Abstract Saussurea plants have a long history of being used for disease prevention and control in Tibetan medicine， and the species have gradually changed along with the development of history. Saussurea is mainly effective in wind??expelling， blood circulation， spasmolysis， pain relief， heat??clearing and detoxification. Characteristics， major chemical constituents and pharmacological studies of Saussurea stella Maxim. were summarized in this review based on the utilization of Saussurea medicinal plants in Tibetan areas， with the aim to provide adequate theoretical bases and references for exploring the further medicinal value and development and utilization of S. stella.
　　Key words Saussurea stella Maxim.； Chemical composition； Pharmacological activities； Heat??clearing and detoxification； Medicinal value
　　Recorded in "Flora of Tibet"， Saussurea stella Maxim. is one of representative plants of the subgenus Eriocoryne in genus Saussurea. With good pharmacological activities， Saussurea has been widely used as folk medicine for a long history to treat diseases in Tibet. However， the uses are different because of the different understandings and the various species of the medicinal plants of Saussurea in Tibet. In different parts， different species share the same name and the same name refer to different species of Saussurea， and there are also differences in the using parts and uses of Saussurea plants. So far， there are few comprehensive and systematic studies on Saussurea stella. Characteristics， major chemical constituents and pharmacological studies of Saussurea stella were summarized in this review based on the utilization of Saussurea medicinal plants in Tibetan areas， with the aim to provide adequate theoretical bases and references for exploring the further medicinal value and development and utilization of Saussurea stella， which also had important scientific value for the protection and utilization of the plant resources of S. stella[1].
　　Pharmacognostic Identification
　　Habitats and characteristics
　　S. stella， commonly known as ground??lying Saussurea， is a kind of herb in the subgenus Eriocoryne in genus Saussurea mainly grown and distributed in Tibetan areas such as Qinghai， Gansu， Sichuan， Tibet and Yunnan Provinces. It is also distributed in places such as Sikkim and Bhutan， and Tibetan doctors call it "Sorgon". S. stella usually grow in alpine grasslands， alpine meadows， hillside shrub grasslands， riverside or marsh meadows， and beach floodplains at altitudes of about 2 000-5 400 m. In the majority of Tibetan areas， it is mainly used to treat symptoms like toxic fever， rheumatic pain and bone fractures[2]. 　　S. stella are annual or biennial herbaceous plants. The roots are inverted cone??shaped， fleshy， brown outside and yellow??white inside. The plants almost have no stem but grow close to the ground in lines with vertical stripes. The leaves are produced in a dense basal rosettes or stellate， and in the linear??lanceolate of 3-19 cm long， 3-10 mm wide. The leaves are usually larger at the bases， and turn purple with acuminate tips and entire margins in the late growth period with no hairs on both sides. The flowers are lavender and lip??shaped with capitulums but no pedicels， and are densely integrated into hemispheres in the rosette leaves of 0.7-1.0 cm in diameter without tootstalks. The involucres are of cylindric shape with the sepals of approximately 5??layered. There is one ovule per plant. The cylindric achenes are covered with strumaes and black spots with light smell and bitter taste of 0.3-0.4 cm long. The flowering and fruiting stages usually last from June to September. They are entomophilous pollination plants.
