Antinociceptive Profiles of Crude Extract from Roots of Angelica gigas NAKAI in Various Pain Models

Department of Pharmacology, College of Medicine, Hallym University, Chunchon, Kangwon Do, South Korea.
Biological & Pharmaceutical Bulletin (Impact Factor: 1.83). 10/2003; 26(9):1283-8. DOI: 10.1248/bpb.26.1283
Source: PubMed


To characterize the antinociceptive profiles of Angelica gigas NAKAI (ANG; Korean angelica), methanol extract from the dried roots of ANG was made and mice were administered orally at the various doses (from 0.25 to 3 g/kg). ANG produced the increased latencies of the tail-flick and hot-plate paw-licking responses in a dose-dependent manner. In acetic acid-induced writhing test, ANG dose-dependently decreased writhing numbers. Moreover, the cumulative response time of nociceptive behaviors induced by intraplantar formalin injection was reduced during both the 1st and the 2nd phases in a dose-dependent manner in ANG-treated mice. Furthermore, oral administration of ANG did not cause licking, scratching and biting responses induced by TNF-alpha (100 pg), IFN-gamma (100 pg) or IL-1beta (100 pg) injected intrathecally (i.t.), especially at higher dose (3 g/kg). Additionally, in ANG treated mice, the cumulative nociceptive response time for i.t. administration of substance P or capsaicin was dose-dependently diminished. Finally, nociceptive responses elicited by i.t. injection of glutamate (20 microg), N-methyl-D-aspartic acid (60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (13 ng) or kainic acid (12 ng) were decreased by oral administration of ANG. Our results suggest that ANG produces antinociception via acting on the central nervous system and shows antinociceptive profiles in various pain models, especially inflammatory pain.

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    • "The perennial herb, Angelica gigas Nakai, commonly known as Korean angelica, is a member of the Umbelliferae family and one of the most important Indigenous medicinal plants in Korea. The root of A. gigas (Angelicae gigantis Radix) has been used as a traditional herbal medicine to treat anemia, abdominal pain, injuries, migraine, arthritis, female afflictions, and the material has also been prescribed for health-promoting effects (Chi and Kim, 1970; Choi et al., 2003; Sarker and Nahar, 2004). "
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    ABSTRACT: Hairy root culture of Angelica gigas was studied using different media, strength of medium and addition of various concentrations of sucrose to the culture media to optimize the growth and pyranocoumarins production. Hairy roots in SH medium showed the highest levels of root growth (9.26 g D.W./L) as well as the highest amount of decursin (2.69 mg/g D.W.). MS media produced decursinol angelate a little more than SH media. Half-strength of SH medium produced 43% more hairy root growth, double amount of decursin and 93% more decursinol angelate from the lowest producing double strength of SH media. Hairy root and pyranocoumarins production increased with increasing the level of sucrose concentration up to 40 g/L and then started to decline. These findings indicate that hairy root cultures of A. gigas using half strength SH media and 40 g/L sucrose treatment in medium could be a good approach for pyranocoumarins production.
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    • "An often underappreciated principle of herbal medicine is that changing the extraction solvents can lead to the recovery of different chemicals and therefore to novel medicinal and pharmacological properties. In fact, many pyranocoumarin compounds have been identified from the alcohol extract of A. gigas Nakai [17,18] with diverse pharmacological activities including cytotoxic action against leukemia cells [19-22], antibacterial action [23], pain-killing action [24] and antimemory loss action [25]. "
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    ABSTRACT: Estrogen and estrogen receptor (ER)-mediated signaling are crucial for the etiology and progression of human breast cancer. Attenuating ER activities by natural products is a promising strategy to decrease breast cancer risk. We recently discovered that the pyranocoumarin compound decursin and its isomer decursinol angelate (DA) have potent novel antiandrogen receptor signaling activities. Because the ER and the androgen receptor belong to the steroid receptor superfamily, we examined whether these compounds affected ER expression and signaling in breast cancer cells. We treated estrogen-dependent MCF-7 and estrogen-independent MDA MB-231 human breast cancer cells with decursin and DA, and examined cell growth, apoptosis, and ERalpha and ERbeta expression in both cell lines - and, in particular, estrogen-stimulated signaling in the MCF-7 cells. We compared these compounds with decursinol to determine their structure-activity relationship. Decursin and DA exerted growth inhibitory effects on MCF-7 cells through G1 arrest and caspase-mediated apoptosis. These compounds decreased ERalpha in MCF-7 cells at both mRNA and protein levels, and suppressed estrogen-stimulated genes. Decursin and the pure antiestrogen Faslodex exerted an additive growth inhibitory effect on MCF-7 cells. In MDA MB-231 cells, these compounds induced cell-cycle arrests in the G1 and G2 phases as well as inducing apoptosis, accompanied by an increased expression of ERbeta. In contrast, decursinol, which lacks the side chain of decursin and DA, did not have these cellular and molecular activities at comparable concentrations. The side chain of decursin and DA is crucial for their anti-ER signaling and breast cancer growth inhibitory activities. These data provide mechanistic rationales for validating the chemopreventive and therapeutic efficacy of decursin and its derivatives in preclinical animal models of breast cancer.
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    ABSTRACT: CML-1 is a purified extract from a mixture of 13 Oriental herbs (Achyranthis Radix, Angelicae Gigantis Radix, Cinnamomi Cortex Spissus, Eucommiae Cortex, Glycyrrhizae Radix, Hoelen, Lycii Fructus, Paeoniae Radix, Rehmanniae Radix Preparata and Atractylodis Rhizoma, Zingiberis Rhizoma, Zizyphi Semen, Acori Graminei Rhizoma) that have been widely used for the treatment of inflammatory diseases in Asia. The aim of this study was to investigate the anti-inflammatory and analgesic potential of CML-1. The animals used in this study were administered either vehicle or CML-1 (30, 100, 300 and 600 mg/kg) orally. The vascular permeability induced by acetic acid was significantly reduced by CML-1 in all doses. The swelling of the rat's hind paw induced by carrageenan was significantly inhibited by CML-1 in doses of 100, 300 and 600 mg/kg. In the case of rheumatoid arthritis induced by complete Freund's adjuvant in rats, the treatment with CML-1 at a dose level of 300 mg/kg inhibited edema. CML-1 at a dose level of 600 mg/kg inhibited acetic acid-induced writhing syndrome, however it did not have any anti-nociceptive action in the Randall-Selitto assay or the hot plate test. Our findings suggest that CML-1 has a potent anti-inflammatory activity.
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