Journal of Experimental Pharmacology最新文献

Acne vulgaris is a prevalent dermatological condition characterized by comedones, papules, and pustules, with significant physical and psychological implications. Conventional treatments for this condition, including antibiotics and retinoids, face challenges, such as side effects and antibiotic resistance, necessitating alternative treatments. Recent studies show the potential of probiotics to modulate skin microbiome and alleviate acne symptoms. Therefore, this study aimed to consolidate evidence from randomized controlled trials (RCTs) and clinical investigations, evaluating the efficacy of probiotics in acne management. A comprehensive literature search was conducted across PubMed, Scopus, and Cochrane databases using several keywords, such as "probiotic", "microbiome", and "acne vulgaris". Inclusion criteria are RCTs and clinical studies from 2009 to 2024 examining probiotics for acne treatment. Studies were selected, screened, and analyzed based on population, intervention, design, and results. Descriptive statistics were used to summarize study characteristics. Fifteen studies including 811 participants met the inclusion criteria. The studies tested various oral and topical probiotics, including Lactobacillus, Bifidobacterium, Bacillus, and Enterococcus strains, over treatment periods ranging from 4 to 12 weeks. The results showed that probiotics, reduced acne lesions, improved skin barrier function, and decreased inflammatory markers. Both oral and topical probiotics showed potential in balancing skin microbiome and reducing acne severity. Some studies reported outcomes comparable to conventional acne treatments, such as antibiotics and benzoyl peroxide. However, there is variability in individual responses to different probiotic strains, and potential side effects, though rare, have been reported in some cases. Probiotics presented a natural, effective alternative to conventional acne treatment. However, future studies are needed to determine optimal treatment protocols.

Purpose: Endoplasmic reticulum (ER) stress has a prominent role in the pathogenesis of high-fat diet-induced non-alcohol related fatty liver disease (NAFLD). The aim of this study is to investigate the effects of 6-G on the reduction of ER stress-induced NAFLD in metabolic syndrome (MetS) rats.

Methods: Twenty-five male Sprague-Dawley rats were fed with a high-fat high-fructose (HFHF) diet for 16 weeks. The rats were treated orally with 6-G (50,100, and 200 mg/kgBW) once daily for eight weeks. At Week 16, all animals were sacrificed, and serum and liver tissue were harvested for biochemical and structural analysis.

Results: NAFLD liver rats were shown to have elevated protein expression of GRP78, and ER-associated apoptotic protein, such as IRE1, TRAF2, p-JNK, and p-NF-κB, which were considerably reduced by the 6-G at three doses treatment. Furthermore, a significant increase in liver apoptosis and non-alcoholic steatohepatitis (NAS) score were observed in the NAFLD rat liver and which were also attenuated by the 6-G treatment at three doses. 6-G treatment also reduced ALT, AST, and ALP serum levels.

Conclusion: Considering all the findings, it is suggested that the 6-G treatment could be a potential candidate therapy in treating ER stress-induced NAFLD in rats.

Background: Fluoxetine (FLX) is a Selective Serotonin Re-uptake Inhibitor (SSRI) commonly used as a first-line treatment for depression, anxiety, and mood disorders. It can cause infertility in the male reproductive system through the release of Reactive Oxygen Species (ROS). This study aimed to evaluate the testiculo-protective potential of ascorbic acid against fluoxetine-induced spermatotoxicity in male Wistar rats.

Methods: This study assessed Vitamin C's effect on male fertility in fluoxetine-treated Wistar rats. Thirty rats (130 ± 40 g) were divided into six groups (n=5): Control (distilled water), fluoxetine 20 mg/kg, Vitamin C 100 mg/kg, fluoxetine 20 mg/kg + Vitamin C 50 mg/kg, fluoxetine 20 mg/kg + Vitamin C 100 mg/kg, and fluoxetine 20 mg/kg + Vitamin C 150 mg/kg. Treatments were administered daily via oral gavage for 60 days, followed by assessments of testicular weight, semen analysis, oxidative stress biomarkers (CAT and GPx), and histomorphology. The data was analyzed using one-way ANOVA and Turkey's post-hoc multiple comparison test, reporting as mean±SEM using The GraphPad Prism version 6.0 for Windows, with significance set at p<0.05.

