An extract (THC‐002) of Ba‐Wei‐Die‐Huang‐Wan inhibits expression of tachykinins, and P2X3 and TRPV1 receptors, and inhibits ATP‐induced detrusor overactivity in spontaneously hypertensive rats

Imamura, Tetsuo; Ishizuka, Osamu; Chen, Zhong; Ogawa, Toshihide; Nakayama, Tsuyoshi; Kurizaki, Yoshiki; Tanabe, Tomoaki; Nishizawa, Osamu; Andersson, Karl‐Erik

doi:10.1002/nau.20702

Cited by 22 publications

(21 citation statements)

References 16 publications

(14 reference statements)

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“…The binding activity of HE for purinergic receptors in the bladder is consistent with the recentˆnding that HE treatment reduced the expression of purinergic P2X 3 receptors and inhibited ATP-induced detrusor overactivity in the bladder. 16) Furthermore, the currentˆnding provides pharmacological evidence to support the notion that purinergic receptor-related mechanisms in the urothelium and smooth muscle may be altered in the bladder of patients with interstitial cystitis (IC). 17) ATP levels were signiˆcantly elevated in the urine of patients with IC and the stretch-activated release of ATP was augmented in the urothelium.…”

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confidence: 79%

Pharmacological Effects of Hachi-mi-jio-gan Extract (Harncare<sup>®</sup>)on the Contractile Response and on Pharmacologically Relevant Receptors in the Rat Bladder

et al. 2009

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Hachi-mi-jio-gan extract (Harncare ; HE), a galenical produced from the traditional Chinese herbal mixture BaWei-Die-Huang-Wan, has been reported to improve lower urinary tract symptoms (LUTS) in patients. The present study was undertaken to clarify the pharmacological eŠects of HE on smooth muscle contraction and on pharmacologically relevant (muscarinic, 1,4-DHP and purinergic) receptors in the rat bladder. Additionally, the eŠects of repeated oral treatment with HE on the hepatic cytochrome P-450 (CYP) and on blood biochemical values in rats were examined. HE (10 mg/ml) inhibited signiˆcantly the acetylcholine-induced contraction of isolated rat bladder strips. The pD 2 value in the absence and presence of HE (10 mg/ml) was 5.14±0.16 and 3.99±0.17, respectively. HE (0.1 to 10 mg /ml) inhibited the speciˆc binding of .23 mg/ml. Based on IC 50 values, the binding activity of HE for purinergic receptors was shown to be signiˆcantly (about 7 times) greater than that for muscarinic and 1,4-DHP receptors. Repeated oral administration of HE (10, 30 and 100 mg/kg/day) for 4 weeks had little or no eŠect on the level and activity of hepatic CYP or on blood biochemical values in rats. In conclusion, the present study has shown that HE exerts signiˆcant binding activity for pharmacologically relevant receptors in the rat bladder and a relaxant eŠect on the acetylcholine-induced contraction of isolated muscle strips. HE seemed to exhibit little pharmacokinetic interaction with drugs.

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confidence: 79%

Pharmacological Effects of Hachi-mi-jio-gan Extract (Harncare<sup>®</sup>)on the Contractile Response and on Pharmacologically Relevant Receptors in the Rat Bladder

et al. 2009

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“…These results demonstrated that TRPM8 channel blocker could act on the bladder afferent pathway to attenuate the bladder micturition reflex in the rat. A reduction of the bladder expression of tachykinins and TRPV1 and P2X3 purine receptors could explain the beneficial effects of some traditional Chinese herbal mixture extracts used for the treatment of OAB symptoms [34,35]. …”

Section: Ion Channels and Receptors Mechanismsmentioning

confidence: 99%

Insight into New Potential Targets for the Treatment of Overactive Bladder and Detrusor Overactivity

Cerruto¹,

Asimakopoulos

Artibani³

et al. 2012

Urol Int

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Although overactive bladder (OAB) and detrusor overactivity (DO) are not synonyms, they share therapeutic options and partially underlying physiopathological mechanisms. The aim of this overview is to give insight into new potential targets for the treatment of OAB and DO. A narrative review was done in order to reach this goal. Ageing, pelvic floor disorders, hypersensitivity disorders, morphologic bladder changes, neurological diseases, local inflammations, infections, tumors and bladder outlet obstruction may alter the normal voluntary control of micturition, leading to OAB and DO. The main aim of pharmacotherapy is to restore normal control of micturition, inhibiting the emerging pathological involuntary reflex mechanism. Therapeutic targets can be found at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord and brain. Increased expression and/or sensitivity of urothelial-sensory molecules that lead to afferent sensitization have been documented as a possible pathogenesis of OAB. Targeting afferent pathways and/or bladder smooth muscles by modulating activity of ligand receptors and ion channels could be effective to suppress OAB.

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“…We simultaneously showed that THC‐002, a galenical produced from the traditional Chinese herbal mixture Hachimi‐jio‐gan, can partially decrease the expression of these tachykinins. This reduction mitigates the C‐fiber afferent activity‐related detrusor overactivity in SHRs 14. Therefore, in this study we determined if the expression of neurokinin A, neurokinin B, and substance P within the urethras of SHRs was also increased by the aging process and salt‐loading.…”

Section: Introductionmentioning

confidence: 97%

“…The traditional Chinese herbal mixtures are empirically given in order to terminal urine dribbling, though it is difficult to estimate the degree of relief based on international standard questionnaires such as the International Prostate Symptom Score. These traditional Chinese herbal mixtures have effects that inhibit C‐fiber afferent nerve activation within the urinary bladders 12–14…”

Section: Introductionmentioning

confidence: 99%

“…This study is a preliminary investigation of the expression of C‐fiber afferent nerve‐associated neurotransmitters within the urethras of spontaneously hypertensive rats (SHRs). When activated, these fibers produce the tachykinin peptides neurokinin A, neurokinin B, and substance P. Previously, we reported that the expression of these tachykinins within urinary bladders of SHRs is higher than that of wild‐type normal Wistar Kyoto rats 14. The presence of these tachykinins is increased by various factors, such as the aging process and salt loading 12.…”

Section: Introductionmentioning

confidence: 99%

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A galenical of traditional chinese herbal mixture (THC‐002) reduces expression of tachykinin peptides within urethras of spontaneously hypertensive rats

Ishikawa

Imamura

Ishizuka

et al. 2011

Neurourology and Urodynamics

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An extract (THC‐002) of Ba‐Wei‐Die‐Huang‐Wan inhibits expression of tachykinins, and P2X3 and TRPV1 receptors, and inhibits ATP‐induced detrusor overactivity in spontaneously hypertensive rats

Abstract: In SHRs, THC-002 reduced the bladder expression of tachykinins and P2X3 and TRPV1 receptors, and inhibited ATP-induced detrusor overactivity. These effects may explain part of its beneficial effects on LUTS.

Cited by 22 publications

References 16 publications

Pharmacological Effects of Hachi-mi-jio-gan Extract (Harncare<sup>®</sup>)on the Contractile Response and on Pharmacologically Relevant Receptors in the Rat Bladder

Pharmacological Effects of Hachi-mi-jio-gan Extract (Harncare<sup>®</sup>)on the Contractile Response and on Pharmacologically Relevant Receptors in the Rat Bladder

Insight into New Potential Targets for the Treatment of Overactive Bladder and Detrusor Overactivity

A galenical of traditional chinese herbal mixture (THC‐002) reduces expression of tachykinin peptides within urethras of spontaneously hypertensive rats

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