IDENTIFICATION OF A BIOMARKER: A NECESSARY APPROACH IN HERBAL INDUSTRY

Introduction

Herbs are different in its own unique way;
each herb has its own physiological,
chemical, biological characteristics with a
unique cultivation method required for
each. Earlier some crops were only
available in regions that were best suited
for it, regions that had high yield and high
active chemical constituents.
But, human beings changed the habitat of
crops and consequently the genes of the
seeds also changed, resulting in an increase
in the chemical constituent content and a
reduction in the growth period of these
plants. Herbal drugs were foremost used in
ancient times for treating various ailments
and these drugs had a rapid onset of action
and targeted specific efficacy. Nowadays,
these herbs do not show such significant
effects in clinical assessments. There are
many reasons that may be causing a
reduction in potency such as spurious
seeds, non-favorable cultivation
environments, usage of toxic chemical
pesticides during cultivation, adulterated or
spurious herbal drugs, inability to identify
the correct solvent for extraction, herbherb
interaction and many more [1]. To
overcome these limitations it is important
to identify biomarkers.. A biomarker helps
to identify a given herb both qualitatively
and quantitatively. Moreover, the
biomarker helps in identifying that the
sample is the same as the prescribed by
comparing with the said standard of the
same species and this process may help in
determining the presence of adulterated or
spurious drugs. A biomarker can be easily
identified by simple spectroscopic
analysis, a cost effective method.[2].

Herbs are also identified by their physical
characteristics (macroscopically and
microscopically), chemical analysis and
other physicochemical parameters [3].
There are many agencies that have
standards available for these parameters
such as the Indian Pharmacopeia (IP),
United States Pharmacopeia (USP),
European Pharmacopeia (EU) and
Therapeutic Goods Administration of
Australia (TGA). Recently, the Department
of Ayurveda, Yoga and Neuropathy, Unani,
Siddha and Homeopathy (AYUSH), under
the Ministry of Health and Family
Welfare(Government of India) has started
developing monographs for herbs and
herbal extracts by collaborating with
different companies such as Green Chem,
Bangalore, India. This will help in setting
up a database that could be used as the
standard for determining the herbs [4]. The
World Health Organization (WHO) has
also given different standards for research
and evaluation in traditional medicine for
different herbs [5].
Herbal fingerprinting

Research on herbal medicine is carried out
to check the consistency, safety, quality,
efficacy and its mode of action. Herbal
drugs have been proved to have
significant drug activity in different
formulations but its consistency is
sometimes questionable. To overcome this
problem some standards need to be
followed in steps such as identifying
required species, maintaining the
consistency of plant source (plant
environment and cultivation pattern),

selecting the season of collection of plant
parts and washing and storing these herbs.
Herbal drugs are generally considered to
be safe due to its natural origin. But, in
today’s world the use of chemical pesticide
and different chemicals for the faster
germination of crops with higher quantity
output is generally preferred to increase
profits. Due to the use of these chemicals
the plant may absorb some of these
chemicals and become toxic and the plant
needs to be checked for its microbial load,
heavy metal analysis and toxicity level and
drug-drug interaction before usage [6]. In
the health care system quality is an
important criterion that has to be
maintained.

WHO has given different standard
monographs of different plant drugs to
maintain the quality standard of a given
plant drug.

Efficacy of a plant extract or a plant drug
depends on the above characteristics of
consistency, safety and quality. Various
analyses should be carried out to know the
effectiveness of the drug for a given
symptom. Herb-Herb interactions and
Herb-Drug interactions; if present, need to
be specified to avoid adverse drug
reactions. Also, it is conceptualized that the
slow mode of actions of herbal drugs may
be due to fact that the above criteria are not
followed [7]. Moreover, the active
chemical constituent from the plant for the
required activity needs to be isolated. This
will help in determining the higher efficacy
and identification of the constituent giving
the said activity [8].

Application of Biomarkers

Biomarkers help in the identification of a
given disorder and detect the presence of a
compound in a given product. In the herbal
industry, biomarkers play an important role
in identifying herbs and in identifying the
chemical constituent giving the respective
herb activity. In herbal drugs, sometimes
adultered and spurious drugs are also used.
The low quality/sub-standard drugs are
generally mixed with the pure drugs to
increase the profit margin. In order to
identify the correct drug and its
constituent, the biomarkers play an
important role [9]. Biomarkers ensure that
the distributor is providing the correct
sample. There are various detection
methods for identification of biomarkers
such as the ultraviolet visible spectra, high
performance thin layer spectroscopy
spectra, high performance liquid
chromatography spectra, infrared spectra
and many more. The simpler the method,
the faster and more cost effective it is.
Herbal drugs have complex constituents
and identification of these active
constituents can be difficult. There are
some markers that are present in all the
species of one genus so identification of
the correct biomarker is important [10].
Regulatory Requirement

Regulations may vary from country to
country as they are influenced by their
environmental conditions. Earlier the
herbal industry didn’t have any regulatory
body. Nowadays, with use of plant
hybridization techniques and other

chemicals for growth of herbs, the
regulations have become necessary to
maintain the safety and efficacy of these
drugs [11].

