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 have been discovered and
cataloged worldwide, many 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.

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.

Herbs have been used in medicines and
cosmetics from centuries. Their potential to treat different skin diseases, to
adorn and improve the skin appearance is well-known. As ultraviolet (UV)
radiation can cause sunburns, wrinkles, lower immunity against infections,
premature aging, and cancer, there is permanent need for protection from UV
radiation and prevention from their side effects. Herbs and herbal preparations
have a high potential due to their antioxidant activity, primarily.
Antioxidants such as vitamins (vitamin C, vitamin E), tannin, flavonoids, and
phenolic acids play the main role in fighting against free radical species that
are the main cause of numerous negative skin changes. Although isolated plant
compounds have a high potential in protection of the skin, whole herbs extracts
showed better potential due to their complex composition. 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. Extract of Krameria triandra has a major
component octyl methoxycinnamate which can absorbs 25 to 30% of the amount of
UV radiation. Sesame oil resists 30% of UV rays, while coconut, peanut, olive,
and cottonseed oils block out about 20%. A “sclerojuglonic” compound can be
formed from naphthoquinone and it can produce keratin in the reaction that
provides UV protection. Traditional use of plant in medication or
beautification is the basis for researches and making new trends in cosmetics.
This 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 ie 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. One
of the promising solutions lies in nano-formulation of polyphenols that
prevents their degradation and thus enables significantly higher concentrations
to reach the target cells. 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.

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.