The Pharmacologically Active Ingredient of Noni
by
R.M. Heinicke, Ph.D.
In The Bulletin, April 1972,
Maria Stewart described how the Hawaiians solved many of their medical problems
by drinking infusions of the fruit of the noni tree (Morinda citrifolia , Rubiaceae).
The missionaries, who frequently had to minister to the body as well as the
soul, were impressednwith the efficacy of these
options. Yet identifying the pharmacologically active ingredient of Noni has
been difficult - for an understandably good reason. The active ingredient is
not present in the plant or fruit! Only after the potion has been drunk does
the active ingredient form. Sometimes!
My search for the ingredient which is active in Noni began with a
series of studies on the pineapple plant. Since about 1972 I had been
attempting to identify the unknown ingredient in "bromelain" which
gives crude preparations of this enzyme their potent pharmacological
properties. (Sometimes!) After many discouraging years
of research I eventually identified this ingredient as a new alkaloid to which
I gave the name "xeronine." Noticing that the clinical claims of
efficacy for bromelain and noni were practically
identical, I tried the same techniques on Noni fruit which I had developed for
isolating xeronine from the pineapple plant. The technique worked! Not only was
I able to isolate the same compound from noni fruit,
but the yields were excellent. Today Noni is one of the best raw materials to
use for the isolation of xeronine.
Xeronine is a relatively small alkaloid which is physiologically active
in the picogram range. (Ed. note: a picogram is one trillionth of a gram) It occurs in
practically all healthy cells of plants, animals and microorganisms. However,
the amount of free alkaloid is minute and is well below the limits of normal
chemical analytical techniques.
Even though Noni fruits have a negligible amount of free xeronine, they
contain appreciable amounts of the precursor of xeronine. This precursor, which
I have named "proxeronine", is a strange molecule. The molecular
weight is relatively large, namely about 16,000. In contrast to most plant
colloids, this colloid contains neither sugars, amino acids
nor nucleic acids. Thus most biochemists have overlooked this relatively
abundant molecule which occurs in most tissues.
Noni fruits also contain the inactive form of the enzyme which releases
xeronine from proxeronine. Unless this proenzyme
becomes properly activated, however, Noni juice will cause few pharmacological
reactions. Fortunately if Noni juice is taken on an empty stomach, the critical
proenzyme escapes digestion in the stomach and enters
the intestines. Here the chances are high that it may become activated.
Many years of research are still required to demonstrate convincingly
how xeronine functions at the molecular level in a cell. In the meantime I can
suggest certain hypotheses which can act as a guide in planning experiments. I
am basing these hypotheses both on clinical results with bromelain pills as
well as on a limited number of laboratory and animal experiments carried out
with pure xeronine.
I am proposing that the primary function of xeronine is to regulate the
rigidity and shape of specific proteins. Since these proteins have different
functions, we have the usual clinical situation where administering one simple
drug causes an unbelievably wide range of physiological responses.
The action which xeronine has on a person depends upon which of his
tissues has a suboptimal level of xeronine. Thus xeronine can alleviate certain
subsets of almost any known disease. For no disease, however, will xeronine be
a panacea. A physiological disease, for example senility, may be caused by a
deficiency or imbalance of a number of different biochemicals as well as by
malfunctioning blood vessels, hormone systems or immune bodies. Only if the
disease is specifically caused by a lack of xeronine will xeronine alleviate
the symptoms of the problem.
I believe that each tissue has cells which contain proteins which have
receptor sites for the absorption of xeronine. Certain of these proteins are
the inert forms of enzymes which require absorbed xeronine to become active.
Thus xeronine, by converting the body's procollagenase
system into a specific protease, quickly and safely removes the dead tissue
from burns. It is for this reason that aloes, bromelain and Noni are such
effective treatments for burns. Other proteins become potential receptor sites
for hormones after they react with xeronine. Thus the action of ginseng,
bromelain and Noni in making a person feel well is probably caused by xeronine
converting certain brain receptor proteins into active sites for the absorption
of the endorphine, the well being hormones. Other
proteins form pores through membranes in the intestines, the blood vessels and
other body organs. Absorbing xeronine on these proteins changes the shape of
the pores and thus affects the passage of molecules through the membranes. Thus
the action of bromelain, Noni and ginseng in improving digestion may be
ascribable to this action. These are just a few of the many exciting actions of
this newly discovered alkaloid. Since Noni is a potential source of this
alkaloid, Noni juice can be a valuable herbal remedy.
