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Network Pharmacology-Based Analysis of Pogostemon cablin (Blanco) Benth Beneficial Effects to Alleviate Nonalcoholic Fatty Liver Disease in Mice.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is associated with high morbidity and mortality. Pogostemon cablin (Blanco) Benth/Huo Xiang (HX) is a perennial herb with unique anti-oxidant and anti-inflammatory properties, and thus, can positively affect liver function. In this study, we used network pharmacology to predict the potential mechanism of HX on NAFLD. Pharmacological experiments were used to verify the effect of HX on the functions of NAFLD. Network pharmacology identified nine components that interacted with 82 NAFLD-related targets, revealing four target genes: TNF, IL6, TP53, and AKT1. HX prevents the development and progression of NAFLD through different pathways and targets with quercetin-regulated lipid metabolism, anti-inflammatory, and anti-oxidant pathways playing an essential role in the treatment of NAFLD. Compared with feeding HFD, HX significantly attenuated lipid accumulation in vivo with mice and also in vitro with mouse liver cells. A high dose of HX decreased hepatocyte lipid accumulation and the abundance of SREBF1 and FASN. Validation experiments revealed that HX inhibited the activation of NF-κB/IκB signaling and decreased the release and levels of pro-inflammatory factors (TNF-α and IL-6). These data suggest that HX can attenuate abnormal lipid metabolic responses and enhance antioxidant mechanisms. Thus, the pharmacological effects from plants used in traditional Chinese medicine are achievde through a multi-level response.

SUBMITTER: Cui Y

PROVIDER: S-EPMC8652055 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Influenza is historically an ancient disease that causes annual epidemics and, at irregular intervals, pandemics. At present, the first-line drugs (oseltamivir and zanamivir) don't seem to be optimistic due to the spontaneously arising and spreading of oseltamivir resistance among influenza virus. Pogostemon cablin (Blanco) Benth. (P. cablin) is an important traditional Chinese medicine herb that has been widely used for treatment on common cold, nausea and fever. In our previous study, we have identified an extract derived from P. cablin as a novel selective neuraminidase (NA) inhibitor. RESULTS:A series of polyphenolic compounds were isolated from P. cablin for their potential ability to inhibit neuraminidase of influenza A virus. Two new octaketides (1, 2), together with other twenty compounds were isolated from P. cablin. These compounds showed better inhibitory activity against NA. The significant potent compounds of this series were compounds 2 (IC50 = 3.87 ± 0.19 ? mol/ml), 11, 12, 14, 15, 19 and 20 (IC50 was in 2.12 to 3.87 ? mol/ml), which were about fourfold to doubled less potent than zanamivir and could be used to design novel influenza NA inhibitors, especially compound 2, that exhibit increased activity based on these compounds. With the help of molecular docking, we had a preliminary understanding of the mechanism of the two new compounds (1-2)' NA inhibitory activity. CONCLUSIONS:Fractions 6 and polyphenolic compounds isolated from fractions 6 showed higher NA inhibition than that of the initial plant exacts. The findings of this study indicate that polyphenolic compounds and fractions 6 derived from P. cablin are potential NA inhibitors. This work is one of the evidence that P. cablin has better inhibitory activity against influenza, which not only enriches the compound library of P. cablin, but also facilitates further development and promises its therapeutic potential for the rising challenge of influenza diseases.

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Network Pharmacology-Based Analysis of Pogostemon cablin (Blanco) Benth Beneficial Effects to Alleviate Nonalcoholic Fatty Liver Disease in Mice.

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