26 bioprospecting and new cosmetic product - urp journals

26 International Journal of Natural Products Research 2011;1 (3):26-37

ISSN: 2249-0353

Review

Bioprospecting and new cosmetic product development:

A brief review on the current status

Arun Duraisamy, Venkat krishnan and K P Balakrishnan*

Personal care division, ITC R&D centre, peenya industrial area,

Bangalore 560058, India

Email id: [email protected]

Received 25 August 2011; accepted 17 September 2011

Abstract

Life in the earth is impossible without plants. They not only cater to our basic needs like food, shelter and clothing but also

extend their support in curing the imbalances of the body. Plants possess their medicinal properties because of the reserved

secondary metabolites. These metabolites are used from ages for treating the illness. Exploring such medicinal plant leads for

their application in cosmetic industry opens a wide scope in the area of prospecting research. The article makes an attempt to review the needs of personal care industry for prospecting the herbs and the modern day consumer needs. It also throws an

insight into the understanding of the bio-targets for the leads to act upon, the biochemical approaches for screening the potent

herbs and the herbs known in the literature for their respective cosmetic application. The article opens the way for exploiting

the biotechnological and chemi-informatics tools to commercialize the active molecules and thereby conserving the

biodiversity.

© 2011 Universal Research Publications. All rights reserved

Key words: secondary metabolites, medicinal plant, biotechnological, chemi-informatics, biodiversity.

1.0. Introduction:

Plants are the wonderful gift of nature for the welfare of all

other creatures. We consume the plant products for our

survival, use their core wood for making our shelter, through the transpiration process they help in the raining and through

photosynthesis they consume the carbon dioxide and releases

oxygen thereby purifies the air too. They are used for these

basic needs and their applications are extended in the

remediation of the diseases to the humans, animals and now

even to the polluted environment. Search of such potential

plants or plant based products/molecules to add value to the

health of the globe is called bioprospecting.

Bioprospecting can literally be defined as the systematic

search and sustainable use of chemical and genetic

components of biodiversity for creating economic and social

benefits. In earlier days, prospecting is mainly focused on the

forest ecosystem, whereas now-a-days various forms of

biodiversity like insects, algae, microbes of different (soil/ marine) ecosystem have also been explored.

In a biodiversity, the autotrophs dominate because of the self

sustaining ability, where the heterotrophic organisms depend

on autotrophs for the survival. These autotrophic organisms

synthesize their own food with the help of sunlight.

Photosynthesis results in the synthesis of sugar molecules

which paved the way for the yield of other essential

molecules for survival (primary metabolites like proteins,

lipids & nucleic acids). Once after the synthesis of primary

metabolites, the excessive energy in the autotrophs is stored

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in the form of secondary metabolites. The autotrophs utilize

these secondary metabolites to protect themselves from the

biotic and abiotic stress factors.

The quantity & variety of secondary metabolites vary

between organisms. As the complexity of the organism

increases, the molecular diversity in secondary metabolites also increases. Plants/herbals are the complex self sustaining

organisms among the autotrophs and are the richest sources

of the variety of chemical molecules across all the species.

With respective to herbal resources, bioprospecting means the

extraction and screening of chemical compounds from plants

to develop useful leads for potential drugs.

1.1. Need for prospecting:

1.1.1.Pharma industries: Pharma industries prospect the

herbal extracts for various reasons. The candidate drugs from

the natural origin are wide in their chemical diversity and

highly effective in curing the diseases i.e., plant therapeutics,

are not dependent on one single compound for curing the diseases, it’s a mixture of active molecules. Even though the

mechanism of action of herbal actives is relatively known,

these multiple molecules in a herb act on multiple sites to

treat the diseases with less or no side effects compared to a

synthetic one. If the causative factor for any pathogenic

condition is microbes or the host malignant cells, then the

process of developing resistance against these multiple

molecules of natural origin is not so easier when compared to

single synthetic molecules.

1.1.2. Food industries: following the pharma, food industries

have also started the prospecting research in order to address the needs of modern community. Example: as per the WHO,

one third of the Indian population is diabetic and the diabetic

population is not ready to sacrifice the sweetness out of their

life. But the intake of chocolates/ any sweets tends to increase

the blood glucose level which is detrimental to their health.

Hence, the business gap is identified and filled by the

production of chocolates/ sweets for the diabetic patients.

These chocolate products not only have the artificial

sweetener (with zero calories) which imparts the sweetness to

the product but also contains the anti-diabetic functional

active ingredients which reduces the blood glucose level. It is the drug in food format. In the edible food products, the

actives from the natural origin are preferred over the

synthetic ones because of the same advantages. Thus, the

food industries conduct bioprospecting research for

delivering the better value added/functional food products

with natural actives.

1.1.3. Cosmetic industries: nowadays even the cosmetic

industries are also in line in going back to nature. From

ancient history, it is known that the rulers have promoted and

funded vaidyas for finding the anti-aging principles and

beautifying recipes for keeping them young, beautiful &

immortal. There started the application of natural products for

the cosmetic benefits. Those recipes and formulae developed

by vaidyas are not meeting the current day consumer needs.

