|Year : 2018 | Volume
| Issue : 5 | Page : 216-222
Traditional chinese medicine and herbal supplements for treating overactive bladder
Yu-Liang Liu, Wei-Chia Lee
Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
|Date of Web Publication||3-Sep-2018|
Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung
Source of Support: None, Conflict of Interest: None
Overactive bladder (OAB) has a high prevalence of approximately 16%–18% of the population worldwide. Currently, the understanding of and strategies for pharmacological treatment of OAB remain limited to antimuscarinics and β3 agonists. Ethnopharmacology applies knowledge from traditional medicine to treat diseases. For example, several presently used drugs, such as aspirin, digoxin, and artemisinin, have originated from plant extracts. Ancient people have historically required treatments for urinary urgency, urinary frequency, nocturia, and urgent incontinence. Traditional Chinese medicine (TCM) has been developed in China over the course of thousands of years. Some regimens and single-herb medicines of TCM have been demonstrated to manage such OAB symptoms. Herein, we summarize the evidence, obtained through current scientific methodology, which supports the use of regimens and single-herb medicine for treatment of OAB. An understanding of the pros and cons of TCM from the viewpoint of current science would improve future research and provide patients with more alternative and complementary therapies.
Keywords: Herb, overactive bladder, traditional Chinese medicine
|How to cite this article:|
Liu YL, Lee WC. Traditional chinese medicine and herbal supplements for treating overactive bladder. Urol Sci 2018;29:216-22
| Introduction|| |
Overactive bladder (OAB) is a common medical condition with an estimated prevalence of 16% to 18% of the population. OAB syndrome is a clinical diagnosis characterized by “urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of a urinary tract infection or other obvious pathology.” Patients with symptoms of OAB may curtail their participation in social activities, and their quality of life may consequently decline. From an economic viewpoint, OAB is costly for both individuals and society. Direct costs include preventive, diagnostic, and treatment services related to OAB and indirect costs include a decline in workplace productivity.
Urinary urgency, the cardinal symptom of OAB syndrome, is associated with one or more symptoms such as frequency, nocturia, and urinary incontinence. The severity of OAB symptoms tends to increase with age. In addition, several diseases such as chronic heart failure, chronic obstructive pulmonary disease, constipation, chronic kidney disease, autoimmune disease, and metabolic syndrome cause polyuria, decrease functional bladder capacity, or affect lower urinary tract function exacerbating OAB symptoms. Thefirst-line therapy for OAB is behavior therapy, in which fluid management, avoidance of caffeine intake, body weight loss, pelvic floor muscle training, and bladder control strategies are recommended., As the second-line treatment for OAB, antimuscarinics and β3 adrenoceptor agonists may be helpful in optimizing patient symptom control and quality of life. However, OAB is a complex and chronic condition that cannot be fully resolved by current treatments.
Several studies have indicated that traditional Chinese medicine (TCM) can be used in the management of OAB.,, Over thousands of years, herbal medicines have traditionally been used for the treatment of various diseases and conditions, including lower urinary tract symptoms (LUTS). Various Chinese medicinal herbal preparations have been used in Taiwan to treat LUTS, such as nocturia, urgency, and enuresis. TCM doctors prescribe different TCM formulas on the basis of individual clinical presentation, as determined through four methods of examination: inspection, listening and smelling, inquiry, and palpation. The objective of this review is to describe the pros and cons of using TCM in OAB treatment. Although some studies have reported promising findings regarding the use of using TCM in OAB patients, further large-scale ethnopharmacological surveys are required.
| The Traditional Chinese Medicine System|| |
TCM has been developed during more than 2500 years of medical practice in China, and it includes various forms of herbs, acupuncture, massage, exercise (qigong), and diet therapy. TCM is based on the ancient philosophy of Daoism including Yin-Yang theory and the five phases theory, as illustrated in [Figure 1]. The goal of TCM is to adjust the balance of dynamic functional activity rather than to treat disease directly. In TCM, the view of the human body focuses mainly on body function. Therefore, several types of herbs are necessary to adjust each Zang-Fu organ () and Qi-Xue-Jin-Ye ().
