Journal of Experimental Pharmacology最新文献

Background: Ticks are the second most common vector of human infectious diseases after mosquitoes. Their transovarial transmission contributes to the maintenance of environmental diseases. This study evaluates the phytochemical screening and in vitro efficacy of Calpurnia aurea against the adult survival and egg hatchability of two transovarial transmission vectors: Amblyomma variegatum and Rhipicephalus microplus.

Methods: Plant material was extracted using maceration techniques, and concentrated solutions of 12.5, 25, 50, 100, 200, and 400 ppm were prepared. Distilled water and diazinon were used as negative and positive controls, respectively. Ten adult ticks were exposed for 10 minutes, and dead ticks were counted after 24 hours of recovery. Twenty 15-day-old eggs were immersed for 10 minutes, and after 15 days of incubation, hatched and unhatched eggs were tallied. Preliminary phytochemical constituents were screened. A one-way analysis of variance and the probit regression model determined mean mortality and hatchability and estimated lethal and inhibitory concentrations, respectively.

Results: The ethanolic and aqueous leaf extracts caused 10±0.0% mortality in adult A. variegatum and R. microplus. The effective dose was LC50 of 27 and 29 ppm and LC50 of 37 and 41 ppm, respectively. At 400 ppm, the leaf ethanolic and aqueous extracts showed 18.7±0.9% and 18.3±1.7%; 18.3±1.2% and 19.7±0.3% egg hatching inhibition, respectively. The effective dose had an IC50 of 50 ppm and IC50s of 91 and 79 ppm, respectively. Flavonoids and saponins were found in both leaf and pod extracts.

Conclusion: C. aurea extracts showed a more promising effect on tick survival and hatchability than synthetic diazinon. The susceptibility test indicated that the leaf extract could control vectors and contribute to environmental disease maintenance. Complex phytochemicals, especially phenolic compounds, are additional evidence of effectiveness in vector control. Further investigation of in vivo efficacy and advanced fractionation of phytochemicals is needed.

Background: Malaria is causing high mortality and morbidity due to Plasmodium's resistance to currently available anti-malarial drugs and mosquito's resistance to insecticides. Thus, there is a critical need to search for novel anti-malarial drugs from natural sources. Therefore, this study investigated in vivo antimalarial activities of two Ethiopian medicinal plants, Croton dichogamus Pax and Ehretia cymosa Thonn, in Plasmodium berghei infected Swiss albino mice.

Methods: Soxhlet extraction method using 80% methanol as a solvent was used to prepare crude extracts of the two plants. Acute oral toxicity and 4-day suppressive in vivo antimalarial activity tests were performed on healthy female mice and P. berghei infected male mice, respectively. Antimalarial activity of the crude extracts at doses of 100, 200, and 400 mg/kg and the standard drug, chloroquine were used to assesse in Plasmodium berghei infected Swiss albino mice. Parasitemia level, packed cell volume, body weight, and rectal temperature of the mice were determined before infection (day 0) and after treatment (day 4). Survival time was determined by recording the date on which the mice died, considering the date of infection as day 0. The recorded data were analyzed using ANOVA and SPSS version 24.

Results: The result of the acute toxicity study revealed that the crude extracts were non-toxic at doses up to 2 g/kg. The extract of E. cymosa suppressed parasitemia level by 66.28, 63.44 and 63.14% at 400, 200, and 100mg/kg, levels while C. dichogamus extract suppressed parasitemia level by 45.29% at a dose of 400mg/kg. The remaining two dose levels of C.dichogamus extract suppressed parasitemia level by < 30%.

Conclusion: C. dichogamus and E. cymosa showed anti-plasmodial activities. E. cymosa exhibited a more pronounced anti-plasmodial effect than C. dichogamus. The activities of both plants observed in this study support their traditional use as antimalarial drugs. Further studies on these plants using solvent fractions are required to identify their active ingredients.

Background: Faidherbia albida, popularly known as gawo in Hausa, is traditionally used to treat jaundice in Zuru emirate of Kebbi State. Herein, the ameliorative effect of F. albida against 2.4-dinitrophenylhydrazine-induced hyperbilirubinemia in Wistar albino rats was investigated.

Methods: Thirty healthy rats were administered 75 mg of 2.4-dinitrophenylhydrazine to induce hyperbilirubinemia. Thereafter, groups 1-3 received 500, 750, and 1000 mg/kg body weight of the methanol stem-bark extract, and 15 mg/kg of phenobarbitone (standard drug) was administered to group 4. Groups 5 and 6 served as the untreated and normal controls, respectively. The phytochemical composition was evaluated using standard methods, and acute oral toxicity was evaluated using standard OECD 2008 guidelines.

