Methods for the Estimation of Ellagic Acid and Curcumin in Antidiabetic Herbal Formulations – A Review

Diabetes mellitus is the most common endocrine disorder, affecting 200 million worldwide. Despite the use of advanced synthetic drugs for the treatment, use of herbal remedies is gaining higher importance because of synthetic drugs have drawbacks and limitations. Antidiabetic herbal formulations (AHF) are considered to be more effective for the management of diabetes. Various Antidiabetic Herbal formulations are available in market which contain different constituents whose combine effect is necessary for the activity. Here, 2 constituents are selected i.e. Ellagic acid and Curcumin. An extensive survey of the literature published in various analytical and pharmaceutical chemistry related journals has been conducted and the instrumental analytical methods which were developed and used for determination of Ellagic acid and Curcumin as single or combination with other Herbal constituents in bulk drugs, formulations and biological fluids have been reviewed. This review covers the time period from 1972 to 2015 during which 48 analytical methods including spectrophotometric methods like U spectroscopy Chromatographic methods including HPLC, HPTLC and miscellaneous methods were reported.


INTRODUCTION
Diabetes mellitus is a metabolic disorder detected by chronic hyperglycemia with disturbances in carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.Mainly 3 types of Diabetes are frequently occur.Type I (Insulin dependent Diabetes mellitus), Type II (Non Insulin dependent Diabetes mellitus) and Gestational Diabetes.Nephropathy, Neuropathy, Cardiovascular diseases, Peripheral vascular diseases, Cerebrovascular diseases and Retinopathy are the major long term side effects observed due to the Diabetes mellitus.Currently available therapies for diabetes include insulin and various oral antidiabetic agents, which are used as monotherapy or in combination for obtaining better glycemic regulation.Many of these oral antidiabetic agents have a number of serious adverse effects; thus, managing diabetes without any side effects is still a challenge.Due to low toxicity and known pharmacological activity, herbal drugs have been widely and extensively used for many centuries [1].

DIFFICULTIES IN ANALYSIS OF HERBAL DRUGS
Herbal analysis is a difficult task as compared to analysis of synthetic drugs as several problems not applicable to synthetic drugs influence the quality of herbal drugs [2][3][4][5][6][7].
• Herbal drugs are combination of many components.
• The active principles are, in the majority cases mysterious.
• Selective analytical technique or reference compound could not exist commercially.
• Plant materials are chemically and naturally unpredictable.
• Source and quality of the raw material is inconsistent.
• Adulteration and substitution is a major issue.
Different anti diabetic polyherbal formulations available in market.Different combination of the constituents are responsible for their Antidiabetic activity.Some common constituents are there which are responsible for the activity.Here, we selected some of markers i.e.Ellagic acid and Curcumin.
Drug profiles for different constituents are given in Tables 1 & 2.

ESTIMATION OF ELLAGIC ACID AND CURCUMIN IN SINGLE OR COMBINED FORM BY DIFFERENT ANALYTICAL TECHNIQUES
In today's world, there has been more demand for plant derived products in developed countries.These products are increasingly being sought out as medicinal products, nutraceuticals and cosmetics.During the Nineteenth century the herbal drugs were given in form of Herbal tea mixtures, tinctures, Extracts and juices which in turn were employed in preparing medicinal drops, syrups, infusion, ointment etc., progressed of this science and because of that phytochemist succeeded in isolating active constituents, active constituents which is responsible for replacing the crude drug.Herbs are produced in two main ways: collection from wild plants from their natural habitats and cultivation of herbs that are grown that the plant collected is the one that is desired and having uniform quality attributes while in wild-crafted herbs there is a chance that the wrong herb has been picked, which could lead to serious consequences.So Herbal drugs or it's standardize extracts or pure active compound needs Analytical techniques to confirm its identity, Quality, Purity, Potency, Safety and Efficacy of the plant.

Determination of Ellagic acid and Curcumin
Different analytical methods are developed for the determination of Ellagic acid alone and with other constituents.8 HPLC and 6 HPTLC methods were developed.So, total 14 methods are used to determine Ellagic acid.Diiferent analytical methods are developed for the determination of Curcumin alone and with other constituents.11 HPLC, 22 HPTLC, 1 UV methods were developed.So, total 34 methods are used to determine Curcumin.

CONCLUSION
The presented review highlights on various analytical methods published on Ellagic acid and curcumin, alone or in combination with other herbal constituents.HPLC method for determination of ellagic acid along with taxol was found to be most sensitive among all methods listed here.Various analytical methods like spectrophotometry, chromatography and in combinations are presented in the Tables.There is no doubt on the fact that spectroscopic methods are rapid and far more economical than chromatographic methods but their destructive nature and lack of sensitivity is huge.On the other side, estimation in Herbal formulation and impurities estimation are possible by the help of chromatography methods.Only one spectrophotometric method for the determination of curcumin was reported.In this way various analytical methods for the estimation of these Ellagic acid and curcumin in bulk or in formulation with other drugs is discussed.There are more HPLC methods are found in the literature for the determination of ellagic acid in various fruits, while HPTLC methods are used more for the determination of ellagic acid in formulations.On the contrary, there are many more HPTLC methods are reported compared to HPLC for the determination of curcumin.The wavelength used for estimation of ellagic acid was 254 nm for HPLC and 280 nm for HPTLC in most of the reviewed literature.The presented information is useful for the researchers especially those involved in the Method development and quality control of Ellagic acid and Curcumin.This review covers the time period from 1972 to 2015 during which 48 analytical methods were developed.All Methods were found to be reproducible, accurate and can determine at Nanogram level.

FURTHER PERSPECTIVE
In Herbal Formulations, major variations are there in active constituents due to many reasonslike change in weather, change in geographical sources.Also in same place, there are observable change in amount and little change in structure of the active constituents.Due to these reasons, the effectiveness of Herbal formulation is not same all the time.To decrease these effect, exact determination of active constituents are necessary.So From the above review of Analytical methods, we can get idea of development of more specific and robust method for determination of ellagic acid and curcuminso that variation in the effectiveness of Herbal Formulations can be minimized.

Simultaneous Analysis and Quantification of Markers of ManjisthadiChurna Using High Performance Thin Layer Chromatography.
 Stationary phase :-TLC plates precoated with 0.2-mm layers of silica gel 60F254  Mobile phase:-toluene:ethylacetate:methanol:formic acid (10:9:6:5 v/v)  plate was dried in hot air oven at 105° for 5 min  Scanning: Camag thin layer chromatography (TLC) scanner-III linked to Wincats software