acteoside and Disease-Models--Animal

Stachytarpheta cayennensis (Verbenaceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory diseases.. To investigate the effects of different doses of standardized hydro-ethanolic (SCH) and aqueous (SCA) extracts of aerial parts of S. cayennensis using a murine ovalbumin (OVA)-induced asthma model.. The major constituents of the plant extracts were identified and standardized by ultra-performance liquid chromatography coupled with mass spectrometry. Balb/c mice were challenged with OVA solution and treated concomitantly by intraperitoneal injection of standardized SCH or SCA extracts at 50, 100, and 200 mg/kg concentrations. OVA-challenged control animals were treated with either dexamethasone (OVA-DEX) or saline solution (OVA-SAL). After challenge, we assessed in vivo bronchial hyperresponsiveness, airway inflammation (number of cells), peribronchial inflammation (histological analysis) and production of OVA-specific IgE and interleukin (IL)-4, IL-5, and IL-13 (ELISA).. Acteoside, isoacteoside, and ipolamiide were the major constituents of SCH and SCA. The respective concentrations of acteoside in SCH and SCA were 78 and 98 μg/mL, while those of ipolamiide were 30 and 19 μg/mL. Treatment with 200 mg/kg of SCH or SCA decreased IL-4, IL-5, and IL-13 in lung homogenates. These reductions were accompanied by a lower influx of inflammatory cells (eosinophils, lymphocytes, and macrophages) to the airways and lungs. In addition to the anti-inflammatory effects, administration of SCA, but not SCH, ameliorated the parameters of bronchial hyperresponsiveness and decreased levels of circulating OVA-specific IgE.. The results presented herein demonstrate for the first time the anti-asthmatic activity of S. cayennensis extracts in a murine model, thereby supporting the ethnopharmacological uses of the plant.

Topics: Animals; Anti-Asthmatic Agents; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Immunoglobulin E; Inflammation; Interleukin-13; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Verbenaceae

The present study investigated the effects of

Topics: Animals; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Flowers; Gastrointestinal Microbiome; Glucosides; Mice; Mice, Inbred C57BL; Phenols

Verbascoside, a representative phenylethanoid glycoside, is widely distributed in plants and has various activities beneficial for human health. Although systemically administered verbascoside has an antinociceptive effect, little is known about the site and mechanism of its activity. The aim of the present study was to determine whether verbascoside attenuates neuropathic pain in the spinal cord and which pain regulatory systems are involved.. Chronic constriction injury of the sciatic nerve was introduced to male Sprague Dawley rats. The effects of intrathecal administration of verbascoside and its components (caffeic acid and hydroxytyrosol) on mechanical hyperalgesia and cold hyperalgesia were examined using the electronic von Frey test and cold-plate test, respectively. Several antagonists of spinal pain processing receptors were administered intrathecally to evaluate their effects on the antihyperalgesic action of verbascoside. A rotarod test was performed to assess the effects on motor coordination.. Verbascoside attenuated mechanical and cold hyperalgesia and affected motor performance in a dose-dependent manner. Caffeic acid suppressed hyperalgesia only at high doses, whereas hydroxytyrosol did not affect hyperalgesia. The inhibitory effects of verbascoside on hyperalgesia and motor coordination were reversed by naloxone, a µ-opioid receptor antagonist.. These findings imply that verbascoside exerts an antihyperalgesic effect by activating µ-opioid receptors in the spinal cord, and that neither caffeic acid nor hydroxytyrosol alone mediates its activity. Verbascoside shows promise for the treatment of neuropathic pain.. Currently available treatments for neuropathic pain have limited efficacy in most patients. Some natural products have favourable biological activities for long-term administration such as antioxidative and neuroprotective effects. Verbascoside inhibits spinal nociceptive transmission without serious side effects to the same degree as gabapentin, a first-line remedy for neuropathic pain. Natural products may be promising candidates for novel treatments of neuropathic pain.

Topics: Analgesics; Animals; Biological Products; Constriction; Disease Models, Animal; Glucosides; Humans; Hyperalgesia; Male; Neuralgia; Phenols; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Receptors, Opioid, mu

This study aims to show the corrective effect of verbascoside on histomorphological and biochemical differences in the colon mucosa of rats in which colon ischemia-reperfusion (I/R) injury was induced.. Fifty Sprague Dawley male rats were divided into 5 groups, of control, sham, ischemia (I), I/R, and I/R+verbascoside. Ischemia and reperfusion were applied to the suitable groups for 30 minutes and 120 minutes respectively, and 10 mg/kg verbascoside was administered intraperitoneally. Histomorphological assessment was done in the colon tissues obtained, and the goblet cells were assessed using the Alcian blue method. Proliferating cell nuclear antigen (PCNA), TUNEL, and hypoxia-induced factor 1 (HIF-1α) assays were used to assess oxidative stress with the immunohistochemical method. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and total thiol (TT) levels were checked, for a biochemical analysis of oxidative stress.. Compared with the I/R group, histomorphological differences were seen to be corrected in colon epithelium in the I/ R+verbascoside group. The goblet cell number increased and cell proliferation was increased, as seen with the PCNA assay; and apoptosis was decreased, as seen with the TUNEL assay. HIF-1α expression also decreased in the drug group. In the drug group, SOD, GSH-Px, TAS, and TT levels increased, but TOS, OSI, and MDA levels decreased.. It was seen that verbascoside had a corrective effect on histomorphological and biochemical differences caused by I/R injury.

