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ABSTRACT: To assess the anti-nociception and anti-inflammation pharmacodynamics of Asarum heterotropoides var. mandshuricum and A. sieboldii.
Both the writhing test and hot plate test were conducted to assess the anti-nociceptive effect of Asarum and Xylene-induced mouse ear edema was conducted to assess the anti-inflammatory effect of Asarum.
Twelve samples of A. heterotropoides var. mandshuricum and A. sieboldii from different producing areas showed anti-nociceptive and anti-inflammatory effects. Specifically, 27% to 61% of the seven samples of A. heterotropoides var. mandshuricum showed anti-nociceptive effect and while 34% to 48% of A. sieboldi showed anti-nociceptive effect. The inflammatory inhibition rate of A. heterotropoides var. mandshuricum produced in six producing areas (38%-57%) is higher than that of A. heterotropoides var. mandshuricum produced in five producing areas (34%-48%). The same kind of Asarum produced in different areas showed significant differences. A. heterotropoides var. mandshuricum produced in Jilin province (38%-57%) showed better anti-nociceptive effect than sample produced in Heilongjiang province (34%) in writhing test. A. heterotropoides var. mandshuricum produced in Heilongjiang (43%) province showed a better anti-nociceptive effect than samples produced in Liaoning province (29%-36%) in hot plate test. A. sieboldii produced in Shaanxi province (47%-49%) showed a better anti-nociceptive effect than samples produced in Hubei province (40%) in writhing test. A. sieboldii produced in Shaanxi province (45%-59%) showed better anti-nociceptive effect than samples produced in Chongqing (40%) in hot plate test. A. heterotropoides var. mandshuricum produced in Jilin province (51%-63%) showed better anti-inflammatory effect than samples produced in Heilongjiang province (50%). In totality, the results from analysis of geoherbalism showed that famous-region A. heterotropoides var. mandshuricum and A. sieboldii had a better anti-nociception effect than Asarum produced in other producing areas, famous-region A. heterotropoides var. mandshuricum had a better effect than those produced in other producing areas in anti-inflammation. But famous-region A. sieboldii showed no obvious difference from those produced in other producing areas in anti-inflammation.
All samples of Asarum showed anti-nociceptive and anti-inflammatory effects, but with significant differences among Asarum produced in different areas, indicating the eoherbalism to some extent.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 03/2012; 37(5):625-31.
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ABSTRACT: The new emerging immunosuppressive effects displayed by iminosugars have not been much investigated so far. Several new N-alkyl dideoxy iminoalditols were designed and synthesized to explore their immunosuppressive effects. These iminosugars inhibited the proliferation of mouse splenocytes and the secretion of both IFN-γ and IL-4, which are the hallmark cytokines of Th1 and Th2 cells, respectively. Some compounds exerted good inhibitory effects. More importantly, the synthetic iminosugars prolonged the allograft survival in the mouse skin transplantation experiment. Our results provide a lead for further elucidation of the structure–activity relationships and modifications of iminosugars for better immunosuppressive agents.Keywords: Iminosugar; immunosuppressive agent; mouse skin allograft; synthesis
07/2011;
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ABSTRACT: A series of monospirocyclopiperazinium salts were designed and synthesized to search for a peripherally-acting analgesic drug with low side effects. Extensive SAR studies revealed that a suitable NR(2)R(3) was critical for the analgesic activity, which might be beneficial to expose the cationic nitrogen to bind to the receptor, and possibly interact with the receptor via π-π interaction. Introduction of substituting group on the N(4)-phenyl ring could improve the activity, and the best position was the 4-position. Compound 14n showed more potent analgesic activity (63%, 20 μM/kg, sc) and holds promise for development as a mechanically new analgesic drug.
Bioorganic & medicinal chemistry letters 02/2011; 21(3):940-3. · 2.65 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the antinociceptive effects and potential mechanisms of the spirocyclopiperazinium compound LXM-15. We found that LXM-15 produced significant antinociceptive effects in a dose- and time-dependent manner in mice. The maximum inhibition ratio was 70% in the acetic acid writhing test; the effect started at 1.0 h, peaked at 2.0 h with the MPEs of 61%, and persisted 3.5 h in the hot-plate test; LXM-15 reduced the time spent licking or biting the injected paw remarkably with inhibitions of 53% in formalin test. LXM-15 did not affect motor coordination, spontaneous activity, body temperature, heart rate, or liver enzyme activity, the LD(50) values was 616.26 μmol/kg. The antinociceptive effect of LXM-15 was blocked by mecamylamine, hexamethonium, atropine or atropine methylnitrate, and was also blocked by MLA, tropicamide. In contrast, the effect was not blocked by naloxone. Meanwhile, competition receptor binding assays showed LXM-15 can bind to α7 nAChR or M4 mAChR. Our studies show that LXM-15 may be via activating peripheral α7 nicotnic and M4 muscarinic receptors, resulted in antinociceptive effects.
