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Hair growth and rejuvenation: An overview

Article in Journal of Dermatological Treatment · June 2011

DOI: 10.3109/09546630903578574 · Source: PubMed

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 Journal of Dermatological Treatment. 2010; Early Online, 1–10

REVIEW ARTICLE

Hair growth and rejuvenation: An overview

MONA SEMALTY1, AJAY SEMALTY1, GEETA PANT JOSHI2 &

MOHAN SINGH MANIYARI RAWAT2
1
Department of Pharmaceutical Sciences, and 2Department of Chemistry, HNB Garhwal University Srinagar (Garhwal),
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Uttarakhand, India

Abstract
Hair has psychological and sociological importance throughout the ages in framing the personality and general appearance of
an individual. Significant progress is being made on discovering an effective and safe drug for hair growth. Angiogenesis, androgen
antagonism, vasodilation, potassium channel opening and 5-alpha reductase inhibition are the major non-surgical therapeutic
strategies of hair growth promotion. In spite of a flood of drugs claiming to be useful as hair growth promoters, more rational
strategies, which can target the problem areas or stages of the hair growth cycle effectively, are still awaited. This article highlights
the developments in hair rejuvenation strategies and reviews the potential of herbal drugs as safer and effective alternatives.
For personal use only.

Key words: alopecia, baldness, hair growth, hair loss, herbal drugs, minoxidil

Introduction Over the past several years about 300 000 products
have claimed to help hair regrowth. With the excep-
Hair has been a sign of beauty and a contribution to an tion of minoxidil and finasteride, none of them was
individual’s personality since time immemorial. Alo- found to be effective in hair growth promotion.
pecia (baldness), a dermatological disorder, is a com- Minoxidil, a synthetic (cardiovascular) drug, was
mon problem of cosmetology as well as primary scientifically proved to help the treatment of alopecia.
health practice. It is common throughout the world The hair growth activity of minoxidil is actually the
and has been estimated to affect between 0.2% and side effect of this cardiovascular drug (5). Currently,
2% of the world’s population (1–3). The clinical minoxidil (useful in both male and female pattern
severity of alopecia in a patient may not be a good baldness) and finasteride (useful in male pattern
indicator of a subsequent downturn in quality of life baldness) are two US FDA-approved synthetic drugs
or psychological well-being of the patient. finding concomitant use for treatment of androgenic
Drugs which claim to treat hair loss target a steadily alopecia, but their side effects have reduced their
growing, multi-billion dollar market worldwide. usage (6,7). Moreover, both the drugs are the result
Great expectations are associated with pharmaceuti- of serendipity, not of rational hair drug design.
cal hair loss management, but still there is no radical Therefore, to search for more precise therapies for
improvement in the availability of more precise ther- alopecia, newer synthetic drugs or drugs of plant
apies (4). Much of that disappointment appears to origin need to be explored. Herbal drugs have
result from unrealistic expectations, ill-targeted (and been widely used for hair growth promotion since
therefore inefficient) drug therapy and insufficient ancient times in Ayurveda, Chinese and Unani sys-
industrial interest in dissecting the basic mechanisms tems of medicine. Natural products are very popular
by which hair loss occurs and by which human hair and well accepted in the cosmetic and hair care
growth promoters exert their effects. industries (8,9).

Correspondence: Mona Semalty, Department of Pharmaceutical Sciences, PB No.-32, HNB Garhwal University Srinagar (Garhwal)-246174, India.
Fax: 91 1346 252174. E-mail: monasemalty@gmail.com

(Received 26 September 2009; accepted 21 December 2009)

ISSN 0954-6634 print/ISSN 1471-1753 online
2010 Informa UK Ltd.
DOI: 10.3109/09546630903578574
 2 M. Semalty et al.

