Evaluation of the Hepatotoxicity of the Zhi-Zi-Hou-Po Decoction by Combining UPLC-Q-Exactive-MS-Based Metabolomics and HPLC-MS/MS-Based Geniposide Tissue Distribution.

With traditional Chinese medicine (TCM) becoming widespread globally, its safety has increasingly become a concern, especially its hepatoxicity. For example, Gardenia jasminoides Ellis is a key ingredient in the Zhi-Zi-Hou-Po decoction (ZZHPD), which is a commonly-used clinically combined prescription of TCM that may induce hepatoxicity. However, the underlying toxicity mechanism of ZZHPD is not fully understood. In this study, a plasma metabolomics strategy was used to investigate the mechanism of ZZHPD-induced hepatotoxicity through profiling entire endogenous metabolites. Twenty-four Sprague-Dawley rats were randomly assigned into four groups, which were orally administered with 0.9% saline, as well as 2.7 g/kg/day, 8.1 g/kg/day, or 27 g/kg/day of ZZHPD for 30 consecutive days, respectively. Biochemical assay and metabolomics assay were used to detect serum and plasma samples, whilst histopathological assay was used for detecting liver tissues, and the geniposide distribution in tissues was simultaneously measured. The results showed that the concentration of 20 metabolites linked to amino acid, lipid, and bile acid metabolism had significant changes in the ZZHPD-treated rats. Moreover, toxic effects were aggravated with serum biochemical and histopathological examines in liver tissues as the dosage increased, which may be associated with the accumulation of geniposide in the liver as the dosage increased. Notably, our findings also demonstrated that the combined metabolomics strategy with tissue distribution had significant potential for elucidating the mechanistic complexity of the toxicity of TCM.

The effectiveness of an additional lingual infiltration in the pulpal anesthesia of mandibular teeth: a systematic review.

OBJECTIVES: The aim of this systematic review is to investigate the effect of an additional lingual infiltration on the pulpal anesthesia of mandibular teeth. METHOD AND MATERIALS: Prospective clinical trials were searched from Medline, EMBASE, Cochrane Library, Pubmed, SCI, and the China National Knowledge Infrastructure. Papers that met the inclusion criteria were accepted. Data was extracted by two investigators using a designed extraction form. The anesthetic efficacy of an additional lingual infiltration on the pulpal anesthesia of mandibular teeth was analyzed. RESULTS: Seven prospective randomized controlled trials were included. All subjects of these studies were volunteers with healthy pulps, without patients with pulpitis. Compared to buccal infiltration alone, an additional lingual infiltration following buccal infiltration is more likely to achieve a successful pulpal anesthesia in the mandibular incisor area, with a relative risk for success of 2.00 [1.08, 3.72] for 2% lidocaine and 1.32 [1.15, 1.51] for 4% articaine. For mandibular canines and premolars, the additional lingual infiltration following inferior alveolar nerve block did not enhance the anesthetic efficacy. In the mandibular molar area, no significant difference was found after an additional lingual infiltration with either 2% lidocaine or 4% articaine. CONCLUSION: An additional lingual infiltration following buccal infiltration can enhance the anesthetic efficacy compared with buccal infiltration alone in the mandibular incisor area. For mandibular canines, premolars, and molars, an additional lingual infiltration is not recommended, since no data exist to support such usage. Lingual infiltration of articaine in the mandibular teeth with pulpitis should be studied further.