The market demand on personal care products nowadays are

so vast like skin whitening, anti-aging, antiacne, antidandruff,

hair growth promotion and cellulite reduction as some representative examples. Hence, the cosmetic industries are

also interested in prospecting research in search of lead

molecules and actives from natural origin which act on the

bio-targets to deliver the beauty from within.

1.2. Traditional system of medicine:

Once the searching of leads from nature is decided, it is

always useful to look into the traditional knowledge /

traditional system of medicine. Traditional knowledge is the

knowledge and practices of indigenous and local

communities embodying traditional life style. It is sometimes

the undocumented wisdom passed down by word of mouth over many generations of holistic traditional scientific

utilization of the natural resources and environment.

Traditional system of medicine can be defined as health

practices, approaches, knowledge and beliefs incorporating

plant, animal and mineral-based medicines, spiritual

therapies, manual techniques and exercises, applied

singularly or in combination to treat, diagnose and prevent

illnesses or maintain well-being. In such cases, India is one

among the richest custodians of such traditional knowledge.

The Indian systems of medicine covers ayurveda, siddha, yoga , naturopathy, unani and homeopathy which originated

in India and abroad, but which got adopted and adapted in

India in the course of time.

1.2.1. Ayurveda: The word ayurveda can be read as ayu &

veda. Ayu stands for life and veda stands for science or

knowledge. Hence, ayurveda can be understood as science of

life. Ayurveda teaches the ways of preventing diseases,

maintaining good health and treatment therapies. Ayurveda

believes that any imbalance in physical (body) and mental

(mind) elements that reduces the body’s resistance will result

in diseases. It recommends the herbal formulae, life style change and the diet to boost the body’s defense mechanisms

to correct the imbalance.

1.2.2. Siddha: Siddha system of medicine uses herbs and

green leaves as medicines. When the disease condition is

chronic, siddha practioners used metals, minerals and salts in

the calcined forms to treat them. The herbal drugs used for

curing the diseases may be a single herb or combination of

herbs. Generally, the basic concepts of the siddha medicine

are almost similar to ayurveda. The only difference appears to

be that the siddha medicine recognizes predominance of

vatham, pitham and kapham in all the stages of life like

childhood, adulthood and old age respectively, whereas in

http://en.wikipedia.org/wiki/Ayurveda


ayurveda it is totally reversed: kapham is dominant in

childhood, vatham in old age and pitham in adults.

Siddha / ayurvedic herbs and formulae exhibit wide spectrum

of therapeautic activity. One such example is guggul. It is

recommended in ayurveda for more than 25 ailments because

of its anti-inflammatory, anticoagulant, hypolipidemic and antibacterial activity. It was found to have anti-inflammatory

activity in both polar and non-polar solvents indicating that

several constituents with different physical and chemical

properties exerting the same neuropharmacological actions.

1.2.3. Unani: The unani system of medicine originated from

greece and roman literature was translated into arabic &

persian languages. Thus, the arabs and persians introduced

unani system of medicine in India. Various therapies

employed in unani system are

Ilaj-bid-dava: using the drugs from herbal, mineral and

animal origin.

Ilaj-bit: regimental therapy like cupping, diaphoresis,

turkish bath, massage, purging, exercises etc.,

Jarahat: surgery

Unani medicines mainly act as immunomodulators besides

their combating function on disease causing factors.

1.2.4. Homeopathy: This system of medicine is developed by

samuel hahnemann (1755–1843) and is being practiced in

many parts of the world. It is governed by two main

principles. One is “like cures like” in which the patients with

particular signs and symptoms can be helped by a

homeopathic remedy that produces these signs and symptoms

in healthy individuals. The second principle is that these remedies retain biological activity after repeated dilution

which is beyond avagadro’s number.

In order to apply such knowledge available in the traditional

system of medicine for discovering the cosmetically

beneficial leads, one needs to have a good biochemical

understanding of the cosmetic substrates like skin and hair.

Hence, the current review is directed in understanding the

biochemical targets and the herbal remedies known in the

literature to attain the properties like skin whitening, anti-

acne, hair growth promotion, hair colours and cellulite

reduction. It is concluded with the tips for commercializing such identified novel molecules in a sustainable way from the

natural origin.

2.0. Skin whitening

Skin, being the outermost organ acts as an important barrier

in protecting our body. Melanin is the important pigment of

the skin whose protective role should not be underestimated.

Melanin protects the skin by absorbing the harmful ultraviolet

radiations [1]. It also acts as an endogenous antioxidant by

combating the free radicals generated due to UV irradiation.

Fig 1: Irradiation of UV on to skin enhances the biogenesis

of melanosomes in the melanocytes. Synthesized melanosomes acts as a vehicle for the transport of melanin

from the melanocytes to keratinocytes. The delivered

melanosomes releases the melanin in the nuclueolus of the

keratinocytes, where in the melanin caps the DNA and

renders protection from UV radiation.

