piperidines and aloperine

In this review, an effort towards presenting an all-around account of the recent progress on the natural product, aloperine, is made, and the antivirus structure-activity relationship of its derivatives is also summarized comprehensively. In addition, the principal pharmacological effects and corresponding molecular mechanisms of aloperine are discussed. Some new structural modifications of aloperine are also given, which might provide brief guidance for further investigations on the natural product aloperine.

Topics: Biological Products; Piperidines; Quinolizidines; Structure-Activity Relationship

Sudden cardiac death (SCD) remains a major cause of global mortality. In addition to modern interventions, botanical folk medicines have long been used to treat cardiovascular disease, although the efficacy and underlying mechanisms are often unresolved. Aloperine, a bioactive quinolizidine alkaloid isolated from Sophora alopecuroides plants, exhibits antioxidant, anti-inflammatory, antitumor, and vasorelaxant properties, but possible antiarrhythmic effects of aloperine in SCD are unclear. Here, we examined whether aloperine protects against ischemia and reperfusion injury-associated lethal ventricular arrhythmia and sudden cardiac death. Rats were divided into sham, control, and aloperine groups, and reperfusion-provoked ventricular arrhythmogenesis, cardiac damage markers, and signaling pathways quantified following left main coronary artery ischemia and reperfusion. In vitro studies of effects of aloperine on hERG and Kv4.3 cardiac voltage-gated potassium (Kv) channels were performed using two-electrode voltage clamp analysis of cloned channels expressed in Xenopus laevis oocytes. Aloperine pretreatment (10 mg/kg) did not affect baseline cardiac electrical stability; yet, it reduced ventricular arrhythmogenesis and susceptibility to SCD (mortality rate: control: 64.3%; aloperine: 0%) induced by reperfusion injury. Aloperine also reduced serum levels of LDH, CK-MB, α-HBDH, and cTnI post-I/R, and stimulated phosphorylation of ventricular ERK1/2 and STAT-3, which are key components of RISK and SAFE signaling pathways. Inhibition of either ERK1/2 (with U0126) or STAT-3 (with Ag490) abolished aloperine-induced anti-arrhythmic effects and ERK1/2 and STAT-3 phosphorylation. Interestingly, while aloperine (100 μM) had no effect on cloned Kv4.3 activity, aloperine (1 μM and up) negative-shifted the voltage dependence of hERG activation by ~10 mV and increased peak hERG current by 35%. Thus, aloperine exerts striking anti-arrhythmic effects against myocardial ischemia and reperfusion injury-induced severe lethal ventricular arrhythmia and sudden cardiac death via the ERK1/2/STAT-3 signaling pathway, with potential additional contribution from increased cardiac myocyte repolarization capacity via augmented hERG activity.

Topics: Alkaloids; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Myocardial Reperfusion Injury; Myocytes, Cardiac; Piperidines; Rats

Type 1 diabetes (T1D) is a metabolic dysfunction characterized by the selective destruction of islet β-cells, with oxidative stress playing an essential role in the manifestation of this disease state. Aloperine (ALO) represents the main active alkaloid extracted from the traditional Chinese herbal Sophora alopecuroides L. and features outstanding antioxidative properties. In this study, T1D was induced by a single high dose streptozotocin (STZ, 150 mg/kg, intraperitoneal) in mice. Diabetic animals were intragastrically administered ALO at a dose of 50 mg/kg/day. Notably, treatment of ALO (50 mg/kg/day) for seven consecutive days could observably reverse the onset of diabetes induced by STZ accompanied by weight gain, lower blood glucose levels, and relief of β-cells damage. Our in vitro study further demonstrated that ALO protected β-cells from STZ/hydrogen peroxide-induced oxidative damage as manifested by increased expression of MnSOD and CAT. Furthermore, a network pharmacology study revealed that NOS1 represented the main target of ALO. Mechanistic studies subsequently showed that treatment of ALO increased the expression of NOS1, whereas NOS2 was decreased. Moreover, a docking study carried out suggested that ALO could fit into the binding pocket of human NOS1 and molecular dynamics simulation further validated this docking event. Collectively, the administration of ALO prior to diabetes could be a viable approach to the prevention of β-cell injury. This study may offer a novel potential herbal medicine against T1D and may further help improve the understanding of the underlying molecular mechanisms of ALO-mediated protection against oxidative stress.

Topics: Animals; Blood Glucose; Cytoprotection; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Insulin-Secreting Cells; Mice; Nitric Oxide Synthase Type I; Oxidative Stress; Piperidines; Quinolizidines; Streptozocin

Alveolar epithelial cell death, inflammation, and oxidative stress are typical features of acute lung injury (ALI). Aloperine (Alo), an alkaloid isolated from Sophora alopecuroides, has been reported to display various biological effects, such as anti-inflammatory, immunoregulatory, and anti-oxidant properties. In this study, we investigated the effects and mechanisms of Alo in treating a lipopolysaccharide (LPS)-induced ALI in a murine model.. The effects of Alo in LPS-induced ALI were investigated in C57BL/6 mice. The RIPK1 inhibitor (Nec-1) and the RIPK3 inhibitor (GSK'872) were used to evaluate the relationship of necroptosis, NF-κB activation, and PDC subunits in LPS-treated mouse alveolar epithelial cells (MLE-12). Then the effects of Alo on necroptosis, inflammation, and oxidative stress of LPS-stimulated MLE-12 cells were evaluated.. Alo significantly attenuated histopathological lung injuries and reduced lung wet/dry ratio in LPS-induced ALI mice. Alo also remarkedly reduced total protein and neutrophils recruitment in bronchoalveolar lavage fluid of ALI mice. Meanwhile, Alo ameliorated the LPS-induced necroptosis in the lungs of ALI mice. The RIPK3 inhibitor GSK'872, but not the RIPK1 inhibitor Nec-1, reversed LPS-induced p65 phosphorylation and translocation to the nucleus in MLE-12 cells. GSK'872 also reversed the LPS-induced increase in ROS and binding of RIPK3 and PDC subunits in MLE-12 cells. Moreover, Alo down-regulated the levels of p-RIPK1, p-RIPK3, p-MLKL, p-p65, the translocation of p65 to the nucleus, and reduced the expression of IL-6 and IL-8 in LPS-stimulated MLE-12 cells. Alo also inhibited the binding of RIPK3 and PDC-E1α, PDC-E1β, PDC-E2, and PDC-E3 and the ROS production in LPS-treated MLE-12 cells.. The present study validated the beneficial effects of Alo on LPS-induced ALI , suggesting Alo may be a new drug candidate against ALI.

