Annual advances of Chinese minority traditional medicine in 2019

Shao-Hui Wang

1Medical College, Qingdao Binhai University, Qingdao 266555, China; 2Affiliated Hospital of Qingdao Binhai University,Qingdao 266555,China.

Abstract

Keywords: Chinese minority traditional medicine, Tibetan medicine, Uyghur medicine, Mongolian medicine,Korean medicine,Zhuang medicine

Highlights

The annual review summarizes the research pertaining to different Chinese minority traditional medicine(CMTM) published in 2019.The focus of these studies is on the pharmacological effects and mechanisms of the ethnodrug and prescriptions/therapies used in ethnic areas.

Traditionality

CMTM is an important part of traditional Chinese medicine.It exhibits characteristics of nationality,region,and tradition.Tibetan medicine first appeared around 500 B.C.E.At the end of the 8thcentury C.E., the development of “Si Bu Yi Dian (Four Medical Tantras)” by the Tibetan medicine scientist Yutuo Ningma Yundan Gongbu provided a theoretical foundation for Tibetan medicine.Before the 7thcentury C.E.,Mongolian medicine was in its infancy.In the 16thcentury C.E., Mongolian medicine assimilated several classical medical theories and useful experiences from Tibetan,Han,and other nationalities.This eventually leads to the development of a Mongolian medical theory system with Mongolian characteristics.Uyghur medicine has arduously developed over a period of more than 2,500 years.The origin of Uyghur medicine traces back to the ancient Neolithic period in the Western Regions.At the beginning of the 12thcentury,the Uyghur medicine scientist Alaodin Mohanmude Hetianni wrote the “Zubdatul Kawanil Ilaj (Zhi Liao Jing Hua, Healing Essences)” and “TibbiFitki (Fa Yi, Forensics)”.The copy of this handwritten work is circulating to this day.

Background

China is a multi-ethnic country with a long history, a vast territory,and a large population.In addition to the Han nationality(the main ethnic group in China),there are 55 ethnic minorities in the country.Historically,almost each ethnic group has developed its own traditional medicine system and health care technology.Chinese minority traditional medicine (CMTM) is a summary of the rich medical knowledge and practical experiences of disease prevention and treatment accumulated by people of various ethnic minorities over the centuries.The examples include, urine diagnosis and bloodletting in Tibetan medicine [1, 2],sand therapy in Uyghur medicine [3, 4] and the medicated thread moxibustion method and tendon therapy in Zhuang medicine (one of the Chinese minority traditional medicines) [5, 6].All these have made important contributions to the health and development of the nation.In modern society, the CMTM still plays an important role in disease prevention and health care of various ethnic groups.Prominent examples include Tibetan medicine for plateau diseases and digestive system diseases [7–10],Mongolian medicine for orthopedic diseases [11, 12]and detoxification method of Zhuang medicine[13].At the same time, it has gradually become the focus of attention of international scholars [14–16].A recent review found a gradually increasing trend in the publication of academic research in the field of CMTM,especially in the WOS core database.However, the growth rates in each research area were slightly different;most published research pertained to the field of Tibetan medicine, Korean medicine and Mongolian medicine(Figure 1).

The annual review focuses on the pharmacological effects and mechanisms of action of minority traditional ethnodrugs and prescriptions or therapies used in ethnic areas, especially Tibetan medicine,Uyghur Medicine, Mongolian medicine, Korean medicine and Zhuang medicine.The objective is to provide a reference for the development of CMTM.

