shan, Li, Bin. (1404). 'Ethanol extract of Garcinia kola seeds alleviates HGHFD/STZ-induced nonalcoholic fatty liver disease in diabetic rats by modulating oxidative stress, inflammation, and lipid accumulation', , 28(5), pp. 662-670. doi: 10.22038/ijbms.2025.82786.17889
Sun, Xiaojing, Yuan, Yanxiang, Xin, Xianhao, Sun, Ping, Sun, Yunqi, Xie, Mi, Wang, Yuefei, Huang, Shan, Li, Bin. Ethanol extract of Garcinia kola seeds alleviates HGHFD/STZ-induced nonalcoholic fatty liver disease in diabetic rats by modulating oxidative stress, inflammation, and lipid accumulation. , 1404; 28(5): 662-670. doi: 10.22038/ijbms.2025.82786.17889

Ethanol extract of Garcinia kola seeds alleviates HGHFD/STZ-induced nonalcoholic fatty liver disease in diabetic rats by modulating oxidative stress, inflammation, and lipid accumulation

Iranian Journal of Basic Medical Sciences
مقاله 14، دوره 28، شماره 5، مرداد 2025، صفحه 662-670    اصل مقاله (471.71 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2025.82786.17889
نویسندگان
Xiaojing Sun1؛ Yanxiang Yuan1؛ Xianhao Xin1؛ Ping Sun1؛ Yunqi Sun1؛ Mi Xie1؛ Yuefei Wang2؛ Shan Huang1؛ Bin Li* 1
1Department of Pharmaceutical Engineering and Pharmaceutical Chemistry, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China
2National Key Laboratory of Chinese Medicine Modernization, State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
چکیده
Objective(s): To investigate the ameliorative effects of Garcinia kola ethanol extract (EGK) on type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) and to explore its underlying mechanisms. 
Materials and Methods: In vivo, a T2DM rat model was established using HGHFD/STZ. In vitro, HepG2 cells were induced with FFA to create a model of lipid accumulation. Lipid accumulation (LA), oxidative stress (OS) levels, and inflammatory markers were measured using kit methods. Additionally, the expression of the SREBP-1c pathway was detected by immunohistochemistry and western blot (WB) to further understand the potential mechanism of EGK’s protective effect on diabetic liver injury. 
Results: In vivo, EGK significantly reduced blood glucose levels (P<0.01), restored body weight (P<0.01), and improved liver LA, OS, and inflammatory levels (P<0.01) in diabetic rats. Histopathological results indicated that EGK effectively ameliorated diabetes-induced liver injury. Immunohistochemistry and WB results revealed that EGK significantly down-regulated the expression of the SREBP-1c pathway (P<0.01). In vitro, EGK markedly improved lipid accumulation, oxidative stress, and inflammation levels in HepG2 cells (P<0.01). Immunofluorescence and WB results showed that EGK significantly reduced the expression of the SREBP-1c pathway (P<0.01). 
Conclusion: EGK alleviates T2DM combined with NAFLD by reducing lipid accumulation through the inhibition of oxidative stress, inflammatory responses, and the SREBP-1c signaling pathway.
کلیدواژه‌ها
Garcinia kola؛ HepG2؛ Lipid accumulation؛ SREBP-1c؛ T2DM combined with - NAFLD
مراجع
1. Guo H, Wu H, Li Z. The pathogenesis of diabetes. Int J Mol Sci 2023; 24:6978-7000.
2. Teck J. Diabetes-associated comorbidities. Prim Care 2022; 49:275-286.
3. Muzica CM, Sfarti C, Trifan A, Zenovia S, Cuciureanu T, Nastasa R, et al. Nonalcoholic fatty liver disease and type 2 diabetes mellitus: A bidirectional relationship. Can J Gastroenterol Hepatol 2020; 2020:6638306. 
4. Han X, Zhang X, Liu Z, Fan H, Guo C, Wang H, et al. Prevalence of nonalcoholic fatty liver disease and liver cirrhosis in Chinese adults with type 2 diabetes mellitus. J Diabetes 2024; 16:e13564. 
5. Kim H, Lee DS, An TH, Park H-J, Kim WK, Bae K-H, et al. Metabolic spectrum of liver failure in type 2 diabetes and obesity: From NAFLD to NASH to HCC. Int J Mol Sci 2021; 22:4495-4524. 
6. Paul B, Lewinska M, Andersen JB. Lipid alterations in chronic liver disease and liver cancer. JHEP Rep Innov Hepatol 2022; 4:100479-100496. 