Topics: Acute Lung Injury; Animals; Disease Models, Animal; Inflammation; Lipopolysaccharides; Lung; Mice; Mice, Inbred C57BL; Necroptosis; NF-kappa B; Oxidative Stress; Piperidines; Quinolizidines; Reactive Oxygen Species

So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1β, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.

Topics: Animals; Antiviral Agents; Cathepsin B; Chlorocebus aethiops; Cytokines; HEK293 Cells; Humans; Male; Mice; Microbial Sensitivity Tests; Molecular Structure; Piperidines; Quinolizidines; Rats, Sprague-Dawley; SARS-CoV-2; Structure-Activity Relationship; Vero Cells; Virus Internalization

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and ranked top in terms of incidence and mortality in men and women. Recently, improvements in treatment approaches for NSCLC have reported, but still, there is a need to devise innovative treatment strategies, especially to manage the advanced and metastatic stage of NSCLC. Aloperine (ALO), an herbal alkaloid, has exerted anti-cancer effects in many cancers. However, the use of any chemotherapeutic agents is dose limited due to possible adverse effects and drug-resistance issues. Therefore, a combination of chemotherapy with viral-based targeted gene therapy may provide a novel treatment strategy for NSCLC.. In conclusion, ALO-Adbic combination can produce synergistic anti-cancer effects at low doses, and may offer a more effective and less toxic new treatment strategy for NSCLC.

Topics: Adenoviridae; Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Combined Modality Therapy; Genetic Therapy; Genetic Vectors; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Piperidines; Quinolizidines; Random Allocation; Tumor Suppressor Protein p14ARF; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays

The currently available anti-inflammatory drugs often cause diverse side effects with long-term use. Exploring anti-inflammatory drugs with better efficacy and lower toxicity presents an ongoing challenge. Aloperine is an alkaloid extracted from the leaves and seeds of Sophora alopecuroides L. However, the anti-inflammatory effects of Aloperine have not been fully elucidated. This study aimed to investigate whether Aloperine suppresses lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages.. RAW264.7 macrophages were stimulated with LPS (1 μg/mL) in the presence or absence of Aloperine (50 and 100 μM). mRNA expression was measured by real-time PCR, and protein expression was assessed by western blot analysis. The secretion of pro-inflammatory cytokines was measured by ELISA. The levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured by staining. The transcriptional activity of NF-κB was assayed by a luciferase activity assay.. The results proved that Aloperine inhibited the expression of LPS-induced pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-17A (IL-17A)] in macrophages. Treatment with Aloperine inhibited NO production through suppressing inducible nitric oxide synthase (iNOS) expression and the secretion of prostaglandin E. Taken together, our findings show that Aloperine could suppress LPS-induced macrophage activation by inhibiting the TLR4/Myd-88/NF-κB pathway.

Topics: Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Cytokines; Dinoprostone; Lipopolysaccharides; Macrophage Activation; Mice; Myeloid Differentiation Factor 88; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Piperidines; Quinolizidines; RAW 264.7 Cells; Signal Transduction; Toll-Like Receptor 4

Ovarian cancer is the most lethal gynecologic malignancy worldwide with poor prognosis owing to chemotherapy resistance and cancer relapse. Hence, there is an urgent need to develop novel anticancer agents against ovarian cancer.. The aim of this research is to investigate the possible anticancer activity of aloperine, an active ingredient from a traditional Chinese medicine Sophora alopecuroides, and to explore the possible Reactive Oxygen Species (ROS)-related mechanism.. Cell viability, cytotoxicity, apoptosis, ROS generation, and oxidant stress indicators were analyzed.. Our results demonstrated that aloperine significantly induced inhibition of cell viability, promoted cytotoxicity and mitochondrial-related apoptosis, and increased ROS generation in ovarian cancer cells. Furthermore, the antioxidant α-lipoic acid reversed apoptosis in aloperinetreated cells. In addition, we identified hydrogen peroxide as the main type of ROS, and the antioxidant catalase suppressed the apoptotic inducing effect of aloperine whereas hydrogen peroxide supplement exacerbated the effect of aloperine in ovarian cancer cells.. Taken together, our results indicated that aloperine could exert anti-ovarian cancer cell activity through a reactive oxygen species activation mechanism and suggested aloperine as a potential agent against ovarian cancer.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Female; Humans; Ovarian Neoplasms; Piperidines; Quinolizidines; Reactive Oxygen Species

