Potential Curative Effects of Aqueous Extracts of Cissus quadrangularis (Vitaceae) and Jatropha gossypiifolia (Euphorbiaceae) on Acetaminophen-Induced Liver Injury in Mice.

Background: Acetaminophen-induced liver injury remains a significant public health problem because available treatments are limited due to their adverse effects. Medicinal plants, which are an important source of bioactive molecules, could be an alternative treatment for liver disease. Objective: This study was designed to investigate the curative effect of aqueous extracts of Cissus quadrangularis (Vitaceae) and Jatropha gossypiifolia (Euphorbiaceae) on acetaminophen-induced liver injury in mice. Methods: Mice were divided into groups and treated with distilled water, silymarin (50 mg/kg), a reference hepatoprotective agent, and aqueous extracts of C quadrangularis and J gossypiifolia (50 and 100 mg/kg, PO, respectively). These substances were given as a single daily dose 4 hours after acetaminophen administration (300 mg/kg, PO) for 2 days. Mice were humanely put to death 24 hours after the last dose and serum alanine aminotransferase and aspartate aminotransferase activities, total bilirubin and protein levels, reduced glutathione, superoxide dismutase, malondialdehyde, catalase, and nitrite tissue levels were assessed. Histology of the livers of the mice was performed by hematoxylin and eosin staining. Results: Acetaminophen administration induced a significant (P < 0.05) mean (SEM) body weight loss (-14.45% [5.92%]), a significant elevation of alanine aminotransferase activity (15.08%), total protein and bilirubin levels (25.80%), and a significant (P < 0.05) increase in liver superoxide dismutase (67.71%), catalase (63.00%), glutathione (40.29%), malondialdehyde (30.67%), and nitrite levels compared with the control group. In curative treatment, C quadrangularis and J gossypiifolia (50 and 100 mg/kg) significantly (P < 0.05) reduced mean (SEM) body weight loss (16.67% [7.16%] and 1.25% [0.51%], respectively), serum alanine aminotransferase activity (17.62% and 11.14%, respectively), bilirubin level (29.62% and 49.14%, respectively) compared with acetaminophen group, and J gossypiifolia normalized serum total protein level. Both extracts significantly (P < 0.05) reduced the levels of glutathione and malondialdehyde and normalized that of nitrite, superoxide dismutase, and catalase compared with the acetaminophen group. Hepatocyte necrosis and inflammatory cell infiltration were remarkably reduced by the plant extracts. Conclusions: The results obtained are evidence in favor of the development of a formulation based on the extracts of these plants against liver diseases.

Hepatoprotective and in vivo antioxidant effects of granulometric classes and decoction of Ficus dicranostyla Mildbread leaves powders against carbon tetrachloride-induced hepatotoxicity in Wistar rats.

Ficus dicranostyla is a plant from the Moraceae family commonly used in African countries for its nutritional value and its believed medicinal properties. Its antioxidant in vitro capacity and its richness in phenolic compounds have been previously demonstrated. This work aimed at evaluating the hepatoprotective and in vivo antioxidant activities of different granulometric fractions of the F. dicranostyla leaves against carbon tetrachloride-induced hepatotoxicity in rats. Powdery fractions (<125, 250-125, and ≥250 µm), and the unsieved powder, obtained from the F. dicranostyla leaves were water-dissolved and given orally to rats at the same dose (250 mg/kg body weight) before administering carbon tetrachloride intraperitoneally (1 mL/Kg bw). The lipid status parameters (total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol), hepatic toxicity through aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in blood plasma, and antioxidant status by measuring the malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in liver homogenate were performed. The activities of all parameters registered a significant (p < .05) alteration in CCl4-treated rats, which were significantly recovered toward an almost normal level in coadministered with Ficus dicranostyla leaf powder samples in a particle size-dependent manner. Results suggest that the smaller particle size of the powder fraction, as well as the decoction powder of Ficus dicranostyla, may be used as hepatoprotective and antioxidant agents.

The extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum mixture ameliorates diabetes-associated cognitive dysfunction.

Diabetes-associated cognitive dysfunction is linked to chronic hyperglycemia, oxidative stress, inflammation, cholinergic dysfunction, and neuronal degeneration. We investigated the antidiabetic and neuroprotective activity of a mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) in type 2 diabetic (T2D) rat model-induced memory impairment. Fructose (10%) and streptozotocin (35 mg/kg) were used to induce T2D in male Wistar rats. Diabetic animals received distilled water, metformin (200 mg/kg), or SNP mixture (75, 150, or 300 mg/kg). HPLC-MS profiling of the mixture was performed. Behavioral testing was conducted using the Y-maze, NORT, and Morris water mazes to assess learning and memory. Biochemical markers were evaluated, including carbohydrate metabolism, oxidative/nitrative stress, pro-inflammatory markers, and acetylcholinesterase activity. Histopathological examination of the pancreas and hippocampus was also performed. Fructose/STZ administration resulted in T2D, impaired short- and long-term memory, significantly increased oxidative/nitrative stress, pro-inflammatory cytokine levels, acetylcholinesterase activity (AChE), hippocampal neuronal loss and degeneration in CA1 and CA3 subfields, and neuronal vacuolation in DG. SNP mixture at 150 and 300 mg/kg significantly improved blood glucose and memory function in diabetic rats. The mixture reduced oxidative/nitrative stress and increased endogenous antioxidant levels. It also reduced serum IL-1ß, INF-γ and TNF-α levels and ameliorated AChE activity. Histologically, SNP protected hippocampus neurons against T2D-induced neuronal necrosis and degeneration. We conclude that the aqueous extract of SNP mixture has antidiabetic and neuroprotective activities thanks to active metabolites identified in the plant mixture, which consequently normalized blood glucose, protected hippocampus neurons, and improved memory function in diabetic rats.