Other Asian countries including Japan and Korea also have traditional medical systems. Some of these systems are influenced by Chinese medicine. For example, Japanese traditional medicine (Kampo medicine, ) and traditional Korean medicine (Hanuihak, , ) use most of the Chinese therapies including acupuncture, moxibustion, and herbs, in their systems of diagnosis. The World Health Organization currently recognizes TCM as an essential component of primary health care.
Chinese herbs are usually combined into formulas on the basis of TCM theory. TCM formulas are more effective and comprehensive than single herbs in treating diseases. TCM doctors believe in a “synergistic effect” or “emergence effect.” For example, an engine consists of several parts that must work together for the engine to function. The composition of a formula includes components similar to those in a government, including Jun (the sovereign), Chen (the minister), Zuo (the assistant), and Shi (the courier), as illustrated in [Figure 2]. The Jun herb is irreplaceable and primarily determines the entire direction of the formula. If the Jun herb is changed, the natures of the formula become different. The Chen herbs are second in influence and are often used to complement the Jun herb's major function. The Zuo herbs are used to enhance the formula's primary function or to limit its adverse effects. The Shi herbs guide the active ingredients to the target organs and coordinate the actions of these agents. Not all formulas contain the full complement of ingredients, and all other components of the formula follow the basic functional direction established by the Jun herb. Hence, doctors should combine herbs in accordance with patients' specific conditions. Many TCM formulas have been used for clinical purposes in China for hundreds of years.
|Figure 2: The composition of a formula includes components similar to those in a government, including Jun (the sovereign), Chen (the minister), Zuo (the assistant), and Shi (the courier)|
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| Overactive Bladder Etiology|| |
The etiology underlying OAB can involve myogenic, neurogenic, and urotheliogenic factors. The myogenic factor is unstable contraction of the bladder during the filling phase, which might be related to periodic ischemia of the bladder and intrinsic neuronal damage in the bladder wall. Under such circumstances, smooth muscle properties are affected. These alterations in detrusor myocyte properties can lead to detrusor hypersensitivity to incoming signals. The neurogenic factor is associated with abnormal central inhibitory pathways in the brain and spinal cord or sensitization of peripheral afferent terminals in the bladder. Several neurotransmitters and specific receptors are involved in afferent signal transduction. Oxybutynin and β3-androgen receptor agonists have been reported to inhibit bladder afferent activity in rats., M2 and M3 receptors are the dominant muscarinic receptor subtypes expressed in the bladder. Patients with idiopathic DO and bladder pain syndrome have a higher density of M2 and M3 receptors in the bladder, and the density of suburothelial muscarinic receptors is correlated with urgency scores. The urotheliogenic OAB factor relates to abnormalities in signal molecules and ion channels in the urothelium. The urothelium not only serves as a barrier but also can sense thermal, mechanical, and chemical stimuli. An absence of urothelium may increase spontaneous detrusor activity. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in amplifying the responses of the urothelium in intravesical chemical stimulation and is associated with cystitis-induced bladder hyperactivity. Overexpression of suburothelial TRPV1 receptors has been observed in patients with urgency or detrusor overactivity. In addition, urothelial P2X3 and P2X2/3 receptors are essential for receiving mechanical and chemical stimuli of bladder and relate to the sense of urgency. P2X3 and TRPV1 expression in nerve fibers appear to be abnormally upregulated in the bladders of patients with neurogenic detrusor overactivity. An experiment indicated that P2X3 receptor antagonists might be effective in the treatment of OAB and bladder pain. Bladder outlet obstruction, inflammatory reactions, metabolic syndrome, and diabetes also contribute to the pathophysiology of OAB. When patients present with symptoms indicative of OAB, a basic evaluation to exclude an underlying cause of the symptoms is necessary.
| Traditional Chinese Medicine Formulas for Treatment of Overactive Bladder|| |
Ba-Wei-Di-Huang-Wan (BWDHW) is one of the most common traditional Chinese herbal preparations used to treat abnormal thirst, polydipsia, polyuria, and urinary frequency with diabetes-like symptoms. Zhongjing Zhang () is thought to have created the BWDWH regimen >1800 years ago. BWDHW is a mixture containing Rehmanniae radix (dì huáng), Cornus officinalis (shān zhū yú), Dioscoreae rhizoma (shān yào), Alismatis rhizoma (zé xiè), Porica cocos (fú líng), Moutan radicis cortex (muˇ dān pí), Cinnamomi cortex (guì pí), and heat-processed Aconiti radix (fù ziˇ) and is used to warm the kidney yang and while relieving frequent urination.