Tibetan medicine

Tibetan medicine has evolved over time by assimilating folk therapies used in the snowy plateau and the medical culture, Buddhist theories of the central plains, and medicine systems of India and Arabia.Tibetan medicine has made immense contributions to the health and survival of the Tibetan people in the snowy plateau and nearby areas.Moreover, it has also spread to other parts of China and overseas with cultural exchanges and made important contributions to the cause of human health[17, 18].For instance, Swertia species have been used to treat various ailments in traditional Indian medical systems, Chinese traditional systems, and traditional Tibetan medicine.It is also used to treat hepatitis,cholecystitis, osteomyelitis, pneumonia, scabies, and dysentery [19].Through statistical analysis of the relative percentage of Tibetan medicine-related publications in different countries and study areas in 2019, we found that the research areas mainly pertained to the field of pharmacology,pharmacy,plant sciences, medicinal chemistry and integrated complementary medicine.The top three countries where the research was conducted were China, USA,and India (Figure 2).First of all, traditional Tibetan ethnodrug is used as a source of alternative complementary medicine.For example,as a traditional Tibetan medicine, turnip seeds and tubers can reduce the risk of liver fibrosis, inhibit the activity of human breast and colon cancer cells and enhance the body's ability to resist hypoxia [20].Rhododendron anthopogonoides has been used in antitussives,expectorants, antiasthmatics, stomachic and swelling agent, heat-clearing and detoxicating therapies [21].Mirabilis himalaica is endemic to the Himalayas and is used in traditional Tibetan folk medicine [22].Juniperus tibetica is used in Tibetan medicine to treat rheumatic arthritis [23].A special form of Tibetan medicine meditation is shown to reduce the psychological distress of women with breast cancer[24].TongFengTang powder is an ancient prescription comprising of Tinospora sinensis, Terminalia chebula Retz, and Trogopterori faeces; it is used to treat joint diseases like gout, swelling, gout arthritis, and pain[25].Chinese and overseas scholars have conducted many studies to clarify the active ingredients and the mechanism of action of Tibetan medicine, including the study of traditional Tibetan ethnodrugs; the examples include, Brassica rapa [26],Herpetospermum caudigerum[27,28],Veronica ciliate[29], Rhodiola crenulate [30], Swertia chirayita [16,31, 32], the stems of Tinospora sinensis (Kuanjinteng)[33].Pterocephalus hookeri[34],Juniperus pingii[35],1-hydroxy-3,7,8-trimethoxyxanthone from Tibetan medicine Gentianopsis paludosa [36].Moreover,several traditional Tibetan medicine formulations have been studied, such as Zhenlong Xingnao capsule(ancient prescription) [37], Jikan Mingmu drops(ancient prescription) [38], PC (A PC containing H.rhamnoides fruit pulp, P.armeniaca fruit pulp, and R.imbricata dry root extract (100: 50: 1), experimental formula) [39], Yinian Kangbao tea (patent drug) [40].Qiwei Tiexie capsule(ancient prescription)[41],Anzhi jinhua powder (ancient prescription) [42].Srolo Bzhtang (ancient prescription) [43], and Qingpeng ointment (patent drug) [44].The pharmacological effects and mechanisms of the above traditional Tibetan ethnodrugs and prescriptions are summarized in Table 1.Other scholars have studied the chemical composition of Tibetan medicine.For example, seven major antioxidants are isolated from the Tibetan medicine Lancea tibetica: (+) -pinoresinol-beta-Dglucoside, acteoside, anthelminthicol, tibeticoside,isoacteoside, epipinoresinol, and phillygenol [45].Two new diterpenoid alkaloids (chrysotrichumine A and delphatisine D) and ten known diterpenoid alkaloids and 3β,6 alpha-dihydroxysclareolida are isolated from the Tibetan medicine Delphinium chrysotrichum [46].In addition, the toxicity of Tibetan medicine Zuotai(gTso thal, a mercury preparation that contains 54.5%mercury sulfide (HgS)) is also evaluated.Zuotai is a precious adjuvant in Tibetan medicine that has long been used to treat cardiovascular diseases, liver and bile diseases, spleen and stomach diseases; however,its application has been controversial.Recent studies have shown that Zuotai can effectively induce liver toxicity at a certain dose; however, this liver toxicity may occur through other mechanisms that do not rely on HgS, β-HgS, and is different from chemical forms of environmental mercury pollutants (MeHgCl and HgCl2).The neurotoxicity of β-HgS in Neuro-2a cells is much less than that of MeHgCl and HgCl2[47–49].

