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INVITED MEDICAL REVIEW

Traditional Chinese medicine and oral diseases: today and tomorrow

LW Zheng

1

, H Hua

2

, LK Cheung

1

1Oral & Maxillofacial Surgery, Faculty of Dentistry, The University of Hong Kong;2Department of Oral Medicine and Traditional Chinese Medicine, Peking University, School and Hospital of Stomatology, Beijing, China

With a history of over 2000 years, traditional Chinese medicine (TCM) evolves into a unique system of diag- nosing and treating illnesses. It is a challenge to convey the fundamentals of this traditional medicine to our Western colleagues because of the differences in lan- guage, philosophy and concept of diagnosis and treat- ment. This review attempts to tackle these barriers by introducing several widely used Chinese medicines for treating oral diseases. China Journals Full-text Database and Pubmed were used as the searching engines.

Although many studies have demonstrated that the Chinese medicines are effective in treating oral diseases including recurrent aphthous stomatitis, oral lichen pla- nus, leukoplakia, and Sjo¨ gren’s syndrome, most of them lacked standard criteria of post-treatment assessment and laboratory evidence. Randomized controlled clinical trials with specific assessment criteria are required to close the gap between TCM and evidenced-based medi- cine.

Oral Diseases (2011) 17, 7–12

Keywords: Chinese medicine; oral disease; treatment; herbology

Introduction

With a history of more than 2000 years, Traditional Chinese Medicine (TCM) has formed a unique system to diagnose and treat a variety of diseases. The therapeutic approaches in typical TCM include herbal therapy, acupuncture, dietary therapy, and qigong exercises.

Herbology is one of the most important treatment modalities utilized in TCM. Each herbal medicine

prescription is a cocktail of several herbs. The Chinese pharmacopoeia lists over 6000 medicinal substances and their properties. Among these substances around 600 herbs are commonly used today (Unschuld, 1986, Fratkin and Dharmananda, 2001).

Chinese patent medicine (zhong che´ng ya`o) referes to the drugs made according to a standardized formula (even though the word ‘‘patent’’ is used none of the manufactures have exclusive rights over these formulae).

Several herbs and other ingredients are dried, ground and mixed according to the formulae. These drugs are available in pharmacies as condensed pills, oral liquids, granules or capsules. Thus all Chinese patent medicines with the same name are expected to have the same proportions of ingredients. Most Chinese medicines with natural ingredients can be taken as a long-term treatment with fewer side effects. Chinese medicines are not indicated for the treatment of acute illness but are best suited for managing non-severe chronic diseases.

Although TCM has been used for treating oral diseases for a very long time, it is barely known and understood by clinicians and scientists outside China. It is a challenge to make this traditional medicine under- stood by our Western colleagues because of the huge differences in language, philosophy and concept of diagnosis and treatment. This review attempts to tackle this difficulty by introducing five Chinese medicines widely used in the treatment of some common oral diseases, such as recurrent aphthous stomatitis (RAS), oral lichen planus (OLP), leukoplakia and Sjo¨gren’s syndrome (SS) (Table 1). Totally 128 clinical reports were retrieved from the China Journals Full-text Data- base and Pubmed. However, most of the articles were case reports or case series without standard criteria for evaluating the effectiveness of treatment. Therefore only reports using the standard criteria issued by Society of Oral Mucosal Disease of Chinese Stomatological Asso- ciation (2001, 2005) were selected.

Liuwei Dihuang (liu ` we`i dı` hua´ng)

Liuwei Dihuang is consists of six ingredients extracted from natural herbs including: radix rehmanniae, fructus

Correspondence: Prof. Lim Kwong Cheung, Oral & Maxillofacial Surgery, The Prince Philip Dental Hospital, 34 Hospital Road, Hong Kong SAR, China. Tel: 852 28590262, Fax: 852 28575570, E-mail:

lkcheung@hku.hk; Prof. H. Hua, Department of Oral Medicine and Traditional Chinese Medicine, Peking University, School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Beijing, 100081, China.

