31MAR

Welcome To Mediterr J Med Res

Manuscripts are accepted for consideration with understanding that they are represent original material and they are not being considered for publication elsewhere. The editors welcome the submission of relevant articles for editorial consideration. Manuscripts and all scientific and professional data should be addressed to Editor-in-Cheif (Fmosherif@yahoo.com).

Mediterranean Journal of Medical Research
https://app.periodikos.com.br/journal/mjpe/article/doi/10.5281/zenodo.18120112

Mediterranean Journal of Medical Research

Original article Pharmacology

Urtica diocia L. ameliorative efficiency against CCl4-induced hepatic fibrosis in rats

Khatema M. Moukhtar, Afia D. Awhida

Downloads: 1
Views: 184

Abstract

Carbon Tetrachloride (CCl4) is a hepatotoxin causing hepatic necrosis, release of proinflammatory and profibrotic cytokines, and increased oxidative stress. Urtica dioica L. (stinging nettles) is traditionally used as having medicinal and pharmaceutical benefits and uses in cosmetic and food industries. Leaves are rich in bioactive compounds. Extracts of nettle leaves and roots possess antibacterial, antioxidant, anti-inflammatory, antiviral, anti-carcinogenic, and anti-rheumatic properties. This study aimed to illustrate the potential efficiency of nettle against CCl4-induced liver fibrosis in male Albino rats. Rats were divided into five groups: untreated group (I), an olive oil group (II) given 0.2 ml/100 gm olive oil by intraperitoneal injection, Nettle leaves water extract group (III) treated with nettle water extract (2.0 ml/kg), CCl4 group (IV), and CCl4-injured and nettle-treated group (V). After four weeks, rats were decapitated, and liver tissue and blood samples were obtained. CCl4 injection raised liver biomarkers and lipid peroxidation, decreased antioxidant levels, induced histopathological alterations in the liver, and induced DNA damage. Treatment with nettle restored the normality of the liver and overcome oxidative stress.

