Plant Derived Ribosome Inactivating Proteins: An Overview


Nitin Kumar, Satyendra Singh, Manvi  and Rajiv Gupta*

Department of Pharmacognosy, Faculty of Pharmacy, Babu Banarasi Das National Institute of Technology and Management, Dr. Akhilesh Das Nagar, Faizabad Road, Lucknow 227 105 U.P (India)

*Corresponding Author E-mail:



Many plants accumulate proteins that are commonly referred to as ribosome-inactivating proteins (RIPs). Biological effects described to these proteins go back to ancient times because of the high toxicity of seeds of castor bean (Ricinus communis) and jequirity bean (Abrus precatorius), as well as anti-HIV, the abortifacient activity of some plants like Trichosanthes kirilowii and Momordica charantia, rely on the presence of RIPs. Pokeweed antiviral protein, and ricin, previously described as ribosome-inactivating proteins were shown to damage single-stranded DNA by removal of a protein-specific set of adenines. RIPs are enzymes and some have multiple enzymatic activities. These enzymes are expected to damage DNA rather than participate in repair processes. All RIPs depurinated DNA extensively and some released adenine from all adenine-containing polynucleotides. The entire class of plant proteins, called ribosome-inactivating proteins, may be classified as polynucleotide: adenosine glycosidases. The significance of this DNAase activity to the biological function of these plant proteins along with their toxicity effect to animal cells remains to be fully understood.


KEYWORDS: Ribosome inactivating protein, Trichosanthin, Cytotoxicity, Antiviral protein, Abortifacient



‘Ribosome-inactivating protein’ inactivates animal ribosomes before the structure and enzymatic activity. RIPS are grouped into two types: Type-1 RIPs are single chained such as trichosanthin and type 2 RIPs are double chained such as ricin. The A chains of type-2 RIPs possess the RIP activity and B chain bind the proteins to eukaryotic cell surface and help a chains to enter the cytosol. Both trichosanthin and ricin are RNA-N glycosidases and both inactivate ribosomes by cleaving the n- glycosidic bond of A4324 of 28S rRNA in a hydrolytic fashion1. The identification of ricin was an important milestone in biochemistry because for the first time a well-defined biological activity was described to a plant protein. Moreover, abrin, a similar toxic protein from the seeds of A. precatorius, also played an important role in the early development of immunology. Since the isolation and characterization of ricin, many structurally and functionally related proteins have been identified in various plants2. The interest in RIPs focused on possible medical and therapeutical applications because several of these proteins were found to be more toxic to tumor cells than to normal cells, and hence offered a theoretical opportunity to develop antitumor drugs that selectively target tumor cells 3.


Along with the efforts to develop some RIPs into anticancer compounds, attempts were made to find out what RIPs do and how they act. This led to the finding that RIPs are RNA N-glycosidases that inactivate ribosomes through a site-specific deadenylation of the large ribosomal RNA4,5. RIPs are also capable of inactivating many nonribosomal nucleic acid substrates6,7,8. The enzymatic activity enhances exploitation of the unique properties and activities of RIPs for diverse applications like immunotoxins9, abortifacients10, and anti-human immunodeficiency virus agents11,12.



After the mode of action of RIPs on ribosomes was elucidated, the term RIP was used exclusively for these N-glycosidases. This is important because other types of proteins that inactivate or damage ribosomes by other mechanisms (e.g., RNases or proteases) are not considered RIPs. Two major classes are distinguished: holo-RIPs and chimero-RIPs. Holo-RIPs consist exclusively of a single RNA N-glycosidase domain. Most holo-RIPs consist of a single, intact polypeptide of ~30 kDa and are usually referred to as type 1 RIPs. Besides these classical type 1 RIPs, there are also a few examples of type 1 RIPs in which the original 30 kDa polypeptide is proteolytically processed so that the protein consists of two shorter polypeptides held together by noncovalent interactions. These proteins have been named type 3 RIPs. Chimero-RIPs are constructed of one or more protomers consisting of an N-glycosidase domain linked to a structurally different and functionally unrelated domain. Most chimero-RIPs are so-called type 2 RIPs. Type 2 RIPs may be toxic or non toxic. Besides the classical type 2 RIPs, a 60 kDa RIP (called JIP60) has been identified in barley (Hordeum vulgare) that consists of an amino-terminal domain resembling type 1 RIPs linked to an unrelated carboxyl-terminal domain with unknown function13.



