Vitae

Computational screening, synthesis and neuroprotective evaluation of small molecule for the treatment of alzheimer's disease

Nerlis Pajaro-Castro — 2024-12-18

BACKGROUND: Current treatments for Alzheimer’s disease primarily address symptoms, as no definitive therapeutic targets have been identified.
OBJECTIVES: This study aims to conduct a virtual screening of small molecules and synthesize and evaluate one of the most promising candidates for Alzheimer’s therapy.
METHODS: Using AutoDock Vina, compounds with drug-like properties were docked against key proteins implicated in Alzheimer's pathology: β-Secretase, γ-Secretase, Pin1, and Cdk5. The molecule with the highest in silico affinity (PubChem ID: 84378305) was synthesized and evaluated experimentally. Cytotoxicity and neuroprotective effects were assessed using the MTT assay in the presence of the Aβ25-35 peptide.
RESULTS: Four candidate molecules showed strong binding affinity, ranging from -6.8 to -9.1 kcal/mol. The results showed that when SK-N-SH cells were simultaneously treated with Aß25-35 peptide (5 µM) and compound 84378305 (0,1 µM), the molecule exhibited significant neuroprotection (33%) after the 48 h of incubation.
CONCLUSION: Findings indicate that this lead compound exhibits potential neuroprotective activity, highlighting its promise as a candidate for further development in Alzheimer’s disease treatment.

Metabolite profile of Passiflora mollisima leaf using UHPLC-ESI-MS and its potential anxiolytic activity in mice

Carmen Luisa Marìn-Tello — 2024-12-10

Background: Traditionally, extracts of Passiflora mollisima leaves are used as anxiolytics, but the existing metabolites are unknown.
Objectives: To identify by UHPLC-ESI-MS/MS some of the metabolites and the anxiolytic activity of the leaf extract.
Materials and Methods: The extract was subject to UHPLC-ESI-MS/MS analysis and administered intraperitoneally (VIP) to 4 groups of mice: G1: white group 0.1mL of saline solution, G2: positive control group 1mg Kg¯¹ of diazepam and to treatment groups, namely, G3 50 mg Kg¯¹ and G4 100 mg Kg¯¹ and anxiety levels were evaluated with the light/dark transition test for mice.
Results: Six flavone C-glycosides were tentatively identified, namely vicenin 2, lucenin 2, schaftoside, orientin, vitexin, and glucopyranosyl methyl luteolin. Lower levels of anxiety were observed in animals of groups G3 and G4 based on the number of transitions, with a mean of 11±2 and 21±2, respectively, compared to G1, which was 2±1 (p<0.05). The groups displayed a significant difference among them (p<0.05). There was an increase in the total time spent in darkness in G3 and G4 Passiflora-treated mice with a mean of 70±8 and 113±8 respectively, compared to G1, which was 8±1 with a p<0.05.
Conclusion: The metabolites identified have biological activities, neuroprotective, antioxidant, anti-inflammatory, antibacterial, and anticancer effects. The results of the effects of the 50mg Kg¯¹ and 100 mg Kg¯¹ doses of ethanolic extract of Passiflora mollisima leaves significantly decreased anxiety levels (p<0.05). This information contributes towards its further use in a therapeutic, clinical setting.

In-vitro effect of the methanolic extract of Morinda citrifolia against the life cycle of Dermatobia hominis

Dumar Alexander Jaramillo Hernández — 2024-12-26

Background: bovine cutaneous dermatobiosis or furuncular myiasis caused by Dermatobia hominis is a parasitosis that mainly affects bovines in the tropics and represents a particular interest in public health as zoonosis. Its control is based on ivermectins, which have long withdrawal times, affecting the productive dynamics within dairy cattle herds.
Objective: to assess the in-vitro effect of the methanolic extract of the M. citrifolia ripe fruit against the life cycle of D. hominis.
Methods: D. hominis larvae were taken directly from naturally parasitized bovine skins. These larvae were exposed by immersion to different concentrations of the methanolic extract of M. citrifolia (10, 50, 100, 200, 300, 400, 460 mg/mL) diluted in distilled water. Ivermectin 1% was used as a positive control, and distilled water as a negative control. Subsequently, the larvicidal activity was evaluated in the first 48 hours post-immersion (PI), the pupicidal activity within 10 to 23 days PI, and the inhibition of the imagos emergence as well as their anatomical alterations, were evaluated within 24 to 35 days PI; recreating the pupal development and their hatching in the soil under controlled laboratory conditions. CL₅₀ and CL₉₀for the larvae phase were estimated through Probit regression analysis.
Results: M. citrofolia concentrations of 400 and 460 mg/mL had a significant (p<0.05) larvicidal effect of 40% (95% CI 34.7 - 43.9) and 60% (95% CI 56.8 - 67.3), respectively. The pupicidal effect on the surviving larvae was significant (p<0.05) at 300, 400, and 460 mg/mL: 40% (95% CI 37.9 - 42.3), 60% (95% CI 55.7 - 65.9) and 70% (CI 95% 67.1 – 76.7), respectively. The inhibition of the emergence of imagos was significant (p<0.05) 50% (95% CI 42.3 - 57.8) in all concentrations equal to or greater than 200 mg/mL. Finally, 20% (95% CI 12.6 - 29.3) of the emerging imagos at 460 mg/mL presented morphoananomic alterations (p<0.05). The LC₅₀ and LC₉₀ estimated (larval phase) were 22.36 mg/mL (95%CI 15.06-33.19) and 245.08 mg/mL (95%CI 165.10-363.82), respectively.
Conclusions: The methanolic extract of M. citrifolia was effective as larvicide, altering the pupation and the emergence of imagos of D. hominis. In addition, it modified the imagos morphoanatomy; interesting results to promote in-situ and other bioguided fractionation studies of this extract in different D. hominis stages; being M. citrifolia a plant species widely adapted to the conditions of the Meta department, Colombia.