Tel: 86-10-62179977 ext 5349, Fax: 86-10-62173402, E-mail:

honghua1968@yahoo.com.cn

Received 30 March 2010; revised 1 April 2010, accepted 1 April 2010

 2010 John Wiley & Sons A/S All rights reserved

www.wiley.com

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corni officinalis, radix dioscoreae oppositae, alismatis rhizoma, sclerotium poriae cocos and cortex moutan radicis. It is one of the most commonly used Chinese medicines in the treatment of various local and systemic chronic diseases.

Several reports demonstrated that long-term admin- istration of LiuWei DiHuang could modulate the cell- mediated immune response of RAS patients by correct- ing the imbalance of T-lymphocyte subsets (Zou and Zhang, 2003, Sun, 2004). Following the investigation of 30 RAS patients and 30 healthy volunteers, Sun (2004) reported that the RAS patients had depressed CD3+, CD4+cell counts and elevated CD8+ cell counts. The CD4+⁄ CD8+ratio was also depressed. Six months after oral administration of Liuwei Dihuang, the CD3+, CD4+ cell counts and CD4+⁄ CD8+ ratio became elevated significantly. All these values were not statis- tically different from the healthy volunteers. Clinical studies in different centers showed a varied response of the RAS patients to Liuwei Dihuang: 13.3–70.0%

healed, 10.0–76.9% improved, and 3.3–20.0% patients had no positive response to this medication (Table 2) (Zhou, 1995, L , 2001, Sun, 2003, Xie, 2004, Jia and Luo, 2006, Tong and Feng, 2008, Wang, 2009).

Shen (2002) used Liuwei Dihuang to treat 30 SS patients. Three months after the treatment, Schimer test, tear break-up time test, rose-bengal score dye test and salivary flow test demonstrated a reduction of dryness of the mouth and eyes in all the patients. The rheumatoid factor became negative in 10⁄ 16 (62.5%) patients. Six

months after the treatment, antinuclear antibodies of 10⁄ 23 (43.5%) patients and anti-SSA ⁄ anti-SSB anti- bodies of 13⁄ 28 (46.4%) patients became negative. Zhao (2006) reported the outcome of a long-term administra- tion (1–3 years) of Liuwei Dihuang for patients with SS.

At the 6-month follow-up after stopping the mediation, two patients (6.7%) had complete remission and 15 patients (50%) had reduced dryness without recurrence.

Nine patients (30%) had alleviated symptoms while taking the medication but recurred after stopping it.

Four patients (13.3%) did not respond to the treatment.

Xuan (1997) investigated the combined administra- tion of Liuwei Dihuang and retinoic acid cream in treatment of 43 patients with OLP. They found that the combined medications were more effective than retinoic acid cream alone, particularly for treating the patients with a history of OLP less than 3 years.

Tripterygium glycosides (le´i g ong te´ng du o da`i)

Tripterygium wilfordii is a native plant that grows in many parts of China and Burma. It has been commonly used in the treatment of a wide spectrum of autoimmune and inflammatory diseases (Tao et al, 2001, 2002, Qiu and Kao, 2003, Kumar et al, 2005, Canter et al 2006).

Studies have demonstrated that T. wilfordii was capable of reducing the serum levels of IgG and correcting the imbalanced T-lymphocyte subsets (Li et al, 1996, Wong et al,1998, Fang et al, 2006). A recent study also showed that T. wilfordii inhibited tumor progression by its anti- angiogenic activity (He et al, 2009). However, it is notable that T. wilfordii is the most toxic among all the Chinese herbs. Its adverse effects mainly include gastro- intestinal disturbance, infertility and suppression of immune system (Wang, 1993). Tripterygium glycosides are extracted from the peeled roots of T. wilfordi. This is effective at a much lower dosage and has less adverse effects compared to other preparations of T. wilfordii.

