Hao Shanshan,Mou Haidi,Chen Mingxia,Han Yahui,Yi Bin

Beijing Scrianen Pharmaceutical Co.,Ltd.,China

Chen Sumei

Jiangchangbang Pharmaceutical Co.,Ltd.,China

Abstract This paper will review the progress of study on Cistanche application in cosmetics and introduce the main active ingredients of Cistanche briefly,including phenylethanoid glycosides,polysaccharide,etc.And will clarify the difference of the main active ingredients of Cistanche in different conditions through summarizing the main active ingredients of Cistanches of different types,different origins,different harvest periods and different hosts.This paper will mainly review the mechanism of Cistanche in skin beauty and care,as well as the efficacy of Cistanche in cosmetics,including skin whitening,anti-aging,sun-screening,bacteriostasis,moisturizing.Also,will clarify the application status of Cistanche in raw materials of cosmetics and in cosmetics,and analyze the development defect and technical shortcomings of Cistanche in cosmetics as raw materials.Finally,the article will point out the future research direction of Cistanche in the cosmetic field.

Key words cosmetics;Cistanche;application

Cistanche has a history of more than 2,000 years in China,and was initially recorded in the Shennong's Classic of Materia Medica,being listed as top grade.It is sweet and salty in taste and has been praised as “Desert Ginseng”,“Chinese Celestial Grass”,etc.[1].Cistanche contains a variety of active ingredients and has efficacy in health care &beauty products.The ancients recorded that Cistanche can“make people vigorous after long-term use”,“nourish the five internal organs and promote muscle growth”,“nourish marrow,improve the complexion,and prolong life”,“improve mental exhaustion,blackish complexion,internal lesion caused by overexertion,etc.” In recent years,the development and application of Cistanche in cosmetic field have been gradually carried out,and relevant scientific researches have shown its good efficacy in skin whitening,anti-aging,sun-screening,anti-inflammation,bacteriostasis,moisturizing and radiation protection.This article reviews and summarizes the following aspects about Cistanche:the main active ingredients,mechanism in beauty skin care,the efficacy and application status of cosmetics,etc.,to provide certain theoretical basis for the further application of Cistanche in cosmetics.

1 Main active ingredients of Cistanche

The active ingredients of Cistanche include both the volatile constituents,and more than 100 isolated non-volatile constituents,including phenylethanoid glycosides,polysaccharide,oligosaccharide,lignans,iridoid,flavone,alkaloid,amino acids,trace elements,etc.Phenylethanoid glycosides and polysaccharide are the main active ingredients that have undergone in-depth research,with significant neuroprotection,immunomodulation and antioxidant effects[1].Currently,Cistanche has a total of more than 70 isolated phenylethanoid glycosides,among which echinacoside and verbascoside are key compounds of phenylethanoid glycosides to measure quality standard of Cistanche[2].The structure of echinacoside and verbascoside is shown in Figure 1.The polysaccharide isolated polysaccharides from Cistanche include cistan A,CDA-1A,CDA-3B,CDP-4,ACDP-2,SPA,etc.,mainly composed of monosaccharides such as glucose,galactose,rhamnose,arabinose,and fructose[3].Studies have shown that factors such as different types,different origins will affect the content of active ingredients of Cistanche,such as phenylethanoid glycosides,polysaccharide.

Figure 1.Structure of echinacoside and acteoside

1.1 Differences in active ingredients of Cistanche

Cistanche genera has approximately 20 species,and in China there are 4 species and 1 variant:Cistanche deserticola Y.C.Ma (also known as Cistanche deserticola);Cistanche tubulosa (Schenk)R.Wight;Cistanche salsa (C.A.Mey.) G.Beck;Cistanche sinensi G.Beck;and C.salsa variant albiflora P.F.Tu et Z.C.Lou[4].Tu Pengfei et al[5]performed a qualitative analysis on constituent of phenylethanoid glycosides contained in the 5 Cistanches in China,and a quantitative analysis on echinacoside and verbascoside.The qualitative analysis showed that the constituents of phenylethanoid glycosides were similar in Cistanche deserticola,Cistanche tubulosa,Cistanche salsa and C.salsa var.,but largely different from Cistanche sinensis.The quantitative analysis showed that the contents of echinacoside and verbascoside in the five Cistanches were different,with the highest content of Cistanche salsa,and the lowest content of Cistanche sinensis.

