Metabolomic Profiling for Identification of Potential Biomarkers in the Protective Effects of Modified Sinisan against Liver Injury in Dimethylnitrosamine Treated Rats

Liu, Chenggang; Wang, Xiaoli; Du, Xiaomei; De-you, Jiang; Geng, Naizhi; Zhang, Shuoxin; Zhou, Yuanyuan; Kuang, Hai‐Xue

doi:10.1248/bpb.b13-00127

Cited by 18 publications

(6 citation statements)

References 31 publications

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“…The liver is the principal site of the hydroxylation of phenylalanine to tyrosine and further tyrosine degradation. Previous studies have shown that metabolic disturbance of phenylalanine and tyrosine is responsible for many clinical disorders of livers [54,55]. In our study, the levels of phenylalanine and tyrosine in the DM groups were significantly less than those in the DM groups at the 5th and 9th weeks, indicating that phenylalanine and tyrosine metabolism were impaired during DM development.…”

Section: Liver Amino Acid Metabolism During Dm Developmentsupporting

confidence: 45%

Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation

Chen

Zheng

et al. 2019

Bioscience Reports

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Background: The present study aimed to explore the changes in the hepatic metabolic profile during the evolution of diabetes mellitus (DM) and verify the key metabolic pathways. Methods: Liver samples were collected from diabetic rats induced by streptozotocin (STZ) and rats in the control group at 1, 5, and 9 weeks after STZ administration. Proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabolomics was used to examine the metabolic changes during the evolution of DM, and partial least squares-discriminate analysis (PLS-DA) was performed to identify the key metabolites. Results: We identified 40 metabolites in the 1H NMR spectra, and 11 metabolites were further selected by PLS-DA model. The levels of α-glucose and β-glucose, which are two energy-related metabolites, gradually increased over time in the DM rats, and were significantly greater than those of the control rats at the three-time points. The levels of choline, betaine, and methionine decreased in the DM livers, indicating that the protective function in response to liver injury may be undermined by hyperglycemia. The levels of the other amino acids (leucine, alanine, glycine, tyrosine, and phenylalanine) were significantly less than those of the control group during DM development. Conclusions: Our results suggested that the hepatic metabolic pathways of glucose, choline-betaine-methionine, and amino acids were disturbed during the evolution of diabetes, and that choline-betaine-methionine metabolism may play a key role.

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Section: Liver Amino Acid Metabolism During Dm Developmentsupporting

confidence: 45%

Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation

Chen

Zheng

et al. 2019

Bioscience Reports

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“…Serum Tyr concentrations are significantly increased in patients with liver injury [36]. Zhao et al .…”

Section: Discussionmentioning

confidence: 99%

Shaofu Zhuyu decoction ameliorates obesity-mediated hepatic steatosis and systemic inflammation by regulating metabolic pathways

et al. 2017

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Shaofu Zhuyu decoction (SFZYD, also known as Sobokchugeo-tang), a classical prescription drug in traditional East Asian medicine, has been used to treat blood stasis syndrome (BSS). Hepatic steatosis is the result of excess caloric intake, and its pathogenesis involves internal retention of phlegm and dampness, blood stasis, and liver Qi stagnation. To evaluate the effects of treatment with SFZYD on obesity-induced inflammation and hepatic steatosis, we fed male C57BL/6N mice a high fat diet (HFD) for 8 weeks and then treated them with SFZYD by oral gavage for an additional 4 weeks. The results of histological and biochemical examinations indicated that SFZYD treatment ameliorates systemic inflammation and hepatic steatosis. A partial least squares-discriminant analysis (PLS-DA) scores plot of serum metabolites showed that HFD mice began to produce metabolites similar to those of normal chow (NC) mice after SFZYD administration. We noted significant alterations in the levels of twenty-seven metabolites, alterations indicating that SFZYD regulates the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism. Increases in the levels of TCA cycle intermediate metabolites, such as 2-oxoglutaric acid, isocitric acid, and malic acid, in the serum of obese mice were significantly reversed after SFZYD treatment. In addition to inducing changes in the above metabolites, treatment with SFZYD also recovered the expression of genes related to hepatic mitochondrial dysfunction, including Ucp2, Cpt1α, and Ppargc1α, as well as the expression of genes involved in lipid metabolism and inflammation, without affecting glucose uptake or insulin signaling. Taken together, these findings suggest that treatment with SFZYD ameliorated obesity-induced systemic inflammation and hepatic steatosis by regulating inflammatory cytokine and adipokine levels in the circulation and various tissues. Moreover, treatment with SFZYD also reversed alterations in the levels of metabolites of the TCA cycle, the pentose phosphate pathway and aromatic amino acid metabolism.

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“…This prescription consists of four herbal medicines: Bupleuri Radix, Paeoniae Alba Radix, Aurantii Immaturus Fructus, and Honey-fried Licorice Root in equal proportions. Si-Ni-San can alleviate liver injury through protecting hepatocyte membranes, increasing NO release and facilitating apoptosis of liver-infiltrating cells[14], and modified Si-Ni-San also has hepatoprotective effects[15]. Moreover, glycyrrhizin[16] and paeoniflorin[17], two components of Si-Ni-San, have shown beneficial effects on NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Freeze-dried Si-Ni-San powder can ameliorate high fat diet-induced non-alcoholic fatty liver disease

Zhu

Feng

et al. 2019

WJG

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BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. However, to date, there is no ideal therapy for this disease. AIM To study the effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice. METHODS Twenty-four male C57BL/6 mice were randomized into three groups of eight. The control group (CON) was allowed ad libitum access to a normal chow diet. The high fat diet group (FAT) and Si-Ni-San group (SNS) were allowed ad libitum access to a high fat diet. The SNS group was intragastrically administered Si-Ni-San freeze-dried powder (5.0 g/kg) once daily, and the CON and FAT groups were intragastrically administered distilled water. After 12 wk, body weight, liver index, visceral fat index, serum alanine aminotransferase (ALT), portal lipopoly-saccharide (LPS), liver tumor necrosis factor (TNF)-α and liver triglycerides were measured. Intestinal microbiota were analyzed using a 16S r DNA sequencing technique. RESULTS Compared with the FAT group, the SNS group exhibited decreased body weight, liver index, visceral fat index, serum ALT, portal LPS, liver TNF-α and liver triglycerides ( P < 0.05). Intestinal microbiota analysis showed that the SNS group had different bacterial composition and function compared with the FAT group. In particular, Oscillospira genus was a bacterial biomarker of SNS group samples. CONCLUSION The beneficial effects of Si-Ni-San freeze-dried powder on high fat diet-induced NAFLD in mice may be associated with its anti-inflammatory and changing intestinal microbiota effects.

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Metabolomic Profiling for Identification of Potential Biomarkers in the Protective Effects of Modified Sinisan against Liver Injury in Dimethylnitrosamine Treated Rats

Cited by 18 publications

References 31 publications

Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation

Changes in hepatic metabolic profile during the evolution of STZ-induced diabetic rats via an 1H NMR-based metabonomic investigation

Shaofu Zhuyu decoction ameliorates obesity-mediated hepatic steatosis and systemic inflammation by regulating metabolic pathways

Freeze-dried Si-Ni-San powder can ameliorate high fat diet-induced non-alcoholic fatty liver disease

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