Investigation of the Therapeutic Effect of Total Alkaloids of Corydalis saxicola Bunting on CCl4-Induced Liver Fibrosis in Rats by LC/MS-Based Metabolomics Analysis and Network Pharmacology

Abstract

: Liver fibrosis is a pathological result of liver injury that usually leads to a pathophysiological wound healing response. The total alkaloids of Corydalis saxicola Bunting (TACS) have been used for hepatoprotective effects on the liver. However, its exact therapeutic mechanisms of liver fibrosis are not yet well understood. To explore the potential anti-fibrosis mechanism of TACS, metabolomics coupled with network pharmacology were applied to reveal the underlying mechanisms. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with multivariate statistical analyses were performed to estimate changes in metabolic profiles. As a result, a total of 23 metabolites in rats with liver fibrosis were altered; of these, 11 had been downregulated and 12 had been upregulated compared with the control group. After TACS treatment, the levels of 13 metabolites were significantly restored compared with the CCl4-treated group, of which 4 metabolites were up-regulated and 9 metabolites were down-regulated. Many of these metabolites are involved in the bile acid metabolism, glutathione metabolism, tryptophan metabolism and purine metabolism. Then, three key targets, including cytochrome P450 family1 subfamily A member 1 (CYP1A1), ornithine decarboxylase 1 (OCD1) and monoamine oxidase Type B (MAOB) were predicted as potential therapeutic targets of TACS against liver fibrosis through network pharmacology analysis. Finally, palmatine, tetrahydropalmatine and dehydrocavidine were screened as potential active compounds responsible for the anti-fibrosis effect of TACS by molecular docking analysis. This study reveals that TACS exerted anti-fibrosis effects by regulating the liver metabolic pathway with multiple components and multiple targets, which is helpful to further clarify the hepatoprotective mechanisms of natural plant extracts.

Nutraceutical Activity of Anthocyanins from the Edible Berries of Rhamnus pompana

“…Previous studies sustain that K69, H197, R277, D332, and R154 are essential for the optimal function of ODC [22–23] . Key ligand‐protein interactions include those with K69, D332, D361, H197, Y389, F170, and S200 which are interaction sites of LOHA7 and xanthohumol with ODC [22–23] . In the same context, ODC/tetrahydropalmatine complex shows similar interrelation with H197, N398, and S200 [23] .…”

“…The rutinoside portion was linked to D159, S200, R277, and D332 by hydrogen bonds, as well as by carbon‐hydrogen bonds interaction with H197 and the cofactor pyridoxal phosphate (PLP) attached to K69. Previous studies sustain that K69, H197, R277, D332, and R154 are essential for the optimal function of ODC [22–23] . Key ligand‐protein interactions include those with K69, D332, D361, H197, Y389, F170, and S200 which are interaction sites of LOHA7 and xanthohumol with ODC [22–23] .…”

“…Key ligand‐protein interactions include those with K69, D332, D361, H197, Y389, F170, and S200 which are interaction sites of LOHA7 and xanthohumol with ODC [22–23] . In the same context, ODC/tetrahydropalmatine complex shows similar interrelation with H197, N398, and S200 [23] . Interestingly, the residues A162, L363, K161, and V168 networked with the pelargonidin portion through π‐alkyl interactions in the active site 2.…”

Inhibitory Effects of Corydalis saxicola Bunting Total Alkaloids on Macrophage Pyroptosis

“…The filtrate was mixed and concentrated to 1g/ mL under reduced pressure to obtain the extraction. The chemical profile was characterized using ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (Milford, MA, USA), as described in a previous study [45] . Ten components of CSBTA were identified: cheilanthifoline, berberrubine, epiberberine, tetrahydropalmatine, jatrorrhizine, coptisine, dehydrocavidine, palmatine, berberine, and chelerythrine.…”

The Protective Effect of Lycium barbarum Betaine and Effervescent Tablet Against Carbon Tetrachloride-Induced Acute Liver Injury in Rats

“…[4][5][6][7] Carbon tetrachloride (CCl 4 ) is a common industrial solvent, cleaning agent, and a potent hepatotoxin, widely used in the laboratory to induce liver injury and fibrosis. 8 CCl 4 generates highly reactive CCl 3 through the mediation of cytochrome p450, which leads to lipid peroxidation by stress, which eventually leads to hepatocellular damage. It is thus commonly used to establish an acute liver injury mice model of acute liver injury.…”