7. Stefan N, Cusi K. A global view of the interplay between nonalcoholic fatty liver disease and diabetes. Lancet Diabetes Endocrinol 2022; 10:284-296. 
8. Lee E-H, Lee J-H, Kim D-Y, Lee Y-S, Jo Y, Dao T, et al. Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2. Exp Mol Med 2024; 56:1001-1012. 
9. Zhang N, Zhang W, Guo X, Liu J, Li S, Zhang H, et al. Genistein protects against hyperglycemia and fatty liver disease in diet-induced prediabetes mice via activating hepatic insulin signaling pathway. Front Nutr 2022; 9:1072044-1072058. 
10. Vesković M, Šutulović N, Hrnčić D, Stanojlović O, Macut D, Mladenović D. The interconnection between hepatic insulin resistance and metabolic dysfunction-associated steatotic liver disease-the transition from an adipocentric to liver-centric approach. Curr Issues Mol Biol 2023; 45:9084-9102. 
11. Shehnaz SI, Roy A, Vijayaraghavan R, Sivanesan S, Pazhanivel N. Modulation of PPAR-γ, SREBP-1c and inflammatory mediators by luteolin ameliorates β-cell dysfunction and renal damage in a rat model of type-2 diabetes mellitus. Mol Biol Rep 2023; 50:9129-9142. 
12. Zachou M, Flevari P, Nasiri-Ansari N, Varytimiadis C, Kalaitzakis E, Kassi E, et al. The role of anti-diabetic drugs in NAFLD. Have we found the Holy Grail? A narrative review. Eur J Clin Pharmacol 2024; 80:127-150. 
13. Cho HJ, Lee E, Kim SS, Cheong JY. SGLT2i impact on HCC incidence in patients with fatty liver disease and diabetes: A nation-wide cohort study in South Korea. Sci Rep 2024; 14:9761-9773. 
14. Bao S, Wang X, Ma Q, Wei C, Nan J, Ao W. Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR/LXR-mediated P2X7R/NLRP3/NF-κB pathway activation. Chin Herb Med 2022; 14:367-375. 
15. Tauchen J, Frankova A, Manourova A, Valterova I, Lojka B, Leuner O. Garcinia kola: A critical review on chemistry and pharmacology of an important West African medicinal plant. Phytochem Rev Proc Phytochem Soc Eur 2023; 23: 1-47. 
16. Emmanuel O, Uche ME, Dike ED, Etumnu LR, Ugbogu OC, Ugbogu EA. A review on Garcinia kola heckel: Traditional uses, phytochemistry, pharmacological activities, and toxicology. Biomark Biochem Indic Expo Response Susceptibility Chem 2022; 27:101-117. 
17. Wang X, Li R, Liu X, Huang S, Li B, Wang H, et al. Study on characteristics of biflavanones distribution in Garcinia kola seeds and identification of compounds in gum resin exuded from fresh slices. J Pharm Biomed Anal 2020; 190:113512. 
18. Fu T-D, Zhang W-L, Zhang Y, Deng C-S, Qi W, Xu Q, et al. Garcinia biflavonoid 1 from Garcinia kola ameliorates glycolipid metabolism disorder in type 2 diabetic db/db mice. Nat Prod Commun 2024; 19:1934578X231224993. 
19. Dong J, Li W, Du X, He X, Deng B, Zheng H, et al. Garcinia cambogia water extract alleviates insulin resistance and hepatic lipid accumulation in mice fed a high-fat diet. Food Nutr Res 2023; 14: 67-77.
20. Sun P, Wang X, An M, Feng Q, Huang S, Wang Y, et al. The ethanol extract of Garcinia kola seeds ameliorates renal injury in HFD/STZ-induced diabetic rats and inhibits mesangial cells apoptosis via improving mitochondrial dysfunction. J Funct Foods 2024; 119:106341. 
21. Chen H-X, Yang F, He X-Q, Li T, Sun Y-Z, Song J-P, et al. Garcinia biflavonoid 1 improves lipid metabolism in HepG2 cells via regulating PPARα. Mol Basel Switz 2022; 27:1978-1990. 
22. Zhang C, Xu Q, Xu C, Yang K, Xia T, Hasi W, et al. Sex differences in the association between AST/ALT and incidence of type 2 diabetes in Japanese patients with nonalcoholic fatty liver disease: A retrospective cohort study. Endocr Res 2024; 49:1-11. 
