1 HNMR-based metabonomic study of sub-chronic hepatotoxicity induced by realgar

Huo, Taoguang; Fang, Ying; Zhao, Longshan; Xiong, Zhili; Zhang, Yinghua; Wang, Yanlei; Cong, Feng; Yuan, Mingmei; Wang, Shouyun; Chen, Mo; Jiang, Hong

doi:10.1016/j.jep.2016.07.003

Cited by 25 publications

(18 citation statements)

References 25 publications

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“…Similarly, the intestinal flora‐catalyzed deglycosylation of most glycosides in the individual herbs ( S. baicalensis , G. uralensis , Paeonia lactiflora ) of Huangqin‐Tang was improved by combined incubation . Realgar, a main component of Niuhuang‐Jiedu‐Tablet (NJT), a TCM prescription for the treatment of acute tonsillitis, pharyngitis, periodontitis, and mouth ulcer, is toxic when used alone because it impairs systemic host and gut metabolism, but, interestingly, the toxicity is significantly alleviated by co‐administration with the other HMs in NJT, namely Rheum palmatum root and rhizome (RRR), S. baicalensis root (SR), Platycodon grandiflorus root (PR), and G. uralensis root and rhizome (GRR) . The processed product prepared from Aconitum carmichaelii daughter root (PADR), a well‐known herb used to treat heart failure and rheumatism, must be used cautiously due to its toxic components, diester diterpenoid alkaloids, mainly aconitine, hypaconitine, and mesaconitine, but when paired with GRR, as in clinical practice, it is less toxic.…”

Section: Hms and Gut Microbiotamentioning

confidence: 99%

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota

Chen

2017

Medicinal Research Reviews

260

183

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Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota-metabolized HMs, direct microbial analysis of HM-targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM-based drug discovery.

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Section: Hms and Gut Microbiotamentioning

confidence: 99%

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota

Chen

2017

Medicinal Research Reviews

260

183

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“…Citric acid, 2‐oxoglutaric acid and malic acid are intermediates of the TCA cycle. One study reported that increased levels of citric acid and 2‐oxoglutaric acid were observed in realgar‐induced hepatotoxicity, indicating that energy metabolism is disturbed after the treatment of realgar (Huo et al, ). Other studies revealed that disturbance of the TCA cycle could lead to an increased in the content of malic acid in rats exposed to CCl 4 (Gao et al, ).…”

Section: Discussionmentioning

confidence: 99%

Metabolic alterations in triptolide‐induced acute hepatotoxicity

Zhao

Xie

et al. 2018

Biomedical Chromatography

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Triptolide, a major active constitute of Tripterygium wilfordii Hook. F, is prescribed for the treatment of autoimmune diseases in China. One of its most severe adverse effects observed in the clinical use is hepatotoxicity, but the mechanism is still unknown. Therefore, the present study applied an LC/MS-based metabolomic analysis to characterize the metabolomic changes in serum and liver induced by triptolide in mice. Mice were administered triptolide by gavage to establish the acute liver injury model, and serum biochemical and liver histological analyses were applied to assess the degree of toxicity. Multivariate data analyses were performed to investigate the metabolic alterations. Potential metabolites were identified using variable importance in the projection values and Student's t-test. A total of 30 metabolites were observed that were significantly changed by triptolide treatment and the abundance of 29 metabolites was correlated with the severity of toxicity. Pathway analysis indicated that the mechanism of triptolide-induced hepatotoxicity was related to alterations in multiple metabolic pathways, including glutathione metabolism, tricarboxylic acid cycle, purine metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism and amino acid metabolism. The current study provides new mechanistic insights into the metabolic alterations that lead to triptolide-induced hepatotoxicity.

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“…Alanine plays a key role in glucose-alanine cycle between tissues and liver, in which alanine is formed by transamination of glucose-derived pyruvate and is transported to the liver, where its carbon skeleton is reconverted to glucose [ 40 ]. The decreased level of alanine in serum from Realgar treated animals implied a Realgar induced slowdown of glucose-alanine cycle [ 1 ]. It has been demonstrated that branched chain amino acids are physiologically important as regulators of the protein and glucose metabolisms [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Realgar (As 2 S 2 ), as a type of mineral drug that contains arsenic, has been used in traditional Chinese medicines (TCMs) for thousands of years. It has been used for the treatment of carbuncles, boils, insect and snake bites, intestinal parasitosis, convulsive epilepsy, and psoriasis [ 1 ]. Rather than being used alone, Realgar is commonly prescribed with other herbal medicines or minerals in Chinese compound formulae.…”

Section: Introductionmentioning

confidence: 99%

“…Although Realgar is poorly soluble in water and considered to be less poisonous, upon ingestion of Realgar -containing TCMs, the potential of arsenic poisoning cannot be ignored [ 4 ]. Recently, studies on the acute and chronic toxicological effects and poisoning cases of Realgar have been reported [ 1 , 3 , 5 ]. The safety of NJT is of concern.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Profiling Analysis of the Alleviation Effect of the Fractions of Niuhuang Jiedu Tablet on Realgar Induced Toxicity in Rats

Pei

Wang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Niuhuang Jiedu Tablet (NJT) is a classical formula in treating acute tonsillitis, pharyngitis, and so on. In the formula, significant level of Realgar as a potentially toxic element is contained. Our previous experiments revealed that it was less toxic for combined Realgar in NJT. However, the active fraction of this prescription with toxicity alleviation effect on Realgar was still obscure. NJT was divided into five different polar fractions (NJT-PET, NJT-25, NJT-50, NJT-75, and NJT-95), and we explored the toxicity alleviation effect on Realgar. Based on 1H NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. With pattern recognition analysis of metabolites in urine and serum, Realgar group showed a clear separation from control group, while the metabolic profiles of NJT-PET, NJT-25, NJT-50, and NJT-95 groups were similar to Realgar group, and the metabolic profiles of NJT and NJT-75 groups were very close to control group. Statistics results were confirmed by the histopathological examination and biochemical assay. The present work indicated that 75% EtOH fraction of NJT was the most valid fraction with the toxicity alleviation effect on Realgar.

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1 HNMR-based metabonomic study of sub-chronic hepatotoxicity induced by realgar

Cited by 25 publications

References 25 publications

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota

Metabolic alterations in triptolide‐induced acute hepatotoxicity

Metabolic Profiling Analysis of the Alleviation Effect of the Fractions of Niuhuang Jiedu Tablet on Realgar Induced Toxicity in Rats

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