Marker Compounds

Marker Compounds: Marker compounds are the pure and single isolated chemical constituents within a crude drug that confirms the exact botanical identity of that starting material or the crude drug. Marker compounds are of interest for quality control purposes and they may or may not contribute to the therapeutic activity.

Role of markers in the standardization of herbal products:

As per WHO, there are three kinds of herbal medicinal products: raw plant materials, processed plant materials, and medicinal herbal drugs. Herbal drugs are finished labeled products that contain active ingredients such as; aerial or underground parts of plants or other plant materials or a combination thereof, whether in the crude state or as plant preparations. The use of herbal medicines has increased with the global trend of people returning to natural therapies. Herbal medicinal products and dietary supplements that people take to improve their health are sold as tablets, powders, capsules, teas, extracts, and fresh or dried plants. Correct identification and quality assurance of the starting materials is, therefore, an essential requirement to ensure reproducible quality of herbal medicine which contributes to its safety and efficacy.

Marker compounds may serve to calculate the number of active components of the herbal drug in the preparation or the finished product. Markers are used at various stages of the development and manufacturing of herbal medicine like authentication and differentiation of species, collecting and harvesting, quality evaluation and stability assessment, diagnosis of intoxication, and detection of lead compounds.

Types of Marker compounds:

  1. Chemical Markers
  2. Biochemical Markers
  3. Molecular or DNA Markers

1. Chemical Markers:

Chemical markers are a unique component that contributes to the therapeutic effects of herbal medicine. The study of chemical markers applies to many research areas including; the authentication of genuine species, search for new resources or substitutes of raw materials, optimization of extraction and purification methods, structure elucidation, and purity determination.

Types of Chemical Markers Include:

Table: Different Types of Chemical Markers

Sr. No.Types of Chemical MarkersDefinition with examples  
1.Active principles  Well-defined chemicals with known clinical activity.
e.g.: Withanolides in Withania somnifera.
2.Active markers  They are the constituents or group of constituents with a known pharmacological activity that contribute to efficacy. They may or may not have proven clinical efficacy.
e.g.: Allin in Allium sativum.      
3.Analytical markersThey are the constituents or group of constituents that serve solely for analytical purposes and have no clinical or pharmacological activities. They help in the identification of raw materials and extracts or are used to achieve standardization.
e.g.: Different alkyl amides found in the roots of Echinacea purpurea and Echinacea Angustifolia but absent in Echinacea pallida.
4.Negative markers  Negative markers demonstrate allergenic or toxic properties.
e.g.: Ginkgolic acid in Ginkgo, showed signs of apoptosis as well as necrosis.

Applications of chemical markers:

  • Identification of adulterants.
  • Differentiation of herbal medicines with multiple sources.
  • Determination of the best harvesting time.
  • Confirmation of collection sites.
  • Assessment of processing methods.
  • Identification and quantitative determination of proprietary products.
  • To evaluate the stability of proprietary product quality over time and determine the recommended shelf life.
  • Diagnosis of herbal intoxication in which, toxic components may be used as chemical markers in screening methods. e.g.: Rapid diagnosis of acute-hidden aconite poisoning in urine samples by HPLC-MS and other techniques.
  • Detection of lead compounds for new drug discovery. Eg.: Gambogic acid is a potential lead compound for new anti-cancer drugs.

2. Biochemical Markers:

Biochemical markers are either proteins or isozymes. Isozymes, also known as Allozymes, are enzymes that are functionally similar but differ from each other in location, structure, net charge, electrophoretic mobility, types of activators and inhibitors, and heat stability. The isozymes pattern has been used in many population genetic studies including measurement of outcrossing rates, sub-population structure, and population divergence. These are particularly valuable to distinguish closely related species and therefore, useful to study diversity and identification of crops. E.g.: The Isozymes pattern of glucose 6 phosphate dehydrogenase has been used for the identification of Eclipta prostrate (False daisy). The peroxidase isozymes pattern is used to distinguish the three Gastrodia elata variants.

3. Molecular or Genetic markers or DNA markers:

DNA markers are the most widely used type of marker mainly due to their abundance. DNA markers are unlimited in number and are not affected by environmental factors, age, and physiological conditions of the plant. DNA can be extracted from fresh or dried plant tissue hence, the physical form of the sample for assessment does not restrict detection.

Application of DNA markers:

(i) In Herbal drug technology: DNA-based molecular markers have proved their utility in fields like; taxonomy, physiology, embryology, and genetics.

(ii) Genetic variation/genotyping: Random Amplified Polymorphic DNA (RAPD) based molecular markers are useful in differentiating different accessions of Andrographis paniculata, Azadirachta indica, Allium schoenoprasum collected from different geographical locations.

Interspecies variation has been studied using Restriction Fragment Length Polymorphism (RFLP) in different genera such as; Glycyrrhiza, Curcuma, and Echinacea.

(iii) Authentication of Medicinal plants: Rare and expensive medicinal plant species are often adulterated or substituted by morphologically similar, easily available, or less expensive species. Sequence Characterized Amplified Region (SCAR), PCR, RAPD, and RFLP are used for differentiation of the plants and to detect substitution or adulteration by other closely related species. Eg: Swertia chirata is frequently adulterated or substituted by Andrographis paniculata.

(iv) Medicinal plant breeding: Molecular markers have been used as a tool to verify sexual and apomictic offspring of intraspecific (means within the same species) cross in Hypericum perforatum (St. John’s wort), a well-known diuretic and anthelmintic drug.

(v) Food and Nutraceuticals: Capsicum, maize, and soybean have been successively categorized from Non-GMO products.

(vi) As a new pharmacognostic tool: DNA markers have shown utility in quality control of commercially important botanicals like; Ginseng, Andrographis paniculata, and Echinacea. Although DNA analysis is currently considered to be innovative technology. It has certain limitations due to which, its use has been limited to academia. Another important issue is that DNA fingerprint will remain the same irrespective of the plant parts used, while the phytochemical content will vary with the physiology, plant parts used, and environment.

Make sure you also check our other amazing Article on : WHO Guidelines on Safety Monitoring of Herbal Medicines
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