Background: Earlier studies reported the anti-inflammatory activity in several species of Piper, and Piper umbellatum Linn. leaves containing some phytochemicals that are potent anti-inflammatory agents. However, there was no thorough investigation on the anti-inflammatory activity of the locally grown P. umbellatum in the Philippines. Objective: The study aimed to determine the anti-inflammatory activity of Piper umbellatum leaves using in vitro and in vivo assays. Methodology: Crude extracts were obtained from P. umbellatum leaves using polar and non-polar solvents. The anti-inflammatory activities of all crude extracts were determined using the carrageenan-induced paw edema test in mice and phytochemical analysis. The crude extract with the highest activity was partially purified using column chromatography. The fractions with similar TLC profile were pooled and tested for antiinflammatory activity. COX-1 and COX-2 enzyme inhibitory activity were determined in pooled fractions that showed initial activity in animal model. Results: Among the crude extracts of P.umbellatum, the crude ethyl acetate extract exhibited a significant dose-dependent inhibition on paw edema test with doses of 500 mg/kg bw, 1,000 mg/kg bw and 1,500 mg/kg bw (p<0.05). Among the 20 pooled fractions (PF) collected from the ethyl acetate extract, PF58, PF60 and PF64 had the highest COX-2 enzyme inhibitions of 83.12 %, 84.78% and 77.47%, respectively (p<0.05). PF60 also exhibited the highest anti-inflammatory activity on paw edema with inhibitions of 62.45% at low dose (250 mg/kg bw) and 76.10 % at high dose (1,000 mg/kg bw) in mice. Conclusion The ethyl acetate extract of P. umbellatum leaves and its fraction-PF60 exhibited a significant anti-inflammatory activity in in vitro and in vivo assays and contained high amounts of total phenolic and total flavonoid.
Prostaglandin-Endoperoxide Synthases ; Carrageenan ; Inflammation

Study on oxidant stress status in rat with carrageenan-induced inflammation and intervention’s ability with Artocarpus tonkinensis extract and the aqueous extract (unidentified scientific name), collected in Phu Tho. Results: carragenin 1% injection into sole of the foot of white mice that caused paw edema in mice after 4 hours. The edema status gained medium value of 118.98±15.94mg in sole of the foot. Mivce was preventively administrated by oral diclofenac. Flavonoid extract from Artocarpus tonkinensis leaves and the aqueous extract in studying doses had reduced clearly edema. There were significantly decreases in SOD activities of inflammation mice and increases of MDA level - an indicator of lipid superoxide reaction - in correlation with inflammation status of different mice groups. There was a positive correlation between edema level of mice groups and MDA levels
Plants, medicinal ; Superoxide Dismutase ; Mice ; Carrageenan ; Inflammation

This study was performed to test whether endomorphin-1 has analgesic effect, when locally administrated into inflamed peripheral tissue. Carrageenan suspension (0.5%) was injected intraplantarly into the right paw of Sprague-Dawley male rats, and the rats were subjected to a series of mechanical stimuli with von Frei filaments before and after the injection. Carrageenan-injected rats showed typical inflammatory hyperalgesic signs and decrease of withdrawal threshold, peaked at 3 to 6 hours after the injection and lasted more than 3 days. Endomorphin-1 was intraplantarly injected with carrageenan, simultaneously or 3~4 hours after carrageenan. Simultaneous injection of endomorphin-1 with carrageenan significantly reduced hyperalgesia and thd analgesic effect was prolonged up to 8 hours. The delivery of endomorphin-1 (50 microgram) into the inflamed area after 3 to 4 hours of carrageenan injection significantly increased the threshold of hyperalgesic mechanical withdrawal response, but only partially. Intrathecal treatment of endomorphin-1 completely reversed carrageenan-induced hyperalgesia. This report is the first to show that peripherally delivered endomorphin-1 relieved inflammatory hyperalgesia. But a control through peripheral mu-opioid receptors appears to be not sufficient for complete pain treatment.
Animals ; Carrageenan ; Humans ; Hyperalgesia* ; Inflammation ; Male ; Rats* ; Rats, Sprague-Dawley

