Rhein– A potential biological therapeutic drug for intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is a public health problem. IDD is generally regarded as an important cause of low back pain [1], which continues to be a common disability that reduces patients’ quality of life and increases health care expenditures . IDD is thought to involve sequential changes of intervertebral disc (IVD) that lead to the reduction of disc cells and the extracellular matrix, which is made predominantly of proteoglycans, collagens, and noncollagenous proteins. In addition, inflammation has been shown to contribute to IDD . However, current clinical treatments of IDD mainly focus on the clinical symptoms of IDD, and no attempt has been tried to interfere with the biochemical and pathophysiologic processes of degeneration for effective prevention and therapy of IDD.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) (RH) is an anthraquinone molecule derived from the rhizome of Rheum palmatum and related species . The anti-inflammatory and -tumor activities of RH have been well-documented . Recently, diacerein, a metabolic precursor of RH, has been used in the treatment of osteoarthritis (OA) and demonstrated significant effects on pain relief and function improvement. Two main abilities of RH have been validated to be responsible for the effects: anti-inflammatory activity and enhancing the synthesis of matrix components, such as types I, II collagen and aggrecan .

However, up to now, no reported studies have examined the therapeutic effects of RH for IDD. Given the occurrence of matrix degeneration and involvement of inflammation in IDD, we hypothesize that RH might be a potential biological therapeutic drug for IDD.

Based on the above, we hypothesize that RH could slow the progression of IVD by diminishing IL-1 induced apoptosis of IVD cells, and inhibiting IL-1 induced secretion of MMPs and aggrecanases, and thus may be a potential biological therapeutic drug for IDD.

RH has the ability to diminish IL-1 induced apoptosis of IVD cells, as well as inhibit IL-1 induced secretion of MMPs and aggrecanases, which together will contribute to the inhibition of the progression of IDD. If our hypothesis is supported by further experiments, RH will be applied as a potential biological therapeutic drug for IDD.

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