PLoS One. 2023 Sep 15;18(9):e0291125. doi: 10.1371/journal.pone.0291125. eCollection 2023.
ABSTRACT
INTRODUCTION: The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl4), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats.
MATERIALS AND METHODS: Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically.
RESULTS AND DISCUSSION: Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase (γ-GT) in CCl4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p<0.05 & p<0.01, respectively. On the other hand, G. procumbens and silymarin displayed Statistically significant (p<0.05) and high significant(p<0.01) increased levels of HDL, CAT SOD (here p<0.05 & p<0.01 for different doses) when the treatment groups were compared with the disease control group. Because the therapeutic activity imparted by plants and drugs accelerates the movement of the disturbed pathophysiological state toward the healthy state. In the molecular docking analysis, G. procumbens phytoconstituents performed poorly against transforming growth factor-beta 1 (TGF-β1) compared to the control drug silymarin. In contrast, 26 phytoconstituents scored better than the control bezafibrate against peroxisome proliferator-activated receptor alpha (PPAR-α). The top scoring compounds for both macromolecules were observed to form stable complexes in the molecular dynamics simulations. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity. It can, thus, be inferred that the extract of G. procumbens showed good hepatoprotective properties in rats.
PMID:37713406 | DOI:10.1371/journal.pone.0291125
