Major Project

Draft II_Major Project

Antioxidant, antimutagenic and antibacterial activities of curcumin-β-diglucoside

Parvathy et al. (2009) conducted to prepare curcumin-β-diglucoside as a curcumin prodrug and to determine water solubility, antioxidant, antimutagenic and antibacterial activities of its by comparing with curcumin. Curcumin is a natural compound in turmeric, which has various pharmacological activities. However, curcumin has a low oral bioavailability because of its low water solubility and instability in aqueous and basic solutions. The use of a prodrug approach as a chemical and biochemical stabilization to overcome various barriers which can increase water solubility and stability. Curcumin-β-diglucoside was synthesized by glycosylation of curcumin at the phenolic hydroxyl group. Evaluation of water solubility found that curcumin-β-diglucoside was soluble in water at 10 mg/ml concentration, whereas curcumin was insoluble in water. The antioxidant activity showed that radical scavenging values of curcumin-β-diglucoside and curcumin were 50% and 41%, respectively. The antimutagenicity by protection the mutagenicity of sodium azide to Salmonella typhimurium demonstrated that the both of curcumin-β-diglucoside and curcumin afforded high activity. The antibacterials activity in Staphylococcus aureus and Escherichia coli found that curcumin-β-diglucosides had antibacterials activitiy with minimum inhibitory concentration (MIC) 0.051 and 0.469 µM, respectively, whereas, curcumin had antibacterials activitiy with MIC 0.081 and 0.611 µM, respectively. These activities between curcumin-β-diglucoside and curcumin were not significantly different. The researchers suggested that conjugation of the phenolic hydroxyl group of curcumin with sugar moiety improved only the water solubility of curcumin but does not affect its antioxidant, antimutagenic and antibacterial activities.

        This study provides scientific evidence to synthesis curcumin-β-diglucoside as a curcumin prodrug for improve the problems of curcumin. However, there are some limitations.

1)               The researchers did not explained method and analysis of solubility in the water of curcumin and curcumin prodrug.

2)               This study did not investigate the stability property. Curcumin-β-diglucoside should be determined stability property in aqueous and basic solution, which is an important problem of curcumin bioavailability (Zhang et al., 2011).

3)               This study investigated the activities of curcumin prodrug by using in vtro model may render of not significance in the results because prodrug refers to a pharmacologically inactive compound that is transformed by enzymes such as esterase, phosphatase and carboxylase in the mammalian system into an active substance by either chemical or metabolic process (Hosokawa, 2008). Therefoer, this study should be investigated the activities of curcumin prodrug by using in vivo model too.

The strength of this study is that synthesis of curcumin prodrug by conjugation of the phenolic hydroxyl group of curcumin with sugar, which had a solubility property and non-toxicity. Effects of curcumin prodrug determine by comparing with curcumin, which is the  parent compound. Moreover, this study is the clearly the methodology for synthesis and analysis of curcumin prodrug.

References

            Hosokawa, M. (2008). Structure and catalytic properties of carboxlyesterase isozymes                           involved in metabolic activation of prodrugs. Molecules, 13, 412-431.

Parvathy, K. S., Negi, P. S., & Srinivas, P. (2009). Antioxidant, antimutagenic and antibacterial activities of curcumin-β-diglucoside. Food Chemistry, 115, 523-530.

Zhang, F., Koh, G. Y., Jeansonne, D. P., Hollingsworth, J., Russo, P. S., Vicente, G., Stout, R. W., & Liu, Z. (2011). A novel solubility-enhanced curcumin formulation showing stability and maintainance of anticancer activity. Journal of pharmaceutical sciences, 100(7), 2778-2789.          

