Benefits of Curcumin

ABSTRACT

Various modalities of treatment are available for different dental diseases, but the major drawback of these conventional drug therapies is the numerous side effects associated with their use. This has led to renewed interest in the discovery of novel anti-infective natural compounds derived from plants.

Turmeric has been attributed a number of medicinal properties in the traditional system of medicine. The objective of this article is to review the efficacy of turmeric herb (curcumin) in maintainence of oral health, in particular and overall health, in general.

INTRODUCTION

Turmeric (haldi), a rhizome of Curcuma longa, is a flavourful yellow –orange spice.^1,2 It’s plant is 3 feet in height and has lance-shaped leaves and spikes of yellow flowers that grow in a fleshy rhizome or in underground stem. An orange pulp contained inside the rhizome constitutes the source of turmeric medicinal powder . Components of turmeric are named curcuminoids^3,4, which include mainly curcumin (diferuloyl methane), demethoxycurcumin, and bisdemethoxycurcumin. Curcumin (diferuloylmethane) is a polyphenol derived from Curcuma longa plant, commonly known as turmeric. The active constituents of turmeric are the flavonoid curcumin (diferuloylmethane) and various volatile oils including tumerone, atlantone and zingiberone. Other constituents include sugars, proteins, and resins. The best researched active constituent is curcumin, which comprises 0.3- 5.4 % of raw turmeric. Its chemical name is 1,7-bis (4-hydroxy, 3-methoxyphenyl) 1,6-heptadiene-3,5-dione. Curcumin has been used extensively in ayurvedic medicines for centuries, as it is nontoxic, and has a variety of therapeutic properties including antioxidant, analgesic, anti-inflammatory⁹, antiseptic activity, antimicrobial^5,6 and anticarcinogenic activity.^7,8

About 40-85% of an oral dose of curcumin passes through the gastrointestinal tract unchanged, with most of the absorbed flavonoid being metabolized¹⁰ in the intestinal mucosa and liver. Due to its low rate of absorption, cucumin is often formulated with bromelain for increased absorption and enhanced anti-inflammatory effect.

Curcuma zedoaria rosc, also known as white turmeric or gajutsu, is a perennial rhizomatous herb, that belongs to Zingiberacea family, found in topical countries, such as India, Bangladesh, Sri Lanka, Japan and Thailand. Various parts of this plant are used in Ayurveda and other folk medicines for the treatment of different ailments as pain¹¹, menstrual disorders, diarrhea, cancer, flatulence, degenerative eye disorder^12,13 and dyspepsia. In India, its popular vernacular names are Krachura (in Sanskrit), Gandamatsi (in Hindi) and Sutha (in Bengali)

The rhizome oil has been reported to contain antioxidants such as curzerene and epicurzerene (Mau et al., 2003). The tuber extracts of Curcuma zedoaria act as carminative, digestive stimulant, and exhibit antimicrobial action against Aspergillus niger, Bacillus subtilis, Candida albicans, and Klebsiella pneumonia (Wilson et al., 2005). In addition, it has been shown to benefit the kidneys.¹⁴ Despite its reported benefits via inflammatory and antioxidant mechanisms, one of the major problems with ingesting curcumin by itself is its poor bioavailability¹⁵, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. For example, piperine, a known bioavailability enhancer, is the major active component of black pepper¹⁶ and is associated with an increase of 2000% in the bioavailability of curcumin.¹⁷ Therefore, the issue of poor bioavailability appears to be resolved by adding agents such as piperine that enhance bioavailability, thus creating a curcumin complex.

It also contains curcemenol and sesquiterpene, which possess anti-inflammatory, antitumor, hepatoprotective and neuroprotective effects. These compounds also aid in decreasing lipopolysachharide (LPS)-induced nitric oxide production, thus reducing the level of proinflammatory cytokines (Lo et al., 2015). Curcuzedoalide, found in the rhizomes of C. zedoaria, displays antiproliferative action against human gastric cancer cell lines by inciting apoptosis (Jung et al., 2018).

MEDICAL IMPLICATIONS OF CURCUMIN

Anti-oxidant effects

A study of ischemia in the feline heart demonstrated that curcumin pre-treatment decreased ischemia induced changes in the heart. Evaluating the outcome of curcumin by an in vitro study on endothelial heme oxygenase-1, an inducible stress protein, which was carried out by utilizing bovine aortic endothelial cells. Incubation with curcumin ensued in intensified cellular resistance to oxidative changes.

Anti-inflammatory

It reduces inflammation by lowering histamine levels and possibly by increasing the production of natural cortisone by the adrenal glands. Oral administration of curcumin in instances of acute inflammation was found to be as effective as cortisone or phenylbutazone, and half as effective in cases of chronic inflammation. Its anti-inflammatory properties may be attributed to its ability to inhibit both biosyntheis of inflammatory prostaglandins from arachidonic acid and neutrophil function during inflammatory states.