Aloperine is a major active component in Sophora alopecuroides L that plays diverse pharmacological properties. Recent studies have indicated the potential effect of aloperine against hypertension and cancers. However, possible toxicity of aloperine has not been carefully studied in vivo. The aim of this study was to assess the effect of intraperitoneal aloperine injection on mouse liver and kidney tissues and to investigate the role of CYP450 genes in aloperine-induced toxicity. 72 BALB/c mice were randomly divided into four groups: vehicle control group (normal saline), low-dose group (4 mg/kg), medium-dose group (8 mg/kg), and high-dose group (16 mg/kg). 18 mice in each group were intraperitoneally injected with aloperine daily for 4 weeks, and were then kept for another 1 or 4 weeks without aloperine treatment. Serum was colleted for analysis of serum biochemical indexes including ALT, AST, BUN and CRE. The liver and kidney were collected for analysis of histopathologic changes and CYP450 expression and activity. Vacuolization of cytoplasm in liver cells, swelling in kidney tubular cells, increased levels of ALT, AST, BUN, and CRE, and alteration in the expression and activity of CYP450 were observed in the high-dose group after 4 weeks of treatment. However, all aloperine-induced damages were recovered to a certain degree after maintained without aloperine for 1 week, and fully recovered after maintained without aloperine for 4 weeks. These findings suggested that aloperine regulated the expression of CYP450, which was possibly involved in aloperine-induced reversible toxicity in mouse liver and kidney tissues.

Topics: Animals; Antihypertensive Agents; Antineoplastic Agents; Cytochrome P-450 Enzyme System; Female; Injections, Intraperitoneal; Kidney; Liver; Male; Mice; Mice, Inbred BALB C; Piperidines; Protective Agents; Quinolizidines; Sophora

Aloperine, a natural alkaloid isolated from the Chinese traditional herb Sophora alopecuroides, is a broad-spectrum antiviral agent with anti-inflammatory activity. Here, we found that aloperine effectively inhibited hepatitis C virus (HCV) propagation in Huh7.5 cells and primary human hepatocytes without cytotoxicity, and it blocked HCV cell-to-cell viral transmission. The antiviral mechanism evidence demonstrated that aloperine inhibits HCV internalisation from endocytosis to the membrane fusion process, and the target may be associated with host factors. Aloperine additively inhibited HCV propagation with direct-acting antivirals (DAAs) and was effective against HCV variants resistant to known DAAs. Therefore, aloperine might be a natural lead compound for the development of innovative antivirals, and the combined use of aloperine with DAAs might contribute to eliminating liver diseases caused by HCV infection.

Topics: Antiviral Agents; Cell Line; Endocytosis; Hepacivirus; Hepatitis C; Hepatocytes; Host-Pathogen Interactions; Humans; Membrane Fusion; Piperidines; Quinolizidines; Virus Internalization; Virus Replication

Twenty-seven novel 12

Topics: Cell Line; Collagen Type I; Collagen Type I, alpha 1 Chain; Cytoprotection; Drug Design; Fibrosis; Gene Expression Regulation; Humans; Liver; Piperidines; Promoter Regions, Genetic; Quinolizidines; Safety; Structure-Activity Relationship; Transforming Growth Factor beta

Aloperine, an alkaloid isolated from

Topics: Autophagic Cell Death; Cell Cycle Checkpoints; Cell Line, Tumor; Humans; MAP Kinase Signaling System; Neoplasm Proteins; Piperidines; Quinolizidines; Thyroid Neoplasms

Programmed death-ligand 1 (PD-L1) is a T-cell inhibitory checkpoint molecule that suppresses antitumor immunity. Anti-PD-L1 antibodies have shown remarkable promise in treating tumors, but the patient response rate is low. Therefore, small-molecule checkpoint inhibitors blocking PD-L1 function are urgently needed.. Changes of protein expression and phosphorylation levels were determined by immunoblotting. The level of Membrane PD-L1 was examined by flow cytometer. Cytotoxicity of T cells and NK cells toward tumor cells were detected using LDH and cell index assays. Lysosome function was investigated by NAG assay. Changes in lysosomal-related genes were measured by RT-PCR. In vivo anti-NSCLC cancer effects were assessed using C57BL/6 mice bearing Lewis tumor xenografts.. We identified SA-49 as a new regulator of PD-L1 expression from a series of novel aloperine derivatives. SA-49 decreased the expression of PD-L1 in NSCLC cells and enhanced the cytotoxicity of co-cultured T and NK cells toward tumor cells. Importantly, lysosomal pathway contributed to SA-49-mediated down-regulation of PD-L1. SA-49 increased the biogenesis of lysosome and promoted translocation of PD-L1 to lysosome for proteolysis, which was associated with nuclear translocation of MITF. SA-49-induced MITF translocation acted through activation of PKCα and subsequently suppression of GSK3β activity. Furthermore, SA-49 suppressed Lewis tumor xenograft growth by activating immune microenvironment in C57BL/6 mice.. Our data demonstrate that SA-49 can be used to regulate PD-L1 in cancer cells and trigger its degradation by activating lysosome function.

Topics: Animals; B7-H1 Antigen; Cell Line, Tumor; Female; Glycogen Synthase Kinase 3 beta; Heterografts; Humans; Lymphocytes, Tumor-Infiltrating; Lysosomes; Mice; Microphthalmia-Associated Transcription Factor; Models, Biological; Piperidines; Protein Kinase C-alpha; Proteolysis; Quinolizidines; Signal Transduction; T-Lymphocyte Subsets; Tumor Microenvironment

