Zhang Jingjing,Xia Liming,Meng Xiangyan,Shi Huizhe

Guangzhou JNUMESO Biotechnology Co.,Ltd.,China

Abstract This summarizes the research progress of domestic and foreign experts on the methods and technologies of hair growth,including the hair growth effects of natural plant extracts,mesotherapy and stem cell therapy.Looking forward to the development trend in the field of hair growth,mesotherapy has the advantages of convenient operation,good targeting,fewer side effects,and high cost performance.Combining it with anti-hair loss cosmetic products containing natural plant extracts to treat hair loss has very broad application prospects.

Key words hair growth;plant extracts;mesotherapy;stem cell therapy

1 Current status of hair loss

As an important part of the body,hair has the functions of beautifying the appearance,protecting the scalp,reducing and avoiding external mechanical and chemical damage,and preventing or reducing the damage of ultraviolet rays to the scalp and internal tissues and organs.[1]The basis for the existence and normal growth of hair is hair follicles.Hair follicles grow periodically,so the life of hair is also periodic.[2]

Hair loss is a phenomenon of hair loss and is one of the more common dermatological diseases.With the continuous increase of work and life pressures of modern people and the influence of environmental factors,the number of hair loss has been increasing in recent years.In 2014,Xinhua News Agency reported that the number of people with hair loss in my country was 160 million.The latest report issued by the Health Commission in 2019 stated that there are more than 250 million people with hair loss in China,and one in six people has hair loss.In the past five years,the number of hair loss has increased from 160 million to 250 million,and the hair loss population has become younger.

According to data released by Ali Health,the post-80s accounted for 38.5% of the population with hair loss,followed by the post-90s accounted for 36.1%,the post-70s accounted for 17.8%,and the pre-70s only 7.6%.As the problem of hair loss is becoming more and more common,the demand for preventing hair loss and growth has become more and more urgent,and various anti hair loss products and treatment methods have entered the attention of consumers.

Hair loss is mainly divided into androgenic alopecia,alopecia areata,anagen alopecia,telogen alopecia,and chemical/physical alopecia.Among them,Androgenic alopecia(AGA)is the most common type of hair loss in clinic,also known as seborrheic alopecia.It accounts for 90% of the population with alopecia.It can occur in both men and women,and it is more common in men.[3]The incidence of AGA may be related to factors such as genetic factors,fungal infections,poor living and eating habits,and high pressure in life and work.In addition,the hair follicles on the top of the head of people with AGA hair loss are more sensitive to androgens,and the activity of 5α-reductase is also relatively high,which makes the conversion of testosterone into dihydrotestosterone(DHT)in the hair loss area increase.When DHT acts on the hair follicle,it will shrink and degenerate,so that the hair is shortened for a long time,and the proportion of telogen hair increases.[4]

At present,the main treatments for hair growth include drug,[5,6]hair transplantation,[7,8]and cosmetics for preventing hair growth.[9]In addition,there are also researches on stem cell induction and mesotherapy treatment of hair loss at China and abroad.

2 Natural plant extracts

At China and abroad,there are more and more researches on natural plant extracts in preventing hair loss and growth.Some plant extracts have been used in anti-hair loss products,such as ginger,[10]oriental arborvitae,[11]ginseng,[12]fleece-flower root[13]and so on.With the rapid development of science and technology,more and more plant extracts have been deeply explored and studied.In recent years,more new functions of plant extracts have been unearthed,including anti-hair loss.

Chiba rhododendron extract is used as a traditional medicine in South America to treat many diseases,including inflammatory diseases.Studies have also shown that the extract of Rhododendron chinense has excellent anti-inflammatory properties.[14]Rambwawasvika et al[15]studied the effect of Chiba rhododendron extract in promoting hair growth.BalB/c mice were used as the experimental object.The experiment was evaluated from the dimensions of hair growth completion time,hair length,weight,hair follicle length and area,etc.At the same time,the effective ingredients of the extract were identified.The results showed that the extract had a certain promoting effect on hair growth and contained three active ingredients:steroid glycosides,triterpene glycosides and flavonoid glycosides,among which flavonoid glycosides have strong hair regeneration ability.Flavonoid glycosides have a certain anti-inflammatory ability and are a good antioxidant.They can improve hair follicle cell activity and proliferation by removing inflammation caused by excessive free radicals.Studies have shown that[16]flavonoid glycosides can cause the muscles around the hair follicles to relax,provide more nutrients for hair growth and stimulate hair growth.According to this mechanism of action,other plants containing flavonoid glycosides may also have similar hair growth effects,such as loosestrife,[17]mountain round leaf[18]etc,which can provide some ideas for subsequent research on plant extracts in the field of preventing hair loss.