Li et al (1996) treated 27 RAS patients with oral Tripterygium glycosides for 3 months. The plasma soluble interleukin-2 receptor levels reduced from 601.5 ± 225.2 U ml)1 to 380.8 ± 94.2 U ml)1 which was not significantly different from the healthy volun- teers (302.0 ± 105.3 U ml)1). Studies also reported that

Table 1 Application of Chinese medicines in oral diseases

Chinese medicine Oral mucosal diseases

Liuwei Dihuang Recurrent aphthous stomatitis Sjo¨gren’s syndrome

Oral lichen planus

Tripterygium glycosides Recurrent aphthous stomatitis Oral lichen planus

Sjo¨gren’s syndrome

Stomatitis-healing granule Recurrent aphthous stomatitis Composite Taixian tablet Oral lichen planus

Zengshenping Oral lichen planus

Oral leukoplakia

Table 2 Effect of Liuwei Dihuang for treating RAS

Number of cases

Prognosis

Heal (%)

Marked improvement

Moderate

improvement No improvement (%)

L , 2001 30 13.3 36.7% 43.3% 6.7

Xie, 2004 50 18.0 38.0% 34.0% 10.0

Sun, 2003 40 25.0 50.0% 17.5% 7.5

Tong, 2008 30 70.0 10.0% 20.0

Zhou, 1995 52 19.2 76.9% 3.9

Wang, 2009 80 55.0 32.5% 12.5

Jia, 2006 120 52.5 26.7% 17.5% 3.3

Heal: complete remission of the pain and lesions, no recurrence within 1 year; Marked improvement: complete remission of the pain and lesions, no recurrence within 6 months;

Moderate improvement: reduction of pain, size and number of lesions, interval of recurrence is prolonged; No improvement: no reduction⁄ worsening in the pain, size and number of lesions (Society of Oral Mucosal Disease of Chinese Stomatological Association 2001).

LW Zheng et al 8

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Tripterygium glycosides reduced the serum nitric oxide of RAS patients to normal levels (Bu et al, 2006, Ma et al,2006). Zhang (2003) compared the effectiveness of Tripterygium glycosides and hydrocortisone for treating RAS patients. Thirty patients received oral hydrocorti- sone (started at 60 mg day)1and gradually reduced to 10 mg day)1for 10 days), and 30 patients were treated with oral Tripterygium glycosides (60 mg day)1 for 10 days). Results showed that Tripterygium glycosides was as effective as hydrocortisone.

Many studies have demonstrated the effectiveness of Tripterygium glycosides in the treatment of OLP patients (Table 3). In all these reports, an overall 20.0–

84.0% of the patients markedly improved, 12.0–45.8%

moderately improved, and 4.0–50.0% had no improve- ment after treatment (Zheng, 1988, Yin et al, 1996, Jiang and Wang, 2000, Xu, 2001, Han et al, 2007). Zheng (1988) investigated 100 OLP patients, 66 without erosive lesions and 34 with erosive lesions. All patients with reticular OLP showed improvement after 1 month treatment with Tripterygium glycosides, while plaque- like lesion required longer treatment and improvement was found after 2–3 months. However, effectiveness of Tripterygium glycosides for treating erosive lesions was less. Tripterygium glycosides also demonstrated prom- ising results in the treatment of OLP while being used in combination with other therapies such as Nd-YAG laser, triamcinolone and chloroquine (Yin et al, 1996, Guan and Zhu, 2003, Zhang et al, 2008).

Huang and Chen (1996) reported a clinical trial where T. wilfordiiwere used to treat 18 patients with SS. Three months after treatment, 16 patients showed increased salivary and tear flow and reduced symptoms of dry mouth and dry eye. The increased erythrocyte sedimen- tation rate in 7⁄ 11 (63.6%) and IgG in 10 ⁄ 13 (76.9%) patients returned to normal levels. The circulatory immune complex in 12⁄ 15 (80%) and antinuclear antibody in 7⁄ 11 (63.6%) patients became negative.