Topics: Animals; Antioxidants; Colon; Disease Models, Animal; Glucosides; Intestinal Mucosa; Male; Oxidative Stress; Phenols; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The deleterious effects of diabetes mellitus (DM) over development are apparently due to an increase in oxidative stress. Some antioxidants could prevent developmental alterations produced by diabetic state. Extracts of plants of the genus Buddleja are used traditionally for Mexican indigens to ameliorate some diseases. The purpose of this work was to evaluate the effect of the extract of Buddleja cordata over diabetic embryopathy.. Two experimental approaches were used: an in vivo study and an in vitro model. In the first, rats were treated with streptozotocin, streptozotocin plus methanolic extract of B. cordata, or none. Females were sacrificed at gestational day (GD) 19, and biochemical clinical parameters were measured; also, the fetuses were obtained and morphologically analyzed. In the in vitro model, a verbascoside-enriched fraction (VEF) of the extract was used in whole embryo culture in order to search for the mechanisms for embryoprotection effect over hyperglycemia-induced malformations.. In the in vivo experiments, B. cordata extract reduces the frequency and severity of fetal malformations produced by chemically induced diabetes, and additionally partially ameliorates the diabetic condition; in the in vitro model, both severity and frequency of embryo dysmorphogenesis were reduced by the VEF; also, this fraction reduces lipoperoxidation without affecting the activity of the antioxidant enzymes.. The results suggest that verbascoside of methanolic extract and enriched fraction can directly affect the redox state, and thus, prevents the embryotoxicity mediated by oxidative stress, in embryos of diabetic pregnancy.

Topics: Animals; Buddleja; Diabetes Mellitus; Disease Models, Animal; Fetal Diseases; Glucosides; Phenols; Pregnancy; Rats

The objective of this study was to assess the anti-stroke activity of acteoside isolated from methanolic root extract of C. oppositifolia METHODS: Ischemia-reperfusion(I/R) brain injury was induced in Wistar rats to assess the anti-stroke activity of acteoside. Rats were pretreated with acteoside (10, 25 & 50 mg/kg, p.o.) before the induction of I/R injury. Parameters such as neurological, motor-cognitive functions were evaluated along with morphological (brain volume, infarct size), biochemical (SOD, Catalase, GSH, lipid peroxidation, TNF-α, IL-6, IL-10, ICAM-1, HIF-1α, VEGF, and NF-κB), histopathological, and gene expression studies (HIF-1α, VEGF) were performed to study the protective effect of acteoside against I/R induced brain injury.. I/R injury caused significant deterioration of neurological (p < 0.01), motor (p < 0.01) and cognitive (p < 0.01) functions, associated with increase in the brain volume (p < 0.01), and infarct size (p < 0.01); increase in the levels of MDA, TNF-α, IL-6, ICAM-1, HIF-1α, VEGF, and NF-κB along with significant decrease in SOD, catalase, GSH, and IL-10 (p < 0.01 for all parameters) compared to Sham control group. Histology of brain tissue of disease control group exhibited significant vascular changes, neutrophil infiltration, cerebral oedema, and necrosis of the neuronal cells. Further, the gene-expression studies showed significant increase in the HIF-1α (p < 0.01) and VEGF (p < 0.01) mRNA levels in the I/R control compared to Sham control. Interestingly, the acteoside (10, 25 & 50 mg/kg) has prevented the neurological, motor and cognitive dysfunctions, along with inhibiting the morphological, biochemical, histological and gene expression changes induced by I/R-injury (p < 0.05 for 10 mg; p < 0.01 for 25 & 50 mg/kg of acteoside for all the parameters).. These findings suggest that acteoside possess potent anti-stroke activity through modulation of HIF-1α, NF-κB, and VEGF pathway along with its potent antioxidant activity.

Topics: Animals; Antioxidants; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosides; Hypoxia-Inducible Factor 1, alpha Subunit; Lamiaceae; Male; NF-kappa B; Phenols; Plant Extracts; Rats; Rats, Wistar; Reperfusion Injury; Stroke; Vascular Endothelial Growth Factor A