RIPs were initially detected in plants, mostly in family Angiospermae, in both mono- and dicotyledons, in mushrooms14 and in an alga, Laminaria japonica15. Some examples of plants16 having Ribosome-inactivating proteins are given in table 1, 2 and 3.


Table 1: Type 1 ribosome-inactivating proteins

Name and part of  Plant

Name of RIP

Agrostemma githago seeds


Amaranthus viridis leaves


Asparagus officinalis seeds


Basella rubra seeds


Beta vulgaris leaves


Bryonia dioica leaves, roots


Citrullus colocynthis seeds


Momordica balsamina seeds

Momordin II

Phytolacca americana leaves, seeds

Pokeweed antiviral proteins (PAP)

Trichosanthes kirilowii roots, seeds

Trichosanthins, Trichokirin

Dianthus barbatus leaves

Dianthin 29

Gelonium multiflorum seeds


Saponaria officinalis leaves, roots, seeds


Laminaria japonica leaves


Lyophyllum shimeij fruiting bodies



Table 2: Type 2 toxic ribosome-inactivating proteins

Name of Plant  and part

Name of RIP

Abrus precatorius seeds


Abrus pulchellus seeds


Ricinus communis seeds


Viscum album leaves



Table 3: Type 2 non-toxic ribosome-inactivating proteins

Name of Plant and part

Name of RIP

Cinnamomum camphora seeds


Cinnamomum porrectum seeds


Cucurbita foetidissima root


Sambucus nigra bark, fruits and seeds

Nigrin b, Nigrin f



Both type 1 and type 2 RIPs have been identified on the basis of a well-defined biological activity. Type 2 RIPs were discovered more than a century ago when Stillmark isolated the toxic principle from castor bean seeds. The high toxicity of ricin was attributed to its agglutinating activity, which means that the carbohydrate binding activity of type 2 RIPs was recognized long before their enzymatic activities and their inhibitory activity on protein synthesis17. Type 2 RIPs owe their carbohydrate binding activity to the B-chain, which contains two or possibly three binding sites18. Various biological activities of RIPs has been reported and some of them has been mention below.



Cytotoxicity of type 2 RIPs is determined by the binding of the B-chain to a sugar-containing receptor on the cell surface. Ricin, causes 50% cell death at concentrations below 1 mg/ml whereas some elderberry type 2 RIPs show no effect at 1 mg/ml19.


Type 1 RIPs were discovered in 1925 when Duggar and Armstrong observed that Phytolacca americana antiviral protein (PAP) inhibits the transmission of tobacco mosaic virus (TMV) in plants20. However, only in 1978 PAP was recognized as an inhibitor of protein synthesis21. Many, but certainly not all, type 1 RIPs are antiviral proteins. Unlike some type 2 RIPs, type 1 RIPs are not cytotoxic and do not behave as toxins because they are not able to cross the cell membrane on their own. Some specialized animal cells, however, can import type 1 RIPs by endocytosis and subsequently become sensitive to the RIP activity. The five tested RIPs show very similar characteristics2.


Table 4: The five tested RIPs showing inhibition of protein synthesis  Full-size table

Ribosome-inactivating protein

Level in tissue (seeds) (mg/

100 g)

Inhibition of protein synthesis

Toxicity to mice

LD50 (mg/kg)

Cell-free IC50 (nM)

HeLa cells                       

IC50 (nM)                      





















Saporin S-6






Abortifacient activity:

Trichosanthin, a ribosome-inhibiting protein obtained from Trichosanthes kirilowii roots and seeds is currently used in China to induce early and mid-term abortion with over 95% success rate and minimal side effects. The abortifacient effect of trichosanthin is described to the active uptake of the RIPs by trophoblasts. Trichosanthin (0·3 mg/25 g) and momorcharin (0·2 mg/25 g) given intraperitoneally to mice on Days 4 and 6 of pregnancy led to an inhibition of implantation22. Ricin, abrin, and PAP inhibit cell-free protein synthesis by irreversibly inactivating the ribosomes in such a way that the function of elongation factors EF-1 and EF-2 is blocked23.


