Anti-trypanosomal and cytotoxic effects of extracts from commiphora swynnertonii burtt 1935
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Date
2018
Authors
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Sokoine University of Agriculture
Abstract
Application of trypanocides both curatively and prophylactically is a key component of
beset with many problems including drug toxicity and treatment failure due to widespread
resistance ofthe parasites. Given little progress in vaccine development, there is a pressing
need for discovery of new alternative trypanocidal molecules that can further be developed
into trypanocidal drugs. Plants are one such source from which alternative trypanocidal
molecules could be obtained. Commiphora swynnertonii is a member of the family
Burseraceae which is reported to possess a number of compounds active against protozoa.
This thesis provides
Commiphora swynnertonii extracts, and its potential as a source of lead molecules for
development of alternative trypanocidal drug for trypanosomosis control. The main results
are presented in two published papers and one submitted manuscript. The first paper
presents the in vitro trypanocidal activity of Commiphora swynnertonii extracts on
Trypanosoma congolense in which, the motility of T. congolense was evaluated after
incubation for 20 minutes with ethanolic stem-bark and resin extracts at concentration of2
mg/ml and 4 mg/ml. In the second study, T. congolense was incubated with the extracts at
concentrations of 0.4 mg/ml and 2 mg/ml for 36 - 56 min after which 0.08 ml of the
aliquots were inoculated intraperitoneally into mice to assess infectivity. In both studies,
negative (phosphate buffered saline with glucose without the extract) and positive
(diminazene diaceturate) controls were used. The findings showed that C. swynnertonii
ethanolic stem bark extract caused complete cessation of T. congolense motility in 30
minutes at the concentration of 4 mg/ml. Resin extract had a delayed effect on the
cessation of T. congolense motility observed after 90 and 100 minutes of incubation at
concentrations of 4 mg/ml and 2 mg/ml respectively. The drug incubation showed that
ethanolic stem bark extract reduced significantly (P=0.000) the infectivity of T. congolense at concentration of 2 mg/ml compared to negative control and was not
significantly (P=0.S97) different from the positive control. It was concluded that, C.
swynnertonii ethanolic stem bark extract possesses in vitro trypanocidal activity. The
second paper presents the results ofin vivo activity of C. swynnertonii ethanolic stem bark
extract on T. congolense parasitaemia and its effect on immunological components in
mice. Groups of mice infected with T. congolense were treated with the stem bark extracts
at 1000 mg/kg, 1500 mg/kg and 2000 mg/kg, twice a day in one set and thrice a day in
another setting for three days consecutively, and parasitaemia monitored. In the other
setting, uninfected mice randomized in five groups were treated with the extract that was
categorized as thorough mixed extract (TME) and supernatant extract (SE)) each at 500
mg/kg and 1500 mg/kg, in 8 hourly intervals respectively for three days consecutively.
The groups that received the extracts (1000 mg/kg and 2000 mg/kg) at eight hourly
intervals had drastically reduced parasitaemia (P<0.05). It was concluded that C.
swynnertonii ethanolic stem bark extract possesses in vivo trypanocidal activity. On the
other hand, SE at the dose of 1500 mg/kg significantly (P<0.05) reduced the percentage of
peripheral lymphocytes. Both doses (500 mg/kg and 1500 mg/kg) of TME significantly
(P<0.05) reduced lymphocytes percent while neutrophils and monocytes percent
increased significantly (P<0.05). Histopathology of the spleen in the mice treated with
1500 mg/kg of SE and TME showed apoptosis of lymphocytes around the marginal zone
and lymphoid follicles. Hence, it was concluded that C. swynnertonii ethanolic stem bark
extract within anti-trypanosomal therapeutic dose range possesses cytotoxic effect on
lymphocytes. The submitted manuscript provides the results on anti-trypanosomal
activities of fractions and sub-fractions of C. swynnertonii ethanolic stem bark extract
against T. congolense. Negative (phosphate buffered saline with glucose without the
extract) and positive (diminazene diaceturate) controls were used. In addition,
chromatographic techniques were employed to determine bioactive molecules in the sub-fractions. The findings indicated that anti-trypanosomal activity in the fractions of
aqueous, dichloromethane and petroleum ether were decreasing in that order. In this study,
four terpenoids (bomeol, geranylgeraniol, coronopilin and 4,8,13-duvatriene-l,3-diol)
were detected and were considered to be likely responsible for trypanocidal activity of
Commiphora swynnertonii ethanolic stem bark extract. Further studies to evaluate the in
vivo trypanocidal potential are recommended. As a general conclusion, this study has
shown that C. swynnertonii stem bark extract possesses in vitro and in vivo trypanocidal
activity. The in vivo trypanocidal activity is probably affected by cytotoxic effect on
lymphocytes at the therapeutic dosage. It was further found that bomeol, geranylgeraniol,
coronopilin and 4,8,13-duvatriene-l,3-diol could be responsible for observed trypanocidal
efficacy of C. swynnertonii stem bark extract. Further studies to determine their
therapeutic trypanocidal potentials are recommended
Description
PhD-Thesis
Keywords
Anti-trypanosomal, Cytotoxic, Commiphora Swynnertonii, African Animal Trypanosomosis (AAT), Parasite resistance, Trypanosoma congolense