The goal of the present article is to provide an the hair follicle is that the follicle is a regenerating
overview of available hair loss treatment alternatives. system (Figure 1). By traversing the phases of the
The article provides a brief review of the hair growth cycle (growth, regression, resting, shedding, then
cycle and different causes of hair loss, followed by growth again), the follicle demonstrates the unusual
focuses on the various types of drugs available for ability to completely regenerate itself (11). Normal
alopecia. The article reviews various studies show- hair follicles cycle between a growth stage (anagen),
ing hair growth-promotion efficacy of modern and a degenerative stage (catagen), a resting stage
herbal drugs. (telogen) and a shedding stage (exogen). The scalp
hairs have a relatively long life cycle: the anagen stage
Hair growth cycle ranges from 2 to 5 years, the catagen stage ranges from a
few days to a few weeks, and the telogen stage is
Hair is the cumulative, physical result of a coordi- approximately 3 months (12,13). Hair cycle distur-
nated process of cellular proliferation and differ- bances have dramatic effects on visible hair growth. If
entiation within a hair follicle. Hair follicles are anagen gets prematurely terminated and catagen
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epidermally derived appendages which arise as a occurs too early, this must result in effluvium and
result of inductive events between specialized dermal alopecia; the affected skin region will subsequently sport
fibroblasts acting on bipotential epithelial stem cells. largely catagen and/or telogen follicles, whose loosely
The stem cells which commit to a hair follicle fate anchored club hairs are eventually shed (i.e. the normal
enter a period of massive proliferation that culminates anagen/telogen rate on the scalp [roughly 4:1] changes in
in the formation of a mature hair follicle (10). favor of telogen). This is exactly what happens, for
The hair follicle cycle is a complex process and example, as a consequence of drug-induced damage
entails involvement of cell differentiation, epithelial– to the proliferating cells of the anagen hair bulb,
mesenchymal interactions, stem cell augmentation, such as in drug-induced telogen effluvium or when
pattern formation, apoptosis (programmed cell death), inflammatory cells attack the anagen hair bulb in
For personal use only.

cell and organ growth cycles, and pigmentation. alopecia areata (12). Therefore, the therapeutic
The most important reason for studying the cycling of manipulation of hair follicle cycling is a key challenge

Folliculogenesis
Epithelium/ Anagen Catagen
messenchyme Placode Germ Peg Bulbose peg

B Telogen
B

E
P
IRS H
S
ORS
CTS B
P

H B
B
M P
P

Figure 1. The formation of hair follicles in the fetus and cycling transformations in the adult. In the fetus, a thickening forms at one focus of the
primitive epithelium to form a placode. Below the placode dermal cells aggregate and thereafter the epithelium grows down as a finger to
produce the multilayer, shaft-producing hair follicle. In the adult, three phases of the growth cycle are recognized: a growth phase (anagen), a
regressing phase (catagen): and a resting phase (telogen). It is the lower follicle that regenerates at the beginning of each cycle by utilizing
intimate and powerful epithelial–mesenchymal interactions of the stem cells in the bulge (B) and the inductive mesenchymal cells of the
papilla (P). CTS, connective tissue sheath; E, epidermis; H, hair shaft; IRS, inner root sheath; M, hair matrix; ORS, outer root sheath;
S, sebaceous gland.
 Hair growth and rejuvenation 3

