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REVIEW ARTICLE
Year : 2023 | Volume
: 9
| Issue : 1 | Page : 8-20
Effective common chinese herbal medicines used in treating chronic cholecystitis with liver-gallbladder dampness-heat syndrome: A review of clinical studies in the past 10 years
Desmond Wei Kang Tee, Hon Foong Wong
Centre for Complementary and Alternative Medicine, International Medical University, Kuala Lumpur, Malaysia
Correspondence Address:
Hon Foong Wong
Department of Chinese Medicine, Centre for Complementary and Alternative Medicine, International Medical University, No. 126, Jalan Jalil Perkasa 19, 57000 Kuala Lumpur
Malaysia
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2311-8571.364414
The objective of the study is to identify the effective common Chinese herbal medicines used in treating chronic cholecystitis with liver-gallbladder dampness-heat syndrome (CCLGDHS) through reviewing relevant clinical studies published in the past 10 years. Data were collected from ScienceDirect and Chinese National Knowledge Infrastructure. Data screening was carried out for the abstracts and full texts of the data. The top 15 Chinese herbal medicines with the highest occurring frequency were selected, statistically analyzed, and classified by their medicinal properties, actions, and indications according to the Chinese Pharmacopoeia 2015 edition. The top 15 effective common Chinese herbal medicines comprise Chai Hu, Huang Qin, Jin Qian Cao, Bai Shao, Yin Chen, Yu Jin, Chuan Lian Zi, Yan Hu Suo, Zhi Shi, Ban Xia, Bai Zhu, Pu Gong Ying, Gan Cao, Zhi Zi, and Qing Pi. The predominant natures were cold, cool, and warm. This combination can clear stagnant heat, warm Yang, and regulate Qi dynamics. In addition, bitter, pungent, and sweet were the predominant flavors. They can clear dampness-heat, regulate Qi dynamics to relieve cramps and pain, as well as tonify the deficiency. Along with entering the liver and gallbladder meridians, these herbal medicines also entered the spleen, stomach, and lung meridians to prevent potential disease transmission. The combinatorial medicinal actions of the effective common Chinese herbal medicine highlight the importance of the holistic concept of traditional Chinese medicine when treating CCLGDHS. In addition, the inclusion of activating blood to promote blood circulation, relieving cramps and alleviating pain, and tonifying the spleen and stomach represents a new finding in the treatment principle for CCLGDHS.
Keywords: Chronic cholecystitis, common Chinese herbal medicines, liver-gallbladder dampness-heat syndrome, traditional Chinese medicine treatment
Chronic cholecystitis is defined as chronic inflammatory disorder of the gallbladder. It is the result of emptying dysfunction of the gallbladder, usually due to prior episodes of acute cholecystitis, infections, and occlusions of the common bile duct by gallstone. The clinical presentations of chronic cholecystitis vary widely from person to person. The possible symptoms are recurrent dull pain in the right upper abdomen that may radiate to the middle back or right scapular tip, abdominal distension, nausea, vomiting, increased bloating and flatulence, intolerance of oily food, etc. These symptoms are often associated with and aggravated by fatty food ingestion. Chronic cholecystitis can also result in prolonged intermittent digestive disturbances and abdominal discomfort that may impact a patient's quality of life.[1],[2] The diagnosis of chronic cholecystitis can neither rely on single clinical presentation nor a combination of clinical presentations.[2] The preferred diagnostic approach for chronic cholecystitis is ultrasonography. Findings of ultrasonography may include gallbladder wall thickening, variable adhesions to the mucosa surface of gallbladder, gallstone formation, etc. Currently, there are various Western medicine treatments available for chronic cholecystitis. Medications such as antibiotics and antispasmodic drugs are the preferred approach for patients who refuse to undergo any surgical procedure. However, surgical procedures such as laparoscopic cholecystectomy may be required for patients with severe impaired gallbladder and patients who are intolerant of the recurrent attacks of pain.[1] Despite having a variety of Western medicine treatment options, the symptoms of chronic cholecystitis persist in some patients. The incidence of postcholecystectomy syndrome has also been reported.[3],[4],[5],[6]
Traditional Chinese medicine (TCM) has been gradually gaining recognition in the past decades. In Chinese medicine, chronic cholecystitis can be categorized as “Hypochondrium Pain,” “Jaundice,” “Chest Retention,” etc.[7],[8] According to TCM textbooks and classics, Chinese medicine has developed a complete diagnosis and treatment system on identifying the etiology, pathogenesis, diagnosis, and treatment principles of chronic cholecystitis. Clinically, chronic cholecystitis is associated with several TCM syndromes. One of the predominant TCM syndromes is liver-gallbladder dampness-heat syndrome.[9] The main signs and symptoms include fullness or dull pain in the hypochondrium, abdominal distension, bitter taste, jaundice, red tongue with yellow or thick greasy tongue coating, and wiry or slippery pulse. The treatment principles for chronic cholecystitis with liver-gallbladder dampness-heat syndrome (CCLGDHS) are mainly clearing heat, resolving dampness, promoting bile flow, and purging the bowels.[8] In recent years, a large number of clinical research regarding treating chronic cholecystitis with Chinese herbal medicines have been carried out, and most have shown high effectiveness rate. It is evident that Chinese herbal medicine is an effective alternative treatment for patients with chronic cholecystitis.