23. Pan M, Cai C, Li W, Cao T, Liu Y, Yang L, et al. Ebselen improves lipid metabolism by activating PI3K/Akt and inhibiting TLR4/JNK signaling pathway to alleviate nonalcoholic fatty liver. Cytokine 2024; 181:156671. 
24. Mak K-K, Zhang S, Chellian J, Mohd Z, Epemolu O, Dinkova-Kostova AT, et al. Swietenine alleviates nonalcoholic fatty liver disease in diabetic mice via lipogenesis inhibition and anti-oxidant mechanisms. Antioxid Basel Switz 2023; 12:595-608. 
25. Skuratovskaia D, Komar A, Vulf M, Quang HV, Shunkin E, Volkova L, et al. IL-6 reduces mitochondrial replication, and IL-6 receptors reduce chronic inflammation in NAFLD and type 2 diabetes. Int J Mol Sci 2021; 22:1774-1788. 
26. Rusu I, Pirlog R, Chiroi P, Nutu A, Budisan L, Puia VR, et al. Distinct morphological and molecular profiles of NAFLD and NAFLD-associated HCC revealed by immunohistochemistry and MicroRNA analysis. J Gastrointest Liver Dis JGLD 2023; 32:356-366. 
27. Qi X, Li J, Caussy C, Teng G-J, Loomba R. Epidemiology, screening, and co-management of type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease. Hepatol Baltim Md 2024; doi: 10.1097/HEP.0000000000000913.
28. Mateus I, Prip-Buus C. Hydrogen sulphide in liver glucose/lipid metabolism and nonalcoholic fatty liver disease. Eur J Clin Invest 2022; 52:e13680. 
29. Furse S. Lipid metabolism is dysregulated in a mouse model of diabetes. Metabolomics Off J Metabolomic Soc 2022; 18:36-41. 
30. Artasensi A, Pedretti A, Vistoli G, Fumagalli L. Type 2 diabetes mellitus: A review of multi-target drugs. Mol Basel Switz 2020; 25:1987-2006. 
31. Mantovani A, Dalbeni A. Treatments for NAFLD: State of Art. Int J Mol Sci 2021; 22:2350-2374. 
32. Weinberg Sibony R, Segev O, Dor S, Raz I. Drug therapies for diabetes. Int J Mol Sci 2023; 24:17147-17166. 
33. Newman DJ. Natural products and drug discovery. Natl Sci Rev 2022; 9:nwac206. 
34. Ayepola OR, Cerf ME, Brooks NL, Oguntibeju OO. Kolaviron, a biflavonoid complex of Garcinia kola seeds modulates apoptosis by suppressing oxidative stress and inflammation in diabetes-induced nephrotoxic rats. Phytomedicine Int J Phytother Phytopharm 2014; 21:1785-1793. 
35. Xu X, Wang W, Lin L, Chen P. Liraglutide in combination with human umbilical cord mesenchymal stem cell could improve liver lesions by modulating TLR4/NF-kB inflammatory pathway and oxidative stress in T2DM/NAFLD rats. Tissue Cell 2020; 66:101382. 
36. Hendrikx T, Binder CJ. Oxidation-specific epitopes in nonalcoholic fatty liver disease. Front Endocrinol 2020; 11:607011-607020. 
37. Mooli RGR, Mukhi D, Ramakrishnan SK. Oxidative stress and redox signaling in the pathophysiology of liver diseases. Compr Physiol 2022; 12:3167-3192. 
38. Li S, Liu R, Xia S, Wei G, Ishfaq M, Zhang Y, et al. Protective role of curcumin on aflatoxin B1-induced TLR4/RIPK pathway mediated-necroptosis and inflammation in chicken liver. Ecotoxicol Environ Saf 2022; 233:113319. 
39. García JG, Ansorena E, Milagro FI, Zalba G, de Miguel C. Endothelial Nox5 expression modulates glucose uptake and lipid accumulation in mice fed a high-fat diet and 3T3-L1 adipocytes treated with glucose and palmitic acid. Int J Mol Sci 2021; 22:2729-2745. 
40. Moldogazieva NT, Zavadskiy SP, Astakhov DV, Terentiev AA. Lipid peroxidation: Reactive carbonyl species, protein/DNA adducts, and signaling switches in oxidative stress and cancer. Biochem Biophys Res Commun 2023; 687:149167. 
