Danielle Claude Bilanda

Antihypertensive and antioxidant effects of Allanblackia floribunda Oliv. (Clusiaceae) aqueous extract in alcohol- and sucrose-induced hypertensive rats.

AIM OF THE STUDY Allanblackia floribunda Oliv. (Clusiaceae), an evergreen tree of the rain-forest has long been used in traditional African medicine to treat hypertension. The aim of this study was to evaluate the protective effect of Allanblackia floribunda aqueous extract on alcohol- and sugar-induced hypertension in rats. MATERIAL AND METHODS Alcohol-induced hypertensive rats (AHR) were obtained by oral administration of ethanol (3g/kg/day) while sucrose (5, 6 and 7% in drinking water) was used for sucrose-induced hypertensive rat (SuHR). Both models of animals concomitantly received either aqueous extract (200 or 400mg/kg; p.o.) or nifedipine (10mg/kg; p.o.) all along the 8 weeks of experiment. Blood pressure and heart rate were measured using the direct cannulation method. The effects of the plant extract on lipid profile, oxidative stress markers, as well as on kidney and liver functions were evaluated at the end of the treatment by the colorimetric method. RESULTS At the doses of Allanblackia floribunda (200 and 400mg/kg/day) significantly prevented (21.74; 26.65% and 11.71; 24.58% of reduction) the increase in mean blood pressure on AHR and SuHR, respectively. Administration of the plant extract at the dose of 400mg/kg led to the prevention of total cholesterol (42.82%), HDL-cholesterol (36.59%) and triglycerides (9.67%) increase in serum lipid in AHR as compared to the untreated AHR. In SuHR, the extract significantly prevented the high concentrations of total cholesterol (44.08%) and triglycerides (33.05%) induced by sucrose treatment as compared to the untreated SuHR, without affecting that of HDL-cholesterol. Allanblackia floribunda (200 and 400mg/kg) also prevented the increase in atherogenic index by 54.45 and 42.94% in AHR and by 23.70 and 44.32% in SuHR, respectively. Allanblackia floribunda (400mg/kg) prevented the increase in bilirubine (19.59 and 16.56%), urea (33.36 and 28.2%), ALT (29.55 and 33.09%) and AST (36.28 and 37.12%) of AHR and SuHR, respectively. Treatment with plant extract significantly prevented the increase of superoxide dismutase (SOD), malondialdehyde (MDA) and catalase and the decrease of reduced glutathione (GSH) concentration in aorta, heart, kidney and liver of AHR and SuHR. CONCLUSION These results demonstrate that the aqueous extract of Allanblackia floribunda can prevent alcohol- and sugar-induced hypertension and oxidative stress in rats. These findings could therefore justify its use in traditional medicine.

The aqueous extract of Terminalia superba (Combretaceae) prevents glucose-induced hypertension in rats☆

AIM OF THE STUDY The stem bark of Terminalia superba (Combretaceae) (TS) is used in traditional Cameroonian medicine as antihypertensive remedy. The aim of this study was to investigate the hypotensive and the antihypertensive effects of the aqueous extract of the stem bark of Terminalia superba. MATERIALS AND METHODS Hypertension was obtained in rats by oral administration of 10% D-glucose for 3 weeks. The acute effects of Terminalia superba were studied on blood pressure (BP) and heart rate (HR) after intravenous administration in normotensive rats (NTR) and glucose hypertensive rats (GHR). The antihypertensive effects were studied after oral administration of the extract (50 and 100 mg/kg/day) or nifedipine (10 mg/kg/day) for 3 weeks. At the end of the experiment, BP and HR were measured and reduced glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) activity levels were measured in heart, aorta, liver and kidney. RESULTS Intravenous administration of the aqueous extract of Terminalia superba induced a significant hypotensive response without any change in HR. The hypotensive effect of the extract was unaffected by atropine or propranolol but decreased by reserpine (5 mg/kg) and yohimbine (0.1 mg/kg). In addition, the oral administration of the extract significantly prevented the rise in BP in glucose-hypertensive rats. Finally, the treatment with plant extract significantly blunted the decrease in GSH and the increase in MDA levels associated with hypertension, and significantly prevents the increase in aortic SOD activity. CONCLUSIONS The present study demonstrates that the aqueous extract of the stem bark of Terminalia superba exhibits hypotensive and anti-hypertensive properties that are, at least in part, related to a withdrawal of sympathetic tone and to an improvement of the antioxidant status, respectively. Overall data validate the use of Terminalia superba as antihypertensive therapy in traditional medicine.

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats.

ETHNOPHARMACOLOGICAL RELEVANCE The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties. MATERIALS AND METHODS Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration. RESULTS Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity. CONCLUSION The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This antihypertensive activity is associated with an improvement of antioxidant status. Overall, results justify and support the use of Kalanchoe pinnata as antihypertensive medicine.