The objective of this study is to identify effective common Chinese herbal medicines used in treating CCLGDHS patients by reviewing relevant clinical studies published in the past 10 years. Due to methodological difference, this study only covers the modern interpretation of Chinese herbal medicines used in treating CCLGDHS. Therefore, the outcome of this study may differ from Chinese medicine textbooks and classics.
Literature ReviewRecently, An (安娜) had researched on the correlation between TCM syndromes and objective indexes of chronic cholecystitis. In An's study, four predominant TCM syndromes were identified among 188 patients with chronic cholecystitis. They were liver-gallbladder dampness-heat, liver-Qi stagnation, blood stasis, and liver-Yin deficiency syndromes, accounting for 41%, 31.4%, 16.5%, and 11.2%, respectively. The researcher thus proposed that liver-gallbladder dampness-heat was the most predominant syndrome in chronic cholecystitis.[10]
The frequency of Chinese herbal medicine usage for treating CCLGDHS has been increasing in the past decade. In 2014, Zhong (宗学银) investigated on the clinical effectiveness of the Chai Hu Mai Ya Qing Dan Li Shi Tang (柴胡麦芽清胆利湿汤) in treating 241 chronic cholecystitis patients with liver-gallbladder dampness-heat syndrome and gallbladder-Qi stagnation syndrome. The results of the study showed that the total effectiveness rate of Chai Hu Mai Ya Qing Dan Li Shi Tang was 95.44%. 52.7% of the patients recovered completely, 42.74% of the patients had significant improvement, and 4.56% of the patients showed no response upon receiving the treatment. Chai Hu Mai Ya Qing Dan Li Shi Tang was thus recommended by Zhong in treating chronic cholecystitis patients with syndromes of liver-gallbladder dampness-heat and gallbladder-Qi stagnation.[11]
In 2014, Wang and Du (王华宁等) treated 70 cases of liver-gallbladder dampness-heat–type chronic cholecystitis with Shu Gan Qing Dan Tang (疏肝清胆汤). The experimental group was prescribed with Shu Gan Qing Dan Tang, while the control group was given Xiao Yan Li Dan Pian (消炎利胆片). The study showed that the experimental group had achieved an effectiveness rate of 94.29% while the control group had a mere 74.29% only. As a result of the significant statistical difference (P < 0.05) between the two groups, the researchers inferred that Shu Gan Qing Dan Tang (疏肝清胆汤) had an apparent clinical effect in treating chronic cholecystitis patients with liver-gallbladder dampness-heat syndrome.[12]
In 2016, Zhen (郑玉坤) studied on the clinical effectiveness of self-formulated Hua Shi Li Dan Tang (自拟化湿利胆汤) in treating 90 chronic cholecystitis patients with liver-gallbladder dampness-heat syndrome. Similarly, the formula was compared to Xiao Yan Li Dan Pian (消炎利胆片) in the experiment. The total effectiveness rate of the experimental group (93.3%) was significantly higher (P < 0.05) than the control group (73.3%). In addition, an ultrasound was conducted on both groups to further evaluate the effectiveness of the medicine in correcting pathological changes. The total effectiveness rate of the experimental group was 88.9%, higher than the control group which was 71.1%. Zhen thus suggested that self-formulated Hua Shi Li Dan Tang was effective in treating CCLGDHS.[13]
In 2019, Wang and Wang (王中甫等) conducted a clinical treatment by using Chai Qin Qing Dan Tang (柴芩清胆汤) to treat 41 chronic cholecystitis patients with liver-gallbladder dampness-heat syndrome. The experimental group was given Chai Qin Qing Dan Tang while the control group was given amoxicillin combined with Xiao Yan Li Dan Pian (消炎利胆片) to observe the effectiveness difference between both groups. The study showed that the experimental group (95.12%) improved significantly (P < 0.05) than the control group (78.05%). Chai Qin Qing Dan Tang was thus thought to be superior in improving the condition of CCLGDHS.[14]
In 2015, Fang (房阳) studied the clinical experience of Prof. Xie Jing Ri (谢晶日) in treating chronic cholecystitis. A total of 96 Chinese medicines were identified in the study and the frequency of his prescriptions was systematically analyzed according to medicinal properties. Through statistical analysis, Fang discovered that Chai Hu (柴胡), Yu Jin (郁金), Jin Qian Cao (金钱草), Fo Shou (佛手), Zhi Qiao (枳壳), Xiang Fu (香附), Chao Bai Zhu (炒白术), etc., were prescribed most frequently. Moreover, the study also revealed that Prof. Xie preferred to use Qi-regulating, tonifying, dampness-resolving, blood-activating, and stasis-resolving medicines when treating chronic cholecystitis. The Chinese medicines used also had the characteristics of bitter, pungent, and sweet in flavor, warm and cool in nature, as well as entering the spleen, liver, and stomach meridians. Furthermore, Prof. Xie would prescribe different sets of Chinese medicines in accordance with the five associated TCM syndromes of chronic cholecystitis. Heat-clearing and dampness-resolving medicines such as Long Dan Cao (龙胆草), Huang Qin (黄芩), and Zhi Zi (栀子) as well as bile flow-promoting and bowel-purging medicines such as Yu Jin (郁金), Bing Lang (槟榔), and Da Huang (大黄) were the common Chinese medicines in Prof. Xie's prescriptions used in treating CCLGDHS.[15] Although Fang had mentioned the common Chinese medicines used in treating CCLGDHS, this study cannot represent the modern interpretations of the Chinese herbal medicines as it is solely based on a single practitioner's clinical experience.
