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Cajanus cajan ameliorated CCl4-induced oxidative stress in Wistar rats via the combined mechanisms of anti-inflammation and mitochondrial-membrane transition pore inhibition.
J Ethnopharmacol. 2022 May 10; 289:114920.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Liver diseases is a public health issue in sub-saharan Africa and has been reported to be the major cause of many hospital admissions. Oxidative stress, mitochondrial dysfunction and inflammation play important roles in several diseases including liver injury. Cajanus cajan is an indigenous medicinal plant useful in the traditional treatment of jaundice, inflammation and liver injury.

AIM OF STUDY

This study assessed the effects of methanol extract Cajanus cajan (MECC) on mitochondrial permeability transition (mPT) pore opening, biomarkers of oxidative stress and inflammation in CCl4-induced liver injury in rats.

METHODS

Wistar albino rats (200-210g) were completely randomized into five (5) groups of six animals each. Group I (control) was given distilled water orally once daily. Animals in group II were administered CCl4 in parafin (1:1) at a dose of 0.5 mL/kg i.p on the seventh day. Animals in groups III, IV and V were administered methanol extract of Cajanus cajan (MECC) at doses of 100, 200 mg/kg and silymarin (100 mg/kg) respectively for 7 days prior to a single intraperitoneal dose of CCl4. After 24 h of CCl4 treatment, serum and liver tissues were collected. Mitochondrial permeability transition (mPT) pore opening, mitochondrial ATPase activities and biomarkers of oxidative stress were determined spectrophotometrically. Tumor necrosis factor (TNFα), NF-κB and COX-2 were determined by immunohistochemistry and the phytochemicals present in the extract were determined by GC-MS.

RESULTS

Liver enzyme (AST, ALP, ALT and γGT) activities and MDA levels were significantly decreased in rats pretreated with MECC at the dose of 100, 200 and silymarin (100 mg/kg) when compared to the rats administered CCl4 alone (p < 0.05). GSH, GST, CAT and SOD increased and the expressions of TNFα, NF-κB and COX- 2 were also reduced when compared to the CCl4- treated animals. In addition, the liver histopathological analyses revealed that MECC markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. GC-MS analysis yielded 23 compounds including flavonoids, terpenoids and fatty acids.

CONCLUSION

Cajanus cajan leaf extract elicited hepatoprotective action on CCl4-induced liver injury via inhibition of mPT pore opening, prevention of CCl4-induced hepatic oxidative stress and suppression of inflammatory response thus it may become useful for chemoprevention of liver injury. This supports its traditional use.

Authors+Show Affiliations

Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria; Department of Biochemistry, Lead City University, Ibadan, Nigeria. Electronic address: olajualao2204@gmail.com.Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria; Department of Biochemistry, Landmark University, Omu-aran, Nigeria.Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria; Department of Biochemistry, University of Lagos, Nigeria.Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