Uyghur medicine

Uyghur medicine is a traditional medical system developed by Uyghur ancestors residing in the Xinjiang Uyghur Autonomous Region of China over centuries.It has rich practical experience and unique theoretical content [50].Statistical analysis of the relative percentage of Uyghur medicine-related publications in different countries reveals that the research areas mainly pertain to the disciplines of chemistry, pharmacology, pharmacy, and food science technology.Most of the publications are from China(Figure 3).The most researched subject is the pharmacological effects and mechanisms of some traditional Uyghur drugs.For example, some studies have demonstrated significant anti-respiratory syncytial virus effects(both in vivo and in vitro)of the three active ingredients derived from the Uyghur medicine Radix Isatidis, i.e., lignans, organic acids,and total alkaloids.The lignans and total alkaloids are shown to play a multi-target synergistic role through the melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I signal pathways [51].The extracts of Uyghur medicine Psoralea corylifolia,including 8-methoxypsoralen, 5-methoxypsoralen and 4,5,8-trimethylpsoralen are used for the repigmentation of leukoderma (vitiligo) [52].A homogeneous polysaccharide isolated from female flowers of Uyghur medicine Humulus lupulus shows a significant anti-osteoporotic activity [53].A recent study demonstrated the efficacy of Citrullus colocynthis in the treatment of rheumatic arthritis or diseases caused by abnormal black bile; in addition, it also showed good neuroprotective effect on PD [54].Some scholars have applied analytical chemistry methods to study Tibetan medicines.For example, a ultra performance liquid chromatography-quadrupole time of flight/mass spectrometry method was developed to characterize the chemical differences of Flos Carthami(the “king of medicine” in Uyghur medicine).It provided a basis to improve the stability of the quality of Flos Carthami and ensure its clinical application[55].In another study, high performance liquid chromatography and ultra performance liquid chromatography-quadrupole time of flight/mass spectrometry were used to analyze the active ingredients in the root of Uyghur medicine Anacyclus pyrethrum.Finally, 20 N-alkylamides were identified,including two N-methylisobutyramides, six 4-hydroxyphenylethylamides, eleven N-isobutyramides and one 2-phenylethylamide [56].In short, research on the pharmacology, pharmacy, and chemistry of Uyghur medicine has immensely contributed to the development of Uyghur medicine.

Mongolian medicine

Mongolian medicine represents the medical practice experience accumulated by Mongolian ancestors.At the same time, it has absorbed the essence of Tibetan,Han, and ancient Indian medical theories, and has gradually developed into a national traditional medicine with a unique theoretical system and clinical characteristics.Moreover, Mongolian medicine has significant ethnic and regional characteristics and has contributed to the prosperity of the peoples of all ethnic groups in the north of China, especially in the Inner Mongolia region of China [57].We found that the Mongolian medicine-related publications mainly pertained to pharmacology pharmacy, analytical chemistry, biochemistry, molecular biology, and experimental medicine research.The publications are mainly from China and Mongolia (Figure 4).Some scholars have studied the traditional Mongolian ethnodrugs, including the study of chemical composition,pharmacological effects,and mechanisms of action.The Mongolian medicine “Dogel ebs”(Sophora flavescens)shows a therapeutic effect against damp-heat dysentery, scrofula, and cumulative dampness toxicity syndrome [58].Gentianella acuta has been widely used to treat cardiovascular diseases in Mongolian medicine.A study demonstrated that Gentianella acuta prevents cardiac dysfunction caused by ISO by preventing fibrosis and oxidative stress; the likely underlying mechanism was inhibition of the NF-κB pathway [59].In addition, Gentianella acuta extract and its active ingredient-Desmethylbellidifolin is shown to inhibit trinitrobenzenesulfonic acid-induced ulcerative colitis and reduce inflammation and relieve colon muscle spasm [60].Another scholar isolated and identified 31 active ingredients from the dried roots of Mongolian medicinal and edible plant Pugionium cornutum; four of these are rare natural thiohydantoin derivatives[61].Lomatogonium rotatum is an important Mongolian medicine used to treat febrile diseases related to liver and gallbladder.The flavonoids and xanthones are the main chemical constituents of the 50%ethanol fraction of Lomatogonium rotatum, and sulfation and glucuronidation are the key enzyme-induced metabolic pathways involved post-administration [62].Another study identified eight metabolites produced after treatment with Lomatogonium rotatum, including choline, succinic acid, phosphopantothenic acid,AMP,arachidonic acid, glycerol 3-phosphate, DHA, and linoleic acid;these can be used as potential biomarkers to assess the hepatoprotective effect of Lomatogonium rotatum [63].Some scholars have studied some traditional Mongolian formulas.For example,RuXian-I (a traditional Mongolian recipe consisting of 30 kinds of Mongolian herbs)is shown to exhibit high efficacy for treatment of mammary gland hyperplasia of in a clinical study with few side effects [64, 65].Mongolian medicines Naru-3 and Jonlon-5 are shown to exhibit anti-inflammatory effects against collagen-induced rheumatoid arthritis and carrageenan-induced arthritis in rats, respectively [11,12].Dedu seven-ingredient pill with safflower is shown to promote the expression of death-associated protein kinase protein by downregulating the expression of miR-23a, thereby preventing the proliferation, migration, and invasion of cancer cells[66](Table 2).In addition,Mongolian medicine is also used in food nutrition and health care.For instance, a study demonstrated the health-promoting properties and therapeutic effect of Chigee, a traditional fermented mare milk [67].The aqueous extract of Allium mongolicum (a traditional Mongolian medicine herb) may be used as a functional food or health supplement for the prevention and treatment of obesity and hypertension.Researchers have shown that it has high antioxidant content and suppresses vital enzymes relate to hypertension and obesity [68].In Mongolian medicine,warm acupuncture is commonly used to treat insomnia.It can enhance body functions, regulate Qi,somatostatin, strengthen immunity, as well as prevent and treat many diseases.Mongolian medical warm acupuncture promotes glucose metabolism in the brain of insomnia model rats mainly by increasing the level of miR-18 and reducing the level of N-Myc downstream regulated gene 2[69].