Glycerin containing carrageenan as a non-aqueous carrier for vitamin C (Vc) was prepared in this study. The stabilities of Vc at room temperature and after high temperature accelerating treatment were investigated. The effects of Vc as well as carrageenan on rheological properties were analyzed. The results showed that, with the increases of Vc, the viscosity of the non-aqueous system decreased and the shear-thinning phenomenon disappeared. Furthermore, the stability of Vc was kept well in this non-aqueous system, and the retention rate maintained at a high level-over 99% a month later in room temperature, and over 97% after high temperature accelerating treatment for 20 days. The retention rate of Vc was improved with the increasing of carrageenan. It was proved that this non-aqueous system was an ideal drug delivery system for Vc.
Ascorbic Acid ; chemistry ; Carrageenan ; Drug Carriers ; chemistry ; Drug Stability ; Glycerol ; chemistry ; Oxidation-Reduction ; Solutions

The anti-inflammatory effects of fuciodan and Cistanche tubulosa (CT) extract were investigated in vitro macrophage culture system and in vivo carrageenan-induced air pouch inflammation model. CT extract inhibited nitric oxide production from activated RAW 264.7 macrophage cells, while fucoidan was inactive. In vivo air pouch inflammation model, carrageenan-induced vascular exudation and increased nitric oxide and prostaglandin E2 concentrations in the exudates were synergistically suppressed by co-administration of fucoidan or CT extract. Moreover, tissue inflammation was substantially attenuated by the combinational therapy. However, there was no synergistic effect against the inflammatory cell infiltration, although fucoidan and CT extract each markedly reduced the cell numbers. Therefore, it is suggested that fucoidan blocks infiltration of inflammatory cells, while CT extract inhibits activation of the cells, and that their combinational treatment could be a promising candidate for the relief of various types of inflammation.
Carrageenan ; Cell Count ; Cistanche ; Dinoprostone ; Exudates and Transudates ; Inflammation ; Laminaria ; Macrophages ; Nitric Oxide ; Polysaccharides

The distribution of fibronection was investigated in the carrageenan-induced keratitis of rabbitis. Keratitis was induced by the injection of carrageenan into corneas of the rabbits, and specimens were taken at various intervals. Histological examinations were done with H and E, silver impregnation and PTAH stains. The distribution of fibronectin was observed by using avidin-biotin-peroxydase(ABC) technique. The results were follow. 1. The histological changes in early stages showed acute inflammatory exudate in stroma. After two weeks, granulation tissues were formed. And then after the fourth week, the granulation tissues began to mature with the apperance of fascicle of collagen fibers and thickened epithelium. 2. Fibronectin was demonstrated in a fibrillar appearance in the acute inflammatory exudate of the stroma, which was normally absent. With the development of chronic inflammatory lesions and granulation tissues, the amount of fibronectin was increased, relative to the increase and codistribution of reticular fibers, but with the appearance of mature collagen fibers, the amount was markedly reduced. 3. The fibronectin which was absent in the normal epithelium was prominent in the regenerating epithelium.
Carrageenan ; Collagen ; Coloring Agents ; Cornea ; Epithelium ; Exudates and Transudates ; Fibronectins* ; Granulation Tissue ; Keratitis* ; Rabbits ; Reticulin ; Silver

Dandelion (DA) possesses the therapeutic ability to eliminate heat and alleviating swelling, choleresis, dieresis, and inflammation. In order to investigate the anti-arthritic effect of DA, several behavioral parameters such as paw volume, squeaking score, and weight distribution ratio were investigated in a carrageenan-induced arthritis rat model. At the maximum severity of arthritis, the daily administration of DA was initiated and lasted for 9 days. The therapeutic effects of DA were observed on 9th day after the arthritis induction, as compared to saline-treated control group. Oral administration of DA significantly alleviated apparent symptoms of paw volume, squeaking score, and weight distribution ratio in rats. In conclusion, DA was found to be effective in alleviating the inflammatory response and thus arthritic symptoms in carrageenan-induced arthritic rats.
Administration, Oral ; Animals ; Ankle ; Arthritis ; Carrageenan ; Hot Temperature ; Inflammation ; Rats ; Taraxacum