Salvia plebeia extract promotes the proliferation and differentiation of hair follicle cells by regulating the signal-mediated factors in hair follicle cells.Jin et al[19]found that salvia plebeia extract inhibited the activity of GSK3b,promotes the expression of β-catenin,and further promotes the proliferation of hair follicle cells.In addition,studies had shown that minoxidil can inhibit the activity of Smad2/3 factor during the treatment of hair loss.Salvia plebeia extract can also inhibit the expression of Smad2/3 factors to down-regulate the expression of TGF-b1 mRNA,[20]preventing the transition of hair follicle cells from the growth phase to the degenerative phase.The experimental results showed that the hair follicles in the back skin tissue sections of the mice in the experimental group were in the early growth phase,while the hair follicles in the control group were still in the resting phase.It showed that salvia plebeia extract promoted hair growth by affecting the growth cycle of hair follicle cells.[19]

Xiao Lei et al[21]selected 90 subjects for the test,and the subjects used a scalp care solution containing 0.5% Anemarrhena saponin-II for 28 consecutive days.Test evaluation indicators included cortisone content in hair follicles,number of hair fall,gloss,dandruff content,scalp hydration,oil content,red zone and pH value.The results showed that relative to the baseline value,each index had a significant improvement.Anemarrhena saponins-II[22]has immune enhancement and anti-inflammatory effects.It inhibits the production of NO,ROS and pro-inflammatory cytokines by inhibiting the phosphorylation of MAPK and NFB downstream of the TLR4 signaling pathway.

Houttuynia cordata extract can promote hair growth by promoting the proliferation of dermal papillary cells(DPCs)and extending the growth period of hair follicles.Kim et al[23]showed that the extract of Houttuynia cordata increased the production of nicotinamide adenine dinucleotide and adenosine triphosphate(ATP),ATP leads to enhanced cell energy metabolism and promotes the proliferation of DPCs.Houttuynia cordata extract can also extend the growth period of hair follicles by regulating the expression of key cell cycle signaling molecules,apoptosis and growth factors.

3 Mesotherapy

Mesotherapy uses ultra-micro penetration technology to apply a variety of nutrients to the 1-1.5 mm of the skin,the nutrients are slowly released,have a longer durability,and the use of nutrients is low.[24-25]

Mesotherapy has been applied in areas such as hair loss,wrinkles,and chloasma.[26]The effect of mesotherapy on the scalp is to restore and enhance the local microcirculation of the scalp,provide nutrients to the hair follicles,enhance the vitality of the hair follicles,and slow down the degeneration process of the hair follicles.There are many studies on the use of mesotherapy combined with 5α-reductase inhibitors to improve androgenic alopecia.5α-reductase inhibitors include minoxidil,finasteride,dutasteride,etc.Dutasteride,the second-generation 5α-reductase inhibitor,is more effective than finasteride because of its ability to inhibit type 1 and type 2 enzymes.It can lead to a 90% reduction in DHT serum levels,while finasteride only reduces 70%.[27]

In 2009,Abdallah et al[28]first reported the research on hair mesotherapy.In this study,a total of 28 subjects with androgenetic alopecia took part in the test,and 14 of them used a sample containing 0.05% dutasteride once a week.The results of the test showed that 92.9% of the patients in the experimental group had increased hair density,compared to only 7.1% in the placebo group.No adverse reactions were,observed between the groups.In a study conducted in 2013,Sobhy et al[29]found that compared with the placebo group,the number of hair follicles in the head of the experimental group containing 0.05% dutasteride increased significantly.And there were no adverse reactions such as loss of libido and sexual dysfunction.Another clinical report published in 2013[30]reported that 126 female AGA subjects used mesotherapy to improve hair loss(using a sample containing 0.05% dutasteride).The subjects received 12 mesotherapy treatments within 16 weeks.In the experimental group,62.8% of subjects showed improvement in hair loss,while in the control group,only 17.5%.?zdo?an et al[31]used a complex of minoxidil,biotin,dexpanthenol,herbal complex and procaine to improve androgenetic alopecia through mesotherapy,and detected a significant increase in hair thickness and number,and the number of hair loss is obviously reduced.It has a better effect of improving hair loss.Melo et al[32]used a mixture of minoxidil,finasteride,biotin,and panthenol to apply mesotherapy to the scalp of patients with hair loss.After 20 treatments,they found that the thickness and density of the hair were significantly improved.

4 Stem cell therapy

With the advancement and development of science and technology,stem cell-based therapies have opened up new ways to improve traditional hair loss,and transplantation of multifunctional stem cells has become a recognized therapy for improving hair loss.Stem cells participate in the development and regeneration of tissues and organs,and have selfrenewal ability and multi-directional differentiation potential.Sources of pluripotent stem cells with the potential to regenerate skin and hair follicles include adipose tissue,bone marrow,unaffected hair follicles,and cord blood.[33]

Elmaadawi et al[34]mainly studied the safety and effectiveness of autologous bone marrowderived monocytes(BMMC)and follicular stem cells(FSC)obtained from unaffected scalp areas.All subjects used autologous stem cell(BMMC or FSC)samples.Evaluation by immunostaining and electronic dermoscopy after 6 months showed that the symptoms of hair loss were significantly improved,there were no significant differences between subjects,and no adverse effects.

