“INVESTIGATION OF HEAVY METAL CONTENT IN SELECTED TOP TRADED MEDICINAL PLANTS COLLECTED FROM DIFFERENT SOURCES”
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
FARHEEN FATHIMA
I M.PHARM
DEPARTMENT OF PHARMACOGNOSY
AL AMEEN COLLEGE OF PHARMACY
BANGALORE - 560027
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATE AND ADDRESS / FARHEEN FATHIMA#173, 3RD CROSS, WILSON GARDEN,
BANGALORE-560 027
KARNATAKA
2. / NAME OF THE INSTITUTION / AL- AMEEN COLLEGE OF PHARMACY
HOSUR ROAD, BANGALORE – 560027
3. / COURSE OF STUDY AND SUBJECT / M. PHARM - PHARMACOGNOSY
4. / DATE OF ADMISSION / JUNE – 2009
5. / TITLE OF TOPIC: -
“INVESTIGATION OF HEAVY METAL CONTENT IN SELECTED TOP TRADED MEDICINAL PLANTS COLLECTED FROM DIFFERENT SOURCES”
6.0 / BRIEF RESUME OF THE INTENDED WORK :
6.1 / NEED OF STUDY
Despite the popularity of traditional medicines, scientific research on safety and efficacy is limited. However documented fatalities and severe illness due to lead poisoning are increasingly recognized to be associated with traditional medicinal use. As society becomes more globalized, it is imperative for pharmacists and health care providers to learn about the safety of traditional medical practices. While some scientific evidence exists regarding their benefits, many key questions remain unanswered. Are these therapies safe? Do they work for the diseases or medical conditions for which they are recommended? Also unregulated or inappropriate use of traditional medicines and practices can have negative or dangerous effects1.
Contamination by heavy metals is among the main problem related to phytotherapy. Contamination with heavy metals generally originates from polluted irrigation water, particulate air material, polluted soils and in appropriate storage conditions. Despite this, analytical methodology to determine heavy metals in medicinal plants has not received the same research effort as has been dedicated to the evaluation of phytotherapeutic properties2.
Heavy metals are a well established cause of severe illness, and these concerns need to be addressed. “Metals”, “Heavy metals” and “Toxic Metals” are all terms used for a group of elements which include lead, mercury, arsenic and others that are known or suspected to cause toxicity in certain forms and at certain doses3.
In the present day scenario, the importance of herbal drugs is increasing due to their lesser side effects and acceptability to the majority of the population of third world countries. Thus, there is an urgent need to establish the identity, purity and quality assurance of herbal drugs in order to have full efficacy and safety of the herbal products4.
When the levels of heavy metals exceed in plants and animals, it can induce a variety of acute and chronic effects in wide range of organisms in various eco systems. In USA for example, heavy metals have caused natural forest to decline5.
The control of the heavy metal contents in medicinal and aromatic plants represents one of the factors for the evaluation of the quality. Since these plants originate from different growing areas, great differences in the uptake and concentrations of heavy metals in the plant tissue can be expected. The high heavy metal contents in some medicinal plants arises from their ability to accumulate particular metals especially cadmium. However, high heavy metal uptake can also be found in growing areas located in mountain regions, due to certain properties of these soils, such as acidity and/ or the presence of metal bearing minerals, which favor the mobility of heavy metals in a soil and their availability to plants6.
Ayurvedic medicines are divided into 2 major types: herbal only and rasa shastra. Rasa shastra is an ancient practice of deliberately combining herbs with metals (eg: Hg, Pb, Fe, Zn) and Minerals (eg: mica) and gems (eg: pearl).
Rasa shastra experts claim that these medicines, if properly prepared and administered are safe and therapeutic.7
The bhasmas are biologically produced nanoparticles and are taken along with milk, butter, honey, or ghee (a preparation from milk), thus, this makes these elements easily assimilable, eliminating their harmful effects and enhancing their biocompatibility8. According to this medicinal system, metal based drugs known as ‘bhasma’ involve the conversion of a metal into its mixed oxides. During these transformations, the zero valent metal state gets converted into a form with higher oxidation state and the most important aspect of this synthesis (known traditionally as ‘bhasmikarana’) is that the toxic nature of the resulting metal oxide is completely destroyed while inducing the medicinal properties into it. The important step involved in the procedure for making ‘bhasma’ is repeated treatment of a particular metal with plant juices and high temperature calcination in an earthen pot. Various tests both physical and chemical for confirming the formation of metal oxides (bhasmas) have been described in the ancient Ayurvedic literature, are carried out, thus confirming that metal has totally transformed into its oxide form, ‘bhasma’. However, all these are highly empirical and hardly provide any information on the composition and structural properties of these mixed metal oxides. Therefore, it is highly desirable that these drugs should be characterized with the help of modern methods9.