Hepatocellular carcinoma (HCC) ranks third among the most common causes of cancer-related deaths worldwide. The chemotherapy for HCC is still insufficient, so far. In searching for effective anti-HCC agents from traditional Chinese medicine, we discovered that aloperine (ALO), a quinolizidine alkaloid from Sophora alopecuroides L., exerts anti-HCC activities. However, the effects of ALO on HCC have been rarely studied, and its underlying mechanisms remain unknown.. This study aims to evaluate the anti-HCC activities of ALO and explore its underlying mechanisms.. MTT assay and colony formation assay were used to investigate the anti-proliferative effects of ALO on human HCC Hep3B and Huh7 cells. Hoechst 33258 staining was used to observe the morphological changes of cells after ALO treatment. Flow cytometry was used to analyze apoptosis induction, the collapse of the mitochondrial membrane potential and cell cycle distribution. Western blotting was used to examine the expression levels of proteins associated with apoptosis and cell cycle arrest, and key proteins in the PI3K/Akt signaling pathway. Small interfering RNA (siRNA) transfection was used to investigate the role of Akt in ALO-induced apoptosis and cell cycle arrest. Zebrafish tumor model was used to evaluate the anti-HCC effects of ALO in vivo.. We first demonstrated that ALO induced apoptosis and G2/M cell cycle arrest in HCC cells through inhibition of the PI3K/Akt signaling pathway. This study provides a rationale for ALO as a potential chemotherapeutic agent for HCC.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle Checkpoints; Cell Line, Tumor; Embryo, Nonmammalian; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Phosphatidylinositol 3-Kinases; Piperidines; Proto-Oncogene Proteins c-akt; Quinolizidines; Xenograft Model Antitumor Assays; Zebrafish

Aloperine (ALO) is a novel type of alkaloid drug that is extracted from S. alopecuroide, and exert an anti-inflammatory, anti-allergenic, antitumor and antiviral effects. In our study, we evaluated the effects and underlying mechanisms of ALO on MG-63 and U2OS osteosarcoma (OS) cells. ALO suppressed the proliferation and clonogenecity of both cell lines in a dose- and time-dependent manner as observed by CCK-8 and clonogenic survival assays. Data of morphologic changes, DAPI assays and flow cytometry showed that ALO induced apoptosis of OS cells, and the results of western blotting and qRT-PCR indicated that ALO upregulated protein and mRNA of Bax and cleaved caspase-3, while downregulated Bcl-2. Besides, ALO inhibited the invasion of MG-63 and U2OS cells as shown by transwell invasion assay. The protein and mRNA of MMP-2 and MMP-9 were decreased with ALO treatment. ALO also downregulated the protein and mRNA expression of PI3K and p-AKT1. In conclusion, ALO induced apoptosis and inhibited invasion in MG-63 and U2OS cells, which maybe through suppression of PI3K/AKT signaling pathway.

Topics: Alkaloids; Apoptosis; Bone Neoplasms; Cell Line, Tumor; Cell Survival; Humans; Neoplasm Invasiveness; Osteosarcoma; Piperidines; Quinolizidines; Signal Transduction

Aloperine (1), a Chinese natural product with a unique endocyclic scaffold, was first identified to be a potent hepatitis C virus (HCV) inhibitor in our laboratory. Thirty-four new aloperine derivatives were designed, synthesized and evaluated for their anti-HCV activities taking 1 as the lead. Among them, compound 7f exhibited the potential potency with EC

Topics: Administration, Oral; Animals; Antiviral Agents; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Design; Female; Hepacivirus; Humans; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Molecular Structure; Piperidines; Quinolizidines; Structure-Activity Relationship; Time Factors; Virus Replication

Topics: Antineoplastic Agents; Apoptosis; Biomarkers; Caspases; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Flow Cytometry; Humans; Piperidines; Proto-Oncogene Proteins c-akt; Quinolizidines; Signal Transduction; Thyroid Neoplasms

Preventing filoviruses in the entry stage is an attractive antiviral strategy. Taking aloperine, a Chinese natural herb with an endocyclic skeleton, as the lead, 23 new aloperine derivatives were synthesized and evaluated for their anti-filovirus activities including ebola virus (EBOV) and marburg virus (MARV) using pseudotyped virus model. Structure-activity relationship (SAR) analysis indicated that the introduction of a 12N-dichlorobenzyl group was beneficial for the potency. Compound 2e exhibited the most potent anti-EBOV and anti-MARV effects both in vitro and in vivo. It also displayed a good pharmacokinetic and safety profile in vivo, indicating an ideal druglike feature. The primary mechanism study showed that 2e could block a late stage of viral entry, mainly through inhibiting cysteine cathepsin B activity of host components. We consider compound 2e to be a promising broad-spectrum anti-filovirus agent with the advantages of a unique chemical scaffold and a specific biological mechanism.

Topics: Antiviral Agents; Cathepsin B; Chlorobenzenes; Filoviridae; Humans; Piperidines; Quinolizidines; Structure-Activity Relationship; Virus Internalization

Aloperine is a quinolizidine alkaloid extracted from Sophora alopecuroides. It has been proven to alleviate oxidative stress and effectively promote tumor cell apoptosis in mice. Herein, we investigated whether aloperine could also mediate its protective effects on bleomycin (BLM)-induced pulmonary fibrosis. Pathological staining, western blot, RT-PCR and flow cytometry were used to evaluate the impact of aloperine on the development of pulmonary fibrosis. The effect of aloperine on fibroblast proliferation, differentiation and related signaling pathways were next investigated to demonstrate the underlying mechanisms. In the present report, we showed that aloperine provided protection for mice against BLM-induced pulmonary fibrosis as manifested by the attenuated lung injury and reduced fibrosis along with alleviated fibroblast proliferation and differentiation. Additionally, we provided in vitro evidence revealing that aloperine inhibited cellular proliferation in PDGF-BB-stimulated mouse lung fibroblasts by repressed PI3K/AKT/mTOR signaling and fibroblast to myofibroblast differentiation by repressed TGF-β/Smad signaling. Overall, our data showed that aloperine could protect the mice against BLM-induced pulmonary fibrosis by attenuated fibroblast proliferation and differentiation, which indicated that aloperine may be therapeutically beneficial for IPF patients.

