Introduction: and toothpastes etc. that have been

Introduction:

The number of molecules in nature can be
considered virtually unlimited, thanks to the various possible combinations of
the arrangement and rearrangement of the atoms. Since the year 1800 thru the
first half of 2015, over 101 million organic and inorganic molecules had been
revealed and assembled globally, numerous of which produced by natural,
synthetic and biosynthetic mechanisms of chemical engineering (1). This number,
however, seems to be only a fraction of the molecular universe, yet unexplored,
of our planet. Throughout the ages mankind has benefited from natural medicines
to treat or prevent a broad spectrum of diseases. Indeed, secondary metabolites
from plants, microorganisms and marine products have been long considered as
valuable sources of novel molecules with potential for drug development in
numerous biomedical areas (2). To date, a very high number of conditions
affecting the oral health can be prevented, ameliorated and/or treated with the
use of natural product (NP)-based drugs or formulations. There is a long list
of NP-derived and NP-inspired drugs (3), mouthwashes, and toothpastes etc. that
have been available over the counter or under prescription. Longer yet is the
list of reasons why the search for novel treatment modalities should not cease.
Microbial resistance, short- and long-term toxicity, adverse and side effects,
high costs for the end user, compromised sustainability of industrial
large-scale production, among many others.

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Furthermore, the consumer
demand for nutritional, medicinal and cosmetic products derived from natural
sources has been increasing in last decade. Accordingly, the industry of
natural products has consecutively been growing. Back the middle 1970s, natural
products industry represented an estimated US $2.4 billion/year. In 2011, it
was value at US $91 billion/year with a growth rate of 7.4% from the previous
year in the global sales 8, 9. Particularly, natural cosmetic products has
an annual growing of 9-10% across Europe, North America and Asia Pacific
regions with US $8.2 billion in sale in 2013 10, 11.

The renewed consumer interest
in natural cosmetic products has also sparked the increase of research in field
of medicinal, aromatic and cosmetic (MAC) plants extracts to use and/or take
advantages from them in health and cosmetic care products 12. The discovery
of the biological properties of natural sources and derivatives allows the
formulation of new bioactive products that contribute to health, beauty and
wellness of humans, and add value to products marketed 12–14.

According to the European
Union (EU) Cosmetics Regulation, anything which can perform the followings for
external parts of the human body (epidermis, hair system, nails, lips and
external genital organs), teeth and mucous membranes of the oral cavity in
order to cleaning them, perfuming them, changing their appearance and/or
correcting body odors and/or protecting them or keeping them in good condition
can be classified as cosmetic products 15. Opposing to the European
legislation, Food and Drug Administration (FDA) considers that sunbath
products, moisturizers and makeup marketed with sun-protection claims,
skin-whitening products, anti-wrinkle products, antidandruff shampoos,
toothpastes that contain fluoride, deodorants that are also antiperspirants,
and cosmetic textiles are drugs, since these products include one or more
compounds with biological activity and/or affect the body’s structure or
functions 16, 17.

Cosmetics can be grouped in 7
categories: skin care and maintenance; cleansing; odor improvement; hair
removal; hair care and maintenance; care and maintenance of mucous membranes;
and decorative cosmetics 18. Though not consensual, textile cosmetics can be
a skin care cosmetic 19, 20. The cosmetic properties of aromatic plants,
especially as fragrance, are attributed to essential oils (EOs) and extracts.
Hence, EOs are normally an ingredient present in all categories of cosmetic
products 21.