Antiviral activity:

Dodecandrin, a newly discovered ribosome-inhibiting protein, has been isolated and purified from the leaves of the plant, Phytolacca dodecandra. Dodecandrin has a molecular weight of approx. 29,000. It cross-reacts with antiserum prepared against pokeweed antiviral protein from Phytolacca americana and exhibits similar requirements for antiribosomal activity. It is more basic than pokeweed antiviral protein, and comparison of the first 30 amino-terminal residues of the two proteins reveals 83% homology. This level of homology is greater than that between pokeweed antiviral protein and pokeweed antiviral protein S, another antiviral protein found in P. americana. Such conservatism in sequence, coupled with the high efficiency of the proteins in deactivating ribosomes and with their abundance in plant tissue, suggests that they serve an important function in the life of the plant, as a defense against infection 24.



GAP31 (gelonin anti-HIV protein of 31kDa) is an anti-HIV protein which we have identified and purified from a medicinal plant, Gelonium multiflorum. It is capable of inhibiting HIV-1 infection and replication. GAP31 also exhibits DNA topoisomerase inhibitor activity and RNA N-glycosidase activity25.


Recent advances in trichosanthin; a ribosome-inactivating protein with multiple pharmacological properties has been also reported. Trichosanthin (TCS), a ribosome-inactivating protein extracted from the root tuber of Chinese medicinal herb Trichosanthes kirilowii has multiple pharmacological properties including abortifacient, anti-tumor and anti-HIV. It is traditionally used to induce abortion but its antigenicity and short plasma half-life have limited the repeated clinical administration.  Studies on structure–function relationship and mechanism of cell entry are also covered. Recently, TCS has been found to induce apoptosis, enhance the action of chemokines and inhibit HIV-1 integrase. These findings give new insights on the pharmacological properties of TCS and other members of ribosome-inactivating proteins26.


Immunological effects (immunogenicity, allergenicity and immunosuppression):

The knowledge of the immunogenicity of RIPs goes back to Paul Ehrlich, who obtained the very first antibodies against ricin. Ricin27 and all RIPs are strongly immunogenic, and their administration to animals gives rise to formation of antibodies, with cross-reaction only among RIPs from plants belonging to the same family28. Ricin administration induced an IgE response, and also enhanced the response against other antigens given at the same time. Formation of IgE has been observed in mice after administration of several type 1 RIPs29.


RIPs have immunosuppressive effects, both on humoral and cell-mediated response, in that their administration prevents formation of antibodies and retards graft rejection30. This only if RIPs are given before the antigen, suggesting that they interfere with an early step in the immune response.


It is now generally accepted that all RIPs are enzymes and that some have multiple enzymatic activities.


Classical enzymatic activities Site-specific RNA N-glycosidase activity toward ribosomes:

Although all RIPs exhibit RNA N-glycosidase activity toward ribosomes, there are marked differences in substrate specificity. Both RIPs and ribosomes contribute to the apparent substrate specificity. Since the rRNA target structure is universally conserved, differences in sensitivity between ribosomes most likely reside within the ribosomal proteins, which may either allow or prevent access of the RIPs to the sarcin/ricin loop. Vater et al. identified rat liver ribosomal proteins L9 and L10e as the binding target of the ricin A-chain 31, whereas yeast ribosomal protein L3 was identified as the binding factor of PAP 32. The specific interaction between PAP and L3 probably explains the broad-spectrum activity of PAP toward ribosomes from species of different taxonomic groups because L3 is highly conserved in ribosomes. Differences in activity and ribosome substrate specificity are also due to differences in the structure of different RIPs. PAP-ricin A-chain protein hybrids were created and examined for activity on rabbit reticulocyte and E. coli ribosomes. According to the results of these experiments, the amino-terminal half of the hybrid proteins determine the substrate specificity.  RIPs do not affect ribosomes of the plant in which they are expressed; recent studies have unambiguously demonstrated that RIPs are fully capable of deadenylating and inactivating nonspecific ribosomes33.


Site-specific RNA N-glycosidase activity toward ribosomal RNA:

Although the rRNA in native ribosomes is the preferred substrate for RIPs, naked (deproteinized) rRNA and a synthetic 35-residue oligoribonucleotide that mimics the sarcin/ricin loop can also serve as the substrate for RIP activity34.


