Journal of Experimental Pharmacology最新文献

Purpose: We unravel the effect of anthocyanin-containing purple sweet potato synbiotic yogurt (PSPY) on 3T3-L1 adipocyte differentiation and its fundamental molecular mechanisms.

Methods: Molecular docking simulation was performed to observe and identify the affinity and interaction between bioactive compounds and targeted proteins. MDI (isobutylmethylxanthine, dexamethasone, and insulin)-containing medium, a cocktail that stimulates adipogenesis, was used in this study. The toxic effect possibility of the yogurt product was evaluated using 3-[4, 5-dimethylthiazol-2-yl]-2.5 diphenyl tetrazolium bromide (MTT) assay. A 0.25%, 0.5%, 1%, and 5% (v/v) plain or purple sweet potato yogurt supernatant was given to 3T3-L1 preadipocyte culture medium from 24 h after seeding until day 11 of MDI-induced differentiation. The mRNA expression and lipid accumulation were analyzed using RT-qPCR and Oil red O staining, respectively, on day 11 after differentiation induction.

Results: In silico study suggested that anthocyanin-derived compounds have the potential to inhibit peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator for white adipogenesis. Anthocyanin-containing PSPY significantly suppressed the expression of Pparg, Adipoq, Slc2a4, and Pgc1a. PSPY significantly suppressed Pparg with 1% and 5% concentrations, while with a concentration of 0.25%, PSPY significantly suppressed Adipoq expression as compared to control. Significant inhibition of Slc2a4 and Pgc1a was observed starting from a 0.25% concentration of PSPY. The suppression of adipogenic genes was also observed with the treatment of plain yogurt; however, the effects were relatively lower than the PSPY. The group treated with 1% and 5% of PSPY also showed inhibition effects on lipid accumulation.

Conclusion: This study demonstrated PSPY inhibition effect on white adipocyte differentiation through suppression of Pparg and its downstream genes, Adipoq and Slc2a4, indicating the potential of this yogurt as a functional food for obesity management and prevention.

Background: Local anaesthetics are medications that cause numbness that can be reversed by applying them topically. Local anaesthetics are clinically used to control pain during minor surgeries or to treat other acute and chronic pain. The present investigation intended to investigate the anesthetic as well as analgesic potential of Injection Harsha 22, a novel polyherbal formulation in Wistar albino rats.

Methods: The anesthetic potential of Injection Harsha 22 was evaluated by a heat tail-flick latency (TFL) test, whereas the analgesic effect was elevated by electrical stimulation testing. Here, lignocaine (2%) was used as the standard anesthetic drug.

Results: In TFL, Injection Harsha 22 showed anesthetic effects up to 90 minutes after application. Also, the duration of anesthesia in rats that were administered subcutaneously with Injection Harsha 22 was comparable to that of the rats treated with commercial lignocaine (2%). In an electrical stimulation test, single administration of Injection Harsha 22 to rats significantly prolonged analgesia compared with the normal control group. The median duration of analgesia in rats administered subcutaneously with Injection Harsha 22 and lignocaine solution was 40 minutes and 35 minutes, respectively. Furthermore, Injection Harsha 22 does not interfere with the hematopoietic system of the experiment animals.

Conclusion: Thus, the present investigation established the in vivo anesthetic and analgesic potential of Injection Harsha 22 in experimental animals. Hence, it can be concluded that Injection Harsha 22 can become a prominent substitute for lignocaine as a local anaesthetic agent after establishing its efficacy through stringent clinical trials in humans.

Background: The development of novel and intriguing nanoparticle (NP)-based materials with antibacterial activity has recently received attention due to the problem of bacterial resistance to conventional antibiotics becoming more and more frequent. Thus, this study aimed to investigate the antibacterial effectiveness of a synthetic zeolite-supported AgZnO nanoparticle against selected bacteria in vitro.

Methods: Using the disc diffusion method, the antibacterial activity of synthetic zeolite-supported AgZnO nanoparticles was assessed against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Zinc oxide (ZnO) and Ag/ZnO nanoparticles were used to create the zeolite-supported Ag/ZnO composite. Chloramphenicol was used as a standard drug. The nanoparticles and composites were characterized using powder X-ray diffraction (XRD), Fourier transform infrared (FTIR), and atomic absorption spectroscopy (AAS).