Over the
centuries herbs had been used as medicines and cosmetics. Their prospective to cure
diverse skin ailments, to embellish and increase the skin look is greatly
documented. Ultraviolet (UV) radiation can be a reason behind sunburns,
wrinkles, lower immunity against infections, premature aging, and cancer. There
is a stable requirement for defense mechanism against UV radiation and
deterrence from its side effects. Natural herbs and their herbal preparations can
have a high potential due to their inherited antioxidant activity. Antioxidants
such as vitamins (vitamin C, vitamin E), tannin, flavonoids, and phenolic acids
play the key role in fighting against free radical species that are the core
source of many negative skin variations. Though sequestered plant compounds
have a high probable in protection of the skin, whole herbs extracts had shown
better potential due to their multifaceted alignment. Earlier studies had shown
that green and black tea (polyphenols) ameliorate adversative to the skin
reactions for UV exposure. The gel from aloe-vera is believed to stimulate skin
and assist in new cell growth. Review covers all essential aspects of potential
of herbs as radioprotective agents and its future prospects 7. Phenolic compounds are secondary plant
metabolites, produced in response to different stresses such as infections, wounding,
ultraviolet (UV) irradiation, ozone, pollutants, etc. The
anti-inflammation, inhibit tumor growth, pro-apoptotic and anti-angiogenic
actions, antimicrobial, antiviral, and antiaging properties, modulate the
immune system, increase capillary resistance, protect the cardiovascular and
neurological systems, limit weight gain, promote wound healing, etc can be
achieved by using single type of secondary metabolite i.e. flavonoids. Polyphenolics
are used in numerous sectors of the food and cosmetic industry as natural
additives (natural coloring agents, conservative agents, natural antioxidants,
nutritional additives) 24. Polyphenols currently contributes on their bioavailability, antioxidative and
anticarcinogenic properties. Polyphenols protective role can be seen against
reactive oxygen and nitrogen species, UV light, plant pathogens, parasites and
predators. It results in several beneficial biological activities giving rise
to prophylaxis or possibly even to a cure for several prevailing human
diseases, especially various cancer types. Omnipresence, specificity of the
response and the absence of or low toxicity is crucial advantages of polyphenols
as anticancer agents. The main problem represents their low bioavailability and
rapid metabolism. A very common process of solution is the use of mixtures of
various polyphenols that bring synergistic effects, resulting in lowering of
the required therapeutic dose and in multi targeted action. Existing drug and
polyphenols combination therapies also shown a promising output with
significantly lower toxicity 25.

EOs are a complex liquid
mixture of volatile, lipophilic and odoriferous compounds bio synthesized by
living organisms, predominantly aromatic plants 29. The major plants families
from which EOs are extracted include Asteraceae, Myrtaceae, Lauraceae,
Lamiaceae, Myrtaceae, Rutaceae and Zingiberaceae, the dicotyledonous angiosperm
plant families. They are secondary metabolites produced in cytoplasm and
plastids of plant cells 22 and stored in secretory cells, cavities, canals,
epidemic cells or glandular trichomes 27. Present in different parts of the
plants (buds, flowers, leaves, stems, twigs, seeds, fruits, roots, wood, bark,
or rhizome), EOs are usually extracted by processes of steam distillation,
solid phase extraction, cold pressing, solvent extraction, supercritical fluid
extraction, hydro distillation 13, 23, 27, or simultaneous
distillation-extraction 28, 30. Among cosmetics, the EO are mainly used in
perfumes, and skin and hair care products 23. In the global beauty
market,  skin care products, most
valuable category, accounting for 23% value share of total sales in 2009 34.
However, EOs have a short shelf life, since they are volatile and reactive in
presence of light, heat, moisture, and oxygen. To overcome these challenges,
microencapsulation has been considered as one of the most effective techniques
26. Furthermore, microencapsulation provides the controlled-release delivery
and improves the handling of the EOs 35.

Although EOs include
substances with distinct organic functional groups, such as alcohols,
aldehydes, esters, phenols, hydrocarbons, EOs are mostly monoterpenes,
sesquiterpenes and diterpenes 31. 300 of approximately 3000 EOs produced by
using about 2000 plant species are commercially important. Their characteristic
flavor and fragrance properties, as well as various biological activities, have
been increasingly studied and reported in the scientific literature. In
cosmetic products, EOs play a major rule as fragrance ingredients 32.
However, additional properties of EOs may be very capable and fascinating for
cosmetics products, for example EOs with antibacterial or antifungal activities
countenance reducing the use of preservatives components in a product 33.

However, a systematic review undertaken by
Freires IA group (4) revealed that 22 and 40% of the studies on the anti-caries
activity of essential oils, natural products and their isolated constituents do
not report any chemical and botanical characterization data, respectively.