Ginseng (G) and Prepared Rehmannia Root (PRR) are commonly used in traditional Chinese medicine for blood supplementation. This study aimed to study G and PRR with different compatibility ratios changes in chemical composition and inhibition of cyclophosphamide-induced myelosuppression. HPLC was used to determine the chemical constituents of 13 ginsenosides, 5-hydroxymethylfurfural (5-HMF) and verbascoside in different proportions of G-PRR. Balb/c mice were injected intraperitoneally with cyclophosphamide (CTX) to induce bone marrow suppression. The effects of different proportions of G-PRR on peripheral blood, bone marrow nucleated cells, thymus and spleen index of myelosuppressed mice were analyzed. The results showed that the compatibility of G and PRR can promote the dissolution of ginsenosides, and the content of conventional ginsenosides decreased, and the content of rare ginsenosides increased. Different proportions of G-PRR increased the number of peripheral blood and bone marrow nucleated cells in cyclophosphamide-induced bone marrow suppression mice (p < 0.01), increased thymus index (p < 0.01), decreased spleen index (p < 0.01). Different proportions of G-PRR can improve the myelosuppression induced by cyclophosphamide in mice, and the combined effect of G-PRR is better than the single decoction of G and PRR. Among them, G-PRR 2 : 3 and G-PRR 1 : 2 were better than the other groups. These results indicate that different proportion of G-PRR can improve bone marrow suppression, and the combined decoction of G-PRR is better than the separate Decoction in improving bone marrow suppression. This improvement may be related to the changes of the substance basis and active ingredients of G-PRR.

Topics: Animals; Antineoplastic Agents, Alkylating; Bone Marrow; Cyclophosphamide; Disease Models, Animal; Dose-Response Relationship, Drug; Furaldehyde; Ginsenosides; Glucosides; Injections, Intraperitoneal; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred BALB C; Molecular Structure; Panax; Phenols; Plant Roots; Rehmannia; Structure-Activity Relationship

BACKGROUND Cartilage degeneration during osteoarthritis (OA) most adversely affects the quality of life by hindering the movement. The present study investigated the role of verbascoside in the protection of cartilage degeneration induced by osteoarthritis. MATERIAL AND METHODS The enzyme-linked immunosorbent (ELISA) and western blot assays were used for determination of inflammatory cytokine secretion in serum and cartilage tissues, respectively. RESULTS Treatment of the OA rats with verbascoside inhibited overproduction of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and IL-1ß in serum as well as cartilage tissues. The expression of P2X7R and matrix metalloproteinase (MMP)-13 was much higher in the rats induced with OA. However, administration of verbascoside reversed the OA-induced upregulation of P2X7R and MMP-13 expression in the cartilage tissues. The OA-mediated increase in substance P (SP) and prostaglandin E2 (PGE2) expression was also reduced in the cartilage tissues by the verbascoside treatment. Western blot assay revealed that verbascoside treatment markedly decreased the activation of IkappaBalpha and NF-kappaB p65 in the OA rats. CONCLUSIONS Thus, verbascoside inhibited inflammatory cytokine secretion in the OA rats by targeting P2X7R expression, production of matrix metalloproteinase, PGE2 and downregulation of NF-kappaB signaling pathway. Therefore, verbascoside may be used as potent agent for osteoarthritis treatment.

Topics: Animals; Cartilage, Articular; Cytokines; Disease Models, Animal; Down-Regulation; Glucosides; Immunosuppressive Agents; NF-kappa B; Osteoarthritis; Phenols; Purinergic P2X Receptor Antagonists; Quality of Life; Rats

Topics: Animals; Animals, Newborn; Autophagy; Disease Models, Animal; Glucosides; Hypoxia-Ischemia, Brain; Neuroprotective Agents; Oxidative Stress; Phenols; Rats; Rats, Sprague-Dawley; Recovery of Function

Cerebral hemorrhage (ICH) is a common cerebrovascular condition with high mortality, disability and recurrence rates. TLR4-mediated acute inflammatory injury plays a pivotal role in ICH. Verbascoside (VB) is an active component of multiple medicinal plants, and exerts neuroprotective effects in ischemic stroke by targeting the inflammatory response. However, the effects of VB on ICH and the underlying mechanisms remain unclear. In this study, we analyzed the therapeutic effects of VB on acute ICH, and the possible involvement of TLR4-mediated inflammation. VB improved the behavioral score and reduced the hematoma volume, brain edema and neuronal apoptosis in a murine model of acute ICH. Mechanistically, VB attenuated macroglia activation and decreased inflammatory factor levels, which in turn protected the neurons. Furthermore, TLR4 knockout abolished the effects of VB both in vivo and in vitro. Taken together, VB attenuates the symptoms of ICH by targeting the TLR4-mediated acute inflammatory response.

Topics: Animals; Antioxidants; Apoptosis; Brain Edema; Cerebral Hemorrhage; Disease Models, Animal; Glucosides; Inflammation; Male; Mice, Inbred C57BL; Mice, Knockout; Neurons; Neuroprotective Agents; Phenols; Plants, Medicinal; Toll-Like Receptor 4