BWDHW may have potential in treating diabetes and metabolic syndrome associated bladder overactivity in rats., In addition, several animal studies have indicated that BWDHW treatment modulates bladder target receptors involved in the sensory web of the bladder, suppresses inflammation and oxidative stress of the bladder, and decreases bladder overactivity., Tong et al. reported the effects of BWDHW on the cholinergic function of the bladder in streptozotocin-induced diabetic rats and suggested that BWDHW suppresses the overexpression of M2 receptors and alleviates bladder overactivity. Furthermore, Imamura et al. tested the effects of THC-002, an ethanol extraction of the starch component of BWDHW, on spontaneously hypertensive rats and reported that THC-002 inhibits adenosine triphosphate (ATP)-induced detrusor overactivity by decreasing the bladder expression of tachykinins and P2X3 and TRPV1 receptors.
For bladder dysfunction induced by chemical stimuli, BWDHW can modulate the bladder sensory web and directly alleviate bladder overactivity. Lee et al. reported that BWDHW ameliorates cyclophosphamide-induced ongoing bladder overactivity and acidic ATP solution-induced provoking bladder overactivity in rats. BWDHW treatment may modulate mucosal P2X2, P2X3, M2, and M3 receptors, as well as detrusor M2 and M3 receptors in rat bladders subjected to cyclophosphamide insult. Furthermore, BWDHW pretreatment prevents TRPV1 receptor hypersensitization in bladder mucosa inflamed by acidic stimulation. Moreover, Tsai et al. suggested that loganin might be the active element of BWDHW that modulates substance P-induced oxidative injury and inflammation by suppressing substance P/neurokinin-1 receptor and nuclear factor kappa B/intercellular adhesion molecule 1 signaling pathways. BWDHW has been used for >1000 years in China, and no severe adverse effects have been reported in the literature. Preliminary toxicology studies in an in vivo rat model with orally administered BWDHW indicated minimal perturbation of hepatic function.
Ji-Sheng-Shen-Qi-Wan (JSSQW) treats water accumulation caused by kidney yang deficiency. JSSQW wasfirst described during the Southern Song Dynasty (AD 1127–1279). JSSQW is a variation of BWDHW and is composed of 10 crude drugs in fixed proportions: processed steamed Rehmanniae radix ( dì huáng), Corni fructus (Cornus officinalis) ( shān zhū yú), Moutan radicis cortex (muˇ dān pí), Alismatis rhizoma ( zé xiè), Dioscoreae rhizoma ( shān yào), Cinnamomi cortex ( guì pí), Hoelen (Poria cocos) ( fú líng), heat-processed Aconiti radix ( fù ziˇ), Achyranthis radix ( niú xī), and Plantaginis semen ( chē qián ziˇ). JSSQW, also known as Gosha-jinki-gan, has been widely used in Japan to treat patients with LUTS, diabetic neuropathy, and nocturia. Yagi et al. reported that patients with nocturia receiving Gosha-jinki-gan treatment for 12 weeks exhibited reductions in both episodes of nocturia and the International Prostate Symptom Scores.
In basic research, Nishijima et al. demonstrated that Gosha-jinki-gan-fed rats compared with untreated controls exhibited increased intercontractile intervals and decreased contraction amplitudes in cystometry as well as decreased dopamine and serotonin levels in plasma; these results suggest that Gosha-jinki-gan may affect the afferent and efferent micturition reflex and may have central effects on micturition mechanisms. Furthermore, Imamura et al. showed that pretreatment with Gosha-jinki-gan may prevent the bladder urothelium from increasing expression of tachykinins and TRPV1 and P2X3 receptors during intravesical acetic acid stimulation in rats; these authors further suggested that Gosha-jinki-gan may decrease expression of transmitter proteins and sensory receptors without destroying nerve fibers.
