Abstract
Materials and Methods Various aqueous extracts were prepared from this plant and preadministered per os to albino mice 3 h before APAP administration, once daily for one week. Animals from the normal group were given only distilled water while those from negative control received only APAP 250 mg/kg. After treatment, mice were sacrificed, the liver was collected for histopathology analysis, and different biochemical markers (alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNFα)) were measured. The content of the active extract was analyzed by HPLC/UV. Molecular docking was conducted using iGEMDOCK software, and the drug-likeness and pharmacokinetic profiles were evaluated using Swiss ADME. Results APAP administration significantly increased (p < 0.001) ALT in liver homogenates when compared to normal controls whereas the stem decoction at 250 mg/kg significantly (p < 0.001) reduced this activity to a normal value comparable to silymarin 50 mg/kg which is better than leaf and root extracts. Moreover, the stem decoction also significantly reduced the MDA levels (p < 0.05) and increased those of GSH, SOD, and CAT (p < 0.001) at doses of 250 and 500 mg/kg compared to the negative control. A significant (p < 0.001) decrease of TNFα levels and leukocyte infiltration was observed following treatment with this extract. The HPLC/UV analysis of the decoction revealed the presence of dihydroxycoumarin, quinine, and scopoletin with the following retention times: 2.6, 5.1, and 7.01 min, respectively. In silico studies showed that quinine and dihydroxycoumarin had great potentials to be orally administered drugs and possessed strong binding affinities with TNFα, TNF receptor, cyclooxygenase-2, iNOS, cytochrome P450 2E1, and GSH reductase. Conclusion Based on these results, L. hastata could be considered a source of promising hepatoprotective compounds with antioxidant and anti-inflammatory properties.
Highlights
The liver is a central organ in energy metabolism and the biotransformation of xenobiotics
We found that the posttreatment of mice with the stem decoction reduced by 67.32% of the liver ALT activity, less than silymarin (72.95%, 6:83 ± 1:08 IU/L) and better than infusion (50.49%, 12:5 ± 0:86 IU/L) and macerate (44.55%, 14:00 ± 0:57 IU/L) (Figure 2(b))
Further analysis demonstrated that this effect was dose-dependent (Figure 2(c)) while no toxic effect was observed at 500 mg/kg
Summary
The liver is a central organ in energy metabolism and the biotransformation of xenobiotics. Mice were sacrificed, the liver was collected for histopathology analysis, and different biochemical markers (alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and tumor necrosis factoralpha (TNFα)) were measured. APAP administration significantly increased (p < 0:001) ALT in liver homogenates when compared to normal controls whereas the stem decoction at 250 mg/kg significantly (p < 0:001) reduced this activity to a normal value comparable to silymarin 50 mg/kg which is better than leaf and root extracts. The stem decoction significantly reduced the MDA levels (p < 0:05) and increased those of GSH, SOD, and CAT (p < 0:001) at doses of 250 and 500 mg/kg compared to the negative control. Based on these results, L. hastata could be considered a source of promising hepatoprotective compounds with antioxidant and anti-inflammatory properties
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