Characteristics of Tibetan medicine preparations used in the Chinese-Tibetan Hospital of Derong County

Purpose: To investigate the Tibetan medicine preparations used in Derong Chinese-Tibetan Hospital. Methods: In this study, 115 preparations were collected from the Chinese-Tibetan Hospital of Derong County. A statistical table of information on medicine preparation was prepared in Excel format, and it included information on the forms of preparations, medicinal materials, medicinal parts used, frequency of use, and clinical applications. Results: The 115 preparations were mainly pills. In clinics, they were used for treating liver disease, stomach-ache, gastric ulcer, nephrotic pain and fever. It was found that 226 medicines were used in various preparations. The plant components used varied from whole herbs, fruits, seeds, roots, rhizomes, and animal-based medicines, to flowers. The most frequently used plants/herbs were Terminalia chebula Retz., Carthamus tinctorius L., Aucklandia lappa Decne., Alpinia katsumadai Hayata and Phyllanthus emblica L. The most commonly used drug combinations involved three fruits (Terminalia chebula Retz., Terminalia billerica (Gaertn.) Roxb and Phyllanthus emblica L.). The preparations and medicinal materials used for liver and stomach diseases are described in detail in this article. These include Terminalia chebula Retz., Aucklandia lappa Decne. and Carthamus tinctorius L. Conclusion: The study has analysed the characteristics and clinical uses of Tibetan medicine preparations and summarised the diseases and medicinal materials in the Tibetan area. These preparations and medicinal materials, with their many years of clinical use, may become invaluable gifts of Tibetan medicine to the world.


INTRODUCTION
Tibetan medicine has a long history of textual research. It has incorporated the essence of ancient Indian medicine, Chinese medicine and Greek-Arab medicine, and it occupies a unique position in the world's traditional medical system [1].
In the 15 th century, based on the theoretical system of the classic Tibetan medicine Four
The preparations of 114 medical institutions in Derong County in Ganzi Prefecture have been used in clinical practice for many years, with definite curative effects, low toxicity, minimal side effects, as well as good development and utilisation value. At present, more than 80 % of the medicines used in Tibetan medical clinics are pharmaceutical preparations of medical institutions. Hospital preparations are the major drugs used clinically in Derong Tibetan Medicine Hospital. This study used data mining of prescription information to analyse the characteristics, dosage forms, diseases treated, frequently-used medicinal materials, and other information on prescriptions. These preparations had only two dosage forms pill and powder, which were the more frequently-used forms (93.91 %). The number of medicinal species in the preparations ranged from 3 to 35, but most preparations comprised 25 species, while others had 7 species (Figure 1). Several medicines in the preparations (67 %) had between 3 and 15 species, so as to avoid repeated drug use and reduce waste of medicinal resources. Modern medical names were used in the descriptions for diseases in DCTH. In the course of clinical applications, the characteristics of Chinese, Western and Tibetan medicines were integrated. Preparations were widely used to treat various diseases within the same systems, or to treat diseases from different systems, including the digestive system and urinary system. Preparations were also used to treat typical Tibetan diseases, especially liver disease, dyspepsia, stomach-aches, vomiting and diarrhoea, gastric ulcers and nephropathy pain. Statistical analysis showed that the preparations were targeted at treating 17 different kinds of diseases. The types of diseases included characteristic diseases of the digestive system, urogenital system, respiratory system, musculoskeletal system and connective tissues, as well as Tibetan medicine. A total of 24 types of preparations were used for the treatment of liver diseases, followed by 16 preparations for fever, and 14 each for nephropathy and dyspepsia. The clinical classification of the preparations is shown in Figure 2. A total of 226 medicinal materials were involved, with the most commonly used drugs being Terminalia chebula Retz., Carthamus tinctorius L., Aucklandia lappa Decne, Alpinia katsumadai Hayata and Phyllanthus emblica L. (Table 1). There was consistency in rankings of the most frequently used five-dish Tibetan medicines obtained by the Institute of Tibetan Medicine Preparations, based on the quality standards of medicines [5].
(The fruits of these three plants are often used together and are customarily the so-called "three fruits"), C. tinctorius L. and A. lappa Decne ( Table 2).