The Aqueous Extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum Mixture Protects Striatal Neurons and Movement-Associated Functionalities in a Rat Model of Diabetes-Induced Locomotion Dysfunction.

Among the many complications of type 2 diabetes (T2D), locomotor disorders have been poorly studied and understood. Therefore, no disease-modifying treatment is usually considered. The study aimed to investigate the effect of the aqueous extract of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) mixture on locomotor activity in fructose/streptozotocin-induced diabetic rats. T2D was induced by 10% fructose orally (6 weeks) and streptozotocin (STZ, 35 mg/kg, i.v.) in 25 male rats. Diabetic animals received distilled water, metformin (200 mg/kg), or the aqueous extract of the SNP mixture (75, 150, or 300 mg/kg). A 10-minute open field test was performed in diabetic rats (glycemia: 126 and 350 mg/dL) to assess locomotor activity before and after treatment. A group of 5 normal rats (NC) served as controls throughout the study. Rats were sacrificed, and the striatum was removed for biochemical and histological studies. In untreated diabetic rats, fructose/STZ administration resulted in hyperglycemia that altered locomotor function as characterized by increased freezing time, decreased mobility time, number of lines crossed, and total travel time compared to NC. MDA, TNF-α, INF-γ, and nitrite levels were elevated in the striatum of diabetic rats, while catalase activity and GSH levels were decreased, indicating oxidative stress and neuroinflammatory changes. In untreated diabetic rats, the microstructure of the HE-stained striatum revealed lipid vacuolation (hydropic degeneration) of the parenchyma, indicating a loss of neuronal integrity. The locomotor dysfunction was significantly improved by the aqueous extract of the SNP mixture, both biochemically and histologically. As a result, our findings support the mixture's ability to correct diabetes-related locomotion disorders as a glucose-lowering product and antioxidant, anti-inflammatory, and neuroprotective agent. These results justify the use of the aqueous extract of a combination of these three plants to manage diabetes and neuroinflammatory complications in Northern Cameroon.

Chromolaena odorata (L.) R. M. King and H. Robinson Leaves Aqueous Extract Improves the Femoral Head in Ethanol-Induced Osteonecrosis in Rats.

Chronic alcohol consumption damages bone formation and causes bone pathology, including osteonecrosis of the femoral head. The aim of this work was to evaluate the effects of the leaf aqueous extract of Chromolaena odorata (C. odorata) on the femoral head in ethanol-induced osteonecrosis in rats. Animals received alcohol (40°) at 3 g/kg for 12 weeks. A group of animals were sacrificed to attest to the instalment of osteonecrosis by using histopathological analysis. The remaining animals received alcohol concomitantly with the plant extract (150, 300, or 600 mg/kg) or diclofenac (1 mg/kg) for 28 additional days. At the end of the experimental period, biochemical parameters including total cholesterol, triglycerides, calcium, alkaline phosphatase (ALP), reduced glutathione (GSH), malondialdehyde (MDA), nitrite, superoxide dismutase (SOD), and catalase activities were measured. Histopathological and histomorphometry analyses of femurs were also assessed. The administration of alcohol, irrespective of the experimental period, induced a significant increase in total cholesterol (p < 0.05) and triglyceride (p < 0.01) and a decrease in ALP (p < 0.05) and calcium (p < 0.05-p < 0.001) levels. Intoxicated animals showed an alteration in oxidative stress parameters accompanied by a significant drop in bone cortical thickness and density with necrosis and marked bone resorption. The concomitant administration of the plant with ethanol reversed the alcohol-induced bone defect, characterized by the improvement of the lipid profile (p < 0.001), bone calcium concentration (p < 0.05), bone ALP activity (p < 0.001), oxidative stress parameters, improved cortical bone thickness (p < 0.01), and bone density (p < 0.05). These results are supported by the absence of bone resorption with an obvious effect at a dose of 300 mg/kg. The pharmacological effect of the extract on ethanol-induced osteonecrosis of the femoral head is probably due to its osteogenic, hypolipidemic, and antioxidant properties, justifying its use in Cameroonian folk medicine for articulation and bone pain management.