Results: Vitamin C, administered particularly at higher doses, significantly increased body weight, testicular weight, and antioxidant enzyme levels (glutathione peroxidase and catalase) while improving fertility parameters such as sperm count, motility, and viability in treated rats (P<0.05). Fluoxetine alone led to a significant reduction (P<0.05) in these parameters, but the combination with Vitamin C mitigated these effects. Histological analysis showed improved testicular structure in Vitamin C-treated groups, highlighting its protective role against fluoxetine-induced testicular damage.

Conclusion: Ascorbic acid has testiculoprotective potential in fluoxetine-induced spermatotoxicity, mainly owing to its antioxidant properties.

Background: Depression continues to be a serious mental health problem among communities in Uganda, with limited access to mental healthcare services. Communities often use medicinal plants, such as L. angustifolia, in the management of depressive disorders with limited information on its effectiveness.

Objective: Study assessed antidepressant-like effects of stem-leaf aqueous and total crude extracts of L. angustifolia in depression-like induced behavior in Wistar albino rats.

Methods: An experimental laboratory study was conducted on 36 Wistar albino rats (18 males, 18 females). Group I received normal saline, Group II received 10 mg/kg bwt escitalopram, Group III received 200 mg/kg bwt, Group IV received 1000 mg/kg bwt aqueous extract and same doses of total crude extract were used for Group V and Group VI, respectively, using intragastric tube. Depression-like behavior in rats was induced by several manipulations of CUS for 1-5 weeks. Sucrose preference test (SPT) was used to confirm depressive-like behaviors. Antidepressant-like effects were determined by FST. Durations of immobility, swimming, and struggling were recorded. Data were analyzed using STATA version 13.

Results: In the chronic mild stress group, 19.2% preferred sucrose compared to 66.9% in the unstressed group (p<0.05). L. angustifolia extract (LAE) exhibited antidepressant-like effects in the rats in a completely dose dependent manner at aqueous doses of 200 mg/kg bwt and 1000 mg/kg bwt, respectively. In the FST, dose of 200 mg/kg bwt and 1000 mg/kg bwt of the extract showed a significant reduction in mean immobility time of 1.33±0.52 min and 1.83±1.17 min (p<0.0001) as compared to 1.00±0.00 min for escitalopram drug and 3.17±0.41 min of the normal saline control groups.

Conclusion: Aqueous extract of L. angustifolia at a dose of 200 and 1000 mg/Kg bwt reduced the duration of immobility and similar findings were observed on struggling and swimming. Findings have provided evidence on the use of L. angustifolia by local communities in the management of depressive-like behaviors in Uganda.

Background: Croton oligandrus Pierre & Hutch is a tropical tree that grows in West and Central Africa, used in ethnomedicine to treat cancer, diabetes, headaches, convulsions, urinary diseases, and inflammatory diseases. As other Croton species have been observed to possess chemical compounds that target HIV latency-reversal, we hypothesized that this species may have similar properties.

Aim of the study: The identification of extracts and compounds of this species, which have HIV-1 latency-reversing activity in J-Lat T cell lines.

Methods: The stem bark was obtained, air-dried, powdered, and extracted using dichloromethane. In vitro flow cytometry was used to monitor GFP expression, a marker of HIV latency reversal, following treatment of J-Lat T cells with extracts and compounds.

Results: Four extracts were found to reverse HIV latency, the most active extract showing better activity (ie, latency reversal in 69.7 ± 7.1% [mean ± s.e.m.] of J-Lat 10.6 cells at 1 µg/mL) than control agents prostratin (46.2 ± 9.5% at 1.2 µg.mL) and the "Mukungulu" (Croton megalobotrys) extract (34.9 ± 24.2% at 1 µg/mL). Extracts reversed HIV latency through mechanisms over and above protein kinase C (PKC) activation and distinct from histone deacetylase (HDAC) inhibition. The most active extract also synergized with the control HDAC inhibitor romidepsin but did not synergize with other extracts. Isolated compounds (β-Stigmasterol and lupeol) had limited but consistent latency reversal on their own.

Conclusion: The plant extracts and compounds reverse HIV latency through mechanisms additional to PKC activation and/or synergize with romidepsin in vitro. Extracts and compounds from this plant may enhance the activity of current HIV latency-reversing agents being assessed in HIV cure studies.

