Abstract
Silkworm excrement (SE), is used as a traditional antirheumatic medicine in China. The present study was designed to investigate the therapeutic efficacy of water fraction of SE (ST) and ethanol fraction of SE (CT) at two different doses on adjuvant induced arthritis (AA) rats. Arthritis severity was evaluated by body weight, paw thickness, histological changes and index of paws oedema and spleen. Serum samples were collected for estimation of biochemical indicators and cytokines. In addition, a metabonomic method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of SE by serum and urine. Multivariate statistical approaches, such as partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were built to evaluate the therapeutic effects of SE and find potential biomarkers and metabolic pathways. Administration with SE significantly ameliorated the AA severity, including body weight loss, paw swelling, histological changes and the levels of biochemical index. 33 endogenous metabolites had been identified (10 in serum and 23 in urine) in the AA rats. Urinary and serum metabolic profiling revealed that the metabolites underpin the metabolic pathway including nicotinate and nicotinamide metabolism; pentose and glucuronate interconversions; TCA cycle; beta-Alanine metabolism; purine metabolism and glycolysis or gluconeogenesis. The altered metabolites could be regulated closer to normal level after SE intervention. The results suggested SE possesses substantial anti-arthritic activity and demonstrated that metabonomics is a powerful tool to gain insight in the mechanism of SE formula in therapy.
Highlights
IntroductionRheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that affects different parts of the body, inevitably causing pain, swelling and loss of function in joints [1]
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that affects different parts of the body, inevitably causing pain, swelling and loss of function in joints [1].RA significantly impacts quality of life, leading to severe disability in the patient
The paw swelling degrees of rats in the groups treated with ST and CT were significantly decreased compared with the adjuvant induced arthritis (AA) models (Figure 1)
Summary
Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that affects different parts of the body, inevitably causing pain, swelling and loss of function in joints [1]. RA significantly impacts quality of life, leading to severe disability in the patient. Current conventional therapies for RA patients, including disease-modifying antirheumatic drugs (DMARDs) and biologics, Molecules 2018, 23, 1490; doi:10.3390/molecules23061490 www.mdpi.com/journal/molecules. Molecules 2018, 23, 1490 are not satisfactory. To the best of our knowledge, there is no unified theory about the pathogenesis of RA. Metabolomics is one of the newest methods focused on the association between disease and metabolic profile. Several analytical techniques have been widely used to determine the metabolites, including mass spectroscopy, 1 H-NMR spectroscopy and liquid chromatography-mass spectroscopy [2]
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