Olufunmilayo O. Adeyemi

Anti-obesity and antihyperlipidaemic effect of Hunteria umbellata seed extract in experimental hyperlipidaemia

AIM OF THE STUDY In Nigerian folk medicine, water infusion of the dried seeds of Hunteria umbellata (K. Schum.) Hallier f. has a reputation for the local management of obesity and hyperlipidaemia. The present study is aimed at evaluating the anti-obesity and antihyperlipidaemic activities as well as the underlying mechanisms of action of the aqueous seed extract of Hunteria umbellata (HU) in normal, triton-induced, and olive oil-induced hyperlipidaemic rats. MATERIALS AND METHODS Normal and olive oil-induced hyperlipidaemic, and triton-induced hyperlipidaemic rats were pre-treated with single, daily oral administration of 10 ml/kg of distilled water, 20 mg/kg of simvastatin, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in 10 ml/kg of distilled water for 28 days and 24 h. The effects of these drugs on % body weight change, feeding pattern, serum lipids, coronary artery risk index (CRI) and atherogenic index (AI) and Lees index (LI) were investigated. RESULTS Oral pre-treatment with simvastatin and graded oral doses of HU significantly (p<0.05) reduced the weight gain pattern and caused dose related (p<0.05, p<0.01 and p<0.001) reductions in the serum lipids, CRI, AI and LI. Also, HU pre-treatment significantly improved triton-induced hepatic histological lesions. CONCLUSIONS Results of this study showed that HU has both anti-obesity and antihyperlipidaemic effects which may partly be mediated via inhibition of intestinal lipid absorption and de novo biosynthesis of cholesterol. Thus, the results justify the ethnopharmacological use of the extract in the management of obesity and hyperlipidaemia.

Anticonvulsant, anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata Fresen.

AIM OF THE STUDY The objective of this study is to investigate the anticonvulsant, anxiolytic and sedative activities of the aqueous root extract of Securidaca longepedunculata. MATERIALS AND METHODS The anticonvulsant effect of the aqueous root extract (100, 200 and 400 mg/kg) was evaluated in mice using the strychnine- and picrotoxin-induced seizure models. Its anxiolytic activity was evaluated using the elevated plus maze (EPM) and the Y maze (YM) methods (Hogg, 1996; Yemitan and Adeyemi, 2003) while the hexobarbitone induced sleep and the hole board models were used to evaluate the sedative and exploratory activities in mice respectively. The acute toxicity studies and phytochemical analysis of the extract were also carried out. RESULTS The extract (100-400 mg/kg) produced a significant (P<0.01) dose dependent increase in onset of convulsion compared to the control for strychnine- and picrotoxin-induced seizures. It also produced a significant (P<0.01) dose dependent prolongation of the cumulative time spent in the open arms of the elevated plus maze and Y maze compared with the control. The extract (100-400 mg/kg) produced significant (P<0.01) reduction in the time of onset of sleep induced by hexobarbitone. The prolongation of hexobarbitone sleeping time by the extract (200 mg/kg) was comparable to that produced by diazepam (3 mg/kg). At doses of 100-400 mg/kg, the extract produced a dose dependent decrease in exploratory activity of the mice. The reduction in exploratory activity produced by the extract (400 mg/kg) was greater than that of chlorpromazine (1 mg/kg). The results obtained from the experiments indicate that the extract has central nervous system depressant and anxiolytic activities. The LD(50) obtained for the acute toxicity studies using both oral and intraperitoneal routes of administration were 1.74 g/kg and 19.95 mg/kg respectively. CONCLUSION These findings justify the use of Securidaca longepedunculata in traditional medicine for the management of convulsion and psychosis.

Evaluation of the antidiarrhoeal effect of Sanseviera liberica Gerome & Labroy (Agavaceae) root extract