Curative anti-typhoid effect of Detarium microcarpum Guill. & Perr. (Leguminosae) hydroethanolic extract root bark based-on in vivo and molecular docking analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Detarium microcarpum is used to treat typhoid fever, a major public health problem, by indigenous population in Africa. Though its preventive activities have been documented, the curative effect is still to be confirmed. AIM OF THE STUDY: This study aimed at evaluating the curative effects of the hydroethanolic extract of Detarium microcarpum root bark on Salmonella typhimurium-induced typhoid in rat and exploring the in-silico inhibition of some bacterial key enzymes. STUDY DESIGN: In vitro antioxydant, in vivo antisalmonella of the extract and in silico molecular docking assay on the isolated compounds were carried out to explore the anti-salmonella effects of Detarium microcarpum. MATERIAL AND METHODS: The in vitro antioxidant properties of the extract were evaluated using DPPH, ABTS and FRAP tests. The anti-salmonella activity of the extract was assessed through feacal sample from Salmonella typhimurium-infected rat cultured in Salmonella-Shigella agar (SS agar) medium. The affinity of isolated compounds (Rhinocerotinoic acid and Microcarposide) from the extract were performed on four key enzymes (Adenylosuccinate lyase, Acetyl coenzyme A synthetase, Thymidine phosphorylase and LuxS-Quorum sensor) using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: Crude extract of D. microcarpum root bark showed variable activities on DPPH (RSa50: 6.09 ± 1.04 µg/mL), ABTS (RSa50: 24.46 ± 0.27), and FRAP (RSa50: 23.30 ± 0.23). The extract at all the doses exhibited significant healing effect of infected rats, with the complete clearance. The extract restored hematological, biochemical and histological parameters closed to the normal control. The molecular docking results indicates that rhinocerotinoic acid and microcarposide present more affinity to the LuxS-Quorum sensor and Acetyl coenzyme A synthetase protein as compared to the others. CONCLUSION: These results demonstrate potent anti-typhoid activities of the hydroethanolic of Detarium microcarpum root bark extract through antioxidant properties and high inhibitory affinity of its compounds on some bacterial key enzymes that justify its use as traditional medicine to typhoid fever.

Acute and Subchronic Toxicity Studies on the Aqueous Extract of the Plant Mixture (Bidens pilosa and Cymbopogon citratus Aerial Parts) in Rat Model.

Bidens pilosa (B. pilosa) and Cymbopogon citratus (C. citratus) are plants used individually or in combination in the traditional treatment of several ailments such as cardiovascular disorders. In order to valorise their traditional use, a toxicological study was conducted on the aqueous extract of the mixture of aerial parts of B. pilosa and C. citratus. The acute and subchronic toxicity studies were conducted according to the OECD 425 and 407 guidelines. Regarding the acute study, the aqueous extract of the mixture of B. pilosa and C. citratus 50 : 50 (2000 and 5000 mg/kg) was administered once to rats of both sexes. In the subchronic study, the aqueous extract of the mixture of B. pilosa and C. citratus (200, 400 and 800 mg/kg) was administered once daily to rats for 28 days. The aqueous extract of the mixture of B. pilosa and C. citratus (2000 and 5000 mg/kg) did not cause death and did not induce any apparent sign of toxicity during the 14 days of observation. The DL50 of the extract is therefore greater than 5000 mg/kg. Taken daily for 28 days, the extract had no significant effect on selected parameters (creatinine, AST, ALT, urea, and uric acid) of renal and hepatic function, as well as on the number of some blood cells. However, the aqueous extract of the mixture of B. pilosa and C. citratus (200 and 400 mg/kg) caused a significant (p < 0.05; p < 0.001, respectively) decrease in creatinine levels in male rats as compared to normal control animals. In females, the aqueous extract of the mixture of B. pilosa and C. citratus (200 and 400 mg/kg) resulted in a significant (p < 0.05) increase in total cholesterol levels as compared to normal control animals. The study showed that the aqueous extract of the mixture of B. pilosa and C. citratus has a low toxicity and does not cause any injury to the liver, kidney, lungs, or spleen.

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways.