1.2 Differences in active ingredients of Cistanche of different origins

Chinese herbs always have the characteristic of “geoherbalism”,that means,there is a certain difference in active ingredients between herbs of different origins.Liu Xiong et al[6]determined the contents of echinacoside in Cistanches from Zhangye (Gansu),Jingyuan (Gansu),Xinjiang,and Inner Mongolia,and found that the mass fraction of echinacoside in Cistanche was 0.42%～1.52%.The content was the highest in those from Zhangye,and the lowest from Jingyuan.Wang Guoping,etc.[7]found that there was significant difference in the content of echinacoside in Cistanche tubulosas from different places in South Xinjiang,with a mass fraction of 2.78%～11.93%;and that there was also difference in the content of echinacoside between the cultivated and wild Cistanche tubulosas from the same place.Xue Dejun et al[8]compared and analyzed the content of polysaccharide in Cistanches of different origins,and found that there was difference in content of polysaccharide in Cistanches of different origins,and that the monosaccharide constituents of polysaccharide were also different.

1.3 Differences in active ingredients of Cistanche from different harvest periods

Under the Cistanche category in Chinese Pharmacopoeia (2020 Edition,Volume I),it is stated that,Cistanche should be picked when the spring seedlings break through the soil,or dug out before the earth is freezing in autumn[9];the Cistanches obtained in the spring and autumn have different qualities.Qian Hao et al[10]compared the contents of 4 constituents of phenylethanoid glycosides in Cistanche obtained in the spring and autumn:echinacoside,Cistanoside A,verbascoside and 2’- ethanoyl verbascoside.The results found significant difference in contents of the 4 constituents in Cistanches obtained in different seasons,with higher contents of echinacoside and Cistanoside A in Cistanches obtained in autumn,and higher contents of 2’- ethanoyl verbascoside and echinacoside in Cistanches obtained in spring.Wang Xueyuan et al[11]investigated the contents of active ingredients such as echinacoside,verbascoside,polysaccharide in Cistanches obtained in the spring and autumn.The results found that the total content of echinacoside and verbascoside in Cistanches obtained in spring was more than 3 times higher compared to those obtained in the autumn,up to 12.21 mg/g;and the content of polysaccharide in Cistanches obtained in autumn was significantly higher compared to those obtained in the spring.

1.4 Differences in active ingredients of cistanches from different hosts

Cistanche is a perennial,its roots fully parasitize in herbaceous plants,for example,in the roots of host plants such as sacsaoul,kalidium foliate,etc.Cistanche and host are closely related,and the host plants transport nutrients and moisture to cistanche.Zhang Xuan et al[12]determined the contents of echinacoside and verbascoside in 3 different varieties of Cistanches in 5 natural hosts and 2 cultivated hosts,and found significant difference in the contents of echinacoside and verbascoside in the same variety of Cistanches in different hosts.For Cistanche salsa,when the content of echinacoside is used as an index,the order is:beet ＞ reaumuria soongonica ＞ suaeda physophora (cultivated) ＞ Kalidium foliatum;when the content of verbascoside is used as an index,the order is:suaeda physophora (cultivated) ＞ beet ＞reaumuria soongonica ＞ Kalidium foliatum.

2 The skin beauty and care mechanism and efficacy of Cistanche

Studies have proved that Cistanche not only has wide pharmacological effects,but also has good efficacy in skin improvement and beauty.

2.1 Skin whitening

There is a Chinese saying that “Fair skin covers up a hundred flaws”,which means that fair,smooth,and delicate skin has always been the beauty goal for the oriental women.Therefore,the development of skin whitening agents has always been a key topic in the beatify and skin care industry.At present,the development of skin whitening agents mainly focused on inhibiting tyrosinase activity[13].The compounds containing benzene ring or phenolic hydroxyl structure have potential skin whitening effect,for example,one of the currently used skin whitening agents,arbutin,can introduce skin whitening effect by inhibiting the activity of tyrosinase.

