| dc.description.abstract | The importance of the organic constituents in medicinal plant extracts
and herbal medicines have often been acknowledged. There is also
increasing evidence implicating inorganic constituents, particularly
essential trace metals in diseases. For example, the role of the common
electrolytes like sodium, potassium, magnesium, and calcium in these
preparations have frequently been investigated. But, little attention, if
any, has been paid to the role of the trace elements present in these
materials, especially in cases where the preparation is essentially
inorganic such as those from ashcd materials. It is therefore being
suggested that there is an important therapeutic role being played by
essential trace elements found in the plant-derived preparations and
aqueous extracts of plant materials often used in the preparation of
herbal medicines in Kenya. The role of these trace elements 111
pathophysiology of diseases is of particular interest especially in the
treatment of epilepsy where the use of modern anticonvulsant drugs
have shown effects of altering levels the trace metals in both human and
experimental animals. The aim of this study was therefore first, to
determine the levels of trace elements in some selected traditional
anticonvulsants and other medicinal preparations used in Kenya and to
investigate their effects OJl the levels of trace clements in brain of rats
treated with these traditional medicinal preparations. Secondly, to
investigate the effects of modern allopathic drugs on the levels of trace
metals in rat tissues and finally, to correlate these results to see whether
both type of drugs have any similaf effects.
Five analytical techniques were used in this work: Energy Dispersive XRay
Fluorescence (EDXRF), Atomic Absorption Spectrometry (AAS),
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Colorimetry and Inductive Coupled Plasma Mass Spectrometry (ICPMS)
techniques were used to evaluate the trace and some major metal
content in various herbal preparations, medicinal plant extracts and
brains of rats fed with these preparations. Particle Induced X-ray
Emission (PIXE) analysis was used to investigate the effects of three
anticonvulsant drugs, Valproic acid (VPA), Gamma-Vinyl Gamma
amino-butyric acid (CiVCi), .uid Phcnytoiu (PI-IT), on the tr;ICC clements
levels in rat serum and tissues (thymus, liver, spleen and brain).
For EDXRF analysis, it was found that ash extracts and herbal
medicines for hypertension all had high levels of bromine (51 to 12000
ppm), rubidium (6 to 281 ppm), and strontium (5 to 234 ppm). One
sample from Taveta near Mt. Kilimanjaro had high molybdenum (785
ppm) while zinc levels (6 to 20 ppm) were found in the samples
analyzed for hypertension. Aqueous preparations for the treatment of
epilepsy by the traditional doctors showed high levels of zinc (31.1 to
3000 ppm), iron (210 to 540 ppm), and strontium (41.8 to 124 ppm),
while manganese (42.3 to 293 ppm), hromine n1 to 27R ppm). and
rubidium (15 to 67.8 ppm). Leaf extracts of the samples from plants
used to treat Plasmodium [alciparum malaria had significant amounts of
Strontium (13 to 248 ppm). Of the trace elements detected and
quantified in this group of samples, ten were transition elements (Ti, Cr,
Mn, Fe, Ni, Cu, Y, Zr, Mo) while others were calcium, potassium,
bromine, rubidium and strontium. The total brain analysis of control
group of rats and those treated with traditional medicaments used for
hypertension, epilepsy and malaria showed no major differences in the
levels of various trace elements in the brains. There was no ma.Jor
differences between the weight gains (over 140 %) for both treated and
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control group of rats which were initially of normal health and had
good appetite for food.
For AAS analysis of plant materials, it was found that the highest
potassium level (6.4%) was from a sample KTK 1652, from the root of
Aspilia mossambicensis, from Kwale. The same sample had also the
highest level of aluminium (0.82%). The sample KTK 1660, from the
root sample Ocimum basilicum, also from Kwale, had the highest level
of magnesium (1.16%). The colorimetric analysis revealed that the
highest level of phosphorus (0.71 %) was found in the samples from the
leaves of Turraea mombassiana, from the Taita Hills.
Rat brain analysis by AAS and colorimetric technique showed no
significant level changes in sodium, potassium, phosphorus, magnesium
and manganese after the treatment of rats with extracts from
Synadenium glaucescens and Zanthoxylum chalybeaum. Only the
treatment with extracts from Azadirachsa indica led to a decrease (0.70
to 0.49 ppm) in sodium levels. Rat treatment with extracts from
Synadenium glaucescens led to significant increases of: calcium (0.056
to 0.44 %); phosphorus (1.32 to 1.64 %); zinc (41 to 52 pprn); iron
(117 to 170 ppm) and a decrease of aluminium levels (103 to 51.8 ppm).