Parkia biglobosa (Jacq.) R. Br. (Fabaceae) is a widely distributed tree, used in traditional medicine to treat amebiasis, hookworm infection, ascariasis, asthma, sterility, dental pain, headaches, cardiac disorders, and epilepsy. To date, no study on the effect of an aqueous extract of P. biglobosa on epileptogenesis and associated neuropsychiatric disorders has been undertaken. Therefore, this study aimed to investigate antiepileptogenic-, antiamnesic-, and anxiolytic-like effects of an aqueous extract of P. biglobosa using pentylenetetrazole (PTZ)-induced kindling in mice. Animals were divided into six groups of eight mice each. Thus, a PTZ group received distilled water (10 ml/kg, per os), a positive control group received sodium valproate (300 mg/kg, p.o.), and three test groups received the aqueous extract of P. biglobosa (80, 160, and 320 mg/kg, p.o.).In addition, a control group of eight mice receiving distilled water (10 ml/kg, p.o.) was formed. The treatments were administered to mice, 60 min before administration of PTZ (20 mg/kg, i.p.). These co-administrations were performed once daily, for 22 days. The number and duration of seizures (stages 1, 2, 3, and 4 of seizures) exhibited by each mouse were assessed for 30 min during the treatment period. Twenty-four hours following the last administration of the treatments and PTZ, novel object recognition and T-maze tests were performed to assess working memory impairment in mice, while the open field test was performed to assess anxiety-like behavior. After these tests, the animals were sacrificed, and the hippocampi were collected for biochemical and histological analysis. During the period of PTZ-kindling, the extract at all doses completely (p < 0.001) protected all mice against stages 3 and 4 of seizures when compared to sodium valproate, a standard antiepileptic drug. The extract also significantly (p < 0.001) attenuated working memory impairment and anxiety-like behavior. In post-mortem brain analyses, the extract significantly (p < 0.001) increased γ-aminobutyric acid (GABA) level and reduced oxidative stress and inflammation. Histological analysis showed that the aqueous extract attenuated neuronal degeneration/necrosis in the hippocampus. These results suggest that the extract is endowed with antiepileptogenic-, anti-amnesic-, and anxiolytic-like effects. These effects seem to be mediated in part by GABAergic, antioxidant, and anti-inflammatory mechanisms. These results suggest the merit of further studies to isolate the bioactive molecules responsible for these potentially therapeutically relevant effects of the extract.

An aqueous macerate of Ziziphus jujuba reduces long-term spatial memory impairment in D-galactose treated rats: role of anti-inflammatory pathways.

Pharmacological treatments against Alzheimer disease provide only symptomatic relief and are associated with numerous side effects. Previous studies showed that a concoction of Ziziphus jujuba leaves possesses anti-amnesic effects in scopolamine-treated rats. More recently, an aqueous macerate of Z. jujuba leaves has been shown to reduce short-term memory impairment in D-galactose-treated rats. However, no study on the effect of an aqueous macerate of Z. jujuba on long-term memory impairment was performed. Therefore, this study evaluates the effect of an aqueous macerate of Z. jujuba on long-term spatial memory impairment in D-galactose-treated rats. Long-term spatial memory impairment was induced in rats by administering D-galactose (350 mg/kg/day, s.c.), once dailyfor 21 days. On the 22nd day, the integrity of this memory was assessed using the Morris water maze task. Rats that developed memory impairment were treated with tacrine (10 mg/kg, p.o.), or aspirin (20 mg/kg, p.o.), or extract (41.5, 83, and 166 mg/kg, p.o.), once daily, for 14 days. At the end of the treatment, memory impairment was once more assessed using the same paradigm. Animals were then euthanized, and some pro-inflammatory cytokine markers were analyzed in the hippocampus or blood. The extract at all doses significantly reduced the latency to attain the platforming of the water maze test. The extract (83 mg/kg) also increased the time spent in the target quadrant during the retention phase. The extract markedly reduced the concentration of pro-inflammatory cytokine markers in the hippocampus and blood. Together, these results suggest that this aqueous extract Z. jujuba reduces long-term spatial memory impairment. This effect may be mediated in part by its anti-inflammatory activity.

An aqueous extract of Khaya senegalensis (Desv.) A. Juss. (Meliaceae) prevents seizures and reduces anxiety in kainate-treated rats: modulation of GABA neurotransmission, oxidative stress, and neuronal loss in the hippocampus.

Ethnopharmacological relevance: Temporal lobe epilepsy is the most common form of drug-resistant epilepsy. Therefore, medicinal plants provide an alternative source for the discovery of new antiepileptic drugs. Aim of the study: This study was aimed at investigating the antiepileptic- and anxiolytic-like effects of an aqueous extract of Khaya senegalensis (K. senegalensis) in kainate-treated rats. Methods: Seventy-two rats received a single dose of kainate (12 mg/kg) intraperitoneally. Those that exhibited two hours of status epilepticus were selected and monitored for the first spontaneous seizure. Then, animals that developed seizures were divided into 6 groups of 8 rats each and treated twice daily for 14 days as follows: negative control group received per os (p.o.) distilled water (10 ml/kg); two positive control groups received either sodium valproate (300 mg/kg, p.o.) or phenobarbital (20 mg/kg, p.o.); and three test groups received different doses of the extract (50, 100, and 200 mg/kg, p.o.). In addition, a group of 8 normal rats (normal control group) received distilled water (10 ml/kg, p.o.). During the treatment period, the animals were video-monitored 12 h/day for behavioral seizures. At the end of the treatment period, animals were subjected to elevated plus-maze and open field tests. Thereafter, rats were euthanized for the analysis of γ-aminobutyric acid (GABA) concentration, oxidative stress status, and neuronal loss in the hippocampus. Results: The aqueous extract of K. senegalensis significantly reduced spontaneous recurrent seizures (generalized tonic-clonic seizures) and anxiety-like behavior compared to the negative control group. These effects were more marked than those of sodium valproate or phenobarbital. Furthermore, the extract significantly increased GABA concentration, alleviated oxidative stress, and mitigated neuronal loss in the dentate gyrus of the hippocampus. Conclusion: These findings suggest that the aqueous extract of K. senegalensis possesses antiepileptic- and anxiolytic-like effects. These effects were greater than those of sodium valproate or phenobarbital, standard antiepileptic drugs. Furthermore, these effects are accompanied by neuromodulatory and antioxidant activities that may be related to their behavioral effects. These data justify further studies to identify the bioactive molecules present in the extract for possible future therapeutic development and to unravel their mechanisms of action.