Results: Synthetic zeolite-supported AgZnO nanoparticles showed promising antibacterial properties with the largest zone of inhibition against S. aureus bacteria in comparison to E. coli. The synthetic zeolite-supported AgZnO nanoparticle displayed a zone of inhibition against S. aureus and E. coli without a remarkable difference compared to the respective standard drug (Chloramphenicol). Zinc peaks were visible in the X-ray diffractograms, which supported the theory that the characteristic hexagonal wurtzite structure of zinc oxide was present.

Conclusion: All types of ZnO, AgZnO, and AgZnO-Zeolite showed wide-spectrum activity with better effect against gram-positive bacteria, while the Zeolite-Ag/ZnO composite showed even better antibacterial activity. The findings suggest a potential bactericide that needs further evaluation in future studies was observed in synthetic zeolite-supported Ag/ZnO nanoparticles.

Introduction: Leishmaniasis is one of the neglected tropical diseases, threatening lives of about 350 million people globally. Brucea antidysenterica seeds are used for the treatment of cutaneous leishmaniasis in the traditional medicine in Ethiopia.

Objective: This study aimed to evaluate Brucea antidysenterica seeds' anti-leishmanial activity in vitro.

Methods: The crude (80% methanol) extract of Brucea antidysenterica seeds and its fractions were evaluated for their anti-leishmanial activities against promastigotes and intracellular amastigotes of Leishmania donovani and Leishmania aethiopica, and for their cytotoxic effects against mammalian cells. The quantitative estimations of total phenolic compounds (TPCs), flavonoids (TFCs) and alkaloids (TACs) were determined, spectrophotometrically. Median inhibitory concentration (IC₅₀) and median cytotoxic concentration (CC₅₀) of the extract and its solvent fractions were calculated using GraphPad Prism 9.1.0 computer software. Data was presented as mean ± standard error of the mean (SEM).

Results: The crude extract and its hexane, ethyl acetate and butanol fractions showed anti-leishmanial activities, with IC₅₀ values of 4.14-60.12 µg/mL against promastigotes, and 6.16-40.12 µg/mL against amastigotes of both Leishmania species. They showed moderate cytotoxicity against Vero cell lines and peritoneal mice macrophages, with CC₅₀ values of 100-500 µg/mL, but >1600 µg/mL against red blood cells. Selectivity indices ranged from 7.97 to 30.97. The crude extract, and its ethyl acetate and hexane fractions possessed 54.78-127.72 mg of gallic acid equivalent TPC, 18.30-79.21 mg of quercetin equivalent TFC, and 27.62-97.22 mg of atropine equivalent TAC per gram of extracts.

Conclusion: The seeds of the plant possessed anti-leishmanial activities against L. aethiopica and L. donovani that might provide a scientific justification for its use in the treatment of leishmaniasis by traditional healers. Future works are recommended to isolate, purify and identify the possible secondary metabolites attributed to the anti-leishmanial activity.

Introduction: Herbal products have been widely used for the treatment of diseases throughout the ages. In this research, we investigated antioxidant, antibacterial, anti-adipogenic, and anti-inflammatory activities of methanolic extracts of five ethnomedicinally important plants; namely, Alnus nepalensis, Dryopteris sparsa, Artocarpus lacucha, Litsea monopetala, and Lyonia ovalifolia.

Methods: We investigated the DPPH free radical scavenging potential, sensitivity of selected bacterial strains towards the extracts using a disc diffusion assay, anti-inflammatory activity in RAW-264.7 cells, and anti-adipogenic activity by the ORO assay in 3T3-L1 preadipocytes.

Results and discussion: The extract of A. nepalensis showed significant antioxidant activity (IC₅₀=4.838 µg/mL), followed by A. lacucha, L. monopetala, and L. ovalifolia, exhibiting comparable IC₅₀ values to that of ascorbic acid (IC₅₀=5.063 µg/mL). Alnus nepalensis also showed good antibacterial activity in disc diffusion methods, with remarkable zones of inhibition in A. baumannii (14.66 mm) and P. mirabilis (15.50 mm) bacterial species. In addition, A. nepalensis was found to increase adipogenesis in 3T3-L1 cells, evidenced by increased lipid deposition in differentiated 3T3-L1 cells. A similar pattern of increased adipogenesis was observed on treatment with L. ovalifolia extracts. On the other hand, A. lacucha effectively reduced lipid deposition in 3T3-L1 cells at 100 µg/mL (75.18±6.42%) by inhibiting adipogenesis, showing its potential use in the management of obesity. Furthermore, A. lacucha 100 µg/mL (15.91±0.277 µM) and L. monopetala 75 µg/mL (12.52±0.05 µM) and 100 µg/mL (11.77±0.33 µM) significantly inhibited LPS-induced nitric oxide production in RAW 264.7 cells. Also, A. nepalensis and L. ovalifolia inhibited NO production significantly, endorsing their anti-inflammatory potential.