　　In recent years， there have been more and more studies on the phylogeny， chromosome number and karyotype analysis and genetic relationship of the plants of Saussurea， which play an important role in the classification of the plants of Saussurea. Wang et al.[3]examined the phylogeny of Saussurea using the chloroplast DNA trnL??F sequences. The results showed that variation of the trnL??F sequences was very low among the sampled species， and the section Pseudoeriocoryne delimitated based on morphological characters was a polyphyletic group， which had no close relationship with the other species in subgenus Eriocoryne. Chen et al.[4]performed cytological studies on 8 species of Compositae plants from Hengduan Mountains and its neighboring regions. The chromosome numbers and karyotype were reported firstly for Pertya berberidoides， Tricholepis fucate， S. dschungdienensis， S. likiangensis， S. retroserrata and S. peduncularis， and B chromosome was first discovered in S. dschungdienensis. The results showed that all species had type 2B karyotype asymmetry， except for S. dschungdienensis and P. berberidoides， which had type 1B. In addition， only diploid and tetraploid were found in Saussurea from Hengduan Mountains， and polyploidization might played a minor role in the chromosomal evolution of the Saussurea in the Hengudan Mountains. Li et al.[5]analyzed the chromosome numbers and karyotypes of 6 species of Saussurea DC. in the Hengduan mountains with conventional squashing slides， and first reported the chromosome number of S. polycolea var. acutisquama and S. columnaris. The results showed that the karyotypes of S. polycolea var. acutisquama， S. globosa， S. columnaris and S. hieracioides belonged to stebbins 2B type， the karyotypes of S. katochaete and S. graminea belonged to stebbins 3B type， and no satellites were found in these 6 species. Wang et al.[6]studied the chromosome numbers and karyotypes of 5 species of 5 species of Saussurea （S. iodostegia， S. hieracioides， S. epilobioides， S. parviflora， S. variiloba） in the eastern edge of Qinghai??Tibet Plateau， and the results showed that no satellites were found in these 5 species. Zhang et al.[7]analyzed the relationship between achene shapes and germination characteristics with geographical distribution of 12 species in the genus Saussurea DC. The results showed that the major achene shapes included 3 types， namely oblanceolate， cylindrical and cylindrical??obtriangular； the amplitude of achene length， width and thickness was large with the mean value reaching over 10%， the surface of achenes were divided into 3 types based on micro??morphological characters， namely striate ornamentation， reticulate ornamentation and pitted ornamentation with the stripe type most common； the percentage of germination differed greatly among species with the highest of 98% and lowest of only 40%. In addition， it also found that the geographical distribution of species of Saussurea was in significantly correlated with their length of achene pappus and 100??grain weight. Qiao et al.[8]studied the genetic relationships among 15 species of Saussurea DC. with the method of cluster analysis of karyotype resemblance??near coefficient. The results showed that there were the biggest karyotype resemblance??near coefficient （0.978 8） and the smallest karyotype evolutionary distance （0.021 5） between S. hieracioides and S. przewalskii， indicating the closest relationship， and there were the minimum karyotype resemblance??near coefficient （0.714 5） and the maximal evolutionary distance （0.336 1） between S. sobarocephala and S. parviflora， indicating the widest genetic relationship. It also found that the results of clustering analysis disagreed with the phylogeny based on the morphology of these species， providing some references for the study on resources utilization， taxonomy and phylogeny of Saussurea. 　　Microscopic identification
　　S. stella powder contains stigma epidermal cells， non??glandular hair， secretory cells， pollen grains， and sheath sheath fibers[9]. Microscopically， the flowers， leaves and roots of the powder show different microscopic characteristics. First， the flower powder is tan， and the cells are filled with reddish??brown substances. The flowers have duct??like secretory cells in all parts. The pollen grains are spherical or elliptic， and the outer walls have short spines and braided gills with 3 germination apertures. The epidermal cells of the flowers are square on surface. The stigmatic epidermal cells differentiate into papillary villi， and the front ends are blunt round. The fibers are mostly shuttle??shaped， and there are also crystalline sheath fibers， but mostly square crystals. The oil cavities are more broken and there are a lot of non??glandular hairs[10]. Second， the leaf powder is tan， and there are 1 row of cells on both the upper and lower epidermis， most of which are rectangular or square， closely arranged with many stomata. The mesophyll cells are large， loosely arranged， contain more brown inclusions， and have no differentiation of palisade tissues and spongy tissues. There are laticifers besides leaf veins. Glands and scales are covered on the upper and lower surfaces. The glandular heads are spherical or oblate spheroids， and the adenophores are monoplast. There are many crystalline fibers containing calcium oxalate crystals[9-10].Thrid， the root powder is yellow??brown and contains inulin， starch granules， stone cells， ducts and square crystals. The cork cells are arranged in the shape of a regular polygon. The fibers are bundled and the walls are straight or microwave??shaped. The debris in resin ducts is easily visible and contains red??brown secretions[9-10].