Osteoarthritis (OA) is a common degenerative disease of synovial joints caused by inflammation. Acteoside (ACT), a major component and lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha, has been reported to regulate the inflammation and immune response. The study aims to investigate the effects of ACT on inflammatory responses and joint protection in OA rats.. Cell proliferation was examined by MTT and colony formation assay. Apoptosis was analyzed using flow cytometry with Annexin V/PI staining. ELISA was employed to examine the concentration of inflammatory cytokines. OA rat model was established by surgery stimulation.. ACT treatment significantly inhibited the upregulation of inflammatory cytokines induced by IL-1β in primary chondrocytes, including IL-6, IL-12, TNF-α and IFN-γ. ACT stimulation also enhanced the cell proliferation, while inhibited cell apoptosis in IL-1β-treated chondrocytes. Consistently, ACT treatment led to downregulation of cleaved-caspase-3 and apoptosis regulator Bax, and upregulation of Bcl-2. Furthermore, ACT treatment inhibited IL-1β-induced activation of JAK/STAT pathway. The results were confirmed in surgery-induced OA rat model. Moreover, ACT treatment significantly inhibited synovial inflammation and articular chondrocyte apoptosis in OA rats.. Our findings indicate that ACT has the potential therapeutic effect on OA through inhibiting the inflammatory responses via inactivating JAK/STAT signaling pathway.

Topics: Animals; Cell Proliferation; Chondrocytes; Disease Models, Animal; Drugs, Chinese Herbal; Glucosides; Humans; Interferon-gamma; Janus Kinases; Ligustrum; Male; Osteoarthritis; Phenols; Rats; Rats, Sprague-Dawley; Signal Transduction; STAT Transcription Factors; Tumor Necrosis Factor-alpha

Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Ethanol; Female; Glucosides; Hep G2 Cells; Hepatitis, Alcoholic; Humans; I-kappa B Proteins; Lamiaceae; Liver; NF-kappa B; Phenols; Plant Leaves; Rats; Rats, Wistar; Signal Transduction; Toxicity Tests, Acute; Treatment Outcome

Topics: Animals; Biomarkers; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Disease Models, Animal; Female; Glucosides; Mice; Models, Biological; Organ Size; Osteoporosis; Ovariectomy; Phenols; Protective Agents; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; TNF Receptor-Associated Factor 6

Osmanthus fragrans flower extract (OFE) is an organic extract from O. fragrans flower, which exhibits neuroprotective, free radical scavenging, and antioxidant effects. Therefore, the protective effect of OFE and acteoside against aging was studied. An aging ICR mouse model was established by chronically administering d-galactose (250 mg/kg) for 8 weeks. d-galactose induced spatial learning and memory impairments that were successfully inhibited by OFE and acteoside, which could shorten escape latency, improve platform crossing times, and increase zone time. The antioxidant potential of OFE and acteoside in vivo was evaluated by estimating the following: activities of antioxidant enzymes, such as glutathione peroxidase and aging-related enzyme, particularly monoamine oxidase; contents of lipid peroxidation methane dicarboxylic aldehyde, advanced glycation end products, and 8-hydroxy-2'-deoxyguanosine (a DNA damage product); and levels of nuclear factor-erythroid 2-related factor 2. OFE and acteoside also inhibited d-galactose-induced neurological aging by suppressing the increase in glial fibrillary acidic protein and neurotrophin-3. Considering the dose-dependent protective effects of OFE and acteoside, we concluded that OFE, rich in acteoside, was a good source of natural antiaging compounds.

Topics: Aging; Animals; Disease Models, Animal; Flowers; Galactose; Glucosides; Humans; Magnoliopsida; Male; Memory; Mice; Mice, Inbred ICR; Phenols; Plant Extracts; Protective Agents

Parkinson's disease (PD) is characterized by the progressive degeneration of the dopaminergic neurons in the substantia nigra (SN) region. Acteoside has displayed multiple biological functions. Its potential role against PD and the underlying signaling mechanisms are largely unknown. Here, we showed that oral administration of acteoside significantly attenuated parkinsonism symptoms in rotenone-induced PD rats. Further, acteoside inhibited rotenone-induced α-synuclein, caspase-3 upregulation and microtubule-associated protein 2 (MAP2) downregulation in PD rats. The molecular docking and molecular dynamics (MD) simulation results indicated that acteoside may directly bind to and inhibit caspase-3. Acteoside formed hydrogen bonds with at least six residues of caspase-3: ThrA177, SerA178, GlyA238, SerB339, ArgB341 and TrpB348. In addition, a pi-pi interaction was formed between acteoside and caspase-3's HisA237, which might further stabilize the complex. MD simulation results demonstrated that the binding affinity of the caspase-3-acteoside complex was higher than that of caspase-3 and its native ligand inhibitor. Together, we show that acteoside binds to caspase-3 and exerts neuroprotection in the rotenone rat model of PD.