in hair loss management. Effective therapeutic strategies normally found on the adult scalp is replaced by
for hair loss in declining order of importance are: vellus hairs which are shorter, finer and
non-pigmented. Concomitantly, the average length
. inhibition of catagen development in order to
of time spent by hairs in anagen (growth phase)
prolong anagen
.
decreases, and the proportion of hairs in telogen
induction of anagen in telogen follicles
.
(resting phase) increases (16).
inhibition of exogen.
Baldness or alopecia can be classified as follows:
male pattern baldness, female pattern baldness,
Hair loss and alopecia alopecia areata (an autoimmune disorder causing
small, patchy circular bald patches in several parts
Hair loss is a natural daily phenomenon, but this of the scalp), alopecia totalis (total loss of scalp hair),
shedding of hair cannot be the main cause of hair and alopecia universalis (total loss of hair from the
loss. Every strand of hair on a human head is genet- entire body) (17). Another way in which hair loss
ically programmed to a cycle that includes growth, (alopecia) can be classified is according to factors
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stabilization, aging and shedding. On average, every leading to it. There are two different types of hair
day a human head sheds about 50–125 hairs (depend- loss, known medically as:
ing on sex), but most of them will come back after the Anagen effluvium: caused by medications taken
resting stage as the follicle itself is not destroyed (14). internally, such as chemotherapy representatives,
Trouble begins when the loss exceeds re-growth, or excessive doses of vitamin A or some hypertension
the re-growth is weak and unhealthy. A loss of 100 medications.
hairs per day can be considered ‘normal’ not patho- Telogen effluvium: caused by an increased number
logic. But a loss of more than 100 hairs per day of hair follicles entering the latent or rather dead stage.
constitutes a pathological effluvium. Androgenetic The most common causes of telogen effluvium
alopecia (AGA) is one of the dermatological condi- leading to alopecia could be physical and emotional
For personal use only.

tions most commonly faced by the dermatologist or stress, and thyroid or another hormonal irregularity.
general physician. The condition affects up to 30% of The growth of hairs is affected by various factors,
men under the age of 30 and more than 50% of men which are listed in Table I (18).
over the age of 50. Despite a widespread belief that
AGA is only experienced by men, it also affects Current strategies for hair growth and
women, although the clinical signs are usually milder rejuvenation
and the phenotype is different (15). As the condition
progresses, scalp hairs and their follicles become There are a number of ways in which a drug may
progressively miniaturized, and the terminal hair stimulate hair growth: it may increase the linear

Table I. Factors leading to hair loss.

Factors Description

Major physical–emotional stress Surgery, severe illness, diet or nutrition changes and emotional stress can cause hair loss
Chemotherapy Cholesterol-lowering drugs, Parkinson medications, anti-ulcer drugs, anticoagulants, agents for
gout, anti-arthritic drugs derived from vitamin A, anticonvulsants for epilepsy, antidepressants,
beta-blocker drugs, antithyroid agents, antineoplastics, blood thinners, male hormones
(anabolic steroids)
Genetic predisposition Genetic component to androgenetic hair loss exists (polygenic inheritance)
Dihydrotestosterone (DHT) Increased level of DHT (the testosterone metabolite) shortens the hair cycle and progressively
miniaturizes scalp follicles and this may be due to the atherosclerotic process blocking the
microvasculature that nourishes the hair follicles
Excessive sebum Excessive sebum causes a high level of 5-alpha reductase and pore clogging, thus malnutrition of
the hair root
Cardiovascular diseases High levels of LDL in cardiac patients are converted to 5-alpha reductase enzyme, which produces
DHT from testosterone, causing hair loss
Smoking Tobacco smoke damages the lining of blood vessels, leading to less production of nitric oxide and
thus inducing hair loss
Endogenous substances bax, bcl-2 and insulin-like growth factor binding protein-3 (e.g. VEGF) promote hair growth

LDL = low-density lipoprotein; VEGF = vascular endothelial growth factor.

 4 M. Semalty et al.

growth rate of hair; increase the diameter of the hair in promoting angiogenesis as well as influencing
fibre; alter the hair cycle, either shortening telogen or diverse cell functions, including cell survival, prolif-
prolonging anagen; or act through a combination of eration and the generation of nitric oxide and pros-
these effects. Among the surgical treatment methods, tacyclin (21). The perifollicular capillary network is
the introduction of micrografts (one to two hair fol- coupled to the hair cycle, increasing during anagen
licular unit grafts) and minigrafts (three to four hair and then regressing during catagen and telogen.
follicular unit grafts) has made a most significant It has been investigated that metabolically ‘resting’
advancement in the care of male pattern baldness telogen follicles have considerably lower perfusion
and female androgenic alopecia; natural requirements than larger, rapidly growing, anagen
and aesthetically pleasing results are possible. Addi- hair follicles. With the use of standardized quantita-
tionally, many other applications in the reconstruction tive histomorphometry, electron microscopy, and
of facial and scalp hair have been found; some of these CD31 (platelet endothelial cell adhesion molecule-1
include restoration of hair loss due to (iatrogenic) [PECAM-1]) immunohistochemistry as an endothe-
post-surgical causes (i.e. after facial rejuvenation pro- lial cell marker, it was shown that the cutaneous
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cedures or procedures involving incisions on hair- microvasculature is substantially rearranged during