Usage of preparations
The frequencies of medicine intake were twice daily (46.96 %), three times a day (21.74 %), and 2 -3 three times a day (13.04 %). Daily doses of preparations not exceeding 8 g were the most used (93.04 %), while the highest daily dose of Zhitu Riga RiBu was 15 g. There were 4 methods of administration of medications: chewing (93.91 %), decoction (54.35 %), bathing (only Dezi Jueluo powder), and swallowing (only Tabu Mana powder). Some preparations had special requirements: Shaizhu Anba Ribu was taken on an empty stomach in the morning, while Basang Manma Ribu was taken once at night in winter and spring.

Digestive diseases and common drugs
Digestive tract diseases have always been the most common diseases in Tibet. As a result of the cold climate and lack of oxygen in residential areas, Tibetans have developed particular habits and dietary patterns. They tend to eat yak meat, mutton, yak butter tea and other high-calorie and high-protein foods, and also drink barley wine in large quantities to keep out the cold. They eat less of fruits and vegetables. Long-term maintenance of these dietary habits lead to high incidence of digestive tract diseases. Gastric and liver problems are the main diseases of the digestive system. Liver and gastric cancers accounted for 75.2 % of all cancer deaths in 2004 -2005 [6]. Gastric diseases were recorded in detail as early as in The Four Medical Tantras and Yue Wang Yao Zhen [7].
In modern Western medicine, gastric diseases comprise superficial gastritis, chronic atrophic gastritis, peptic ulcer and Helicobacter pylori infection. In addition to gastric diseases, the number of preparations for the treatment of liver diseases is particularly prominent in the category of digestive diseases. Data on the use of Tibetan medicine in the treatment of liver diseases indicate the involvement of 193 different medicines comprising 181 types of plant-based drugs, 7 different animal-derived drugs, and 5 mineral drugs [8]. Through data mining of preparations in Derong Hospital, some frequently used preparations and plants for the treatment of gastric and liver diseases were identified and briefly introduced. These preparations may be potential candidate drugs for the treatment of digestive tract diseases.
It has been reported that the ethanol extract of T. chebula suppressed acetylcholine chlorideinduced excitation of intestinal smooth muscles, inhibited gastric emptying and intestinal motility in normal mice, prevented contraction of isolated intestinal smooth muscles, and reduced serum motilin content in rats [11]. Moreover, serum containing T. chebula extract mitigated CCl4induced morphological changes in cells, significantly increased cell viability, effectively inhibited CCl4-induced lipid peroxidation in hepatocytes, and enhanced the activities of lipid peroxidase, SOD and GSH-Px [12].

Carthamus tinctorius L.
Carthamus tinctorius L. is a commonly used herb in China. It is grown mainly in Henan, Hunan, Sichuan, Xinjiang and Tibet Provinces. The medicinally-used parts of C. tinctorius are the dried flowers which are known as Ku-gong in Tibetan, Honghua in Chinese, and safflower in English. Carthamus tinctorius L. is used for the treatment of dysmenorrhea, dystocia, traumatic injury and blood stasis in TTM and TCM. Kugong is also used in Tibetan medicine for treating hepatitis and hepatic heat. Modern pharmacological studies have shown that safflower has pharmacological properties that protect the myocardium, as well as antioxidant, anti-apoptotic, anti-inflammatory and anti-tumor effects. Hydroxysafflor yellow A, the effective bioactive component in safflower, is the material basis for its pharmacological effects [13]. Studies have shown that safflower exerts protective effect against acute liver injury induced by CCl4 in rats as a result of its anti-inflammatory and antioxidative properties; it inhibits activation of JNK signaling pathway and regulates the expression of apoptotic factors [14]. A study determined the effect of safflower on the expressions of Bax and Bcl-2 and their ratios in rats with acute liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN) [15]. Compared with the traditional hepatoprotective drug (reduced glutathione (GSH)), safflower significantly protected the rats from LPS/D-GaIN-induced hepatocyte injury. Moreover, extract of C. tinctorius exerted significant inhibitory effect on diethylnitrosamineinduced liver cirrhosis in rats [16].