　　Major Chemical Components
　　The pharmacological experiments on the different extracts of S. costus showed that that its active ingredients were mainly volatile oils， alkaloids， and some terpenoids. Yang also reported that the chemical constituents of the genus Saussurea were mainly sesquiterpenes， flavonoids， alkaloids， lignans， saccharides， coumarins， terpenes and essential oils. Jia et al.[11]and Zheng et al.[12]reported that S. stella contained various components such as flavonoids， flavonoid glycosides， lignans， and mineral elements[11-12].
　　Flavonoids
　　Jia et al.[11]isolated 3 kinds of flavonoids and 3 kinds of flavonoid glycosides from S. stella， which were respectively identified as apigenin， acacetin， tilianin， kaempferol， kaempferol??3??O??????L??rhamnoside， and quercetin??3??O??????L??rhamnoside on the basis of the spectroscopic chemical method and the comparison with authentic samples. It was the first time to find Acacetin， tilianin and kaempferol??3??O??????L??rhamnoside in genus Saussurea. Shen et al.[13]isolated and identified 15 compounds from the whole plant of S. stella using column chromatography， 11 of which were flavonoids， flavonols and their glycosides （5-15）. It was the first time to isolate flavonoids 5，9， 10 and 13-15 were isolated from S. stella， and it was also the first time to isolate grosin??4????O??????glucoside and other four lignan compounds from S. stella. The results also showed that flavonoids were the main components of S. stella， and it was presumed that flavonoids may be related to the pharmacological activities of S. stella， which may also be related to other chemical components such as lignans， phenolic aldehydes. Yu et al.[14]used dynamic microwave extraction and reversed??phase high??performance liquid chromatography to isolate and determine the content of luteolin from S. stella. As a result， it was found that the content of luteolin in S. stella was 81.69 ??g/g， which was the first study to report the content analysis of luteolin in S. stella[14]. In addition， related studies showed that the almost all the chemical components in the subgenus Eriocoryne were flavonoids， and 2 kaempferol flavonols kaempferol??3??O??????L??rhamnosides and kaempferol were obtained from S. stella. And 2 quercetin flavonol quercetins and its 3??position glycoside ligand substitution quercetin??3??OD??glucoside were isolated from S. medusa and S. gossypiphora， and a methoxy??substituted flavonoids acacetin was isolated from S. stella. In addition， a cadinene sesquiterpene 1-2 cininol and a limonene monotonin were also isolated from S. simpsoniana. The research results also showed that almost all species of subgenus Eriocoryne were flavonoids. Among them， apigenin flavonoids and luteolin flavonoids were predominant， which were more evolutionary than kaempferol flavonols and quercetin flavonols， and the methoxy substituted flavonoid acacetin was also a more evolved flavonoid. Shi et al.[15]isolated 16 compounds from the aerial parts of S. japonica DC.， namely kaempferol??3??O??（6????O??crotonoyl）??????D??glucoside， quercetin??3??O??（6????O??crotonoyl）??????D??glucoside， syringin methyl ether， kaempferol??3??O??????D??glucoside， quercetin??3??O??????D??glucoside， syringin， ????amyrinyl palmitate， ????amyrinyl palmitate， lupeol palmitate， lupeol acetate， lupeol， ????sitosterol， palmitic acid， tetracosanoic acid， hexacosanoic acid and pentacosane， in which kaempferol??3??O??（6????O??crotonoyl）??????D??glucoside， quercetin??3??O??（6????O??crotonoyl）??????D??glucoside， syringin methyl ether were new compounds[15]. 　　Agricultural Biotechnology 2018Phenylpropanoids
　　Wang et al.[16]isolated and identified the phenylpropanoids from S. hieracioides using silica gel column chromatography and high performance liquid chromatography， and the analysis on the spectra data identified 7 phenylpropanoid compounds （umbelliferone， scopoletin， caffeic acid， esculetin， skimmin， scopolin and chlorogenic acid， among which caffeic acid， esculetin and chlorogenic acid were the new compounds first isolated from the plant）. Liu et al.[17]also isolated 9 compounds from the aerial part of S. hieracioides， which were identified as scopoletin， umbelliferone， chrysoeriol， luteolin， arctilin， skimmin， luteolin??7??O??????D??glucose， syringin and a new sesquilignan， saussol. And it was the first time to isolate skimmin and syringing from this genus.