bearing facial skin or scalp) and burns or traumatic anagen development, that there is endothelial cell
injuries (19). proliferation, and that there is an increase in endo-
Various non-surgical pharmacotherapeutic alter- thelial cell numbers in anagen (22).
natives available for hair growth and rejuvenation Taken together, these studies suggest that anagen
are discussed in the following sections. development, at least in species with a synchronized
hair cycle, is associated not only with a rearrangement
Vitamins, nutrients and minerals of the skin vasculature and a concomitant increase in
skin perfusion, but also with genuine and substantial
Vitamin deficiencies are also thought to be the cause angiogenesis. Therefore, modulation of angiogenesis
For personal use only.

of alopecia and for which the treatment would be is considered as therapeutic strategies of great impor-
dietary vitamin supplementation. The use of biotin as tance for hair growth (23). The role of various nutri-
a treatment for alopecia was suggested by evidence ents and minerals in preventing hair loss is
that biotin (vitamin H) deficiency causes hair loss. summarized in Table II.
Biotin is a water-soluble vitamin that acts as an
essential cofactor for four different carboxylases,
each of which catalyzes an essential step in interme- Table II. Role of nutrients and minerals in the prevention of
diary metabolism. An analysis of hair shows that it hair loss.
is composed of iron, oxygen, hydrogen, nitrogen Nutrients and minerals Mechanism of preventing hair loss
and sulphur. The blood must be supplied with these
Niacin (vitamin B3) . Enhances blood flow
minerals so that nourishment will be carried to
to scalp through vasodilatory
the scalp. effects
Angiogenesis, the formation of new blood vessels . Reduces the level of cholesterol
from the pre-existing vascular network, is a driving and hence the level of 5-alpha
force of hair growth. It is indispensable for embryonic reductase on scalp
Vitamin B complex . Improves blood flow
development as interruption of angiogenic events
to scalp
blocks the growth of the embryo and results in early . Decreases cholesterol
mortality. After birth, angiogenesis plays both adap- accumulation to scalp
tive role enabling the regeneration of damaged body . Protects hair and scalp from
parts and is also involved in numerous pathological free radical damage
Ascorbic acid (vitamin C) . Improves blood flow to scalp
changes. Understanding of the basic mechanisms of
and maintains capillaries
blood vessel formation is necessary for the establish- carrying blood to follicles
ment of effective therapeutic strategies for ameliora- Tocoferol (vitamin E) . Enhances oxygen uptake and
tion of diseases. The major angiogenic regulator is thus improves blood flow to
vascular endothelial growth factor (VEGF), named scalp
Zinc . Enhances immune function
also VEGF-A, which is one of several members of the
and thus stimulates hair growth
VEGF family. In adult organisms, physiological Essential fatty acids . Improves hair texture
angiogenesis is limited and occurs during regenera- (primrose and salmon oil) . Prevents loss of dry brittle hairs
tion of uterine epithelium in the menstrual cycle, Amino acids (L-cysteine . Improves quality of
development of the ovum and formation of corpus and L-methionine) hair texture
luteum and hair growth (20). VEGF has a central role
 Hair growth and rejuvenation 5

