Natural inhibitors of NF-kB are beneficial in a mouse model of multiple sclerosis.
Triptolide, the presumed active component of T. wilfordii, is known to be an inhibitor of NF-kB.In the study briefly summarized below, oral administration of triptolide was shown to be therapeutic in a mouse model of multiple sclerosis, both when used as an acute treatment (after development of disease) and when used in the prevention of disease onset.
Experimental autoimmune encephalomyelitis (EAE) is a well accepted animal model of human demyelinating disease such as multiple sclerosis. However, it should be noted that the condition studied is not multiple sclerosis, and that the ‘patient’ is a mouse, not a human.
Nonetheless, the results of oral administration of the natural NF-kB inhibitor triptolide were encouraging:
- Disease onset was delayed.
- Clinical symptoms were reduced.
- Relapse rate was decreased.
- Inflammation and demyelination in CNS tissue were both diminished.
Triptolide was shown to inhibit NF-kB, which is presumed to be the mechanism by which it acts.
It is reasonable to conclude that other natural NF-kB inhibitors might be of equal or greater efficacy.
Natural NF-kB inhibitors are abundant, safe and inexpensive. Given the effect on the onset and course of MS observed in this study, further investigation of natural NF-kB inhibitors seems warranted.
Existing medications in use for the treatment of multiple sclerosis are of limited efficacy and are associated with often severe and sometimes life-threatening side effects. If natural NF-kB inhibitors are effective, they should be put to use – perhaps in combination with presently existing therapies, especially to the extent that they are determined to be compatible with same and especially because they are generally free from side effects.
Unfortunately, triptolide is unpatentable, and is therefore unlikely to be further investigated.
The publication:
[stextbox id="grey"]
J Neuroimmunol. 2009 Dec 10;217(1-2):28-37.
Oral administration of triptolide ameliorates the clinical signs of experimental autoimmune encephalomyelitis (EAE) by induction of HSP70 and stabilization of NF-kappaB/IkappaBalpha transcriptional complex.
Kizelsztein P, Komarnytsky S, Raskin I.
Biotech Center, SEBS, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901, USA.
Summary of the abstract
Available treatments for multiple sclerosis (MS) require frequent injections and have significant side effects.
This study examined the immunomodulatory properties of orally administered triptolide, a major diterpenoid triepoxide isolated from a twining vine Tripterygium wilfordii.
Mice were orally treated with triptolide from the day of EAE induction (preventive regime) and after the onset of clinical signs (therapeutic regime).
Triptolide delayed disease onset, reduced clinical symptoms, decreased the relapse rate, and suppressed inflammation and demyelination in CNS tissue of EAE mice when compared to vehicle-treated animals.
Molecular analysis revealed a marked increase of heat shock protein 70 (Hsp70) mRNA and protein in the CNS tissue of triptolide-treated animals. Cytokine and chemokine expression analysis from EAE tissues and in vitro macrophages detected a decrease of key pro-inflammatory mRNAs. Triptolide inhibited NF-kB, possibly due to a direct physical interaction between NF-kappaB and Hsp70 proteins.
Lymph node cell proliferation assay in EAE confirmed the immunosuppressive efficacy of triptolide.
Our data indicate that daily oral administration of triptolide exhibits not only a preventive but also a therapeutic effect on EAE. These effects might be explained by the increase in Hsp70 levels driven by triptolide and stabilization of the NF-kappaB/IkappaBalpha complex leading to an attenuated inflammatory response.
[/stextbox]