Background: Asthma is a chronic respiratory disease that is characterized by inflammation, bronchial hyperreactivity, and airway remodeling. The long-term use of corticosteroids at high doses causes various side effects. Traditional herbal medicine has been suggested as an alternative therapy that is safe and effective in dealing with asthma. Natural plants such as turmeric and mangosteen are known to treat asthma and reduce inflammation.

Objective: The purpose of this study was to investigate the effects of turmeric and mangosteen pericarp ethanol extracts on the eosinophil counts, TNF-α and TGF-β1 gene expression, and inflammatory cell counts in the histopathology of an asthmatic rat model.

Methods: The preliminary study used 30 rats, which were divided into a normal group, negative control group (OVA-sensitized), turmeric normal group, mangosteen group, and positive control group. Blood samples were collected after the sensitization period to determine eosinophil counts. TNF-α and TGF-β1 gene expression, and histopathology were observed in the rat's lungs. The follow-up study used 30 rats divided into a normal group, negative control group (OVA-sensitized), combination of turmeric and mangosteen group (54m/200gr rats, 36mg/200gr rats, and 36mg/200gr rats), and positive control group. The examination procedures were the same as in the preliminary study.

Results: The administration of single ethanol extracts of turmeric and mangosteen significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p<0.05). The combination of turmeric and mangosteen extracts at all doses significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p<0.05). Both the single and combined administration of turmeric and mangosteen ethanol extracts did not cause significant changes in TNF-alpha and TGF-beta (p>0.05).

Conclusion: Turmeric ethanol extract and mangosteen pericarp ethanol extract have a reductional effect on the parameters of asthma based on the eosinophil counts, the inflammatory cell counts and score, and bronchial smooth muscle thickness.

Introduction: Oral mucosal wounds present significant clinical challenges due to their susceptibility to infection, inflammation, and delayed healing. The limitation of standard anti-inflammatory drugs (both steroidal and non-steroidal) highlights the urgent need for plant-derived alternative therapies. Granola potato (Solanum tuberosum L.) from Pangalengan, West Java, Indonesia, has shown promise due to its bioactive compounds. However, its potential for wound healing and anti-inflammatory effects, specifically for oral mucosal wounds, remains largely unexplored.

Purpose: To evaluate the wound healing and anti-inflammatory activity of Granola potato peel ethanol extract (GPPEE) on the oral mucosa of Wistar rats based on histopathological analysis.

Materials and methods: Forty-eight Wistar rats were wounded on the palatal mucosa using a 4 mm punch biopsy and subsequently divided into four groups: placebo gel, 0.1% triamcinolone acetonide ointment (TCA), 4% GPPEE gel, and 6% GPPEE gel. The rats were euthanized on days 0, 1, 3, 7, and 14. Histopathological parameters assessed included fibroblast proliferation, collagen deposition, angiogenesis, and the presence of inflammatory cells.

Results: Phytochemical screening revealed the presence of phenolic compounds, flavonoids, tannins, and alkaloids in the Granola potato peel ethanol extract (GPPEE). Significant differences in the number of inflammatory cells were observed on days 1, 3, 7, and 14 (p<0.05), with the groups treated with 4% and 6% GPPEE gel initially exhibiting pro-inflammatory effects on day 3, followed by significant anti-inflammatory effects on days 7 and 14. The 6% GPPEE gel treatment demonstrated a notable increase in fibroblasts on days 1, 7, and 14 (p<0.05), as well as collagen deposition on days 7 and 14 (p<0.05). However, no significant difference was observed in angiogenesis (p>0.05).

Conclusion: The application of 4% and 6% GPPEE gel demonstrated superior wound healing efficacy compared to 0.1% TCA and exhibited comparable anti-inflammatory activity to 0.1% TCA.

Introduction: Antimicrobial resistance is a critical global issue, and medicinal plants, as a key source of therapeutic agents, offer potential solutions by offering new antibacterial agents. Acacia polyacantha tree, known as Al Kakamout in Sudan, is a significant source of Gum Arabic and has been traditionally used to treat bacterial diseases. This study aimed to investigate a hydro-ethanol extract of Kakamout stem bark through GC-MS analysis, evaluate its antibacterial activity against two standard bacterial strains, and conduct molecular docking and ADME studies.

Methods: The stem bark of the plant was extracted by maceration using a hydro-ethanol solvent and analyzed via GC-MS. The antibacterial activity of the extract was evaluated against Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 using the well diffusion method. The identified compounds were studied in silico to investigate their binding affinities with the target bacterial proteins. The ADMET properties were predicted for the top scoring compounds.

