Abstract
The mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear to date, but reports showed that bladder inflammation and increasing number of activating mast cells in bladder tissues were common in patients with IC/BPS. Houttuynia cordata is widely used in Chinese traditional medicine, and its function of anti-inflammation has been proved. The purpose of this study was to investigate the efficacy and possible mechanisms of the Houttuynia cordata (HC) extract in the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). In the current study, a total of 30 adult female rats were randomly divided into three groups: sham group (n = 10), cyclophosphamide + saline (CYP + NS) group (n = 10), and cyclophosphamide + Houttuynia cordata extract (CYP + HC) group (n = 10). The animal model of IC/BPS was induced with cyclophosphamide (75 mg/kg, intraperitoneal injection, once every 3 days for 10 days) in the CYP + NS group and CYP + HC group, and sham rats received a volume-matched injection of saline. After anesthesia with urethane (0.8 g/kg, intraperitoneal injection), intravesical administration of either saline (1 ml) or Houttuynia cordata extract (1 ml, 2 g/ml) was continued once per day for a week in the CYP + NS group and CYP + HC group, respectively. Subsequently, urinary frequency, nociceptive behaviors, cystometry, bladder weight, histological changes, and cytokine (IL-6, IL-8, TNF-α) concentration were evaluated and compared among the three groups. Variables including inflammatory grade, mast cell number, proportion of activated mast cells, bladder weight, cytokine concentration of bladder homogenates, and frequency of urination significantly increased in the CYP + NS group compared with the sham group (P < 0.01) and CYP + HC group (P < 0.01). Besides, compared with the CYP + NS group, longer intercontraction interval, bigger bladder capacity, higher nociceptive threshold, fewer number of mast cells, and lower proportion of activated mast cells were found in the CYP + HC group (P < 0.01). Our study demonstrated that the Houttuynia cordata extract can effectively inhibit mast cell proliferation and activation and downregulate proinflammatory cytokine in a rat model of IC/BPS induced with cyclophosphamide and might be potentially valuable for the treatment of IC/BPS.
Highlights
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder inflammatory disease, characterized by urinary urgency, frequency, nocturia, and suprapubic pain, in the absence of infection or other identifiable causes [1]. e prevalence of interstitial cystitis/bladder pain syndrome (IC/BPS) is increasing, and to date there is no cure. e unpleasant symptoms persist or relapse frequently and cost lots for treatment [2]
The underlying mechanism of IC/ BPS remains unclear and the consensus on the pathophysiology is lacking, bladder inflammation appears to be common in many IC/BPS patients and increased number of activating mast cells in the bladder tissues were detected [3]. e inflammatory mediators such as interleukin-6 (IL-6), interleukin8 (IL-8), and tumor necrosis factor-α (TNF-α) released from mast cells play important roles in the inflammation and bladder-associated pelvic pain of IC/BPS [4]. us, the suppression of mast cell proliferation and control of inflammatory reaction may be an important aspect for treating IC/BPS
Animal Groups and Treatment Protocol. irty adult female Sprague-Dawley rats (200–250 g in weight) were treated under a protocol approved by the Sun Yat-sen University Institutional Animal Care and Use Committee (IACUC-2013-0803). e rats were randomly assigned to three groups (10 rats in each group): (1) sham group, (2) cystitis induced by cyclophosphamide (CYP) and treated with saline (CYP + NS group), and (3) cystitis induced by cyclophosphamide and treated with the Houttuynia cordata extract (CYP + HC group)
Summary
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic bladder inflammatory disease, characterized by urinary urgency, frequency, nocturia, and suprapubic pain, in the absence of infection or other identifiable causes [1]. e prevalence of IC/BPS is increasing, and to date there is no cure. e unpleasant symptoms persist or relapse frequently and cost lots for treatment [2]. The underlying mechanism of IC/ BPS remains unclear and the consensus on the pathophysiology is lacking, bladder inflammation appears to be common in many IC/BPS patients and increased number of activating mast cells in the bladder tissues were detected [3]. E inflammatory mediators such as interleukin-6 (IL-6), interleukin (IL-8), and tumor necrosis factor-α (TNF-α) released from mast cells play important roles in the inflammation and bladder-associated pelvic pain of IC/BPS [4]. Its function of anti-inflammation had been proved, and it has been used for treating various inflammatory diseases such as suppuration, chronic bronchitis, pneumonia, and pleurisy [8,9,10]. As for the mechanism, a previous study reported that HC could inhibit mast cell activation effectively [11]. Some reports demonstrated that HC suppresses the release of inflammatory mediators such as IL-6, IL-8, and TNF-α in LPS-treated RAW 264.7 cells and HMC-1 human mast cells [12,13,14]
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