Major Project

Draft I_Major Project

Antioxidant, antimutagenic and antibacterial activities of curcumin-β-diglucoside

Parvathy et al. (2009) conducted to prepare curcumin-β-diglucoside as a curcumin prodrug and to determine water solubility, antioxidant, antimutagenic and antibacterial activities of its by comparing with curcumin. Curcumin is a natural compound in turmeric, which has various pharmacological activities. However, curcumin has a low oral bioavailability because of its low water solubility and instability in aqueous and basic solutions. The use of a prodrug approach as a chemical and biochemical stabilization to overcome various barriers which can increase water solubility and stability. Curcumin-β-diglucoside was synthesized by glycosylation of curcumin at the phenolic hydroxyl group. Evaluation of water solubility found that curcumin-β-diglucoside was soluble in water at 10 mg/ml concentration, whereas curcumin was insoluble in water. The antioxidant activity showed that radical scavenging values of curcumin-β-diglucoside and curcumin were 50% and 41%, respectively. The antimutagenicity by protection the mutagenicity of sodium azide to Salmonella typhimurium demonstrated that the both of curcumin-β-diglucoside and curcumin afforded high activity. The antibacterials activity in Staphylococcus aureus and Escherichia coli found that curcumin-β-diglucosides had antibacterials activitiy with minimum inhibitory concentration (MIC) 0.051 and 0.469 µM, respectively, whereas, curcumin had antibacterials activitiy with MIC 0.081 and 0.611 µM, respectively. These activities between curcumin-β-diglucoside and curcumin were not significantly different. The researchers suggested that conjugation of the phenolic hydroxyl group of curcumin with sugar moiety improved only the water solubility of curcumin but does not affect its antioxidant, antimutagenic and antibacterial activities.

         This study provides scientific evidence to synthesis curcumin-β-diglucoside as a curcumin prodrug for improve the problems of curcumin. However, there are some limitations.

1)               The researchers did not explained method and analysis of solubility in the water of curcumin and curcumin prodrug.

2)               This study did not investigate the stability property. Curcumin-β-diglucoside should be determined stability property in aqueous and basic solution, which is an important problem of curcumin bioavailability (Zhang et al., 2011).

3)               This study investigated the activities of curcumin prodrug by using in vtro model may render of not significance in the results because prodrug refers to a pharmacologically inactive compound that is transformed by enzymes such as esterase, phosphatase and carboxylase in the mammalian system into an active substance by either chemical or metabolic process (Hosokawa, 2008). Therefoer, this study should be investigated the activities of curcumin prodrug by using in vivo model too.

Minor Project

Minor Project

          My research question is to enhance solubility and stability for increase oral bioavailability of curcumin. Curcumin has not yet been approved as a therapeutic agent, because of its low bioavailability, which is caused by low water solubility and instability in aqueous and basic solutions. There are several methods used nowadays, such as nanoparticles, liposomes, and prodrug method.

        Researchers who have looked at this subject are Parvathy et al. (2010) and Bhawana et al. (2011). They used difference method for increase solubility and stability of curcumin such as prodrug and nanoparticle methods, respectively.

Parvathy et al. (2010) used a prodrug method found that curcumin prodrugs, which are synthesized by conjugation of curcumin with amino acids via ester bond shown solubility and stability in the aqueous higher than curcumin.

Bhawana et al. (2011) used a nanoparticle method found that curcumin nanoparticles had aqueous solubility higher than curcumin but not different in stability.

Debate centers on the basic issue is a prodrug method could increase solubility and stability, whereas nanoparticle method could increase only solubility of curcumin.

My work will be closer to Parvathy’s because I will use a prodrug method for to enhance solubility and stability for increase oral bioavailability of curcumin. A curcumin prodrug, curcumin diglutaric acid, was synthesized by conjugation of curcumin with diglutaric acid via ester bonds. Curcumin diglutaric acid was designed to improve aqueous solubility and enhance chemical stability by comparing with curcumin.

Hopefully my contribution will be to improve aqueous solubility and enhance chemical stability for increase oral bioavailability of curcumin.

Reference List

Parvathy, K. S., Negi, P. S. and Srinivas, P. (2010). Curcumin–amino acid conjugates: Synthesis, antioxidant and antimutagenic attributes. Food Chemistry, 120: 523-530.