Topics: alpha-Synuclein; Animals; Caspase 3; Disease Models, Animal; Glucosides; Humans; Microtubule-Associated Proteins; Molecular Dynamics Simulation; Parkinson Disease; Phenols; Protein Binding; Rats; Rats, Sprague-Dawley; Rotenone

Acteoside, also known as verbascoside or orobanchin, is a common compound found in many important medicinal plants including the Chinese herb Cistanche deserticola Y. C. Ma, which is used for its neuroprotective and memory enhancement properties. We have investigated the effects of acteoside using a senescent mouse model induced by a combination of chronic intraperitoneal administration of d-gal (60 mg/kg/day) and oral administration AlCl3 (5 mg/kg/day) once daily for 90 days. After 60 days, acteoside (30, 60, and 120 mg/kg/day) was orally administered once daily for 30 days. The memory enhancing effects of acteoside were evaluated using the Morris water maze test. The results showed that 30-120 mg/kg/day of acteoside reduced the escape latency in finding the platform, and increased the number of crossings of the platform. A 30-120 mg/kg/day of acteoside increased significantly the expression of nerve growth factor and tropomycin receptor kinase A mRNA and protein in the hippocampus, measured using real-time RT-PCR, immunohistochemical analysis, and western blotting. These results support the use of C. deserticola for memory enhancement and indicate that the effects of acteoside are induced via promotion of nerve growth factor and tropomycin receptor kinase A expression.

Topics: Administration, Oral; Aging; Aluminum Chloride; Aluminum Compounds; Animals; Chlorides; Cognition Disorders; Disease Models, Animal; Galactose; Glucosides; Hippocampus; Memory; Memory Disorders; Mice; Nerve Growth Factors; Phenols; Receptor, trkA

Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d-galactose and AlCl3 , and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step-down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase-3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase-3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss.

Topics: Aging; Aluminum Chloride; Aluminum Compounds; Animals; Antioxidants; Caspase 3; Chlorides; Cistanche; Disease Models, Animal; Galactose; Glucosides; Hippocampus; Memory; Memory Disorders; Mice; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase; Phenols; Vitamin E

We investigated the role of the HIPK2-p53 signaling pathway in tumorigenesis and resistance to the drug Verbascoside (VB) in colorectal cancer (CRC), using in vivo and in vitro experiments.. Primary human CRC samples and normal intestinal tissues from patients were analyzed for HIPK2 expression by immunohistochemistry (IHC) and its expression was correlated against patients' clinicopathological characteristics. Human CRC HCT-116 cells were implanted in BALB/c nude mice; mice with xenografted tumors were randomly administrated vehicle (control), 20, 40, or 80 mg/mL VB, or 1 mg/mL fluorouracil (5-FU). HIPK2, p53, Bax, and Bcl-2 expression in these tumors were determined by IHC. In vitro effects of VB on CRC cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry; HIPK2, p53, p-p53, Bax, and Bcl-2 were measured by western blot.. IHC analysis for 100 human CRC tumor samples and 20 normal intestinal tissues, showed HIPK2 expression to inversely correlate with Dukes stage and depth of invasion in CRC (P<0.05). In vivo, the inhibition rates of 20, 40, and 80 mg/mL VB on CRC xenograft tumor weight were 42.79%, 53.90%, and 60.99%, respectively, and were accompanied by increased expression of HIPK2, p53, and Bax, and decreased Bcl-2 expression in treated tumors. In vitro, VB significantly inhibited proliferation of CRC cell lines HCT-116, HT-29, LoVo, and SW620, in a time- and dose-dependent manner. The apoptosis rates of 25, 50, and 100 μM VB on HCT-116 cells were 10.83±1.28, 11.25±1.54, and 20.19±2.87%, and on HT-29 cells were 18.92±6.12, 21.57±4.05, and 25.14±6.73%, respectively. In summary, VB treatment significantly enhanced the protein expression of pro-apoptotic HIPK2, p53, p-p53, Bax, and decreased anti-apoptotic Bcl-2 expression in CRC cells.. HIPK2 protein modulates the phosphorylation status of p53, and levels of Bax and Bcl-2 in CRC. We also found that VB effectively activated the HIPK2-p53 signaling pathway, resulting in increased CRC cell apoptosis.

Topics: Adult; Aged; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carrier Proteins; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Disease Models, Animal; Female; Gene Expression; Glucosides; Heterografts; Humans; Male; Mice; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Phenols; Protein Serine-Threonine Kinases; Signal Transduction; Tumor Suppressor Protein p53

The leaves, flowers and whole aerial parts of Verbascum L. species have been used to treat respiratory problems, haemorrhoids and other types of inflammatory conditions in traditional Turkish medicine.. In order to evaluate this traditional information, the anti-inflammatory, antinociceptive and wound healing activities of Verbascum mucronatum Lam. which is used as haemostatic in Turkish folk medicine were investigated.. In vivo inhibitory effect of the extracts on the carrageenan-induced hind paw edema model in mice was studied for the assessment of anti-inflammatory activity. Moreover, the wound healing potential of the plant were evaluated by using in vivo wound healing experimental models, i.e. incision and excision models on mice and rats, were comparatively assessed with a reference ointment Madecassol(®). Skin samples were also evaluated histopathologically.. The results of these experimental studies exhibited that Verbascum mucronatum displays anti-inflammatory, antinociceptive and wound healing activities. Through bioassay-guided fractionation and isolation procedures four iridoid glucosides, ajugol (1), aucubin (2), lasianthoside I (3), catalpol (4), two saponins, ilwensisaponin A (5) and C (6) and a phenylethanoid glycoside, verbascoside (7) were isolated and their structures were elucidated by spectral techniques. Verbascoside (7) was found to possess significant wound healing activity as well as antinociceptive and anti-inflammatory potentials, per os without inducing any apparent acute toxicity or gastric damage.. The experimental study revealed that Verbascum mucronatum displays remarkable antinociceptive, anti-inflammatory and wound healing activities.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Disease Models, Animal; Edema; Flowers; Glucosides; Iridoid Glycosides; Male; Mice; Molecular Structure; Phenols; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Skin; Triterpenes; Verbascum; Wound Healing