　　Essential oils
　　Yang et al.[18]studied the components of essential oil from 9 species of Saussurea DC. of the eastern margin of the Qinghai??Tibet Plateau. The results showed that the main components of essential oils of subgenus Saussurea were benzyl 2??ethylhexyl ester， benz[a]??azulene and phenanthrene， and benzyl 2??ethylhexyl ester， cedren??13??ol， 8?? and phenanthrene were the main components of the essential oils from S. stella. The results of cluster analysis of the volatile oils from 9 species of Saussurea also showed that the habitat had a certain influence on the essential oil components in Saussurea， which was of important taxonomic significance and could be used as a basis for the classification of subgenus and species of Saussurea. Wang et al.[19]studied the essential oil components of 3 dominant species of S. katochaete， S. stella and S. parviflora from the genus Saussurea DC. of the family Compositae in the eastern of the Qinghai??Tibet Plateau using capillary gas chromatography and GC/MS spectrometry， and the isolated components were identified by mass spectrometry. The results showed that the major components of S. katochaete were dibenzofuran， fluorene and caryophylleneoxide； the main component of S. stella was phenanthrene； decahydro??1，1，7??trimethyl??4??methyl??1H??cyclopropane[e]azulen??7??ol， caryophyllene oxide were the main components for S. parviflora， confirming that the similarities and diversities in their chemical components coexisted. The complexity degree of components of essential oil showed that S. parviflora was the most primitive and S. stella was the most evolutionary. In addition， the conclusions of the systematic position and phylogenetic relationship supported the results of morphological clustering analysis， indicating that the components of essential oils had an important classification significance. Wang et al.[20]studied the essential oil components from 3 common species （6 populations） of Saussurea DC. family derived from the eastern of the Qinghai??Tibet Plateau by steam distillation and GC??MS analysis. A total of 77 chemical components were identified. S. arenaria had 2 kinds of major components and 1 kind of unique component， S. hieracioides had 3 major components and 5 unique ones， and S. graminea had 5 major and 5 unique components. There were 4 kinds of components shared by the 6 populations from the 3 species. The cluster analysis results showed that the components of essential oils could be used as the basis to divide the subgenus， sect and species of Saussurea. 　　Trace elements and amino acids
　　Yu et al.[21]compared the contents of trace elements in 6 species of Saussurea from Qinghai using flame atomic absorption spectrometry. The results showed that the contents of the 5 trace elements （Ca， Fe， Mn， Zn， and Cu） were 4 343.90， 1 888.29， 95.32， 17.73， and 3.43 mg/kg， respectively. The contents of Ca and Mn were the highest in S. medusa， 8 148.58 mg/kg and 312.55 mg/kg respectively， the contents of Fe and Zn were the highest in S. tangutica， reaching 5 798.98 and 46.22 mg/kg， and the content of Cu was the highest in S. katochaete of 6.09 mg/kg. Guo et al.[22]used inductive coupling plasma emission spectrometry to identify 16 trace elements from S. stella， and 8 kinds which were essential for humans and animals reached a certain contents， especially the content of Fe reached above 860 ppm. In addition， 17 amino acids were identified by using an amino acid analyzer， 7 of which had health effects on normal development of humans and animals， and the main ????amino acids contained in the amino acid hydrolysate mainly existed in free states， except for Thr and Cys.
