Journal of Experimental Pharmacology最新文献

Background: Local wisdom food ingredients in North Sumatra, Indonesia, are a source of phenolics which have antioxidant, antihyperlipidemia, neuronal survival, and growth. Administering products with antioxidant properties can provide a supporting effect in preventing inflammation and neurodegenerative process.

Objective: The main objective of this study was to analyze the formulation of red palm oil (Elaeis guineensis Jacq), koja bay leaves (Murraya koenigii L Spreng), and passion fruit seeds (Passiflora edulis Sims) to improve lipid profile, antioxidant activity, Brain-Derived Neurotrophic Factor (BDNF), and lipase enzyme activity of Sprague-Dawley rats.

Methods: This study was an in vivo and pre-post experimental study, starting with analyzing flavonoid of the three extract ingredients, then tested by giving it to rats for 14 days and ending with induction administration of lipopolysaccharide (LPS) for two days. This pre-post study on animals involved 36 rats divided into 6 groups. At the end of the study, termination and examination of malondialdehyde, lipid profile, glucose, BDNF, lipase enzyme activity and histopathological examination were carried out.

Results: The study results showed that there were significant values in several parameters, which were body weight, LDL, LDL/HDL ratio, BDNF, and lipase enzyme activity especially in the group of rats given LPS and the group with high calories-fat-protein. This study showed that there were significant differences in body weight, LDL levels, and LDL/HDL ratio in each group of rats, especially in the group given the formulation of the three extract ingredients, the significant dose showed in 300mg/kg body weight (p < 0.001).

Conclusion: The formulation of red palm oil, koja bay leaves, and passion fruit seeds showed significant reduction in LDL levels, LDL/HDL ratio, BDNF, and lipase enzyme activity.

Background: The diuretic activity of the Cucumis dipsaceus leaf, which is used in indigenous medicine, has been claimed but has not yet undergone scientific evaluation.

Objective: The objective of this study was to assess the diuretic activity of the aqueous and 80% methanol extracts derived from the leaves of Cucumis dipsaceus in rats.

Methods: For the extraction process, the maceration technique was employed to obtain the aqueous and 80% methanol extracts from the Cucumis dipsaceus leaves. Male rats were then divided randomly into eight groups, with six rats in each group. These groups consisted of a negative control group, a positive control group, and three different groups for each extract at varying doses. The urine output volumes, the concentrations of urinary electrolytes (sodium, potassium, and chloride) and urinary pH, were measured and analysed to compare the results among the different groups.

Results: Both the aqueous and 80% methanol extracts of Cucumis dipsaceus leaves demonstrated a significant increase in urinary output at doses of 200mg/kg body weight (p<0.01) and 400mg/kg body weight (p<0.001). When comparing the urinary electrolyte excretion with the negative control group, the groups treated with the 400mg/kg body weight dose of the aqueous extract showed significant differences in the urinary excretion of sodium (p<0.05), chloride (p<0.01), and K+ (p<0.01). Similarly, the urinary excretion of K+ and Cl- also exhibited significant differences at moderate doses (K+: p<0.01, Cl-: p<0.05) and the highest doses (both: p<0.01) of the 80% methanol extract. Furthermore, the highest doses of both the aqueous (p<0.01) and 80% methanol (p<0.01) extracts demonstrated significant differences in saluretic effect.

Conclusion: Both crude extracts of C. dipsaceus leaves have significant diuretic activity, providing support for the traditional use of the plant as a diuretic agent.

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.