Treatment of rats with extracts from /vzadirachta indica had the
opposite effect in the levels of trace metals discussed above. The
treatment of rats with extracts from Zanthoxylum chalybeaum resulted
ill no major differences in trace metal levels except the increase or iron
(from 117 to 155.5 ppm). .•
For ICP-MS analysis, it was found that the traditional medicines (for
epilepsy, malaria, asthma, aids, hypertension and psoriasis) used in
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Kenya had very low levels of cadmium (:s;170 ppb) and mercury (30 to
410 ppb). The sample KMN 1356 used by a traditional healer in
treatment of epileptic patients contained high levels of manganese (286
ppm).
In PIXE analysis of rat tissues after treatment with modern allopathic
drugs, it was found that all the three anticonvulsants used decreased
significantly (p<O.05) the levels of serum zinc (from a control value of
1.76 mgll to 1.37 mg/l after phenytoin treatment and to a value of 1.26
mgll after both valproic acid and gamma vinyl gamma amino-butyric
acid (GABA) treatments; significant increases(p<0.05 and p<O.OI
respectively) of liver zinc (from a control level of 96.3 ppm to 123.1
ppm after gamma vinyl gamma amino-butyric acid (GABA) treatment
and to a value of 120.9 ppm after valproic acid treatment). In the liver,
it was also found that after gamma vinyl GABA treatment, the content
of copper increased from a control value of 13.3 ppm to 16.5 ppm
while the iron increased from 452 ppm to 813 ppm and manganese
increased from 7.4 ppm to 10.2 ppm. The valproic acid treatment also
led to an increased level of liver manganese from a control level of 7.4
ppm to 8.8 ppm. In addition, valproic acid treatment decreased serum
copper level from a control value of 1.42 mgll to 1.20 mg/l; serum
selenium from a control level of 0.65 mg/l to 0.54 mg/l, and serum
bromine from a control value of 11.5 mg/l to 6.27 mg/l. The phenytoin
treatment produced a significant increase (p<O.Ol) in serum copper
from a control level of 1.42 mg/l to 1.72 mg/l while the gamma vinyl
gamma amino-butyric acid (GABA) treatment resulted in increased
(p<O.Ol) thymus iron level from a control level of 150.9 ppm to 209.]
ppm.
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Gamma vinyl gamma-amino butyric acid (GVG) treated rats had 28%
loss of weight while those treated with valproic acid(VPA) had no
weight gain. Rats treated with phenytoin(PHT) had a 3 percent average
gain ill weight.
Sensitivity tests on the Central Nervous System (CNS), showed that the
traditional anticonvulsants did depress the CNS. When administered, rats
treated with the traditional medicine(KMN 1641) had longer
pentobarbital sleeping times (71.2 ± 18.1 minutes) than the control
. group which had a sleeping time of 39.3 ± 9.3 minutes.
This study shows that there is the presence and important role(s) being
played by the essential trace elements in the successful utilization of
some traditional medicines and medicinal plant extracts in Kenya. These
medicines made our forefathers survive for many years without modern
allopathic drugs because they did provide the essential therapeutic agents
with minimum side effects.
The study also shows that some traditional medicines and medicinal
plant extracts are specially prepared from particular plants through
processes such as maceration, boiling, drying, grinding, ashing and
freeze drying. These processes do change the chemical or physical
composition of the materials. As a result there is preconcentration in the
levels of the essential trace elements and perhaps enhancing their
speciation and bioavailability. ..
This work was propelled by the knowledge that bioinorganic scientists
have for many years been attempting to extract from plants the active
ingredients but have not succeeded in their approach to solving most
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disease remedies and finding the active principles in these materials. In
this work, it is suggested that there is an important therapeutic role
being played by the essential trace elements. These elements have been
identified in the plant-derived preparations and medicinal plant extracts
often used in the preparation of herbal medicines in Kenya especially the
use of traditional medicines in anticonvulsant therapy. However, other
important metal ions including those currently being regarded as toxic
plus their bioinorganic chemistries have not been analyzed and discussed
here. Therefore, some future research challenges include:-
determination of the speciation of the essential trace elements in the
medicinal plant extracts and preparations; determination of the existence
of radicals such as NO which is known to be important in cognition and
neurotransmission; determination of metabolic pathways and
mechanisms on the role played by essential trace elements in drug
functions by use of radiolabelled compounds; inorganic modeling and
determination of trace metal interactions to elucidate possible chemical
mechanisms, reactivity, magnetic and electronic structure of biological
catalysts | en |