Topics: Animals; Bleomycin; Cell Differentiation; Cell Proliferation; Fibroblasts; Mice; Phosphatidylinositol 3-Kinases; Piperidines; Pulmonary Fibrosis; Quinolizidines; Signal Transduction; Transforming Growth Factor beta

Aloperine (Alo), as a quinolizidine alkaloid extracted from S. alopecuroide, has the positive activities of anti-inflammatory, anti-allergenic, antitumor and anti-viral. However, the role and mechanism of Alo in breast cancer have not been studied yet. In the present study, Alo markedly inhibited the proliferation and suppressed the colony formation ability of the breast cancer cell lines MCF-7 and MDA-MB-231 in a dose-dependent manner by Cell Counting kit-8 and colony formation assays, respectively. In addition, the results of confocal microscopy analysis and flow cytometry detection revealed that Alo induced the apoptosis of MCF-7 and MDA-MB-231 cells, and western blotting indicated that Alo upregulated the protein levels of Bax, caspase-3 and caspase-9, and downregulated the expression of Bcl-2. Furthermore, the results of wound healing, Transwell migration and invasion assays demonstrated that Alo inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells, and reduced the protein levels of matrix metalloproteinase (MMP)-2 and MMP-9. Alo also downregulated the protein expressions of Ras, phosphorylated (p)-Raf proto-oncogene, serine/threonine kinase 1 and p-extracellular signal-regulated kinase 1/2. Furthermore, ISIS 2503, a Ras inhibitor, inhibited colony formation, induced apoptosis, and suppressed the migration and invasion of MCF-7 and MDA-MB-231 cells. These effects were more marked in the presence of ISIS 2503 and Alo, when compared with those of either agent alone. In conclusion, the present study reported a novel use of Alo in inhibiting the proliferation, migration and invasion, and inducing the apoptosis of human breast cancer cells by blocking the Ras signaling pathway.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; MCF-7 Cells; Neoplasm Invasiveness; Piperidines; Proto-Oncogene Mas; Quinolizidines; ras Proteins; Signal Transduction; Sophora

Topics: Alzheimer Disease; Animals; Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Glutathione; Glutathione Peroxidase; MAP Kinase Signaling System; Mice; Mitochondria; Models, Biological; Neuroprotective Agents; Oxidative Stress; Piperidines; Quinolizidines

The aim of this study was to investigate the vasodilatory effects of aloperine, one of main\ alkaloid was extracted from Sophora alopecuroides, on rat isolated thoracic aortic rings and its\ possible mechanisms. The isolated aortic arteries from normotensive Sprague Dawley rats were precontracted\ with phenylephrine (1 × 10⁻⁶ M) or KCl (60 mM). Then, aloperine (3.44 × 10⁻³ – 17.21 × 10⁻³ M)\ was added cumulatively and the tension curves was observed and recorded. The changes in tension\ in both endothelium-intact and endothelium-denuded aortic rings were also recorded. Afterwards,\ the interaction between aloperine with NG-nitro-L-arginine methylester (0.1 mM), indomethacin (1 ×\ 10⁻³ mM), tetraethylammonium (10 mM), 4-aminopyridine (5 mM), BaCl₂ (1 mM) and glibenclamide\ (0.01 mM) was evaluated. In this study, aloperine caused concentration-dependent relaxations in\ aortic rings precontracted with phenylephrine, but this effect was not observed in KCl-pretreated\ rings. Removal of endothelium showed no influence on vasodilatory effects of aloperine. In\ addition, preincubation with NG-nitro-L-arginine methylester and indomethacin did not inhibit the\ vasodilatory effects of aloperine, suggesting that the vasodilative action is endothelium-independent.\ Relaxant responses to aloperine were inhibited by tetraethylammonium and 4-aminopyridine.\ However, the vasorelaxant effect of aloperine was also not influenced by the preincubation with BaCl₂\ and glibenclamide. These findings suggest that aloperine-induced vasorelaxation effects are mainly\ due to the operations of voltage-operated potassium channels and ATP-sensitive potassium channels.

Topics: Animals; Aorta; Piperidines; Quinolizidines; Rats; Rats, Sprague-Dawley; Vasodilation; Vasodilator Agents

To explore the effects of aloperine (ALO) on allergic airway inflammation, we investigated whether its mechanism is related with NF-κB, MAPK, and Nrf2/HO-1 signaling pathways. Histochemical staining and inflammatory cell count were used to observe lung histopathological changes in mice. ELISA was used to detect the content of inflammatory cytokines and IgE in the mouse bronchoalveolar lavage fluid (BALF). Airway hyperresponsiveness (AHR) to inhale methacholine was measured by the plethysmography in conscious mice. Immunohistochemical method was used to detect the expression levels of Nrf2 and HO-1 in lung tissues. The key proteins of MAPK, NF-κB, and Nrf2/HO-1 in lung tissues were quantitatively analyzed by Western blot. Finally, the in vitro effect of ALO on the production of pro-inflammatory mediators and cytokines by lipopolysaccharide-stimulated RAW 264.7 cells was also evaluated. In the ovalbumin (OVA)-induced asthma mouse model, ALO reduced the exudation and infiltration of inflammatory cells and suppressed goblet cell hyperplasia. ALO-treated asthmatic mice also decreased the protein levels of interleukin (IL)-4, IL-5, IL-13, IFN-γ, and IgE in BALF and attenuated AHR. Furthermore, ALO inhibited the expression of key proteins of MAPK and NF-κB pathways, and increased the expression of Nrf2/HO-1 in OVA-challenged mice. Additional in vitro study has shown that ALO abrogates the macrophage production of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, IL-6, and IL-1β. Taken together, ALO attenuated allergic airway inflammation through regulating NF-κB, MAPK, and Nrf2/HO-1 signaling pathways. The results suggest the utility of ALO as an anti-inflammatory agent for the treatment of asthma.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Female; Heme Oxygenase-1; Humans; Hypersensitivity; Inflammation; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2; NF-kappa B; Piperidines; Quinolizidines; Respiratory System; Signal Transduction