Anti-androgen therapy solution must be applied to the balding area twice a

day, every day. Decreasing the dosage to once a day
Flutamide and cyproterone acetate in combination results in some hair loss, and discontinuing applica-
with ethinyl-estradiol have been reported to show tion causes regression to pretreatment baldness within
some effectiveness in female pattern baldness. Spir- 3–6 weeks.
onolactone is a steroid used mainly as a diuretic and The disadvantages of minoxidil are: (i) lifetime
antihypertensive agent. Side effects cause androgen- commitment; (ii) high cost: it is not covered by health
receptor blockade and direct inhibition of testoster- insurance schemes as it is considered a cosmetic; (iii)
one production by the adrenal gland. Therefore, this its side effects – including itching and prickling,
aldosterone antagonist (spironolactone) is used in headaches, dizzy spells and, in some, heartbeat irreg-
dosages from 75 mg to 150 mg per day with some ularities (34). Although apparently safe when rubbed
benefit in hair loss. into the scalp – since little is absorbed into the
bloodstream – it is a vasodilator and not recom-
mended for anyone with heart trouble. Its safety in
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pregnant women, men over the age of 49 years and

Heterocyclics
long-term use is unknown.
Minoxidil

Minoxidil was first used in tablet form as a medicine Pyridine derivatives

to treat high blood pressure, but it was noticed that
some patients being treated with minoxidil experi- These include pinacidil, nicorandil, RP-49356 and
enced excessive hair growth (hypertrichosis) as a side P-1075. They are K+-channel openers. They play a
effect. Further research showed that by applying role in regulation of the hair growth cycle. Potassium
topical minoxidil solution directly to the scalp, it channel biology is a widely diverse field that has an
For personal use only.

could prove to be beneficial to those people experi- impact on many aspects of physiology. More than 15
encing hair loss. Topical minoxidil (2,4-diamino- different types of potassium channels have been iden-
6-piperidino pyrimidine-3-oxide) is the only drug tified in various tissues. These channels are classified
approved by the Food and Drug Administration to into four subtypes: voltage dependent, calcium
treat male and female pattern baldness. Orally admin- dependent, receptor coupled, and miscellaneous.
istered minoxidil lowers blood pressure by relaxing Specific classes are defined by the magnitude of the
vascular smooth muscle through the action of its electrical conductance of the channel, the types of
sulphated metabolite, minoxidil sulphate, as an pharmacological agents that block the channel, and
opener of sarcolemmal KATP channels (24). There the physiologic properties of the channel. Potassium
is some evidence that the stimulatory effect of minox- channel openers stimulate proliferation of cells in
idil on hair growth is also due to the opening of cultured vibrissae and skin keratinocytes. They elicit
potassium channels by minoxidil sulphate, but this hypertrichosis in humans (35–37). Buhl et al. tested
idea has been difficult to prove and to date there has the effect of topical application of minoxidil and
been no clear demonstration that KATP channels are three other potassium channel openers on scalp
expressed in the hair follicle (25,26). Minoxidil sti- hair growth in balding macaques. Minoxidil, croma-
mulates mitosis in epithelial cells, inhibits collagen kalim and P-1075 (a pinacidil analogue) all stimu-
synthesis, prolongs the survival of epithelial cells in lated hair growth over a 20-week treatment period.
tissue culture and stimulates vascular endothelial A fourth potassium channel opener, RP-49,356,
growth factor and prostaglandin synthesis (27–30). was not effective. Systemic pinacidil induces
It has therefore been suggested that the drug slows the hypertrichosis in 2–13% of patients (38).
aging of hair matrix cells. It is postulated that it delays
or prevents the entry of some follicles into the next
anagen phase for long periods of time and stimulates Benzothiazide derivative
these follicles back into active production. Various
studies have verified the hair growth-promotion Diazoxide is also a K+-channel opener. Diazoxide was
activity of minoxidil (31,32). Also, both 5% and reported to increase the uptake of thymidine in a
2% topical minoxidil helped improve psychosocial dose-dependent fashion in 4-day cultures of mouse
perceptions of hair loss in women with female pattern vibrissae follicles (31,39). Oral diazoxide causes
hair loss (33). Topical minoxidil is effective at a hypertrichosis in most hypoglycemic children and
concentration of 2%. Successful treatment, however, about 1% of adults, and induces some scalp hairs
does require a lifetime commitment. The topical in 25% of the balding patients (40).
 6 M. Semalty et al.