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection.

BACKGROUND: One of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice. METHODOLOGY/PRINCIPAL FINDINGS: Two months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-ß gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2. CONCLUSION/SIGNIFICANCE: This study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.

Preventive Potential of the Aqueous Extract of the Mixture of Bidens pilosa (Asteraceae) and Cymbopogon citratus (Poaceae) Aerial Parts on Hypertension Induced by a Chronic Salt and Alcohol Consumption on the Rats.

High blood pressure (HBP) is currently one of the main risk factors for cardiovascular and kidney diseases. Nowadays, populations make extensive use of alternative medicine for their health problems. Bidens pilosa (B. pilosa) and Cymbopogon citratus (C. citratus) are used individually in the traditional treatment of cardiovascular disorders. This study assessed the effects of the mixture of these two plants aqueous extract on HBP in rats. Male rats (42) were divided into 7 groups of 6 rats each. Normotensive rats received only distilled water and formed group 1. The other animals received ethanol + salt preceded by distilled water (10 mL/kg; group 2) and spironolactone (10 mg/kg; group 3); the aqueous extracts of the mixture (100 and 200 mg/kg; groups 4 and 5) isolated plants B. pilosa (200 mg/kg; group 6) and C. citratus (200 mg/kg; group 7). Animals were treated for 7 weeks during which water consumption and urine volume were assessed; then, hemodynamic parameters were recorded, and rats were sacrificed. Serum and some organs (liver, kidney, heart, and aorta) were used to evaluate biochemical parameters. Ingestion of ethanol + salt leads to a significant increase in urinary volume and water intake that were significantly prevented by the extracts from the mixture and isolated plants. Ethanol + salt solution significantly increased the blood pressure, heart rate, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-chol), very-low-density lipoprotein cholesterol (VLDL-chol), atherogenic indices, liver and kidney function parameters, and malondialdehyde (MDA) levels. However, the levels of high-density lipoprotein cholesterol (HDL-chol), albumin, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activity were significantly reduced. The extracts of the mixture and isolated plants significantly prevented all these variations with a more pronounced action for the lowest dose of the mixture on the lipid profile, oxidative stress, and kidney function. These observations confirm the beneficial effects of B. pilosa and C. citratus to manage hypertension.

In Vitro Assessment of the Cercaricidal Activity of Sida acuta Burm. F. and Sida rhombifolia Linn. (Malvaceae) Hydroethanolic Extracts, Cytotoxicity, and Phytochemical Studies.

Despite the global efforts, schistosomiasis remains a public health problem in several tropical and subtropical countries. One of the major challenges in the fight against schistosomiasis is the interruption of the parasite life cycle. Here, we evaluated the anticercarial, cytotoxicity, and phytochemical profiles of Sida acuta (HESa) and Sida rhombifolia (HESr) hydroethanolic extracts (Malvaceae). Schistosoma mansoni cercaria was collected from fifteen Biomphalaria pfeifferi-infected snails. Twenty-five cercariae were incubated in duplicate with different concentrations (31.25-1,000 µg/mL) of HESa or HESr. The cercaria viability was monitored at 30 min time intervals for 150 min, and the concentration-response curve of each plant extract was used to determine their respective lethal concentration 50 (LC50). Additionally, the cytotoxicity profile of each plant extract was evaluated on the Hepa 1-6 cell line at a concentration range of 15.625-1,000 µg/mL using the WST-8 assay method and its inhibitory concentration 50 (IC50) was calculated. Moreover, phytochemical characterization of each plant extract was carried out by HPLC-MS. Both extracts exhibited cercaricidal activity in a time- and concentration-dependent manner. At 30 min time point, HESa (LC50 = 28.41 ± 3.5 µg/mL) was more effective than HESr (LC50 = 172.42 ± 26.16 µg/mL) in killing S. mansoni cercariae. Regarding the cytotoxicity effect of both extracts, the IC50 of HESa (IC50 = 109.67 µg/mL) was lower than that of HESr (IC50 = 888.79 µg/mL). The selectivity index was 3.86 and 5.15 for HESa and HESr, respectively. Fifteen compounds were identified from HESa and HESr after HPLC-MS analysis. N-Feruloyltyramine, a polyphenol, and thamnosmonin, a coumarin, were identified in both extracts. HESa and HESr displayed cercaricidal activity and were not toxic on Hepa 1-6 cell line. Based on the selectivity index of these extracts, S. rhombifolia extract could be more effective on S. mansoni cercariae than S. acuta extract. This study could provide baseline information for further investigations aiming to develop plant-based alternative drugs against S. mansoni.