The main active ingredient of Cistanche,phenylethanoid glycoside,is a type of natural glycoside compound,formed by the linkage of ester bond and glucosidic bond of nuclear parent glycosyl,phenyl acrylic acid,and a portion of phenylethyl alcohol.Yang Jianhua et al[14]found that the total phenylethanoid glycosides with purity of 48.2%can effectively inhibit the activity of tyrosinase,and the effect on tyrosinase is expressed as competitive reversible inhibition.Afterwards,Yang Jianhua’s team et al[15]investigated the inhibitory effect of total phenylethanoid glycosides with purity of 87.6%on tyrosinase activity and melanogenesis of human epidermal melanocytes.The results showed that the inhibition of the total phenylethanoid glycosides on tyrosinase was superior to arbutin,with the IC50of 716.51 μg/mL.Further studies have found that the total phenylethanoid glycosides of 400 μg/mL could significantly inhibit melanogenesis,with an inhibition rate up to 31.43%,which was comparable to arbutin.Meanwhile,a separate comparison on the inhibitory effects of 10 phenylethanoid glycosides compounds on melanogenesis was performed,and found that the inhibitory capability was related to the number of phenolic hydroxyl groups and aglycones,the location of phenolic hydroxyl group,the steric hindrance,the substituent groups on uronic groups of nuclear parental glycosyl.Furthermore,Yang Jianhua et al used microemulsion technology[16]and transfersome technology[17]to resolve the problems of poor dissolving property and transdermal absorption of phenylethanoid glycosides,to provide guidance for application of phenylethanoid glycosides in skin whitening cosmetics.Yang et al[18]also found that Cistanche extracts had strong inhibitory effect on tyrosinease activity,and the Cistanche extracts of 10 mg/mL had a inhibition rate of up to 78.5% on tyrosinase activity.

2.2 Anti-aging

Aging is one of the most basic natural laws in the biological world,and is a progressive process during which all the individuals will decline in functions and organs over time.Skin aging is synchronized with the body aging.With people’s better understanding of the skin aging mechanism,there are more than 30 kinds of mechanism theories in skin aging[19].The delaying effect of Chinese herbs on skin aging mainly include removing free radicals,repair collagen,etc.

Yang et al[18]found that Cistanche extracts could clear DPPH free radicals and have antioxidant capacity.At the same time,Cistanche extracts can significantly reduce the expression level of collagenase and elastinase mRNA,inhibit the activity of collagenase,elastase,and hyaluronidase,and can delay skin aging.Studies have shown that the active ingredients of Cistanche,such as phenylethanoid glycosides and polysaccharide,have certain effects on delaying skin aging.The aging pathways corresponding to different active ingredients of Cistanche are presented in Table 1.

Table 1.Active ingredients of Cistanche and the pathway of their anti-aging effects

2.3 Sun-screening

With further research on skin damage caused by light,people's sun-screening awareness is continuously increased.However,the sun-screening agents in sun-screening cosmetics in in the market,including physical sun-screening agents and chemical sun-screening agents,have certain hazards,and are difficult to meet the needs.The broad-spectrum,safe sun-screening agents from natural plants have become a hot spot in recent researches.