35032580

Citation

Nwaechefu, Olajumoke Olufunlayo, et al. "Cajanus Cajan Ameliorated CCl4-induced Oxidative Stress in Wistar Rats Via the Combined Mechanisms of Anti-inflammation and Mitochondrial-membrane Transition Pore Inhibition." Journal of Ethnopharmacology, vol. 289, 2022, p. 114920.
Nwaechefu OO, Olaolu TD, Akinwunmi IR, et al. Cajanus cajan ameliorated CCl4-induced oxidative stress in Wistar rats via the combined mechanisms of anti-inflammation and mitochondrial-membrane transition pore inhibition. J Ethnopharmacol. 2022;289:114920.
Nwaechefu, O. O., Olaolu, T. D., Akinwunmi, I. R., Ojezele, O. O., & Olorunsogo, O. O. (2022). Cajanus cajan ameliorated CCl4-induced oxidative stress in Wistar rats via the combined mechanisms of anti-inflammation and mitochondrial-membrane transition pore inhibition. Journal of Ethnopharmacology, 289, 114920. https://doi.org/10.1016/j.jep.2021.114920
Nwaechefu OO, et al. Cajanus Cajan Ameliorated CCl4-induced Oxidative Stress in Wistar Rats Via the Combined Mechanisms of Anti-inflammation and Mitochondrial-membrane Transition Pore Inhibition. J Ethnopharmacol. 2022 May 10;289:114920. PubMed PMID: 35032580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cajanus cajan ameliorated CCl4-induced oxidative stress in Wistar rats via the combined mechanisms of anti-inflammation and mitochondrial-membrane transition pore inhibition. AU - Nwaechefu,Olajumoke Olufunlayo, AU - Olaolu,Tomilola Debby, AU - Akinwunmi,Ifeoluwa Racheal, AU - Ojezele,Omotunde Oluwaseyi, AU - Olorunsogo,Olufunso Olabode, Y1 - 2022/01/13/ PY - 2021/07/26/received PY - 2021/12/07/revised PY - 2021/12/13/accepted PY - 2022/1/16/pubmed PY - 2022/3/17/medline PY - 2022/1/15/entrez KW - Cajanus cajan KW - Carbon tetrachloride KW - Inflammation KW - Mitochondrial permeability transition pore KW - Oxidative stress SP - 114920 EP - 114920 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 289 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Liver diseases is a public health issue in sub-saharan Africa and has been reported to be the major cause of many hospital admissions. Oxidative stress, mitochondrial dysfunction and inflammation play important roles in several diseases including liver injury. Cajanus cajan is an indigenous medicinal plant useful in the traditional treatment of jaundice, inflammation and liver injury. AIM OF STUDY: This study assessed the effects of methanol extract Cajanus cajan (MECC) on mitochondrial permeability transition (mPT) pore opening, biomarkers of oxidative stress and inflammation in CCl4-induced liver injury in rats. METHODS: Wistar albino rats (200-210g) were completely randomized into five (5) groups of six animals each. Group I (control) was given distilled water orally once daily. Animals in group II were administered CCl4 in parafin (1:1) at a dose of 0.5 mL/kg i.p on the seventh day. Animals in groups III, IV and V were administered methanol extract of Cajanus cajan (MECC) at doses of 100, 200 mg/kg and silymarin (100 mg/kg) respectively for 7 days prior to a single intraperitoneal dose of CCl4. After 24 h of CCl4 treatment, serum and liver tissues were collected. Mitochondrial permeability transition (mPT) pore opening, mitochondrial ATPase activities and biomarkers of oxidative stress were determined spectrophotometrically. Tumor necrosis factor (TNFα), NF-κB and COX-2 were determined by immunohistochemistry and the phytochemicals present in the extract were determined by GC-MS. RESULTS: Liver enzyme (AST, ALP, ALT and γGT) activities and MDA levels were significantly decreased in rats pretreated with MECC at the dose of 100, 200 and silymarin (100 mg/kg) when compared to the rats administered CCl4 alone (p < 0.05). GSH, GST, CAT and SOD increased and the expressions of TNFα, NF-κB and COX- 2 were also reduced when compared to the CCl4- treated animals. In addition, the liver histopathological analyses revealed that MECC markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. GC-MS analysis yielded 23 compounds including flavonoids, terpenoids and fatty acids. CONCLUSION: Cajanus cajan leaf extract elicited hepatoprotective action on CCl4-induced liver injury via inhibition of mPT pore opening, prevention of CCl4-induced hepatic oxidative stress and suppression of inflammatory response thus it may become useful for chemoprevention of liver injury. This supports its traditional use. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/35032580/Cajanus_cajan_ameliorated_CCl4_induced_oxidative_stress_in_Wistar_rats_via_the_combined_mechanisms_of_anti_inflammation_and_mitochondrial_membrane_transition_pore_inhibition_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(21)01150-8 DB - PRIME DP - Unbound Medicine ER -