Study on hepatotoxicity of different dosages of Polygoni multiflori radix praeparata in rats by metabolomics based on UPLC-Q-TOF-MS.

As a kind of replenishing Chinese medicine, polygoni multiflori radix praeparata (PMP) had high application value in clinic. However, with the increase of clinical applications, more and more hepatotoxicity reports have been reported which had shown has a dose-time-toxicity dependent correlation of PMP hepatotoxicity. Therefore, it was particularly important to investigate the safe and effective dose of PMP in clinical drug administration. At the same time, reliable and sensitive biomarkers were used to characterize phenotypic biochemical disturbances in the body, thereby reflecting the hepatotoxicity mechanism caused by PMP, and providing a basis for clinical drug safety. 10, 20, and 40 g·kg-1 doses PMP were intragastricly administered to rats respectively for consecutive 28 days. serum and liver tissue were collected to measure biochemical markers using blood biochemical analyzers and observe the histopathological examination. Serum metabonomics studies were performed by UPLC-Q-TOF-MS to reveal the dose-dependent biochemical disturbances caused by PMP. Compared with the blank group, the results of biochemical analysis showed that the indicators were significantly changed in the medium dose and high dose groups. however, there was no significant difference in the low dose group. A total of 12 characteristic metabolites were obtained through metabolomic analysis. The topological analysis involved 7 metabolic pathways, resulting in significant disturbance in amino acid metabolism, energy metabolism, and bile acid metabolism. Through comprehensive histopathological examination and biochemical analysis, we concluded that the dose of 20 g·kg-1 and 40 g·kg-1 PMP water extracts lead to liver damage after taking over four weeks, and the toxicity was enhanced as the dose increased. The identification method was used to characterize the disorder of hepatic metabolism induced by PMP in a dose-dependent manner. The experimental results provided the basis for the further study of the different doses of hepatotoxicity of PMP, and also provided a warning to the clinical dosage of PMP for a long time.

[Safety and risk factor analysis on Polygoni Multiflori Radix base on ancient traditional Chinese medicine literatures].

Traditional Chinese medicine Polygoni Multiflori Radix is dried roots of Polygonaceae Polygortum multiflorum Thunb. Its clinical application records were first discovered in literatures of the Tang dynasty. The origins, efficacy, toxicity, processing and taboos of Polygoni Multiflori Radix have been discussed in many ancient herb literatures. In recent years, with the increase in the public awareness in health, Polygoni Multiflori Radix admits preparations have been more widely applied in the treatment and prevention of diseases. However, there have been more and more reports about Polygoni Multiflori Radix induced liver injury, the safety of Polygoni Multiflori Radix has increasingly attracted attention of the society. In this paper, the authors summarized and analyzed the toxicity and medication risk factors of Polygoni Multiflori Radix recorded in ancient herb literatures, and proposed that more attention shall be given to the effect of the planting and processing methods on the components and toxicity of Polygoni Multiflori Radix in safety studies, which provides clues for the further studies.

CYP1A2 polymorphism in Chinese patients with acute liver injury induced by Polygonum multiflorum.

The objective of this study was to evaluate the genotype and allelic frequencies of CYP1A2 in Chinese patients with acute liver injury induced by Polygonum multiflorum. We examined the clinical mechanism of acute liver injury induced by P. multiflorum. According to the diagnostic criteria for drug-induced liver injury (DILI), 43 cases of P. multiflorum-induced liver injury admitted to the First Affiliated Hospital, Zhejiang University were identified between January 2008 and December 2012. An additional 43 control subjects were also chosen. Several alleles, including 1C, 1F, 2, 7, 9, and 11 of CYP1A2 were amplified from genomic DNA and sequenced. We used the chi-square test to determine whether CYP1A2 allele polymorphisms are associated with acute liver injury induced by P. multiflorum. The frequency of the CYP1A2 1C allele was 46.5% in P. multiflorum-induced DILI patients, which was significantly different from the frequency of 27.9% observed in healthy subjects. The frequency of the CYP1A2 1F allele was 63.9% in P. multiflorum-induced DILI patients, compared to 57.0% in healthy controls; the difference was not significant. The allelic frequencies of CYP1A2 2, CYP1A2 7, CYP1A2 9, and CYP1A2 11 were too low to be detected. The frequency of the CYP1A2 1C mutation in Chinese patients with P. multiflorum-induced acute liver injury differed from that in healthy Chinese people, indicating that CYP1A2 1C is probably related to metabolism of P. multiflorum, which is followed by acute liver injury.

Herbal hepatotoxicity: analysis of cases with initially reported positive re-exposure tests.