Topics: Animals; bcl-2-Associated X Protein; Cardiomegaly; Cyclin-Dependent Kinase Inhibitor p27; Electrocardiography; Hemodynamics; Hypertension, Pulmonary; Lung; Male; Monocrotaline; Piperidines; Proliferating Cell Nuclear Antigen; Protective Agents; Pulmonary Artery; Quinolizidines; Rats, Sprague-Dawley; rho-Associated Kinases; rhoA GTP-Binding Protein; RNA, Messenger; Vascular Remodeling

Topics: Animals; Apoptosis; Cell Line; Colitis; Dextran Sulfate; Disease Models, Animal; Flow Cytometry; Humans; Inflammatory Bowel Diseases; Jurkat Cells; Mice; Phosphatidylinositol 3-Kinases; Piperidines; Proto-Oncogene Proteins c-akt; Quinolizidines; Signal Transduction; TOR Serine-Threonine Kinases

Pulmonary hypertension (PH) is serious, fatal disease which is promoted by oxidative stress. Aloperine have antioxidation effects, which effects on pulmonary arteries remain unclear. Therefore, this study is designed to investigate whether aloperine has protective effects on PH induced by monocrotaline and whether these effects are associated with oxidative stress. PH was induced by monocrotaline (60mg/kg), and subsequently oral administration of aloperine (25, 50, 100mg/kg/day). At the end of the experiment, hemodynamic, pathomorphologic, electrocardiographic and echocardiographic data from the rats were obtained. At same time, oxidative stress biomarkers (superoxide dismutase, malonyldialdehyde, catalase, glutathione peroxidase, total antioxidant capacity) and the protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-2, NOX-4 in the lung of rat has been detected. The result shows that aloperine treatment showed significantly improvement in hemodynamic, pathomorphologic, electrocardiographic and echocardiographic data. Moreover, aloperine treatment can alleviate the changes of oxidative stress biomarkers and suppress the expression levels of NOX-2, NOX-4. In summary, this study indicates that aloperine have protective effects on monocrotaline-induced PH. And these effects may be related to inhibit oxidative stress.

Topics: Animals; Antioxidants; Biomarkers; Dose-Response Relationship, Drug; Echocardiography; Electrocardiography; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Oxidative Stress; Piperidines; Protective Agents; Pulmonary Artery; Pulmonary Circulation; Quinolizidines; Rats; Rats, Sprague-Dawley

Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin-mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection.

Topics: Cells, Cultured; Dynamins; Endocytosis; Humans; Hydrazones; Keratinocytes; Microtubules; Mouth Mucosa; Piperidines; Porphyromonas gingivalis; Quinolizidines

Aloperine, a natural alkaloid constituent isolated from the herb Sophora alopecuroides displays anti-inflammatory properties in vitro and in vivo. Our group previously demonstrated that aloperine significantly induced apoptosis in colon cancer SW480 and HCT116 cells. However, its specific target(s) remain to be discovered in multiple myeloma (MM) and have not been investigated.. Human myeloma cell lines (n = 8), primary myeloma cells (n = 12), drug-resistant myeloma cell lines (n = 2), and animal models were tested for their sensitivity to aloperine in terms of proliferation and apoptosis both in vitro and in vivo, respectively. We also examined the functional mechanisms underlying the apoptotic pathways triggered by aloperine.. Aloperine induced MM cell death in a dose- and time-dependent manner, even in the presence of the proliferative cytokines interleukin-6 and insulin-like growth factor I. Mechanistic studies revealed that aloperine not only activated caspase-8 and reduced the expression of FADD-like interleukin-1β-converting enzyme (FLICE)-like inhibitory protein long (FLIPL) and FLICE-inhibitory proteins (FLIPS) but also activated caspase-9 and decreased the expression of phosphorylated (p)-PTEN. Moreover, co-activation of the caspase-8/cellular FLICE-inhibitory protein (cFLIP)- and caspase-9/p-PTEN/p-AKT-dependent apoptotic pathways by aloperine caused irreversible inhibition of clonogenic survival. Aloperine induce more MM apoptosis with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or borterzomib. A U266 xenograft tumor model and 5T33 MM cells recapitulated the antitumor efficacy of aloperine, and the animals displayed excellent tolerance of the drug and few adverse effects.. Aloperine has multifaceted antitumor effects on MM cells. Our data support the clinical development of aloperine for MM therapy.

Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Multiple Myeloma; Piperidines; Quinolizidines; RNA, Small Interfering; Transfection; Xenograft Model Antitumor Assays

Aloperine (ALO), one of the alkaloids isolated from Sophora alopecuroides L., is traditionally used for various diseases including neuronal disorders. This study investigated the protective effects of ALO on neonatal rat primary-cultured hippocampal neurons injured by oxygen-glucose deprivation and reperfusion (OGD/RP). Treatment with ALO (25, 50, and 100 mg/l) attenuated neuronal damage (p < 0.01), with evidence of increased cell viability (p < 0.01) and decreased cell morphologic impairment. Furthermore, ALO increased mitochondrial membrane potential (p < 0.01), but inhibited intracellular-free calcium [Ca(2+)] i (p  < 0.01) elevation in a dose-dependent manner at OGD/RP. ALO also reduced the intracellular reactive oxygen species and malondialdehyde production and enhanced the antioxidant enzymatic activities of catalase, superoxide dismutase, glutathione peroxidase and the total antioxidant capacity. The results suggested that ALO has significant neuroprotective effects that can be attributed to anti-oxidative stress.