Mineral constituents and toxicological profile of Jateorhiza macrantha (Menispermaceae) aqueous extract

ETHNOPHARMACOLOGICAL RELEVANCE Jateorhiza macrantha is a medicinal plant used in popular medicine to treat several diseases, including cardiovascular disorders. To date, there is no documented report available on the toxicological profile of this medicinal plant. THE AIM OF THE STUDY The present study was carried out to investigate the mineral content and the safety of the oral administration of the leaf aqueous extract of Jateorhiza macrantha in mice. MATERIALS AND METHODS The presence of Ca, Mg, K, Na, Cu, Mn, Fe and Zn in the extract was analyzed using Atomic Absorption Spectrophotometer. In the acute toxicity study, Male and female Balb-C mice were administered single doses of 2.5 and 5 g/kg of body weight by gavage, and were monitored for 7 days. In the subacute toxicity study, the extract was administered by gavage at doses of 150, 300 and 600 mg/kg body weight daily for 6 weeks to mice (8 mice/dose/sex). After this period of treatment, 5 mice per sex and per group were sacrificed. The rest of animals per group were observed without any treatment for 2 weeks. After the treatments, some biochemical and hematological parameters were analyzed. RESULTS Our findings indicate the presence of all mineral elements tested. Acute study indicates no signs of toxicity at the doses used. The LD50 value is >5.00 g/kg body weight, since there was no death registered at that dose. In subacute study, hematological and biochemical parameters showed a significant decrease in platelet and significant increases in ALT and AST in both sexes and creatinin levels only in male suggesting that some compounds of the plant extract were responsible of disturbances of hematopoiesis, liver and kidney functions. CONCLUSIONS Our results show that Jateorhiza macrantha acute toxicity towards animals is very low. However, in subacute administration, this extract induces slight injuries on hematopoiesis, liver and kidney functions, suggesting its use with caution.

Safety assessment of the aqueous extract of the flowers of Nymphaea lotus Linn (Nymphaeaceae): Acute, neuro- and subchronic oral toxicity studies in albinos Wistar rats

Abstract Background Nymphaea lotus Linn (N. lotus) is a medicinal plant widely used in Cameroon popular medicine, to treat neuropsychiatric conditions, male sexual disorders or as food supplement. However, scientific data on the pharmacotoxic profile of this plant are not available. The safety of N. lotus was assessed in acute, neuro- and subchronic toxicity studies by following the OECD guidelines. Effectively, no data have been published until now in regard to its safety on the nervous system. Methods Aqueous extract of N. lotus at doses of 200, 400 and 600 mg/kg body weight (BW) was evaluated for nitrites contents and orally administered to rats daily for 28 days (5 male, 5 female per group). The control group received distilled water (10 mL/kg) and a satellite group was used to observe reversal effects. Neurotoxicity of the plant was determined using open field test for motor coordination, ataxia and gait analysis. Clinical signs and state of livelihood were recorded during the 24 h, then for 28 days of treatments. At the end of 28-day period, animals were anesthetized and decapitated. The whole brain was homogenized for neurobiochemical analysis. Blood samples were collected with or without anticoagulant for hematological examinations and serum analysis. Specimens of liver, kidney, testis, ovaries, and brain were fixed in 10 % formalin and processed for histopathological examinations. Results Our findings indicate dose-dependent elevation of nitrites contents in the flowers aqueous extract of N. lotus. Acute toxicity study revealed no signs of toxicity neither at the dose 2,000 mg/kg nor at 5,000 mg/kg. Thus the LD50 value of aqueous extract of N. lotus flowers is superior to 5,000 mg/kg. The repeated administration of N. lotus during 28 days, induced no signs of neurobehavioral changes in male, but female rats exhibited dose-dependent response in the open field test, suggesting sex and dose-relative psychotropic effects of N. lotus. The evaluation of neurobiochemistry revealed consistent rise of brain cholesterol by 44.05 %; 158.10 % and 147.62 % respectively in male rats treated with the doses of 200, 400 and 600 mg/kg. In female rats, these levels were significantly increased (p<0.001) only at the dose of 600 mg/kg compared to control. This trend persisted after 14 days withdrawal. Brain potassium and calcium concentrations were increased in all rats compared to their respective control receiving distilled water, suggesting transmembrane current stabilizing properties of brain cells by our extract. Further, serum biochemical analysis demonstrated that 28-day administration of N. lotus flowers increased depending on the dose and sex, the levels of serum urea, proteins, creatinine and bilirubin and reduced γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) activities. These results suggest liver alterations that are endowed by lower liver relative weight and histology damages observed in female rats treated with the dose of 600 mg/kg of our extract. We also observed a rise in the low-density lipoprotein (LDL) fraction and AI of male rats undergoing N. lotus treatment. In female rats, the latter remains unaltered, confirming the dose- and sex-dependent response of our extract. The levels of white blood cells (WBC) and granulocytes were higher in male irrespective to their control, revealing stimulatory properties of the male hematopoietic system. Such variations (sex- and dose-dependent) are without biological relevance for the majority of the biochemical parameters evaluated, indicating a wide margin of safety for the traditional use of N. lotus. The alkaloids, nitrites and phytosterols contained in N. lotus flowers extract may probably account for its neuroprotective, anti-oxidant, and immunoboosting properties. Conclusions N. lotus do not possesses neurotoxicity but is able to induce behavioral changes in rats. Therefore, the application of this plant as either drug or supplementary food should be carefully considered.