Conclusion: The findings from these in-vitro studies suggest that the selected five plants possess remarkable antioxidant, antibacterial, anti-adipogenic, and anti-inflammatory activities. This study opens the door to conduct further advanced in-vivo experiments to find possible lead compounds for the development of valuable therapeutic agents for common health problems.

Background: The emergence and spread of resistant microbes continue to be a major public health concern. Effective treatment alternatives, particularly from traditionally used medicinal plants, are needed.

Objective: The main objective of this study was to conduct phytochemical screening and antimicrobial activity evaluation of selected traditionally used medicinal plants in Ethiopia.

Methods: The ethnomedicinal use value frequency index (FI) was used to select twelve medicinal plants. Phytochemical classes of compounds were screened using different standard methods. Anti-microbial activities of plant extracts were evaluated against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Candida albicans. Minimum inhibitory concentrations were measured using the broth micro-dilution method. The data were analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0 and the findings were presented descriptively and using non parametric one-way ANOVA analysis (Kruskal-Wallis/Ddunn's test).

Results: The phytochemical constituents identified were flavonoids, alkaloids, glycosides, phenols, saponins, steroids, and terpenoids, with flavonoids, alkaloids, and phenols being the most abundant. The crude extracts and chloroform fractions of the extracts showed an activity against the tested strains. The crude extract of Thalictrum rhynchocarpum Quart.-Dill. and A.Rich root demonstrated superior activity against all the tested strains with the lowest minimum inhibitory concentrations of 0.48 μg/mL against Staphylococcus aureus and Escherichia coli; 0.98 μg/mL against Klebsiella pneumoniae, Pseudomonas aeruginosa; and 3.90 μg/mL against Candida albicans, which are even better than the reference drug, gentamicin and clotrimazole.

Conclusion: The majority of evaluated medicinal plants demonstrated remarkable activity against tested microbial strains, which can be attributed to the presence of secondary metabolites of different classes of compounds. The finding provided scientific evidence for the use of these traditionally used medicinal plants.

Purpose: Management of decompensated cirrhosis may include the use of vasoconstrictors that can lead to serious adverse events. OCE-205 was designed as a highly selective V1a receptor partial agonist, intended to have a wider therapeutic window than full vasopressin agonists.

Methods: We aimed to characterize the activity of OCE-205 treatment in two rat models of portal hypertension (PHT). For both models, OCE-205 was administered as a subcutaneous bolus injection. Thirty male Wistar rats were fed a methionine/choline-deficient (MCD) diet to model PHT. Animals received OCE-205 (10, 25, 100, or 500 µg/kg) or intra-arterial terlipressin (100 µg/kg). In a more severe model of PHT, 11 male Sprague Dawley rats had the common bile duct surgically ligated (BDL) and received OCE-205. Portal pressure (PP) and mean arterial pressure (MAP) were measured.

Results: For PP in the MCD model, MAP increased while PP decreased in rats treated with OCE-205 or terlipressin; the peak changes to MAP were 14.7 and 33.5 mmHg, respectively. Changes in MAP began to plateau after 10 min in the OCE-205 groups, whereas in the terlipressin group, MAP rapidly increased and peaked after 20 min. Across all treatment groups in the BDL model, a dose-related decrease from baseline in PP was observed following OCE-205, plateauing as the dose increased. In all treatment groups, PP change remained negative throughout the 30-min testing period. In both PHT rat models, a reduction in PP was coupled to an increase in MAP, with both plateauing in dose-response curves.

Conclusion: Data support OCE-205 as a promising candidate for further development.

Institutional protocol number: Procedures were approved by the Ferring Research Institute (FRI) Institutional Animal Care and Use Committee on July 13, 2011, under protocol FRI-07-0002.

Purpose: Prunus africana is a well-known plant that is used in Ethiopian traditional medicine for the treatment of wounds and other ailments, although there is no scientific evidence to back up the claims of its wound-healing properties. Thus, the objective of this study is to evaluate the wound-healing potential of P. africana bark extract in mice.