Steroids temple. These side effects may last for as long as the
medicine is taken. Besides finasteride, other 4-aza
4-Aza steroids steroidal drugs are dutasteride, episteride and
turosteride.
Finasteride is a 4-aza steroidal drug which acts by
inhibiting the 5-alpha reductase (enzyme) that trans-
forms testosterone into the dihydrotestosterone 6-Aza steroids
(DHT) form, responsible for hair loss (41,42). It
was originally used to treat benign prostate hyperpla- These are 6-aza androstane derivatives and show
sia or prostate enlargement. Blocking the action of hair growth activity. They are type I 5-alpha reductase
DHT seems to stimulate growth of stronger, thicker (located in the sebaceous glands) inhibitors but are
and more pigmented hair. In a study, finasteride was not time-dependent like finasteride, which is a
administered orally at 0.5 mg/day, alone or in com- time-dependent inhibitor of type II 5-alpha reductase
bination with topical 2% minoxidil, for 20 weeks to (45,46).
determine the effects on scalp hair growth in balding
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adult male stump tail macaque monkeys. A l-day

dose-finding study showed that both 0.5- and Natural products
2.0-mg doses of the drug produced a similar dimi-
nution in serum DHT in male stumptails (42). In ano- Many ancient Ayurvedic (ancient Indian system of
ther study, finasteride was found to regrow a noticeable medicine) and Chinese herbal drugs have been
amount of hair in about 40% of balding men (43). reported and documented as potent hair growth pro-
Finasteride may not be very effective in men over moters. The natural products are reported to be more
60 years (44). As DHT is required for normal sexual effective alternatives for hair growth therapy than the
functions in men, the side effects of finasteride synthetic drugs. Numerous bioactive plant com-
For personal use only.

include sexual performance problems (in about 3% pounds have been tested for potential clinical applica-
of the sample), such as impotence, loss of libido, tions. Various natural products associated with hair
reduced sperm counts or erectile dysfunction. growth activity are listed in Table III.
Finasteride is also not approved for women (even In the search for a safe and effective alternative
in small concentrations it causes a specific birth therapy for hair loss, many studies on herbal drugs
defect – hypospadias, which involves abnormalities have been performed in the last few decades.
of the external genitalia of a male fetus) and has not Recently, it was reported that epigallocatechin-3-gal-
been shown to work for a receding hairline at the late, a major polyphenolic constituent of green tea,

Table III. Herbal drugs for hair growth promotion.

Herbal drug Mechanism of preventing hair loss

Grape seed . Contains proanthocyanidins, which are potent antioxidants and act as a smooth muscle relaxant in
blood vessels and capillaries, preventing or offsetting damage to the hair follicle blood supply
Rosemary oil . Improves blood flow to scalp
. Cleansing the scalp and stimulating the hair root
Sage (Salvia officinalis) . Thickens hair shafts and helps dissolve sebum deposits
. Improves blood flow to scalp
Emu oil . Inhibits 5-alpha reductase and thus lowers the DHT level in the scalp
Aloe vera . Its proteolytic enzymes slough off dead skin cells and open pores
. Increases membrane fluidity and permeability and the outward flow of toxins and inward flow of
nutrients
Ginkgo biloba . Inhibits 5-alpha reductase activity
. Protects small blood vessels and micro-capillaries against loss of tone and fragility
Bee pollen . Being rich in L-cysteine, it stimulates hair growth (since hair is 8% L-Cysteine)
Green tea . A potent inhibitor of 5-alpha reductase and thus lowers the DHT level in the scalp
Saw palmetto (Serenoa repens) . Blocks DHT production
Nettles (Urtica dioica) . Provides silica for hair growth
. Improves blood flow to scalp
Hibiscus rosasinensis . Improves blood flow to scalp which leads to dense hair growth