Liu and Guo (刘向津等) conducted a research in 2017 to analyze the composition and the prescription patterns of Chinese herbal formulae in treating chronic cholecystitis. Literatures on the treatment of chronic cholecystitis with Chinese herbal prescriptions were collected from the Chinese National Knowledge Infrastructure (CNKI) database. A total of 165 Chinese herbal formulae and 133 Chinese herbal medicines were selected to be analyzed. Chinese herbal medicines with higher frequency were documented, and their medicinal properties, including natures, flavors, meridians, and functions, were systematically analyzed.[16] Although the research had successfully identified certain composition and prescription patterns of Chinese herbal formulae and common Chinese herbal medicines used in treating chronic cholecystitis, the lack of specificity of the common Chinese herbal medicines concerning different TCM syndromes may lead to poor clinical practice guidance, for the diagnosis of TCM syndromes is crucial in addition to disease diagnosis. A disease may comprise several TCM syndromes and Chinese medicine treatments are mainly designed in accordance with syndrome diagnosis. In the case of chronic cholecystitis, the identification of effective common Chinese medicine for liver-gallbladder dampness-heat syndrome will be more clinically oriented.
MethodologyStudy design
This is a retrospective study. Data are collected from the past research only. [Figure 1] shows the flow of the research methodology.
Data collection
Relevant clinical studies regarding Chinese medicine herbal treatment in chronic cholecystitis patients with liver-gallbladder dampness-heat syndrome are systematically collected from different scientific databases including EBSCOhost, ScienceDirect, PubMed, and CNKI. The search keywords are “chronic cholecystitis + TCM treatment,” “chronic cholecystitis + herb + treatment,” “chronic cholecystitis + TCM herbs” in both English and Chinese. Software including Microsoft Excel 2016 and Microsoft Word 2016 are used to categorize and sort the selected data by title, date of publication, and source.
Data screening
The abstracts are screened to exclude data that do not outline research methodology and data that do not show statistical significance in the experimental group. Duplicated data that consist of identical group of subjects and research venues are also excluded. In addition, the full texts are screened to exclude research that uses Western medicine treatments, a mixture of Chinese herbal medicines and western medicines, or other Chinese Medicine treatments such as acupuncture, cupping, moxibustion, and Chinese therapeutic massage in the experimental group. Compositions of Chinese herbal prescriptions that are not completely listed in the research as well as subjects that do not match the inclusion and exclusion criteria will also be excluded. Subjects involved are regardless of gender, age, and ethnicity as the scope of this study is limited to specific diagnosis of the disease and TCM syndrome only.
Data analysis
The composition of Chinese herbal prescriptions will be extracted from the screened data. After extraction of data, Chinese herbal medicines are listed into a table in Microsoft Excel 2016 and arranged by their occurring frequency. The frequency of Chinese herbal medicines is counted in accordance with the frequency of the prescriptions. The top 15 highest Chinese herbal medicines are then statistically analyzed and classified by their medicinal properties, actions, and indications according to the Chinese Pharmacopoeia (ChP) 2015 edition. Efforts will be made to ensure that the above list of Chinese herbal medicines will account for more than 50% of the total count of Chinese herbal medicines in all studies. Recommendations for areas of improvement, if any, will also be provided for the generation of more valid and reliable data in the future studies.