This issue has raised concerns not only about
the scientific validation of the findings reported but also because this could
create a gap between the in vitro and in vivo bioactivity identified and an
effective use of that information to develop novel drugs or formulations with
advantageous clinical efficacy and safety in humans. Although 49% of the new
chemotherapeutic drugs and 73% of the new antibacterials approved by the US
Food and Drug Administration are NP or NP-derived drugs (3), a tremendous
number of herbal molecules do not reach the minimum requirements to be tested
in and used by humans, particularly for oral care product development. Apart
from the biological effectiveness of the molecule itself, in several cases this
is a result of poorly designed, superficial basic research that does not
provide consistent evidence to support the clinical testing of NP and derived
molecules. Jeon et al. (5) pointed out that most studies in caries research
have focused on general aspects (microbial inhibitory effects) rather than
addressing the actual pathophysiological aspects of the disease, which is
biofilm-dependent and involves physicochemical processes of tooth de- and
remineralization. It seems consensual that there is a persistent need for more
potent, effective, low-cost, safe and well tolerated drugs and oral care
formulations in dentistry, skin care formulations in cosmetics. As the years go
by, a high number of studies concerning bioactivity of plant extracts and isolated
molecules with clinical interest have been published worldwide. There have been
reports on antibacterial, antifungal, anti-inflammatory, antinociceptive,
saliva stimulant, anti-halitosis, anti-caries, anti-ageing, anti elastase, low
telomerase affectivity etc.
properties of the most diverse plant materials and molecules nature can
provide.

Hence, the precise mechanisms of action and
effectiveness of the tested extracts/compounds remain fatally unknown until
further research—if relevant—is carried out. Another critical limitation lies
in the non-use of modern methods and technology, including bioinformatics,
identification of molecular targets in the human genome (6), high-throughput
screening and appropriate statistical models, among others. These tools allow
the researcher to comprehensively characterize the extract, fraction or
molecule prior to clinical testing concerning bioactivity, local or systemic
toxicity, pharmacokinetics and pharmacodynamics. As such, they may provide
consistent evidence on natural product effectiveness and safety along with
reduced financial burden and risk of failure at further stages.

India have a big spectrum of diverse phytodiversity
comprising plethora of medicinal plants like Turmeric, Manjistha, Chironji, Mulethi, Pudina, Tulsi, Neem, Aloe-vera,
Clove, Cinnamon, Bhringraj and Coleus etc.
These plants are been used since time immemorial to treat and cure many
diseases. Some of them also been used for beautification of human being
suggesting to the potential candidacy towards cosmetics. The isolation and
identification of the specific phytochemical molecules remain as a biggest
hurdle till today. The challenge get multifold when it’s being assigned to
determine the structure of novel molecule and assigning bioactivity against it
thru in vivo and in vitro lab tests.

Given these limitations, what has been the real
impact of natural product research on the oral health care and cosmetic
industry over the last 15 years? How far has research led to novel NP-based
therapeutic modalities to guide decision-making in dentistry and cosmetic
product, is still unknown to the scientific world. Here I propose my thesis
work to bridge the gap between knowledge and formulation of Indian Traditional
Medicinal plants in oral healthcare and cosmetics.

 

 

 

 

 

 

 

 

 

 

Objective:

Keeping these facts in mind, the main objective of
present research is to screen and utilize various Natural Actives & their
Derivatives to formulate personal care products (oral, hair and skin care) and
establishment of their efficacy at in vitro and in vivo so that those can be
translated into cost effective products.

Chapter
I

This chapter briefs introduction to plant sources of
bioactive and their use in Herbal Cosmetic (Personal care) Formulations to
treat many problems related to Skin, Hair and Oral cavity and the importance of
present research work.

Chapter
II

This chapter gives detailed literature survey that
is made on the selected plants Aloe barbedensis, Curcuma longa, Buchanania
latifolia, Glycyrrhiza glabra, Rubia cordifolia, Simmondsia chinensis, Triticum
sativum, Mentha piperita, Syzygium aromaticum, Ammomum sabulatum, Cinnamomum
zeylanium, Ocimum sanctum, Coleus barbatus etc. This chapter also
contains a brief review on above species which includes phytochemical
constituents, biological activities and their use in Herbal Cosmetics (Personal
Care Products).

Chapter
III

This chapter deals with the present work on
Evaluation of Biological Activity of Natural and Synthetic actives and their
synergy in Personal care Formulations (Skin care), identification of bioactive
from various plants Aloe barbedensis, Buchanania lanzan, Phyllanthus niruri, Triticum
vulgare, Curcuma longa, Simmondsia chinensis, Indian rhubarb, Glycyrrhiza
glabra and Rubia cordifolia and evaluation of their Skin Whitening
activity (anti-melanogenesis), antioxidant and anti-ageing activity.