DHT = dihydrotestosterone.
 Hair growth and rejuvenation 7

might be useful in the prevention or treatment of showed that it can be used as a potential hair
androgenetic alopecia by selectively inhibiting 5-alpha growth promoter (57).
reductase activity (47–49). Polyphenolic compounds An independent study was designed to test the
(such as epigallocatechin-3-gallate) and catechins of effectiveness of topical crude onion juice (Allium
green tea are the major phytoconstituents that are cepa L.) in the treatment of patchy alopecia areata.
responsible for its hair growth activity. Adhirajan et al. The patients were divided into two groups. The first
(2003) evaluated the petroleum ether extract of the group (active: onion juice) consisted of 23 patients
leaves and flowers of Hibiscus rosasinensis for its poten- (16 males and seven females). The second group
tial on hair growth by in vivo and in vitro methods. (control: tap-water) consisted of 15 patients (eight
From the study it is concluded that the leaf extract, males and seven females). The two groups were
when compared to the flower extract, exhibits more advised to apply the treatment twice daily for
potency on hair growth (50). In another study, Adhir- 2 months. Re-growth of terminal coarse hairs started
ajan et al. (2001) studied a mixture of petroleum ether after 2 weeks of treatment in the active group. At
extract of Eclipta alba Hassk. (compositiae), Citrullus 4 weeks, hair re-growth was seen in 17 patients
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colocynthis Schrad. (cucerbitaceae) and Tridax procum- (73.9%), and at 6 weeks hair re-growth was observed
bens Linn. (compositeae) in various concentrations in in 20 patients (86.9%); it was significantly higher
the form of herbal cream and herbal oil (51). The ratio among males (93.7%) compared with females
of E. alba, C. colocynthis and T. procumbens in 3:1:2 (71.4%). In the control group, hair re-growth was
showed excellent hair growth activity with 35% more apparent in only two patients (13%) at 8 weeks of
anagen hair follicles as compared to 20% with a treatment with no sex difference (58).
standard drug (2% ethanolic solution of minoxidil). The extract of Illicium anisatum increases subcuta-
Roy et al. studied the effect of successive petroleum neous blood flow in mice. In a study, an organ culture
ether and ethanol extracts of C. colocynthis and Cuscuta system was used to examine the hair follicle elonga-
reflexa on hair growth in albino rats (52,53). The tion effect of this extract (59). In this study,
For personal use only.