Polynucleotide: adenosine glycosidase activity:

Saporin-L1, a type 1 RIP from the leaves of Saponaria officinalis, is capable of removing multiple adenine residues from various nucleic acid substrates 35. RIPs present in the starting material in some plant species and tissues are assayed translation inhibitory and polynucleotide adenine glycosylase activities of edible plant extracts. Plants having translation inhibitory activity and adenine glycosylase activity are mention in table 5.


Polynucleotide: guanosine glycosidase activity:

Highly purified gelonin, momordin, PAP-S, and saporin-S6, these RIPs are able to remove bases other than adenine37.


RNase activity:

Mock et al. demonstrated that preparations of α and especially β momorcharin (corresponding to momordin I and momordin II, respectively) possess RNase activity38.



Table 5: Plants having translation inhibitory activity and adenine glycosylase activity36


Genus Species Subspecies or variety

Common         name

Translation inhibitory activity

Adenine glycosylase activity

Specific activity

(U g−1  of basic protein) × 10−6

Tissue activity (U g−1 of starting tissue)

Specific activity (U g−1 of basic protein) × 10−3

Tissue activity (U g−1 of starting tissue)



Cichorium intybus






Cichorium endivia






Cynara scolymus








Capsicum annuum

Red pepper





Lycopersicon esculentum

Cherry tomato





Solanum melongena

Egg plant






Beta vulgaris

Common beet










Apium graveolens dulce






Apium graveolens rapaceum






Daucus carota






Foenuculum vulgare

Sweet fennel





Pastinaca sativa






Petroselinum crispum








Glycine max

Wild soybean





Phaseolus vulgaris

Kidney bean







DNase activity:

Dianthin 30, saporin-S6, and gelonin indicated that these type 1 RIPs exhibit nuclease activity toward single-stranded DNA39. MAP30, one of the type 1 RIPs from seeds of the bitter melon (Momordica charantia), have been used to support the idea that RIPs are DNA glycosylase/AP lyases40. In addition, it was suggested that the DNA glycosylase/AP lyase activity of MAP30 makes the HIV long terminal repeat unsuitable as a substrate for the HIV integrase as well as the DNA gyrase and that the DNA glycosylase/AP lyase may contribute to the antiviral and antitumor activities of MAP30.

The anti-HIV-1 activity has been desscribed to the inhibition by MAP30 and gelonin of the three specific reactions catalyzed by the viral integrase41.



RIPs are studied primarily because of their unique biological activities toward human and animal cells and the perspectives they offer for antiviral and antitumor activities in therapeutical applications. Highly toxic type 2 RIPs like ricin and abrin are believed to protect the seeds they inhabit against plant-eating organisms. Though the oral toxicity of most other type 2 RIPs is much lower than that of ricin, the accumulation of large quantities of these low-toxicity proteins (e.g., in vegetative storage tissues) probably offers some protection against phytophagous invertebrates and/or herbivorous animals. It has been suggested that abundant type 2 RIPs are storage proteins that can be used as a specific defense proteins if the plant is challenged by a predating organism42.


The active protein component was isolated and named as pokeweed antiviral protein. Subsequently, purified RIPs from many sources have been shown to potently inhibit the infection of test plants with diverse plant viruses. All RIPs with proven antiviral activity toward plant viruses are type 1 RIPs except the type 2 RIP from Eranthis hyemalis43.



The properties of RIPs raises some hope for their utilization for various purpose along with possible applications in medicine and also in plant sciences. In former, they have been studied as immunotoxins or as antiviral agents, mainly against HIV, although promising but with the difficulties as outlined above. Possibly, there exists some realistic hopes of their use for the therapy of topical tumors etc. Ribosome-inactivating proteins definitely exhibit RNA N-glycosidase and polynucleotide: adenosine glycosidase activity. Most biological activities of RIPs undoubtedly rely on their enzymatic activity. RIPs probably plays a role in plant defense. Type 2 RIPs are defense proteins directly targeted against plant consuming organisms, whereas type 1 RIPs are involved in the defense against viruses and microorganisms. To conclude the authors see no reason that the scope for further research is still there in this promising area.