Aqueous Extract from Cinnamomum zeylanicum (Lauraceae) Stem Bark Ameliorates Gentamicin-Induced Nephrotoxicity in Rats by Modulating Oxidative Stress and Inflammatory Markers.

Nephropathies and especially nephrotoxicity have become one of the serious causes of life-threatening conditions because of intensive exposure to xenobiotic whether by environmental pollution or by drug abuse. The present study was undertaken to assess the protective effects of Cinnamomum zeylanicum stem bark aqueous extract (AECZ) on gentamicin-induced nephrotoxicity. AECZ was prepared by maceration in water and tested orally at the doses of 200 and 400 mg/kg/day to prevent gentamicin-induced nephropathies in male Wistar rats. Gentamicin (100 mg/kg/day) was administered for 14 consecutive days by intraperitoneal route, concomitantly with AECZ or silymarin (50 mg/kg/day) used as reference drug. Animal body weight was monitored during the treatment. After the last treatment on the 14th day, animals were sacrificed. Blood was collected for the evaluation of hematological and renal function biomarkers. The homogenate of one kidney was used to assess oxidative stress markers and proinflammatory cytokines, while the other one was fixed in formaldehyde for histopathological studies. Gentamicin decreased body weight, serum total proteins, and calcium level but increased kidneys' relative weight, serum creatinine, urea, and uric acid. Moreover, the levels of reduced glutathione, catalase, and superoxide dismutase activities were decreased, while an increase in malondialdehyde, proinflammatory cytokines (TNF-α, IL-1ß, and IL-6), and nitrites was observed in the negative control group as compared to normal control. Histological analysis of the kidney revealed the presence of tubular necrosis, glomerular degeneration, and macrophage infiltration in the gentamicin-treated group. All these impairment parameters were prevented by AECZ and silymarin treatments. AECZ has a protective effect against gentamicin-induced nephrotoxicity. The antioxidant and anti-inflammatory potentials of this extract may highly contribute to its nephroprotective activity.

Antiamnesic and Neuroprotective Effects of an Aqueous Extract of Ziziphus jujuba Mill. (Rhamnaceae) on Scopolamine-Induced Cognitive Impairments in Rats.

BACKGROUND: Alzheimer's disease is a neurological condition that affects about 44 million people worldwide. The available treatments target symptoms rather than the underlying causes. Ziziphus jujuba (Rhamnaceae) is widely used in traditional Cameroonian medicine to treat diabetes, pain, infections, and dementia. Previous studies reported that Z. jujuba aqueous macerate improves working memory impairment, but no study on the antiamnesic effect of a concoction of Z. jujuba in rats has been performed. Therefore, this study aimed to assess the antiamnesic and neuroprotective effects of an aqueous extract of Z. jujuba on scopolamine-induced cognitive impairments in rats. METHODS: Learning and memory impairments were induced in rats by administering scopolamine (1 mg/kg, i.p.) to 58 rats for 15 days. Rats that developed learning and memory impairments in Morris water maze and Y-maze paradigms were divided into 7 groups (8 rats each) and treated daily for 15 days as follows: the normal control group received distilled water (10 ml/kg, p.o.), the negative control group received distilled water (10 ml/kg, p.o.), positive control groups either received donepezil (1.2 mg/kg, p.o.) or tacrine (10 mg/kg, p.o.), and the three test groups were given the extract (29, 57, and 114 mg/kg, p.o.). At the end of treatments, learning and memory impairments were determined using the same paradigms. Animals were then euthanized, and biochemical parameters of oxidative stress, inflammation, and apoptosis were analyzed in the hippocampus and prefrontal cortex. RESULTS: On the 4th day of the acquisition phase in the Morris water maze, Z. jujuba (29 and 114 mg/kg) reduced (p < 0.001) the latency to reach the platform, while in the retention phase, Z. jujuba (57 and 114 mg/kg) decreased (p < 0.001) the time to reach the platform and increased the time in the target quadrant (p < 0.05) compared to control. Surprisingly, the extract failed to affect spontaneous alternations in the Y-maze. Furthermore, the extract (29, 57, and 114 mg/kg) reversed (p < 0.001) scopolamine-induced oxidative stress, inflammation, and apoptosis. This was supported by the reduction of neuronal alterations in the hippocampus and prefrontal cortex. CONCLUSIONS: Compared to donepezil, a standard drug against Alzheimer's disease, these findings suggest that Z. jujuba extract possesses antiamnesic and neuroprotective effects, and these effects are mediated in part through antioxidant, anti-inflammatory, and antiapoptotic activities. These findings help to explain its use in treating psychiatric disorders in Cameroon's folk medicine.