Neuropharmacology 10/2010; 60(2-3):446-52. · 4.81 Impact Factor
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ABSTRACT: Drugs typically used to treat pain are limited by their undesirable side effects, which has prompted a search for mechanistically different analgesic agents. We report the antinociception effect of the spirocyclopiperazinium compound LXM-10 via activation of peripheral alpha7 nicotinic and muscarinic acetylcholine receptors in mice. This effect was attenuated by hexamethonium, atropine methylnitrate, methyllycaconitine citrate, tropicamide, bicuculline, and phaclofen. Competition receptor-binding assays in vitro showed that LXM-10 binds with high affinity alpha7 nAchR and with low affinity M4 receptors. Our findings show that the antinociception signaling pathway of LXM-10 underlies activation of peripheral alpha7 nicotinic and possibly of M4 muscarinic receptors, which activate GABA(A) and GABA(B) receptors, resulting in antinociceptive effects without obvious side effects.
Pharmacology Biochemistry and Behavior 04/2010; 95(2):192-7. · 2.53 Impact Factor
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ABSTRACT: Several N-alkyl and hydroxyethyl-substituted iminosugar derivatives, including L-altro and D-galacto epimers, were synthesized and the effects of these synthetic iminosugars on proliferation of mouse splenocytes were evaluated in the MTT assay. The experimental data demonstrated that the N-alkylated D-galacto iminosugars showed better inhibitory activities than L-altro analogues, which might hold potential as immunosuppressive agents.
Carbohydrate research 02/2010; 345(6):780-6. · 2.03 Impact Factor
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ABSTRACT: Gaultheria yunnanensis. are used widespreadly in the south of China to treat rheumatoid arthritis. The aim of this study was to provide an experimental basis for G. yunnanensis to therapy rheumatoid arthritis.
We prepared water extracts, ethanol extracts, n-butanol extracts, ethyl acetate extracts and the rest of ethanol extracts from G. yunnanensis. Then, the n-butanol extracts were applied to macroporous resin and eluted with water, 30% ethanol, and 95% ethanol. Rheumatoid arthritis was induced by Freund's complete adjuvant injected into right postpedes in Wistar rats which was utilized to elucidate the anti-inflammatory effect of different extracted liquid of G. yunnanensis. Rats were intragastric injected (ig) with extracts as experimental group or normal saline as control group.
Freund's complete adjuvant induced arthritis was successfully established: paw edema were increased after Freund's complete adjuvant injection, peaked at 2 or 3 day, then decreased, the paw edema were increased again at 7 or 8 day, and persisted 15 d. Water extracts, n-butanol extracts or ethyl acetate extracts could a significantlly decrease the paw edema as compared with the control group (P < 0.05, P < 0.01). The effect of n-butanol extracts was the most powerful. Further, n-butanol extracts eluant with water and 30% ethanol decreased the paw edema. The activity of extracts eluant with 30% ethanol was stronger than that of eluant with water.
G. yunnanensis displays considerable effects against Freund s complete adjuvant induced arthritis in rats, which is in concordance with clinical practice. n-Butanol extracts and both of the eluants with water and 30% ethanol produce a significant decrease in the paw edema. 30% ethanol eluants show a stronger activity than others. The effects against rheumatoid arthritis of different parts of G. yunnanensis differ in degree. It is deserved to explore the potential mechanisms of anti-inflammtion of the G. yunnanensis, especially the n-butanol extracts eluant with 30% ethanol.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 10/2009; 34(19):2516-9.