The molecule of the main active ingredient of Cistanche (phenylethanoid glycoside) has multiple benzene rings and conjugated structures;researchers have found that[32]phenylethanoid glycosides have strong absorption at 280～380 nm,and can be used as a natural sun-screening agent,to alleviate UV damage to the skin.The sun-screening cream containing 1%-2% phenylethanoid glycosides has no adverse reactions,and has good stability and light protection effect.Facino et al[33]has found that echinacoside can protects the skin from UVA/UVBinduced oxidative damages,remove free radicals and prevent degradation of collagen.Zhang et al[34]used UVB to irradiate the mouse skin damage model and human immortalized epidermis cell (HaCaT) damage model,to further study the photoprotection effect of echinacoside on UVB-induced skin damage and the potential mechanism of action.The experimental results of mouse showed that the topical echinacoside creams could significantly improve the UVBinduced skin lesions of mice,including edema,roughness,erythema,ulceration,wrinkles,epidermal thickening,disorganized tissue arrangement,etc.,and the improving effects were positively correlated with the content of echinacoside.The experimental results of HaCaT cells indicated that,echinacoside had significant protection effect on UVB-induced DNA damage and apoptosis.Echinacoside can increase the activity of SOD,CAT,GSH-Px,reduce the content of MDA,ROS in cells,produce antioxidation effect,reduce oxidative damage of cells,prevent DNA fragmentation,inhibit apoptosis;additionally,echinacoside can also reduce expression of ATM/Rad3 related protein (ATR),Chk1,p53,caspase (Caspase-3),poly(adp-ribose) polymerase(PARP),reduce apoptosis,increase expression of XPA protein,and promote repair of DNA.AVILA et al[35]investigated photoprotection of verbascoside,and found that the protecting effect of verbascoside on UVB-induced apoptosis was superior to the sunscreening agent ethylhexyl methoxycinnamate,and the SPF values obtained using guinea pig model were four times higher than that of the ethylhexyl methoxycinnamate.In summary,the phenylethanoid glycoside constituents of Cistanche can not only absorb ultraviolet rays,but also have antioxidant effect,and ability to repair DNA damage and reduce apoptosis,and have potential application values in sun-screening cosmetics.

2.4 Bacteriostasis

Cosmetics are rich in nutrients such as grease,moisture,protein,suitable for microorganism growth and reproduction.Therefore,a certain number of preservatives need to be added into cosmetics to prevent putrefaction and deterioration.Relative to commonly used chemical synthetic preservatives,the preservatives in Chinese herbs have a variety of advantages such as low toxicity,high safety,natural origins,which are more popular among consumers.

Cistanche has good bacteriostasis effect.Wang Xiaoqin et al[36]found that Cistanche polysaccharide had certain inhibitory effects on growth of micrococcus tetragenus,escherichia coli,bacillus subtilis,beer yeast,and penicillium citrinum.Du Rui et al[37]found that cistanche decoction also had obvious inhibitory effect on S.aureus.Najeeb et al[38]studied the antibacterial (salmonella typhi,staphylococcus aureus ,streptococcus pneumoniae,klebsiella pneumoniae,proteus mirabilis and escherichia coli) and antifungal (aspergillus fumigatus,aspergillus niger and aspergillus flavus)activity of methanol extract,water extract,ethyl acetate extract,chloroform extract,n-hexane extract,butanol extract,and found that different extracts of Cistanche tubulosa had different effects on bacteriostasis,which may be related to the different active ingredients contained in different extracts.

2.5 Moisturizing

Moisturizing is the basic appeal for skin care,and also the important condition to ensure skin’s health and delay aging.When the water content in the skin corneum is maintained at 10%～20%,the skin is in the optimal physiological state,soft,moist,full,bright and elastic;when the water content is less than 10%,the skin conditions deteriorate,dry,rough,and after a long period of dry state,dark and wrinkled.Optical use of moisturizing cosmetics can improve the water content in corneum,reduce water dispersion,and maintain normal function of the skin.

Studies have shown that[39],Cistanche extracts have excellent water holding capacity,and application of 30% Cistanche alcohol extracts on the skin can significantly reduce moisture evaporation,thus,can be used in moisturizing cosmetics.Fan Qianwen et al[40]invented a Cistanche bulb extract containing oligosaccharide mixture,and used fluorescence tagging method to observe the expression levels of involurin,aquaporins (AQP-3),and hyaluronic acid receptor CD44 protein by epidermis cells,to futher judge the water locking performance of the extract.The results showed that this Cistanche bulb extract could significantly increase the expression levels of the three proteins in keratinocytes,and improve the water-blocking ability of epidermal layer itself,to produce long-lasting moisturizing effect.Meanwhile,the mannitol,glycine betaine,and allantoin constituents contained in Cistanche were all classic moisturizing constituents,also indicating the moisturizing effect of Cistanche.

2.6 Radiation protection

All objects in the natural world,as long as the temperature is above the absolute zero degree,transmit heat to the outside in the form of electromagnetic waves,and this kind of energy transmitting approach is referred to as radiation.Radiation causes damage to the skin,immune system,nervous system,hematopoietic system,etc.,and even carcinogenesis and death;the natural active ingredients for radiation protection have become a hotspot in current researches.

