Journal of Experimental Pharmacology最新文献

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.

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.