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ABSTRACT: Anti-inflammatory drugs are clinically limited because of their side effects. The aim of this study was to evaluate the anti-inflammatory activities and mechanisms of the spirocyclopiperazinium compound LXM-10 (2, 4-dimethyl-9-beta-phenylethyl-3-oxo-6, 9-diazaspiro[5.5]undecane chloride). We found that LXM-10 produced a significant, dose-dependent decrease in xylene- and carrageenin-induced edema. The anti-inflammatory effect was attenuated by hexamethonium, methyllycaconitine citrate, atropine methylnitrate, and tropicamide. The serum level of TNF-alpha was reduced by LXM-10 in lipopolysaccharide-challenged mice, and this effect was also inhibited by methyllycaconitine and tropicamide. LXM-10 also reduced the prostaglandin E(2) concentration in rat paw tissue. LXM-10 minimised the carrageenin-induced pathological changes and did not affect mice heart rate. LXM-10 did not induce significant changes in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) activity. Median lethal dose (LD(50)) of LXM-10 was 1573.0 micromol/kg. Our findings suggest that LXM-10 has anti-inflammatory effects by activating alpha7 nicotinic and M(4) muscarinic acetylcholine receptors with limited side effects.
European journal of pharmacology 10/2009; 626(2-3):290-6. · 2.59 Impact Factor
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ABSTRACT: Liqi, an herbal preparation used in traditional Chinese medicine, has been used to treat cancer in China for centuries. We investigated the anti-tumor effects of liqi and their mechanisms in mice that had been xenografted with tumors.
Sarcoma 180 tumor, Lewis lung carcinoma, and SGC-7901 cells were implanted in BALB/c mice, C57BL/6 mice, and BALB/c nude mice, respectively. Liqi was administered to subgroups of these mice. The tumor weight and size were measured. Cell cycle analysis and T lymphocyte subsets were determined by flow cytometry. The activity of NK cells and TNF was tested using cytotoxicity assay on YAC-1 cells and L929 cells, respectively, and the activity of IL-2 was tested with an IL-2-dependent CTLL-2 cell proliferation assay. Platelet aggregation was monitored by measuring electric impedance, and the levels of thromboxane A2 (TXA2) and prostacyclin (PGI2) in blood were measured by 125I-TXB2 and 125I-Keto-PGF1alpha radioimmunoassay.
The results showed that liqi inhibited tumor growth in tumor-implanted mice and arrested the cell proliferation in the G0/G1 phase and reduced the portion of cells in S and G2/M phase for SGC-7901 cells. Liqi increased the activity of NK cells and TNF-alpha, stimulated IL-2 production and activity, and regulated T lymphocyte subpopulations. Liqi inhibited the Lewis lung carcinoma metastasis by inhibiting platelet aggregation and normalizing the balance between TXA2 and PGI2.
All these findings demonstrated that liqi has an anti-tumor effect in vivo. The mechanism may be related to immune regulation and anticoagulation effects.
BMC Complementary and Alternative Medicine 08/2009; 9:20. · 2.24 Impact Factor
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ABSTRACT: In this study, we established a drug screening system based on transcriptional regulation of vascular endothelial growth factor (VEGF) under hypoxia-inducible factor-1alpha control. We cloned the neomycin-resistance gene into the plasmid GL (pGL)3-promoter vector to generate the pGL3-promoter-neo vector. The 3 copies of the 47-bp fragment that contained the hypoxia response element of VEGF were synthesized and inserted in front of the minimal promoter of the pGL3-promoter-neo vector to generate p3HRE-luc-neo. The recombinant reporter gene vectors were transfected into EAhy926 cells, and stable cell lines were obtained. The positive cell line was selected for its ability to express luciferase in response to hypoxia. We demonstrated that CoCl(2) significantly enhances luciferase activity in a concentration-dependent fashion. We then optimized the cell density and incubation time under hypoxia which were used to screen. The assay exhibited a low background and was an ideal model for high-throughput screening for human VEGF regulators.
Biological & Pharmaceutical Bulletin 01/2009; 31(12):2255-9. · 1.66 Impact Factor
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ABSTRACT: Hydroxysafflor yellow A (HSYA), is a component of the flower, Carthamus tinctorius L. In this study, we investigated its effect on Human Umbilical Vein Endothelial Cells (HUVECs) under hypoxia. We evaluated cell viability using the MTT kit. The cell cycle distribution was analyzed by PI staining flow cytometric analysis. PI AnnexinV-FITC detection and the TUNEL assay were performed to evaluate the apoptosis rate. Nitric oxide (NO) generation in cell supernatant was measured by the Griess assay. RT-PCR, Western blot and Immunocytochemistry analysis were used to evaluate the changes of Bcl-2, Bax, p53 and eNOS. Our data showed that HSYA inhibited cell apoptosis and cell cycle G1 arrest induced by hypoxia. HSYA treatment increased the Bcl-2/Bax ratio of protein and mRNA, reduced p53 protein expression in cell nucleus. In addition, HSYA enhanced the NO content of cell supernatant under hypoxia, accompanied with upregulating eNOS mRNA expression and protein level. Taken together, these results demonstrate that HSYA could protect HUVECs from hypoxia induced injuries by inhibiting cell apoptosis and cell cycle arrest. These findings have partly revealed the molecular mechanism of HSYA on treating of ischemic heart disease. We expected our experiments might provide some clues for further research.