Stomatitis-healing granule (ko ˇ u ya´n qing ch ong jı`)

Stomatitis-healing granule is made of cochinchinese asparagus root, tuber ophiopogonis japonici, radix scrophulariae ningpoensis, flos Lonicerae japonicae

and radix glycyrrhizae uralensis. An animal study using a mice model showed that Stomatitis-healing granule reduced the permeability of capillaries, inhibited delayed-type hypersensitivity and decelerated granu- loma growth. In vitro assessment demonstrated inhibi- tion of Staphylococcus aureus, Streptococcus pneumoniae and hemolytic streptococcus A and B (Li et al, 1999).

Clinically Stomatitis-healing granule is mainly used for treating RAS. In all these studies an overall 0–60%

patients healed, 17.1–62.5% improved markedly, 11.6–

44.8% improved moderately after treatment. 3.1–12.1%

patients had no positive response to this medication (Table 4) (Zhen et al, 2002, Wang and Wang, 2004, Meng, 2006a, 2006b, Huang, 2007).

Composite Taixian tablet (fu ` f ang ta´i xiaˇn pia`n)

Composite Taixian tablet contains radix ligustici chu- anxiong, radix ginseng, radix paeoniae lactiflorae, semen persicae and radix et caulis jixueteng. It is mainly used for the treatment of OLP. An in vitro study showed that Composite Taixian tablet reduced the platelet adhesion of OLP patients without affecting platelet aggregation, which suggested its ability for improving blood viscosity and microcirculation (Lin and Zhou, 1992, Lin et al, 1992).

Studies demonstrated that after being treated with Composite Taixian tablet, the overall rates of marked improvement were 23.3–36.9%, moderate improvement were 35–46.7%. Around 16.4–41.7% patients had no positive response (Table 5) (Zeng et al, 1993, Pan and Yi, 1997, Zhang et al, 2001). A clinical trial by Pan and Yi (1997) recruited 30 patients (26 with non-erosive and 4 with erosive OLP). The 26 patients with non-erosive OLP were randomly assigned to an experimental group (composite Taixian tablet) and a control group (pla- cebo). The four patients with erosive OLP were evenly

Table 3 Effect of Tripterygium glycosides for treating OLP

Number of cases

Prognosis (%)

Marked improvement

Moderate improvement

No improvement

Zheng, 1998 100 84.0 12.0 4.0

Yin, 1996 30 23.3 30.0 46.7

Xu, 2001 30 20.0 30.0 50.0

Jiang, 2000 24 41.7 45.8 12.5

Han, 2007 30 66.7 13.3 20.0

Marked improvement: complete remission of erosion and pain, no⁄ - mild white streak; Moderate improvement: reduction of pain, white streak, and size of erosion; No improvement: no reduction⁄ worsening of pain, white streak, and size of erosion (Society of Oral Mucosal Disease of Chinese Stomatological Association 2005).

Table 4 Effect of Stomatitis-healing granule for treating RAS

Number of cases

Prognosis (%)

Heal

Marked improvement

Moderate improvement

No improvement

Meng, 2006b 32 56.3 28.1 12.5 3.1

Huang, 2007 70 60.0 17.1 14.3 8.6

Wang, 2004 32 0 62.5 34.4 3.1

Huang, 2007 70 60.0 17.1 14.3 8.6

Meng, 2006a 116 19.2 23.9 44.8 12.1

Zhen, 2002 86 48.8 29.1 11.6 10.5

Table 5 Effect of Composite Taixian tablet for treating OLP

Number of cases

Prognosis (%)

Marked improvement

Moderate Improvement

No improvement

Pan, 1997 15 36.9 46.7 16.4

Zeng, 1993 139 26.6 54.7 18.7

Zhang, 2001 60 23.3 35.0 41.7

LW Zheng et al

9

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assigned to the experimental and control groups. After 3 months of treatment, six patients in the experiment group improved markedly (40%), seven patients improved moderately (47%) and two patients did not response to the medication (13%). In the control group, none of the patients showed marked improvement, five patients improved moderately (33%) and 10 patients did not improve (67%). However, the study did not specif- ically state the prognosis of the four patients with erosive lesions.