Results: Phytochemical analysis revealed the presence of alkaloids, phenols, and a substantial amount of tannins. A significant (P<0.05) reduction of direct bilirubin, total bilirubin, and total protein levels for all the doses of the extract and standard drug compared to untreated groups was observed. Similarly, there were significant reductions in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels of the group treated with the standard drug and all extract-treated groups compared to elevated levels observed in untreated controls. However, a significant (P<0.05) increase in serum albumin (ALB) levels, red blood cells, hemoglobin, and pack cell volume was observed in all extract-treated compared to the untreated control in contrast to a significant decrease in MCH levels in treated groups compared to the untreated group.

Conclusion: F. albida ameliorated the hyperbilirubinemia induced by 2.4-dinitrophenylhydrazine in Wistar albino rats, thus providing some support for its use in traditional medicine to treat jaundice.

Background: The burden of obesity and overweight associated morbidity and mortality is increasing in epidemic proportions worldwide. Suppression of appetite is one of the mechanisms that has been shown to reduce weight. Most of the drugs on the market currently for appetite suppression are not readily available or affordable in resource-limited settings. Additionally, previous studies have shown that most of these drugs are associated with significant adverse effects, which demonstrates a need for alternative or complementary options of drugs for appetite suppression. In Uganda, herdsmen commonly chew the raw stems and leaves of Rumex usambarensis, a wild shrub, and this is believed to reduce hunger. This study aimed at determining the effect of Rumex usambarensis aqueous extract on food intake as a measure of appetite in Wistar albino rats.

Methods: This study was carried out in two phases: the fattening phase and the treatment phase. Female albino Wistar rats were fed a high-fat diet for 49 days. The fattened animals were then randomly separated into 4 groups, which received 1 mL of distilled water (negative control), 500 mg/kg body weight of aqueous extract of Rumex usambarensis, 1000 mg/kg body weight of the extract and 20 mg/kg body weight topiramate (positive control), respectively. Food intake was measured every day, and weights were taken every two days for every group.

Results: Rumex usambarensis extract significantly reduced body weight of fattened rats compared to the control group at both doses: for the 500mg/kg dose (Mean difference, MD = 17.2, p < 0.001) and for 1000mg/kg dose (MD = 25.9, p < 0.001). Additionally, both doses of the aqueous extract showed a significant reduction in food intake: for the 500mg/kg dose (MD = 16.1, p < 0.001) and for the 1000mg/kg dose (MD = 37.3, p < 0.001). There was a strong correlation between food intake and weight for both doses for the 500mg/kg dose (r = 0.744, p = 0.009), and the strongest association observed with 1000mg/kg dose (r = 0.906, p < 0.001).

Conclusion: The aqueous extract of the leaves and stems of Rumex usambarensis has appetite suppressing and weight reduction effects in fattened female Wistar albino rats and could be an efficacious alternative medicine for management of overweight, obesity and other related disorders.

Background: Cisplatin chemotherapy induces nephrotoxicity by producing reactive oxygen species, hence, discovering add-on nephroprotective drugs for patients with cancer is challenging. Boesenbergia rotunda has been reported for its antioxidant properties.

Purpose: This study aims to explore the nephroprotective mechanism of the ethanol extract of Boesenbergia rotunda rhizome (EEBR) in cisplatin-induced rats.

Methods: The rats were randomly assigned into 6 groups: the normal control (treated with saline); the negative control (cisplatin-induced without any treatment); the positive control (treated with quercetin 50 mg/kg BW); and 3 treatment EEBR (125 mg/kg BW; 250 mg/kg BW; 500 mg/kg BW) groups for 10 days. The % relative organ weight, kidney histopathology, and nephrotoxicity biomarkers expression were evaluated.

Results: EEBR decreased creatinine, urea nitrogen, glutamic pyruvate transaminase, and malondialdehyde levels in the blood of cisplatin-induced rats. An insignificant increase in GOT was observed in rats treated with the highest dose of EEBR. EEBR did not significantly alter the BW and the % kidney relative weight. An abnormal shape of the Bowman capsule is observed in the negative control group. EEBR reduced the expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 genes in rats' kidneys.

Conclusion: Boesenbergia rotunda could be considered a potential candidate for add-on therapy in cisplatin-treated patients, but further studies are needed to verify its efficacy and safety.

Background: The roots of Verbascum sinaiticum have been used traditionally for the management of wound in different regions of Ethiopia. Despite the presence of several claims and in vitro studies regarding its role in wound healing, no scientific studies have been conducted so far. Therefore, this study aims to scientifically evaluate the wound healing activities of the crude extract and solvent fractions of the roots of Verbascum sinaiticum in Swiss albino mice.

Methods: The dried root powder of Verbascum sinaiticum was extracted using 80% methanol by maceration technique. This was then fractionated with chloroform, ethyl acetate, and water. These extracts were formulated as ointment at 5% and 10% concentration by using simple base. Acute dermal toxicity was performed on mice. The wound healing potential was evaluated using excision, incision, and burn wound models.