This study reports on the rapid isolation of verbascoside from Lippia citriodora H.B.K. (Verbenaceae), an inexpensive and widespread source, and the evaluation of its antihyperalgesic activity.. Isolation of verbascoside was achieved by size exclusion chromatography with Sephadex LH-20 eluting with 50% EtOH, which is proposed as a fast and efficient method of separation.. The antihyperalgesic activity of verbascoside was tested by in-vivo assay using the paw-pressure test in two animal models of neuropathic pain: a peripheral mononeuropathy produced either by a chronic constriction injury of the sciatic nerve (CCI) or by an intra-articular injection of sodium monoiodoacetate (MIA).. Verbascoside administered intraperitoneally at a dose of 100 mg/kg reverted the mechanical hyperalgesia in both CCI and MIA treated rats, as evaluated in the paw-pressure test. Verbascoside was also effective against mechanical hyperalgesia after oral administration at doses of 300 and 600 mg/kg.

Topics: Administration, Oral; Analgesics; Animals; Disease Models, Animal; Drugs, Chinese Herbal; Glucosides; Hyperalgesia; Injections, Intraperitoneal; Iodoacetates; Lippia; Male; Neuralgia; Phenols; Phytotherapy; Rats; Rats, Sprague-Dawley; Rotarod Performance Test; Sciatic Nerve

Verbascoside has previously been characterized as an effective scavenger of active free radicals and an inhibitor of lipid peroxidation. In the present study, we have investigated the effects of verbascoside from Syringa vulgaris in a rat model of ligature-induced periodontitis.. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received vebascoside 2 mg/kg orally, daily for 8 days.. On the eighth day after placement of the ligature, we evaluated several markers of inflammation: (i) myeloperoxidase activity, (ii) thiobarbituric acid-reactant substance measurements, (iii) NF-κB expression, (iv) iNOS expression, (v) the nitration of tyrosine residues, (vi) activation of the nuclear enzyme poly(ADP-ribose) polymerase, (vii) Bax and Bcl-2 expression and (viii) a degree of gingivomucosal tissue injury. Oral administration of verbascoside (2 mg/kg daily for 8 days) significantly decreased all of the parameters of inflammation as described above.. These results demonstrate that verbascoside exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage associated with ligature-induced periodontitis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Cells, Cultured; Disease Models, Animal; Gingiva; Glucosides; Inflammation Mediators; Ligation; Male; Molar; Mouth Mucosa; Periodontitis; Phenols; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Syringa

Evidences have suggested that Tectona grandis (TG) attenuates gastric mucosal injury; however its mechanism has not yet been established. The aim of present study was to evaluate the gastroprotective mechanism of ethanolic extract of TG (E-EtOH), butanolic fraction (Fr-Bu) and to identify its active constituents. Anti-ulcer activities were evaluated against cold restraint (CRU) and pyloric ligation (PL) induced gastric ulcer models and further confirmed through H(+) K(+)-ATPase inhibitory activity. Cytoprotective activity was evaluated in alcohol (AL) induced gastric ulcer model and further through PGE(2) level. E-EtOH and Fr-Bu attenuated ulcer formation in CRU. Moreover E-EtOH and Fr-Bu displayed potent anti-secretory activity as evident through reduced free acidity and pepsin activity in PL, confirmed further by in vitro inhibition of H(+) K(+)-ATPase activity. In addition cytoprotective potential of E-EtOH and Fr-Bu were apparent with protection in AL model, increased PGE(2) content and enhanced mucin level in PL. Phytochemical investigations of Fr-Bu yielded terpenoides and a phenolic glycoside, verbascoside. The anti-secretory mechanism of verbascoside mediated apparently through inhibition of H(+) K(+)-ATPase with corresponding decrease in plasma gastrin level, is novel to our finding. Gastroprotection elicited by TG might be through proton pump inhibition and consequent augmentation of the defensive mechanism.