The JSSQW (Gosha-jinki-gan) formula is a modification of BWDHW with the addition of Achyranthis radix ( niú xī) and Plantaginis semen ( chē qián ziˇ). Both BWDHW and JSSQW mixtures may have the potential to provide additional therapeutic effects in treating OAB.
Suo-Quan-Wan (SQW) is an effective traditional Chinese prescription containing three ingredients: Alpinia oxyphylla Miq ( yì zhì rén), Lindera radix ( wū yào), and Dioscorea opposita Thunb ( shuˇ yù), whose function is similar to that of Dioscoreae rhizoma ( shān yào) in BWDHW. Shān yào () is the tubers of shuˇ yù (). Since many Dioscoreae species have tubers, accurate identification of the origin of the plants from which they are derived is not possible. SQW wasfirst described in the Southern Song Dynasty (AD 1127–1279) and is commonly used to relieve frequent urination. SQW modulates bladder TRPV1 receptors in rats. Lai et al. used an animal model of partial bladder outlet obstruction to demonstrate that SQW decreases the expression of TRPV1 receptors in rat bladders and slows the progression of bladder overactivity. Using TRPV1 knockout mice, they further demonstrated that SQW improves bladder function through the regulation of TRPV1 receptors.
Sang-Piao-Xiao-San (SPXS) is effective in treating heart and kidney deficiency with urinary incontinence with spermatorrhea. SPXS wasfirst described during the Northern Song Dynasty (AD 960–1127). Several formulas of SPXS have been recorded and used, all of which formulas use Mantidis ootheca ( sānɡ piāo xiāo) as the Jun herb. Sānɡ piāo xiāo means “mantis eggs in a foamy pouch.” Sānɡ piāo xiāo has been found to relax vascular smooth muscle through endothelium-dependent PI3K/AKT-mediated nitric oxide-cyclic guanosine 3′,5′-monophosphate (GMP)-protein kinase G signaling in vascular smooth muscle cells. Lin et al., in an investigation of the effects of SPXS and Bu-Zhong-Yi-Qi-Tang () in patients with OAB, demonstrated that SPXS combined with Bu-Zhong-Yi-Qi-Tang reduces urinary frequency, urgency and urge incontinence, and increases the voided volume and patient quality of life.
Wenglitong capsule ()
Wenglitong capsule (WLT) is a mixture of herbal medicines, including Ma-yuen jobstears seed ( yì yiˇ rén), Chekiang fritillary bulb ( zhè bèi muˇ), Armand clematis stem ( chuān mù tōng), Cape jasmine ( zhī ziˇ), Japanese honeysuckle flower bud ( jīn yín huā), Japanese inula flower ( xuán fù huā), Hirsute bugleweed herb ( zé lán), Verdigris ( tóng lǜ), and Liquorice root ( gān cǎo) with Astragali radix ( huáng qí). In a clinical trial involving women with OAB, treatment with WLT alone, compared with tolterodine treatment, resulted in slower onset and was less efficacious in decreasing urgency incontinence, urinary frequency, and OAB symptom scores. However, the effects of WLT combined with tolterodine were superior to those of tolterodine alone in alleviating OAB symptoms.
| Single-Herb Medications for Overactive Bladder|| |
Several currently used drugs, such as aspirin, digoxin, and artemisinin, have originated from plant extracts. Here, we review several single- herb medications that may be used to treat OAB.
Resiniferatoxin and capsaicin
Resiniferatoxin and capsaicin are TRPV1 agonists. Intravesical instillation of capsaicin and resiniferatoxin can desensitize TRPV1 receptors of afferent nerves, decrease neural firing, and inhibit the micturition reflex. Intravesical resiniferatoxin attaches to the TRPV1 receptor and selectively blocks afferent nerves that transmit pain sensations to the brain. Resiniferatoxin increases the maximum cystometric capacity in patients with detrusor overactivity and decreases bladder pain in patients with either interstitial cystitis or detrusor overactivity. However, some studies have shown an opposite result of increased pain sensation and higher urinary frequency after instillation of resiniferatoxin into rat bladders. Resiniferatoxin is rarely used clinically, owing to difficulties in delivery, inconsistent efficacy, and acute pain. Resiniferatoxin has not been approved by the FDA for treatment of OAB.