Aucklandia lappa Decne.
Aucklandia. lappa Decne is a Compositae plant, and its medicinal value resides in its dried roots, commonly known as Ru-da in Tibetan or Muxiang in Chinese. It is native to India, and it grows on high mountains. The plant was introduced to, and is cultivated in Shanxi, Gansu, Hubei, Hunan, Guangdong, Guangxi, Sichuan, Yunnan and Tibet. In Tibetan medicine, it is used to treat qi stagnation, chest and abdomen pain, vomiting, diarrhoea, pneumonia and 'Long' disease.
Modern pharmacological pharmacodynamic studies have shown that A. lappa Decne improves gastrointestinal motility, protects the gastric mucosa, enhances gallbladder contraction and vasodilation, inhibits platelet aggregation and resists pathogenic microorganisms. Moreover, A. lappa Decne has anti-inflammatory and anti-tumour properties. The main bioactive compounds and quality control markers of A. lappa Decne are costunolide and dehydrocostus lactone.
Costunolide alleviated lipopolysaccharideinduced acute liver injury in animal models. It has been reported that aqueous and alcohol extracts of stems and leaves of A. lappa Decne. promoted small intestinal propulsion in mice, an effect which may be related to M cholinergic receptors [17]. Recent studies have shown that costunolide regulated the expressions of lipid metabolism-related transcription factors SREBP-1c and PPARα by activating AMPK, thereby reducing lipid production and accumulation in hepatocytes [18]. Thus, costunolide may be used as a potential preventive drug for alcoholic fatty liver.
In this study, a total of 115 preparations used in Derong medical institutions were collected, mainly from Fanbian Medical Works, The Four Medical Tantras and Secret Prescriptions of Medicine. Traditionally, the preparations were in only two formulations: pills and powders. The primary health issues for which these preparations were used were digestive system diseases, urogenital system diseases, characteristic diseases of Tibetan medicine and respiratory system diseases. The doses used for 67.83 % of the preparations did not exceed 5 g per day. A total of 226 kinds of medicines were involved in the 115 preparations, with the use of botanical medicines being the most common, followed by animal-based medicines. The medicinal parts used were roots, stems, leaves, flowers and some parts of flowers and fruits, as well as animal bones, horns, organs, excreta and blood. Fruits and seeds were the most commonly used medicinal materials, followed by roots and rhizomes. Based on frequency of use, the top five drug plants were T. chebula, C. tinctorius L., A. lappa Decne., A. katsumadai Hayata and P. emblica. T. chebula, safflower, Muxiang, Yuganzi and pomegranate were introduced, including their traditional uses, phytochemistry and pharmacological effects.
This study summarizes the characteristics and clinical uses of Tibetan medicine preparations. It is one of the few countries with relatively complete preservation of the southern Tibetan medicine culture. The selected areas have limited research data on Tibetan medicine preparations. Further research is needed to improve research on Tibetan medicine.

CONCLUSION
This study has provided vital information on the characteristics and clinical uses of Tibetan medicine preparations and summarized the common diseases and medicinal materials in the Tibetan area. These preparations and medicinal materials, with their many years of clinical use, may become invaluable contributions of Tibetan medicine to the modern world.

Ethical approval
None provided.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conflict of Interest
No conflict of interest associated with this work.

Contribution of Authors
We declare that this work was done by the authors named in this article, and all liabilities pertaining to claims relating to the content of this article will be borne by the authors. Meiling Zhao and You Zhou participated in the establishment of the database, statistics and writing of manuscript. Ke Fu, Xiaoli Li and Min Xu participated in the establishment of the database for the study. Yuan Liang, Xuemei Zeng, Gang Fan and Jing Zhang participated in statistical analysis of data. Qupi Arong, Zhenzhui Luorong and Zhang Wang collected data from the Chinese-Tibetan Hospital of Derong County. Meiling Zhao and You Zhou contributed equally to this work.

Open Access
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/rea d), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.