Compounds with Anti-Inflammatory Effects

See also Products for Arthritis See also autoimmunity and inflammation

Many plant derived compounds have anti-inflammatory activities. Most of their actions are related to their ability to inhibit cytokine, chemokine or adhesion molecule synthesis and/or action. Many inflammatory disorders including sepsis, rheumatoid arthritis and asthma are intimately associated with an imbalance of the cytokine network.

Polyphenols

A substantial body of evidence obtained from both in vivo and in vitro studies supports the concept that various plant-derived compounds with anti-inflammatory properties exert their effects through the modulation of the cytokine system. Plant-derived medicines such as flavonoids, tannins, and anthraquinones have been shown to exhibit anti-inflammatory cactivities, although their exact anti-inflammatory mechanissms are not well established.

Artemisia: has been traditionally used in Korean herbal medicine to treat uteritis and jaundice. Flavonoids, such as 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (p7F), isolated from Artemisia are also known to possess anti-inflammatory activityies. For example, p7F reportedly inhibited the epxression or production of proinflammatory mediators such as COX-2/PGE2 and iNOS/NO in LPS stimulated RAW 264.7 cells. p7F also suppressed the sesrium level of TNF-alpha in mice treated with collagen and inhibited NF-0kB as well as NF-kB promoter activity in RAW 264.7 cells stimulated with LPS.

Coumarins (known as 1,2-benzopyrone or o-hydroxy-cinnamic acid-8-lactone) compirse a very large class of phenolic derivative found in plants and consist of fused benzene and alpha-pyrone rings. Over 1300 have been identified, chiefly as seocndary metablolites in green plants in fugi and bacteria.

Curcumin: is a non-nutritive, non-toxic compound in turmeric, a spice that has been used for centuries in India and elsewhere as an herbal medicinal treatment of wounds, jaundice and rhematoid arthritis. In addition, it inhibits the proliferation of a variety of tumor cells and exhibits potent anti-oxidant activity, which depends upon dthe presence of phenolic groups in the aryl rings. a compound obtained from the rhizome of Curcuma longa L (Zingiberaceae) is a polyphenol with antiflammatory activity and was reported to significantly block IL-12 mediated T cell proliferation and Th1 differentiation, an action that possibly implies its ability to reduce the production of pro-inflammatory cytokines.

Baicaline, Baicalein and wogonin are flalvonoids present in Scutellaria baicalensis (Georgi (Lamiaceae), a plant used in the treatment of a variety of inflammatory dieases such as bronchitis, nephritis, hepatitis, astham, and atopic dermatitis. The anti-inflammatory activites of these falvonoids have been attributed to their antioxidant properties and to their ability to inhibit LPS pinduced NO production and iNOS gene expression, as well as the increase in TNFalpha levels by RAW264.7 cells.

Dietary Polyunsaturated fatty acids (PUFAs): especially the n-3 series that are found in marine fish oils have significant benefits such as decreased morning stiffness and numbers of tender joints.

Ginkgo biloba: Clinical trails with AD pateints have demonstrated potential benefits in cognitive function and memory impairments from treatment with the antioxidant extract of Ginkgo biloba, known to be enriched with flavonoids. Ginkgo biloba extract has been shown to proten hippocampal neurons from nitric oxide or beta-amyloid derived peptides-induced neutrotoxicity.

Green tea: appears to act like true antioxidants such as vitamin C, being protective at low concentrations, while at high concentrations becoming pro-oxidant.

Terpenes

Extract of T. wilfordii could be useful as a source and template for novel antiarthritic and cartilage-protective drugs. It has been reported to markedly inhibt mRNA synthesis and protein expression of MMP-3 and MMP-13, incuded by the pro-inflammatory cytokines IL-1β, IL-17 and TNFα as assessed in primary osteoarthritic human or normal bovine chondrocytes.

Celastrol has been reproted to inhibt rat adjuvant-induced arthritis. Celastrol has been rpoposed as possibly useful for improving performance in memory, learning and psychomotor activites, and common features of the nuerodegenerative diseases accompanied by inflammation, such as Alzheimer's disease.

Ginsenosides Rb1 and Rb2, the major constituents of Panax ginseng C.A. Meyer are reported to inhbit RNF-alpha production in RAW 264.7 and U937 cells stimulated with LPS. The inhibtory activity of Rb1 and Rb2 was significantly increased by inhibitors of protein kinase C and A, protein tyrosine kinase or by drugs used for the treatment of arthritis (chloroquine and steroid drugs), but not by AMP phosphodiesterase inhibitors. It has been susggested that ginenosides could be of clinical interest for the management of TNF-alpha mediated diseases, such as arthritis.

1,25(OH)2D3: is the activated form of Vitamin D. It is a secosteroid hormone that has, in addition to its central function in calcium and bone metabolism, important effects on the grwoth and differentiation of many cell types and pronounced immunoregulatory properties. Its biological effects are mediated by the Vitamin D receptor (VDR), a member of the superfamily of nuclear hormone receptors functioning as a ligand activated transcription factor that fbinds to specific DNA sequence elements, Vitamin D responsive elements, in Vitamin D responsive genes and ultimately influences theri rate of RNA polymerase II-mediated transcription. APCs, and notably DCs, express teh VDR and are key targets of VDR ligands. See also drugs which inhibit DC maturation

inhibits pro-inflammatory and Th-1 cytokine production, reducing the expression of co-stimulatory and MHC class II molecules on antigen presenting cells. Out of many drugs targeting DCs, only 1,25(OH)2D3 and its analogues were able to enhance the secretion by DCs of IL-10, a potent anti-inflammatory cytokine.

Macrolid antibiotics: have been shown to affect a number of processes involved in inflammation, including migration of neutrophils, the oxidative burst in pahgocytes, and the production of various cytokines by bronchial epithelial cells, lympocytes, and monocytes. Although it is presumed that NF-kB and AP-1 which are crucial regulators of proinflammatory gene expression, are potentially the most important targets for at least some anti-inflammatory effects of macrolides, the precise mechaisms remain to be clarified.

Parthenolide is a sesuiterpene lactone in Tanacetum parthenium which is one of Mexican-Indian medicinal plants used as anti-infalmmatory agents. It has reported antinocicptive action and anti-inflammatory effect in vitro. Parthenolide exerts anti-inflammatory activity by inhibiting the expression of inducible cycolooxygenase, proinflammatory cytokines and inducible nitirc oxide synthase. In addition, sesquiterpene lactones specifically inhibit activaiton of NF-kB by preventing the degradation of IkB-alpha and IkB-beta.

Triptolide: has been used extensively as an anti-inflammatory and immunosuppressive agent for the treatment of various autoimmune diseases and prolongation of allograft survival in organ transplantation.