Subacute and subchronic oral toxicity assessments of Acridocarpus smeathmannii (DC.) Guill. & Perr. root in Wistar rats.

Recent adverse herb reactions have stimulated interest documenting the safety profile of medicinal agents. Thus, subacute and subchronic oral toxicity of the hydroethanolic extract of Acridocarpus smeathmannii root (HEASR) in Wistar rats was investigated. In the 28 and 90-day subacute and subchronic toxicity tests, sixty-four rats (n = male: female = 1:1 = 32) were divided into four of eight/group and ninety-six (n = male: female = 1:1 = 48) into twelve/group respectively. Distilled water (10 mL/kg) or HEASR4, HEASR5 and HEASR6 (250, 500 and 1000 mg/kg/day) respectively were administered via oral gavage. Animals were killed humanely 24 h after the last administration. Using standard methods, acute oral toxicity dose of HEAR (2000 mg/kg) was non-lethal in rodents. Subacute administration of HEASR6 increased total bilirubin (p < 0.05) in female rats. HEASR moderately altered both haematological and biochemical indices in rats. HEASR6 administration reduced ovary weight in both studies while follicle stimulating hormone level in male was reduced at all doses used. HEASR modulated lipid peroxidation, sperm quality and elevated cyclooxygenase-2 levels in rats. Histology revealed gastritis and congestions in vital organs. The low-observed adverse effect level for HEASR was below 250 mg/kg for both sexes. Overall, HEASR demonstrated inherent toxicity evidenced by our current findings. The exaggeration of its folklore medicine applications calls for cautions.

Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root enhanced reproductive behavior and sexual function in male wistar rats: Biochemical and pharmacological mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Novel therapeutic opportunities from medicinal agents continue to arouse scientific interest in recent times. Still, there is a dearth of information as regards experimental evidence generated from medicinal plants that would yield pharmacological agents for the treatment of erectile dysfunction. Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root (ASR) has a long history as an aphrodisiac in African traditional medicine. Thus, this study investigated the reproductive potentials and associated biochemical mechanisms of its hydroethanolic extract (HEASR) in male Wistar rats. Also, the bioactive compounds were identified. MATERIALS AND METHODS: Fifty-four male albino rats (180 ±â€¯20 g) were divided into nine groups of six rats/group. Control, group 1 received normal saline (10 mL/kg). Groups 2-6 rats were administered sildenafil (1.43 mg/kg/day), mesterolone (0.36 mg/kg/day), doxazocin (0.03 mg/kg/day), HEASR1 (50 mg/kg/day) and HEASR2 (200 mg/kg/day) respectively. Others received co-administration of HEASR2 with standard drugs. Treatment lasted for 28 days via oral gavage. RESULTS: An acute oral toxicity of HEASR up to 2 g/kg produced no mortality in mice p.o. while the median lethal dose was estimated to be 810 mg/kg i.p. HEASR2 administration or in combination with sildenafil, mesterolone and doxazocin increased mounting frequencies on day 28 by 77.44%, 122.65%, 148.5% and 93.88% and sperm counts by 38.29%, 55.21%, 42.48%, and 48.98% respectively in treated rats. HEASR2 + sildenafil elevated testosterone and follicle stimulating hormone levels by 36.33% and 24.55% while HEASR2 + doxazocin elevated luteinizing hormone levels by 97.44% in rats. HEASR modulated prostate-specific antigen and malondialdehyde levels respectively. Reduced glutathione, superoxide dismutase, and catalase activities were raised in five selected organs. Serum nitric oxide but not cyclooxygenase-2 or tumor necrosis factor-α levels was moderately improved in rats. CONCLUSION: Overall, the results obtained demonstrated the potential of HEASR as a male reproductive enhancer, thus justify its folklore applications. Further, octadecanoic acid ethyl ester was the most abundant bioactive component present.

Polycyclic Aromatic Hydrocarbon, Haematological and Oxidative Stress Levels in Commercial Photocopier Operators In Lagos, Nigeria.