1.       Jain-Ping Xiong, Zong-Xiang xia, and Yu Wang, Identification of stable complex of trichosanthin with nicotinamide adenine dinucleotide phosphate. Journal of protein chemistry 1995; 14: (3), 139.

2.       Barbieri, L., Battelli, M. G., Stirpe, F., Ribosome-inactivating proteins from plants. Biochim. Biophys. Acta 1993; 1154: 237-282.

3.       Lin et al., Abrin and ricin: new anti-tumour substances. Nature (London) 1970; 227: 292-293.

4.       Endo et al., The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes: The site and the characteristics of the modification in 28S ribosomal RNA caused by the toxins.  J. Biol. Chem. 1987; 262: 5908-5912.

5.       Endo, Y., Tsurugi, K., RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes. J. Biol. Chem. 1987; 262: 8128-8130.

6.       Li et al., Trichosanthin, a potent HIV-1 inhibitor, can cleave supercoiled DNA in vitro. Nucleic Acids Res. 1991; 19: 6309-6312.

7.       Barbieri et al., Polynucleotide: adenosine glycosidase activity of ribosome-inactivating proteins: effect on DNA, RNA and poly (A). Nucleic Acids Res. 1997; 25: 518-522.

8.       Hudak, K. A., Wang, P., and Tumer, N. E., A novel mechanism for inhibition of translation by pokeweed antiviral protein: depurination of the capped RNA template. RNA. 2000; 6: 369-380.

9.       Sandvig, K., van Deurs, B., Entry of ricin and shiga toxin into cells: molecular mechanisms and medical perspectives. EMBO J. 2000; 19: 5943-5950.

10.     Yeung et al., Trichosanthin, alpha-momorcharin and beta-momorcharin: identity of abortifacient and ribosome-inactivating proteins. Int. J. Pept. Protein Res. 1988; 31: 265-268.

11.     McGrath et al., GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage. Proc. Natl. Acad. Sci. 1989; 86: 2844-2848.

12.     Zarling et al., Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+ cells by monoclonal antibodies. Nature 1990; 347: 92-95.

13.     Reinbothe et al., JIP60, a methyl jasmonate-induced ribosome-inactivating protein involved in plant stress reactions. Proc. Natl. Acad. Sci. 1994; 91: 7012-7016.

14.     Yao et al., Isolation and characterization of a type 1 ribosome-inactivating protein from fruiting bodies of the edible mushroom (Volvariella volvacea). J. Agric. Food Chem 1998; 46: 788–792.

15.     Liu, R.S., Yang, J.H. and Liu, W.Y., Isolation and enzymatic characterization of lamjapin, the first ribosome-inactivating protein from cryptogamic algal plant (Laminaria japonica A). Eur. J. Biochem. 2002; 269: 4746–4752.

16.     Stirpe, F., Ribosome-inactivating proteins.  Toxicon 2004; 44: 371–383.

17.     Frankel et al., Ricin toxin contains at least three galactose-binding sites located in B chain subdomains 1{alpha}, and 1ß, Biochemistry 1996; 35: 14749-14756.

18.     Steeves et al., Identification of three oligosaccharide binding sites in ricin. Biochemistry 1999; 38: 11677-11685.

19.     Battelli et al., Toxicity and cytotoxicity of nigrin b, a two-chain ribosome-inactivating protein from Sambucus nigra: comparison with ricin. Arch. Toxicol 1997; 71: 360-364.

20.     Duggar, B. M., Armstrong, J. K., The effect of treating virus of tobacco mosaic with juice of various plants. Ann. Mol. Bot. Gard. 1995; 12: 359-365.

21.     Dallal, J. A., Irvin, J. D., Enzymatic inactivation of eukaryotic ribosomes by the pokeweed antiviral protein. FEBS Lett. 1988; 89: 257-259.

22.     Law, L. K., Tam, P. P., and Yeung, H. W., Effects of {alpha}-trichosanthin and {alpha}-momorcharin on the development of peri-implantation mouse embryos. J. Reprod. Fertil. 1983; 69: 597-604.

23.     Sperti et al., Relationship between elongation factor I- and elongation factor II-dependent guanosine triphosphatase activities of ribosomes: Inhibition of both activities by ricin. Biochem. J. 1975; 148: 447-451.

