Journal of Experimental Pharmacology最新文献

The COVID-19 pandemic is prompting extensive investigation into potential treatments, including the use of corticosteroids to manage inflammation and mitigate severe disease outcomes. Therefore, this systematic review aimed to evaluate the efficacy of oral/intravenous corticosteroids in the management of COVID-19. A comprehensive search was conducted across major scientific databases such as MEDLINE, Scopus, and Cochrane for relevant studies published from 2019-2024. The inclusion criteria included studies investigating the use of oral/intravenous corticosteroids in COVID-19 patients >18 years with a randomized placebo-controlled trial method. Non-placebo-controlled studies, studies using combined treatments with other drugs, as well as protocol articles, conference proceedings, review articles, and non-English studies were excluded. A narrative synthesis approach was adopted given the significant methodological diversity. The results showed that a total of 12 studies met the inclusion criteria covering the use of three drugs, including dexamethasone (three), hydrocortisone (two), and methylprednisolone (seven). The outcome parameters used for each study were different. Among the total 12 studies, five showed insignificant results for hydrocortisone (two) and methylprednisolone (three), while others reported significant results. This systematic review suggested that oral/intravenous corticosteroids might confer clinical benefits in the management of COVID-19, particularly in reducing mortality and severe disease outcomes. However, further investigation was needed to establish standardized protocols regarding dosage, duration, and safety considerations to optimize efficacy and minimize potential adverse effects.

Introduction: Plant treatment has been used for thousands of years and has been proven to treat acute and chronic diseases. The function of the traditional plant Centella asiatica is as an antimicrobial agent, anticancer, antioxidant, and therapeutic gene in healing wounds and inflammation. Lung fibrosis caused by bleomycin can develop into chronic lung disease, which ends in tissue death if not treated immediately. The purpose of this study is to predict and explain the impact of Centella asiatica extract on model rats exposed to bleomycin in their lungs as a treatment or anti-fibrinolysis.

Methods: This research is an analytical study with a randomized in-vivo experimental design divided into 3 groups of 5 male Wistar rats aged 10 weeks. Negative control group (K) with intratracheal induction of bleomycin alone. The positive group was given intratracheal bleomycin 4 mg/kg/BB on days 0 and 21 and added Centella asiatica induction at 400 mg (P1) on days 15 to 49. The other positive group was given intratracheal bleomycin 4 mg/kg/BB on days 0 and 21 and added Centella asiatica induction at 800 mg (P2) on days 15 to 49. Data were collected according to findings of lung histology analysis of rat samples.

Results: In the interalveolar septum group, there was a difference in Masson's Trichrome staining results in groups K and P1 with p<0.05 (p=0.036). However, there was no difference in histopathological staining results in groups K and P2 (p>0.05).

Conclusion: The induction of bleomycin 4 mg/kg/BB was proven to cause fibrosis in the lungs of rats, and Centella asiatica extract was used as a treatment. Therefore, further research regarding antifibrotic drugs is hoped to reduce fibrotic areas significantly.

Background: Human monoacylglycerol lipase (MGL) is accountable for the hydrolysis of 2-arachidonoylglycerol (2-AG), thus contributing pivotally to neuroprotection because 2-AG is the main source of arachidonic acid, the precursor of prostaglandins production. Inhibiting MGL reduces inflammatory damage in the ischemic brain and enhances cerebral blood flow. Plants have been reported for their neuroprotective effect, such as Morinda citrifolia on pentylenetetrazol (PTZ)-induced kindling seizures in mice, by reducing the seizures and restoring behavioral and biochemical changes, although the mechanism is not described.

Purpose: To evaluate the binding affinity and stability of phytoconstituents in M. citrifolia fruits toward human MGL (PDB ID 3PE6), compared to the known MGL inhibitors (JZL195 and ZYH). The in silico pharmacology study was validated by an in vitro study of the phytosterols and the ethanol extract of M. citrifolia fruits (EEMC) towards MGL.

Methods: Initially, nine phytoconstituents of M. citrifolia fruits were docked to the catalytic pocket of human MGL (PDB ID: 3PE6), and compounds with the best affinity were subjected to a molecular dynamic (MD) simulation. The in vitro study was performed using the MGL inhibitor screening assay kit.

Results: The best binding affinity and stability toward human MGL were shown by stigmasterol and beta-sitosterol, and the MM-PBSA total binding energy of stigmasterol and beta-sitosterol to MGL is stronger than that of JZL195 and ZYH. Moreover, beta-sitosterol and EEMC inhibit MGL with an IC₅₀ value of, respectively, 8.10 μg/mL and 196.20 μg/mL, while JZL195 shows an IC₅₀ of 0.028 μg/mL.

Conclusion: Beta-sitosterol of Morinda citrifolia fruits may have the potential to protect human neurons by occupying the catalytic site of human MGL, thus competitively inhibiting the substrate of the enzyme. However, the inhibitory activity towards human MGL is lower than JZL195.

Dermal allyl isothiocyanate (AITC) administration and whole-body heat stress (WBHS) are two challenge models that are used to evaluate physiological mechanisms of vasodilation and pharmacological activity in humans. Their exact vasodilatory mechanisms in humans are not fully elucidated but are likely to be nitric oxide (NO)-mediated. This study aimed to evaluate whether there is overlap in the vasodilatory pathways of dermal AITC application and WBHS by combining the challenges. In this open-label interventional study, healthy volunteers underwent dermal administration of AITC twice: under basal conditions and during WBHS. Dermal blood flow (DBF) was non-invasively measured using laser speckle contrast imaging four times, once in each of the following situations: baseline, WBHS only, AITC only, and WBHS combined with AITC. A total of 12 male volunteers, aged 18-61 years, participated in the study. Compared to baseline, following AITC application, their DBF increased by 63.43 AU (baseline: 32.55, 95% CI [17.78, 47.31] AU, AITC only: 95.97, 95% CI [81.21, 110.7] AU, p < 0.0001). During WBHS, the increase in DBF after AITC was 42.76 AU (WBHS only: 87.25, 95% CI [72.49, 102.0] AU, WBHS+AITC: 130.0, 95% CI [115.2, 144.8] AU, p < 0.0001). The combination of WBHS and AITC resulted in a lower DBF than the sum of the DBF responses to AITC and WBHS when applied separately (ED 20.67, 95% CI [-3.532, 44.88], p = 0.0916). This might point towards the presence of an interaction in the vasodilatory mechanism of AITC application and WBHS, possibly indicating overlap in their NOS-driven vasodilatory pathways.

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.