Inflammation is a response to injury; it is therefore not surprising that inflammation and pain are closely connected. Inflammation is driven by immune cells, which release pro-inflammatory cellular messengers such as nitric oxide, COX-2 and matrix-degrading enzymes, IL-1, IL-6, TNF-a, and TGF-ß. Macrophages are intrinsically linked to inflammation. In chronic inflammatory conditions such as rheumatoid arthritis, specific enzymes are released by macrophages and lead to the destruction of the surrounding tissues. In arthritis, this process inflicts serious damage to cartilaginous structures. This leads to weak and inflamed joints. In a study that assessed the usefulness of 14 plants and plant extracts with regards to inflammation, it was found that Angelica Gigantis Radix is the most potent at inhibiting the pro-inflammatory activity of macrophages. Further purification of the plant extract led to the identification of decursin as the agent responsible for the observed effect. In addition, treatment with decursinol did not affect substance P levels. Substance P is an important factor in the tolerance and withdrawal symptoms associated with some analgesics. Therefore, long-term use of decursinol is not associated with an increased tolerance, a significant benefit over other analgesics.

A clinical study using decursinol for pain management in patients suffering from chronic degenerative joint arthritis showed an impressive pain reduction in 67.5% of patients after treatment with decursinol for a period of two weeks. No significant changes in blood pressure, pulse rate, respiration rate, electrocardiogram and blood oxygen saturation were observed in the patients given the herbal extract.

Other studies demonstrated that decursinol is a powerful neuroprotective agent. Decursinol possesses acetylcholinesterase inhibitory activity. Several acetylcholinesterase inhibitors are approved for the treatment of Alzheimer's disease and appear to prevent the programmed cellular death of neurons through the reduction of glutamate toxicity. Acetylcholinesterase inhibitors also improve cognitive function by preventing the breakdown of acetylcholine, a neurotransmitter found in unusually low levels in Alzheimer's disease. In an animal model for Alzheimer's disease, decursinol prevented the memory loss associated with senile plaque formation.

Through its influence on nerve cells, decursinol offers relief for those who are in constant agony because their pain pathways are over stimulated. In addition, decursinol normalizes inflammatory pathways and exhibits powerful anti-inflammatory activity, one of the root causes of pain.

References:

Choi SS, Han KJ, Lee HK, Han EJ, Suh HW. Antinociceptive profiles of crude extract from roots of Angelica gigas NAKAI in various pain models. Biol Pharm Bull. 2003 Sep;26(9):1283-8.

Choi SS, Han KJ, Lee JK, Lee HK, Han EJ, Kim DH, Suh HW. Antinociceptive mechanisms of orally administered decursinol in the mouse. Life Sci. 2003 Jun 13;73(4):471-85.

Kim JH, Jeong JH, Jeon ST, Kim H, Ock J, Suk K, Kim SI, Song KS, Lee WH. Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages. Mol Pharmacol. 2006 Jun;69(6):1783-90.

Ohshiro T, Namatame I, Lee EW, Kawagishi H, Tomoda H. Molecular target of decursins in the inhibition of lipid droplet accumulation in macrophages. Biol Pharm Bull. 2006 May;29(5):981-4.

[Inhibitory effects of 11 coumarin compounds against growth of human bladder carcinoma cell line E-J in vitro]
Zhong Xi Yi Jie He Xue Bao. 2007 Jan;5(1):56-60.
Yang XW, Xu B, Ran FX, Wang RQ, Wu J, Cui JR.

OBJECTIVE: To screen antitumor active compounds, drug-like or leading compounds from Chinese traditional and herbal drugs.
METHODS: Eleven coumarin compounds isolated from the Chinese traditional and herbal drugs were studied for their antitumor activities in vitro by determining the inhibition rates against growth of human bladder carcinoma cell line E-J.
RESULTS: It showed that umbelliferone, scoparone, demethylfuropinarine, isopimpinellin, forbesoside, columbianadin, decursin and glycycoumarin inhibited the growth of human bladder carcinoma cell line E-J in vitro and their activities showed a concentration-effect relationship. The inhibitory effects of forbesoside, columbianadin, decursin and umbelliferone, with IC50 values of 7.50x10(-7), 2.30x10(-6), 6.00x10(-6) and 1.30x10(-6) mol/L, respectively, were stronger than those of the other tested compounds. However, xanthotoxin, esculin and sphondin did not inhibit the growth of human bladder carcinoma cell line E-J in this assay condition.
CONCLUSION: These findings indicate that forbesoside, columbianadin, esculin, decursin and umbelliferone would be effective or regarded as potent drug-like or leading compounds against human bladder carcinoma.


Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages.
Mol Pharmacol. 2006 Jun;69(6):1783-90. Epub 2006 Mar 1.
Kim JH, Jeong JH, Jeon ST, Kim H, Ock J, Suk K, Kim SI, Song KS, Lee WH.

In the course of screening inhibitors of matrix metalloproteinase (MMP)-9 induction in macrophages, we isolated decursin, a coumarin compound, from the roots of Angelicae gigas. As a marker for the screening and isolation, we tested expression of MMP-9 in RAW264.7 cells and THP-1 cells after treatment with bacterial lipopolysaccharide (LPS), the TLR-4 ligand. Decursin suppressed MMP-9 expression in cells stimulated by LPS in a dose-dependent manner at concentrations below 60 microM with no sign of cytotoxicity. The suppressive effect of decursin was observed not only in cells stimulated with ligands for TLR4, TLR2, TLR3, and TLR9 but also in cells stimulated with interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha, indicating that the molecular target of decursin is common signaling molecules induced by these stimulants. In addition to the suppression of MMP-9 expression, decursin blocked nitric oxide production and cytokine (IL-8, MCP-1, IL-1beta, and TNF-alpha) secretion induced by LPS. To find out the molecular mechanism responsible for the suppressive effect of decursin, we analyzed signaling molecules involved in the TLR-mediated activation of MMP-9 and cytokines. Decursin blocked phosphorylation of IkappaB and nuclear translocation of NF-kappaB in THP-1 cells activated with LPS. Furthermore, expression of a luciferase reporter gene under the promoter containing NF-kappaB binding sites was blocked by decursin. These data indicate that decursin is a novel inhibitor of NF-kappaB activation in signaling induced by TLR ligands and cytokines.