24.     Ready M.P., Adams R.P., Robertus J.D., Dodecandrin, a new ribosome-inhibiting protein from Phytolacca dodecandra. Biochim Biophys Acta 1984; 791: (3), 314-319.

25.     Sylvia et al., Human immunodeficiency virus type 1 (HIV-1) inhibition, DNA-binding, RNA-binding, and ribosome inactivation activities in the N-terminal segments of the plant anti-HIV protein GAP31 Proc. Nati. Acad. Sci. 1994; 91: 12208-12212.

26.     Pang-Chui Shaw, Ka- Ming Lee and Kam-Bo Wong, Recent advances in trichosanthin, a ribosome-inactivating protein with multiple pharmacological properties. Toxicon 2004; 45: (6), 683-689.

27.     Thorpe, S.C., Murdoch, R.D., and Kemeny, D.M., The effect of castor bean toxin, ricin, on rat IgE and IgG responses. Immunology 1989; 68: 307–311.

28.     Strocchi, P., Barbieri, L., Stirpe, F., Immunological properties of ribosome inactivating proteins and of a saporin-IgG conjugate. J. Immunol. Methods 1992; 155: 57–63.

29.     Zheng, S.S., Wai, W.L., Hin, W.Y., Wu, A.R.,. Kinetics of IgE antibody response to trichosanthin, a-momorcharin and b-momorcharin in mice. Chin. Med. J. 1991; 104: 292–299.

30.     Spreafico et al. The immunomodulatory activity of the plant proteins Momordica charantia inhibitor and pokeweed antiviral protein. Int. J. Immunopharmacol. 1983; 5: 335–344.

31.     Vater et al., Ricin A chain can be chemically cross-linked to the mammalian ribosomal proteins L9 and L10e. J. Biol. Chem. 1995; 270: 12933-12940.

32.     Hudak, K. A., Dinman, J. D., and Tumer, N. E., Pokeweed antiviral protein accesses ribosomes by binding to L3. J. Biol. Chem. 1999; 274: 3859-3864

33.     Chaddock et al., Major structural differences between pokeweed antiviral protein and ricin A chain do not account for their differing ribosome specificity. Eur. J. Biochem. 1996; 235: 159-166.

34.     Endo et al., Ribosomal RNA identity elements for ricin A-chain recognition and catalysis. J. Mol. Biol. 1991; 254: 848-855.

35.     Barbieri et al., Polynucleotide:adenosine glycosidase activity of saporin-L1: effect on DNA, RNA and poly(A). Biochem. J. 1996; 319: 507-513.

36.     Luigi et al., Ribosome-inactivating proteins in edible plants and purification and characterization of a new ribosome-inactivating protein from Cucurbita moschata.  Biochimica  et Biophysica Acta (BBA) 2006; 1760: ( 5), 783-792.

37.     Barbieri et al., Polynucleotide: adenosine glycosidase is the sole activity of ribosome-inactivating proteins on DNA. J. Biochem. 2000; 128: 883-889.

38.     Mock et al., Demonstration of ribonuclease activity in the plant ribosome-inactivating proteins alpha- and beta-momorcharins. Life Sci. 1996; 59: 1853-1859.

39.     Roncuzzi et al, DNA-nuclease activity of the single-chain ribosome-inactivating proteins dianthin 30, saporin 6 and gelonin. FEBS Lett. 1996; 392: 16-20.

40.     Wang et al., Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell 1999; 99: 433-442.

41.     Lee-Huang et al., Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31. Proc. Natl. Acad. Sci. 1995; 92: 8818-8822.

42.     Van et al. Plant lectins: a composite of several distinct families of structurally and evolutionary related proteins with diverse biological roles. Crit. Rev. Plant Sci. 1998; 17: 575-692.

43.     Kumar et al., Characterization of the lectin from the bulbs of Eranthis hyemalis as an inhibitor of protein synthesis. J. Biol. Chem. 1993; 268: 25176-25183.




Received on 23.04.2010       Modified on 20.06.2010

Accepted on 06.07.2010      © RJPT All right reserved

Research J. Pharm. and Tech.3 (4): Oct.-Dec.2010; Page 1018-1022