BACKGROUND: Human exposure to hazardous substances in the environment has been known to play an important role in the pathogenesis of some diseases. Photocopying machines have become a cheap source of self-employment in Nigeria. For obvious reasons the highest level of patronage is encountered in the campuses of educational institutions. However, the persons who operate the machines are always exposed to possible hazards associated with the job without protective devices. OBJECTIVE: This study investigated the levels of oxidative stress, polycyclic aromatic hydrocarbon (PAH) and haematological parameters in blood samples of photocopier operators. METHODS: The experimental procedure involved 50 consented subjects selected based on some criteria. The haematological parameters, oxidative stress and PAH levels were determined using standard methods. RESULTS: The results showed no significant difference (p ≥ 0.05) in the haematological parameters between the test subjects and the controls. However, there were duration on the job (yrs) dependent significant decrease in the level of superoxide dismutase (SOD) of the photocopier operators compared with the controls (> 5 years p≤ 0.0001; 4-5 years p≤0.001). The level of reduced glutathione (GSH) was significantly decreased across all lengths of duration on the job compared with the controls. CONCLUSION: The findings in this study revealed increased level of oxidative stress in photocopier operators with no significant change in haematological parameters. The health implication of operating photocopiers call for quick health education and intervention tailored to monitoring and guiding the photocopier operators. This will help to prevent or manage continuous exposure to the hazards of photocopying machines.

Effects of ethanolic dried leaf extract of Lecaniodiscus cupanioides on antioxidant enzymes and biochemical parameters in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lecaniodiscus cupanioides is widely used in West African folk medicine for the treatment of inflammatory conditions, fevers and bacterial infections. AIM OF THE STUDY: To evaluate the potential toxic effects of the ethanolic dried leaf extract of Lecaniodiscus cupanioides (LC) on antioxidant enzymes in selected organs and biochemical parameters. MATERIALS AND METHODS: Crude ethanolic extract of Lecaniodiscus cupanioides dried leaves was prepared. A 90-day sub-chronic toxicity study was conducted using albino rats. Reconstituted Lecaniodiscus cupanioides was administered at a dosage of 400, 800 and 1600 mg/kg (high dose) with a control group receiving 10 ml/kg orally. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture after euthanization. Selected organs (liver, kidney and brain) were harvested for antioxidant and histopathological assessments. RESULTS: The extract produced significant (p<0.05) increases in the weights of liver, kidney and brain at 800 mg/kg and 1600 mg/kg compared to the control. Biochemical analysis showed significant increase in Alanine transferase (ALT) at 800 mg/kg and 1600 mg/kg. Assay for antioxidant enzymes showed a reversible decrease in the activity of Catalase (CAT), Superoxide dismutase (SOD) and Glutathione (GSH) with an increase in Malondialdehyde (MDA) at 800 mg/kg and 1600 mg/kg Lecaniodiscus cupanioides. Histopathological study showed reversible congestion in the brain, liver, and kidney at 800 mg/kg and 1600 mg/kg. CONCLUSION: Findings in this study reveal that the ethanolic dried leaf extract of Lecaniodiscus cupanioides has the potential for inhibiting in vivo antioxidant enzymes activity and causing hepatotoxicity after prolonged exposure.

Evaluation of the antidiarrhoeal activity of the hydroethanolic leaf extract of Pupalia lappacea Linn. Juss. (Amaranthaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Pupalia lappacea is a medicinal plant found in savannah and woodland localities and forest path sides from Senegal to Southern Nigeria. It has been used in the management of diarrhoea in Nigerian traditional medicine. This study was designed to evaluate the antidiarrhoeal activity of the hydroethanolic leaf extract of Pupalia lappacea (PL). MATERIALS AND METHODS: The antidiarrhoeal activity of PL was evaluated using the normal and castor oil-induced intestinal transit, castor oil-induced diarrhoea, gastric emptying and intestinal fluid accumulation tests in rodents. RESULTS: PL (100-400mg/kg, p.o.) produced a significant dose-dependent decrease in normal and castor oil-induced intestinal transit compared with the control group (distilled water 10ml/kg, p.o.). This effect was significantly (P<0.05) inhibited by pilocarpine (1mg/kg, s.c.) but not by yohimbine (10mg/kg, s.c.), prazosin (1mg/kg, s.c.), or propranolol (1mg/kg, i.p.). The extract produced a dose-dependent and significant increase in the onset of diarrhoea. PL (100-400mg/kg) also reduced the diarrhoea score, number and weight of wet stools. The in-vivo antidiarrhoeal index (ADIin vivo) of 56.95% produced by the extract at the dose of 400mg/kg was lower compared to that produced by loperamide 5mg/kg (77.75%). However, PL (400mg/kg) significantly increased gastric emptying in rats but significantly reduced the volume of intestinal content in the intestinal fluid accumulation test. Phytochemical analysis of the extract revealed the presence of alkaloids, saponins, and fixed oils and fats. The acute toxicity studies revealed that the extract is relatively safe when given orally; no death was recorded at a dose of 10g/kg. CONCLUSION: Results showed that the hydroethanolic leaf extract of Pupalia lappacea possesses antidiarrhoeal activity possibly mediated by antimuscarinic receptor activity.

