Study On Active Compounds And Anti-nociceptive Activity Of Paederia Scandens

Paederia scandens (Lour.) Merri., a climbing plant, belonging to the family Rubiaceae, is popularly known as the name"Ji Shi Teng"in Chinese which is widely grown in China, Japan, India, Philippines and USA. It has been traditionally used as folklore medicine and food in Southeast of Asia for thousands of years. The leaves of the plant are used as an ingredient in various foods in Vietnam.Recently, it has been reported that the iridoid glycosides and the dimeric iridoid glycosides- paederoside, asperuloside, paederosidic acid, deacetylasperuloside, scandoside were isolated from the MeOH extract from the stems and roots of P. scandens. These chemical constituents of P. scandens have biological activities such as anti-virus, anti-tumor, anti-inflammation and anti-microbial activities. In folklore medicine, the roots, leaves, barks and fruits of P. scandens have been used to treat toothache, chest pain, piles, inflammation of the spleen, diuretic, emetic, rheumatic arthritis and cure bacillary dysentery in China, Japan, Vietnam and other countries in the south-east Asia for thousands of years. Although P. scandens is a particularly useful pain- relief in folklore medicine, there has been no report on the anti-nociceptive activity of this plant and its mechanisms of analgesic activity so far.Based on investigation above, we study the analgesic activity of the MeOH extracts of P. scandens and the anti-nociceptive activity of the petroleum ether, chloroform, n-butanol and water fractions from the MeOH extracts.The MeOH extract from Paederia scandens was administered orally and studied on analgesic activity in chemical- and thermal- induced nociception models in mice. In acetic acid-induced writhing test, formalin test and tail-flick test, the significant inhibition of nociception was observed at the doses of 600 and 900 mg/kg. Moreover, the MeOH extract could relieve the central and peripheral nociception in the formalin test.The n-butanol fraction of the MeOH extract from Paederia scandens was evaluated for antinociceptive activity in mice using chemical and thermal models of nociception. The n-butanol fraction, given orally at doses of 150, 300 and 600 mg/kg produced significant inhibition of chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections, and of thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at a dose of 600 mg/kg. In the pentobarbital sodium-induced sleeping time test and the open-field test, the n-butanol fraction neither significantly enhanced pentobarbital sodium-induced sleeping time nor impaired motor performance, indicating that the observed anti-nociception was unlikely to be due to sedation or motor abnormality. Moreover, the n-butanol fraction-induced anti-nociception in both the capsaicin and formalin tests was insensitive to naloxone or glibenclamide but was significantly antagonized by nimodipine. These results suggest that the n-butanol fraction produced anti-nociception possibly related to nimodipine-sensitive L-type Ca²⁺ channels, which merits further studies regarding the precise site and mechanism of action. Furthermore, iridoid glycosides isolated from the n-butanol fraction might be related to its antinociceptive action fraction. Therefore, the effect on analgesic activity of each chemical compound in large quantity might well be considered in a further study.The petroleum ether fraction of MeOH extract from Paederia scandens was evaluated on anti-nociceptive activity in mice using chemical and thermal models of nociception. Given orally, the petroleum ether fraction (PEF) at doses of 20, 40 and 80 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at dose of 80 mg/kg of the petroleum ether fraction. In the pentobarbital sodium-induced sleeping time test and the open-field test, the petroleum ether fraction neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-nociception was unlikely due to sedation or motor abnormality. Moreover, the petroleum ether fraction-induced anti-nociception in both capsaicin and formalin tests was insensitive to naloxone, but was significantly antagonized by glibenclamide. These results suggested that the petroleum ether fraction produced anti-nociception possibly related to glibenclamide-sensitive K⁺-ATP channels, which merited further studies regarding the precise site and mechanism of action. The major constituents of the petroleum ether fraction (PEF) determined by GC/MS analysis, are linoleic acid, the sterols and vitamin E. Therefore it can be suggested that they exert synergetic effects and are together responsible for the antinociceptive activity of the PEF-fraction. We test the anti-nociceptive activity of iridoid glycosides isolated from the n-butanol fraction of the MeOH extract from Paederia scandens. Then we found the paederosidic acid methyl ester showed the potential anti-nociception. This iridoid glycoside was evaluated for anti-nociceptive activity in mice using chemical and thermal models of nociception. The paederosidic acid methyl ester, given intraperitoneal injection at doses of 20, 40 and 60 mg/kg, produced significant inhibition of chemical nociception induced by intraperitoneal acetic acid and subplantar formalin or capsaicin injections, and of thermal nociception both in the tail-flick test and in the hot plate test. More significant inhibition of nociception was observed at a dose of 60 mg/kg. In the pentobarbital sodium-induced sleeping time test and the measurement of core body temperature, the chemical compound neither significantly enhanced pentobarbital sodium-induced sleeping time nor influent the temperature of core body, indicating that the observed anti-nociception was unlikely to be due to sedation or toxicity. Moreover, the paederosidic acid methyl ester -induced anti-nociception in the hot-pate test was insensitive to naloxone or nimodipine, but was significantly antagonized by methylene blue, L-NAME and glibenclamide. These results suggest that the paederosidic acid methyl ester produced anti-nociception possibly related to the anti-nociception pathway- NO-cGMP-K⁺-ATP, which merits further studies regarding the precise site and mechanism of action.