ETHNOPHARMACOLOGICAL RELEVANCE The aqueous root extract of Sansevieraliberica (Agavaceae), SL, is used in Traditional African Medicine (TAM) for the treatment of diarrhoea. However, the scientific basis for this usage has not been established. AIM OF THE STUDY To evaluate the antidiarrhoeal activity of SL using various pharmacological models. MATERIALS AND METHODS The intestinal transit, castor oil induced diarrhoea, enteropooling, and gastric emptying methods were used in this study. RESULTS SL (25-400 mg/kg, p.o.) produced significant (P < 0.05) dose dependent reduction in propulsive movement in both the normal and castor oil induced intestinal transit tests in mice. Peak effect was elicited at 200 mg/kg but this effect was lower than that produced by morphine (10 mg/kg, s.c.). The effect of SL on castor oil induced intestinal transit was antagonized by isosorbide dinitrate, IDN (150 mg/kg, p.o.) but not by yohimbine (1 mg/kg, s.c.). In the castor oil induced diarrhoea test, SL significantly delayed the onset and decreased the frequency and severity of diarrhoea. The effect at 200 mg/kg was comparable to that of morphine and was reversed by IDN. SL at the dose of 200 mg/kg significantly reduced the volume of intestinal secretion induced by castor oil but produced no effect on gastric emptying. The extract was practically nontoxic administered p.o. The LD(50) was 631 mg/kg given i.p. Phytochemical analysis revealed the presence of oils, reducing sugars, alkaloids, saponins, anthraquinones, and tannins in the extract. CONCLUSION The results obtained in this study suggest that the aqueous root extract of Sanseviera liberica possesses antidiarrhoeal property due to inhibition of gastrointestinal propulsion and fluid secretion, possibly mediated through inhibition of the nitric oxide pathway. This justifies the use of the plant extract in TAM for the treatment of diarrhoea.

Antidepressant and anxiolytic effects of amentoflavone isolated from Cnestis ferruginea in mice

The root decoction of Cnestis ferruginea (CF) Vahl DC (Connaraceae) is used in traditional African medicine in the management of psychiatric disorders. This study presents the antidepressant and anxiolytic effects of amentoflavone (CF-2) isolated from the root extract of C. ferruginea. The antidepressant effect was studied using the forced swimming (FST) and tail suspension tests (TST) while the hole-board, elevated plus maze (EPM) and light/dark tests were used to evaluate the anxiolytic effect. Acute treatment with CF extract and amentoflavone significantly (p<0.001) reduced the duration of immobility in FST and TST with peak effects observed at 100 and 50mg/kg respectively in comparison to control treated. Antidepressant effects of CF and amentoflavone were significantly higher (p<0.05) when compared to imipramine in FST but comparable to the fluoxetine treated group in TST. The pretreatment of mice with metergoline (4mg/kg, i.p., a 5-HT2 receptor antagonist), prazosin (62.5μg/kg, i.p., an α1-adrenoceptor antagonist), and yohimbine (1mg/kg, i.p., an α2-adrenoceptor antagonist), but not sulpiride (50mg/kg, i.p., a dopamine D2 receptor antagonist), cyproheptadine (3mg/kg, i.p., a 5-HT2 receptor antagonist), atropine (1mg/kg, i.p., a muscarinic receptor antagonist) 15mins before the administration of amentoflavone (50mg/kg; p.o.) significantly prevented its antiimmobility effect in the FST. CF extract and CF-2 significantly (p<0.05) attenuated anxiety by increasing the number of head-dips in the hole-board test, the time spent on the open arms in the EPM, and the exploration of the light chamber in the light/dark test. Pretreatment with flumazenil (3mg/kg, i.p., ionotropic GABA receptor antagonist) 15min before oral administration of amentoflavone (25mg/kg) significantly reduced the time spent in the open arms in EPM. It is concluded from the results obtained that amentoflavone produces its antidepressant effect through interaction with 5-HT2 receptor and α1-, and α2-adrenoceptors while the anxiolytic effect involved the ionotropic GABA receptor.

Analgesic and anti-inflammatory activities of Cnestis ferruginea Vahl ex DC (Connaraceae) methanolic root extract

ETHNOPHARMACOLOGICAL RELEVANCE Cnestis ferruginea Vahl ex DC (Connaraceae) is a shrub widely used in traditional African Medicine (TAM) for the treatment of various painful and inflammatory conditions. AIM OF THE STUDY The objective of this study was to investigate the analgesic and anti-inflammatory properties of the methanolic root extract of Cnestis ferruginea. MATERIALS AND METHODS Analgesic activity was evaluated using the acetic acid-induced writhing, formalin, tail clip, and hot plate tests in mice. The carrageenan- and egg albumin-induced rat paw oedema, formaldehyde-induced arthritis inflammation, and xylene-induced ear oedema tests were used to investigate the anti-inflammatory actions of Cnestis ferruginea. RESULTS The methanolic root extract of Cnestis ferruginea (100, 200, and 400mg/kg; p.o.) produced significant (P<0.05) dose-dependent inhibition of pain response elicited by acetic acid and formalin while also increasing the nociceptive reaction latency in the tail clip and hot plate tests. In respect of anti-inflammatory activity, Cnestis ferruginea caused significant (P<0.05) dose-dependent inhibition of oedema development in the carrageenan, egg albumin, formaldehyde, and xylene-induced inflammation tests. The effects of the extract in the various models were generally comparable to those of the standard drugs used. CONCLUSION The findings in this study suggest that the methanolic root extract of Cnestis ferruginea possesses analgesic and anti-inflammatory activities possibly mediated through peripheral and central mechanisms involving inhibition of release and/or actions of vasoactive substances (histamine, serotonin and kinins) and prostaglandins. The results justify the use of the extract in TAM for the treatment of painful and inflammatory conditions.

