Curcumin Extract
- What is Curcumin?
- Chemical structure of Curcumin
- Molecular targets of curcumin
- Pharmacological activity of curcumin
Curcumin is the yellow pigment of turmeric (Curcuma longa L.), the most popular spice in Indian cuisine and a major ingredient of day to day diet of Indians since ancient time. Curcumin a natural polyphenolic compound having anti-inflammatory and antioxidant properties. The biggest issue is its poor water solubility and high hydrolytic degradation.
The food intake of curcumin in mostly in South Asian countries generally found as 200 mg/day. In similar to South Asian countries other population like UK population, the mean and maximum reported use levels of curcumin have been estimated, combining the use of curcumin from naturally occurring curcumin in foods (turmeric as spice and in curry powder) and from its use as a food colour, at nearly 50 mg/day and 210 mg/day, respectively, in the adult population.
Turmeric well known as ‘Haldi’ in India has a long history of traditional medicinal use in and well reported in Ayurvedic text of India to address many conditions. Modern scientific studies on curcumin reported most of its traditional uses and the potential to address natural life conditions typical in Western peoples.
Indeed, with more than 4000 pre-clinical investigations, curcumin is one of the best studied natural products of the whole biomedical literature. As a result, curcumin has emerged as a controlling button of addressing the natural inflammation response function, with both a direct and a genomic activity on relevant enzymes, transcription factors and cytokines. However, clinical trial relevance of curcumin is little relevant, but it is sure shot preventive yellow gold which almighty showered on earth to fight against all chronic undefined diseases on earth like diabetes, cancer, hypertension and all associated with chronic inflammation. Curcumin is one of the best preventive approach presently emerged in modern nutraceutical industry.
DThe drug curcumin has a symmetric structure and commonly known as diferuloylmethane. The international union of pure and applied chemistry (IUPAC) name of curcumin is – (1E, 6E) -1, 7 -bis (4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5-dione, with chemical formula C21H20O6, and molecular weight of 368.38.
Curcumin structure consists of two aromatic rings an o-methoxy phenolic group connected by carbon linker comprising of α, β-unsaturated and β-diketone moiety. Due to diketo group, a keto-enol tautomerism occurs leading to different types of conformers. Further, in a crystal state, it exists as cis-enol configuration and stabilized by resonance-assisted hydrogen bonding (Scotter).
The effect of curcumin is either upstream or downstream (Sung et al.; S. Aggarwal et al.). The NF-kB acts in downstream thus reduces the potency and inhibit B-cell lymphoma (Bcl)-2, Bcl-xL, cyclin D1, IL6, cyclooxygenase 2 (COX2) and matrix metallopeptidase-9 (MMP9)
The pharmacological activity of curcumin is shown in table 3.5.
Table 3.5: Pharmacological actions of curcumin
| Sr. No. | Therapeutic effect | Mechanism |
| 1 | Anti-inflammatory | Decrease level of TNF α |
| 2 | Anti-cancer | Downregulation to NOS, COX-2, TNF-α and IL-6 due to inhibition of NF-kappa-B |
| 3 | Anti-Alzheimer’s | Inhibition of Beta-secretase and Increase level of Ach |
| 4 | Anti-diabetic | Increase peripheral glucose utilization via enhanced insulin secretion and inhibiting glucose transport activity |
Curcumin has been widely studied for its adverse effects and observed that dose up to 8 g/day does not cause any short-term toxicity (Pungcharoenkul and Thongnopnua).
The minimum effective concentration (MEC) of curcumin is said to be at 500 mg/kg/day and is observed safely up to 12 g/kg/day in clinical study. Moreover, curcumin is generally recognized as safe (GRAS) and approved by United States Food and Drug Administration (USFDA) (Carroll et al.; Sharma et al.; Lao et al.). Furthermore, curcumin formulation is studied taking 1 g of MF-1 (curcumin bound to lecithin) and studied over 8 months have not shown any side-effects
Oral Delivery
Currently, a great research is going on for non-invasive administration like mucosal, intranasal and oral delivery. The biggest lacuna of oral delivery is its non-tissue availability due to poor water solubility. The present study is ongoing to protect drug against enzymatic degradation and to increase the level of drug in epithelium mucosa. Peptides and proteins are used highly as they cause fewer side effects with the potential to cure diseases. The low bioavailability is caused to due to systemic enzymatic degradation and poor penetration in the intestinal membrane. A study on drug absorption from the gastrointestinal tract for macromolecular drugs are also studied (Goldberg and Gomez-Orellana). Further studies have shown that hydrophilic macromolecular drugs are not entrapped by lipid-based carrier system and have slow stability in GI tract.
Challenges associated with curcumin
The major drawback of curcumin is its poor water solubility that in term affects its bioavailability. About 2/3rd phytochemicals are lipophilic which leads to poor aqueous solubility and bioavailability. Great strategies are developing to improve the solubility at the lead to improved bioactivity and bioavailability of curcumin.
A number of concepts for curcumin are like encapsulation, synthesizing a molecule, emulsions, hydrogels, and nanoparticle-based study. The biggest issue is the stability and safety of prepared formulations along with biodegradability, biocompatibility, sustainability and much more. Moreover, the pharmaceutical based application generally require peptides that are generally recognized as safe (GRAS) and its residual organic solvent also need to be studied.