Polycyclic aromatic hydrocarbons in a polyherbal drug: human health exposure-associated risk assessment study.

PAHs are pervasive pollutants known to bioaccumulate in environmental matrices, plants, and humans. Dr. Iguedo Goko Cleanser® is a polyherbal drug with unsubstantiated claims to treat various diseases in sub-Saharan Africa. PAHs were measured following EPA-16 PAHs guidelines using Gas Chromatography (Agilent-6890N, USA). The drug's exposure-associated public health concerns was determined using suitable mathematical paradigms. PAHs present were acenaphthene (2.74 × 10-2), pyrene (2.7598 × 10-2), and chrysene (5.1277 × 10-2) ppm. Dietary intake of chrysene, acenaphthene and pyrene for adults, and children ranged from 2.466-4.615 × 10-3 and 1.215-2.308 × 10-3 ppm/mg/kg, respectively. B[α]Peq, EDB[α]Peq, and incremental lifetime cancer risk were determined to be 5.6777 × 10-4, 5.109912 × 10-5 and 5.3289 × 10-12, respectively. Our results suggest a high risk of non-carcinogenic adverse health effects, especially on chronic exposure among adolescents and adults, necessitating caution and/or avoidance of its chronic use. Therefore, policy formulation and implementation as regards the safety of plant-based remedies and allied products before their distribution among end-users must be ensured.

Mechanistic assessment of the analgesic, anti-inflammatory and antipyretic actions of Dalbergia saxatilis in animal models.

CONTEXT: Aqueous root extract of Dalbergia saxatilis, Hook, f., (Leguminosae) (DS) is reported useful for toothache, pains, and fever, but not scientifically proven. OBJECTIVE: This study determined its effectiveness in pain, inflammation, and fever, applying scientific models. MATERIALS AND METHODS: Swiss mice or Sprague-Dawley rats (n = 5) were pretreated with distilled water, DS (100 or 200 mg/kg), or standard drug for 30 min. The analgesic activity was measured by acetic acid writhing, tail flick, tail immersion, tail clip, hot plate, and formalin pain tests; anti-inflammatory effects were determined via carrageenan and dextran rat paw oedema tests; antipyretic activity was measured by Escherichia coli lipopolysaccharide (ECL) and turpentine in rabbits, and d-amphetamine sulphate (d-AS) pyrexia test in rats. RESULTS: Writhing frequency inhibition was produced by 200 mg/kg DS (33.10%), aspirin (38.19%) and morphine (93.68%). Unlike morphine, DS did not produce significant prolongation of the reaction times in the hot-plate, tail immersion, tail flick, and tail clip tests. In the first and second phases of formalin test, respectively, % inhibition was: 200 mg/kg DS (25.70% and 0%), aspirin (4.76% and 67.33%), morphine (81.42% and 66.11%); for carrageenan and dextran tests, significant difference was recorded between 200 mg/kg DS and control up to 6 h. Significant reduction in ECL, turpentine and d-AS pyrexia was recorded at 100 and 200 mg/kg DS. CONCLUSION: DS produces mild non-steroidal analgesic and anti-inflammatory, as well as significant antipyretic actions involving cyclooxygenase, α2 adrenoceptor and interleukin-1 ß1 due to any of glycosides, saponins or phenolic tannins.

The relaxant actions of ethanolic extract of Tridax procumbens (Linn.) on rat corpus cavernosum smooth muscle contraction.

BACKGROUND: The effect of Tridax procumbens aqueous ethanolic extract on the rat corpus cavernosum smooth muscles was evaluated in the present study. METHOD: Corpus cavernosum strips obtained from healthy, young, adult male Wistar albino rats (250-300 g) were precontracted with phenylephrine (10-7 M) or KCl (60 mM) and then treated with various concentrations of T. procumbens extract (0.15-1.05 mg/mL). The change in corpus cavernosum strip tension was recorded. The interactions between T. procumbens extract with acetylcholine and with sodium nitroprusside were also evaluated. RESULTS: The results indicated that corpus cavernosum strips relaxation induced by T. procumbens extract was concentration-dependent and this was significant (p<0.5). Pre-treatment with a nitric oxide synthase (NOS) inhibitor (N(1) nitro-L-arginine-methyl ester, l-NAME), did not completely inhibit the relaxation. However, T. procumbens extract (0.6 mg/mL) significantly (p<0.5) enhanced both acetylcholine- and sodium nitroprusside-induced corpus cavernosum strips relaxation. CONCLUSIONS: RESULTS suggest that T. procumbens extract has a concentration-dependent relaxant effect on the isolated rat corpus cavernosum. The mechanism of action of T. procumbens extract is complex. A part of its relaxing effect is mediated directly by the release of NO from endothelium which may improve erectile dysfunction.

Role for monoaminergic systems in the antidepressant and anxiolytic properties of the hydroethanolic leaf extract from Adenia cissampeloides.