Ziziphus jujuba (Rhamnaceae) Alleviates Working Memory Impairment and Restores Neurochemical Alterations in the Prefrontal Cortex of D-Galactose-Treated Rats.

Alzheimer's disease is a progressive cognitive dysfunction. However, pharmacological treatments are symptomatic and have many side effects, opening the opportunity to alternative medicine. This study investigated the antiamnesic effect of the aqueous extract of Ziziphus jujuba on D-galactose-induced working memory impairment in rats. Impairment of working memory was induced by subcutaneous (s.c.) injection of D-galactose (350 mg/kg/day) to rats for 21 days. These animals were then subjected to object recognition and Y-maze tests. Rats with confirmed memory impairment were treated per os (p.o.) with tacrine (10 mg/kg), aspirin (20 mg/kg, p.o.), extract (41.5, 83, and 166 mg/kg, p.o.), and distilled water (10 mL/kg, p.o.) daily for 14 days. At the end of the treatments, alteration in working memory was assessed using the above paradigms. Afterward, these animals were euthanized, and cholinergic, proinflammatory, and neuronal damage markers were analyzed in the prefrontal cortex. Rats administered D-galactose and treated with distilled water had impaired working memory (evidenced by decreased time spent on the novel object and discrimination index) and decreased spontaneous alternation in the Y-maze. D-galactose also decreased the levels of acetylcholinesterase and acetylcholine and increased the level of glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and interferon-gamma (IFN-γ). Treatment with the extract (166 mg/kg) reversed the time spent on the novel object and the discrimination index. It equally increased the percentage of spontaneous alternation. Neurochemical analysis revealed that the extract markedly alleviated acetylcholinesterase activity and neuroinflammation. These observations were corroborated by the reduction in neuronal loss. Taken together, these results suggest that Ziziphus jujuba aqueous extract possesses an antiamnesic effect. This effect seems to involve cholinergic and anti-inflammatory modulations. This, therefore, claims using this plant in the treatment of dementia in Cameroon subject to further studies and trials.

Antibacterial and antishigellosis activity of Xylopia staudtii (engl. & diels), Annonaceae.

ETHNOPHARMACOLOGICAL RELEVANCE: Xylopia staudtii is a medicinal plant which fruits are traditionally used in western Cameroon as a spice in the preparation of soups known for their abdominal cramp relieving properties. Often identified as Xylopia africana, its bark is used in the treatment of dysentery in Mont Cameroun localities. This plant could therefore contain active ingredients against intestinal pathogens, including Shigella spp, which are responsible of the deathly dysenteric diarrhoea. AIM OF THE STUDY: This study aims to assess the efficacy of the hydroethanolic extract from Xylopia staudtii bark in immunodepressed mice infected with Shigella flexneri. MATERIALS AND METHODS: Qualitative detection of compounds in the crude extract was done using UPLC-DAD-(HR) ESI-MS analysis in an attempt to link the activity to the chemical composition. The MIC and the MBC of the extract was determined using broth dilution method. Shigellosis was induced by intraperitoneal administration of Shigella flexneri to immunodepressed mice pretreated with streptomycin. These infected mice were then treated with the extract (100, 200 and 400 mg/kg), and reference substances (ciprofloxacin and saline). During the 9 days of treatment, animal morphology, fecal pathology and deaths were recorded. At the end of the treatment period, blood and organs were collected from any surviving animals for hematological, biochemical and histopathological analyses. RESULTS: The extract was found to be significantly active, with a bactericidal effect against Shigella and a bacteriostatic effect against Escherichia coli. It was able to reduce and stop the faecal pathology caused by the infection in mice, as well as the rate of deaths which was brought to zero (0) in animal treated at 400 mg/kg. The bacteria load in faeces was reduced by 100% in animal treated at 400 mg/kg. Xylopia staudtii extract elicited anti-inflammatory properties by reducing MPO activity and Lcn2 intestinal level. It also prevents damages in the intestinal tissue and the shortening of colon which characterise Shigella infection. The serum level of ASAT, ALAT, bilirubin, urea and creatinine in animals treated with the extract was similar to those of normal animal used in the study. These activities of the plant may be due at least in part to the presence of ent-kauran type diterpens such as kaurenoic acid identified in the extract. CONCLUSION: These findings support the usage of Xylopia staudtii as an antimicrobial against bacillary dysentery, making this plant a potential candidate for the formulation of an improved standardized traditional medicine.

Hypolipidemic and anti-atherosclerogenic effects of aqueous extract of Ipomoea batatas leaves in diet-induced hypercholesterolemic rats.