Inclusion criteria
Languages of literature are either Mandarin or EnglishTypes of literature are clinical studiesSources of clinical studies are from online databases including EBSCOhost, ScienceDirect, PubMed, and CNKIDate of publication is between May 2009 and April 2019Subjects involved are regardless of gender and ethnicitySubjects involved are 18 years old or aboveSubjects involved are diagnosed with chronic cholecystitis only, following the guidelines of Merck Manual of Diagnosis and Therapy[17]History of recurrent biliary colicUltrasonography may show gallstonesUltrasonography may show a shrunken and fibrotic gallbladderSubjects involved are diagnosed with liver-gallbladder dampness-heat syndrome only, following the guidelines of Chinese Internal Medicine 《中医内科学》[18]Presence of main clinical signs and symptoms: Hypochondrium distending or burning pain, bitter tastePresence of other possible clinical signs and symptoms: Sticky sensation in the mouth, chest stuffiness, loss of appetite, nausea, vomiting, dark yellowish urine, unsmooth defecation, chills and fever, yellowish coloration of the eyes and body, red tongue with greasy yellowish tongue coating, and wiry slippery rapid pulseSubjects of experimental group are treated with Chinese herbal medicines only which have ingredients targeting the liver and gallbladder system according to the theory of Chinese medicineTreatment effectiveness is based on the following criteria in the Clinical Research Guidelines for New Chinese Medicines 2002 edition[19]Clinically recovered: Sign and symptom score is reduced by more than 95%. Imaging findings show that the gallbladder wall thickening, biliary sludge, or acoustic shadowing has returned to normal. There is also no sign of gallstoneSignificantly effective: Sign and symptom score is reduced by 70%–95%. Imaging findings show that two or more indicators used in clinical recovery have improved. Gallstone size has reduced > 0.5 cm in diameter or the number of gallstones has reduced by >1/3Effective: Sign and symptom score is reduced by 30%–70%. Imaging findings show that one or more indicators used in clinical recovery have improved. Gallstone size has reduced >0.2 cm in diameter or the number of gallstones has reduced by <1/3Ineffective: Sign and symptom score is reduced by less than 30%. Imaging findings do not show improvement in any of the indicators used in clinical recovery. There is no reduction in gallstone size or the number of gallstones has increased.Exclusion criteria
Laboratory experiments that are conducted using animal or tissue samplesResearch that do not include methodologyResearch that do not show statistical significance (P > 0.05) in the treatment provided to the experimental groupResearch that use western medicines, a mixture of Chinese herbal medicines and western medicines, or other Chinese medicine treatment such as acupuncture, cupping, moxibustion, and Chinese therapeutic massage in the experimental groupResearch that do not list the composition of Chinese herbal prescriptions completelySubjects who suffered from mental illness, other organ diseases, acute cholecystitis, acute gallbladder gangrene, acute gallbladder fistula, and gallbladder perforationSubject who are pregnant or lactatingThis study with the project number BCM I/2019(03) has been approved by International Medical University (IMU) Joint-Committee on Research and Ethics on November 8, 2019.
ResultsData collection and data screening
[Figure 2] shows the result of data collection and data screening. 56 relevant clinical studies were retrieved from the four abovementioned online databases, including 55 from CNKI and 1 from ScienceDirect. Comprehensive data screening was conducted before data extraction and data analysis. 31 studies were excluded because ultrasonography was not ordered for diagnosis and/or posttreatment monitoring (n = 29), missing information in diagnosis in Western medicine and/or Chinese medicine (n = 19), western medicines were involved or made fundamental in the experimental group (n = 4), involvement of other TCM syndromes (n = 2), and duplicated data (n = 1) were found. On the contrary, the remaining 25 studies were included as they fulfilled all the criteria of this research, involving 1361 cases and 22 Chinese herbal prescriptions. 58 Chinese herbal medicines are subsequently extracted from the 22 Chinese herbal prescriptions, and the frequency calculation was carried out to determine the top 15 highest frequently used Chinese herbal medicines for data analysis. A summary of the 25 selected studies is shown in [Table 1].
Frequency of the top 15 Chinese herbal medicines
The total frequency of all Chinese herbal medicines of the included studies was 16,819. The top 15 highest Chinese herbal medicines, as shown in [Table 2], were Chai Hu (Radix Bupleuri), Huang Qin (Radix Scutellariae), Jin Qian Cao (Herba Lysimachiae), Bai Shao (Radix Paeoniae Alba), Yin Chen (Herba Artemisiae Scopariae), Yu Jin (Radix Curcumae), Chuan Lian Zi (Fructus Toosendan), Yan Hu Suo (Rhizoma Corydalis), Zhi Shi (Fructus Aurantii Immaturus), Ban Xia (Rhizoma Pinelliae), Bai Zhu (Rhizoma Atractylodis Macrocephalae), Pu Gong Ying (Herba Taraxaci), Gan Cao (Radix Glycyrrhizae), Zhi Zi (Fructus Gardeniae), and Qing Pi (Pericarpium Citri Reticulatae Viride). The total frequency of the top 15 Chinese herbal medicines was 11,137, accounting for 66.22% of the total frequency of all Chinese herbal medicines of the included studies [Figure 3]. Microsoft Word 2016 was used for the classification of the top 15 Chinese herbal medicines in accordance with their medicinal properties, actions, and indications by reference to the ChP 2015 edition.