In the proposed work, measurable amounts of heavy metals- Cd, Hg, As and Pb will be detected in phytopharmaceutical derivatives of selected top traded medicinal plants collected from different sources by flame atomic absorption spectrometry (FAAS) and will be compared with the permissible limits of these heavy metals in herbal drugs as stated by WHO and AYUSH for the quality control of herbal drugs. The permissible limits for these heavy metals are 10ppm, 1ppm, 0.3ppm and 3ppm for lead, mercury, cadmium and arsenic respectively. This will allow reliable determination of heavy metal content in pharmaceutical quality control.
6.2 /
LITERATURE REVIEW
Information about lead encephalopathy due to traditional medicines was provided which educated and made pharmacists and health care providers about the potential of traditional medicines to cause lead encephalopathy1Determination of lead content on medicinal plants by Pre-concentration Flow injection analysis- Flame Atomic Absorption Spectrometry was developed in which it was possible to determine the analyte at the ng/ml level in sample solutions of medicinal plants2.
The National Ayurvedic Medical Association (NAMA), Ayurvedic Practitioners Association (APA) and Verband Europaischer Ayurveda-Mediziner and Therapeuten (VEAT) made a joint response to JAMA 2008;300(27):915 in which they welcomed all efforts to enhance quality and safety of Ayurvedic products3
Accumulation of heavy metals, namely Pb, Cd, Cu and Zn was estimated in market as well as genuine samples of important herbal drugs of India viz., Alpinia galanga, Artemesia parviflora, Butea monosperrma, Coleus forskohlii, Curcuma amada, Euphorbia prostrate, Leucas aspera, Malaxis accuminata and Pueraria tuberose. The concentration of Pb and Cd was found beyond the WHO permissible limits in most samples4.
Bioconcentration of heavy metals in naturally occurring 5 inland plant species and 5 mangrove plant species in Cuddalore district of Tamil nadu state in India was investigated and the average concentration of lead in mangrove plants was 1.7 times that of Inland plants and mercury was 11.3 times that of Inland plants5.
Evaluation of quality of Gentiana lutea L.-roots and galenic forms produced from the parts was performed. The amounts of Ni and Cr found in the analysed roots were high and it was concluded that quality control of the raw material must be carried out before utilization of gentian6
.Determination of lead, mercury and arsenic was carried out in US and Indian manufactured Ayurvedic medicines available via internet and the prevalence of toxic metals in US vs. Indian manufactured medicines was compared by measuring metal concentrations using X-ray fluorescence spectroscopy. One-fifth of both US manufactured and Indian manufactured Ayurvedic medicines contained detectable lead, mercury or arsenic7.
An attempt has been made to correlate the metallic contents with their medicinal importance in Bhasma as a unique Ayurvedic metallic preparation8
A systematic characterization of this traditional drug using various techniques like X-ray diffraction (XRD), scanning electron microscopy (SEM)–energy dispersive X-ray analysis (EDX), X-ray photoelectron spectroscopy (XPS), infrared spectroscopy (IR), thermogravimetry (TG) and surface area measurement. The results obtained were found to match very well with those of a standard copper oxide confirming the composition of the drug sample. In addition, some specific findings were also made which could help in interpreting the therapeutic properties of the traditional drug ‘tamra bhasma’.9.
Determination of heavy metals Cd, Pb, Zn, Ni and Mo in 27 samples of medicinal herbs by Flame AAS and Pulse polarography and stripping voltammetry was carried out. Samples were taken from various places in Bielsko Biata and neighboring areas and were digested by the wet method in a microwave oven10
Analysis of herbal drugs and extracts by disposable electrochemical sensor was carried out and application of disposable electrochemical sensor associated with electro analytical instrumentation for the detection of heavy metal analysis in herbal drugs was proposed. The content of cadmium and lead were evaluated11.
Determination of Cd, Pb and Zn content using two digestion protocols: a microwave assisted total digestion and an aquaregia extraction procedure based on international organization for standardization 11466 method were validated and proposed a rapid, cheap and easily automated digestion method for monitoring heavy metal content in environmental samples12.
Determination of Fe, Zn. Pb, Cd and Se content in medicinal plants by X-Ray Fluorescence analysis and Galvanostatic stripping chronopotentiometric analysis in 5 species Melissa officinalis L, Agrimonia eupatoria L, Hypericum perforatum L, Salvia officinalis L., and Achillea millefolium L was carried out13.
Determination of arsenic species in the various compartments of Typha latifolia using chromatography and mass spectrometry was carried out and these results suggested that arsenic and iron are co-localized in the skin of latifolia , consistent with previous findings14.