BACKGROUND: Adenia cissampeloides (Planch ex. Hook) Harms (Passifloraceae) leaf infusion is used in traditional African medicine as a stimulant to treat depression and insanity. Thus, this study investigates antidepressant and anxiolytic activities of the hydroethanol leaf extract of Adenia cissampeloides (ACE) in mice. METHODS: ACE (50-200 mg/kg, p.o.) was administered to mice 1 h before behavioral studies; the forced swimming test (FST), tail suspension test (TST), elevated-plus maze test (EPM) hole-board test (HBT) and open field test (OFT). In addition, the probable mechanisms of antidepressant- and anxiolytic-like actions of ACE were also investigated. RESULTS: ACE (100 and 200 mg/kg) produced significant (p<0.01) reduction in immobility, along with a significant increase in swimming activity (75.20%) and climbing (190.00%), respectively, similar to anti-immobility effect of imipramine in the FST. Also, in TST, ACE (100 and 200 mg/kg) treatment significantly (p<0.01) reduced the immobility time by 35.60%, and 35.27%, respectively, which was similar to anti-immobility effect of fluoxetine (32.50%). However, the antidepressant-like effect produced by ACE was prevented (p<0.01) by yohimbine (α2-adrenoceptor antagonist), or sulpiride (dopamine D2 receptor antagonist) pretreatment. ACE (50 and 100 mg/kg) treatment (p<0.01) increased number (41.67%) and duration of head-dips (52.27%) in HBT. Similarly, ACE (50-200 mg/kg) increased duration of open arm entries (p<0.001) in EPM. However, this effect was reversed (p<0.001) by pretreatment of mice with cyproheptadine (5-HT2 receptor antagonist) (60.87%). CONCLUSIONS: Findings from these studies revealed antidepressant-like effect of ACE mediated through interaction with dopamine D2- receptor or α2-adrenoceptor. Also an anxiolytic-like effect through interaction with 5-HT2 receptors.

Calcium-dependent mechanisms mediate the vasorelaxant effects of Tridax procumbens (Lin) aqueous leaf extract in rat aortic ring.

BACKGROUND: Tridax procumbens leaf extract has a folk reputation as an antihypertensive agent in Nigeria. Evidence suggests that it has a relaxant effect on smooth muscles. The present study was designed to investigate the role of calcium in the vasorelaxant effect of this extract. METHODS: Concentration-response studies with noradrenaline (NA), KCl and CaCl2 were carried out in rat aortic rings with and without the extract in physiological salt solution (PSS) (n=6 each). Also, the role of intracellular calcium mobilization was studied by measuring the phasic response to NA in Ca2+-free N,N-ethylene glycol tetraacetic acid (EGTA) PSS (n=6). RESULTS: The results showed that the contractile responses to either NA or KCl were attenuated (p<0.05) in the presence of the extract. Also, the extract attenuated the contractile response to CaCl2 in the presence of NA or KCl (p<0.05) in the Ca2+-free EGTA PSS, while the phasic response to NA was significantly (p<0.05) diminished. CONCLUSIONS: These results suggest that the vasorelaxant effect of T. procumbens leaf extract may be mediated by a non-specific, non-competitive inhibition of Ca2+ influx as well as by inhibition of Ca2+ mobilization from intracellular stores. This implies that it may contain vasorelaxant agents that may have calcium antagonistic potential.

Mechanisms of anticonvulsant and sedative actions of the ethanolic stem-bark extract of Ficus sur Forssk (Moraceae) in rodents.

Ficus sur Forssk (Moraceae) is used in traditional African medicine in the treatment of epilepsy, pain and inflammations. Anticonvulsant activity was investigated using picrotoxin (PTX), strychnine (SCN), isoniazid (INZ), pentylenetetrazole (PTZ) and N-methyl-D-aspartic acid NMDA models of convulsion. The phytochemical analysis of the extract revealed the presence of flavonoids, saponins, tannins, alkaloids and anthraquinone. Oral administration of Ficus sur, 1 h before intraperitoneal injection of chemical convulsants significantly (p < 0.05) delayed the onset and prolonged the duration of convulsions in PTX, SCN, INZ, PTZ and NMDA-induced seizures. However, the anticonvulsant activity of the ethanolic extract of Ficus sur was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist), cyproheptadine (5-HT2 receptor antagonist) and L-NNA (nitric oxide synthase inhibitor) in picrotoxin-induced convulsion. The data obtained suggest that ethanol extract of Ficus sur possessed significant anticonvulsant effect, thereby confirming the traditional uses of Ficus sur in the treatment of epilepsies; mechanisms of which could involve interaction with GABAergic, glycinergic, serotonergic and glutaminergic system barks.

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.

Toxicological assessment of the aqueous root extract of Sanseviera liberica Gerome and Labroy (Agavaceae).