Melanogenesis is initiated or accelerated upon exposure to

UV radiation by the feed forward stimulation of tyrosinase

enzyme, which results in skin darkening. The dermal DNA

photodamage, infiltration of neutrophils, expression of

matrixmetalloproteases (MMPS) and interleukin-10 (IL-10) seems to be more in white skin compared with black skin [2].

Thus, melanin protects the skin from sunburn, photo-aging

and carcinogenesis by absorbing and scattering the

detrimental UV rays [3]. On the other hand, over exposure to

UV radiation will result in the pathological increase of

melanin (hyperpigmentation disorders) as seen in the clinical

conditions like melasoma, solar lentigines and ephelides [4].

2.1. Biochemistry of melanogenesis:

The body biochromes namely oxyhemoglobin (red), reduced

hemoglobin (blue), carotenoids (yellow) and most

importantly the production, distribution, type and quantity of melanin (brown) decides the skin colour of the individual [5].

The specialized cells in the epidermis that produce such

brown pigments are called melanocytes [6]. The population

of melanocytes among the keratinocytes in the basal layer of

the skin is in the approximate ratio of 1:10. Even though, the

number of melanocytes among the different racial/ethinic

group is same, the difference arises in the melanocyte density

at different sites of the body [7].

Melanocytes possess a dedicated membrane bound ovoid

organelle called melanosome to synthesize and store the

pigment melanin. Melanocytes transport the melanosomes

through their elongated dendrites to the neighbouring keratinocytes [8] as shown in fig 1. These keratinocytes with


Fig 2: The pathway indicates the biosynthesis of melanin

from the precursor tyrosine. The regulatory enzymes involved in this biochemical pathway of eumelanin and pheomelanin

synthesis includes tyrosinase, DOPA chrome tautomerase

(DCT) and tyrosinase related protein 1 (TYRP1).

the ingested melanosomes proliferates from the suprabasal

epidermal layer to the skin surface. The ingested melanosome

forms a critical barrier/shield on the DNA by forming

supranuclear caps to exhibit photoprotection [9].

There are two types of melanin pigments produced in the

body. They are pheomelanin and eumelanin. The light red or

yellow coloured, alkali soluble sulfur containing pigments

predominantly seen in red hair or in freckles phenotype is pheomelanin [10]. Eumelanin is of two types either in dark

black or dark brown colors which are insoluble, found in the

dark skin and black hair [11]. Human skin contains all the

pigments in varying ratios, which determines the race /

ethinic groups. The ratio is unique to the individuals and

hence forms the body image.

Regulation of melanogenesis is a complex process and it

involves the expression or suppression of more than 125

genes directly or indirectly [12]. The regulation involves

various steps which includes the expression of enzymes

essential for the synthesis of melanin, structural proteins for the formation of melanosome, the membrane bound

transporters for the import of substrate tyrosine to the spot of

synthesis and the signaling proteins for the trafficking of

melanosomes thereby resulting in the distribution of melanin

in the skin [13].

Tyrosinase is the key enzyme which catalyses the initial rate

limiting step of melanin biosynthesis. It catalyses the

hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine

(DOPA) and the subsequent oxidation from DOPA to DOPA

quinone [14]. The DOPA quinone spontaneously cyclizes to

form DOPA chrome. DOPA chrome is the precursor for the

formation of dark/brown melanin called eumelanin [15]. The

enzyme DOPA chrome tautomerase (DCT) acts on DOPA

chrome and forms 5,6-dihydroxyindole-2-carboxylic acid

(DHICA).the DHICA is acted upon by tyrosinase related

protein 1 (TYRP1) and forms eumelanin as shown in fig 2

[16].

The DOPA chrome loses its carboxylic acid group, oxidised

and polymerises to yield eumelanins [17]. This reaction is

also catalysed by TYRP1. In presence of aminoacids like

glutathione/cysteine, the DOPA quinone is converted into the

cysteinyl DOPA and further oxidation results in pheomelanin

[18]. Mutations in any of or all the key regulatory enzymes

like tyrosinase/DCT/ TYRP1 will dramatically affect the

quality and quantity of the melanin synthesized [19].

2.2. Skin whitening actives- screening approaches:

There are various approaches used by the scientific

community to screen the natural or synthetic molecules with

skin lightening property. The tyrosinase enzyme isolated from the microbial/mushroom/ cell line sources were

incubated with the molecule of interest for examining the

skin whitening property through the tyrosinase inhibition

[20]. The s.bikiniensis culture or the B16 melanoma cells

were used as a model system to screen the potent molecules

with pigmentation inhition efficiency [21]. The co-culture of

melanocytes and keratinocytes from mouse or human skin

acts as a skin equivalent model which mimics the in-vivo

system for testing the skin whitening agents [22]. The

establishment of brownish guinea pig model through the

exposure to UV radiation or by the injection of α-melanocyte stimulating hormone (α-msh) was the in-vivo model used to

screen the molecules with potent skin whitening property

[23].

