ANTINOCICEPTIVE ACTIVITIES OF SOME MEDICINAL PLANT EXTRACTS USING ANIMAL MODELS

Citation:
KARIUKI HELLENNYAMBURA. ANTINOCICEPTIVE ACTIVITIES OF SOME MEDICINAL PLANT EXTRACTS USING ANIMAL MODELS. Titus I. Kanui PD, ed. Nairobi: University of Nairobi; 2013.

Thesis Type:

PhD

Abstract:

ABSTRACT
Pain represents the symptom for the diagnosis of several diseases conditions and is widely accepted as one of the most important determinants of quality of life. Plants have been claimed to have analgesic effects by several communities in East Africa and a great number of the people use plants for management of painful conditions.

The aim of this study was to establish the antinociceptive activities of nine plants used in traditional medicine as a painkiller using tail flick test.

Of the nine plants tested in the tail flick test, the root extracts of Toddalia asiatica, Senna singueana and Rhus natalensis showed significant antinociceptive effects at dose 200 mg / kg while T. asiatica at 100 mg / kg dose exhibited highly significant effect (p < 0.001) compared to the control animals and this was comparable to the reference drug morphine (5 mg / kg).

In the hot plate test Senna singuaenae at 200 mg / kg dose showed significant (p < 0.05) antinociceptive effect while Toddalia asiatica roots extract showed a highly significant (p < 0.001) compared to the vehicle treated mice. The antinociceptive effect of T. asiatica was comparable to that of morphine (5 mg / kg) and of acetyl salicylic acid (ASA) (100 mg / kg).
In this study the acetic acid induced writhing test was used to screen the roots and leaves of T. asiatica, plant parts that are commonly used in traditional medical practice. The percentage inhibition was higher (56.3%) at 100 mg / kg of the roots compared to (46.21%) the dose of 200 mg /kg of the leaf extract suggesting that the roots is more potent than the leaf extract. The results also indicated that T. asiatica has peripheral pain modulatory effect.
Roots extract of T. asiatica at 200 mg / kg caused significant antinociceptive effects in the early phase of the formalin test while the 100 mg / kg extract caused a highly significant antinociceptive effect in the late phase. This was comparable to that of the reference drugs indomethacin (50 mg / kg) and ASA (100 mg / kg). The formalin test results suggest that T. asiatica roots extract has both peripheral and central sites of action.
The results of the present study indicate that the roots extracts of T. asiatica possess antinociceptive activity in chemical, thermal, and inflammatory models of pain and that the effects of the extract showed dose-dependent antinociceptive effects. The effects were comparable to those of the reference drugs used ASA, morphine and indomethacin.
The observed antinociceptive effects of T. asiatica roots extract are due to the presence of biologically active chemical compounds in the extracts. In order to identify the active compounds, the roots extract of T. asiatica was fractionated by column chromatography roots and the fractions tested for activity. The polar and non-polar fractions both exhibiting similar antinociceptive activities. The antinociceptive effects of the fractions were comparable to the effects of the morphine and ASA in the tail flick test. The hexane/ dichloromethane (1:1) fraction showed very highly significant antinociceptive effects (p < 0.001) with 50 mg / kg and the 100 mg / kg doses compared to the vehicle treated animals. This effect was comparable to that of ASA and morphine which were used as positive controls. The antinonociceptive effects of the polar fractions (dichloromethane / methanol; 1:1) were also highly significant (p < 0.001) with the 50 mg / kg while the 100 mg / kg dose being highly significant (p < 0.01). However, the fractions with moderate polarity (the fraction eluted with dichloromethane) did not show significant effect compared to the vehicle treated animals.
The roots extract of T. asiatica fractions were purified and yielded seven compounds, four alkaloids and three coumarins. The coumarins, labeled as HK 3 (Isopimpinellin) and HK 5 (6-(3-methylbut-2enyloxy)-8-methoxy2h-chromen-2-one), showed no significant antinociceptive activity in the tail flick test while HK 6 (6,7-dimethoxy-5-(3-methyl-2-oxobutyl) HK7 (8-Acetonyldihydrochelerythrine) and HK 18 (6-(2, 3-dihydroxy-3-methylbutyl)-5,7-dimethoxy-2H-chromen-2-one)) had significant antinociceptive effects compared to the vehicle treated animals. The alkaloids HK 15 (8-oxochelerythrine) and HK 13 (dihydrochlerythrine) showed very highly significant antinociceptive effects with HK 13 showing the most potent antinociceptive effects in the tail flick test. The structure elucidation of compounds of Toddalia asiatica was done using nuclear magnetic resonance (NMR) spectroscopy.
The compound HK 6 is a new compound and it exhibited significant antinociceptive effects when compared to the vehicle treated controls. Compound HK13 (dihydrochlerythrine) was for the first time isolated from T. asiatica and the structure ellucidated. It is also the first time the compound has been assayed for antinociception and exhibited very highly significant effects. No motor, neurological, or other behavioral deficits were observed with the extracts as well as the compounds of T. asiatica.
Data obtained from this study established the analgesic properties of the crude extracts of which the roots of T. asiatica was he most active. From this plant the active compounds have been isolated and identified withdihydrochlerythrine, being the most active compound. More tests to evaluate on the safety and toxicity on dihydrochlerythrine and related compounds need to be conducted in animals before conventional clinical trials can be undertaken.
This study therefore authenticates the use of Toddalia asiatica in the management of pain since it contains compounds which have shown antinociceptive activities.

Key words:
Antinociception, Toddalia asiatica, mice, alkaloid, coumarin, antinococeptive, dihydrochlerythrine

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