Pharmacological Effects of Resveratrol in Intervertebral Disc Degeneration: A Literature Review

Orthopaedic Surgery, 2022 · DOI: 10.1111/os.13560 · Published: December 1, 2022

Pharmacology Orthopedics Spinal Disorders

Simple Explanation

Intervertebral disc degeneration (IDD) is a common musculoskeletal issue leading to spinal problems and lower back pain, causing significant economic strain. Current treatments focus on symptom relief rather than addressing the underlying causes of disc damage. Resveratrol (RSV), a natural compound found in plants and red wine, has shown potential in treating various diseases due to its anti-inflammatory, antioxidant, and regenerative properties. RSV's therapeutic effects on IDD involve reducing inflammation and oxidative stress, as well as influencing cell apoptosis, autophagy, and ECM biosynthesis through multiple signaling pathways. Current research is limited to preclinical studies. This review explores RSV's biological functions in treating IDD and provides insights for future research. The review indicates that RSV has several protective roles in IDD progression, including inhibiting apoptosis and senescence and promoting autophagy of NP cells. It exerts anabolic and anti-catabolic effects on ECM, crucial for regenerating damaged intervertebral discs. Multiple signaling pathways like PI3K/Akt and AMPK/SIRT1 are common targets of RSV in IDD treatment.

Study Duration

Not specified

Participants

Healthy volunteers and animal models

Evidence Level

Review Article

Key Findings

1
RSV exhibits anti-inflammatory effects by inhibiting pro-inflammatory cytokines like IL-1β, IL-6, IL-8, and TNF-α, which ameliorates IDD progression mediated by inflammation.
2
RSV improves ECM homeostasis by increasing proteoglycan content and anabolic factors (Sox-9, aggrecan, and collagen II), while reversing mechanical load-induced ECM degradation by activating the PI3K/Akt pathway.
3
RSV promotes autophagy of NP cells by activating the Nampt/NAD+/SIRT1 signaling pathway, attenuates oxidative stress-induced mitochondrial dysfunction, and inhibits NP cell senescence.

Research Summary

This review synthesizes current research on resveratrol's (RSV) effects on intervertebral disc degeneration (IDD). It highlights RSV's potential to address the limitations of current IDD treatments by targeting the underlying pathological processes. RSV demonstrates protective roles in IDD by inhibiting apoptosis and senescence, promoting autophagy in nucleus pulposus (NP) cells, and exerting anabolic and anti-catabolic effects on the extracellular matrix (ECM). These effects are mediated through various signaling pathways, including PI3K/Akt, NF-κB, AMPK/SIRT1, and ERK1/2. The review acknowledges the limitations of current studies, including their preclinical nature and focus on NP cells. It suggests further research to investigate RSV-containing drugs in clinical trials, explore synergistic effects with traditional drugs, and address the challenges of RSV's poor aqueous solubility and rapid metabolism using methods like US-mediated nanobubbles.

Practical Implications

Therapeutic Potential

RSV could be a promising candidate for IDD treatment due to its anti-apoptotic, anti-senescent, anti-inflammatory, anti-oxidative, and anabolic activities.

Targeted Drug Delivery

Novel methodological approaches, such as nanoparticles and nanobubbles, can improve the poor aqueous solubility and low bioavailability of RSV, enhancing its therapeutic efficacy.

Combined Therapies

Further studies should verify the synergistic effects of RSV combined with traditional drugs in treating IDD to enhance efficacy and decrease drug resistance and side effects.

Study Limitations

1
Published studies are limited to preclinical studies.
2
Current studies are mainly focused on NP, and the effects of RSV on AP and CEP also need systematic investigation.
3
Poor aqueous solubility and rapid metabolism of RSV might restrict its clinical application.

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