　　Saccharides
　　The results of physical and chemical reactions by Yang et al. confirmed that the S. stella contained carbohydrate components[10].
　　Pharmacological Research
　　According to the records of the "Flora of China" and related studies， it is also confirmed that essential oils， alkaloids， and some terpenoids in S. stella have important pharmacological effects. Among them， flavonoids have various physiological activities. Compounds such as lactones， triterpenes， flavonoids， steroids， polysaccharides， and organic acids have pharmacological effects on anti??tumor， anti??inflammatory， anti??aging and improving cardiovascular system functions.
　　Insecticidal activity
　　Li et al.[23]tested the insecticidal activities of acetone extracts obtained from 16 poisonous plants in the Tianzhu Grassland of Gansu Province to Mythimna seperata. The results showed that S. stella had a certain antifeedant activity against M. separata and the antifeedant rate was 13.5%， while the contact toxicity and stomach toxicity were weak， and both were below 10%.
　　Anti??inflammatory and anti??rheumatic effects
　　Tan et al.[24-26]suggested that the coumarins in Saussurea were the main pharmacological substances， which may be related to the treatment of edema and gout of various causes. Tan Rong et al.[27]also pointed out that the commonly used medicinal herb Saussurea in Tibetan folks originated from the dry plants of S. hieracioides and S. pulchra， and S. hieracioides was the most widely used， which was the main medicinal resources included the Tibetan medicine Saussurea. Compound preparations containing Saussurea were mainly used for the treatment of oedema diseases， and were particularly good at renal edema， and the compound preparation Baweiqinpiwan was mainly used for the treatment of fractures and osteomyelitis[27]. 　　Anti??tumor and anti??virus activity
　　Ren et al.[28]reported that sesquiterpene lactone， the main component of Saussurea， was guaiacolactone， and its biological activities mainly included in anti??tumor， anti??virus， anti??ulcer， sleep improvement and plant growth regulation.
　　Ecological Research
　　Effects of biomass and animal activities on distribution of S. stella
　　Han et al.[29]investigated the plant species Menyuan County， finding that the grass populations like S. stella had no obvious layered distribution. S. stella plants were about 1-23 cm high with an average vegetation cover of about 75%-90%， and the grass population was low in height and densely packed， suitable for the habitation and activities of the moles. Guo et al.[30]also found that the major plant associated species in the range of plateau zokor activity were Elymus nutans， Bistorta macrophylla， Polygonum viviparum， Potentilla anserine， S. stella and Pedicularis bella. He et al.[31]also found that the vegetation composition in the rat??free zone and the vegetation composition of various mounds had the presence of S. stella. Zheng et al.[32]reported the preliminary investigation on the foot habits and reproduction of white lipped deer carried out in 1986 by the Sino??Japanese Team of united survey in Yushu， Guoluo Prefectures of Qinghai Province and Garze Prefecture of Sichuan Province， finding that S. stella was one of the 24 plant species that favored by white lipped deer. Ri et al.[33]investigated the medicinal resources of plant Tibetan medicine in the municipality of Judo Prefecture in Yushu Prefecture， finding that the medicinal plants in this area could invigorate the circulation of blood and disperse blood stasis. The plants used for traumatic injuries and bone fractures were mainly S. stella， Lamiophlomis rotate， Meconopsis integrifolia and Pyrethrum tatsienense. Zhang et al.[34]established the biomass estimation models for the plant species on the eastern Qinghai??Tibet Plateau by using the ecological characters such as height， coverage， density based on the traditional harvesting method， which was usually used to measure aboveground biomass of the grassland， and the population characteristics of single species. Power function equation was the best biomass estimation models for species like Kobresia graminifolia， Elymus nutans， Allium sikkimense， and linear equation was the best for other species except S. hieracioides. The results showed that the model had high fitting accuracy， and the correlation coefficient between the estimated value and the measured value was greater than 0.9， and most of the average relative errors were less than 10%. 　　Effects of altitude， nutrition， and light conditions on S. stella