Figure 3: Distribution of total frequency of all Chinese herbal medicinesMedicinal actions of the top 15 Chinese herbal medicines
[Figure 4] shows the frequency of the top 15 Chinese herbal medicines in accordance with their main medicinal actions. Chinese herbal medicines with the medicinal actions of heat-clearing, tonifying, dampness-draining, Qi-regulating, and blood activating were prescribed in a higher frequency, accounting, respectively, for 20.00%, 20.00%, 13.33%, 13.33%, and 13.33%
Figure 4: Frequency of the selected Chinese herbal medicines by medicinal actionsNature of the top 15 Chinese herbal medicines
[Figure 5] shows the frequency of the top 15 Chinese herbal medicines arranged by their natures. Chinese herbal medicines with the natures of cold, cool, and warm were prescribed in a higher frequency, accounting, respectively, for 33.33%, 33.33%, and 26.67%.
Flavors of the top 15 Chinese herbal medicines
[Figure 6] shows the frequency of the top 15 Chinese herbal medicines arranged in accordance with their flavors. Chinese herbal medicines with the flavors of bitter, pungent, and sweet were predominantly applied, representing 80.00%, 46.67%, and 26.67%, respectively.
Meridians of the top 15 Chinese herbal medicines
[Figure 7] shows the frequency of the top 15 Chinese herbal medicines sorted according to the meridian tropism of the medicines. Chinese herbal medicines which enter the liver, spleen, stomach, lung, and gallbladder meridians are used in a higher frequency, accounting for 60.00%, 53.33%, 46.67%, and 33.33%, respectively.
Figure 7: Frequency of the selected Chinese herbal medicines by meridians Discussion According to the theory of TCM, CCLGDHS can be categorized as “Hypochondrium Pain,” “Jaundice,” “Chest Retention,” etc. Chinese internal medicine guidelines suggested that the treatment principles should clear heat, resolve dampness, promote bile flow, and purge the bowels. The following discussion assesses the linkage of effective clinical Chinese herbal medicines used in the past 10 years with the treatment principles stipulated in the guidelines. New discovery will be supported by TCM theories and pharmacological studies for the possible underlying mechanism.
The top 15 Chinese herbal medicines and their medicinal actions
The top 15 effective common Chinese herbal medicines comprise Chai Hu, Huang Qin, Jin Qian Cao, Bai Shao, Yin Chen, Yu Jin, Chuan Lian Zi, Yan Hu Suo, Zhi Shi, Ban Xia, Bai Zhu, Pu Gong Ying, Gan Cao, Zhi Zi, and Qing Pi.
Chai Hu is cool in nature, pungent and bitter in flavor, and is attributed to the liver, gallbladder, and lung meridians. Clinically, Chai Hu is often prescribed as a key herbal medicine for the treatment of liver and gallbladder-Qi stagnation as well as liver-gallbladder stagnant heat. Its pungent flavor can disperse and activate stagnated liver and gallbladder-Qi, whereas its bitter flavor can clear stagnant liver-gallbladder heat, resolve dampness, as well as descend liver and gallbladder-Qi. Chai Hu is highly effective in regulating the Qi dynamics of liver and gallbladder, and its Qi-descending effect promotes the natural movement direction of gallbladder-Qi.[41] The overall medicinal actions of Chai Hu correspond to the general treatment principles of CCLGDHS, which contribute to its highest frequency in the top 15 list. Modern pharmacological research suggested that Chai Hu exhibits anti-inflammatory, antipyretic, antimicrobial, antiviral, immunomodulatory, and hepatoprotective effects.[42] These pharmacological effects are related to Chai Hu's ability in treating liver-gallbladder dampness-heat–type chronic cholecystitis.
Huang Qin is cold in nature, bitter in flavor, and is attributed to the gallbladder, lung, spleen, large intestine, and small intestine meridians. It has the functions of drying dampness and clearing heat, which can directly target dampness-heat in the liver and gallbladder.[43] The extracts of Huang Qin have a wide range of pharmacological effects, including immunomodulatory, hepatoprotective, antimicrobial, antiviral, and antioxidant effects.[44]
Jin Qian Cao is cool in nature, sweet and salty in flavor, and is attributed to the liver, gallbladder, kidney, and bladder meridians. It has the medicinal effects of draining dampness and resolving jaundice, promoting urination, and relieving strangury, as well as detoxifying and relieving edema.[45] Owing to its salty flavor, Jin Qian Cao is commonly prescribed as a diuretic to counteract the accumulation of dampness in the body. A recent pharmacological study pointed out that Jin Qian Cao has hypolipidemic effect as it demonstrates high effectiveness in eliminating preexisting cholesterol gallstones.[46] Moreover, it also has anti-inflammatory, bile flow-promoting, and pain-alleviating effects.[47],[48]
Bai Shao is cool in nature, sour and bitter in flavor, and is attributed to the liver and spleen meridians. Its cooling property can subdue hyperactive liver-Yang and clear liver heat, thus preserving Yin-fluid of the body from exhausting.[49] Furthermore, with its liver-soothing effect, Bai Shao is commonly used as a painkiller for the alleviation of pain around areas where liver meridian travels. Clinically, Bai Shao is often used in a pair with Chai Hu, as seen in a Chinese herbal formula called Xiao Yao San, to alleviate hypochondrium pain due to liver-Qi stagnation. The extracts of Bai Shao have a variety of pharmacological effects, including spasmolytic, analgesic, antipyretic, antioxidative, anti-inflammatory, and immunomodulatory effects.[50],[51]