Korean medicine

The Korean people of China (Chaoxian minority)mainly reside in the Northeast region of China,especially in Yanbian (Jilin Province).Korean medicine of China is a traditional medical system developed on the basis of the inherent culture of the Korean people.It assimilates the traditional Chinese medicine theory and their own ethnic experiences in preventing and treating diseases [70].Korean Oriental Medicine (Korean medicine) of South Korea is theoretically based on the evolution of traditional Chinese medicine.Due to the geographical proximity and the close historical relationship between China and the Korean Peninsula, Korean medicine plays an important role in China and South Korea.Indeed,there is no essential difference between the two systems.Our study revealed that the Korean medicine research publications mainly pertained to the disciplines of integrative complementary medicine, general internal medicine, pharmacology, pharmacy, and medicinal chemistry; the top three countries were South Korea,China,and USA(Figure 5).Korean medicine is widely used in general internal medicine as an alternative and supplementary method.Many studies have found that Korean medicine is effective in treating liver disease[71], potential stroke patients (especially elderly patients) [72], somatic symptom disorder [73], and traumatic injury (blood stasis therapy) [74].Moreover,several South Korean scholars have studied the pharmacological action and mechanism of action of some Korean herbs and formulas.For example, the low-polarity extract of Korean medicine ginseng is shown to regulate the oxygen consumption rate of cardiomyocytes cultured during mitochondrial respiration [75].The extracts of Forsythia suspensa fruits are shown effective in the treatment of peripheral neuralgia in cancer patients receiving oxaliplatin chemotherapy [76].Hyperoside (quercetin 3-O-galactoside), which is isolated from Acer tegmentosum,can be used to treat liver-related diseases.In addition, hyperoside is shown to exhibit neuroprotective effects, which are likely mediated via induction of nuclear factor erythroid-2-related actor 2-dependent heme oxygenase 1 activation and inhibition of neuronal death caused by 6-hydroxydopamine-induced oxidative stress [77].The water extract of Acori Graminei Rhizoma is used to treat arthritis and is shown to reduce the inflammatory indicators [78].A study demonstrated a potent antitumor effect of Trichosanthes kirilowii seeds; the effect might be partly attributed to AMPK activation and induction of mitochondrial-mediated colorectal cancer cell apoptosis [79].Madi-Ryuk is widely used in South Korea for the treatment of arthritis [80].Sang-Hyul-Yun-Boo-Em is a mixed herbal formula used for patients with skin diseases [81].Jakyakgamcho-decoction is shown to be effective in the treatment of colitis; the potential underlying mechanisms are restoration of dysbiosis of gut microbiota and host metabolites[82].

Zhuang medicine

Zhuang medicine has long history, quaint theories,colorful diagnoses,treatment techniques and thousands of consummate prescriptions.It has become an important part of Chinese traditional medicine.Zhuang medicine provides effective means and methods for the prevention and treatment of diseases.It is an important medical and health resource in the Zhuang region of China [83].Our research revealed that the Zhuang medicine-related publications mainly pertained to biochemistry, molecular biology, chemistry multidisciplinary,integrative complementary medicine,and general internal medicine; the publications were mainly from China.For example, a clinical study demonstrated the efficacy of Zhuang medicine moxibustion line therapy in the treatment of alopecia areata [5].Bawei Longzuan granule (a representative Zhuang medicine preparation) can be used as a supplement or an alternative traditional medicine for the treatment of rheumatoid arthritis; its therapeutic effect is mainly mediated via inhibition of the inflammatory response[84].Longzuan Tongbi formula is a Zhuang medicine prescription for the treatment of rheumatoid arthritis.A study employed network pharmacology to study Longzuan Tongbi formula.The results revealed three pathways (inflammatory mediator regulation of transient receptor potential channels, mammalian target of rapamycin signaling pathway and peroxisome proliferator-activated receptor signaling pathway) that may have certain effects in the treatment of rheumatoid arthritis[85].