extracts were incorporated into an oleaginous oint- B6C3HF1 mouse vibrissae follicles were cultured
ment base and were applied topically on the shaved in serum-free medium for 7 days at 31 C. Follicles
denuded skin of albino rats. The time required for treated with water-soluble extracts of the leaves, fruits
initiation of hair growth as well as completion of the and roots of I. anisatum or shikimic acid grew signif-
hair growth cycle was recorded. The hair growth icantly longer than controls.
initiation time was significantly reduced to half on Bisbenzylisoquinoline alkaloids were isolated from
treatment with the petroleum ether extracts compared Stephania cepharantha and their proliferative activities
with untreated control animals. The time required for on cultured hair cells from the murine skin were
complete hair growth was also considerably reduced. evaluated (60). Cepharanthine, cepharanoline, isote-
The treatment was successful in bringing a greater trandrine, and berbamine showed significant acti-
number of hair follicles (> 70%) to the anagen phase vities in the range of 0.01–0.1 mg/ml, but had no
than standard minoxidil. In another study, the poly- activity on cultured keratinocytes or fibroblasts
herbal formulation of C. reflexa (Roxb.), C. colocynthis from the murine skin.
(Schrad.) and E. alba (Hassk.) were developed and Recently, stem cells inducing the anagen phase in
evaluated the same for hair growth-promoting activ- the hair follicle cycle have been discovered in the
ity. The hair growth initiation time was markedly bulge region of the outer root sheath (ORS). To
reduced to one-third on treatment with the prepared find growth-promoting agents for the ORS cells,
formulation compared with control animals (54). The the effect of various botanical extracts on the growth
time required for complete hair growth was also of cultured human hair follicles was evaluated. It was
reduced by 32%. Quantitative analysis (by the method found that Laminaria angustata extract increased
described by Uno) (55) of the hair growth cycle after ORS cell growth. Further, hair growth in the shaved
treatment with prepared herbal formulations and skin of C3H mice was also promoted by the topical
minoxidil (2%) exhibited a greater number of hair application of the extract (61).
follicles in the anagen phase compared with controls. The other herbal drugs studied for hair growth
Rho et al. examined the effects of 45 plant extracts activity include nagarmotha (Cyperus rotundus),
that have been traditionally used for treating hair loss neem (Azadirachta indica), amla (Emblica officinalis),
in oriental medicine in order to identify potential Brahmi (Bacopa monnieri), bahera (Terminalia
stimulants of hair growth. Asiasari radix extract bellirica), methi (Trigonella foenumgraecum), laljari
showed hair growth-promoting potential (56). (Geranium wallichianum), bhallataka (Semecarpus
In another study, Rho et al. studied the hair anacardium) and capsicum. Various patents have
growth-promoting effect of Sophora flavescens and also been granted for hair growth potential of herbal
 8 M. Semalty et al.

drugs such as Ginkgo biloba, Berberis vulgaris, vasodilation through potassium channel opening
Zingiberis recens, Pinellia ternata, Flos carthami, and 5-alpha reductase inhibition are the major
Angelicae sinesis, Paenoiae rubra, Cacumen biotae, non-surgical therapeutic strategies for hair growth
Sesami nigrum, Polygoni multiflori, Fructus mori, promotion.
Capsicum annum and Oleum ricin (62–65). Modern synthetic drugs have been found to show
potential in promoting hair growth. Various clinical
trials and studies have validated the use of hair
Miscellaneous growth-promoting modern synthetic drugs. But, in
spite of proven hair growth-promotion effects, therapy
Various topical sensitizers such as dinitrochloro- with the synthetic drugs has become questionable due
benzene (DNCB), squaric acid dibutylester to their occasional lack of efficacy, safety or their side
(SADBE), and diphenylcyclopropenone (DPCP) effects. Herbal drugs may provide a new revolution for
have determined the re-growth of hair in patients hair growth. A majority of hair growth-promotion
with alopecia. Anthralin, the only non-specific irritant studies performed with herbal drugs are preliminary
J Dermatolog Treat Downloaded from informahealthcare.com by 117.254.208.54 on 06/11/10

widely used for hair growth in alopecia areata, is and more scientific data are necessary to prove those
applied topically as a 0.5% or 1% cream to affected activities. This can be attained by careful and accu-
areas once per day for 20–45 minutes; overnight rate characterization of the active chemical com-
application can also be used in certain patients who pounds, elucidation of the molecular mechanisms
can tolerate the side effects (66). of their actions, development of more reliable hair
LY 191704 (a benzoquinoline derivative), All-trans- follicle organ culture for ex vivo studies, in vivo
retinoic acid [(tretinoin) (3,7-dimethyl-9-(2,6,6-tri- studies on proper animal models of hair loss and,
methyl-1-cyclohexenyl)-non-2,4,6,8 tetraenoic acid)], finally, analysis of their safety and effectiveness in
6-benzyl-aminopurine (6-BA) and pentadecanoic acid clinical trials.
(PDA), cromakalim, etanercept, infliximab, RU58841
For personal use only.

and latanoprost are some newer hair growth-promoting

agents (67,68). Declaration of interest: The authors report no
conflicts of interest. The authors alone are responsible
for the content and writing of the paper.
Patient consideration

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