Topics: Animals; Apoptosis; Glucose; Hippocampus; Neurons; Neuroprotective Agents; Oxygen; Piperidines; Quinolizidines; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Aloperine (ALO) is a quinolizidine alkaloid extracted from the leaves of Sophora alopecuroides (S. alopecuroides) and possesses anti-inflammatory, anti-allergenic, antitumor, and antiviral effects. In this study, when compared with seven other types of alkaloids extracted from S. alopecuroides, ALO treatment produced the most potent effects against HCT116 colon cancer cell types. ALO inhibited proliferation and induced apoptosis in HCT116 cells in a dose- and time-dependent manner as detected by MTT, clonogenic survival, and flow cytometric assays. Results of the western blot analysis and qPCR revealed that ALO increased the protein and mRNA of Bax and decreased Bcl-2 via the mitochondrial death pathway. In addition, ALO induced cell cycle arrest at the G2/M phase with a concomitant increase in p21 and p53 and a decrease in cyclin D1 and B1. ALO also inhibited phosphatidylinositol 3-kinase/Akt and JAK/Stat3. Generally, ALO exerted a significant anti-proliferative effect via apoptotic and cell cycle arrest induction in HCT116 cells. These results suggested that ALO should be investigated further as an agent of chemotherapeutic activity in human colon cancer.

Topics: Apoptosis; Cell Cycle Checkpoints; Cell Division; Cyclin B1; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p21; G2 Phase; HCT116 Cells; Humans; Phosphatidylinositol 3-Kinases; Piperidines; Quinolizidines; Tumor Suppressor Protein p53

To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain.. Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot.. Administration of ALO (80mg/kg and 40mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10mg/kg (i.p.).. ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.

Topics: Animals; Antioxidants; Constriction; Down-Regulation; Hot Temperature; Hyperalgesia; Interleukin-1beta; Interleukin-6; Male; Mice; Neuralgia; NF-kappa B; Piperidines; Quinolizidines; Sciatic Nerve; Tumor Necrosis Factor-alpha

The dry root of Sophora flavescens Ait. (SF) has long been used in a variety of Chinese herbal formulations to treat patients with cancer. Alkaloids are commonly known to present in SF as main active constituents. Here, we report that among the six characterized SF-derived quinolizidine alkaloids including sophoridine, aloperine, sophocarpine, matrine, oxymatrine and cytisine, aloperine exerted the most potent in vitro cytotoxic activity against the human cancer cell lines and oxymatrine exhibited selective anti-cancer activity against hepatocellular carcinoma HepG2 cells. Analysis of DNA fragmentation and PARP cleavage revealed that aloperine treatment for 48 hr induced apoptosis in HL-60 cells. In addition, autophagic formation of acidic vacuole was also observed in HL-60 cells exposed to aloperine. These results suggest that aloperine may be a novel contributor to the anti-cancer properties of SF.

Topics: Alkaloids; Antineoplastic Agents; Apoptosis; Azocines; Drugs, Chinese Herbal; Electrophoresis, Capillary; HL-60 Cells; Humans; Inhibitory Concentration 50; K562 Cells; Matrines; Phytotherapy; Piperidines; Plant Preparations; Plant Roots; Quinolizidines; Quinolizines; Sophora

Aloperine has been shown to inhibit 2,4-dinitrofluorobenzene (DNFB) induced allergic contact dermatitis in BALB/c mice. In the present study, we further investigated the effect of aloperine on DNFB-induced atopic dermatitis-like skin lesions in NC/Nga mice. NC/Nga mice elicited atopic dermatitis-like skin lesions after the topical application of DNFB. Aloperine treatment significantly inhibited dermatitis index and ear thickness in DNFB-treated NC/Nga mice in a dose-dependent manner. Eosinophils, mast cells infiltration into the ears and plasma level of immunoglobulin (Ig) E were also suppressed by aloperine treatment. Finally, cytokine (interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-13, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) productions in ear biopsies homogenates were significantly elevated after DNFB challenge. Topical application of aloperine increased the immunosuppressive cytokine IL-10 level, while it reduced other cytokines production in a dose-dependent manner. Taken together, these data suggest that aloperine may be one of the effective therapeutic agents for the treatment of atopic dermatitis.

Topics: Administration, Topical; Animals; Dermatitis, Atopic; Dinitrofluorobenzene; Down-Regulation; Ear; Female; Immunoglobulin E; Interleukin-10; Mast Cells; Mice; Piperidines; Quinolizidines; Th1 Cells; Th2 Cells; Up-Regulation

To establish a method for determination of 7 alkaloid in Herba Sophorae Alopecuroidis by HPLC.. X-Brige C18 (4.6 mm x 200 mm, 5 microm) column was used with acetonitriles-0.05 mol x L(-1) KH2PO4 solution (2.0 mL x L(-1) triethylamine) with gradient elution as the mobile phase and 1.0 mL x min(-1) as the flow rate. The detection wavelength was 205 nm.. Aloperin curve was linear in the range from 20.66 to 103.32 microg (r = 0.998 8) and the average recovery was 97.12% (RSD 7. 3%); sophoridine curve was linear in the range from 22.82 to 114.12 microg (r = 0.999 7) and the average recovery was 97.47% (RSD 3.0%); oxymatrine curve was linear in the range from 25.10 to 125.52 microg (r = 0.999 1) and the average recovery was 96.21% (RSD 4.5%); oxysophocarpine curve was linear in the range from 23.88 to 119.40 microg (r = 0.997 5) and the average recovery was 94. 64% (RSD 5.2%); matrine curve was linear in the range from 5.00 to 24.99 microg (r = 0.998 6) and the average recovery was 98.04% (RSD 5.4%); sophocarping curve was linear in the range from 4.69 to 23.46 microg (r = 0.999 6) and the average recovery was 96.24 (RSD 5.8%); lehmannine curve was linear in the range from 4.60 to 23.01 microg (r = 0.997 8) and the average recovery was 101.31% (RSD 4.3%).. The method is accurate, simple and feasible. It can be used as a quality evaluation in Herba S. Alopecuroidis.