2.3. Skin whitening actives-a survey:

The potent skin whitening actives used by the cosmetic

industries and well known in the literature are reviewed in

this section.

2.3.1. Licorice extracts:

Licorice (Glycyrrhiza glabra) contains the battery of

secondary metabolites that suppresses the skin pigmentation

system [24]. The actives in the licorice extracts are glabridin, glabrene, isoliquiritigenin, licuraside, licochalcone a,

liquiritin and its iso form. Most of these compounds exhibit

the skin whitening property through one way or the other.

The compounds like glabridin, glabrene and others exhibit

the tyrosinase inhibition in the melanoma cells, whereas

liquiritin has no effect on tyrosinase; however it causes the

skin whitening through alternate route [25].

2.3.2. Mulberry:

The mulberry plant (Morus alba) is the reservoir of various

class of compounds. It contains the phenolic compounds

such as gallic acid, quercetin and the fatty acids like linoleic


acid and palmitic acid. The active component in these leaves

are Mulberroside F (moracin m-6,30-di-o-beta-d-gluco-

pyranoside), which showed the tyrosinase inhibitory activity

and the inhibition of melanin formation in melanoma cells

[26]. These compounds are the potent antioxidants which

inhibit the autooxidation of unsaturated fatty acids and nullify the toxic effect of superoxide radicals.

2.3.3. Aloesin:

The plant genera aloe is rich in the metabolite aloesin.

Aloesin inhibits the tyrosine hydroxylase and DOPA oxidase

activities of tyrosinase from human, mushroom and murine

sources in a competitive fashion. The tyrosinase inhibition

and the photoprotection properties of the aloesin in the in-

vitro & in-vivo system are in a dose dependent manner [27].

The noncompetitive and competitive inhibitors such as

arbutin and aloesin shows synergestic effect on tyrosinase

inhibition.

2.3.5. Hesperidin: The citrus fruits, its peel and the membrane are rich in the

bioflavonoid called hesperedin. The studies documented

reveals that the hesperidin inhibits the melanogenesis without

cytotoxicity in the b16 melanoma cells and human primary

melanocytes. Hesperidin protects the fibroblast and the

collagen fibrils from the UV induced oxidative damage [28].

Thus, hesperidin actively exerts skin whitening property and

thereby improves the skin tone [29].

2.3.6. Bioflavonoids & polyphenols: Bioflavonoids can be divided into flavones, flavonols,

isoflavones, and flavanones. Flavones such as eriodictyol, naringenin have the structure similar to hydroquinone, where

they exhibit a competitive inhition on the active site of

tyrosinase. The cranberry juice and grape seeds are the richest

sources of proanthocyanidins or procyanidins. They possess

potent antioxidant activity than vitamin C or E [30]. The

ellagic acid and ginseng p-coumaric acid are the potent

tyrosinase inhibitors.

3.0. Anti-acne:

Acne is a common skin disorder that affects almost all the

individuals at least once during their lifetime. The occurrence

of acne peaks in the teenage but generally affects the people in the age group of 20-40 years. Acne can have important

negative psychological consequences for the affected

individual, with diminished self-esteem.

3.1. Mechanism of acne formation:

The levels of steroid hormones are peak in teenage

which results in the enhanced production of sebum by

increasing the size and activity of sebaceous glands. This

excessive sebum acts as an excellent culture medium for the

growth of the obligate ananaerobic skin pathogen

Propionibacterium acnes [31]. The triglycerides of sebum is

acted upon by the enzyme from the p.acnes called lipase.

Fig 3: The healthy hair shaft with balanced sebaceous

secretion with no inflammation. Infection with the organism

Propionibacterium acnes triggers the inflammation resulting

in the inflamed hair shaft with excessive sebaceous secretion.

Lipase hydrolyzes sebum triglycerides into glycerol and free

fatty acids. In addition to the chemotactic factors released by

p.acnes, the free fatty acids released from the lipase action, is

metabolised to give proinflammatory cytokines [32]. These factors attract the neutrophils to the follicle resulting in the

early inflammatory lesions of acne (fig 3). The aerobic

organism namely Staphylococcus epidermidis, is usually seen

in superficial infections within the sebaceous unit. This

finding defines the role of staphylococcus epidermidis in the

formation of acne.

The increase in sebum also results in a relative deficiency of

linoleic acid within the follicle and stimulates the follicular

keratinization. Thus, the principal factors like excess

secretion of sebum, microbial infection, altered follicular keratinization and inflammation results in the pathogenic

state called acne vulgaris. The severity of inflammation in the

acne spot is highly influenced by the microbial factors like

Propionibacterium acnes and Staphylococcus epidermidis

than any other. Hence, Propionibacterium acnes and

Staphylococcus epidermidis are the main target sites for

antiacne drugs.