Yin Chen is cool in nature, pungent and bitter in flavor, and is attributed to the liver, gallbladder, spleen, and stomach meridians. It can clear dampness-heat from liver, gallbladder, spleen, and stomach through inducing diuresis. Moreover, it also promotes bile flow and resolves jaundice.[52]Yin Chen Hao Tang, a TCM herbal formula, uses Yin Chen and Zhi Zi together to strengthen the diuresis-inducing effect to treat Yang-jaundice. According to modern pharmacology, Yin Chen has hepatoprotective and anti-inflammatory effects.[53]
Yu Jin is cold in nature, pungent and bitter in flavor, and is attributed to liver, heart, and lung meridians. Yu Jin can clear liver-gallbladder dampness-heat, promote Qi circulation and unblock stagnated liver-Qi, promote bile flow, and resolve jaundice.[54] When treating dampness-heat type of jaundice, it is usually prescribed with Yin Chen, Zhi Zi, and Jin Qian Cao to enhance the effectiveness of dampness-resolving and heat-clearing. In addition, modern pharmacology discovers that Yu Jin has hepatoprotective and choleretic effects.[55]
Chuan Lian Zi is cold in nature, bitter in flavor, has slight toxin, and is attributed to the liver, small intestine, and bladder meridians. The medicinal actions of Chuan Lian Zi are soothing liver and clearing stagnant liver heat, promoting liver-Qi circulation, and alleviating pain around areas where liver meridian travels.[56]Chuan Lian Zi consists of toosendanin, a toxic compound that has been reported to cause injury to the hepatocytes.[57],[58] However, severe side effects from the clinical use of Chuan Lian Zi are rarely reported as optimal dosage and inter-relationships among Chinese herbal medicines within a TCM herbal formula are carefully considered during prescription. A combination of Chuan Lian Zi and Yan Hu Suo is an analgesic pair to treat TCM syndromes where the key manifestation is pain due to liver-Qi stagnation. Moreover, they also constitute the prescription of a TCM formula called Jin Ling Zi San, which is used to treat severe distension and pain in the hypochondrium or abdomen due to liver depression, liver-Qi stagnation, or liver-stomach disharmony.[59] The extracts of Chuan Lian Zi have been proven to exhibit anti-inflammatory and analgesic effects according to modern pharmacology.[60]
Yan Hu Suo is warm in nature, pungent and bitter in flavor, and is attributed to the liver and spleen meridians. Its bitter and pungent flavors are effective in regulating stagnated liver-Qi and alleviating hypochondrium and abdominal pain.[61] A pharmacological study has demonstrated the significant effectiveness of Yan Hu Suo extract in different pain assays without developing tolerance.[62]
Zhi Shi is cool in nature, sour, pungent, and bitter in flavor, and is attributed to the spleen and stomach meridians. As it targets the spleen and stomach meridians, it can resolve Qi stagnation in the middle-Jiao via promoting Qi circulation, relieving epigastric or abdominal stuffiness and fullness, as well as alleviating pain.[63]Zhi Shi is commonly applied with Bai Zhu, as seen in Zhi Zhu Wan, to treat epigastric and abdominal stuffiness, fullness, distension, and indigestion due to spleen-stomach deficiency. In modern pharmacology, the extracts of Zhi Shi possess anti-inflammatory effect.[64]
Ban Xia is warm in nature, pungent in flavor, with toxin, and is attributed to the lung, spleen, and stomach meridians. Ban Xia has the medicinal actions of drying dampness to resolve phlegm, descending adverse rise of Qi to stop vomiting, and relieving stuffiness to dissipate nodulation.[65] Since ancient time, it has been an essential herbal medicine that is widely used for relieving nausea, vomiting, hiccup, belching, epigastric stuffiness, and fullness due to phlegm-dampness obstruction. As the heat in dampness-heat easily condenses the body fluids into phlegm, the addition of Ban Xia in prescriptions can resolve signs and symptoms due to the presence of phlegm. However, raw Ban Xia has been reported to carry certain safety concerns such as irritant toxicity to mucosae of oral, throat, and gastrointestinal tract due to the presence of raphides.[66] However, dosage of Ban Xia has been closely monitored in clinical use to ensure that it suits the patient's age, health, and several other factors. Moreover, additional processing techniques have been developed to minimize the associated toxicity of raw Ban Xia. Some of the more prominent methods include processed with alum (Qing-Ban Xia), processed with ginger and alum (Jiang-Ban Xia), and processed with licorice and lime (Fa-Ban Xia). In various pharmacological studies, Ban Xia was proven to exhibit high bioactivities against vomiting as well as eliminating the stagnation of phlegm.[67],[68],[69]
Bai Zhu is warm in nature, sweet and bitter in flavor, and is attributed to the spleen and stomach meridians. Bai Zhu is renowned for its spleen-invigorating and spleen-Qi-tonifying medicinal actions.[70] Through revitalizing the spleen and drying excessive dampness, Bai Zhu also prevents the function of transportation and transformation of the middle-Jiao from deteriorating. In modern pharmacology, the extracts of Bai Zhu have been recognized to exhibit immuno-enhancing effect.[71]
