The Qingchangligan Formula Alleviates Acute Liver Failure by Regulating Galactose Metabolism and Gut Microbiota

Abstract

The Qingchangligan formula (QCLGF) is a traditional Chinese medicine that has significant clinical potential for patients with acute liver failure (ALF). However, the experimental evidence of the effect of QCLGF on ALF and the associated mechanisms remain elusive. We aimed to evaluate the function of QCLGF in ALF and the underlying mechanism. ALF was induced in rats by intraperitoneal injection of D-GalN (1100 mg/kg). The Qingchangligan formula was administered to the rats (6.725 g/kg · d) for 5 days, and the model group and the control group were given the same amount of physiological saline. Then 16S rRNA gene sequencing, high performance gas chromatography-mass spectrometry (GC-MS), and RNA-seq analysis were performed on the samples. The levels of ALT and AST in the ALF rats were abnormal (5322.08 ± 566.27 U/L and 7655.95 ± 1238.08 U/L, respectively) compared with the normal control (98.98 ± 6.90 U/L and 99.63 ± 10.94 U/L, respectively). The levels of ALT and AST in the QCLGF rats (2997.67 ± 469.24 U/L and 4158.40 ± 596.07 U/L, respectively) were closer the normal control group. Liver HE staining showed that the degree of liver damage in the QCLGF rats was lighter than that in the ALF rats. The overall structure of the gut microbiota after ALF was significantly altered, including Proteobacteria, Blautia, Romboutsia, Parabacteroides, UCG-008, Parasutterella, Ruminococcus, norank_f:Lachnospiraceae, the Eubacterium_xylanophilum_group, Oscillibacter, and Eisenbergiella. QCLGF balanced the structure and abundance of intestinal flora. The levels of D(+)galactose, isopropyl beta-D-1-thiogalactopyranoside and D-mannitol were lighter in the plasma of the ALF rats than in the normal control rats, but there were significantly elevated levels of those metabolites in the QCLGF rats. The gene expression changed significantly in the ALF rats. QCLGF regulated the expression of THBS1 and the KEGG pathways of carbohydrate metabolism, lipid metabolism, signal transduction, the immune system, and infectious disease: bacterial. QCLGF may alleviating intestinal flora disorder, regulating galactose metabolism and downregulating the expression of THBS1 to alleviate D-GalN induced acute liver failure.

Untargeted Metabolomics Based on UPLC-Q-Exactive-Orbitrap-MS/MS Revealed the Differences and Correlations between Different Parts of the Root of Paeonia lactiflora Pall

“…Due to its chemical properties that allow for transmembrane diffusion, galactose is clinically used to generate glycoconjugates for improved drug absorption, as successfully demonstrated in supplementing dopamine for Parkinson’s patients [ 28 ]. Regulating galactose metabolism has been shown to alleviate acute liver damage and improve some complications of endotoxemia [ 29 , 30 ]. Earlier studies indicated that fatty acid and sugar metabolites are more abundant in phl, suggesting that PLP might regulate metabolic pathways through phl, thus exerting hepatoprotective and menstrual regulation effects.…”

Effects of gut microbiota on prostatic cancer: a two-sample Mendelian randomization study

“…Lachnospiraceae UCG-008 is considered a potential harmful genus in human colonic microbiota (Huang et al, 2019). Some medicines improve gut microbial dysbiosis by increasing beneficial bacteria and decreasing harmful bacteria, including Lachnospiraceae UCG-008 in order to relieve diseases (Huang et al, 2019;Yin et al, 2021). In conclusion, how gut microbiota influence the development of PCa by disturbing the metabolism is still unclear; further studies are needed to clarify the specific biological mechanisms.…”

Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome

“…Specific TCM treatments have been shown to reduce potential pathogens, increase SCFA-producing bacteria, and improve gastrointestinal symptoms and the intestinal barrier. In mouse models, these include a combination of curcumin, aloe vera, slippery elm, guar gum, pectin, peppermint oil, and glutamine [429]; a gegen qinlian decoction [430]; a diallyl disulphide garlic extract [431]; a Pi-Dan-Jian-Qing decoction [432]; Qingchangligan [433]; a Buyang Huanwu decoction [434]; Schisantherin A [435]; Chimonanthus nitens Oliv. leaf [436]; Lycium barbarum glycopeptide [437]; a Banxia Xiexin decoction [438]; and a Qing-Fei-Pai-Du decoction [439].…”