The Japanese Herbal Medicine Yokukansan Exerted Antioxidant and Analgesic Effects in an Experimental Rat Model of Hunner-Type Interstitial Cystitis

Abstract

Background and Objectives: The Japanese herbal medicine Yokukansan (YKS) has analgesic properties and is used for various pain disorders. The purpose of the present study was to investigate the effects of YKS in Hunner-type interstitial cystitis (HIC) using an experimental rat model of HIC and to explore its antioxidant activity and role as the underlying mechanism of action. Materials and Methods: The antioxidant capacity of YKS was evaluated by determining its hydroxyl radical (·OH) scavenging capacity using electron spin resonance (ESR). Next, the effects of YKS administration were explored using a toll-like receptor-7 agonist-induced rat model of HIC. The von Frey test was performed to assess bladder pain. Three days after HIC induction, the bladder was removed, and the expression of oxidative stress parameters in the bladder wall was investigated (reactive oxygen metabolites (ROMs), ·OH, and 8-hydroxy-2’-deoxyguanosine (8-OhdG)). Results: YKS had a ·OH scavenging capacity according to the ESR study. In the von Frey test, a significant decrease in the withdrawal threshold was observed in the HIC group compared with the control group; however, the decrease was ameliorated by the administration of YKS. Oxidative stress parameters showed increasing tendencies (ROMs test and 8-OHdG) or a significant increase (·OH) in the HIC group compared with the control group; however, the increase was significantly suppressed by the administration of YKS. Conclusions: These findings suggest that YKS is effective against HIC and that its antioxidant activity is involved in the mechanism of action.

Analgesic Effect of the Kampo Formula Yokukansan via the Suppression of Substance P in an Experimental Rat Model of Hunner-Type Interstitial Cystitis

“…Eighteen rats were randomly divided into three groups: control, HIC, and YKS-treated HIC (YKS+HIC). The HIC model was constructed based on previous reports [ 18 , 21 ]. Briefly, pentobarbital sodium (30 mg/kg Somnopentyl; Kyoritsu Seiyaku Corporation, Tokyo, Japan) was intraperitoneally administered to the rats, which were lightly anesthetized.…”

“…Briefly, pentobarbital sodium (30 mg/kg Somnopentyl; Kyoritsu Seiyaku Corporation, Tokyo, Japan) was intraperitoneally administered to the rats, which were lightly anesthetized. A quantity of 200 μL of 4.5 mM loxoribine (AG-CR1-3584; Adipogen Corp., San Diego, California, United States), a selective TLR7 agonist [ 18 , 21 ], was instilled transurethrally into the bladders of the rats in the HIC and YKS+HIC groups. In the control group, distilled water was used instead of loxoribine.…”

“…YKS was mixed with powdered rodent chow (CE-2; CLEA Japan, Inc.) at a concentration of 3% and fed to the YKS+HIC group for seven days prior to the induction of cystitis. This dose was selected based on the effective doses of YKS used in our previous study [ 18 ]. Rats that were not treated with YKS were fed powdered chow only.…”

“…The rats were placed in a test cage with a wire mesh bottom for 30 minutes prior to testing. The response of rats to von Frey filaments of various diameters was evaluated to determine the threshold for nociceptive stimulation of the target body part [ 18 ]. The surface of the lower abdomen close to the bladder was pressed and the minimum pressure that caused retraction behavior was determined as the threshold value.…”

“…However, the effectiveness and mechanisms of action of YKS in HIC have not been firmly established. We reported that the antioxidant effect of YKS is one of the mechanisms involved in the analgesic effect of YKS on HIC pain [ 18 ]. In the present study, we focused on the excessive expression of SP in the bladder wall and spinal dorsal horn as potential causes of bladder pain [ 19 , 20 ], and examined the impact of YKS on SP secretion.…”