The aqueous root extract of Sanseviera liberica (SL) is used in African folklore medicine for ailments including chronic pain, inflammatory conditions, and convulsive disorders. Because of the potential for long-term uses, the study investigated the acute and subchronic toxicity patterns of the plant. Acute toxicity tests were carried out in mice, and the median lethal dose was estimated. Subchronic (52 days) studies were conducted in rats with oral daily doses of 80, 400 and 2000 mg/kg. Parameters observed for at the end of chronic tests included changes in body and vital organ weights, mortality, haematological, biochemical, hepatic and male reproductive effects. SL did not produce any visible toxicities or mortality with oral doses up to 20 g/kg within 14 days of single treatment, but i.p. administration caused mortalities with LD(50) of 668.3+/-47.6 mg/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. No significant change in the weight of the kidney, liver, heart and spleen, but at 400mg/kg, a significant reduction in weight of the lungs was recorded. Significant increases in the weight of testes, sperm count and motility was produced. There were no changes in the sperm head and tail abnormalities, but significant increases in the percentage normal sperm cells. Biochemical parameters like the AST and ALT were not affected, but significant increase in ALP and uric acid levels, at 2g/kg, was detected. Significant increase and decrease in RBC and WBC were recorded, respectively, but no changes in levels of PCV and Hb. Results indicate that oral doses of SL are relatively safe in rats; however, assessment of hepato-biliary function should be done during chronic use in humans.

Sedative and anticonvulsant activities of the aqueous root extract of Sanseviera liberica Gerome & Labroy (Agavaceae).

The central nervous system (CNS) depressant and anticonvulsant activities of the aqueous root extract of Sanseviera liberica (ASL) were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behaviour for sedation tests, and strychnine, picrotoxin, bicuculline and pentylenetetrazole-induced convulsions in mice. ASL (100-400mg/kg, p.o.), like chlorpromazine HCl (1mg/kg, i.m.), produced a dose-dependent prolongation of pentobarbitone sleeping time and suppression of exploratory behaviour. ASL (100 and 200mg/kg) produced dose-dependent and significant (P<0.05) increases in onset to clonic and tonic convulsions, and at 400mg/kg, showed complete protection against seizures induced by strychnine, picrotoxin and bicuculline, but not with pentylenetetrazole. ASL up to 10 g/kg, p.o. did not produce death, but i.p. treatment produced mortalities with LD(50) of 668.3+/-47.6 mg/kg. Preliminary phytochemical investigations of ASL revealed the presence of carbohydrates, alkaloids, saponins, reducing sugars and oils. The results indicate that ASL has sedative and anticonvulsant activities, therefore, justifying its use in traditional African medicine.

Protective effects of Zingiber officinale (Zingiberaceae) against carbon tetrachloride and acetaminophen-induced hepatotoxicity in rats.

The effect of the ethanol extract of the rhizome of Zingiber officinale was tested against carbon tetrachloride (CCl(4)) and acetaminophen-induced liver toxicities in rats. Increases in serum and liver marker enzymes such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase as well as sorbitol and glutamate dehydrogenases were produced in normal rats that were not pretreated with the extract. However, extract-pretreated rats attenuated in a dose-dependent manner, CCl(4) and acetaminophen-induced increases in the activities of ALT, AST, ALP, LDH and SDH in the blood serum. The protective effect of the extract on CCl(4) and acetaminophen-induced damage was confirmed by histopathological examination of the liver. These results indicate that the oil from the rhizome of Zingiber officinale could be useful in preventing chemically induced acute liver injury.

Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphia nitida AFZEL.

The sedative, anxiolytic and muscle-relaxant effects of the ethyl acetate leaf extract of Baphia nitida (BN) was investigated in intact mice, using the hole-board head-dip test for exploratory behavioural effect, elevated plus maze (EPM) and Y-maze (YM) models of anxiety; chimney, inclined screen, traction and climbing tests for muscle-relaxant effects. In each of these tests, BN (100-400mg/kg, p.o.), diazepam (1mg/kg, i.p.) or distilled water (10ml/kg, p.o.) was administered, 30 or 60min before performing the tests in mice. For exploratory behavioural test, number of head-dip within 15min was counted. For EPM and YM tests, the cumulative time spent in open and closed arms was recorded within 5min. In the muscle-relaxant tests, mice were subjected to modified models such as chimney, inclined screen, traction and climbing tests. BN produced a significant (P<0.05) dose-related decrease in exploratory behaviour in the head-dip test and prolongation of cumulative time spent in open arms of both EPM and YM. BN did not show any significant effect in the chimney and traction tests, but produced significant, dose-dependent muscle relaxation in the inclined screen and climbing tests. Furthermore, BN (200-1200microg/ml) non-competitively shifted the curves of acetylcholine contractions of the toad Rectus abdominis muscle to the right. Oral doses of BN (0.1-20g/kg) did not produce mortality, but the LD(50) when given intraperitoneally, was 645.65mg/kg. Results suggest that the leaf extract of Baphia nitida has sedative, anxiolytic and skeletal muscle-relaxant effects and support its neurosedative use in traditional African medicine.