3.2. Anti-acne actives – screening approaches:

All the antibiotics and antibacterial actives currently in the

market are not highly effective against the above said

pathogens. Hence, paves the scope for screening the actives with potent anti-acne activity. The approaches used are the

traditional methods for screening the antibacterial activity.

i.e., Kirby bauer method to find the zone of inhibition exerted

by the active against bacterial growth. Once the active exerts

the effective zone, the effective concentration required to


inhibit the bacterial growth is found by minimum inhibitory

concentration (MIC) test. The enzyme lipase extracted from

the microbial sources acts as the molecular targets for the

anti-acne drugs. Hence, the lipase inhibition assay is also

carried out to identify the potent drugs using high throughput

screening methods.

3.3. Anti-acne actives- a survey:

The effective anti-acne herbs well known in the literature are

reviewed in this section.

3.3.1. Azadirachta indica:

Azadirachta indica (neem) leaves exhibit the antiacne activity

against the organisms like P.acnes and S.epidermidis.

Inflammatory mediators like reactive oxygen species (ROS)

and pro-inflammatory cytokines (interleukin-8 and tumor

necrosis factor-α) were released by P.acnes, which play a

significant role in acne pathogenesis. The anti-inflammatory role of Azadirachta indica in the acne environment is proved

by treating the polymorphonuclear leukocytes (PMNL) and

monocytes with the culture supernatant of P.acnes in the

presence and absence of herb. It was found that Azadirachta

indica significantly suppresses P.acnes induced ros and pro-

inflammatory cytokines [33]. Based on such promising

results, the herb is used in antiacne creams.

3.3.2. Momordica charantia:

Momordica charantia (bitter melon) is one of the very

common Indian herb having various medicinal properties

used in traditional system for treating skin diseases like psoriasis, leprosy etc., antimicrobial activity of bitter melon

fruit against P.acnes and S.epidermidis was examined. The

antiacne potential of Momordica charantia may be due to its

antibacterial and anti-inflammatory efficacy.

3.3.3. Eucalyptus globulus: The antiacne potential of Eucalyptus globulus and the

chemical constituents in the eucalyptus volatile oil

responsible for the antiacne efficacy has been examined by

Athikomkulchai et al., (2008). The study reveals that the

possible inhibitory effect against acne may be due to the

presence of the major component in the volatile oil namely gamma-terpinene. It is a monoterpene that plays an important

role for its antibacterial activity [34]. It might cross the cell

membranes, thus penetrating into the interior of the cell and

interacting with intracellular sites critical for antibacterial

activity.

3.3.4. Psidium guajava:

The essential oil of guava exhibits antibacterial activity

against wide range of bacteria including Propionibacterium

acnes. The antimicrobial activity of Psidium guajava

determined by disk diffusion method was compared to tea

tree oil (tto), doxycycline and clindamycin antibiotics. The

Fig 4: Hair growth is a cycle of events with the phases like

anagen (growing phase), catagen (involuting phase) and telogen (resting phase). All the hair shaft passes these phases

once in its life cycle. Once after the telogen phase, the hair

follicle is stimulated to enter the anagen phase.

zone of inhibition was significantly higher than those of tto

but less when compared to doxycycline or clindamycin [35].

From these studies, it can be concluded that Psidium guajava

may be beneficial in treating acne especially when they are

known to have anti-inflammatory activities.

3.3.5. Juglans regia:

The medicinal property of the walnuts and the leaves of the

cosmopolitan tree Juglans regia l. Is well known. The insecticidal and bactericidal properties of the leaf extracts of

J. Regia have been reported. The antiacne activity of Juglans

regia was confirmed by testing its efficacy against P.acnes

and S.epidermidis. The organisms were isolated from the

acne lesions of female and male human volunteers and

cultured for the growth of acne causing bacterium in presence

of the herbal extract [36]. The results evidenced that the

bacterial growth inhibitory property was higher in walnut leaf

extract. Thus, the plant extract acts as the potential antiacne

agent.

4.0 Hair growth:

Hair is an important feature of body image due to the unique

styling interest of the individuals. The loss of hair will affect

psychologically with the symptoms of social withdrawal due

to embarrassment and depression. In order to address the hair

loss issues with herbal remedies, the basic understanding of

the hair growth cycle and its deviation in the disease

condition called aloepecia needs to be understood [37].

4.1. Hair growth cycle:

Hair growth cycle is similar to the cell cycle. Each hair seen

in the comb has to pass through the different phases of hair

growth cycle, which are described in the below section.


Fig 5: The excess of the male hormone dihydrotestosterone

(DHT) will ultimately result in the hair loss. The condition is

called male pattern baldness. The binding of DHT to the hair

follicle shortens the growing phase and results in

miniaturizing the hair length.

4.1.1. Anagen phase - growth phase: Approximately 85% of

the hairs are in the growing phase at any one time. The

anagen phase or growth phase can vary from two to six years.

Hair grows approximately 10cm per year and any individual hair is unlikely to grow more than one meter long [38].