The selective removal of low density lipoprotein (LDL) and fibrinogen (Fib) by degraded carrageenan was studied by the present authors. Degraded carrageenan was prepared by acid with carrageenan as the main material. The effects of acid conditions on the molecular weight were investigated, and the proper reaction conditions were ascertained. The results of infrared spectrometry indicated that the degraded carrageenan is a heparin-like polysaccharide. Then the selective removal of LDL/Fibrinogen by degraded carrageenan was studied. When molecular weight was about 10,000, pH was 5.10 and the concentration of degraded carrageenan was 800 mg/L, the average reduction percentages were 60.0% for total cholesterol(TC), 79.4% for LDL and very low-density lipoprotein (VLDL), and 93.8% for fibrinogen. There were no significant changes with relation to the level of high-density lipoprotein (HDL) and total protein (TP). So, degraded carrageenan was shown to be of good selectivity on plasma LDL/Fibrinogen apheresis.
Carrageenan ; chemistry ; Fibrinogen ; analysis ; isolation & purification ; Humans ; Hyperlipidemias ; blood ; Lipoproteins, LDL ; blood ; isolation & purification

This study was designed to investigate the contribution of prostaglandins to the maintenance of inflammatory pain. Inflammation was induced by intraplantar (i.pl.) injection of carrageenan in right hindpaw in rats. Indomethacin (non-selective COX inhibitor) was administered i.pl. 1 h after the carrageenan injection, and paw withdrawal latency (PWL) responding to noxious heat was measured. β-endorphin (β-END) and μ-opioid receptor (MOR) expressed in the inflamed site were examined by using immunocytochemistry, ELISA and RT-PCR techniques. The results showed that indomethacin dose-dependently increased PWL to the levels that were above the baseline on the day 2 and 3, referred to as hypoalgesia. The hypoalgesia was abolished by a local injection of the non-selective opioid receptor inhibitor naloxone methiodide. The number of β-END-positive cells, the content of β-END and the expression of MOR mRNA in the inflammatory site of inflammation model rats were all significantly increased by indomethacin. These results reveal a novel mechanism of prostaglandins for the inhibition of inflammation-induced endogenous opioid activity. This study provides further evidence that inhibition of prostaglandins in inflamed site could be a promising therapy for inflammatory pain.
Analgesics, Opioid ; Animals ; Carrageenan ; Indomethacin ; Inflammation ; Naloxone ; Pain ; Prostaglandins ; Rats ; Receptors, Opioid ; beta-Endorphin

BACKGROUND: Although the inhibitory role of the 5-hydroxytrypatmine receptor 7(5-HT7R) on nociceptive processing is generally recognized, an excitatory effect associated with a reduced 5-HT7R expression has also been observed in the nerve injury model. In the carrageenan model, no significant effect is produced by the 5-HT7R activation, but the change in 5-HT7R expression has not been examined. Lesioning of the spinal serotonergic pathway enhances allodynia in the carrageenan model, but it also relieves several other pain states, including in the formalin model. While lesioning suppresses the activation of the extracellular signal-regulated kinase (ERK) of the spinal cord in the formalin model, its role in the carrageenan model has not been reported. METHODS: Following intraplantar injections of carrageenan, the spinal 5-HT7R expression was examined using Western blotting in male Sprague-Dawley rats. The effect of serotonergic pathway lesioning with intrathecal 5,7-dihydroxytryptamine (5,7-DHT) on the expression of the phospho-ERK was measured. RESULTS: The expression of the 5-HT7R in the carrageenan model was not significantly different from that of naive animals. The expression of the spinal p-ERK in the carrageenan model was significantly increased, but returned to the level of a naive rat 1 hour after the carrageenan injection. However, it remained significantly higher 1 hour after the injection in the animals treated with 5,7-DHT than in the naive and control rats. CONCLUSIONS: The expression of the spinal 5-HT7R is not altered by peripheral inflammation with carrageenan, suggesting that the lack of antinociceptive effect of the 5-HT7R activation is partly attributable to the absence of changes in the expression of the 5-HT7R in the spinal cord. The extended increase of the spinal p-ERK might be related to the enhanced pain behavior in the animals with lesions of the spinal serotonergic pathway in the carrageenan model.
5,7-Dihydroxytryptamine ; Animals ; Blotting, Western ; Carrageenan* ; Formaldehyde ; Humans ; Hyperalgesia ; Inflammation ; Male ; Phosphotransferases ; Rats* ; Rats, Sprague-Dawley ; Spinal Cord