Methods: The bark of the plant was extracted by successive maceration using 80% methanol and then fractionated with aqueous, n-butanol, and chloroform. The crude extract and solvent fractions were formulated as an ointment. Wound healing activity was evaluated using excision and incision wound models. Total phenol, flavonoid, and alkaloid contents of the crude extract, aqueous, and n- butanol fractions of the plant were determined.

Results: In both models, mice treated with 5% (w/w) and 10% (w/w) crude extract ointment exhibited a significant (p < 0.001) wound healing activity compared with control as evidenced by the increased rate of wound contraction and hydroxyproline content, the reduced epithelialization time, and the higher skin breaking strength. Mice treated with aqueous fraction ointment exhibited a high percentage of wound healing effect among all solvent fractions. The aqueous fraction consisted of higher phenolic (49.71 ± 0.73 mg/g) and flavonoid (39.58 ± 0.27 mg/g) content, while alkaloid (3.89 ± 0.55 mg/g) content was the lowest.

Conclusion: Prunus africana stem bark extract demonstrated wound healing activity in mice model which supports the acclaimed use by Ethiopian traditional medicine.

Background: A major cumbersome factor in malaria control measure is the new coming antimalarial drug resistance strains. The increase of resistance to the available marketed antimalarial agents dictates the scientific community to search new alternative antimalarial agent from traditional plants. Therefore, our study assesses the antimalarial activity of the crude root extract and solvent fraction of Sesamum indicum in mice.

Methods: The roots of Sesamum indicum were extracted by 80% methanol and fractionated using three solvents with different polarities. The in vivo antimalarial activity was assessed at 200 mg/kg, 400 mg/kg, and 600 mg/kg of the root crude extract and solvent fraction using the 4-day suppressive test. Similarly, the n- butanol fraction extract, which showed better suppression potential in 4-day suppressive test from other fractions was also evaluated in the curative model to assess its curative potential. The % parasitemia suppression, mean survival time, body weight change, rectal temperature change, and packed cell volume change were also evaluated in both models.

Results: Our finding revealed that the crude extract and solvent fraction treated groups had a statistical significant parasitemia suppression and mean survival time improvement as compared to the negative control (p<0.001) in both models in a dose-dependent fashion. The higher dose n-butanol fraction treated group (600mg/kg) showed the highest suppression effect and mean survival time prolongation in both tests from the other two fractions. However, the lowest suppressive effect was observed in 200 mg/kg aqueous fraction extract-treated groups in the 4-day suppressive test.

Conclusion: The crude root extract and solvent fractions of Sesamum indicum possessed a dose dependent antimalarial activity and a significant change in other parameters in both models that strengthen the traditional claim.

Background: Regardless of the availability of drugs many people still experienced pain and inflammation because current medications often trigger potentially serious adverse effects. A range of medicinal plants with analgesic and anti-inflammatory properties have been widely used by traditional healers. Among them, Gomphocarpus purpurascens is one however there are no experimental studies that support this traditional use.

Objective: This study aimed to evaluate the analgesic and anti-inflammatory activities of 80% methanolic leaf and root extracts of G. purpurascens.

Methods: Air-dried leaves and roots of G. purpurascens were extracted with 80% methanol and an acute oral toxicity study was conducted for the 80% methanolic extract of G. purpurascens according to OECD guideline version eighteen. Preliminary phytochemical screening for the presence of different constituents was carried out. The hot plate method was used to evaluate centrally mediated analgesic activity while peripheral analgesic activity was tested by an acetic acid-induced writhing test. Carrageenan-induced paw edema test and formalin-induced pedal edema test were used to evaluate anti-inflammatory activity.

Results: Dose-dependent inhibition of acetic acid-induced writhing test was observed in mice by 100 mg/kg, 200 mg/kg, and 400 mg/kg of root extract with respective values of 16.6%, 68.9%, and 83%. In the hot plate method, the root extract at doses of 200mg/kg and 400 mg/kg showed a significant (p < 0.05) analgesic effect. Maximum anti-inflammatory effects by all doses of leaf extracts were observed from 2-4hr post-induction in carrageenan-induced paw edema; and all tested doses of the extract inhibited the formalin-induced inflammation significantly (p < 0.001, p < 0.01). The presence of saponins, alkaloids, flavonoids, tannins, terpenoids, anthraquinone, steroids, and phenols might be responsible for these activities.

Conclusion: This study shows that the extract had potential analgesic and anti-inflammatory activity which supports the traditional claim.