Vascular Pharmacology 12/2008; 50(3-4):137-45. · 1.99 Impact Factor
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ABSTRACT: This experiment studied the effect of Cordyceps sinensis extract (CSE) on mice aged by d-galactose and castrated rats to analyse its antiaging effect. Water maze and step-down type avoidance tests were used to examine the effect of CSE on learning and memory. CSE shortened escape latency, prolonged step-down latency and decreased the number of errors in mice aged by d-galactose. The effect of CSE on the sexual function of castrated rats was evaluated by measuring the penis erection latency, mount latency and ejaculation latency. CSE appeared to shorten penis erection latency and mount latency in castrated rats. The study also measured the effect of CSE on the activity of age-related enzymes. The results showed that CSE improved the activity of superoxide dismutase, glutathione peroxidase and catalase and lowered the level of lipid peroxidation and monoamine oxidase activity in the aged mice. The study demonstrated that CSE can improve the brain function and antioxidative enzyme activity in mice with d-galactose-induced senescence and promote sexual function in castrated rats. All of these findings suggest that CSE has an antiaging effect.
Phytotherapy Research 10/2008; 23(1):116-22. · 2.09 Impact Factor
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ABSTRACT: Hydroxysafflor yellow A (HSYA) is a component of the flower Carthamus tinctorius L. The present investigation determines whether HSYA can modify the effects of hypoxia on vascular endothelial cells (EC) and its mechanisms. Human EC line (EAhy926) viability was determined using the MTT assay. EC cycle phase distribution was done with PI staining and flow cytometric analysis, and EC apoptosis was done by AnnexinV-FITC detection and the TUNEL assay. The protein levels of VEGF, Bcl-2, Bax, and HIF-1 alpha were determined by ELISA or Western blot analysis, and the mRNA expression of these genes by RT-PCR analysis. HIF-1 alpha transcriptional activity was measured using a reporter gene assay. HSYA improved cell viability under hypoxia in a concentration-dependent manner by attenuating its cycle arrest and inhibiting its apoptosis. HSYA upregulated the bcl-2/bax ratio, which is downregulated under hypoxia, increased VEGF protein concentration and VEGF mRNA expression and enhanced HIF-1 alpha protein accumulation and its transcriptional activity. In conclusion, HSAY could enhance the survival of ECs under hypoxia, which may be correlated with its effect of upregulating the bcl-2/bax ratio and promoting HIF-1 alpha protein accumulation, which increases VEGF. These findings provide evidence for the mechanisms by which HSYA maintains EC survival under hypoxia.
Journal of cardiovascular pharmacology 09/2008; 52(2):191-202. · 2.83 Impact Factor
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ABSTRACT: Two novel classes of monospirocyclopiperazinium salts were designed, synthesized, and evaluated for their in vivo analgesic activities. Some interesting structure-activity relationships are revealed: (1) Spirocyclopiperazinium moiety is favorable to improve the analgesic activity; (2) The size and conformation of spirocyclopiperazinium moiety significantly affects the analgesic activity; (3) Phenylethyl group of 3d is a crucial pharmacophore. Among the compounds synthesized, 3d exhibited the most potent activity with low toxicity. Further antinociceptive mechanism studies of 3d showed that these compounds will be a new kind of analgesics.
Bioorganic & Medicinal Chemistry Letters 12/2007; 17(22):6245-9. · 2.55 Impact Factor
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ABSTRACT: In order to improve the analgesic activity of lead compound 7a, two series of dispirocyclopiperazinium (DSPZ) salts 9a-h, 10a-e and compounds 14, 15 were synthesized and evaluated for their in vivo analgesic activity both by acetic acid induced writhing test and hot plate test. Compounds 9h, 14, and 15 exhibited better analgesic activities than 7a. Several important structure-activity relationships were revealed from this study: (1) the introduction of aryl group would obviously improve the activity; (2) it was favorable to enhance the analgesic activity and reduce the toxicity to incorporate alkyl group with suitable length in the molecule; (3) carbamate analogues displayed lower toxicity than carboxylic ester analogues; (4) hydroxylation and chlorination of lead compound could increase the analgesic activity in hot plate test.
