OBJECTIVE: Based on their biological capability, various acetogenins were studied in the present study and compared alongside ABT-737 on molecular docking.

METHODS: The docking simulation of acetogenins was performed using AutoDock Vina software.

RESULTS: Our findings have shown eleven acetogenins-BCL-XL protein complex, namely, muricin B (2), muricin F (4), muricin H (6), muricin I (7), xylomaticin (9), annomontacin (12), annonacin (14), squamocin (15), squamostatin A (16), bullatacin (20) and annoreticulin (21) exhibited strong binding affinities lower than - 10.4 kcalmol-1 as compared to ABT-373-BCL-XL complex. Six hydrogen bonds along with hydrophobic interaction were detected on the complex of BCL-XL with muricin B (2), muricin G (5), corossolone (11), and isoannonacin-10-one A (18).

METHODS: Immunofluorescence staining was used to observe the structural features of PC12 cells after culturing in medium with nerve growth factor (NGF). After different doses and different durations of alcohol treatment, CCK-8 assay was performed to detect the viability of PC12 cells, flow cytometry assay was carried out to detect the apoptosis rate of PC12 cells, dual-luciferase reporter assay was used to definitude the regulatory relationship between miR-96-5p and Tp73, and western blot was used to detect the protein expression of TAp73.

RESULTS: The result of immunofluorescence staining demonstrated that PC12 cells abundantly expressed Map2, CCK-8 assay illustrated alcohol exposure significantly downregulated the cell viability of PC12 cells, Treatment with miR-96-5p inhibitor induced apoptosis and upregulated the expression of TAp73 in PC12 cells. Contrastingly, miR-96-5p mimic reversed the above effects and downregulation of TAp73 inhibited the apoptosis of PC12 cells.

METHODS: In vitro cell model of IDD was established by treating human nucleus pulposus cells (HNPCs) with interleukin-1β (IL-1β). The level of peroxisome proliferator-activated receptor γ (PPARγ) was examined in the IDD cell model by Western blot and quantification real-time reverse transcription-polymerase chain reaction (qRT-PCR). The expression level of miR-96-5p was detected by RT-qPCR. Effects of PPARγ or/and PPARγ agonist on inflammatory factors, extracellular matrix (ECM), apoptosis, and nuclear factor-kappaB (NF-κB) nuclear translocation were examined through enzyme-linked immunosorbent assay (ELISA), Western blot, flow cytometry assay, and immunofluorescence staining. The Starbase database and dual luciferase reporter assay were used to predict and validate the targeting relationship between miR-96-5p and PPARγ, and rescue assay was performed to gain insight into the role of miR-96-5p on IDD through PPARγ/NF-κB signaling.