Topics: Animals; Anti-Ulcer Agents; Cold Temperature; Dinoprostone; Disease Models, Animal; Female; Gastric Acid; Gastric Mucosa; Gastrins; Glucosides; Male; Mucins; Pepsin A; Phenols; Phytotherapy; Plant Extracts; Plant Leaves; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Stomach; Stomach Ulcer; Verbenaceae

In this study we evaluated the effect of glycosylated phenylpropanoid verbascoside (VB), isolated from cultured cells of the medicinal plant Syringa vulgaris (Oleaceae) in experimental animal model of spinal cord injury (SCI). SCI was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, tissue damage, and apoptosis. At 1 and 6 h after injury, the mice were treated with VB extract, administered at the dose of 2 mg/kg with intraperitoneal administration. Immunohistochemical examination demonstrated a marked increase on expression for nitrotyrosine, inducible nitric oxide synthase, poly(ADP-ribose), and apoptosis events (increase of Bax and Bcl-2 expression) in the spinal cord tissue. Additionally, we demonstrate that these inflammatory events were associated with the cytokines expression (TNF-α and IL-1β), neutrophil infiltration (myeloperoxidase), and activation of NF-κB. In contrast, all of these parameters of inflammation were attenuated by treatment with VB. In a separate set of experiment, we have clearly demonstrated that VB treatment significantly ameliorated the recovery of function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with VB extract reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Cell Culture Techniques; Chromatography, High Pressure Liquid; Disease Models, Animal; Glucosides; Immunohistochemistry; In Situ Nick-End Labeling; Injections, Intraperitoneal; Interleukin-1beta; Male; Mice; Mice, Inbred Strains; Motor Activity; Nitric Oxide Synthase Type II; Phenols; Plant Extracts; Poly Adenosine Diphosphate Ribose; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Spinal Cord; Spinal Cord Injuries; Syringa; Tumor Necrosis Factor-alpha; Tyrosine

The chromatographic separation of MeOH extract from Clerodendron trichotomum Thunberg leaves led to the isolation of three phenylpropanoid compounds. Using spectroscopic methods, the structures of these compounds were determined as beta-(3', 4'-dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(4-O-caffeoyl)-glucopyranoside, acteoside (verbascoside) (1), beta-(3', 4'-dihydroxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-(6-O-caffeoyl)-glucopyranoside, isoacteoside (2), beta-(3', 4'-dihydroxyphenyl) ethyl-O-alpha-L-rhamnopyranosyl (1-->3)-beta-D-glucopyranoside, and decaffeoylacteoside (3). We measured the anti-inflammatory activity of these three phenylpropanoid compounds both in vitro (DPPH reduction assay, TBARS assay on Cu (2+)-induced oxidized LDL, PGE(2) assay) and in vivo (acetic acid induced vascular permeability in mice and carrageenan-induced hind paw edema in rats). 80% methanol fraction and acteoside had the activity.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Capillary Permeability; Carrageenan; Catechols; Cell Line; Clerodendrum; Dinoprostone; Disaccharides; Disease Models, Animal; Dose-Response Relationship, Drug; Free Radical Scavengers; Glucosides; Humans; Inflammation; Magnetic Resonance Spectroscopy; Mast Cells; Mice; Molecular Structure; Phenols; Picrates; Plant Leaves; Rats; Thiobarbituric Acid Reactive Substances

The aim of the present study was to examine the effects of verbascoside (VB) in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of 2,4 dinitrobenzene sulfonic acid (DNBS; 25 mg/rat). VB was administered daily per os (0.2 and 2 mg/kg) 4 days after DNBS administration in the colon. Treatment with VB significantly (P < 0.01) reduced macroscopic damage score, loss of body weight, myeloperoxidase activity and thiobarbituric acid-reactant substances. Moreover, the intensity of the positive staining for tumor necrosis factor-alpha, interleukin-1beta, intercellular adhesion molecule-1, P-selectin, inducible nitric oxide synthase, and poly(ADP ribose) was also significantly (P < 0.01) reduced by VB treatment. Therefore, VB treatment significantly (P < 0.01) reduced the degree of NF-kappaB p65 and activation of the pro-active form metalloproteinase (MMP)-2 and pro-MMP-9 activity. The results of this study suggested that VB functions as an intracellular radical scavenger and so reduces the microscopic and macroscopic signs of colitis in the rat. Therefore, administration of VB may be beneficial for the treatment of inflammatory bowel disease.

Topics: Animals; Antioxidants; Body Weight; Cells, Cultured; Colitis; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Precursors; Gelatinases; Glucosides; Male; Matrix Metalloproteinase 9; Peroxidase; Phenols; Rats; Rats, Sprague-Dawley; Syringa; Thiobarbituric Acid Reactive Substances; Transcription Factor RelA