　　Wang et al.[35]studied the variation in floral traits of S. stella in 20 populations in response to elevation and mean plant size on the east Qinghai??Tibet Plateau using sample investigation method and dry weight. The results showed that S. stella could offset the effects of few pollinators， low activity frequency and small pollen numbers on pollination through the variation of floral traits， especially style and filament elongation， and investing more resources in attracting the structural petals. Consequently， the variation of floral traits ensured that S. stella pollinated effectively and completed sexual reproduction under high altitude stress conditions. Wu et al.[1]investigated the relative growth rate （RGR）， root mass to shoot mass ratio （R/S） and specific leaf area （SLA） of seedlings of 4 Saussurea species with different ecological breadth. The results showed that nutrient and light had significant effects on the changes of the 3 morphological traits of the 4 species， and there was a certain interactive effect between nutrient and light. Moreover， the morphological plasticity of Saussurea was positively related to their distribution ecological breadth. Li[36]studied the effects of excess UV??B irradiation on physiological and biochemical responses in 3 Saussurea species on eastern Qinghai??Tibet Plateau， finding that S. hieracioides and S. arenaria had stronger capability than S. nigrescens in resisting the stress damage caused by excess UV??B irradiation. Chen[37]set up 3 portions along snowmelt gradients in a seasonal alpine snow field in the east of Qinghai??Tibet Plateau， and measured the snowmelt time， soil moisture and individual growth traits （including leaves per plant， area per leaf and aboveground biomass） of S. hieracioides at each portion. The results showed that the length of growing season at late??melting portion was nearly one month later than that at the early??melting portion， and the individual growth traits of the plants were reverse to snowmelt timing， which was consistent with soil moisture.
　　Conclusion
　　Saussurea is an important Tibetan medicine resource in Tibetan areas of China. It is a type of alpine plant with high economic value. Species differentiation and long??term adaptation to various environments lead to different ecological range for different Saussurea species. Therefore， most Saussurea species in the high??altitude and high??latitude Qinghai??Tibet Plateau are dominant or constructive species of local alpine meadows， and have important medicinal values. 　　Saussurea species have a long history in preventing and treating diseases in Tibetan medicine， and and the types of medicinal products are gradually changing with the development of history. However， the uses are different because of the different understandings and the various species of the medicinal plants of Saussurea in Tibet. In different parts， different species share the same name and the same name referring to different species of Saussurea， and there are also differences in the using parts and uses of Saussurea plants. As a result， the use of Saussurea species varies. At present， the plant species included in Chinese Pharmacopoeia are S. japonica and S. involucrata. Therefore， we should make reference to the operating procedures and pharmacognosy identification of the corresponding quality standards to identify different Saussurea species. According to statistics， Saussurea is mainly effectiveness in wind??expelling， blood circulation， spasmolysis， pain relief， heat??clearing and detoxification. Thus， Saussurea has rich medicinal values.
　　Jiang et al.[38]used literature research method， key informants interviews and field investigations to conduct preliminary studies on the use characteristics， usage patterns， and distribution of medicinal plants of Saussurea based on their efficacy， medication habits， and origin， which laid the foundation for the rational development of Saussurea， and also provides references for the resources investigation and development and utilization of Saussurea plants. In follow??up pharmacological studies， attention should be paid to the practical application of Saussurea plants in the Tibetan region in the treatment of rheumatoid arthritis， gynecological diseases， and traumatic bleeding， and the development of the medicinal value of Saussurea plants should be the focus of research， so as to lay foundation for the wide application of Saussurea in Tibetan region. In addition， it can also provide new ideas and methods for the development and utilization of Saussurea plants， which not only has high medicinal values to guarantee the health of herdsmen and livestock in Tibetan areas， but also has a certain significance in the study of the pharmacological mechanism of S. stella.
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