Results: GC-MS analysis revealed the presence of 11 compounds, with the major ones being dopamine, N, N-dimethyl-, dimethyl ether (43.76%), 4-O-methylmannose (23.27%), sucrose (8.09%), 1,4,7-triazacyclononane, 1-benzoyl- (5.41%), and lupeol, trifluoroacetate (5.24%). The extract demonstrated significant effectiveness against both bacterial strains, even at a low concentration of 50 mg/mL. Molecular docking showed that compounds 1, 3, 4, and 6 had the best docking scores with enoyl-acyl carrier protein reductase (FabI) (PDB ID: 3GR6) from S. aureus (-6.142, -10.843, -6.218 and -7.14 Kcal/mol). Similarly, compounds 1-6 exhibited favorable binding energies with LasR-TP4 complex (PDB ID: 3JPU) from P. aeruginosa (-10.025, -9.127, -8.623, -7.092, -7.722, and -6.019 Kcal/mol).

Conclusion: This study provides the first GC-MS analysis of Acacia polyacantha stem bark, identifying potential antibacterial compounds. Molecular docking and ADMET predictions suggest several promising compounds for further investigation as antibacterial agents.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) is currently of great concern due to its risk of developing T2DM and cardiovascular disease. The development of NAFLD may be initiated by de novo lipogenesis in the hepatocytes. Sirtuin1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK), are responsible for the lipogenesis mechanism. Interestingly, plant sterols, such as beta-sitosterol and stigmasterol, have the potential to lower the LDL-cholesterol in dyslipidemic patients. Beta-sitosterol was present in the ethanol extract of Lygodium microphyllum herbs at a concentration of 283.55 µg/g extract. This sterol interacted with the active allosteric-binding site of SIRT1 and AMPK similarly to the proteins' activators.

Purpose: To investigate the anti-lipogenesis activity of the ethanol extract of L. microphyllum (ELM) in the liver tissue of rats through the SIRT1 and AMPK levels.

Methods: Forty male Wistar rats were used in this study: (1) normal control group; (2) high-fat high-fructose diet (HFHFD) rats; (3) HFHFD rats treated with metformin; (4) HFHFD rats treated with resveratrol; (5) HFHFD rats treated with beta-sitosterol; (6-8) HFHFD rats treated with ELM doses of 200, 400, and 600 mg/kg BW. Rats in the normal control group were fed regular chow, while other groups of rats were given HFHFD for 35 days. All drugs were given orally on D15 till D35. On D35, the rats were sacrificed, and the liver organs were examined for the liver index, morphology, NAFLD activity score (NAS), and levels of SIRT1 and AMPK.

Results: ELM improves the morphology, the liver index, the steatosis condition, and the NAS of HFHFD-induced NAFLD rats. ELM increases the levels of SIRT1 and AMPK in the liver tissue of HFHFD-induced NAFLD rats.

Conclusion: ELM may have the potential to inhibit de novo lipogenesis by increasing the levels of SIRT1 and AMPK.

Purpose: Rope bamboo (Gigantochloa apus) is traditionally used for medicinal purposes, and extracts from stem leaves and shoots have been shown to possess antioxidant and anti-inflammatory activity. Thus, this study looked at the potential compounds present in and the usefulness of Rope bamboo liquid smoke preparations in the wound healing process in mice.

Methods: The fingerprinting of the liquid smoke was done by liquid chromatography-mass spectrometry. In-vivo experiments were conducted to observe the diameter and percentage of wound healing in mice for 14 days using topical formulations containing liquid smoke concentrations of 100%, 50%, 25%, positive control and negative control. Statistical analyses were conducted using the Kruskal-Wallis test and Spearman correlation.

Results: The phytochemical fingerprint showed the presence of alkaloids, flavonoids, vitamins, phenols, and lipids. The 100% undiluted liquid smoke accelerated wound healing faster compared to 50% and 25% dilutions. The differences in wound diameters were statistically significant across treatments having a p-value of 0.020 and dose-dependent (p = 0.029).

Conclusion: Liquid smoke acceleration of the wound healing process was dose-dependent compared to controls. This dose-dependency indicates that the wound healing effects were probably due to the anti-inflammatory, antioxidant, and antimicrobial activities of the elucidated constituents of Rope bamboo liquid smoke.