4.1.2. Catagen phase - transitional phase: At the end of the

anagen phase, the hairs enters into a catagen phase which

lasts about one or two weeks, during the catagen phase the

hair follicle shrinks to about 1/6 of the normal length [39].

The lower part is destroyed and the dermal papilla breaks

away to rest as seen in fig 4.

4.1.3. Telogen phase - resting phase: The resting phase

follows the catagen phase and normally lasts about 5-6

weeks. During this time, the hair does not grow but stays

attached to the follicle while the dermal papilla stays in a

resting phase. Approximately 10-15 percent of all hairs are in this phase at one time [40].

At the end of the telogen phase, the hair follicle re-enters the

anagen phase. The dermal papilla and the base of the follicle

join together again and a new hair begins to form. If the old

hair has not already been shed, the new hair pushes the old

one out and the growth cycle starts all over again.

The excessive androgenic hormones and the genetic

predisposal are the main causes for the male pattern baldness.

The dermal papilla is fundamental for the maintenance of hair

growth and is the probable target for androgen-mediated

changes in the hair cycle resulting in the miniaturisation of the follicle (fig 5). The follicular miniaturisation affects the

papilla, the matrix and ultimately the hair shaft [41].

The excessive androgenic hormones (5α-dihydrotestosterone

(DHT) bind to the hair root and acts via the second

messengers. This alters the hair growth cycle phases. In

aloepecia, the period of anagen phase is so short that the

emerging hair does not reach the skin surface. The presence

of pore is the only evidence for the functioning follicles. In addition, the latency period between telogen hair shedding

and anagen regrowth becomes longer, leading to a reduction

in the number of hairs present on the scalp [42].

4.2. Hair growth promoting herbs – screening approaches:

The hair growth promotion efficacy of the herbs can be

screened by attacking two targets. One is the hair follicle

proliferating potential of the herbs in the in-vitro cultured

model of the hair follicles [43]. The other is reducing the

turnover of the androgen DHT in the hair follicles by

inhibitng the enzyme 5α-reductase. It is an enzyme that

converts the androgenic hormone testosterone to DHT. The

prevalence of DHT and the 5α-reductase in the bald scalp is high compared to a normal scalp [44]. Through in-vitro

follicle culture and the inhibition of 5α-reductase is

monitored for the high throughput screening of the herbs with

potent hair growth promoting property.

4.3. Hair growth promoting herbals- a survey:

The herbs with potent hair growth promoting property known

in the literature and used traditionally are reviewed in this

section.

4.3.1. Hibiscus rosasinensis:

This is a glabrous shrub widely cultivated in the tropics. It is

well documented in the ayurvedic and siddha system of medicine. The leaves and flowers of Hibiscus rosasinensis

have hair growth promoting and antigreying properties. In

India, the herbal products in the market intended for hair

growth include the extract of various parts of Hibiscus

rosasinensis. The leaf extract of this plant has a potential

effect on maintaining the hair growth, are scientifically

validated in the in-vivo and in-vitro model systems [45].

4.3.2. Cuscuta reflexa: It is commonly distributed in tropical, temperate region and

found throughout the Indian subcontinent. It is a leafless,

twinning, parasitic dodder with slender long yellow stems. It is commonly known as amarbel. The Cuscuta reflexa stem

enhances the hair growth by transforming the hair follicle

from telogen to anagen phase on a periodic basis [46].

4.3.4. Asiasari radix:

The root/ rhizome of Asiasarum heterotropoides (belongs to

the family aristolochiaceae) is called Asiasari radix. The

plant extract has hair growth promoting potential, which is

exerted due to its regulatory effects on the expression of

genes that codes for cell growth factor [47].


Fig 6: The henna leaf powder in the form of a paste is applied

on to the hair bundle. The brown colored lawsone molecule from the paste penetrates into the hair shaft and imparts the

brown color to the cuticle of the graying hair.

4.3.5. Ocimum gratissum: It is a herb well flourished throughout India. The essential oil

of Ocimum gratissum leaf (Ocimum oil) has been

investigated for promoting the hair growth in

cyclophosphamide-induced hair loss. The study results

support that the ocimum oil is capable of enhancing the

normal hair growth and promoting follicular proliferation in

cyclophosphamide-induced hair loss [48].

4.3.6. Ginseng radix: This herb is known from the ancient days for improving the

poor body condition, to promote appetite, to increase vitality

and to reduce over sensitivity to cold. It possesses hair

growth promoting activity through one of its potent active

constituent namely g-rb1 in mouse vibrissal hair follicle

organ culture model [49].

5.0. Hair colours:

The hair graying is the natural phenomena happen when the

individual is chronologically aged. The graying of hair

becomes prevalent even in the young age these days due to

various reasons. The graying of hair affects the self-esteem of

the individuals’ results in the poor presentation of themselves in the personal and professional life. Even though the

synthetic hair dyes are well known for their side effects, they

are used to address these issues. Hair colouring with various

coloured dyes becomes the integral part of unique hair styling

which is prevalent among the youngsters these days.

