Diversity-oriented synthesis of marine sponge derived hyrtioreticulins and their anti-inflammatory activities / 中国天然药物

Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.

Effect of the endogenous catecholamines synthesized by lymphocytes on T cell proliferation / 中国应用生理学杂志

<p><b>AIM</b>To provide further evidence for the synthesis of catecholamines (CAs) in lymphocytes and to investigate the effect of the endogenous CAs synthesized by lymphocytes on function of the lymphocytes themselves and the receptor mechanisms involved in the effect.</p><p><b>METHODS</b>RT-PCR was performed to detect the expression of TH mRNA in the lymphocytes from the mesenteric lymph nodes of rats. Different concentrations of pargyline, an inhibitor of monoamine oxydase, and antagonists of alpha1-, alpha2-, beta1-, and beta2-adrenergic receptor (AR) were added to the lymphocyte cultures, and then proliferative response of the lymphocytes to mitogen concanavalin A (Con A) were measured via methyl-thiazole-tetrazolium (MTT) assay.</p><p><b>RESULTS</b>The lymphocytes could express TH mRNA, and the expression of TH mRNA was significantly higher in the Con A-activated lymphocytes than in the resting ones. The treatment of pargyline of 10(-6) and 10(-5) mol/L (not 10(-7) mol/L) notably attenuated Con A-induced lymphocyte proliferation. Beta2-AR antagonist ICI118551 (10(-7) and 10(-6) mol/L) completely blocked, but alpha1-AR antagonist corynanthine and alpha2-AR antagonist yohimbine (10(-7) and 10(-6) mol/L) partly blocked the suppressive effect of pargyline on the Con A-induced lymphocyte proliferation. Nevertheless, atenolol, an antagonist of beta1-AR, had no blocking effect on pargyline inhibition of lymphocyte proliferation.</p><p><b>CONCLUSION</b>Lymphocytes have the ability to synthesize CAs and the ability is enhanced in the activated lymphocytes. The endogenous CAs synthesized by lymphocytes can inhibit T cell proliferation and the inhibition of T cells by the CAs is mediated predominantly by beta2-AR on the lymphocytes.</p>

Stability of physical state on compound hawthorn dropping pills / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the stability of physical state with accelerate test and dropping in process before and after on compound hawthorn dropping pills.</p><p><b>METHOD</b>Scanning electron microscope, TG-DTA, FT-IR and XRD were used.</p><p><b>RESULT</b>The active components presented amorphous, tiny crystal and molecular state in dropping pills, and it had no obvious reaction between PEG 4000 and active components. With time prolonging, a little of active components changed from amorphous state to tiny crystal or molecular state.</p><p><b>CONCLUSION</b>Solid dispersion improved the stability and dissolution of compound hawthorn dropping pills.</p>

Immunoregulatory role of endogenous catecholamines synthesized by immune cells / 生理学报

It has been well known that catecholamines (CAs) in the body, including norepinephrine (NE), epinephrine (E) and dopamine (DA), are synthesized and secreted by neurons and endocrine cells and mainly modulate visceral activities such as cardiovascular, respiratory and digestive functions. The studies over the past nearly 30 years have shown that CAs can also regulate immune function. The immunomodulation of CAs is generally considered as a role mediating the regulation of nervous and endocrine systems. However, recent studies reveal that immune cells can also synthesize CAs, which is an update of traditional concept. A classical metabolic pathway of CAs shared by the nervous and endocrine systems is present in the immune cells, i.e., the immunocytes have the enzymes for synthesis of CAs [e.g. tyrosine hydroxylase (TH)] and the enzymes for degradation of CAs [e.g. monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT)]. The endogenous CAs synthesized by immune cells can regulate many immune functions, including cellular proliferation, differentiation, apoptosis and cytokine production. These roles of the endogenous CAs may be mediated by an autocrine/paracrine pathway via relevant receptors on the immunocytes and intracellular cAMP. Intracellular oxidative mechanism may also be involved in immunoregulation of endogenous CAs in immune cells. In addition, some metabolic abnormalities of CAs in the immune cells probably induce some autoimmune diseases, such as multiple sclerosis (MS) and rheumatoid arthritis. These findings not only provide evidence for the new concept that the immune system is possible to become the third CA system other than the nervous and endocrine systems, but also extend our comprehension on functional significance of the endogenous CAs synthesized by immune cells.

Effect of acetylcholine on the cytotoxicity of natural killer cells / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of acetylcholine (ACh) on the cytotoxicity of natural killer (NK) cells and to explore the receptor mechanisms involved in the effect.</p><p><b>METHODS</b>The effector cells (i. e. NK cells) from the spleens of rats were collected and cultured with the target cells (Yac-1 cells). The various concentrations of ACh, cholinergic receptor agonists or antagonists were added to the cultures, respectively according to distinct experimental purposes. Lactate dehydrogenase (LDH) release assay was used to evaluate NK cell cytotoxicity.</p><p><b>RESULTS</b>NK-cell-mediated lysis of Yac-1 lymphoma cells was reduced by 10(-10) - 10(-6) mol/L ACh. The inhibitory effect of ACh on NK cell cytotoxicity was mimicked by pilocarpine, an agonist of muscarinic receptor, and by nicotine, an agonist of nicotinic receptor, at all applied concentrations (10(-10) - 10(-6) mol/L). Muscarinic receptor antagonist atropine blocked the inhibitory effect of ACh on the cytotoxicity of NK cells. Nevertheless, tubocurarine, an antagonist of nicotinic receptor, had no blocking effect on the suppression of NK cell cytotoxicity by ACh.</p><p><b>CONCLUSION</b>ACh results in an inhibition of the cytotoxicity of NK cells, and this inhibition is realized mainly through M and N1 cholinergic receptor.</p>