For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH(2)-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration.
Morinda citrifolia L. is a plant of the family Rubiaceae and is known as Indian mulberry or Noni in India. It is a perennial herb native to Southeast Asia and has been used over the years as a food supplement and medicinal plant. Noni fruits are reported to possess anticancer, fungicidal, antiviral and antiarthritic effects. The objective of our study is the screening of the immunomodulatory activity of the total extract, fractions, and isolated compounds of Noni fruits to identify their bioactive compounds. To achieve our goal, an ethanol extract (EE) was prepared from Noni fruits. Fractionation and purification of the EE were accomplished. The cell-mediated immune (CMI) response in prednisolone-induced immunosuppression rats was evaluated. The toxicity of the EE, fractions and isolated compounds on the differentiated THP-1 macrophage was assessed using the MTT viability assay. Moreover, the inflammation-related immune responses in lipopolysaccharide (LPS)-induced THP-1 macrophage activation were evaluated. Fractionation of the EE gave three fractions, dichloromethane (DCMF), water (WF) and methanol (MF). Purification of DCMF yielded stigmast-7-ene-3-ol (M1), 28-hydroxy-3β-acetoxy-9-dehydrogramisterol (M2), 3β-acetoxy-taraxast-20(30)-ene-21-ol (M3), 22-dehydroclerosterol (M4) and 22-dehydroclerosterol-3-O-β-d-glucopyranoside (M5), while purification of MF yielded quercetin (M6), hesperidin (M7), naringin (M9) and gallic acid (M8). The results revealed that DCMF elicited an increase in paw edema to the extent of 35.8%. All the tested samples had no cytotoxic effect on THP-1 macrophages. Co-treatment of the LPS-induced macrophages with DCMF, M2, M3, and M6 decreased the production of TNF-α, IL-1β, and IL-6/IL-10. The expression of iNOS, COX-2, and NF-κB decreased to 0.14 ± 0.02, 0.15 ± 0.02, and 0.17 ± 0.03, respectively, after co-treatment with LPS and DCMF. M2 attenuated the expression of iNOS and NF-κB to 0.18 ± 0.03 and 0.17 ± 0.03, respectively. Additionally, M3 attenuated the expression of iNOS to 0.18 ± 0.03, and after co-treatment with M6 and LPS, the expression of COX-2 and NF-κB was down-regulated to 0.2 ± 0.03. Our study proves the immunomodulatory effect of Noni fruits and specifies for the first time the compounds responsible for their activity.