Synthesis, binding, and functional properties of tetrahydroisoquinolino-2-alkyl phenones as selective σ2R/TMEM97 ligands.

Sigma-2 receptor (σ2R/TMEM97) has been implicated to play important roles in multiple cellular dysfunctions, such as cell neoplastic proliferation, neuro-inflammation, neurodegeneration, etc. Selective σ2 ligands are believed to be promising pharmacological tools to regulate or diagnose various disorders. As an ongoing effort of discovery of new and selective σ2 ligands, we have synthesized a series of tetrahydroisoquinolino-2-alkyl phenone analogs and identified that 10 of them have moderate to potent affinity and selectivity for σ2R/TMEM97. Especially, 4 analogs showed Ki values ranging from 0.38 to 5.1 nM for σ2R/TMEM97 with no or low affinity for sigma-1 receptor (σ1R). Functional assays indicated that these 4 most potent analogs had no effects on intracellular calcium concentration and were classified as putative σ2R/TMEM97 antagonists according to current understanding. The σ2R/TMEM97 has been suggested to play important roles in the central nervous system. Based on published pharmacological and clinical results from several regarded σ2R/TMEM97 antagonists, these analogs may potentially be useful for the treatment of various neurodegenerative diseases.

Effects of Tianxiangdan Granule treatment on atherosclerosis via NF­κB and p38 MAPK signaling pathways.

The present study aimed to determine the effects of Tianxiangdan Granule on nuclear factor (NF)-κB p65 and p38 mitogen­activated protein kinase (MAPK) inflammatory signaling pathways, and explored the possible mechanism underlying the effects of Tianxiangdan Granule on prevention and treatment of atherosclerosis. A total of 48 apolipoprotein E­/­ mice (age, 8 weeks) were selected and divided into two groups: The normal control group (n=12) and the modeling group (n=36). In the modeling group, mice were fed a high­fat diet and were maintained in an artificial climate box, in order to stimulate the climate and eating habit characteristics of Xinjiang. Every morning, ApoE­/­ mice in the modeling group were placed in the artificial climate box at 10:00 am and were taken out at 09:00 pm and placed back in the room temperature environment. The temperature of the artificial climate box was set at 6±2˚C, relative humidity was controlled at 25­32.8% and the light­dark cycle was 12 h/day. The purpose of this method was to establish the Huizhuo Tanzu type atherosclerosis model. Following successful generation of the model, mice in the modeling group were randomly divided into three groups: Model group (n=10), Tianxiangdan group (n=10) and atorvastatin group (n=10). After 12 weeks, mice were sacrificed and the serum levels of interleukin (IL)­1ß and tumor necrosis factor (TNF)­α in each group were detected. Furthermore, the expression levels of NF­κB p65 and p38 MAPK in aortic tissue were detected. The results indicated that the concentrations of IL­1ß and TNF­α were significantly higher in mice in the model group compared with in the normal control group (P<0.01), whereas the concentrations of IL­1ß and TNF­α were lower in the Tianxiangdan and atorvastatin groups compared with in the model group (P<0.01). Furthermore, the protein expression levels of phosphorylated (p)­NF­κB p65 and p­p38 MAPK protein were higher in aortic tissues from the model group compared with in the normal control group (P<0.01), p­NF­κB p65 and p­p38 MAPK protein expression was reduced in the atorvastatin and Tianxiangdan groups compared with in the model group. The present study indicated that the mechanism underlying the effects of Tianxiangdan Granule on the prevention and treatment of atherosclerosis may be as follows: Tianxiangdan Granule may decrease the expression of the inflammatory cytokines IL­1ß and TNF­α, and suppress activation of the NF­κB p65 and p38 MAPK signaling pathways.

Dibenzocyclooctane lignans from the stems of Schisandra wilsoniana.

Five new dibenzocyclooctane lignans, schisanwilsonins K-O, together with eighteen known lignans were isolated from the stems of Schisandra wilsoniana. The structures of these new compounds were elucidated by spectroscopic methods, including 2D-NMR techniques. Several compounds were found to show anti-HIV and anti-HBV activity.

[Treatment of rheumatoid arthritis arthralgia by xiaoyan zhitong paste: a clinical observation].