Capsaicin, another TRPV1 channel agonist, stimulates the release of calcitonin-gene-related peptide and substancePfrom the sensory nerves. Capsaicin disrupts conduction in sensory afferent fibers and produces long-term regional analgesia with substance P depletion, but often causes local irritation and edema.
Pumpkin seed oil extract
Pumpkin seed oil extract has been used to treat various ailments including benign prostatic hyperplasia, hypertension, hyperlipidemia, urinary disorders, diabetes, and various cancers. Pumpkin seed oil has a strong antioxidant activity. Zhang et al. reported that pumpkin seed oil preparations decrease bladder pressure, increase bladder compliance, and decrease urethral pressure in rabbits. Pumpkin seed oil extracted from Cucurbita maxima was studied in 45 patients with OAB symptoms. Pumpkin seed oil extract improved the OAB symptom scores of these patients without adverse effects after 12 weeks of treatment.
Rhynchophylline is derived from Uncariae Ramulus Cum Uncis ( gōu ténɡ). Rhynchophylline had been found to inhibit the contraction of isolated rat urinary bladder strips by blocking L-type calcium channels and activating calcium-activated potassium channels. Rhynchophylline at a low concentration (10 μmol/L) inhibited the intracellular-calcium-induced contractions of rat urinary bladder strips, whereas at a high concentration (20 μmol/L), it had inhibitory activity toward both intracellular- and extracellular-calcium-induced contractions. In an in vivo study, Jiang et al. demonstrated that intraperitoneal injection of rhynchophylline alters urodynamic parameters in rats. However, no clinical data demonstrating the efficacy of rhynchophylline in OAB patients have been reported.
Fangji is used throughout China and has traditionally used as a diuretic and an antirheumatic remedy. Fangji (Stephaniae tetrandrae radix), a type of calcium channel blocker, inhibited the KCl-induced contraction of normal and hypertrophic detrusor muscle, ameliorated morphological changes due to detrusor hypertrophy, and inhibited collagen deposition in the bladder in an animal model of benign prostatic hyperplasia.
| How to Study Traditional Chinese Medicine|| |
Limited but growing evidence in the literature indicates that TCM may be used in the prevention and treatment of OAB.
The quality, content, and focus of TCM research vary, and the ancient theory of TCM is complicated, thus hindering TCM's acceptability to the global scientific community. Exploring TCM using current scientific techniques, methods, and theories is valuable. Some of the following key principles listed may improve understanding and aid in investigation of TCM. Although some high-quality trials have been published in English, numerous trials have been published and are accessible only in Chinese. Researchers might overlook many relevant studies and draw different conclusions if Chinese databases are not searched. Research collaboration with Mandarin-speaking researchers can reduce language bias.
The same TCM formulas or herbs may be described by different names. For instance, “Ba-Wei-Di-Huang-Wan” (Pinyin) may be denoted as (Chinese) or Hachi-mi-jio-gan (Japanese romanization). Moreover, the plant species used in the same regimen may vary among publications. In addition, a given ingredient of TCM herbs may not always be sourced from a single plant species. Therefore, the Latin scientific names for plant species should never be derived from Chinese herb names alone. The quality of herbs directly influences clinical effectiveness, therefore, identifying authentic herbs is important. In TCM, geo-authentic herbs, which are grown in specific areas, are considered to have the higher quality than samples from different regions. For studies on TCM, choosing GMP pharmaceutical manufacturers and legitimate sources of herbs may standardize the active compounds and ensure the quality and safety of Chinese herbs as well as the scientific accuracy of studies.
| Conclusion|| |
TCM has specific effects on OAB, and no severe adverse effects have been reported. Thus, TCM appears to be safe, efficacious, and worthy of clinical use. Rigorously designed randomized, double-blind, controlled trials must be conducted to demonstrate the efficacy of TCM treatment in patients with OAB.
This work is supported by Grants CMRPG891571, CMRPG8B0281-2, CMRPG 8F1211, and CMRPG8F0052 from Chang Gung Memorial Hospital.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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