Keywords

Antioxidants, CCL4, nettle, hepato-protection, oxidative stress

References

  1. Somnay K, Wadgaonkar P, Sridhar N, Roshni P, Rao N, Wadgaonkar R. Liver fibrosis leading to cirrhosis: basic mechanisms and clinical perspectives. Biomedicines. 2024; 12(10): 2229.  doi: 10.3390/biomedicines 12102229
  2. Aborehab NM, Saleh SM, Mehanna ET. Alcohol-induced hepatic fibrosis and the relation between hepcidin and liver fibrosis. Records of Pharmaceutical and Biomedical Sciences. 2024; 8(1): 37-44. doi: 10.21608/ rpbs .2024.221578.1239
  3. Algefare AI, Alfwuaires M, Famurewa AC, Elsawy H, Sedky A. Geraniol prevents CCl4-induced hepato-toxicity via suppression of hepatic oxidative stress, pro-inflammation and apoptosis in rats. Toxicology Reports. 2024; 12: 128-134. doi: 10.1016/j.toxrep.2024.01.007
  4. Chaudhary P, Janmeda P, Docea AO, Yeskaliyeva B, Abdull Razis AF, Modu B, et al. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Frontiers in Chemistry. 2023; 11: 1158198. doi: 10.3389/fchem.2023.1158198
  5. Bh Akhlaq M, Alum MK, Alam MM. Anti-inflammatory potential of medicinal plants. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2022; 2(1): 13-21. doi: 10.5281/zenodo.6399381
  6. Nkollo MI, Ngwuede R, Efejene IO, Olele CH, Iwelumo BC, Chibuogwu C, Aisuodionoe EM. Phytochemistry and pharmacological insights into Kalanchoe pinnata: A brief review. Mediterranean Journal of Medical Research. 2025; 2(2): 26-31. doi: 10.5281/zenodo.15368110
  7. Bazine HA, Shlaka MA, Sherif FM. A neuropharmacological profile of Lycium schweinfurthii (solanaceae) methanolic extract in mice. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2023; 3(1): 43-50. doi: 10.5281/zenodo.7771364
  8. Han KSS, Win KT, Chit MT. Evaluation of antimicrobial, antioxidant, antidiabetic activities, and acute toxicity of Elephantopus scaber L. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2025; 5(2): 87-95. doi: 10.5281/zenodo.15365040
  9. Irabor EEI, Eze PN, Eze IG, Omoruyi U, Imafidon MI, Ogbeide K, Okunzuma IG. A toxicity study of oral methanolic extract of Calliandra surinamensis seeds on liver functions in rodents. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2023; 3(2): 59-67. doi. 10.5281/zenodo.8076230
  10. Munguti JK, Makanya AN, Obimbo MM, Kipkorir VK, Njuguna BM. Crude beetroot extract ameliorates metabolic-dysfunction associated steatotic liver disease by improving the MAS-activity score in an experimental rat model. Mediterranean Journal of Medical Research. 2025; 2(4): 217-229. doi: 10.5281/zenodo. 17587262
  11. Bhusal KK, Magar SK, Thapa R, Lamsal A, Bhandari S, Maharjan R, et al. Nutritional and pharmacological importance of stinging nettle (Urtica dioica L.): A review. Heliyon. 2022; 8(6): e09717. doi: 10.1016/j.heliyon. 2022.e09717
  12. Sahal A, Hussain A, Kumar S, Dobhal A, Ahmad W, Chand, K, et al. Nettle (Urtica dioica) leaves as a novel food: Nutritional, phytochemical profiles, and bioactivities. Food Chemistry: X. 2025; 30(28): 102607. doi: 10.1016/j.fochx.2025.102607
  13. Omar GA, Mohammed LY. Antihyperglycemic effect of aqueous extract of Urtica dioica L. leaves growing in Kurdistan Region, Iraq. Egyptian Journal of Veterinary Sciences. 2024; 55(3): 862-872. doi: 10.21608/ejvs. 2023.240984.1633
  14. Constandinou C, Henderson N, Iredale JP. Modeling liver fibrosis in rodents. Methods in Molecular Medicine. 2005; 117: 237-250. doi: 10.1385/1-59259-940-0:237
  15. Olive PL, Banáth JP, Durand RE. Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay. Radiation Research. 1990; 122(1): 86-94. PMID: 2320728.
  16. Alkreathy HM, Khan RA, Khan MR, Sahreen S. CCl4 induced genotoxicity and DNA oxidative damages in rats: Hepatoprotective effect of Sonchus arvensis. BMC Complementary and Alternative Medicine. 2014; 14: 452. doi: 10.1186/1472-6882-14-452
  17. El-Shorbagy HM. Molecular and anti-oxidant effects of wheat germ oil on CCl4-induced renal injury in mice. Journal of Applied Pharmaceutical Science. 2017; 7(5): 94-102. doi: 10.7324/JAPS.2017.70517
  18. Solter PF. Clinical pathology approaches to hepatic injury. Toxicologic Pathology. 2005; 33(1): 9-16. doi: 10.1080/01926230590522086
  19. Mohamed NA, Hashem MA, Alzahrani AM, Abdel-Moneim AM, Abdou HM. Hepatoprotective effect of Spirulina platensis against carbon tetrachloride-induced liver injury in male rats. The Journal of Pharmacy and Pharmacology. 2021; 73(11): 1562-1570. doi: 10.1093/jpp/rgab107
  20. Lee HY, Lee GH, Yoon Y, Chae HJ. R. verniciflua and E. ulmoides extract (ILF-RE) protects against chronic CCl4-induced liver damage by enhancing antioxidation. Nutrients. 2019; 11(2): 382. doi: 10.3390/nu11020382
  21. Sahreen S, Khan MR, Kha, RA. Ameliorating effect of various fractions of Rumex hastatus roots against hepato‐and testicular toxicity caused by CCl4. Oxidative Medicine and Cellular Longevity. 2013; 2013(1): 325406. doi: 10.1155/2013/325406
