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IMPORTANCE OF PROPER ANALYTICAL METHODOLOGY AND THE 10% GUGULIPID MYTH

 
 
Muhammed Majeed, Ph.D.
Lakshmi Prakash, Ph.D.
S. Natarajan, Ph.D.
 
 

Gugulipid®, a registered trademark of Sabinsa Corporation, is the standardized extract of the oleogum resin of Commiphora mukul, an Indian medicinal plant. This resin is a mixture of diterpenes, sterols, steroids, esters and higher alcohols. The active ingredients responsible for the use of the plant in the maintenance of healthy cholesterol levels, are the guggulsterones, specifically guggulsterone E and guggulsterone Z1. When purchasing guggul products, it is vital that the extract be assessed for purity and appropriate standardization. Sabinsa's product Gugulipid® (supplied in powder form) is purified and standardized to contain a minimum of 2.5% guggulsterones E and Z. The Indian Pharmacopeia (IP) limits the maximum level of guggulsterones (E and Z) to 4.0 to 6.0%2 in a soft extract.

It is probable that powdered guggul products which claim an active ingredient level in excess of 6.0% may be crude and unpurified extracts. In clinical studies, the administration of crude (unpurified) guggul caused mild side effects such as skin rashes, diarrhea and irregular menstruation3. There are no reports of these undesirable effects with a purified and appropriately standardized extract3,4.

The chemical constituents of Gugulipid® include guggulsterols, sterol compounds and steroidal ketones (guggulsterones)1,4,5,6.



GUGGULSTEROLS



 




Estimation of Guggulsterones in Gugulipid® extract:

The methods used include UV (ultraviolet) spectrophotometry7 and HPLC (High Pressure Liquid Chromatography)2.

UV Analysis7

This method involves measuring the optical density of a solution of a known concentration at a particular wave length. All components that have the UV absorption spectrum at that wave length will absorb UV light in proportion to their amount in solution. Since UV is a cumulative function, the results will be for the total amount of sterone, sterol and steroidal components present.

An examination of the chemical structures reveals that the guggulsterones, Z&E, and the guggulsterols have the following similarities:

  • They are tetracyclic
  • They have an alpha-beta unsaturated ketone Carbonyl at Position 3
  • They have an olefinic double bond at Position 4

Therefore, if a sample of powdered guggul extract is analyzed by UV method, the results would be cumulative, including a variety of structurally similar compounds and in excess of the actual guggulsterone levels.


HPLC ANALYSIS2

This method offers a more accurate analysis of the guggulsterols and guggulsterones content. It involves the following steps:

  • Physical separation of the mixture into individual components
  • Elution of the separated components from the chromatographic column at different rates.
  • Using UV detector, only the eluted components (one particular compound at a time) is quantitated.

This procedure ensures that each component is quantitated separately.



HPLC CHROMATOGRAMS OF THE Z AND E GUGGULSTERONES
(STANDARDS)

 

HPLC CHROMATOGRAM OF GUGULIPID®

TYPICAL ANALYTICAL RESULTS :

GUGGULSTERONES CONTENT IN
COMMERCIAL Commiphora mukul extract SAMPLES

Sample ID

Label claim (%)

By HPLC (%)

By UV (%)

1

2.5

2.5

4.8

2

2.5

2.6

5.3

3 (SE)*

16.0

3.6

16.5

4

10.0

1.1

10.6

* SE : Soft extract

Thus a sample analyzed as containing 10.6% active constituents (by UV method) could be erroneously labeled as containing 10% guggulsterones. It would actually contain only 1.1% guggulsterones (the value determined by HPLC), the remainder being sterol compounds.



REFERENCES:

  1. Satyavati, G.V. (1991) Guggulipid : A promising hypolipidaemic agent from gum guggul (Commiphora wightii). Economic and Medicinal Plant Research , Volume 5. Plants and Traditional Medicine, 47-80.

  2. Indian Pharmacopoeia (IP 1996). Pp 357-358

  3. Satyavati, G.V. (1966) Effect of an indigeneous drug on disorders of lipid metabolism with special reference to atherosclerosis and obesity (Medoroga). M.D. Thesis (Doctor of Ayurvedic Medicine), Banaras Hindu University, Varanasi, 1966.

  4. Satyavati, G.V. (1988). Gum guggul (Commiphora mukul)-The success story of an ancient insight leading to a modern discovery. Ind. J. Med. Res. 87: 327.

  5. Patil, V.D. et al. (1972). Chemistry of Ayurvedic Crude Drugs-1. Guggulu (resin from Commiphora mukul) 1. Steroidal constituents Tetrahedron, 28(2):2341-2352

  6. Bajaj, A.G. and Sukh Dev (1982). Chemistry of Ayurvedic Crude Drugs-V. Tetrahedron 38(9):2949-2954

  7. Roy, S.K. et al. (1989) TLC Separation and Quantitative Determination of Guggulsterones. Indian J. Pharm. Sci., Nov-Dec.:251-253.
 
     
 
   
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