Prospecting the nature for the colours/dyes to style the hair

with nil side effects reveals the scope. Hence, the current

section describes the colouring of hair using natural herbal

active lawsone and reviews the other colours available in

nature for the hair applications.

5.1. Mechanism of hair colouring using lawsone: The lawsone is the secondary metabolite present in the leaves

of the plants such as Lawsonia alba, Lawsonia spinosa and

Lawsonia inermis (henna). Lawsone is responsible for

imparting the red colour to hair when applied as paste. The

compound is also found in the plant Juglans regia (walnut).

When the henna paste is applied on the hair shaft, the

lawsone molecule penetrates inside the hair shaft and binds with the keratin fibre. When the light bounce on the henna

applied hair, the lawsone molecules in the outer layer of the

hair shaft shimmers / reflects the light in such a way to

present the hair to be in red colour [50]. The hair colouring

mechanism of lawsone is shown in fig 6.

The use of henna for dyeing the hair and nail is known in the

practice for more than 5000 years.

The content of lawsone in the henna makes it a substantive

dye for keratin in the acidic medium. The dye is formed

within the hair and not as a coating as in the case of other

metallic dyes. Henna is quite innocuous and very few cases of allergy have been reported for its use in hair and nail.

5.2. Natural hair colours – screening approaches:

The various parts of the herbs or trees were collected and

immersed in the hydrophobic and hydrophilic solvents to

extract the colouring material based on its solubility. The

extracts were spotted on the thin layer chromatography.

Based on the colour and intensity of the bands, the coloured

materials are eluted through column chromatography and

concentrated. The concentrated colors were applied to the

greyed hair / black hair and the integrity of the colour to hair

shaft is measured using minolta spectrophotometer [51].

5.3. Natural colours for hair- a survey:

The current section reviews the colours from the natural

origin which have the scope to be used in hair styling.

5.3.1. Indigotin:

The dye indigotin is a blue to mauve colour, extracted from

the fermented leaves of the plant Indigofera tinctoria (was

also known as Pigmentum indicum). The indigo dye is found

in the numerous indigofera species which is a glucoside

component namely indican. The blue dye indigotin is

obtainted by the enzymatic treatment of the glucoside

indican. This dye is quite colourful and mixed with other color components to produce a wide range of colorants. It is

also used in the treatment of mouth and infected ulcers.

5.3.2. Juglon:

The plant species like Juglans cinerea, J. Regia, J. Nigra

(butternut, walnut, black walnut) are the resources for the

class of naphthoquinone compounds including juglone and

juglandin. Juglon is a yellow-brown colour and referred as

juglandic acid or nucin. The hulls of the nut contain dark

colorant which is used in the colour ranging from pink,

brown to dark brown.


Fig 7: The epidermis and the dermis layer of the male and

female skin are similar. The arrangement of subcutaneous /

adipose tissue in male is rigid, where as the circular shape in

the females facilitates the cellulite deposition.

5.3.3. Lapachol:

Lapachol is a yellow crystalline material belongs to the class

of naphthoquinone compound isolated from the heart wood of the plant Tabebuia avellanedae belongs to the family

bignoniaceae. It is reported for the medicinal properties like

anti-ulcers, anti-inflammatory, antiseptic, antiviral,

bactericidal, fungicidal, insecticidal, pesticidal and viricidal.

5.3.4. Pratol:

The natural colorant pratol is extracted from the plant

Trifolium pretense (clover). Pratol is chemically named as 7-

hydroxy-4’-methoxyflavone, which is a dull, golden yellow

in shade. Clover has been traditionally used in treating the

eczematous skin conditions, boils and pimples.

It is known from the literature that the occurrence of pratol in the yellow sweet clover botanically named as Melilotus

officinalis. The flower heads are used externally in the

treatment of ulcers, burns, sores and skin complaints.

5.3.5. Sanguinarine:

Sanguinarine is a quaternary ammonium salt belongs to the

group benzylisoquinoline alkaloids extracted from the plants

like Sanguinaria canadensis (bloodroot), Argemone

mexicana (mexican prickly poppy), Chelidonium majus and

Macleaya cordata. It is also found in the root, stem and

leaves of the opium poppy. Sanguinarine, an alkaloid

extracted from dried rhizome sanguinaria canadensis, is used

as an anti-plaque agent in toothpaste and mouthwash preparations.

6.0. Cellulte reduction:

The term “cellulite” is originated from the french medical

literature. The synonymous meaning for cellulite is adiposis,

edematosa, dermopanniculosis, deformans, status protrusus

cutis, and gynoid lipodystrophy [52]. It is most commonly

seen in the post pubertal females and rarely seen in males

[53]. Cellulite is the orange peel or cottage cheese type

dimpling of skin seen most commonly on the thighs and

buttocks. Cellulite can be located in any area of the body that

contains subcutaneous adipose tissue. This excessive deposit of fat on one or more susceptible spots gives irregular

physical appearance resulting in the distress of the

individuals.