Analgesic and anti-inflammatory activity of Crinum glaucum aqueous extract

The anti-inflammatory and analgesic effects of the aqueous extract of Crinum glaucum were evaluated in mice and rats using the carrageenan- and dextran-induced paw oedema, acetic acid-induced writhing, cold water tail flick and formalin pain tests. The extract (100-400 mg/kg) and acetylsalicylic acid (100 mg/kg) produced a significant (P<0.05) inhibition of the second phase response in the formalin pain model, while only the high dose (400 mg/kg) of the extract showed an antinociceptive effect in the first phase. The extract also showed a dose-dependent inhibition of acetic acid-induced abdominal writhes. The tail flick latency was dose dependently enhanced by the extract but this was significantly (P<0.05) lower than that produced by morphine (2 mg/kg). The extract (125-500 mg/kg) administered 1 h before or after carrageenan-induced paw swelling produced a dose dependent inhibition of the oedema. No effect was observed with the dextran-induced oedema model. The data obtained suggest that the anti-inflammatory and analgesic effects of the extract may be mediated via both peripheral and central mechanisms.

Hepatoprotective and in vivo antioxidant effects of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae)

ETHNOPHARMACOLOGICAL RELEVANCE The leaf decoction of Byrsocarpus coccineus (Connaraceae) is drunk for the treatment of jaundice in West African traditional medicine. AIM OF THE STUDY To investigate the hepatoprotective and in vivo antioxidant effects of Byrsocarpus coccineus in carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. MATERIALS AND METHODS Group allotment in this study included vehicle, CCl(4), Byrsocarpus coccineus 1000 mg/kg alone, Byrsocarpus coccineus 200, 400, and 1000 mg/kg+CCl(4) and Livolin((R)) 20mg/kg+CCl(4), and treatment was carried out accordingly. On the 7th day, rats were sacrificed and blood was withdrawn by cardiac puncture. The levels and activities of serum biochemical parameters and antioxidant enzymes were then assayed using standard procedures. RESULTS CCl(4) significantly (P<0.05) increased the levels of ALT and AST and reduced total protein. In CCl(4) treated animals, Byrsocarpus coccineus (200, 400, and 1000 mg/kg) dose-dependently and significantly decreased ALT, AST and ALP levels with peak effect produced at the highest dose. Conversely, Byrsocarpus coccineus produced significant increases in albumin and total protein levels. The standard drug produced significant effects in respect of ALT (downward arrow), albumin (upward arrow), and total protein (upward arrow). CCl(4) also produced significant (P<0.05) reductions in the activity of catalase, SOD, peroxidase and GSH, and conversely increased MDA level. Byrsocarpus coccineus produced significant and dose-dependent reversal of CCl(4)-diminished activity of the antioxidant enzymes and reduced CCl(4)-elevated level of MDA. The standard drug also significantly increased CCl(4)-diminished antioxidant enzymes activity and reduced CCl(4)-elevated MDA level. In general, the effects of the standard drug were comparable and not significantly different from those of Byrsocarpus coccineus. CONCLUSION The results obtained in this study suggest that the aqueous leaf extract of Byrsocarpus coccineus possesses hepatoprotective and in vivo antioxidant effects. This finding justifies the use of this preparation in West African traditional medicine for the treatment of liver disease.

Inhibition of chemically induced inflammation and pain by orally and topically administered leaf extract of Manihot esculenta Crantz in rodents

The aqueous leaf extract of Manihot esculenta Crantz (MELE) is being used orally and topically in traditional African medicine for the treatment of inflammation and pain, and claimed to be safe. The anti-inflammatory effects of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) were tested against carrageenan-induced paw oedema in rats as well as against xylene-induced ear oedema in mice. The analgesic effect of MELE (100-400 mg/kg, p.o. or 1-4%, w/w in petroleum jelly, topically) was tested against acetic acid-induced (20 microl, 0.6%, v/v in normal saline, i.p.) and acetylcholine-induced (8.3 mg/kg, i.p.) mouse writhing models. At 100-400 mg/kg, p.o. and 1-4% (w/w), topically, MELE produced significant inhibitions of carrageenan-induced rat paw oedema and xylene-induced ear swelling in mice. Effects produced by MELE were significantly higher than those produced by indomethacin (10 mg/kg, s.c. or 1%, w/w in petroleum jelly) in the anti-inflammatory models. For the analgesic effect, MELE (100-400 mg/kg, orally) and (1-4%, w/w, topically), like aspirin (100 mg/kg, i.p.) exhibited significant (P<0.05) inhibition of acetic acid- and acetylcholine-induced mouse writhing tests, compared to untreated control. Effects produced by MELE were significantly lower than those produced by aspirin (100 mg/kg, i.p.) in the analgesic models, except for the topically administered extract on acetylcholine-induced pain. Acute oral administration up to 10 g/kg did not cause death within 14 days, but mortalities were produced in i.p. administered extract with LD(50) of 2.5+/-0.3 g/kg. Based on these, the extract may contain orally safe, topically and orally effective anti-inflammatory and analgesic principles, which justify its use in traditional African medicine.

