The incidence of gout continues to increase every year, and an acute attack is often triggered by multiple factors in its chronic course. NSAIDs, systemic corticosteroids, and oral colchicine are recommended by the 2012 ACR guide for treating AGA ; however, the side effects of these drugs limit their use in the clinic. Recent studies on AGA treatment with traditional Chinese medicine have shown unique advantages and fewer side effects. In this study, the T2 group had a significant reduction in the VAS score of joint pain, arthrocele, and decreasing pain duration compared with the control and T1 group (P < 0.05), indicating that the external application of CQBG on AGA, combined with Western–medicine–bastic treatment, had therapeutic effects of quickly alleviating clinical symptoms such as pain and swelling, shortening disease course, and reducing patients’ burden.
Accumulated dampness-heat syndrome is a common syndrome of AGA in the clinic. In the theory of traditional Chinese medicine, a deficiency of spleen qi and imbalance of metabolism of water and food can induce the accumulation of damp. Additionally, eating too much greasy food with stronger flavor can cause accumulation of damp, leading to heat accumulation in the skin and joints and resulting in a gout attack. Hence, the external application of prescription in traditional Chinese medicine for gout focused mainly on clearing heat and expelling dampness, which was demonstrated in some studies with clear efficacy for AGA, namely, good therapeutic effect in controlling symptoms in acute gout and reducing recurrence rate. For instance, oral Jiawei Simiao Powder and external application of Sihuang water–honeyed pill had significant effects in decreasing the blood UA level and improving the joint function of patients with AGA .
In this study, CQBG was found to be effective in improving the function of anti-inflammatory and analgesic drugs as well as lowering blood CRP and blood UA levels. Its mechanism might be related to the decline in inflammatory cytokine release caused by effective components of this compound drug. CQBG is formulated with Cortex Phellodendri and Herba tuberculate speranskia. Cortex Phellodendri with cold nature was originally documented in the Holy Husbandman's Classic on Roots and Herbs (finished in 1616 AD), which was always used against pyogenic infections with active elements of tetrandrine and berberine that exerted anti-inflammatory and immunoregulatory effects by reducing the expression of inflammatory cytokines and increasing the expression of anti-inflammatory cytokines [18, 19]. Clinically, Cortex Phellodendri can be used in the treatment of arthritis, gout, and so forth, through lowering UA and creatinine levels in model rats with hyperuricemia and inhibiting arthrocele in model rats with acute gout arthritis. Herba tuberculate speranskia, which is pungent and warm in nature, was originally documented in Jiuhuang Beneao (finished in 1525 AD) with the efficacy of expelling damp and swelling and relieving pain. The anti-inflammatory effect of this Chinese traditional medicinal crop and its components and the inhibition of platelet aggregation were shown in pharmacological studies. Moreover, this drug reduced swelling of the paw in model rats with arthritis; inhibited the proliferation and transfer of synovial cells and release of inflammatory cytokines; decreased the protein expression of inflammasome NLRP3, caspase-1, and IL-1β; inhibited inflammatory cell infiltration and angiogenesis; promoted apoptosis; reduced serum inflammatory factors IL-1β and TNF-α levels; and significantly inhibited the inflammatory reaction. Clinically, Herba tuberculate speranskia is used mostly for external application in rheumatic arthralgia, bone and muscle contracture, and pyogenic infections[13, 21–25]. In summary, the external application of this compound had antibacterial, anti-inflammatory, analgesic, and anticoagulatory effects against AGA. Among these, the anti-inflammatory function helped reduce the local swelling of joints and prevent local infection. The analgesic effect relieved anxiety produced by pain, and the anti-coagulatory effect helped in the remission of local swelling and pain besides thrombogenesis prevention. Moreover, drugs were efficiently absorbed percutaneously, achieving an obvious clinical effect in a short time.
The external application of this compound combined with Western–medicine–bastic treatment with a significant therapeutic effect in lowering CRP and blood UA levels of patients with AGA was better compared with the conventional treatment (control) group (P < 0.05). CRP is a nonspecific indicator reflecting inflammatory activity, which is involved in the pathological process of chemotaxis and activation of inflammatory cells. CRP is a polypeptide consisting of five identical polypeptide chain subunits and also a calcium-binding protein. It is rarely found in healthy people but rises quickly during inflammation and acute injuries in the body and drops down rapidly with an improvement in condition. Therefore, CRP is important in nonspecific immunity. Additionally, it plays an important role in the clinic by reflecting whether rheumatoid fever and gout can be controlled or whether relapse occurs in patients. CRP in the inflammatory joint fluid positively correlates with CRP in blood. CRP in the inflammatory joint fluid, secreted by monocytes and lymphocytes of the synovium, has high expression in the lower lining layer of the inflammatory synovium of joints with the activation of the NF-κB/P65 pathway of synoviocytes and suppression of its nonspecific factor IκB. CRP can significantly increase the levels of inflammatory factors such as IL-6, MMP-3, and TNF-α produced by synoviocytes, promoting inflammation of the joints. Hence, CRP not only reflects the activity of joint inflammation but also participates in the development of arthritis as a pro-inflammatory factor, as shown in one study . Therefore, it was speculated that one of the therapeutic mechanisms of CQBG on AGA might be through reducing the CRP level, inhibiting the NF-κB/P65 pathway, and reducing the expression of inflammatory factors.
CQBG treatment group could lower the blood UA level and reduce the accumulation of urate crystals in joints, thus further reducing inflammatory cell infiltration and improving the arthritis profile.UA exists in vivo as ionic UA salts, and urate crystal starts to accumulate in tissues when the serum UA level exceeds the normal threshold. A continuous accumulation of urate crystals in joints triggers an acute inflammatory reaction with severe arthralgia, swelling, burning, redness, and difficulty in the movement of involved joints. Meanwhile, early symptoms of mild joint discomfort or stabbing pain can occur in the attack and reach a peak within 24 h. Hence, one of the objectives in clinical treatment is to reduce the blood UA level by inhibition of uric acid production and promotion of the excretion of uric acid. The experimental results indicated that the extract of Cortex phellodendri (One of the components of CQBG)can significantly inhibit xanthione oxidase(XOD) activity in liver, down regulate XOD mRNA and protein expression, and significantly reduce the expression level of mURAT1 mRNA and protein in kidney, therefore, which might be dual effects include the inhibition of production of uric acid and the reabsorption of uric acid in the kidney in hyperuricemia mice.
Ultrasound has the characteristics of easy operation, noninvasiveness, flexibility, and high sensitivity and hence provides vivid and visualized monitoring and assessment for patients with gout . Therefore, it is widely applied in the diagnosis and evaluation of gouty arthritis. Synovium thickening was a typical manifestation of gout in the acute stage. In this study, a significant decline in the thickness of the synovium of joints was observed in the CQBG treatment group compared with the control group. In this study, the detection rate of double track sign under ultrasound is not high. The reason may be that the patients in this study were in-patient with serious condition, and most of them were accompanied with obvious gout stone and bone destruction,so the rear serious sound attenuation affected the detection rate. At the same time, this double track sign should be differentiated from calcium pyrophosphate deposition in the joint (also known as pseudogout).