Bhawana, Basniwal, R. K., Buttar, H. S., Jain, V.K. and Jain, N. (2011). Curcumin Nanoparticles: Preparation, Characterization, and antimicrobial study. J Agric Food Chem, 59(5): 2056-61.

Assignment 2: Writing an introduction

Water Solubility, Stability and Anticancer Activity of Curcumin and

Curcumin Diglutaric Acid

Stage 1:

To date, a number of phytochemicals have been explored for pharmaceutical applications as therapeutic agents by virtue of their high biological activities. They have been shown to play crucial roles in the pathogenesis of chronic diseases, such as inflammation, atherosclerosis and cancer (Aggarwal & Shishodia, 2006).  One of the extensively investigated plants is Curcuma longa L., called turmeric in English and Kamin-Chan in Thai.

Stage 2:

Tumeric contains turmerin, essential oils and curcuminiods. Commercial curcuminiods contain approximately 77% diferuloylmethane (curcumin), 17% demethoxycurcumin, and 6% bis-demethoxycurcumin. Therefore, curcumin has been identified as the major active component of turmeric extract (Jayaprakasha et al., 2002). Curcumin has been identified as the major active component of turmeric extract and shown to exhibit many pharmaceutical actions such as antioxidant (Ruby et al., 1995; Sabari et al., 2005), anti-inflammatory (Aggarwal et al., 2003; Lantz et al., 2005), and anticancer activities (Sugiyama et al., 1996; Sharma et al., 2005). Various animal models or human studies proved that curcumin is extraordinarily safe even at very high doses uptake (Ringman et al., 2005).

Stage 3:

Despite the fact that its efficacy and safety has been known, curcumin has not yet been approved as a therapeutic agent because of a major problem of its low bioavailability caused by low water solubility and instability in aqueous and basic solutions.  

Stage 4&5:

The objective of this study is an attempt to enhance solubility and stability for increase oral bioavailability of curcumin by using a prodrug methodology. A curcumin prodrug, curcumin diglutaric acid, was synthesized by conjugation of curcumin with diglutaric acid via ester bonds. Curcumin diglutaric acid was designed to have improved aqueous solubility and enhanced chemical stability by comparing with curcumin. Moreover, the anticancer activity of curcumin and curcumin diglutaric acid were also tested against human cancer cell lines such as colon and liver cancer cells.

Assignment1_Citation

Abstract

Curcumin, a natural yellow colourant from turmeric, is insoluble in water. It has been rendered water-soluble by preparation of suitable amino acid derivatives. Several amino acid conjugates of curcumin were synthesised in high yields (45–76%). These curcumin derivatives were soluble in water at 1–10 mg/ml concentrations. Derivatives of curcumin with alkyl-substituted amino acids, such as alanine, valine, serine and cysteine, exhibited smaller IC₅₀ values (˜50%) than did curcumin in antioxidant assays. With respect to anti-mutagenicity against Salmonella typhimurium TA 98 and TA 1531, the derivatives showed an effect stronger than or, in a few cases, similar to curcumin. These results clearly demonstrated that the conjugation of curcumin at the phenolic position with amino acids, while rendering the molecule water-soluble, led to the improvement of several of its in vitro biological attributes, the effect being more pronounced in the case of specific alkyl-substituted amino acids.

APA style reference

      Curcumin-amino acid was synthesized by conjugation of curcumin with 
      amino acids improved solubility in the water and increased antioxidant and 
      antimutagenic activities of curcumin (Parvaty et al., 2011).

   1. Parvaty et al. (2011) found that curcumin-amino acid was synthesized 
      by conjugation of curcumin with amino acids improve solubility in the water 
      and increased antioxidant and antimutagenic activities of curcumin.

   2. The solubility in water, antioxidant and antimutagenic activities of curcumin were 
       enhanced by conjugation of curcumin with amino acids (Parvaty et al., 2011).

Reference

 Parvathy K. S., Negi P. S. and Srinivas P. Curcumin–amino acid conjugates: Synthesis, antioxidant and  antimutagenic attributes. Food Chemistry. 2010. 120: 523-530.