OBJECTIVE: To formulate a comprehensive treatment program for rheumatoid arthritis arthralgia by clinical observing the efficacy of Xiaoyan Zhitong Paste (XZP). METHODS: Adopted was stratified, block randomized, double-blinded, placebo parallel controlled method. Subjects were assigned to the treatment group and the placebo group. Those in the treatment group were treated by external application of XZP, one to two pastes each time, covering the painful area, exchange once per 24 h, with one-day interval during a 7-day consecutive medication, two 7-days of treatment consisting of one therapeutic course. XZP placebos were applied for those in the placebo group in the same medication way. Joint pain and VAS were taken as main indices for observing the clinical efficacy of XZP. RESULTS: The improvement of the analgesic effect and the Chinese medical syndrome efficacy of XZP were superior to that of the placebo. CONCLUSION: XZP showed obvious effect in treating rheumatoid arthritis arthralgia with no obvious adverse reaction.

Irisdichotins A-C, three new flavonoid glycosides from the rhizomes of Iris dichotoma Pall.

Three new compounds including one flavonol glycoside, irisdichotin A (1), and two flavanonol glycosides, irisdichotins B (2) and C (3), were isolated from the rhizomes of Iris dichotoma Pall. Their structures were elucidated on the basis of spectroscopic methods.

Chemical constituents and bioactivities of the liposoluble fraction from different medicinal parts of Crocus sativus.

CONTEXT: Crocus sativus Linn. (Iridaceae), commonly known as saffron, becomes more and more popular due to its versatile biological and medicinal properties. At present, studies mainly focus on the traditional medicinal part, the saffron stigma, with less attention to the other parts of saffron, such as the perianth, the stamen, and the corm, which are high yield compared to the stigma and also possess various pharmacological effects. OBJECTIVE: To determine the chemical compositions, antifungal, cytotoxic, and antioxidant activities of the ether fractions from the stamen, perianth, and stigma of saffron. MATERIALS AND METHODS: The chemical constituents of the ether fractions from different parts of saffron were investigated by gas chromatography/mass spectrometry. Several pathogenic fungi isolates and tumor cell lines were employed to evaluate the antifungal and cytotoxic activities of these three ether fractions. 1,1-Diphenyl-2-picrylhydrazyl assay was used to determine the free radical-scavenging activity. RESULTS: The ether fractions composition of the three C. sativus parts are different from each other, but lauric acid, hexadecanoic acid, 4-hydroxydihydro-2(3H)-furanone, and stigmasterol were the common constituents shared by all the three fractions. The stamen ether fraction displayed the strongest antifungal and cytotoxic activities, whereas both of the saffron stamen and perianth ether fractions exhibited significant antioxidant activities. DISCUSSION AND CONCLUSION: These findings demonstrate that the saffron stamen and perianth possess significant antifungal, cytotoxic, and antioxidant activities as well as the stigma, though not to the same extent, prompting us to expand the medicinal resource and make best use of this valuable plant.

Schisanwilsonenes A-C, anti-HBV Carotane sesquiterpenoids from the fruits of Schisandra wilsoniana.

Three carotane-type sesquiterpenoids, schisanwilsonenes A (1), B (2), and C (3), were isolated from the fruits of Schisandra wilsoniana. Their structures and relative configurations were elucidated on the basis of spectroscopic methods including 2D-NMR techniques, and the structure of 1 was confirmed by a single-crystal X-ray diffraction experiment. Schisanwilsonene A, at 50 microg/mL, exhibited antiviral activity, inhibiting HBsAg and HBeAg secretion by 76.5% and 28.9%.

[Discussion of time and space differentiation of three-yin and three-yang in Shanghan Lun].

The concept of "three-yin and three-yang" in Shanghan Lun (Treatise on Cold Pathogenic Diseases), a classic written by Zhang Zhongjing in Han Dynasty, has been always the focus of dispute in successive dynasties. The essence of "three-yin and three-yang" has not been fully revealed up till now. Through studying the six divisions of day and night, the six diseases, the combination of syndromes, the complicated diseases, the complete recovery time and the space division of "three-yin and three-yang", the authors draw a conclusion that the "three-yin and three-yang" in Shanghan Lun is a concept of time-sequence, which is associated with the location of disease in space. So it is suggested that the "six diseases" in Shanghan Lun is a categorization for exogenous febrile diseases, and this categorization reveals a sort of inner relationship between the emergence, development, transformation of the febrile diseases and the time.