Journal of Experimental Pharmacology最新文献

This narrative review intends to provide thorough information on the anti-inflammatory activities of Alpinia plants, the largest genus of the family Zingiberaceae. The articles were searched on the PubMed database using 'Alpinia AND anti-inflammatory activity' as the keywords, filtered to articles published from 2020 to 2024 and free full-text. Of the approximately 248 members of the genus Alpinia plants, the most commonly studied for their anti-inflammatory activities are A. galanga, A. officinarum, A. zerumbet, and A. oxyphylla. Only A. galanga, A. officinarum, and A. zerumbet have been studied in humans. Studies in animal models revealed that the plants contributed as exogenous antioxidants, reduced proinflammatory cytokines, inhibited proinflammatory enzymes, improved gastric acid and gastrointestinal motility, and promoted ulcer healing. The terpenoids, flavonoids (such as kaempferol, quercetin, and galangin), and diarylheptanoids obtained from the rhizomes of these plants may crucially play important roles in their anti-inflammatory activities. These plants did not show toxicity toward numerous normal cell lines (RAW 264.7, IEC-6, HepG2, MT-4, NIH-3T3, Vero cells, human peripheral blood mononuclear cells, and HaCaT) but were toxic to cancer cell lines (HT29). In humans, A. galanga was studied for its effects as psychostimulants improving mental health, improving sperm motility, and erectile dysfunction. Similarly, A. officinarum could improve sperm morphology and idiopathic infertility, whereas A. zerumbet worked as a cardio-myorelaxant in patients with cardiovascular diseases.

Purpose: A promising feature of marine sponges is the potential anticancer efficacy of their secondary metabolites. The objective of this study was to explore the anticancer activities of compounds from the fungal symbiont of Aaptos suberitoides on breast cancer cells.

Methods: In the present research, Aspergillus unguis, an endophytic fungal strain derived from the marine sponge A. suberitoides was successfully isolated and characterized. Subsequently, ethyl acetate extraction and isolation of chemical constituents produced was performed. The structures of the isolated compounds were identified using several spectroscopic methods, ie, UV, NMR, and mass spectrometry. Thereafter, MDA-MB-231, MCF-7 breast cancer cells and HaCat cells were treated with the isolated compounds. Not only viability, apoptosis, and cell cycle analyses were conducted, but also the mRNA expression of MCL1, BCL2L1, AKT1 and CDK2 were evaluated.

Results: The extract showed cytotoxic activity in breast cancer cells. Two novel compounds were successfully isolated and identified, ie, Unguisol A (15.1 mg) and Unguisol B (97.9 mg). Both compounds share the same basic skeleton and comprise an aromatic ring which is attached to a sulphur-containing, seven-membered ring via an oxygen atom. This marked the first-time isolation of Unguisol A and Unguisol B from A. unguis, highlighting their novelty. Both compounds induced early apoptosis (p < 0.01) and cell cycle arrest at the S phase (p < 0.05) in MDA-MB-231 cells, but not in HaCat cells. Both compounds suppressed BCL2L1 and AKT1 mRNA expression (p < 0.01).

Conclusion: Two novel compounds were isolated from A. unguis. Unguisol A and Unguisol B induced apoptosis in MDA-MB-231 breast cancer cells via BCL2L1 mRNA downregulation, while both compounds induced cell cycle arrest at the S phase through AKT1 mRNA downregulation.

Purpose: This study aims to provide new insights into the potential of oyster mushroom (Pleurotus ostreatus) ethanolic extract in preventing obesity through the inhibition of Pparg expression and modulation of methylation level on Pparg promoter during 3T3-L1 adipocyte differentiation.

Methods: This in vitro quantitative experimental study was conducted by treating the 3T3-L1 cell line differentiated using 0.5 mM methyl-isobutyl-xanthine, 1 μM dexamethasone, and 10 μg/mL insulin-containing medium with oyster mushroom ethanolic extract. The extract was obtained from 80 g of dried oyster mushroom powder extracted three times with 800 mL of ethanol, filtered, evaporated, and reconstituted in dimethyl sulfoxide (DMSO) to final concentrations of 0, 25, 50, and 100 µg/mL, with DMSO limited to 0.5% in all solutions. Pparg mRNA expression was quantified by qRT-PCR analysis and Pparg promoter methylation levels were measured quantitatively by pyrosequencing of bisulfite-treated DNA samples.

Results: The addition of 25 µg/mL oyster mushroom ethanolic extract significantly suppressed Pparg mRNA expression with no significant change in the Pparg promoter methylation levels.

Conclusion: Oyster mushroom ethanolic extract inhibited Pparg mRNA expression without altering Pparg promoter methylation, suggesting reduced adipocyte differentiation. This study emphasizes the potential of oyster mushroom in the prevention or treatment of obesity by inhibiting adipocyte differentiation.

Introduction: Lung cancer is recognized as a highly lethal disease, demanding swift and accurate solutions. Previous analysis showed the cytotoxic impact of Callyspongia aerizusa (C. aerizusa) extract containing ergost-22-en-3-one and ergost-7-en3-ol against A549 lung cancer cells, with an IC₅₀ value of 9.38 μg/mL. However, the extract did not have cytotoxicity towards Het-1A esophagus epithelial cells. Several reviews also validated the upregulation of pro-apoptotic molecules and the inhibition of anti-apoptotic molecules linked to the caspase-dependent signaling pathway.

Purpose: The objective of this research was to extend the understanding of the effects of C. aerizusa extract on A549 lung carcinoma, examining its influence on various signaling pathways, malignancy, migration, and invasion.

Materials and methods: PCR was used to measure mRNA expression, targeting PTEN, Akt, mTOR, STAT-3, IL-6, VEGF, and HIF1α. Additionally, Western Blot analysis was adopted to assess PTEN, p-Akt, Akt, p-mTOR, and p-STAT-3 protein expressions. Wound healing and invasion assays were performed to measure the migration and invasion capabilities of A549 cells post-treatment with C. aerizusa extract.

Results: The mRNA expression analysis showed an increase in Akt and m-TOR but a decrease in PTEN and STAT-3 after 24 hours of treatment with C. aerizusa extract. At the protein level, there was a downregulation of p-Akt, Akt, p-mTOR, and p-STAT-3, while PTEN increased during 24-hour treatment. Wound healing and invasion assay results showed a weakened ability of A549 cells after a 24-hour treatment with C. aerizusa extract. Moreover, IL-6 and HIF-1α mRNA expression levels decreased during 24 hours, while VEGF mRNA had a slight decrease compared to untreated cells.

Conclusion: In conclusion, the ergosteroids present in marine sponge C. aerizusa extract signified a remarkable reduction in malignancy, migration, and invasion capabilities in A549 lung carcinoma cells. These results suggested their promising candidacy for future anti-angiogenesis in anticancer therapy.

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.