The studies found that[41],Cistanche had strong protection against damages caused by 60Coγ ray radiation,able to improve the immune function of mice suffering radiation damage,with the possible mechanism of direct or indirect removal of free radicals and reducing production of lipid peroxides,and protecting immune organs,cells and molecules.Yang et al[42]found that verbascoside could reduce Bax/Bcl-2 ratio by clearing ROS,down-regulate procaspase-3 activity,adjust MAPK signal path,protect skin fibroblasts from X-ray damage,and inhibit apoptosis of fibroblasts.

3 Application status of Cistanche in cosmetics

With the growing recognition of the traditional Chinese medicine around the world,the “cosmetics of Chinese herbs” known as "natural,safe and effective" have become the focus in cosmetic industry and been favored by consumers.Cistanche has many effects such as skin whitening,anti-aging,sun-screening,moisturizing,and has been used in certain cosmetics.Zhao Yi et al[43]disclosed the skin whitening and anti-aging cosmetics made of tubulosa extracts of Cistanche,and the preparation method.Cosmetics containing tubulosa extracts of Cistanche can enhance skin elasticity,reduce content of skin melanin,and increase skin brightness.A variety of effective raw materials developed by Nutri-Woods contain Cistanche extracts.For example,for the patent moisturizing raw material “Gum Moisture”[44],the “l(fā)ow temperature time-constant” extraction technique is used to extract four plant-originated natural macromolecular polysaccharides:peach gum,dendrobium officinale,tremella fuciformis,Cistanche,form a plant polysaccharide protective film of spatial network structure,to make the skin soft and smooth.Another example is Nutri-Boost,with the anti-aging raw material of “Youthening Pure Wormgrass Extract”;Nutri-Boost is scientifically combined with 4 Chinese herbs (cordyceps sinensis,tricholoma matsutake,dendrobium officinale,Cistanche) by the formula composing principle of “assistant and guide”,and can effectively remove free radicals and prevent oxidative damage of the skin.Nutri-Boost has been used in the revitalizing and the luxurious DR PLANT protogenetic liquid of cordyceps sinensis,able to add multiple nutrients for and rejuvenate the skin.Many products by Shanghai Jahwa United Co.,Ltd.,such as Herborist and Gough,also contain Cistanche extracts.For example,the Herborist “Novel-Lasting-Beauty”series contain the patent constituent “Constant-3-Extracts Formula”[45],which is derived from 3 Chinese herbs:Cistanche,astragalus membranaceus,and snow lotus,and can prevent skin aging,especially aging caused by light.The Gough multieffect moisturizing mask contain a star moisturizing constituent “Silk Road Water Element”,which is composed of 4 Chinese herbs:Cistanche,astragalus membranaceus,snow lotus and radix ophiopogonis.As can be seen from the current application status of Cistanche in cosmetics,Cistanche,with its natural advantages of Chinese herbs,has been widely used in cosmetics and has great application value.

4 Conclusion

Cistanche,as a famous,life prolonging Chinese herb to maintain beauty and keep young,has many effects such as skin whitening,anti-aging,sunscreening,moisturizing and radiation protection,and has been used in cosmetics.Although Cistanche has been used in cosmetics in a certain way,its active ingredient and mechanism of action are still underresearched,and the research direction of Cistanche as raw materials for Chinese herbal cosmetics should be determined according to the following aspects:① Cistanche’s main active ingredients are largely affected by genus,origin and other factors;as raw materials of cosmetics,attention should be paid to control of quality standard and industrial application.② Cistanche has a variety of skin care effects,but the research data is mostly from in vitro experiments,and somatic data needs to be supplemented.③Currently,the Cistanche is mainly used for its antiaging and moisturizing effect,and Cistanchecontaining compound raw materials are mainly used,but less used for skin whitening and sunscreening effects,etc.Taking theory of traditional Chinese medicine as guidance,combined with modern science and technology,in-depth systematic researches need to be conducted on application of both the monotherapy and combination of Cistanche.In summary,Cistanche has a variety of skin care effects,and is worth further study to develop a broader space for its application in cosmetics.