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-kappaB. 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 (it is only a model of MS,) and that the ‘patient’ is a mouse, not a human.
Nonetheless, the results of oral administration of the natural NF-kappaB 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-kappaB, which is presumed to be the mechanism by which it acts.
It is reasonable to conclude that other natural NF-kappaB inhibitors might be of equal value (some less, others perhaps more.)
Natural NF-kappaB 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-kappaB inhibitors seems warranted.
Existing medications in use for the treatment of multiple sclerosis are of limited efficacy for some patients, and are associated with often severe side effects. If natural NF-kappaB inhibitors are effective, they should be put to use – perhaps in combination with presently existing therapies, especially because the plant-derived therapies may be relatively free from adverse side effects.
Unfortunately, triptolide is unpatentable, and is therefore unlikely to be further investigated. There is no one to champion its use – no one to foot the $100 million (or greater) cost of obtaining FDA approval.
Conditions like multiple sclerosis merit additional research funding. but it might be those dollars could best be spent , not on basic research, but instead on advancing some of those products which have already shown initial indications of efficacy.
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.
Summary of the abstract
Available treatments for multiple sclerosis require frequent injections and have significant side effects.
This study examined the effect on inflammation of orally administered compounds – triptolide from T. wilfordii.
Mice were orally treated with triptolide from the day of experimental encephalitis induction (a model for multiple sclerosis.) The preventive regime was followed and clinical signs observed also in the therapeutic regimen.
Triptolide delayed disease onset and decreased the relapse rate, it reduced clinical symptoms, suppressed inflammation and demyelination in CNS tissue and resulted in better health of the animals.
Cytokine and chemokine expression showed a decrease in key pro-inflammatory cytokines. Triptolide inhibited NF-kappaB, which is its presumed mechanism of action.
Lymph node cells were also suppressed in their proliferation.
The effects demonstrated were preventive as well as therapeutic, and are best explained by inhibition of NF-kB.