Steel magnolias: using magnolol to combat arthritis

The gorgeous display of magnolia flowers around campus has been capturing my attention over the last few weeks, but it turns out they’re just as noteworthy for their therapeutic potential as for their aesthetics. A new article in press for PLoS One (open access for everyone!) describes a novel activity for the Magnolia officinalis derivative magnolol in repressing inflammation, which is a pretty tantalizing topic for a runner like me who’s always a little bit neurotic about the health of her joints.

Flowers of Magnolia x soulangiana, a cross between M. lilliflora and M. deundata.

White buds on the dark glossy evergreen leaves of M. grandiflora, which tower over a good portion of campus.

The focus of the article is on inhibiting the inflammatory hallmarks of arthritis.  In arthritis, the inflammatory response deployed by the immune system in response to tissue damage becomes an enemy rather than a friend (even in conventional arthritis, let alone the auto-immune rheumatoid variety).  The swelling, pain, and limited motion that result from inflammation reflect a well-intentioned effort on the part of the immune system to combat infection, but gone awry in the context of a contained, infection-resistant area: the damaged joint.

Many molecular pathways for inflammation are engaged in arthritis, but a troublesome aspect of disease management is that the anti-inflammatory drugs most of us use (NSAIDs like Tylenol, Advil, and Aspirin) only combat one of these pathways: the cyclooxygenases (COXs).  In this study, the authors were hoping to find something that packed a broader punch.  They found that in cultured synoviocytes (joint cells) that were triggered to produce an inflammatory response, the addition of magnolol inhibited the expression of proteins involved in several inflammation pathways: not just COXs, but also PGE-2, IL-6, and MMPs.

Magnolol, a biphenyl neolignan made from the bark of M. officinalis.

They found an even more striking result when they moved from cultured cells to live rats.  In rat paws, arthritis symptoms in the ankle joint can be induced by “mock” infection with heat-killed bacteria.  It doesn’t cause the rats any lasting harm, but it does make their paws puff up and initiates the release of inflammatory molecules into the bloodstream.  When magnolol was given to mock-infected rats, paw swelling decreased significantly compared to negative controls (p<0.05), and the amount of inflammatory factors like IL-6 present in their serum dropped back to pre-arthritis levels.

Magnolol reduces ankle swelling and paw volume in a rat model of arthritis. Rat paws are normally skinny little things ("Basal"), but when mock-infected with heat-killed bacteria they become swollen and inflamed. When "arthritic" mock-infected rats were treated with a negative control vehicle, their paws stayed swollen (compare "Basal" to "Vehicle"), but when they were instead treated with magnolol, the swelling reduced and paws returned to a smaller volume. (Excerpted from Wang et al., Figure 4)

This isn’t the first time magnolia derivatives have been linked to inflammation: another compound, honokiol, has also been cited for its effects in blocking the TNF inflammatory pathway.  But I found the live animal model aspect of this magnolol study particularly compelling.  The study was a little lean on positive controls and mechanistic explanation, and it didn’t clarify whether their expectation was that magnolol could be useful as an anti-inflammatory in a broad spectrum of scenarios, or just for arthritis.  But regardless, if you’re out for a jog, give a nod in the direction of all the girly pink M. soulangianas and stately evergreen M. grandifloras–their sibling species just may help us stay mobile in the future.

An M. x soulangiana tree in full flower.

Reference:

Wang JH, Shih KS, Liou JP, Wu YW, Chang AS, Wang KL, Tsai CL, & Yang CR (2012). Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model. PloS one, 7 (2) PMID: 22359588

ResearchBlogging.org

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