Analysis of heavy metal contamination in 10 chinese crude herbal drugs marketed in Italy Radix ginseng, Radix astragali, Rhizoma coptidis, Rhizoma atractylodis, Radix bupleuri, Radix rehmanniae, Radix alba, Pericarpium citri, Radix polygalae and Radix salviae was carried out. The heavy metal content was within the limit except for Rhizoma coptidis15.
Determination of heavy metal content in traditional Chinese medicines produced by different manufacturers using ICP-MS was carried out and the efficiencies of different sample digestion methods were compared. The concentration of some metals such as Pb and Cd differed widely with different manufacturers, suggesting that their origin is primarily from external contamination16.
Toxic heavy metals and undeclared drugs in Asian herbal medicines was reviewed which provided the evidence suggesting that some Asian herbal medicines contain toxic heavy metals or undeclared prescription drugs may cause a serious health problem17.
Heavy metal content in soil and selected medicinal plants collected from environmentally different sites like heavy traffic area, industrial area and residential area was carried out in which Pb, Cd, Cr and Ni were estimated. Accumulation of heavy metals varied from plant to plant. Pb was the highest in Calotropis procera root from Heavy traffic area site18.
Estimation of heavy metals in different Berberis species and its market samples was carried out in which ten different samples were procured from different drug markets of India. It was found that market samples were much more contaminated than genuine samples19
Metal content monitoring in Hypericum perforatum pharmaceutical derivatives by atomic absorption and emission spectrometry was performed in which measurable amounts of Ca, Cu, K, Li, Mg, Mn, Na, Ni and Zn were detected. This method allowed reliable determination of mineral contents in pharmaceutical Quality control of medicinal plants20.
6.3 / AIMS AND OBJECTIVES OF THE STUDY
AIM AIM: - To carry out Investigation of Heavy metals in different accessions of top traded medicinal plants by Flame Atomic Absorbtion Spectrometry.
OBJECTIVES: -
1. Collection of medicinal plants from different sources viz; Market, Wild source and Gardens.
2. Development and standardization of method and determination of heavy metal content - Cadmium, Mercury, Arsenic and Lead in collected samples by Flame Atomic Absorption Spectrometry.
3. Estimation of heavy metal content in different collected samples by Flame Atomic Absorption Spectrometry.
4. Comparative assessment of heavy metal content of selected top traded medicinal plants collected from different sources.
7.0
7.1 / MATERIALS AND METHODS
SOURCES OF DATA
vAl-Ameen college of Pharmacy Information Center,
Bangalore.
vLiterature survey.
vJournals and Publications.
vSearch on - Science direct, Pub med, Medline, Google.
vJ-Gate@HELINET search.
PLACE OF WORK:-
· FOUNDATION FOR REVITALISATION OF LOCAL HEALTH TRADITIONS (FRLHT), BANGALORE.
· AL AMEEN COLLEGE OF PHARMACY, BANGALORE.
7.2 /
METHOD OF COLLECTION OF DATA
1. Medicinal plants from different sources will be collected viz: Market, Wild source and Gardens and authenticated from Foundation for Revitalization of Local Health Tradition (FRLHT)2. The method of heavy metal content will be developed and standardized for the base heavy metal contents viz, Cadmium, Mercury, Arsenic and Lead in collected samples by FAAS.
3. Content of heavy metals will be determined individually in the top traded medicinal plants collected from different regions.
4. Comparative assessment of heavy metal content of selected medicinal plants collected from different sources will be made.
7.3 / Does the study require any investigations or interventions to be conducted on patient or other humans or animals? If so please describe briefly.
-NA-
7.4 / Has ethical clearance been obtained from your institution in case of the above query?
-NA-
8.0 / REFERENCES:
1. Surya K. Karri, Robert B. Saper, Stefanos N. Kales. Lead Encephalopathy Due to Traditional Medicines. Curr Drag Saf. Jan 2008; 3(1): 54-59.
2. Marina M.A. Campos , Henry Tonuci, Silvana M. Silva, Bruna de S. Altoe, Dermeval de Carvalho, Eloisa A. Kronka, Ana M. S. Periera, Bianca W. Bertoni, Suzelei de C. Franca and Carlos E.S. Miranda. Determination of Lead Content in Medicinal Plants by Pre-concentration Flow Injection Analysis-Flame Atomic Absorption Spectrometry. Phytochemical Analysis 2009; 20: 445-449.
3. The National Ayurvedic Medical Association (NAMA), Ayurvedic Practitioners Association (APA) and Verband Europaischer Ayurveda-Mediziner and Therapeuten (VEAT) a joint response to JAMA 2008; 300(27): 915.
4. Vartika Rai, Poonam Kakkar, Sayyada Khatoon, A.K.S Rawat, Shanta Mehrotra. Heavy Metal Accumulation in Some Herbal Drugs. Pharmaceutical Biology 2001; 39 (5):384-387.