Pu Gong Ying is cold in nature, sweet and bitter in flavor, and is attributed to the liver and stomach meridians. Pu Gong Ying has the effects of clearing dampness-heat, inducing diuresis, resolving jaundice, and strangury due to dampness-heat.[72]Pu Gong Ying is a potent diuretic owing to the discovery of its diuresis-inducing effect in modern pharmacology.[73]
Gan Cao is neutral in nature, sweet in flavor, and is attributed to the heart, lung, spleen, and stomach meridians. Gan Cao has the medicinal actions of tonifying spleen-Qi, alleviating pain and spasms, clearing heat, and detoxifying as well as harmonizing medicinal properties of other Chinese herbal medicines.[74] It is extensively applied in Chinese herbal formulae to alleviate abdominal pain due to liver excess and spleen deficiency. For instance, Gan Cao and Bai Shao are the only ingredients of Shao Yao Gan Cao Tang. A combination of the sour Bai Shao and the sweet Gan Cao can transform into Yin-fluid to nourish and soothe the hyperactive liver. When the liver returns to its physiological state, smooth flow of liver-Qi can be ensured, and thus, pain and spasms are alleviated. Modern pharmacology proposes that Gan Cao has the pharmacological effects of anti-inflammation, antivirus, and spasmolysis.[75]
Zhi Zi is cold in nature, bitter in flavor, and is attributed to the heart, lung, and San Jiao meridians. The cold and bitter medicinal properties of Zhi Zi contribute to its powerful dampness-draining, heat-clearing, and fire-purging medicinal actions that are capable of clearing dampness-heat throughout San Jiao.[76]Zhi Zi is also proven to have antioxidative, apoptosis-regulating, and anti-inflammatory effects.[77]
Qing Pi is warm in nature, bitter and pungent in flavor, and is attributed to the liver, spleen, and stomach meridians. Qing Pi is a Qi-regulating medicine with the actions of soothing liver and promoting Qi circulation, resolving stagnation, and dissipating nodulation. It is generally indicated for treating hypochondrium or abdominal pain due to liver-Qi stagnation and liver depression.[78] Modern pharmacology has pointed out that Qing Pi has the pharmacological effects of bile flow-promoting, hepatoprotective, and gallbladder muscle-contracting.[79]
The disease nature of CCLGDHS is a mixture of excess and deficiency. It is primarily due to dysfunction of the liver and spleen systems. The combinatorial medicinal actions of the top 15 Chinese herbal medicines target the disease nature as they clear the liver-gallbladder dampness-heat, regulate the liver-gallbladder Qi dynamics to promote smooth flow of Qi and bile juice, activate blood to promote blood circulation, relieve cramps and alleviate pain, and tonify the spleen and stomach. The last three represent a new finding which is not stated in the guidelines.
Nature of the top 15 Chinese herbal medicines
The effective common Chinese herbal medicines used in treating CCLGDHS are generally cold, cool, and warm in nature. Based on the general concept of four Chinese medicinal natures, cool and cold Chinese herbal medicines, such as Huang Qin, Yu Jin, and Zhi Zi, have the medicinal effects of clearing heat and purging fire, while warm Chinese herbal medicines, such as Ban Xia and Bai Zhu, have the medicinal effects of warming the Yang and draining dampness. In the case of CCLGDHS, the dampness-heat consists of both dampness pathogenic factor (a Yin-pathogen) and heat pathogenic factor (a Yang-pathogen). The use of warm medicines indicates that the treatment principles shall not focus on the heat pathogenic factor of the dampness-heat only. Appropriate application of warm medicines can revitalize the spleen and stomach, assist the spleen-Yang to drain dampness, and soothe the Qi dynamics of middle-Jiao. Furthermore, cold and cool medicines can clear the stagnant liver heat and counteract the drying-and-warming nature of warm medicines. Thus, combining Chinese herbal medicines with opposite nature shall be considered when formulating a prescription to treat CCLGDHS.
Flavors of the top 15 Chinese herbal medicines
Chinese herbal medicines with the flavors of bitter, pungent, and sweet are the commonly prescribed medicines in the treatment of CCLGDHS. Among the five Chinese medicinal flavors, herbal medicines with bitter flavor, such as Huang Qin and Zhi Zi, are used in the highest frequency as bitter flavor is capable of drying dampness and purging fire, descending Qi, and promoting bowel movement, which are similar to the primary treatment principles of liver-gallbladder dampness-heat syndrome. Pungent herbal medicines, such as Chai Hu, Qing Pi, and Yan Hu Suo, concentrates on promoting and dispersing Qi and blood circulation as well as regulating the Qi dynamics of liver and gallbladder. Sweet herbal medicines, such as Gan Cao and Bai Zhu, regulates spleen and stomach, tonifies Qi and blood, relieves cramps and alleviates pain, and regulates and harmonizes medicinal properties of other herbal medicines in a Chinese herbal formula. Sweet Chinese herbal medicines are essential in the herbal prescriptions as they also strengthen and protect the spleen and stomach before the potential contraction as well as prevention of the “wood over-restraining earth” condition based on the theory of five elements.
