INTRODUCTION:

Asia has long utilized turmeric, which is a key component of Siddha, Ayurvedic, and Unani traditional Chinese medicine.¹It was first employed as a dye, and then folk medicine claimed to benefit from its purported qualities.^2,3Turmeric, also known by its botanical name, curcuma longa or curcuma aromatica, is derived from the modified stem of the zingiberaceae plant, which is depicted in figure 1.

The ginger family, Zingiberaceae (/ˌzɪndʒɪbɪˈreɪsii/), is a family of flowering plants that comprises approximately 50 genera and approximately 1600 recognized species of aromatic perennial herbs.⁴

Figure 1: Curcuma Longa (Turmeric) rhizome and powder

The rhizomes are used raw or cooked in water, then dried. They are then ground into a deep orange-yellow powder that is widely used in Asian cuisine, particularly curries, for flavoring and coloring purposes. Curcumin, the main ingredient in turmeric, also imparts color to the powder. The World Health Organization, European Parliament, and US Food and Drug Administration have all approved curcumin, a brilliant yellow substance generated by the turmeric plant, as a food ingredient.⁵ It is sold as a herbal supplement, cosmetics ingredient, food flavoring, and food coloring.⁶The anti-inflammatory, antioxidant, anticarcinogenic, antiviral, and anti-infectious properties of curcumin have been the subject of the most thorough investigations. Furthermore, curcumin's ability to heal wounds and cleanse the body has drawn a lot of attention. Owing to a great deal of study on curcumin's medicinal qualities, some knowledge of the compound's cellular, molecular, and biochemical mode of action is beginning to emerge. One important curcuminoid, curcumin (diferuloyl methane), was used in the great majority of these investigations.⁷

Worldwide, curcumin is being acknowledged and utilized in a variety of ways for its possible health advantages. For instance, turmeric, which contains curcumin, is used in curries in India; it is served in tea in Japan; it is used in cosmetics in Thailand; it is used as a colorant in China; it is served in drinks in Korea; it is used as an antiseptic in Malaysia; it is used as an anti-inflammatory agent in Pakistan; and it is used as a preservative and coloring agent in mustard sauce, cheese, butter, and chips in the United States, in addition to available in capsule and powder form. There are many different ways to get curcumin: as pills, capsules, ointments, energy drinks, soaps, and cosmetics. Curcuminoids have been approved by the US Food and Drug Administration (FDA) as “Generally Recognized as Safe” (GRAS).⁸

CHEMISTRY OF CURCUMIN:

Chemically, curcumin is a diarylheptanoid, belonging to the group of curcuminoids, which are phenolic pigments responsible for the yellow color of turmeric.⁹ Curcumin incorporates a seven carbon linker and three major functional groups: an α, β-unsaturated β-diketone moiety and an aromatic O-methoxy-phenolic group. Diketo and keto enol form shown in figure 2.^9,10

Figure 2: (a) Keto enol form (b) Diketo form of curcumin

The aromatic ring systems, which are phenols, are connected by two α,β-unsaturated carbonyl groups.^9,11 It is a diketone tautomer, existing in enolic form in organic solvents and in keto form in water.¹² The diketones form stable enols and are readily deprotonated to form enolates; the α,β-unsaturated carbonyl group is a good Michael acceptor and undergoes nucleophilic addition. [citation needed] Because of its hydrophobic nature, curcumin is poorly soluble in water [9] but is easily soluble in organic solvents.¹⁰

Synthesis:

Commonly vanillin is used as a component along with acetyl acetone and boron oxide. A boron complex is made in the first step by acetyl acetone reacting with boron oxide.¹³ The purpose of the complex is to reduce the reactivity of the methylene group between the carbonyls by making it less nucleofilic. Due to the shielding, the terminal methyl groups will participate in the upcoming aldol reaction instead of the methylene. ^14,15By removing a hydrogen atom from one of the methyl groups, by using n-butyl amine, the carbon will act as a nucleophile on the carbonyl carbon in the vanillin in an ordinary aldol condensation Due to the ease to obtain the conjugated system through the molecule, a dehydration of the obtained aldol product will occur probably through an E1cB mechanism. The boron complex will be destroyed in the final step by addition of a hydrochloric solution. Another method of synthesize curcumin, is by doing a microwave assisted reaction with the same components as mentioned above, by using a domestic microwave oven. conventional heating the heat passes through the vessel wall before it reaches the content. This procedure takes time and energy. By agitating the content with microwaves the electric field makes the dipoles of the molecules to rotate in the try to align with the field. The result of this motion is that the temperature will rise rapidly with a direct interaction of the reacting content. A more homogeneous heating occurs and the time of heating is reduced. The method is also more rapid and environmental friendly than the conventional heating as less or no solvent is needed. The yields of the desired product in microwave-assisted reactions are many times excellent.^15,16