Fig 8: The source of triglycerides for the extracellular

medium is diet. The enzyme lipoprotein lipase located on the

walls of adipose tissue cleaves the triglyceride to free fatty

acids and glycerol. These lipolytic products are taken up and

stored as triglycerides in the adipocytes.

6.1. Physiology of cellulite:

The main factors purport to explain the physiology of

cellulite includes sexually dimorphic skin architecture, altered connective tissue septae and vascular changes [54].

The anatomy of the adipocytes or layer of adipose tissue

organized beneath the skin is different for the man & woman

as indicated in the fig 7. The shape of the adipocytes in the

females facilitates the elastic expansion and prone them to

cellulite accumulation.

The altered connective tissue septa facilitate the skin

dimpling because of the continuous and progressive vertically

oriented stretch within the hypodermal collagen fibrous

strands [55]. A process that weakens the connective tissue

buttress and allows for fat herniation. The accumulation of fat

in the adipose tissue is enzyme dependent which is the key biotarget for the cellulite reducing herbs (which is discussed

in following section).

6.2. Cellulite reduction – screening approaches:

As it is known that adipose tissue is a specialized cell type

which stores the excessive fat beneath the skin. But the

excessive fat in the blood is in the form of lipoproteins (a fat

transporter protein) that transports the triacylglycerol from

liver and intestine to the adipose tissue. Unfortunately

adipose tissue lacks the triacylglycerol transporter protein on

the cell surface. Instead they are equipped with the membrane

bound enzyme called lipoprotein lipase which cleaves the triacyl glycerol into free fatty acids and glycerol as shown in

fig 8.

The liberated free fatty acids and glycerol enter inside the

adiposites and esterified to triacylglycerol to be stored in

[56]. Hence, by blocking the activity of the enzyme

lipoprotein lipase results in preventing the storage of excess

fat which reflects as reduced cellulite [57]. Thus, lipoprotein


lipase becomes the target for screening the herbs with potent

cellulite reducing property.

6.3. Cellulite reducing - herbs survey & scope:

There are lots of physical and mechanical methods like

endermologie, liposuction and subcision are available these

days for cellulite reduction. Because of the cost and complications involved in these treatments, topical therapies

are preferred. Although, there are numerous topical

treatments are available over the counteract pharmacies, spas

and boutiques, there are no large scale clinical studies

demonstrating the effectiveness of these therapies [58].

Currently, two agents namely aminophylline and retinoids

have been critically evaluated. In the herbal plat form, it has

been reported that the extract of the plant Hibiscus sabdariffa

has shown potent lipoprotein lipase inhibition [59].the

clinical efficacy of the herbal extract needs to be evaluated.

This knowledge gap opens up the scope of prospecting the

herbs to reduce the cellulite.

7.0. Conclusion

Various herbal extracts were screened for their cosmetic

benefits using multiple biochemical approaches in order to

establish the inherent potency of the herb. Once the extract/

the compound passes via robust biochemical filters, the

commercialization comes in picture. The quantity of herbal

material required to commercialize the personal care products

with the incorporated potent herbal extract is high.

It is unethical to exploit the wealth of nature for

commercialization, will result ultimately in the disturbed

ecosystem. As mahatma gandhi stated “nature can feed your need; not your greed”, is applicable here. The utilization of

the herbs available from the nature for commercialization will

come to end upon the extinction of the herbal species one

day. Hence, there arises the use of biotechnological tools for

the sustainable growth.

The mass cultivation of the specific herbal material

based on the geographical and seasonal conditions

through contract farming will result in the bulk

availability of herbal species for commercialization.

Tissue culture of the potent herbal species and isolating the active component from the cells will yield the

purified active which can also be incorporated in

cosmetic formulations for delivering the expected

benefit.

Rapid advances in structural biology and computer

technology, structure-based computer-aided drug design

(CADD) using docking techniques, virtual screening

and library design, along with target/structure focusing

combinatorial chemistry, has become a powerful tool to

minimize the time period required for screening the

novel potent candidates [60]. Based on these studies,

the synthesis of such compound will result in the

availability of molecules in bulk for commercialization.

8.0. Scope of prospecting in cosmetics:

The discussions in the earlier sections on skin whitening,

antiacne, hair growth promoters, herbal hair colours and the cellulite reduction are encouragive in prospecting the herbs

with potent cosmetic benefits. The light needs to be thrown in

the areas like antidandruff, antiwrinkling, antilice, skin

moisturisation and sebum control where in the personal care

industry is running short of the effective leads [61]. Hence,

there is a wide scope for prospecting the herbs with potent

cosmetic benefits.

9.0. Acknowledgement

The authors thank Mr. Sandeep Kaul (CEO- PCPB) and Dr.

Venkat Krishnan (Chief scientist – PCPB) for supporting this

work.

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Source of support: Nil; Conflict of interest: None declared

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