Pro‑differentiating compounds for human intervertebral disc cells are present in Violina pumpkin leaf extracts

Area of Science:

• Biochemistry
• Cell Biology
• Natural Product Chemistry

Background:

• Intervertebral disc degeneration (IDD) involves inflammation, oxidative stress, and loss of discogenic phenotype, with limited therapeutic options.
• Current treatments cannot reverse the degenerative process of the intervertebral disc (IVD).

Purpose of the Study:

• To investigate the therapeutic potential of acetone extract from *Cucurbita moschata* (pumpkin) leaves on degenerated IVD cells.
• To identify active compounds in the extract that can reverse IDD hallmarks.

Main Methods:

• Isolation of IVD cells from patient tissues undergoing spinal surgery.
• Treatment of cells with pumpkin leaf acetone extract and its subfractions, particularly Fr7.
• Analysis using Western blot, immunocytochemistry, and scratch assays to assess cellular markers and function.

Main Results:

• Subfraction Fr7, rich in p-Coumaric acid, significantly increased discogenic transcription factors (SOX9, SOX5), extracellular matrix components (aggrecan, collagen type II), and cellular homeostasis regulators (FOXO3a, Nrf2, SOD2, SIRT1).
• Fr7 enhanced stem cell markers (migratory capacity, OCT4 expression) and counteracted H2O2-induced damage, reducing pro-inflammatory miR-221.
• The extract promoted cellular repair mechanisms and countered inflammatory responses in degenerated IVD cells.

Conclusions:

• Pumpkin leaf extract, specifically p-Coumaric acid (Fr7), demonstrates significant potential in reversing key aspects of intervertebral disc degeneration.
• These findings suggest that compounds from pumpkin leaves can stimulate resident cells to restore IVD function and anabolic activity.
• This research highlights a novel, natural therapeutic strategy for IDD, utilizing a plant-derived waste product.