OBJECTIVE: Ipomoea batatas (L.) Lam. is a food plant used in African traditional medicine to treat cardiovascular diseases and related conditions. We assessed the hypolipidemic and anti-atherosclerogenic properties of the aqueous extract of I. batatas leaves in a rat model of diet-induced hypercholesterolemia. METHODS: Hypercholesterolemia was induced in male Wistar rats by exclusive feeding with a cholesterol-enriched (1%) standard diet for four weeks. Then, rats were treated once daily (per os) with I. batatas extract at doses of 400, 500 and 600 mg/kg or with atorvastatin (2 mg/kg), for four weeks. Following treatment, animals were observed for another four weeks and then sacrificed. Aortas were excised and processed for histopathological studies, and blood glucose level and lipid profile were measured. RESULTS: Hypercholesterolemic animals experienced a 21.5% faster increase in body weight, significant increases in blood glucose and blood lipids (148.94% triglycerides, 196.97% high-density lipoprotein cholesterol, 773.04% low-density lipoprotein cholesterol, 148.93% very low-density lipoprotein cholesterol and 210.42% total cholesterol), and increases in aorta thickness and atherosclerotic plaque sizes compared to rats fed standard diet. Treatment of hypercholesterolemic rats with the extract mitigated these alterations and restored blood glucose and blood lipid levels to normocholesterolemic values. CONCLUSION: Our findings suggest that I. batatas leaves have hypolipidemic and anti-atherosclerogenic properties and justify their use in traditional medicine.

Antihypertensive Effects of the Vitex cienkowskii (Verbenaceae) Stem-Bark Extract on L-NAME-Induced Hypertensive Rats.

Vitex cienkowskii stem-bark is used in Cameroonian traditional medicine to treat cardiovascular diseases including hypertension. In previous studies, the methanol/methylene chloride stem-bark extract of Vitex cienkowskii (MMVC) showed a preventive activity in L-NAME-induced hypertension and improved blood pressure of spontaneously hypertensive rats. The present study investigated the curative effects in L-NAME-induced hypertensive rats (LNHR). Hypertension was induced in rats by oral administration of L-NAME (40 mg/kg/day) for 28 days. The animals were divided into 2 groups: one group of 5 rats receiving distilled water (10 ml/kg) and another 20 rats receiving L-NAME. At the end of 4 weeks of administration of L-NAME, the animals were divided into 4 groups of 5 rats each: one group of hypertensive rats receiving distilled water, another one receiving captopril (25 mg/kg), and two groups of hypertensive rats receiving MMVC at doses of 200 and 400 mg/kg, respectively. Body weight, food, and water intake were measured weekly. At the end of the treatment, blood pressure and heart rate were recorded by invasive method. Whole heart, left ventricle, kidneys, and liver were weighed. The effects of plant extract on lipid profile and oxidative stress markers, as well as markers of hepatic and renal functions were assessed spectrophotometrically according to well described protocols. Results show that L-NAME significantly increases the mean arterial blood pressure (MABP), atherogenic index, lipid profile, and creatinine and transaminase activities of normotensive rats. MMVC significantly reduced the blood pressure in LNHR. Body weight, food and water intake, left ventricular hypertrophy, antioxidant level, renal and hepatic markers, and lipid profile were improved by the treatment with MMVC. The curative effect of MMVC on L-NAME-induced hypertension is probably related to its antihypertensive, hypolipidemic, and antioxidant properties. These results confirmed the use of Vitex cienkowskii for the treatment of hypertension in traditional medicine.

Curative effects of the aqueous extract of Tithonia diversifolia (Hemsl.) A. gray (Asteraceae) against ethanol induced-hepatotoxicity in rats.

OBJECTIVES: Tithonia diversifolia (Asteraceae) is used in Cameroonian traditional medicine for the treatment of several diseases amongst which are hepatic disorders. Anti-inflammatory, analgesic and anti-diabetic properties have been reported but, there is no scientific information on its hepato-protective effects. The aim of this study was to evaluate the curative effects of the Tithonia diversifolia (T. diversifolia) leaves aqueous extract on ethanol induced-hepatotoxicity in rats. METHODS: Ethanol 40° (4 g/kg) was administered daily by intragastric gavage for 21 days, and then the extract was administered concomitantly with ethanol for two more weeks. Some biochemical serum and tissue parameters were evaluated. Histopathologic analysis of the liver was carried out. RESULTS: The ingestion of ethanol induced a significant reduction of body weight and a significant increase in some markers of hepatic function (Alanine Amino-transferase, Aspartate Amino-transferase, alkaline phosphatase, gamma glutamyl-transferase, total bilirubin and albumin). These alterations were accompanied by a significant increase in the levels of serum triglycerides (p<0.001). Intoxicated animals were also characterized by a significant decrease of reduced glutathione and nitrites concentrations, catalase and superoxide dismutase activities as well as an increase of malondialdehyde levels. The histopathological examination showed vascular congestion, disorganized parenchyma, liver inflammation and dilation of sinusoid. The extract at the doses of 60 and 120 mg/kg reversed ethanol-induced adverse effects. CONCLUSION: Our study found that, the aqueous extract of T. diversifolia leaves has hepato-protective activity against ethanol-induced liver damages due partly to its antioxidant effect. This result justifies its empirical use for the treatment of liver problems.