Pluripotent stem cells from adipose tissue include adipose-derived stromal vascular cells(ADSVC)or adipose-derived regenerative cells(ADRC).[35,36]Anderi et al[35]studied the results of ADSVC improving 20 subjects with alopecia areata.After 6 months,the thickness of the subject's hair had been significantly improved,which was statistically significant.In addition,there was a statistically significant increase in hair density and a significant drop in the results of the hair tensile test.Another study[36]found that primary pluripotent ADRC can promote hair growth.The test was to add stem cells derived from stromal blood vessels to adipose tissue to improve hair loss in 6 subjects.The results showed that the average hair count increased by 23%,while the control group only increased by 7.5%.

The dermal papilla(DP)area is an important area of the hair follicle,which contains mesenchymal stem cells(MSCs).MSCs are involved in inducing hair growth and controlling hair cycle.DP cells are surrounded by dermal sheath cup cells(DSC),which are also essential for the regeneration and proliferation of DP cells and the growth of hair.[37]It has been suggested that androgens can inhibit DP cell-derived signal transduction,inhibit Wnt-β-catenin pathway signal transduction and cause hair loss.In addition to DP cells,pluripotent stem cells at the bulge are also considered to depend on DSC cells.[38]In a study by Tsuboi et al,[39]55 subjects used autologous DSC cell samples or placebo in 4 random independent areas of the scalp,and the cell sample concentration was 7.5×106,1.5×106or 3.0 ×105.Follow-ups were conducted after 3,6,9,and 12 months.After 9 months,the total hair density and cumulative hair diameter increased significantly at the location where 3.0×105DSC cells were used.These results indicate that using the lowest concentration of autologous DSC cells is a potentially safe and useful way to treat male and female hair loss.

5 Prospect

Consumers are pursuing a healthy and green life,and the application of natural plant extracts in anti-hair loss cosmetics has attracted much attention.The mechanism of action is mostly to activate hair follicles,antibacterial,anti-inflammatory,antioxidant and blood-activating methods to promote hair follicle cell proliferation and hair growth.The effects of more and more plants are slowly being discovered.The well-known anti-hair loss plant extracts in the market include ginger,fleece-flower root,ginseng,etc.The anti-hair loss effects of plants such as houttuynia cordata and rhododendron chinense have also been researched and reported,and more plant extracts based on similar mechanisms will likely be studied and applied to the field of preventing hair loss.At the same time,the efficacy and mechanism of natural plant extracts have been studied more and more thoroughly.Kim et al.[40]found that the extract of Centipeda minima can effectively inhibit the activity of Janus kinase 3(JAK3)to improve mild to moderate baldness,instead of just being described as anti-inflammatory.Kim et al.[41]found that quercetin,a component of Robinia pseudoacacia extract,can stimulate the production of NAD(P)H,increase the expression of Bcl2 and Ki67,enhance cell energy metabolism,activate the MAPK/CREB signaling pathway,increase the production of growth factors,and promote hair growth.Bcl2 is an important marker of hair growth,hair follicles and cell survival.Ki67 is a marker of cell proliferation.However,the anti-hair loss effects of most novel plant extracts are mostly carried out in cell tests and mouse experiments,and no actual efficacy studies have been conducted on humans.The final anti-hair loss effects need further practical research.

Mesotherapy is widely used.In recent years,research in the field of improving hair loss has gradually increased.Compared with the conventional use of anti-hair loss products,the amount of product required for ultra-micro penetration is smaller,and the transdermal absorbability is good.However,the mesotherapy market still needs to standardize operation and management.The choice of products and disinfection before mesotherapy are very critical.

In recent years,mesotherapy has made great progress in skin beauty.The more commonly used mesoplastic apparatus has simple operation technology and comfortable experience,and has been widely used in skin beauty and life beauty.The natural plant extracts with anti-hair loss and hair growth effects are scientifically compounded to make anti-hair growth cosmetics.Then use the mesotherapy instrument to improve hair loss,which has very large application prospects and high penetration rate.However,in view of the particularity of mesotherapy,the safety of the above methods and more kinds of tests need to be studied,but they have very great application value.

The new discoveries surrounding stem cell therapies provide encouraging steps for the development of more effective and successful improvements in hair loss.However,each method has its own limitations and high costs,and it has not been widely used to improve hair loss.In addition,concerns about its biosafety have also hindered its expansion.The application of stem cells in hair regeneration has gained great expectations,so more double-blind controlled trials are needed to evaluate the safety of the exact mechanism based on stem cells to improve hair loss.

With the rapid development of science and technology,various methods and technologies have been introduced,new technologies and new products for improving hair loss more effectively and safely will be continuously developed and utilized.