There are some practical problems, however, in using Noni juice as a
medicine or tonic. If one is dying and all other remedies have failed, then and
only then will the average person drink noni juice.
The flavor of juice made from ripe Hawaiian Noni is terrible. None of my
colleagues would touch the untreated juice. Even after I had removed most of
the disagreeable flavor (several organic acids) from the juice, my colleagues
still found it unfit to drink. For a price the odoriferous chemicals can be
removed from the Hawaiian variety. However, other varieties grown in other
Another critical problem in using Noni juice as a medicine or health
tonic is timing. If the juice is drunk on a full stomach, it will have very
little beneficial action. The pepsin and acid in the stomach will destroy the
enzyme which liberates xeronine. For a seriously sick person taking the juice
on an empty stomach rarely poses a problem; the patient is too sick to want to
eat anything. However, for the average person who wants to drink Noni juice as
a health tonic, timing is critical. I would recommend taking 100 ml of Noni
juice a half hour before breakfast and other meals. (I take @ 2 oz) At this
time the juice will pass rapidly through the stomach and into the intestines,
where it may be converted into the active enzyme. At any other time of the day,
especially at meal times, the primary effects of drinking Noni juice will be
psychological and caloric. Because of the strong flavor the psychological
effect might not necessarily be positive. To obtain the maximum effect of the
active ingredient in Noni, I would recommend also that Noni juice not be taken
with coffee, tobacco or alcohol. At times the combination of these materials
and Noni can give some unexpected side effects. At other times the combination
merely lowers the potentially beneficial effect of xeronine.
Although the Tahitians recommended both green fruit and ripe fruit for
treating various ailments, my personal recommendation would be to use only the
green fruit. The green fruit has more of the potentially valuable components
and less of the undesirable flavor. In light of the new information on the
action of xeronine what are some of the possible applications of Noni juice?
First I should make the caveat that for all of the possible applications which
I am listing, one must always add the phrase "some types but not other
types."
The old Tahitian people were truly
fortunate to have herbal medical doctors who recognized a valuable natural
product and who knew how to administer this medicine with the proper
psychological persuasion.
An immunomodulatory
polysaccharide-rich substance from the fruit juice of Morinda citrifolia (noni) with antitumour activity.
Hirazumi A, Furusawa
E.
Department of Pharmacology, John A., Burns School of Medicine, 1960 East West
Road, University of Hawaii, Honolulu, HI 96822, USA.
The fruit juice of Morinda citrifolia (noni) contains
a polysaccharide-rich substance (noni-ppt) with antitumour activity in the Lewis lung (LLC) peritoneal carcinomatosis model. Therapeutic administration of noni-ppt significantly enhanced the duration of survival of
inbred syngeneic LLC tumour
bearing mice. It did not exert significant cytotoxic
effects in an adapted culture of LLC cells, LLC1, but could activate peritoneal
exudate cells (PEC) to impart profound toxicity when
co-cultured with the tumour cells. This suggested the
possibility that noni-ppt may suppress tumour growth through activation of the host immune system.
Concomitant treatment with the immunosuppressive agent, 2-chloroadenosine
(C1-Ade) or cyclosporin (cys-A)
diminished its activity, thereby substantiating an immunomodulatory
mechanism. Noni-ppt was also capable of stimulating
the release of several mediators from murine effector cells, including tumour
necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-10, IL-12
p70, interferon-gamma (IFN-gamma) and nitric oxide (NO), but had no effect on
IL-2 and suppressed IL-4 release. Improved survival time and curative effects
occurred when noni-ppt was combined with sub-optimal
doses of the standard chemotherapeutic agents, adriamycin
(Adria), cisplatin (CDDP),
5-fluorouracil (5-FU), and vincristine (VCR),
suggesting important clinical applications of noni-ppt
as a supplemental agent in cancer treatment. Copyright 1999
John Wiley & Sons, Ltd.