Metabolism and distribution of two major constituents of 'Xing-Nao-Jing Injection'-germacrone and curdione in rats.

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ.

Clinical evaluation of radiation-induced sinusitis by MRI-based scoring system in nasopharyngeal carcinoma patients.

OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the evaluation of radiation-induced sinusitis (RIS), MRI-based scoring system was used to evaluate the development regularity, characteristics and influencing factors of RIS in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A retrospective analysis was performed by collecting the clinical and MRI data of 346 NPC patients to analyze the characteristics and prognosis of RIS. The predictive model was constructed according to the influencing factors of RIS. RESULTS: (1) In the 2-year follow-up after radiotherapy (RT), there was significant change in L-M score in both groups of NPC patients (sinusitis before RT group: p = 0.000 vs. non-sinusitis before RT group: p = 0.000). After 6 months of RT, the L-M scores of the two groups tended to plateau (sinusitis before RT group: p = 0.311 vs. non-sinusitis before RT group: p = 0.469). (2) The prevalence of sinusitis in two groups of NPC patients (without or with sinusitis before RT) was 83% vs. 93%, 91% vs. 99%, 94% vs. 98% at 1, 6 and 24 months after RT, respectively. (3) In the patients without sinusitis before RT, the incidence of sinusitis in maxillary and anterior/posterior ethmoid, sphenoid and frontal sinuses was 87.1%, 90.0%/87.1%, 49.5%, 11.8% respectively, 1 month after RT. (4) A regression model was established according to the univariate and multivariate analysis of the factors related to RIS (smoking history: p = 0.000, time after RT: p = 0.008 and TNM staging: p = 0.040). CONCLUSION: (1) RIS is a common complication in NPC patients after RT. This disorder progressed within 6 months after RT, stabilized and persisted within 6 months to 2 years. There is a high incidence of maxillary sinus and ethmoid sinus inflammation in NPC patients after RT. (2) Smoking history, time after RT and TNM staging were significant independent risk factors for RIS. (3) The intervention of the risk factors in the model may prevent or reduce the occurrence of RIS in NPC patients.

[Influence of betahistine on the expression of histamine H3 receptor in the medial vestibular nucleus following unilateral labyrinthectomy in guinea pigs].

OBJECTIVE: To observe the influence of betahistine on the expression of histamine H3 receptor in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL). METHODS: Fifty-six healthy guinea pigs were randomly divided into three groups:the sham-operated group (group I), the UL group[group II, and UL+betahistine (BET) group (group III)], BET was intraperitoneally injection at 2.17 mg×kg(-1)×d(-1) for 7 days. The expression of histamine H3 receptor was analyzed by immunohistochemistry at 1 day, 3 days and 7 days after UL. RESULTS: H3 receptors were presented in the MVN and the expression of histamine H3 receptor were increased significantly in the ipsilateral MVN at 1 and 3 days after UL(P < 0.05), the change turned into the normal value at 7 days(P > 0.05). In the UL+BET group, the intensity of histamine H3 receptor was lower than that in the UL at 1 day and 3 days(4.25 ± 0.71, 3.50 ± 0.92 vs 5.75 ± 0.71, 5.50 ± 0.93, P < 0.05). However, the changes turned into the normal values at 3 and 7 days (P > 0.05). CONCLUSIONS: The early stage of the vestibular compensation process may be associated with the change of H3 receptor expression in MVN. In the UL+BET group the histamine H3 receptor recovered quickly.

[Studies on O/W partition coefficient and absorption kinetics of geniposide in fructus gardeniae extract in rat intestine].

OBJECTIVE: To determine the O/W partition coefficient of geniposide in fructus gardeniae extract and investigate the absortion kinetics of geniposide in whole small intestine and different intestinal segments of rats. METHOD: The shake-flask method was employed to determine the O/W partition coefficient of geniposide; an in situ intestinal perfusion model was employed to investigate the absorptive kinetics of geniposide. RESULT: The partition coefficient (P) of geniposide was 0.1077, logP was -0.9678; the absorptive rate constants (K) of geniposide at the concentration of 0.078, 0.311, 0.780 g x L(-1) were (0.130 +/- 0.007), (0.056 +/- 0.003), (0.031 +/- 0.006) h, respectively. The K of geniposide were (0.019 +/- 0.003), (0.015 +/- 0.002), (0.012 +/- 0.002) h at duodenum, jejunum, ileum, respectively. CONCLUSION: According to the P and the logP, it could be indicated that the absorption of geniposide at small intestine was poor absorption; The absorption rate was increased with the decrease of the extract concentration; Their absorption was first-order process besides the passive diffusion mechanism, and facilitated diffusion and active transport may also take part in the transport process. Geniposide was absorbed at all smallintestinal segments of rats, but the duodenal absorption ratewas higher more than other section.