Clinically, pungent and sweet herbal medicines are prescribed together to treat syndromes that comprise Yang pathological condition, whereas sour and sweet herbal medicines are prescribed together to treat Yin pathological condition. Moreover, pungent and bitter Chinese herbal medicines are often applied simultaneously as a unique method to regulate Qi dynamics of the body and expel accumulated pathogenic factors through activating, dispersing, and descending Qi. A combination of bitter, pungent, and sweet herbal medicines can clear heat and dry dampness, regulate the Qi dynamics of liver and gallbladder, relieve cramps and alleviate pain, and tonify the spleen and stomach.
Meridians of the top 15 Chinese herbal medicines
The top 15 Chinese herbal medicines mainly enter the liver, spleen, stomach, lung, and gallbladder meridians. The etiology, pathogenesis, and location of CCLGDHS have close relationships with primarily gallbladder, liver, spleen, and stomach. In addition, the five-element theory in Chinese medicine stated that lung, liver, spleen, and stomach are closely related and they can influence each other when a disturbance of the inter-restraint relationships occurs. Herbal medicines that enter the liver and gallbladder meridians, such as Chai Hu and Qing Pi, can regulate the Qi dynamics of liver and gallbladder. Optimal regulation of Qi dynamics ensures that ideal physiological functions of the liver and gallbladder are preserved, thus leading to smooth flow of Qi and bile juice. Although the major associated organs of CCLGDHS are liver and gallbladder, the prescribing Chinese herbal medicines which enter the spleen and stomach meridians, such as Bai Zhu and Gan Cao, are also essential as it is meant to prevent potential disease transmission based on the identified prognosis of liver and gallbladder disease in Chinese medicine. This demonstrates the embodiment of the philosophy of preventive medicine or “Zhi Wei Bing,” one of the symbolic contexts of Chinese medicine. Interestingly, Chinese herbal medicines which enter the lung meridians, such as Yu Jin and Zhi Zi, are also prescribed frequently when treating CCLGDHS. According to the theory of five elements, wood can reverse-restrain metal, implying that stagnant heat from liver-Qi stagnation may injure the lung. By using Chinese herbal medicines that enter the lung meridian, its transmission is cutoff.
Limitation
Limited access to data is the primary limitation of this review. It is due to lack of language proficiency of the researcher. It restricts the ability to access online databases and interpret data of other languages. Moreover, limited types of literature may also have influenced the research findings as data from questionnaires, clinical cases of textbooks and interviews were not included. The abovementioned limitations may influence the scope of analysis and the research findings of this review. Suggestion for future study is to expand the retrospective study to the past 20–30 years to capture more data, thus ensuring the result is more reliable and holistic.
Despite the research limitations of the study design, this review provides evidence-based guidelines on the use of Chinese herbal medicines in treating CCLGDHS through analyzing the ingredients of herbal prescriptions of various clinical researches in the past decade. In addition, this review also offers insight into the underlying relationships between Chinese herbal medicines and chronic cholecystitis. It also serves as an evidence-based reference to support identification of pattern of the Chinese herbal formulae used in treating CCLGDHS.
ConclusionThe top 15 effective common Chinese herbal medicines used in treating CCLGDHS are Chai Hu, Huang Qin, Jin Qian Cao, Bai Shao, Yin Chen, Yu Jin, Chuan Lian Zi, Yan Hu Suo, Zhi Shi, Ban Xia, Bai Zhu, Pu Gong Ying, Gan Cao, Zhi Zi, and Qing Pi. The predominant natures are cold, cool, and warm, whereas the predominant flavors are bitter, pungent, and sweet. The majority of the herbal medicines enter the liver, spleen, stomach, lung, and gallbladder meridians. The combinatorial medicinal actions of the effective common herbal medicines are clearing the liver-gallbladder dampness-heat, regulating the liver-gallbladder Qi dynamics to promote smooth flow of Qi and bile juice, activating blood to promote blood circulation, relieving cramps and alleviating pain, and tonifying the spleen and stomach. The inclusion of activating blood to promote blood circulation, relieving cramps and alleviating pain, and tonifying the spleen and stomach is a new finding compared to treatment principles stated in the guidelines. This demonstrates a holistic approach to the treatment of CCLGDHS. For instance, it purges the excess and tonifies the deficiency, conjointly focuses on both treatment and prevention, thus achieving high therapeutic effect in clinical use. In addition, the embodiment of the philosophy of preventive medicine to promote the harmonious inter-relationships among the five elements is also remarkable.
Financial support and sponsorship
This research was funded by IMU research fund under the project number BCM I/2019 (03).
Conflicts of interest
There are no conflicts of interest.
References
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