The WHO has set guidelines to detect the
botanical characters, sensory evaluation,
foreign organic matter, microscopic,
histological, histochemical assessment and
quantitative measurement. The WHO has
also set guidelines for, the physical and
chemical identity, fingerprints
chromatography, ash values, extractive
values, moisture content, volatile oil and
alkaloids tests. Also guidelines for the
quantitative estimation protocols,
estimation of biological activity, the values
of bitterness, astringency hemolytic index,
a factor swelling, foaming index, detailtoxicity
pesticides residues, heavy metals,
microbial contamination as viable count,
total pathogens such as E. coli, Salmonella,
P. aeroginosa, S. aureus,
Enterobacteriaceae, microbial
contamination and radioactive
contamination needs to be followed. In
India, the herbal products must satisfy the
requirements specified by the Department
of AYUSH, a department that is preparing
the standards for herbs and herbal extracts.
The other requirements that need to
followed are specified in the Food, Drug
and Cosmetic Act. Now, regulatory
authorities have started to be focused on
labeling requirement such as the botanical
source of the herbs, the quantity used and
the expiry of the same [4].

In the United States, herbal drugs come
under the purview of the Dietary
Supplement Health and Education Act,

which states that any herb, botanical and
natural concentrate, metabolite and
constituent of extract, is classified as a
dietary supplement. Moreover, dietary
supplements do not require approval from
Food and Drug Administration (US FDA).
USFDA considers dietary supplements
safe and only requires that the label is not
misleading or adulteration/spurious drugs
are not added. The label should specify all
the GLP criteria like the drug intended use,
side effect if any, drug-herb interaction and
dosage of the product [12]. The European
Directive provides the guidelines for the
use of herbal medicines pertaining to
Europe. European laws are very stringent
towards the use of herbal medicine. They
have stringent measures such as mandating
that the herbal medicinal products need to
be medically used for atleast a period of 30
years in the European Union, at least 15
years within the EU and 15 years
elsewhere for products outside the EU.
The monographs of the products should
also be attached with comparison to the
standards [13].

Perspective
Since ancient times, herbs have been used
as medicines for treating various disorders
and as supplements for prevention of the
disorder. Medications currently available
are generally derived from plants or from
the bases of plant drugs [14]. So, it is
necessary to prove the safety and efficacy
of these herbs with scientific evaluations.
Due to different plant cultivation regions
and hybridization of plant parts, the
identification of the plant material is

important for better efficacy and activity
[15]. Also, the consistency of the herbs
needs to be evaluated with the available
spectroscopic techniques. For this reason, a
biological fingerprinting or a biomarker is
required to ensure the consistency, safety,
quality, efficacy and mode of action of
these herbs. Ayurveda knowledge and
traditional usage information are excellent,
but using these in a scientific way and
incorporating a pharmaceutical approach
will be more meaningful to ensure the
safety of consumers.
References

[1] Solecki RS. Shanidar IV, a
Neanderthal Flower Burial in
Northern Iraq. Science (80). 1975;
190 (4217): 880–881.

[2] Bensky, D, Gamble A. Chinese
Herbal Medicine: Materia Medica.,
Seattle. Eastland Press; 1993.

[3] Lans C, Harper T, Georges K,
Bridgewater E. Medicinal and
ethnoveterinary remedies of hunters
in Trinidad. BMC Complement.
Altern. Med. 2001; 1:10.

[4] Ministry fo Health and Family
Welfare. Department of AYUSH.
Gov. India. Available

http://indianmedicine.nic.in/index1.a

sp?lang=1&linkid=16&lid=39.
Accessed January 5, 2014

[5] WHO. Essential Medicines and
Health Products Information Portal.
WHO. Available at
http://apps.who.int/medicinedocs/en/

d/Js2200e/ Accessed January 4,
2014.

[6] Liang Y, Ozaki Y, Mok DKW, Chau
F-T. Chemical information of
Chinese medicines: A challenge to
chemist. Chemom. Intell. Lab. Syst.
2006; 82(1): 210–217.

[7] Zeng Z, Chau F, Chan H, et al.
Recent advances in the compoundoriented
and pattern-oriented
approaches to the quality control of
herbal medicines. Chin. Med. 2008;
3:9.

[8] Patwardhan B. Ethnopharmacology
and drug discovery. J.
Ethnopharmacol. 2005; 100(1-2):
50–2.

[9] Wermuth C. Multitargeted drugs: the
end of the “one-target-one disease”
philosophy? Drug Discov. Today.
2004.

[10] Vaidya ADB, Devasagayam TPA.
Current status of herbal drugs in
India: an overview. J. Clin. Biochem.
Nutr. 2007; 41(1): 1–11.

[11] Fukuoka M, Wu YL, Thongprasert S,
et al. Biomarker analyses and final
overall survival results from a phase
III, randomized, open-label, first-line
study of gefitinib versus
carboplatin/paclitaxel in clinically
selected patients with advanced nonsmall-
cell lung cancer in Asia
(IPASS). J. Clin. Oncol. 2011;
29(21): 2866–74.

[12] U.S. Department of Health and
Human Services. U.S. Food and
Drug Administration. USFDA. 2013.
Available at:

http://www.fda.gov/Food/default.htm

Accessed December 28, 2013.

[13] EMA. European Medicines Agency –
Human medicines – Herbal medicinal
products. 2013. Available at:

http://www.ema.europa.eu/ema/index

.jsp?curl=pages/regulation/general/ge
neral_content_000208.jsp.

[14] Heinrich M. Ethnobotany and natural
products: the search for new
molecules, new treatments of old
diseases or a better understanding of
indigenous cultures Curr. Top. Med.
Chem. 2003; 3(2): 141–54.

[15] Vuorelaa P, Leinonenb M, Saikkuc P,
et al. Natural products in the process
of finding new drug candidates. Curr.
Med. Chem. 2004; 11(11): 1375–89.