Multiomics Profiling Reveals Protective Function of <i>Schisandra</i> Lignans against Acetaminophen-Induced Hepatotoxicity

Yan, Caixia; Guo, Huimin; Ding, Qingqing; Shao, Yuhao; Kang, Dian; Yu, Tengjie; Li, Changjian; Du, Yisha; Wang, He; Hu, Kangrui; Xie, Lin; Wang, Guangji; Liang, Yan

doi:10.1124/dmd.120.000083

Cited by 14 publications

(6 citation statements)

References 52 publications

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“…The extraction process of SLE was systematically improved in our previous work 27 , 30 . Briefly, S. chinensis crude powder were weighed and filtered through a fine sieve of 270 μm.…”

Section: Methodsmentioning

confidence: 99%

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines

Xue

Liu

Yan

et al. 2023

Acta Pharmaceutica Sinica B

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“…The extraction process of SLE was systematically improved in our previous work 27 , 30 . Briefly, S. chinensis crude powder were weighed and filtered through a fine sieve of 270 μm.…”

Section: Methodsmentioning

confidence: 99%

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines

Xue

Liu

Yan

et al. 2023

Acta Pharmaceutica Sinica B

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“…HepG2.2.15 cells were treated with 5 μM TMF/TAF/TDF for 3, 6, and 9 days, and then cells were collected for untargeted metabolomics analysis and targeted lipidomics analysis with metabolite identification based on LC-Q/TOF-MS as we described previously ( Yan et al, 2020 ). The compounds involved were semi-quantified through the peak area of each compound weighted by total ion chromatography.…”

Section: Methodsmentioning

confidence: 99%

Improved pharmacokinetics of tenofovir ester prodrugs strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism in preclinical models

et al. 2022

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Tenofovir (TFV) ester prodrugs, a class of nucleotide analogs (NAs), are the first-line clinical anti-hepatitis B virus (HBV) drugs with potent antiviral efficacy, low resistance rate and high safety. In this work, three marketed TFV ester drugs, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) and tenofovir amibufenamide fumarate (TMF), were used as probes to investigate the relationships among prodrug structures, pharmacokinetic characteristics, metabolic activations, pharmacological responses and to reveal the key factors of TFV ester prodrug design. The results indicated that TMF and TAF exhibited significantly stronger inhibition of HBV DNA replication than did TDF in HBV-positive HepG2.2.15 cells. The anti-HBV activity of TMF was slightly stronger than TAF after 9 days of treatment (EC50 7.29 ± 0.71 nM vs. 12.17 ± 0.56 nM). Similar results were observed in the HBV decline period post drug administration to the HBV transgenic mouse model, although these three TFV prodrugs finally achieved the same anti-HBV effect after 42 days treatments. Furthermore, TFV ester prodrugs showed a correcting effect on disordered host hepatic biochemical metabolism, including TCA cycle, glycolysis, pentose phosphate pathway, purine/pyrimidine metabolism, amino acid metabolism, ketone body metabolism and phospholipid metabolism. The callback effects of the three TFV ester prodrugs were ranked as TMF > TAF > TDF. These advantages of TMF were believed to be attributed to its greater bioavailability in preclinical animals (SD rats, C57BL/6 mice and beagle dogs) and better target loading, especially in terms of the higher hepatic level of the pharmacologically active metabolite TFV-DP, which was tightly related to anti-HBV efficacy. Further analysis indicated that stability in intestinal fluid determined the actual amount of TFV prodrug at the absorption site, and hepatic/intestinal stability determined the maintenance amount of prodrug in circulation, both of which influenced the oral bioavailability of TFV prodrugs. In conclusion, our research revealed that improved pharmacokinetics of TFV ester prodrugs (especially intestinal stability) strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism, which provides new insights and a basis for the design, modification and evaluation of new TFV prodrugs in the future.

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“…Omics. Acetaminophen overdose is the most common cause of acute liver failure in Western countries (Yan et al, 2020). Despite decades of research into the mechanisms of this life-threatening event, treatment options remain limited.…”

Section: Australia Complementary Medicinesmentioning

confidence: 99%

“…Lignans contained in the TCM Schisandra chinensis have been shown to exhibit hepatoprotective effects. Yan et al (2020) used a multiomics approach (metabolomics, proteomics, lipidomics) to determine the mechanism of acetaminophen-induced acute liver failure and hepatoprotective effects of a Schisandra lignan extract in mice. Results indicated that the liver failure was associated with lipid regulation and that Schisandra lignan extract exerts hepatoprotective effects by decreasing intrahepatic diglyceride and triglyceride concentrations.…”

Section: Australia Complementary Medicinesmentioning

confidence: 99%

Natural Products: Experimental Approaches to Elucidate Disposition Mechanisms and Predict Pharmacokinetic Drug Interactions

Paine

2020

Drug Metab Dispos

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Natural products have been used by humans since antiquity for both egregious and beneficial purposes. Regarding the latter, these products have long been valued as a rich source of phytochemicals and developed into numerous life-saving pharmaceutical agents. Today, the sales and use of natural products with purported medicinal qualities continue to increase worldwide. However, natural products are not subject to the same premarket testing requirements as pharmaceutical agents, creating critical gaps in scientific knowledge about their optimal use. In addition, due to the common misperception that "natural" means "safe," patients may supplement or replace their prescription medications with natural products, placing themselves at undue risk for subefficacious pharmacotherapy or potentially toxic exposure. Collectively, with few exceptions, researchers, health care providers, and educators lack definitive information about how to inform consumers, patients, and students in the health professions on the safe and optimal use of these products. Recognition of this deficiency by key stakeholders, including the three pillars of biomedical research-industry, academia, and government-has facilitated multiple collaborations that are actively addressing this fundamental knowledge gap. This special issue contains a collection of articles highlighting the challenges faced by researchers in the field and the use of various experimental systems and methods to improve the mechanistic understanding of the disposition and drug interaction potential of natural products. Continued refinement of existing, and development of new, approaches will progress toward the common overarching goal of improving public health. SIGNIFICANCE STATEMENT Natural products with purported medicinal value constitute an increasing share of the contemporary health care market. Natural products are not subject to the same premarket testing requirements as drug products, creating fundamental scientific knowledge gaps about the safe and effective use of these products. Collaborations among industrial, academic, and governmental researchers in multiple disciplines are anticipated to provide the definitive information needed to fill these gaps and improve public health.

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Multiomics Profiling Reveals Protective Function of Schisandra Lignans against Acetaminophen-Induced Hepatotoxicity

Cited by 14 publications

References 52 publications

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines

Improved pharmacokinetics of tenofovir ester prodrugs strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism in preclinical models

Natural Products: Experimental Approaches to Elucidate Disposition Mechanisms and Predict Pharmacokinetic Drug Interactions

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