Zengshengping (z eng sh eng pı´ng)

Zengshengping is composed of vietnamese sophora root, bistort rhizome, north valerianaceae, cortex dictamni, Prunella vulgarisL and Dioscorea bulbifera. Zengsheng- ping is known to modulate immune reactions, inhibit production of inflammatory cytokines, suppress tumor cell proliferation and reduce the incidence of squamous cell carcinoma (Cai et al, 1980, Lin, 1990, Fan, 1993, Wang et al, 1994).

Zengshengping has been used to treat patients with precancerous lesions of the esophagus successfully since 1980s. Lin et al (1998) reported after giving Zengsheng- ping for 3 years, the cancer incidence reduced from 5.3% (102⁄ 1922) to 2.79% (28 ⁄ 1054). Hou and col- leagues (2002) reported that after 3 years blocking treatment of esophageal epithelia dysplasia with the same medication, cancer incidence reduced from 3.85%

(102⁄ 2649) to 2.01% (28 ⁄ 1396). A randomized con- trolled clinical trial by Sun et al (2010) showed that Zengshengping significantly reduced the size of the oral lesion in 67.8% (40⁄ 59) patients with leukoplakia, which was significantly higher than that in the control group (17% (9⁄ 53)) using placebo. The chemopreventive effect of Zengshengping was significantly associated with the decrease of two cell proliferation biomarkers, silver stained nucleoli organizer region and proliferating cell nuclear antigen-labeling index. Shang et al (2004) reported that after treatment with Zengshengping, the size of oral leukoplakia reduced significantly in 74.6%

(47⁄ 63) patients. Zengshengping has been also used for treating OLP, with a 79.4% (50⁄ 63) (Sun et al, 2004) and 90% (90⁄ 100) (Cao et al, 2001) patients positively responding to this medication.

Conclusion

Although TCM has been used for over 2000 years in the treatment of various diseases, it is not fully understood and accepted by the clinicians outside China. Even in China, not all the practitioners believe its effectiveness. The major barrier between the TCM and contemporary medicine is not only the language, but the basic concepts in diagnosis and management of the disease. While the contemporary medicine devel- oped from an evidence-based system, the TCM is basically experience-based. It was a challenge to search and select high quality reports from hundreds of papers related to this topic. Most of the clinical studies were case reports or case series without good controls.

Standard criteria for post-treatment assessment and laboratory evidence supporting the findings and con- clusions were lacking in most of the reports. Many Chinese clinicians and scientists have been making a great effort to build the missing link between the 1000- year-experience based knowledge and the evidence- based medical sciences. Even though the authors planed a systematic review at the beginning, we were compelled to perform a general review giving a glimpse of TCM in oral diseases because of the lack of high quality animal and clinical studies. The effective chemical components, optimal ratios of the herb

‘‘cocktail’’ and the mechanisms of the medicines on different diseases need to be explored by high quality laboratory and animal experiments, as well as ran- domized controlled clinical trials.

Acknowledgements

We gratefully acknowledge Dr. Ma L and Dr. Jayaratne YS of The University of Hong Kong for their great effort in literature searching and technical assistance.

Author contributions

All authors contribute to this manuscript.

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This case emphasizes that oral health practitioners should be familiar with the systemic manifestations and oral complications of blood diseases and leukaemia in par- ticular,

pylori in pathogenesis of oral mucosal lesions or ulcerations is still unclear, it seems that patients with oral lesions as leukoplakia and oral lichen planus, and concurrent

Although osteolipoma is a very rare entity in the oral cavity, it should be considered when a patient presents with a peripheral lesion that has a hard consistency on palpation,

Key words: Oral focal mucinosis, myxomatous lesion, connective tissue diseases,