Synthesis, and anti-inflammatory activities of gentiopicroside derivatives / 中国天然药物

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Study on the Frequency of Receptor Insensitivity to Androgen Using the Androgen-receptor Binding Assay in the Genetic Male Children with Abnormalities of Sexual Differentiation

PURPOSE: The development of external genitalia in genetic male is dependent on the transcriptional regulatory activity of dihydrotestosterone(DHT)-androgen receptor complex in the genital skin. The abnormality of androgen receptor encompasses a wide range of phenotypes. We investigated the androgen receptor binding capacity of genetic males with ambiguous genitalia(grade was determined by Prader grade) for the availability as screening test. METHODS: The binding capacity of the androgen receptor was assessed in fibroblasts established from foreskin or pubic area skin of genetic male [normal control(n=5); Prader grade 2, 3(P23; n= 5); Prader grade 4, 5, 6(P456; n=4), Prader grade 7(P7; n=2)]. RESULTS: There was no significant difference in averages of Bmax(maximum binding capacity) and Kd(equilibrium dissociation constant) of [3H]DHT to the androgen receptor between those of controls and P23. In P456, Bmax was decreased in two patients and Kd was increased in one patient. Bmax and Kd were normal in one patient. In P7, specific binding was not documented and compatible with androgen insensitivity syndrome. CONCLUSION: In genetic male with complete female phenotype without pubic hair(P7), the binding study may be useful as a diagnostic tool. But in genetic male with hypospadia(P23) or incomplete female phenotype(P456), the binding study is not useful as a diagnostic test.

Short Latency Somatosensory Evoked Potentials and Electroencephalography in Stroke

Median nerve somatosensory evoked potentials(SEP) and electroencephalography(E EG) were recorded in 85 patients with stroke(33 with thalamic hemorrhage, 20 with putaminal hemorrhage and 32 with cerebral infarction) to observe the origin of Nl9 and P23 wave responses in median SEP and the origin of slow waves in EEG as well as to evaluate the prognostic correlation between stroke patients and SEP and EEG findings. Nl9 and P23 were absent in 42 4% of patients with thalamic hemorrhage and 70% with putarninal hemorrhage. There was no case in which only P23 was absent in these two groups. In cerebral infarction, the most frequent finding was that both N19 and P23 were absent. P23 was absent with intact Nl9 in 2 cases with localized cortical infarction. Therefore we suggest that N19 develops in thalamus or thalamocatical pathway and P23 in the parietal cortex. There was no significant difference of EEG findings between thalamic hemorrhage and cerebral infarction. It was unlikely that slow waves on EEG is a specific finding in a localized brain lesion. The prognosis was poor in thalamic hemorrhage and cerebral infarction with loss of both Nl9 and P23 in SEP findings and in cerebral infarction with moderate to severe degree of background abnorrnalities in EEG findings. So that, SEP and EEG findings may be useful for prognostic aspect.

Somatosensory and Brainstem Auditory Evoked Potentials before and After Hemodialysis in Chronic Renal Failure

For evaluation of the alterations of the somatosensory evoked potentials(SSEP) and the brainstem auditory evoked potentials(BAEP)before and after hemodialysis, SSEP and BAEP were recorded by using a Medelec ST10 Sensor apparatus before the first dialysis and after subsequent dialyses in 30 urernic patients (19 men and 11 women)and the results were compared with the normal controls. The duration of subsequent hemodialyses varied from 0.5 to 9 months, with a mean of 3.3 months. To evaluate the effect of single hemodialysis on BAEP, BAEP were recorded before and after a single hemodialysis in another 10 uremic patients. According to the results of the median nerve SSEP, the absolute latencies of all responses and all interpeak latencies before hemodialysis and the absolute latencies of all responses and N13-N19 interpeak latency after hemodialysis were significantly delayed compared with normal controls. The absolute latencies of N9 and P23 were significantly delayed in the perdialysis compared with the postdialysis. From the BAEP, the absolute latencies of all responses before and after hemodialysis and the I-V interpeak latency before hernodialysis were significantly delayed compared with the normal controls, but there were no significant changes between predialysis and postdialysis. According to the study of BAEP in another group of 10 uremic patients before and after a single hemodialysis, the absolute latency of wave IV and the I-III interpeak latency were reduced in the postdialysis compared with predialysis but there is no statistical signigicance. The above findings suggest that there are some peripheral or central nervous system dysfunction in chronic renal failure and these dysfunctions might be improved by regular hemodialysis and/or a single hemodialysis. Therefore we suggest that SSEP and BAEP are useful tests for early diagnosis of central and peripheral nervous dysfunction in chronic renal failure and these tests might be useful in evaIuation of the effect of hemodialysis.