Protective effect of selected calcium channel blockers and prednisolone, a phospholipase-A2 inhibitor, against gentamicin and carbon tetrachloride-induced nephrotoxicity.

The ameliorative effect of calcium channel blockers (CCBs) and a phospholipase-A2 inhibitor in drug-/chemical-induced nephrotoxicity was investigated. Rats were divided into 7 groups of 5 rats in each group. In the gentamicin model, group I rats were pretreated with normal saline (10 ml kg(-1)), while groups II-VII rats were pretreated with normal saline (10 ml kg(-1)), ascorbic acid (10 mg kg(-1)), nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)), respectively, perorally 1 h before intraperitoneal (i.p.) injection of gentamicin (40 mg kg(-1)) for 14 days. In the carbon tetrachloride (CCl4) model, rats were pretreated with CCBs and prednisolone for 7 days before inducing nephrotoxicity with 20% CCl4 (1.5 ml kg(-1)). Rats were thereafter killed and blood and tissue samples were collected for assessments. I.p. injections of gentamicin and CCl4 caused significant hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia, and hyperchloremic alkalosis and reduced renal tissue levels of antioxidants. Also, significant reductions in the hemoglobin, packed cell volume, red blood cells, and platelet indices were observed. Pretreatments with nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)) significantly ameliorated the deleterious effects of gentamicin and CCl4 possibly via antioxidant and anti-lipoperoxidation mechanisms. The results obtained in this study suggest potential clinical usefulness of tested CCBs and prednisolone in drug-/chemical-induced nephrotoxicity.

Analgesic and antipyretic activities of Drymaria cordata (Linn.) Willd (Caryophyllaceae) extract.

Drymaria cordata (Linn.) Willd (Caryophyllaceae) is an herbaceous plant widely used in traditional African medicine (TAM) for the treatment of diverse ailments including painful and febrile conditions. This study was conducted to investigate the analgesic and antipyretic properties of the whole plant extract of D. cordata. The acetic acid-induced writhing, formalin, and tail clip tests were used to evaluate analgesic activity while the 2,4-dinitrophenol (DNP)-, d-amphetamine-, and yeast-induced hyperthermia tests were used to investigate antipyretic activity in rodents. D. cordata (100, 200, and 400 mg kg(-1), p.o) produced significant (p<0.05) analgesic activity in the mouse writhing, formalin (second phase), and tail clip tests. The effects of D. cordata were generally comparable to those of acetylsalicylic acid (ASA, 100 mg kg(-1), p.o) and morphine (2 mg kg(-1), s.c). Also, D. cordata produced significant (p<0.05) dose-dependent inhibition of temperature elevation in the 2,4-DNP and yeast-induced hyperthermia models with peak effects produced at the dose of 400 mg kg(-1). The effect at this dose was comparable to that of ASA in the two models. In the d-amphetamine method, D. cordata produced significant (p<0.05) dose- and time-dependent reduction of temperature elevation with peak effect produced at the dose of 200 mg kg(-1). The effect of the extract at this dose was greater than that of ASA. The results obtained in this study demonstrate that the aqueous whole plant extract of Drymaria cordata possesses analgesic and antipyretic properties mediated through peripheral and central mechanisms.

Antidiarrhoeal activity of DAS-77 (a herbal preparation).