Chapter
IV

This chapter includes details regarding actives used
in Herbal Hair Care Products. Extracts from Aloe barbedensis, Eclipta
prostrate and Plectranthus barbatus were evaluated
for Anti-Hair Graying (Melanin Assay) and Hair growth activity.

 

Chapter
V

This chapter includes details related to actives
used in Herbal Oral Care Products. Extracts from Aloe barbedensis, Syzygium
aromaticum, Ammomum sabulatum, Cinnamomum verum and Ocimum
sanctum were evaluated for anti-inflammatory, anti-gingivitis,
anti-plaque and anti-tartar.

 

Expected
Methodology:

 

1.     
Plant selection and identification.

2.     
Plant extracts preparation, extraction of EOs.

3.     
Collection of standardize Naturals from market.

4.     
Physical and Chemical Analysis

4.a.
Physical tests of extracts and EOs

4.b.
HPLC/UPLC- MS/MS analysis. (Plant Extracts)

4.c.
GCMS analysis.(EOs)

4.d.
Metabolite profiling by LCMS- MS/MS process (optional if only to locate orphan
natural molecules in Extracts)

4.e. Chemical Analysis of
Extracts and EOs for quantification.

5.   Biological Activity (in vitro)

5.a Anti
Microbial Activity against standard Strains.

5.b MIC
test of extracts and EOs

5.c
Enzymatic bioassay of extracts and EOs. (Anti Tyrosinase, Anti Elastase, Anti
Ageing, in vitro hair follicle culture etc)

5.d
Different scavenging activity of extracts and EOs.

5.e DNA
Damage activity of extracts and EOs. (Safety study)

5.f
Comet assay of extracts and EOs. (Safety study)

5.g
Fluorescence based cell sorting for activity of extracts and EOs. (Safety
study)

5.h
Cytotoxicity Test of extracts and EOs. (Acute Toxicity)

6.  Biological
Activity (in vivo)

6.a In
vivo pharmaco-dynamics study.

6.b
Acute toxicity study. (Safety study)

7.  Physical Testing of Plant extracts and their
efficacy on Hair Growth and Health. (FTIR, Scanning Electron Microscopy)

8.  The checkerboard assay
(Synergistic affect test of plant extracts in
formulation)

9.   Statistical Analysis of results for validations.

 

Expected
Outcome

 

Natural product research in dentistry and
cosmetics over the last 15 years has not led to pharmaceutical leads but to a
fairly limited development of oral healthcare products and cosmetic products
for topical use, mainly because of inconclusive chemical testing, scarcity of
clinical trials or poorly designed trials, lack of multidisciplinary and
collaborative work as well as of partnership with and investment of the
industry in this sector. Further research is needed in the fields of toxicology
and clinical pharmacology so that to fulfill the gap between the in vitro and
in vivo potential of novel herbal agents and their clinical efficacy and safety
in humans.

I propose a multidisciplinary exhaustive
research theme including biological activity, chemical identification,
cyot-genotoxical efficacy testing and industrial settings, not only to cover
the technical aspects of sustainability, synthesis and cosmoceutical
preparation, but also to comprehensively address the actual disease mechanisms
and patient’s therapeutic needs.

Indeed, natural products represent a potential
and valuable source of leads for development of oral health care and cosmetic
products to manage oral and tropical diseases. As of now some progress has been
achieved, but there still is a long road to be bridged.

 

CONCLUSION

 

In this work I would like to deliver on the use of plant extracts
and essential oils in cosmetic and oral care industry. The multimillionaire
oral health care and cosmetic industry continues to invest in research and
development of innovative products in order to satisfy the needs of
increasingly demanding consumers for products formulated with natural and
nutraceutical ingredients differentiate from competition and add value to the
product. The use of essential oils and plant extracts as cosmetic and oral health
acre ingredients have several advantages, such as enhancing the cosmetic and
medicinal properties and preservation, and marketing image of the final
product. Although there are many techniques available, a multidisciplinary
cooperation is needed to improve them for its efficient large scale
implementation and take full advantage of this technology. Additionally, it is
important to develop a better understanding about the biological activities of
essential oils and extracts for its safety use in cosmetics and oral care and
the modulation the release of active ingredient.

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