Figure 3: Synthesis of curcumin

EXTRACTION OF CURCUMIN:

The ideas behind sample extraction have existed since the beginning of human history. Throughout these ages, key natural chemicals from medicinal and other economically important plants were routinely subjected to percolation through soaking. In fact, to speed up the mass transfer of the target compounds into the organic phase, the necessary products were sometimes leached with the proper solvent while being heated and/or stirred. ¹⁷ Curcumin was first purified by Vogel Jr. in 1842.¹⁸ In 1910, Milobedeska et al. published a report on the structure of curcumin, identifying it as diferuloylmethane, following several decades of research. Lampe and Milobedeska successfully synthesized curcumin in 1913.^18,19 In 1953, Srinvansen recorded the chromatographic separation and by quantification of curcumin.¹⁸ Curcumin can be extracted using either conventional or advanced techniques. Since conventional extraction methods such as solvent extraction and Soxhlet extraction²⁰ require a considerable amount of time, organic solvents, cooling water, and energy^21,22, several researchers have applied novel extraction methods such as ultrasound-assisted extraction²³, microwave-assisted extraction²⁴. In order to address various difficulties, novel extraction methods have been designed.

a. Soxhlet extraction method:

The experimental setup for soxhletation consists of a heating nest, a distillation flask, a Soxhlet extractor, and a condenser. The dried sample is introduced into the thimble and placed in the Soxhlet extractor. By heating the distillation flask, the solvent changes into a vapor state. Then it is condensed and introduced into liquid form over the thimble in the extractor. The solvent penetrates the cellular wall of the solid sample, and the compound of interest is extracted. When the solvent volume reaches the extractor’s overflow level, the liquid is aspirated by a syphon and returned to the distillation flask. The extraction cycle is repeated until the bioactive compound of interest reaches the desired concentration. ^24,25 Soxhlet extraction is nowadays used as a reference extraction method, sometimes leading to extraction yields of curcumin close to 100%; however, it is a lengthy process and requires high energy costs.^26,27

b. Ultraviolet assisted extraction:

The basis of ultrasound is the simultaneous compression and expansion of sound waves with a frequency range of 20 kHz to 100 MHz. Intense shear forces, shock waves, macroturbulences, micromixing, and acoustic streaming are produced as a result of the cavitation phenomena, which are caused by ultrasonic waves. Motion energy is transformed into heat during the sonication process, acting as the activation energy for several physicochemical processes, which facilitate the conveyance of mass.^28,29 Hence, ultrasound-assisted extraction is noted as one of the novel methods for extracting curcumin

c. Microwave assisted extraction:

The present work reports on a novel extraction method using microwaves based on solvent-sample duo-heating synergism, for the extraction of curcumin from Curcuma longa L. The duo-heating mechanism is based on simultaneous heating of sample matrix and extracting solvent under microwave energy. Methanol soaked plant material was used as a modifier to bring about selective and effective heating of the sample under microwave. Acetone was used as the extracting solvent, which has excellent curcumin solubilizing capacity and heats up under microwave owing to its good dissipation factor. Microwave assisted extraction (MAE) under the influence of dual heating mechanism showed better precision and dramatically higher yield with significant reduction in extraction time under optimum extraction conditions, when compared to conventional approaches. ³⁰

Bioavailability of curcumin:

Bioavailability is defined as the part (percentage) of a given dose of the drug that reaches the circulatory system (systemic circulation).³¹ The active substance must also reach the target area within a certain time frame and remain there for a certain period. In the case of intravenous injection, when the medicine is administered directly into the circulatory system, the bioavailability is considered to be 100%.³² Curcumin is characterized by poor solubility and poor absorption in the free form in the gastrointestinal tract, and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. In recent years, several nanoformulation-based methods have been conducted for improving curcumin use in vitro and in vivo studies involving the use of adjuvants, stabilizers, conjugates/polymer conjugates, lipid/liposomes, hydro-/micro-/nanogels, and nanoparticles.³³

Nanotechnological Approaches to Improve Curcumin Bioavailability:

Advances in nanotechnology have reduced the gap between biological and physical sciences through the application of nanostructures such as nanomedicine and nanodrug delivery platforms.³⁴ Nanomaterials are small in size ranging between 1 and 100nm and have revolutionized the field of nanomedicine.³⁵

These nanostructures are employed in the development of biosensors, microfluidic systems, drug delivery, tissue engineering, and microarray testing.³⁶

Types of curcumin nano formulation:

i. Liposomes:

