Background & Aims
Interstitial cystitis (IC) is a non-infectious inflammatory disease of unknown origin, with the Hunner-type being particularly challenging to treat, having been designated as an intractable disease in Japan. Yokukansan (YKS) is a traditional Japanese herbal medicine, known as Kampo medicine, and has demonstrated efficacy in various pain disorders such as fibromyalgia, postherpetic neuralgia, phantom limb pain, headache, and trigeminal neuralgia [1]. Comprising seven crude drugs, including Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix, YKS was investigated in this study for its analgesic effects on Hunner-type interstitial cystitis (HIC) using an animal model [2-3].
Methods
The antioxidant capacity of YKS was assessed through electron spin resonance (ESR), measuring its hydroxyl radical (·OH) scavenging capability. A rat HIC model was induced by transurethrally administering a Toll-like receptor-7 agonist (Loxoribine) into the bladder [2-3]. Eight-week-old female Wistar rats were categorized into three groups: Control group, HIC group, and HIC group treated with YKS (YKS+HIC group). Bladder pain was evaluated using von Frey tests to measure escape behavior. Three days after inducing HIC, bladder and spinal cord tissues were extracted, and hydroxyl radical (·OH)-scavenging activity in the bladder wall, as well as the expressions of Substance P (SP) in the bladder wall and spinal cord, were analyzed.
Results
YKS exhibited ·OH scavenging capacity according to the ESR study. Von Frey tests indicated a significant reduction in escape thresholds in the HIC group compared to the Control group. However, YKS treatment alleviated this reduction. Oxidative stress parameters demonstrated increasing tendencies (ROMs test and 8-OHdG) or a significant increase (·OH) in the HIC group compared with the control group; however, YKS administration significantly suppressed this increase. Furthermore, the examination of SP expression in the bladder wall and spinal cord revealed a noteworthy increase in the HIC group compared to the Control group, yet YKS treatment further mitigated this increase.
Conclusions
Herbal medicines, comprising multiple crude drugs, suggest the involvement of multiple concurrent mechanisms of action. Oxidative stress, peripheral and central sensitization play roles in the onset and exacerbation of HIC. Increased secretion of SP is one mechanism of sensitization. The findings of this study suggest that YKS is effective against HIC, and its mechanism of action involves antioxidant activity and the suppression of SP secretion.
References
[1] Sunagawa M, et al. Kampo formulae for the treatment of neuropathic pain? especially the mechanism of action of yokukansan?. Front Mol Neurosci. 2021; 14, 705023.
[2] Ichihara K, et al. Toll-like receptor 7 is overexpressed in the bladder of Hunner-type interstitial cystitis, and its activation in the mouse bladder can induce cystitis and bladder pain. Pain 2017?158, 1538-1545.
[3]Tabata H, et al. Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a toll-like receptor-7 agonist-induced experimental animal model in rat. BMC Urol. 2021; 21, 156.
[4] Wu KC, et al. Glycine tomentella hayata extract and its ingredient daidzin ameliorate cyclophosphamide-induced hemorrhagic cystitis and oxidative stress through the action of antioxidation, anti-fibrosis, and anti-inflammation. Chin J Physiol. 2019;62(5):188-195.
[5] Tsubota M, et al. Involvement of the cystathionine-?-lyase/Cav3.2 pathway in substance P-induced bladder pain in the mouse, a model for nonulcerative bladder pain syndrome. Neuropharmacology. 2018;133:254-263.
Presenting Author
Masataka Sunagawa
Poster Authors
Masataka Sunsgawa
PhD
Showa University, Japan
Lead Author
Mana Tsukada
Ph.D.
Showa University Showa Research Administration Center (SURAC), Tokyo, Japan
Lead Author
Tatsuki Inoue
Ph.D.
Department of Urology, School of Medicine, Showa University, Tokyo, Japan
Lead Author
Yoshiki Tsunokawa
Ph.D.
Department of Urology, School of Medicine, Showa University, Tokyo, Japan
Lead Author
Takehiko Sambe
Ph.D.
Showa University Showa Research Administration Center (SURAC), Tokyo, Japan
Lead Author
Takashi Fukagai
Ph.D.
Department of Urology, School of Medicine, Showa University, Tokyo, Japan
Lead Author
Tadashi Hisamitsu
Ph.D.
Showa University, Tokyo, Japan
Lead Author
Topics
- Treatment/Management: Complementary and Alternative therapies