Abstract
According to Traditional Chinese Medicine (TCM), Aconiti Radix Cocta (AC) is clinically employed to expel wind, remove dampness, and relieve pain. We evaluated the antirheumatoid arthritis (RA) activities and underlying mechanisms of AC. The chemical constituents of AC were analyzed by high-performance liquid chromatography (HPLC) using three reference compounds (benzoylaconitine, benzoylmesaconine, and benzoylhypacoitine). The anti-RA effects of AC were evaluated in adjuvant-induced arthritis (AIA) rats by hind paw volume and histopathological analysis. The effects of AC on inflammatory cytokines (IL-1β and IL-17A) were determined by enzyme-linked immunosorbent assay. The regulation of cyclooxygenases (COX-1 and/or COX-2) was determined by Western blot and real-time quantitative reverse transcription polymerase chain reaction analyses. AC significantly reduced paw swelling, attenuated the inflammation and bone destruction in joint tissues, and reduced IL-1β and IL-17A in the serum. Moreover, AC downregulated the expression of COX-1 and COX-2 in the synovial tissues. We also identified that AC possesses significant anti-RA activities on AIA, which may be ascribed to the regulation of inflammatory cytokines IL-1β and IL-17, as well as to the inhibition of arachidonic acid signaling pathways. Our findings provide theoretical support for AC as an effective nature-derived therapeutic agent for RA treatment.
Highlights
Rheumatoid arthritis (RA) is a polyarticular symmetric disease that involves multiple joints bilaterally, characterized by progressive joint destruction and deformity [1]
high-performance liquid chromatography (HPLC)-DAD Analysis of Aconiti Radix Cocta (AC). ree chemicals were quantified by calculating the peak area, and they were identified by comparing the retention times of each peak with the authentic references. e contents of the three main chemicals were found to be 0.084% for benzoylaconitine, 0.0276% for benzoylmesaconine, and 0.004% for benzoylhypacoitine (Figure 1)
After booster immunization on day 28, the hind paw volumes (HPV) slowly started to increase from day 35. e entire paw swelling process in the adjuvant-induced arthritis (AIA) group emulated the state of arthritis
Summary
Rheumatoid arthritis (RA) is a polyarticular (often but always) symmetric disease that involves multiple joints bilaterally, characterized by progressive joint destruction and deformity [1]. RA can cause accumulating joint damage, dysfunction, and poor physical functioning, leading to inefficient work capacity, low quality of life, and even death in severe cases [2, 3]. Two main medical treatments are considered for RA [5]: diseasemodifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs). DMARDs, such as methotrexate (MTX), can reduce inflammation, relieve pain, suppress disease activity, and slow cartilage/bone destruction. MTX was the first DMARDs to be approved, and it is currently the most commonly used DMARD for RA patients, as the first-line anchored DMARD to treat RA in clinical settings [6]. Long-term use of MTX may cause severe systemic complications. NSAIDs have been widely used to relieve pain and other inflammatory diseases in clinical settings [7]. Prolonged use of NSAIDs is linked to the manifestation of several adverse side effects such as gastrointestinal distress, high
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