Bioorganic & Medicinal Chemistry Letters 10/2007; 17(18):5078-81. · 2.55 Impact Factor
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ABSTRACT: The compound LXM-10 (2,4-dimethyl-9-beta-phenylethyl-3-oxo-6, 9-diazaspiro [5.5]undecane chloride) is a new spirocyclopiperazinium salt compound. This is the first article to evaluate its antinociceptive effect in the abdominal constriction test induced by acetic acid and the hot-plate test. In the abdominal constriction test, LXM-10 had a significant dose-response effect, and the maximal inhibition ratio was 79.2%. In the hot-plate test, LXM-10 had significant dose-response and time-response effects. The antinociceptive effect began at 1.0 h, peaked at 2.0 h, and persisted 3.0 h after s.c. administration. The hot-plate latency was increased by 126.8% at the dose of 12.0 mg/kg. The antinociceptive effect of LXM-10 was blocked by mecamylamine (a central and peripheral neuronal nicotinic acetylcholine receptor antagonist, 0.25, 0.5, 1.0 mg/kg, i.p.), hexamethonium (a peripheral neuronal nicotinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.), atropine (a central and peripheral muscarinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.), and atropine methylnitrate (a peripheral muscarinic acetylcholine receptor antagonist, 0.2, 1.0, 5.0 mg/kg, i.p.) in a dose-dependent fashion. In contrast, the effect was not blocked by naloxone (a non-selective opioid receptor antagonist, 2.0 mg/kg, i.p.) or yohimbine (a alpha(2)-adrenergic receptor antagonist, 1.0, 2.5, 5.0 mg/kg, i.p.) in the hot-plate test. Therefore, the antinociceptive effects of LXM-10 involve the peripheral neuronal nicotinic and muscarinic acetylcholine receptors; they are not related to opioid receptors or alpha(2)-adrenergic receptors. LXM-10 did not affect motor coordination, spontaneous activity, or body temperature. These findings with LXM-10 suggest that spirocyclopiperazinium derivatives could provide insight on new analgesics.
Pharmacology Biochemistry and Behavior 05/2007; 86(4):643-50. · 2.53 Impact Factor
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ABSTRACT: To study the primary effects of Niuhuang Qingwei wan on the gastrointestinal function in aninmal for justifying its efficacies in clinic.
Mice were twice administered with Niuhuang Qingwei wan (0.83, 1.67, 3.33 g x kg(-1), ig) and rats were twice administered with Niuhuang Qingwei wan (0.59, 1.18, 2.36 g x kg(-1), ig). The effects on the stomach function were evaluated by the gastric emptying test in mice and the gastric analysis in rats. The effect on the intestinal function were evaluated by the propulsive motility of the total gastrointestinal tract test in mice by recording the time and frequency of excreting carbo medicinalis. Its analgesia was explored by using the abdominal constriction test induced by acetic acid.
Niuhuang Qingwei wan decreased the activity and secretion of pepsin in a dose-dependent manner (P < 0.01, P < 0.05), the gastric juice volume at middle and high doses (P <0.01, P <0.05), and the gastric acid volume at high dose (P <0.05); However, it had no significant effects on the gastric emptying in normal mice and the acidity in gastric juice. It shortened the excreting time of feces and increased the frequency of defecation (P < 0.01, P < 0.05). It also inhibited abdominal constriction responses at high dose, and the inhibition rate was 40.0% (P <0.01).
Niuhuang Qingwei wan can promote gastrointestinal motility, decrease gastric acid volume and activity of pepsin and show certain analgesia effect. Those findings are consistent with its treating stomach heat in clinic.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 05/2007; 32(10):957-60.
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ABSTRACT: To investigate anti-aging effect and mechanism of Cordyceps extract(CSE) on aged mice induced by D-galactose.
The aged mice were induced by D-galactose. Meanwhile, they were treated with three doses of CSE. Then the ability of learning and memory, the activity of antioxidase in the different tissue, the contents of MDA of brain and liver were measured after 6 weeks.
CSE could significantly increase the ability of learning and memory, improve the activity of SOD of red blood cells, brain and liver, the activity of Na(+) -K(+) -ATPE of brain, the activity of CAT and GSH-Px of blood, and remarkably decrease the activity of MAO of brain and the contents of MDA of brain and liver.
CSE has good anti-aging effects on the aged mice, which is probably due to effects of improving antioxidation and removing free radicals.
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 09/2004; 29(8):773-6.