BACKGROUND: DAS-77 is a traditional herbal preparation composed of the young callous bark of mango (Mangifera indica Linn., Anacardiaceae) and the dried root of pawpaw (Carica papaya Linn., Caricaceae). This phytomedicine is claimed to have beneficial effects in the treatment of gastrointestinal disorders, including diarrhoea. OBJECTIVE: To investigate the antidiarrhoeal effect of DAS-77 using standard pharmacological models. METHODS: Normal and castor oil-induced intestinal transit, and castor oil-induced diarrhoea tests wore carried out in mice while intestinal fluid accumulation and gastric emptying tests were carried out in rats. Acute toxicity test and preliminary phytochemical analysis were also conducted. RESULTS: The results obtained in this study revealed that DAS-77 had no significant inhibitory effect on normal intestinal transit, castor oil-induced diarrhoea, intestinal fluid accumulation and gastric emptying. However, the inhibitory effect of DAS-77 was significant (p<0.001) relative to control in the castor oil-induced intestinal transit test. Peak effect was produced at the dose of 100 mg/kg (p.o.). The effect of DAS-77 in this respect was reversed by pilocarpine and propranolol, but not by phenoxybenzamine. DAS-77 did not produce any mortality given p.o. up to 10 g/kg, indicating the relative safety of the preparation. The i.p. LD50 was estimated to be 1122 mg/kg. The remedy was found to contain saponins, tannins, phenols and alkaloids. CONCLUSION: Findings in this study suggest that DAS-77 possesses antidiarrhoeal activity due to the inhibition of intestinal motility possibly mediated by muscarinic and alpha adrenergic receptors.

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.

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.

Antiinflammatory activity of the aqueous leaf extract of Byrsocarpus coccineus.

The antiinflammatory effect of the aqueous leaf extract of Byrsocarpus coccineus was evaluated using the carrageenan and egg albumin induced rat paw edema, xylene induced mouse ear edema and formaldehyde induced arthritis inflammation tests. The extract administered orally at doses of 50, 100, 200 and 400 mg/kg b.w produced a significant (P<0.05) dose dependent inhibition of edema formation in all four methods used. The results obtained suggest that the aqueous leaf extract of B. coccineus is endowed with effective antiinflammatory activity mediated via either inhibition of phospholipase A(2) (PLA(2)) activity or cyclooxygenase cascade and by blocking the release of vasoactive substances (histamine, serotonin and kinins). These findings seem to justify the use of the plant in traditional African medicine in the treatment of inflammation, including arthritic conditions.

Evaluation of the antidiarrhoeal activity of Byrsocarpus coccineus.

Based on its use in traditional African medicine, the antidiarrhoeal activity of the aqueous leaf extract of Byrsocarpus coccineus, Connaraceae, was evaluated on normal and castor oil-induced intestinal transit, castor oil-induced diarrhoea, enteropooling and gastric emptying. The extract (50, 100, 200 and 400 mg/kg, p.o.) produced a significant (P<0.05) dose dependent decrease in propulsion in the castor oil-induced intestinal transit in mice. The mean peristaltic index (%) for these doses of extract, control (distilled water; 10 ml/kg, p.o.) and morphine (10 mg/kg, s.c.) were 55.27+/-1.86, 53.12+/-3.73, 38.60+/-3.79, 30.25+/-1.27, 89.33+/-5.62 and 20.29+/-3.38, respectively. The effect of the extract at the highest dose was significantly (P<0.05) lower than that of the standard drug. This effect was antagonised by yohimbine (1 mg/kg, s.c.) but not by isosorbide dinitrate (IDN, 150 mg/kg, p.o.). At 200 mg/kg, the extract produced a significant decrease in propulsion in normal intestinal transit. In a dose dependent manner, it delayed the onset of diarrhoea, produced a significant decrease in the frequency of defaecation, severity of diarrhoea and protected the mice treated with castor oil. Mean diarrhoea scores were 30.83+/-1.72, 22.40+/-1.71, 21.43+/-1.32, 13.80+/-0.33, 18.00+/-3.94 and 7.67+/-2.41 for control, extract (50, 100, 200 and 400 mg/kg) and morphine, respectively. This effect was not antagonized by IDN. The extract (400 mg/kg) significantly decreased the volume (ml) of intestinal fluid secretion induced by castor oil (0.60+/-0.23) compared with 1.27+/-0.12 for control. However, there was no significant effect on gastric emptying. The results obtained suggest that Byrsocarpus coccineus possesses antidiarrhoeal activity due to its inhibitory effect on gastrointestinal propulsion, mediated through alpha(2) adrenoceptors, and also inhibition of fluid secretion. Preliminary phytochemical analysis revealed the presence of alkaloids, tannins, saponins, reducing sugars, glycosides and anthraquinones.