BACKGROUND: Positive re-exposure tests are diagnostic hallmarks for hepatotoxicity. OBJECTIVE: To test validity of positive re-exposures in herb induced liver injury. METHODS: We searched Medline database for cases of herb induced liver injury with positive re-exposures and analysed 34 cases for positive re-exposure test criteria of baseline alanine aminotransferase< 5N before re-exposure, and re-exposure alanine aminotransferase ≥ 2× baseline alanine aminotransferase. Re-exposure test was negative, if baseline alanine aminotransferase< 5N combined with re-exposure alanine aminotransferase< 2× baseline alanine aminotransferase, or if baseline alanine aminotransferase≥ 5N regardless of the re-exposure alanine aminotransferase including no available re-exposure alanine aminotransferase result. RESULTS: In 21/34 cases (61.8%), criteria for a positive re-exposure were fulfilled, with negative tests in 6/34 cases (17.6%) or uninterpretable ones in 7/34 cases (20.6%). Confirmed positive re-exposure tests established potential of herb induced liver injury for Aloe, Chaparral, Chinese herbal mixtures, Chinese Jin Bu Huan, Chinese Syo Saiko To, Germander, Greater Celandine, Green tea, Kava, Mistletoe, Polygonum multiflorum, and Senna, with up to 4 case reports per herb. CONCLUSIONS: Among 34 cases of herb-induced liver injury with initially reported positive re-exposure tests, 61.8% of the cases actually fulfilled established test criteria and provided firm diagnoses of herb induced liver injury by various herbs.

Comparison of laxative and antioxidant activities of raw, processed and fermented Polygoni Multiflori radix.

AIM: To observe the anti-oxidative activity and adverse laxative effect of raw, traditional processed and fermented products of Polygoni Multiflori Radix (PMR), and furthermore, to evaluate the fermentation method used in the processing procedure of PMR. METHODS: In vitro ferric reducing antioxidant power (FRAP) assay was carried out to evaluate the anti-oxidative activity. Modulation of normal defecation and effect on gastrointestinal motility in mice were carried out to investigate their adverse laxative effect. RESULTS: Fermented PMR induced less severe laxative adverse effect than Polygoni Multiflori Radix Praeparata (PMRP). PMR fermented with Rhizopus sp. (FB) could modulate the defecation significantly. The gastrointestinal motility was inhibited by PMRP and PMR fermented with Rhizopus oryzae (FA). FA and FB showed better antioxidant activity than PMRP in 50% and 95% ethanol group. Contents of 2, 3, 5, 4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) were reduced significantly after traditional processing but maintained after fermentation. Emodin and physcion were increased after traditional processing and fermented with Rhizopus oryzae. CONCLUSION: All processing procedure, including fermentation, might reduce its anti-oxidative activity. However, most of the processed products could lessen the adverse effect on gastrointestinal tract compared to PMR. Fermentation with Rhizopus oryzae was considered as a promising processing method of PMR.

[Toxic hepatitis induced by Polygonum multiflorum]. / Toxicka hepatitida po Polygonum multiflorum.

Toxic liver injury is a common cause of acute hepatitis. Here we report a case of 33-year old female with toxic hepatitis caused by unusual agent- extract of chinese plant Polygonum multiflorum. The patient presented with clinical signs of nausea and icterus and laboratory signs of hepatocellular damage following 2 months of readministration of Polygonum mulltiflorum pills. All other causes of hepatocellular damage were excluded. The causality between hepatocellular damage and Polygonum multiflorum ingestion was supported by early recovery after discontinuation, by international scoring system of causality between drug and hepatotoxicity as well as by similarities with other reports from the literature. Considering the growing popularity of herbal products as nutrition supplements we appeal to caution in using these preparations.

[Retrospective study of adverse events of Polygonum multiflorum and risk control].

To provide a reference for rational clinical medication and review the irrational use and factors relating the adverse events of Polygonum multiflorum. The literatures on P. multiflorum published between 1978 and 2008 were reviewed and the reports on clinical use were analyzed. A total of 26 literatures were retrieved. 38 cases of adverse drug event were reported, 10 cases of allergy, 24 cases of liver damage, and 4 cases presented with other adverse events. Irrational use is common in both self-medication and doctor prescription. It is one of the main factors of adverse events. Improving clinical rational use is the most important way to control its risk.

Acute hepatitis due to shen-min: a herbal product derived from Polygonum multiflorum.

Shen-Min is a herbal product sold as a supplement for women to enhance hair growth. It is widely available across Asia, Europe, and the United States and sold without prescription as a hair nutritional supplement. We describe a case of acute liver injury in a 28-year-old white woman who developed symptomatic hepatitis 8 weeks after starting Shen-Min. All other potential causes of acute hepatitis including viral, hypoxic/ischemic, metabolic, and autoimmune etiologies were excluded. The liver injury slowly resolved over 3 weeks after discontinuing the herbal product. Although the mechanism of Shen-Min hepatotoxicity is unknown, we suspect an idiosyncratic reaction because the patient developed a fine maculopapular rash, mild eosinophilia, and did not overdose. Shen-Min is a Chinese herbal product with a mixture of several plants and vitamins including Polygonum multiflorum, a root that has been previously associated with hepatotoxicity. Nonetheless to our knowledge this is the first reported case of herbal-induced hepatotoxicity in a patient taking Shen-Min per se. Clinicians taking care of patients with acute hepatitis of unclear etiology should be aware that the consumption of Shen-Min, a hair supplement widely available in the United States and Western countries might cause acute hepatitis.