Liposome vesicles are an excellent source for drug delivery as they have similar compositions of the cell membrane and are biodegradable. Liposomes have been approved by FDA for drug delivery; however, there are still some obstacles regarding the liposome-based drug delivery system that is making their use as drug delivery vehicles expensive and cumbersome^36,37. Ikiki reported that curcumin-loaded liposomes and lipid-based nanoparticles have successfully been prepared using 1,2-dimyristoyl-sn-glycero-3-phosphocholine and an anionic amphiphile, L-glutamic acid, and N-(3 carboxy-1-oxo propyl)-,1,5-di hexadecyl ester. Bulboaca et al.³⁸ evaluated liposomal curcumin containing polyethylene glycol.

ii. Nano emulsion:

These nanoformulation droplets have a size between 20 and 200nm and are relatively stable compared to other nano-based formulations. In addition to this, nanoemulsion possesses optical transparency and shelf stability which is necessary for extending drug performance³⁹.

iii. Nanosuspensions:

Nanosuspensions possess a range of desirable characteristics that permits efficient drug solubility, increased absorption, and adherence to intestinal walls⁴⁰. As a result of rapid solubility and high penetration through the cell wall, nanosuspensions of curcumin prepared with homogenization technique have great potential for a protective and therapeutic role in diabetic cardiomyopathy and other cardiovascular disorders⁴¹.

THERAPEUTIC USES OF TURMERIC:

As we know curcumin is a natural product obtained from modified stem of plant having high potential to cure or treat disease from the ancient time .curcumin have the ability to treat various disease or various therapeutic effects on the body like anti inflammatory , antioxidant, anticancer etc. They are traditional Chinese medicines that promote blood circulation and remove blood stasis, and have long been used in China to treat pain, inflammation and other diseases. Turmeric is a common spice in India and has been described in Ayurveda, as a treatment for inflammatory diseases.⁴²In western herbalism, turmeric is primarily used as an anti-inflammatory agent.⁴³

In addition, curcumin-containing dietary supplements are extremely popular, and there are many anti-oxidant and anti-inflammatory curcumin dietary supplements on the market.^44,45

i. Anti-inflammatory effect:

Curcumin the main bioactive component of the turmeric has the ability to suppress the acute and chronic inflammation. It reduces inflammation by lowering histamine levels and by possibly increasing the production of natural cortisone by adrenal glands.⁴⁶

ii. Anticancer effect:

Curcumin potentially helps to prevent the new cancers that are caused by chemotherapy or radiation. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumour genesis and metastasis.⁴⁷

iii. Anti microbial effect:

Several studies have reported the broad-spectrum antimicrobial activity for curcumin including antibacterial, antiviral, antifungal, and antimalarial activities. Because of the extended antimicrobial activity of curcumin and safety property even at high doses (12g/day) assessed by clinical trials in human, it was used as a structural sample to design the new antimicrobial agents with modified and increased antimicrobial activities through the synthesis of various derivatives related to curcumin. Results showed that curcumin in combination with aloe vera and chitosan could be a potential suppressor for microbial growth in cotton, wool, and rabbit hair assessed by the exhaustion method.^48,49

iv. Anti hyperglycemia effect:

The spice turmeric, which is derived from the root of the plant Curcuma longa, has been described as a treatment for diabetes in Ayurvedic. The most active component of turmeric, curcumin, has caught scientific attention as a potential therapeutic agent in experimental diabetes and for the treatment of the complications of diabetes patients. Curcumin has been since extensively studied in experimental animal models of diabetes and in a few clinical trials of type 2 diabetic patients to treat their complications. Particular attention will be given to the anti-inflammatory and antioxidant properties of curcumin.⁴⁹

CONCLUSION:

Curcumin, also known as the "golden" molecule, is the main component of turmeric, a condiment that is frequently used in Indian and South Asian cuisine. Many studies currently demonstrate the pharmacological potential of curcumin and its related analogues as well as their potential health advantages, significance of these organic substances. This review seeks to draw attention to the many benefits and advancements of curcumin in contemporary medicine and promotes the development of new synthetic analogs with the best biological activities and the fewest problems with curcumin's bioavailability.

ACKNOWLEDGEMENT:

Author expresses his sincere thanks to Professor Kehar Singh, Pt. LR College of Pharmacy for providing support to carry out this review work.

CONFLICT OF INTEREST:

The authors declare that they have no conflict of interest.

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Received on 15.05.2024 Revised on 11.11.2024

Accepted on 04.02.2025 Published on 18.04.2025

Available online from April 22, 2025

Asian J. Res. Pharm. Sci. 2025; 15(2):135-140.

DOI: 10.52711/2231-5659.2025.00021

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.