Topics: Alkaloids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Matrines; Piperidines; Quality Control; Quinolizidines; Quinolizines; Sophora

Allergic contact dermatitis is a prototypic T-cell-mediated cutaneous inflammatory response. Multiple cell types, inflammatory mediators and cytokines are involved in the regulation of immunologic and inflammatory processes in allergic contact dermatitis. Aloperine is an isolated alkaloid found in the plant of Sophora alopecuroides L. It has been clinically proved effective in China for a long time for skin inflammatory diseases such as allergic contact dermatitis. However, the mechanism of aloperine on allergic contact dermatitis is largely unknown. Therefore, the aim of this study was to investigate the effect of aloperine on 2, 4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis in BALB/c mice and the possible underlying mechanisms. The results showed that topical application of DNFB on the ear provoked typical allergic contact dermatitis with ear swelling and ear erythema in BALB/c mice. Treatments with 1% aloperine suppressed DNFB-induced increase in ear thickness and ear erythema. Moreover, 1% aloperine treatment significantly decreased the up-regulated mRNA and protein levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) induced by DNFB in ear biopsy homogenates. Our findings suggest that aloperine greatly improves the DNFB-induced allergic contact dermatitis in mice. The therapeutic mechanism might be related to the reduction of TNF-alpha, IL-1beta and IL-6 production induced by DNFB.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Cytokines; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Ear; Erythema; Female; Gene Expression Regulation; Mice; Mice, Inbred BALB C; Piperidines; Quinolizidines; RNA, Messenger

To study the chemical constituents of the alkaloid fraction of Kushen decoction.. Constituents were isolated by different kinds of column chromatography and their structures were elucidated with spectral methods.. Eight compounds were isolated and identified as matrine (I), sophoridine (II), sophocarpine (III), sophoramine (IV), oxymatrine (V), oxysophocarpine (VI), aloperine (VII) and sparteine (VIII).. All these compounds were isolated from Kushen decoction for the first time. Aloperine was found firstly in Sophora flavescens, or Scutellaria baicalensis, or Rehmannia glutinosa which constituted Kushen decoction.

Topics: Alkaloids; Drug Combinations; Drugs, Chinese Herbal; Matrines; Piperidines; Plants, Medicinal; Quinolizidines; Quinolizines; Rehmannia; Scutellaria baicalensis; Sophora

Optically pure (S)- and (R)-vinylpiperidine 2 and (S)- and (R)-(hydroxyethyl)piperidine 3, which were key intermediates for the synthesis of aloperine, were synthesized from yeast-reductive products.

Topics: Oxidation-Reduction; Piperidines; Quinolizidines; Saccharomyces cerevisiae; Spectrophotometry, Infrared; Stereoisomerism

[reaction: see text] Total synthesis of aloperine and 6-epi-aloperine is reported. The crucial steps of the synthetic strategy are an aza-annulation reaction and an intermolecular Diels-Alder reaction. The synthetic plan proceeds from commercially available piperidine-2-ethanol.

Topics: Alkaloids; Piperidines; Plants, Medicinal; Quinolizidines; Stereoisomerism

The relative and absolute configuration of the title compound, (6R,7R,9R,11S)-16,17-didehydro-9-de-2-piperidinylormosanine, C15H24N2, has been elucidated. Two X-ray structures, one of the free base of the alkaloid and the second of its dihydrochloride monohydrate salt, C15H26N2(2+).2Cl-.H2O, have been determined to unequivocally establish the stereochemistry of aloperine, the parent member of a rare family of lupinine alkaloids.

Topics: Alkaloids; Anti-Inflammatory Agents, Non-Steroidal; Crystallography, X-Ray; Molecular Structure; Piperidines; Quinolizidines; Stereoisomerism

Aloperine, an alkaloid isolated from Sophora alopecuroides L, showed a marked suppressive effect on the swelling of the rat's hind paw induced by injecting carrageenin, macostatin, PGE2, histamine, 5-HT, on the rat's scald oedema induced by scalding its hind paw, and on the increased permeability of capillaries caused by histamine and the leukocytic migratory response. The swelling induced by injecting carrageenin into the hind paw of adrenolectomized rats was still significantly inhibited. Noticeably, aloperine reduced the content of PGE and histamine in the exudate formed after injecting carrageenin and dextran into the rat's hind paw, and increased the stability of red cell membranes, the activity of catalase (CAT) in hepatic tissue of mice, and reduced the content of malondialdehyde (MDA) in hepatic tissue of intoxicated mice. It had no apparent effect either on the activity of superoxide dismutase (SOD) in mice serum or on the phagocytosis of the monocyte-macrophage system, or on Forssman cutaneous vasculitis and the content of immune complex in serum of rats with Arthus reaction. But it had certain inhibitory effect on the PCA reaction and significant inhibitory effect upon such allergic reaction as Arthus reaction, reversible passive Arthus reaction, the delayed hypersensitivity reaction induced by tuberculin in rats, and adjuvant arthritis.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthus Reaction; Cell Migration Inhibition; Female; Hypersensitivity, Delayed; Inflammation; Male; Mice; Piperidines; Quinolizidines; Rats