41. Sun M, Zhao X, Li X, Wang C, Lin L, Wang K, et al. Aerobic exercise ameliorates liver injury in Db/Db mice by attenuating oxidative stress, apoptosis and inflammation through the Nrf2 and JAK2/STAT3 signalling pathways. J Inflamm Res 2023; 16:4805-4819. 
42. Wang H, Chen H, Gao Y, Wang S, Wang X, Tang X, et al. The effect of wuling capsule on depression in type 2 diabetic patients. Biosci Rep 2020; 40:BSR20191260. 
43. De Wolde SD, Hulskes RH, Weenink RP, Hollmann MW, Van Hulst RA. The effects of hyperbaric oxygenation on oxidative stress, inflammation and angiogenesis. Biomolecules 2021; 11:1210-1256. 
44. Olajide OA, Iwuanyanwu VU, Lepiarz-Raba I, Al-Hindawi AA, Aderogba MA, Sharp HL, et al. Garcinia kola and garcinoic acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation. Phytother Res PTR 2021; 35:6963-6973. 
45. Dehzad MJ, Ghalandari H, Nouri M, Askarpour M. Anti-oxidant and anti-inflammatory effects of curcumin/turmeric supplementation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials. Cytokine 2023; 164:156144. 
46. Li H, Xu Q, Xu C, Hu Y, Yu X, Zhao K, et al. Bicyclol regulates hepatic gluconeogenesis in rats with type 2 diabetes and nonalcoholic fatty liver disease by inhibiting inflammation. Front Pharmacol 2021; 12:644129-644139. 
47. Abulikemu A, Zhao X, Xu H, Li Y, Ma R, Yao Q, et al. Silica nanoparticles aggravated the metabolic associated fatty liver disease through disturbed amino acid and lipid metabolisms-mediated oxidative stress. Redox Biol 2023; 59:102569-102582. 
48. Tan H-L, Guan X-H, Hu M, Wu J, Li R-Z, Wang L-F, et al. Human amniotic mesenchymal stem cells-conditioned medium protects mice from high-fat diet-induced obesity. Stem Cell Res Ther 2021; 12:364-377. 
49. Romero-Gómez M, Lawitz E, Shankar RR, Chaudhri E, Liu J, Lam RLH, et al. A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with nonalcoholic fatty liver disease. J Hepatol 2023; 79:888-897. 
50. Lim SH, Lee HS, Han H-K, Choi C-I. Saikosaponin A and D inhibit adipogenesis via the AMPK and MAPK signaling pathways in 3T3-L1 adipocytes. Int J Mol Sci 2021; 22:11409-11424. 
51. Jiang S-Y, Yang X, Yang Z, Li J-W, Xu M-Q, Qu Y-X, et al. Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis. Hepatol Baltim Md 2022; 76:1466-1481. 
52. Wang MH, Ye Y, Zhang M, Zhou BR, Wang JN, Song YN, et al. Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level. Clin Transl Oncol 2022;24:288-296. 
53. Monirujjaman M, Renani LB, Isesele P, Dunichand-Hoedl AR, Mazurak VC. Increased expression of hepatic stearoyl-coA desaturase (SCD)-1 and depletion of eicosapentaenoic acid (EPA) content following cytotoxic cancer therapy are reversed by dietary fish oil. Int J Mol Sci 2023; 24:3547-3561. 
54. Geng X, Liu H, Yuwen Q, Wang J, Zhang S, Zhang X, et al. Protective effects of zingerone on high cholesterol diet-induced atherosclerosis through lipid regulatory signaling pathway. Hum Exp Toxicol 2021; 40:1732-1745. 
55. Zhang J, Zhang W, Yang L, Zhao W, Liu Z, Wang E, et al. Phytochemical gallic acid alleviates nonalcoholic fatty liver disease via AMPK-ACC-PPARa axis through dual regulation of lipid metabolism and mitochondrial function. Phytomedicine Int J Phytother Phytopharm 2023; 109:154589. 
56. Lu H, Guo T, Fan Y, Deng Z, Luo T, Li H. Effects of diacylglycerol and triacylglycerol from peanut oil and coconut oil on lipid metabolism in mice. J Food Sci 2020; 85:1907-1914. 
57. Mu Q, Wang H, Tong L, Fang Q, Xiang M, Han L, et al. Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway. FASEB J Off Publ Fed Am Soc Exp Biol 2020; 34:13033-13048. 

آمار
تعداد مشاهده مقاله: 158
تعداد دریافت فایل اصل مقاله: 115