Figure 1 Statistical analysis of annual publications of traditional medicine research on different Chinese minorities

Figure 2 Statistical analysis of the relative percentage of Tibetan medicine-related publications in different countries(A)and research areas(B)in 2019

Table 1 The pharmacological effects and mechanisms of the traditional Tibetan ethnodrugs and prescriptions

Table 1 The pharmacological effects and mechanisms of the traditional Tibetan ethnodrugs and prescriptions(Continued)

Figure 3 Statistical analysis of the relative percentage of Uyghur medicine-related publications in different research areas in 2019

Figure 4 Statistical analysis of the relative percentage of Mongolian medicine-related publications in different countries(A)and research areas(B)in 2019

Figure 5 Statistical analysis of the relative percentage of Korean medicine-related publications in different countries(A)and research areas(B)in 2019

Table 2 The source and main constitutive herbs of all compound preparations in Mongolian medicine

Other minority medicine

In addition to the above-mentioned research hotspots pertaining to CMTM, other scholars have studied Yao medicine and Dai medicine (other Chinese minority traditional medicines).Yao medicine represents the crystallization of wisdom acquired by Yao people over the years.It has a long history, rich treatment experience, and unique national style.For instance,Mallotus conspurcatus croizat (Euphorbiaceae) is a medicinal plant that is widely used by the Yao people for treatment of inflammation [86].The whole plant of Jasminum pentaneurum has been widely used to treat rheumatism, stomach pain, asthma, nephritis,bronchitis, and cancer.Twelve active ingredients have been isolated from Jasminum pentaneurum, including a new secoiridoid glycoside, 10-(3-hydroxy-4-methoxy-benzoate) -glucoside, eight phenols, and three secoiridoid glycosides [87].Dai medicine is also one of the ancient traditional medicines in China.Obcordata A is a polyoxypregnane glycoside obtained from Dai medicine Aspidopterys obcordate.Some scholars have shown that obcordata A can be used as NOX4 inhibitor to prevent kidney stones [88].In Dai medicine, areca nut (a common folk herbal medicine of the Dai people) has been used to treat diarrhea,abdominal distention, malaria, and indigestion.Studies have shown that it is composed of areca nut, betel leaf(Piper betle), lime (calcium hydroxide), and sometimes other ingredients (such as tobacco), which can be used to treat toothache, sore throat, gum problems,itching,and hemoptysis[89].

Conclusion and prospectiveIn short, the CMTM has shown considerable developments over time,both in theory and in practice.Indeed, CMTM has made great contributions in preventing and treating various diseases and protecting the health of people of all ethnic groups.The 2019 annual research reports show that the research focus has mainly been on the effects and mechanisms of the active ingredients of minority traditional medicines and the special prescriptions or therapies used in the ethnic areas.However, most research has focused on the preliminary mechanism of action of the crude extracts of ethnic medicines or formulas.The specific effective monomer composition and in-depth mechanism of action are yet to be elucidated.In addition, there is relatively more research on Tibetan medicine, Korean medicine, and Mongolian medicine.There is relatively less research on other ethnic medicine systems such as Dong medicine and Tujia medicine.This may be attributable to the deficient or lacking theories of other ethnic medicines.It is worth mentioning that with the advancement and development of science and technology, collaboration between various disciplines and laboratories, and the efforts of medical scholars of ethnic minorities in China,there is an increasing trend of in-depth research on CMTM.Moreover,the CMTM is gradually evoking the interest of foreign scholars.For example, studies related to Korean medicine have been mostly conducted by South Korean scholars.Therefore,Chinese scholars should pay more attention to the minority traditional medicine in the future.In particular, the exploration, protection, and research on traditional medicines and formulas, including research on chemical composition,pharmacological effects,and in-depth mechanism, will provide a solid theoretical basis for the modern development of the CMTM.