  22. Hafez MM, Al-Harbi NO, Al-Hoshani AR, Al-Hosaini KA, Al Shrari SD, Al Rejaie SS, et al. Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats. Biological Research. 2015; 48(1): 30. doi: 10.1186/s40659-015-0022-y
  23. Huang X, Wang L, Meng M, Zhang S, Pham TTH, Jiang L, et al. Extract of Averrhoa carambola L. (Oxalidaceae) roots ameliorate carbon tetrachloride-induced hepatic fibrosis in rats. Biomedicine and Pharmacotherapy. 2020; 121: 109516. doi: 10.1016/j.biopha.2019.109516
  24. Sun J, Wu Y, Long C, He P, Gu J, Yan, L, et al. Anthocyanins isolated from blueberry ameliorates CCl4 induced liver fibrosis by modulation of oxidative stress, inflammation and stellate cell activation in mice. Food and Chemical Toxicology. 2018; 120: 491-499. doi: 10.1016/j.fct.2018.07.048
  25. Mrwad AA, El-Shafey S, Said NM. Carbon tetrachloride: A classic model for liver toxicity. Biochemistry Letters. 2025; 21(1): 71-88. doi: 10.21608/blj.2025.381090.1070
  26. Almatroodi SA, Almatroudi A, Almasnad FS, Khan AA, Babiker AY, Alruwetei AM, Rahmani AH. Curcumin ameliorates carbon tetrachloride-induced liver injury in rats through modulating various biological activities. International Journal of Pharmacology. 2020; 16(2): 145-153. doi: 10.3923/ijp.2020.145.153
  27. Abd Elzaher F, Moussa MH, Raafat MH, Emara MM. Histological effect of platelet rich plasma on CCL4 induced liver fibrosis in adult albino rat. Egyptian Journal of Histology. 2021; 44(4): 932-940. doi: 10.21608/ ejh.2020.51054.1390
  28. Liu F, Liu Z, Wu N, Cong X, Fei R, Chen H, Wei L. Transplanted endothelial progenitor cells ameliorate carbon tetrachloride-induced liver cirrhosis in rats. Liver Transplantation. 2009; 15(9): 1092-1100.  doi: 10.1002/lt. 21845
  29. Hao T, Chen J, Zhi S, Zhang Q, Chen G, Yu F. Comparison of bone marrow vs. adipose tissue derived mesenchymal stem cells for attenuating liver fibrosis. Experimental and Therapeutic Medicine. 2017; 14(6): 5956-5964. doi: 10.3892/etm.2017.5333
  30. Yang FR, Fang BW, Lou JS. Effects of Haobie Yangyin Ruanjian decoction on hepatic fibrosis induced by carbon tetrachloride in rats. World Journal of Gastroenterology. 2010; 16(12): 1458-1464. doi: 10.3748/wjg.v 16.i12.1458
  31. Diab KA, Fahmy MA, Hassan ZM, Hassan EM, Salama AB, Omara EA. Genotoxicity of carbon tetrachloride and the protective role of essential oil of Salvia officinalis L. in mice using chromosomal aberration, micronuclei formation, and comet assay. Environmental Science and Pollution Research. 2018; 25(2): 1621-1636. doi: 10.1007/s11356-017-0601-2
  32. Chu C-C, Chen S-Y, Chyau C-C, Fu Z-H, Liu C-C, Duh P-D. Protective effect of Djulis (Chenopodium formosanum) and its bioactive compounds against carbon tetrachloride-induced liver injury, in vivo. Journal of Functional Foods. 2016; 26: 585-597. doi: 10.1016/j.jff.2016.08.025
  33. El-Tahan RA, Michel TN, Shams NA, Shaker SA. The protective effect of sesame oil against renal toxicity induced by CCl4 in experimental model. Journal of the Medical Research Institute. 2019; 40(1): 24-31. doi: 10.21608/jmalexu.2019.108591
  34. Akbay P, Basaran AA, Undeger U, Basaran N. In-vitro immunomodulatory activity of flavonoid glycosides from Urtica dioica L. Phytotherapy Research. 2003; 17(1): 34-37. doi: 10.1002/ptr.1068
  35. Gulcin I, Kufrevioglu OI, Oktay M, Büyükokuroglu ME. Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L.). Journal of Ethnopharmacology. 2004; 90(2-3): 205-215. doi: 10.1016/ j.jep.2003.09.028
  36. Cetinus E, Kilinc M, Inanc F, Kurutas EB, Buzkan N. The role of Urtica dioica (Urticaceae) in the prevention of oxidative stress caused by tourniquet application in rats. The Tohoku Journal of Experimental Medicine. 2005; 205(3): 215-221. doi: 10.1620/tjem.205
  37. Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L. and Urtica dioica L. on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World Journal of Gastroenterology. 2005; 11(42): 6684-6688. doi: 10.3748/wjg.v11.i42.6684
  38. Oguz S, Kanter M, Erboga M, Ibis C. Protective effect of Urtica dioica on liver damage induced by biliary obstruction in rats. Toxicology and Industrial Health. 2013; 29(9): 838-845. doi: 10.1177/0748233712445045
  39. Telo S, Halifeoglu I,  Ozercan IH. Effects of stinging nettle (Urtica Dioica L.) on antioxidant enzyme activities in rat model of mammary gland cancer. Iranian Journal of Pharmaceutical Research. 2017; 16 (Suppl) 164-170. PMID: 29844787; PMCID: PMC5963657.
  40. Bray BJ, Perry NB, Menkes DB, Rosengren RJ. St. John's wort extract induces CYP3A and CYP2E1 in the Swiss Webster mouse. Toxicological Sciences. 2002; 66(1): 27-33. doi: 10.1093/toxsci/66.1.27

Submitted date:
10/20/2025

Reviewed date:
12/23/2025

Accepted date:
12/30/2025

Publication date:
01/01/2026

6956e18ea9539503f81360f9 mjpe Articles
Links & Downloads

Mediterr J Med Res

Share this page
Page Sections