Results: In excision wound, 10% and 5% of crude extract ointment provided a significant (P<0.001) percentage of contraction starting from day 4 and day 6 onwards respectively. Moreover, the rate of epithelialization was significantly (P<0.001) improved in 10% crude extract. In burn wound, 10% and 5% crude extract showed significant (P<0.001) wound contraction starting from day 4 and 8 onwards respectively. In both excision and burn wounds, a moderate concentration of fibroblast proliferation and collagen deposition was observed on the 10% crude extract. The 5% and 10% aqueous and ethyl acetate fractions produced a significant (P<0.001) percentage of wound contraction and shortening of epithelialization at different time points compared to simple ointment.

Conclusion: The results of this study demonstrated that the 80% methanolic crude extract, aqueous and ethyl acetate fractions of Verbascum sinaiticum root have wound healing potential which assimilates its traditional use.

Purpose: Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes Mellitus (T2DM). However, whether these effects prevent electrocardiographic changes associated with T2DM altogether remain unknown. Our aim was to investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) model of T2DM.

Methods: Twenty-five (25) rats were randomized into five (5) groups: normal control receiving a normal diet while the other groups received an 8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), electrocardiograms (ECGs), paracardial adipose mass, and left ventricular fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, with the level of significance at p < 0.05.

Results: Compared to the diabetic control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 0.0463). Furthermore, the high dose dapagliflozin group had the lowest paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In contrast, while metformin showed favorable effects on OGT (p = 0.0025), paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did not demonstrate significant antiarrhythmic effects.

Conclusion: Pretreatment with higher doses of Dapagliflozin exhibits prophylactic cardioprotective characteristics against diabetic cardiomyopathy that include antifibrotic and antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could be a more effective initial therapeutic option in T2DM.

Purpose: To observe the effect of soya yoghurt (Soyghurt), which is high in flavonoid substance, on the expression of preeclampsia biomarkers (sFLT-1 and PLGF) on preeclampsia serum-induced trophoblast primary cell culture isolated from placental tissue.

Methods: The trophoblast primary culture was induced by preeclampsia serum (10%). The Soyghurt treatment was performed with 2.5%, 5%, and 7.5% Soyghurt supernatant concentrations in culture media. The expression of preeclampsia markers, sFLT-1 and PLGF, were evaluated using ELISA.

Results: Expression of sFLT-1 on preeclampsia-induced cell culture treated with Soyghurt was significantly lowered compared to the untreated group (p<0.01). However, no significant difference was observed in the PLGF levels of all groups induced by preeclampsia serum (p>0.05).

Conclusion: This study demonstrates the potential effect of Soyghurt's in balancing preeclampsia marker expression by inhibiting the expression of sFLT-1 in preeclampsia serum -induced trophoblast cells.

Purpose: The purpose of this study was to record the utilization of medicinal plants by the Oromo people in the Kofale District, Oromia Regional State, Ethiopia, to control human and animal health problems.

Methods: Data regarding the use of medicinal plants were collected using ethnobotanical methods from 84 traditional medicine practitioners and 304 general informants sampled employing purposive and systematic random sampling methods, respectively, in the Kofale District. Data were analyzed using different indices, including a preference ranking exercise, informant consensus factor (ICF), fidelity level (FL) and relative popularity level (RPL).

Results: In the district, 106 medicinal plants were claimed to be used for the treatment of 43 human and 18 livestock illnesses, of which 75 (71%) were used to manage human health problems, 23 (21.5%) were used to treat both human and livestock ailments and eight (7.5%) were utilized to treat manage livestock health problems. Most (76.4%) plants were harvested from the wild. Leaves were the most commonly used plant part (55.6%) in remedy preparations. Skin diseases scored the highest ICF value (0.97), followed by gastrointestinal disorders (ICF = 0.95), cancer (ICF = 0.93), and hemorrhoids (ICF = 0.91). Medicinal plants that record the highest fidelity level (FL) (100%) and rank order priority (ROP) (100%) values included Justicia schimperiana, Embelia schimperi, Ekebergia capensis and Datura stramonium, which have been used to treat liver disorders, tapeworm infections, babesiosis, and rabies, respectively. There were significant differences (p<0.05) in the mean numbers of medicinal plants claimed by different social groups: older, illiterate, and traditional medicine practitioners reported higher mean numbers of medicinal plants than younger, literate, and general informants, respectively.

Conclusion: This study indicated the richness of medicinal plant species in Kofale District. Medicinal plants with the highest FL and ROP values and those used to treat disease categories with the highest ICF values should be prioritized in future phytochemical and pharmacological investigations.