Further evaluation of antihyperglycaemic activity of Hunteria umbellata (K. Schum) Hallier f. seed extract in experimental diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE In African traditional medicine, water decoction made from the dry seeds of Hunteria umbellata (K. Schum) Hallier f. is highly valued in the management of diabetes mellitus. AIM In the present study, the antihyperglycaemic activity of the seed aqueous extract of Hunteria umbellate (K. Schum) Hallier f. (HU) was investigated in alloxan-induced, high fructose- and dexamethasone-induced hyperglycaemic rats. MATERIALS AND METHODS Alloxan-induced, dexamethasone-induced and high fructose-induced hyperglycaemic rats were treated with single, daily oral administration of 1 mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in Groups III, IV, V and VI, for 14 days, 21 days and 8 weeks, respectively. The effects of these drugs on FBG, free plasma insulin levels, HbA(1c), serum TG and TC, and insulin resistance indices were investigated. RESULTS Data generated in the current study showed that glibenclamide and graded oral doses of HU caused significant dose related (p < 0.05, < 0.01 and < 0.001) reductions in FBG when compared to the values obtained for the model control (Group II) rats. Similarly, daily oral administration of 66.7 g/kg fructose to rats for 8 weeks was associated with significant (p < 0.001) hyperglycaemia, elevations in plasma HbA(1c), free insulin, fasting insulin resistance indices, serum TG, and cholesterol. However, concomitant oral treatments with 1mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg, and 200 mg/kg of HU extract significantly and dose dependently (p < 0.05, < 0.01 and < 0.001) attenuated development of hyperglycaemia, decreased levels of plasma HbA(1c), free insulin, and serum triglyceride and cholesterol, in the Groups III, IV, V and VI rats, respectively, when compared to fructose-induced hyperglycaemic (Group II) rats. Similar effect was also recorded in the dexamethasone-induced hyperglycaemic rats. CONCLUSION Results of this study suggest that the hypoglycaemic and antihyperlipidaemic effects of HU are mediated via enhanced peripheral glucose uptake and improvements in hyperinsulinaemia.

Antidiarrhoeal activity of the ethyl acetate extract of Baphia nitida (Papilionaceae)

In our search for plants useful in the treatment of diarrhoea, we investigated the ethyl acetate extract of Baphia nitida (BN) using intestinal transit, enteropooling and gastric emptying tests in mice and rats. In the castor oil intestinal transit test, BN produced a significant (P<0.05) dose dependent decrease in propulsion with peristaltic index (PI) values of 56.85+/-6.76, 36.84+/-3.04 and 31.98+/-2.60%, respectively at doses of 100, 200 and 400mg/kg vs. 89.33+/-6.28% for control. The effect at 400mg/kg was significantly lower than that of morphine, 10mg/kg, s.c. (20.29+/-3.78%), and was antagonized by isosorbide dinitrate, IDN (150mg/kg, p.o.) but not by yohimbine (1mg/kg, s.c.). This effect was not potentiated by atropine (1mg/kg, s.c.). In the castor oil-induced diarrhoea test, BN produced a significant increase in onset of diarrhoea (103.40+/-8.74, 138.80+/-17.04 and 174.8+/-29.04min, 100 to 400mg/kg, vs. 47.60+/-8.76min for control and 226.10+/-12.57min for morphine). The severity of diarrhoea (diarrhoea score) was dose dependently reduced (19.00+/-2.26, 17.04+/-1.89, 15.00+/-2.05, 100 to 400mg/kg, vs. 31.40+/-2.11 for control and 7.7+/-2.2 for morphine). This effect was not antagonized by IDN or yohimbine. The effect on severity was, however, potentiated by atropine. BN also reduced the number and weight of wet stools but did not have any significant effect on intestinal fluid accumulation and gastric emptying. Results obtained suggest that the ethyl acetate extract of Baphia nitida is endowed with antidiarrhoeal activity possibly mediated by interference with the l-arginine nitric oxide pathway and synergistic with antagonistic action on muscarinic receptors.