Network Pharmacology and Molecular Docking Study on the Multi-Target Mechanisms of Aloe vera for Non-Alcoholic Steatohepatitis Treatment

Abstract

Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with limited treatment options. The widely distributed plant Aloe vera has shown protective effects against NASH in animals, yet the precise mechanism remains unknown. In this study, we investigated the potential mechanisms underlying the anti-NASH effects of Aloe vera using a network pharmacology and molecular docking approach. By searching online databases and analyzing the Gene Expression Omnibus dataset, we obtained 260 Aloe vera–NASH common targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the common targets were strongly associated with the key pathological processes implicated in NASH, including lipid and glucose metabolism, inflammation, apoptosis, oxidative stress, and liver fibrosis. Four core proteins, AKT serine/threonine kinase 1 (AKT1), tumor necrosis factor alpha (TNFα), transcription factor c-Jun, and tumor suppressor protein p53, were identified from compound–target–pathway and protein–protein interaction networks. Molecular docking analysis verified that the active ingredients of Aloe vera were able to interact with the core proteins, especially AKT1 and TNFα. The results demonstrate the multi-compound, multi-target, and multi-pathway mechanisms of Aloe vera against NASH. Our study has shown the scientific basis for further experiments in terms of the mechanism to develop Aloe vera-based natural products as complementary treatments for NASH. Furthermore, it identifies novel drug candidates based on the structures of Aloe vera’s active compounds.

Aloin Attenuates Oxidative Stress, Inflammation, and CCl4-Induced Liver Fibrosis in Mice: Possible Role of TGF-β/Smad Signaling

“…Prior research has demonstrated that overexpression of Smad7 inhibits TGF-β/Smad and suppresses the high expression of HSCs . As reported in previous network pharmacology (selection of specific signaling nodes for multitarget drug molecule design based on systems biology theory) and molecular docking (interaction between receptors and drug molecules) studies for the treatment of nonalcoholic steatohepatitis, aloin has a strong binding affinity to c-Jun . In liver fibrosis, c-Jun is a transcription factor that plays an important regulatory role in cells .…”

“…Research had demonstrated that aloin offers protection against nonalcoholic fatty liver disease, and fibrosis is the development outcome of nonalcoholic fatty liver disease . Therefore, we further studied the antiliver fibrosis effect of aloin.…”

“…Therefore, decreasing the concentrations of proinflammatory cytokine may offer potential benefits in improving fibrosis. Furthermore, aloin was widely used in inflammation, such as lipopolysaccharide-induced acute lung injury and neurodegenerative diseases. , Meanwhile, a molecular docking on Aloe vera also showed a strong correlation of aloin with TNF-α . CCl 4 has shown toxic effects in the liver and could induce inflammation .…”

“…37,38 Meanwhile, a molecular docking on Aloe vera also showed a strong correlation of aloin with TNF-α. 18 CCl 4 has shown toxic effects in the liver and could induce inflammation. 39 In vivo experiments, aloin inhibited the TGF-β/Smad pathway, downregulated TNF-α, IL-6, and IL-1β, and increased IL-10.…”

“…Research had demonstrated that aloin offers protection against nonalcoholic fatty liver disease, and fibrosis is the development outcome of nonalcoholic fatty liver disease. 18 Therefore, we further studied the antiliver fibrosis effect of aloin. In this part of our experiment, we observed a rougher liver surface with jagged edges in the CCl 4 group, and the liver surface was improved in the CCl 4 + Alo groups (Figure 4A).…”