TJN-259 is a chemical substance based on the structural features of the botanically derived ingredient acteoside. This study was performed in order to elucidate the antinephritic effects of TJN-259 in experimental immunoglobulin A (IgA) nephropathy. In this study, 28-week-old ddY mice were used as a spontaneous model of IgA nephropathy. With regard to spontaneous IgA nephropathy, we investigated the effects of TJN-259 administered from 28 to 40 weeks. In addition, an accelerated model of IgA nephropathy was experimentally induced in ddY mice by oral administration of bovine serum albumin, followed by reticuloendothelial blocking by colloidal carbon injection and heminephrectomy. At 10 weeks after the 3rd carbon injection, we also examined the effects of TJN-259 on accelerated IgA nephropathy. To investigate the effects of TJN-259 on transforming growth factor (TGF)-beta1 production in accelerated IgA nephropathy, kidneys were isolated and measured TGF-beta1 by the enzyme-linked immunosorbent assay (ELISA) method. The administration of TJN-259 to mice with spontaneous IgA nephropathy decreased the incidence of mesangial expansion as well as the number of nuclei per glomerular cross-section in comparison with that of non-treated mice. In addition, TJN-259 treatment prevented the increase in the incidence of mesangial expansion, crescent formation, and segmental sclerosis in glomeruli in accelerated IgA nephropathy. TJN-259 also inhibited the increased immunostaining score of collagen type IV and TGF-beta1 in glomeruli of accelerated IgA nephropathy. Treatment with TJN-259 inhibited the increases in renal total and mature TGF-beta1 protein levels in accelerated type IgA nephropathy. TJN-259 failed to inhibit the increase in serum IgA levels in both models. These results suggest that TJN-259 was an effective treatment against IgA nephropathy in ddY mice, acting via the suppression of TGF-beta1 production in glomeruli.

Topics: Animals; Anti-Inflammatory Agents; Cattle; Collagen Type IV; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Glomerular Mesangium; Glomerulonephritis, IGA; Glucosides; Immunoglobulin A; Kidney; Male; Mice; Mice, Inbred Strains; Phenols; Plant Extracts; Pyridines; Sclerosis; Serum Albumin; Stachys; Transforming Growth Factor beta1

Leaf extracts of Buddleja globosa (Buddlejaceae) are used in Chilean folk medicine for wound healing. The anti-inflammatory (topic and per os), analgesic (per os) effects and the antioxidant activity of Buddleja globosa were for the first time reported by us.. Assess the antinociceptive activity of the methanol sequential and global extracts using complementary chemical and thermal models of pain, characterize pharmacologically the antinociception induced, evaluate seasonal influence to support Buddleja globosa medicinal use.. Global methanol, sequential methanol and ethanol (leaves collected in autumn and summer) extracts were evaluated for oral and topic analgesia in tail flick, formalin and writhing models, verbascoside and 7-O-luteolin glucoside were assayed in tail flick and writhing. Ibuprofen was used as reference. For characterization of induced antinociception, naltrexone, naltrindole, tropisetron, nor-binaltorphimine, prazosin, yohimbine, atropine, and N-nitro-l-arginine methyl ester were used as antagonists and inhibitors drugs.. Seasonal influence was observed since autumn extract resulted less active. Extracts showed a dose-dependent antinociceptive activity in all assays, the highest effects were obtained for the formalin and writhing test. Verbascoside was more active than ibuprofen in the writhing test (67.6% and 50.0% at equimolar doses) and showed similar effects in the tail flick (topic and oral) near 25% at equivalent doses - ED25 or EC25 - to ibuprofen. Luteolin 7-O-glucoside was slightly more active in the tail flick test and nearly half active than verbascoside in the writhing assay. Effectiveness was higher for the sequential than for global alcoholic extracts, and can be increased by selective blocking of opioid receptors. Global methanol extract seems modulated only by naltrexone.. Analgesic effect of Buddleja globosa is here demonstrated validating its use in traditional medicine. Season influence is important to be considered.

Topics: Administration, Cutaneous; Administration, Oral; Analgesics; Animals; Buddleja; Chile; Disease Models, Animal; Dose-Response Relationship, Drug; Glucosides; Ibuprofen; Luteolin; Male; Medicine, Traditional; Mice; Pain; Pain Measurement; Phenols; Plant Extracts; Plant Leaves; Seasons

Effects of acetoside (ACT) on crescentic-type anti-GBM nephritis in rats were investigated. When rats were treated with ACT from the 1st day after i.v. injection of anti-GBM serum, ACT inhibited the elevation of protein excretion into urine. In the ACT-treated rats, cholesterol and creatinine contents and antibody production against rabbit gamma-globulin in the plasmas were lower than those of the nephritic control rats. Histological observation demonstrated that this agent suppressed hypercellularity and the incidence of crescent formation, adhesion of capillary wall to Bowman's capsule and fibrinoid necrosis in the glomeruli. Furthermore, rat-IgG and C3 deposits on the GBM were significantly less in the ACT-treated group than in the control nephritic group. When the treatment was started from the 20th day after i.v. injection of anti-GBM serum, by which the disease had been established, ACT resulted in a similar effect on the nephritic rats as stated above. These results suggest that ACT may be a useful medicine against rapidly progressive glomerulonephritis, which is characterized by severe glomerular lesions with diffuse crescents.

Topics: Analysis of Variance; Animals; Antibody Formation; Cholesterol; Complement C3; Complement Hemolytic Activity Assay; Creatinine; Disease Models, Animal; Drug Evaluation, Preclinical; gamma-Globulins; Glomerulonephritis; Glucosides; Immunohistochemistry; Immunosuppressive Agents; Kidney Glomerulus; Male; Phenols; Plant Extracts; Proliferating Cell Nuclear Antigen; Proteinuria; Rats; Rats, Sprague-Dawley