Hepatoprotective

It protects the liver from a number of toxic compounds like carbon tetrachloride (CCl 4), galactosamine, acetaminophen (paracetamol) and Aspergillus aflatoxin. Sodium curcuminate, a salt of curcumin, also exerts choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin as well as by increasing bile solubility, therefore, possibly preventing and treating cholelithiasis. Curcumin has choleretic activity that increases bile output and solubility, which may be helpful in treating gallstones.

Antiplatelet aggregation

It has been shown to prevent platelets from clumping together, which in turn improves circulation. Inhibition of platelet aggregation by curcumin constituents is thought to be via potentiation of prostacyclin synthesis and inhibition of thromboxane synthesis

Antimutagenic

Curcumin is antimutagenic as it potentially helps to prevent new cancers that are caused by chemotherapy or radiation therapy used to treat existing cancers. It effectively inhibits metastasis (uncontrolled spread) of melanoma ( skin cancer ) cells and may be especially useful in deactivating the carcinogens in cigarette smoke and chewing tobacco. Animal studies involving rats and mice as well as in vitro studies utilizing human cell lines have demonstrated curcumin’s ability to inhibit carcinogenesis at three stages: Tumor promotion, Angiogenesis, Tumor growth. In two studies of colon and prostate cancer, curcumin inhibited cell proliferation and tumor growth. The anticarcinogenic effects of turmeric and curcumin are due to direct antioxidant and free-radical scavenging effects and their ability to indirectly increase glutathione levels, thereby aiding in hepatic detoxification of mutagens and carcinogens and in inhibiting nitrosamine formation

Antimicrobial

Turmeric extract and the essential oil of Curcuma longa inhibits the growth of a variety of bacteria, parasites and pathogenic fungi. Improvements in lesions were observed in the dermatophyte – and fungi-infected guinea pigs, as at 7 days post-turmeric application, the lesions disappeared. Curcumin has also been found to have moderate activity against Plasmodium falciparum and Leishmania major.

Cardiovascular effects

Turmeric’s protective effects on the cardiovascular system include lowering cholesterol and triglyceride levels, decreasing susceptibility of low density lipoproteins (LDL) to lipid peroxidation and inhibiting platelet aggregation. These effects have been noted even with low doses of turmeric. Turmeric extract’s effect on cholesterol levels may be due to decreased cholesterol uptake in the intestines and increase conversion of cholesterol to bile acids in the liver

Local effects

Fresh juice from the rhizome or a paste prepared from turmeric or decoction is often used as a local application as well as internally in the treatment of leprosy, snake bites and vomiting associated with pregnancy.

Gastric effects

Curcumin has a significant role in cases of gastric ulcers. An open, phase II trial was performed on 25 patients with endoscopically diagnosed gastric ulcer. Participants were provided 600 mg powdered turmeric, five times daily. After 4 weeks, ulcers had completely healed in 48% patients.

Neurological effects

Curcumin can interact and modulate many molecular targets such as transcription factors, inflammatory cytokines, kinases, growth factors and antioxidant system. All these actions of curcumin will be responsible, at least in part for its neuroprotective. Many of these beneficial effects mentioned before have been demonstrated by several paths in different types of cells from the nervous system, such as neurons, astrocytes and microglia. Some researchers employing primary cell cultures from different regions of the nervous system have also observed the capacity of curcumin to act as neuroprotector due to its antioxidant, anti-inflammatory and anti-protein aggregating properties in cortical, mesencephalic, hippocampal and spinal cord cells.

Furthermore, the capacity of curcumin to decrease neuro-inflammation, which takes place in the progression of neurodegenerative diseases, by reducing the expression of IL-1α, IL-6 and TNF-α in LPS-stimulated BV2 microglia in a dose dependent manner has been well established. AD shows signs of defective phagocytosis that result in an ineffective clearance of Aβ plaques. Curcumin can stimulate microglial phagocytosis and clearance of Aβ plaques in vitro and increase the induction of heat-shock proteins in response to the addition of soluble Aβ aggregates to neuronal cell cultures. It also can attenuate the β-amyloid accumulation and inhibit the formation of Aβ fibrils in these cells. Moreover, in dopaminergic neurons, neurotoxicity triggered by 6-hydroxydopamine (6-OHDA) curcumin attenuated the toxicity in SH-SY5Y and MES23.5 cells through the inhibition of ROS, mitochondrial protection and anti-apoptotic mechanisms.

Effects on Respiratory System

Pulmonary fibrosis is characterized by an accumulation of inflammatory cells in the airways. These cells can generate a high increase in the cytokines, ROS and growth factors which promote in turns the basis of the fibrotic scar. In this sense, several studies performed in animal models have demonstrated that curcumin acts against pulmonary fibrosis mainly by decreasing the inflammatory mediators. Venkatesan and Chandrakasa showed the beneficial effects of curcumin against cyclophosphamide-induced pulmonary fibrosis in rats. These effects were a reduction in leukocytes and inflammatory mediators and an increment in lung antioxidant defences. Similar results were obtained by Venkatesan who also described that rats injected with paraquat, to provoked pulmonary fibrosis and treated with curcumin had a lower inflammatory response, toxicity and mortality associated to this herbicide.

Curcumin has been widely used in ancient Indian medicine for allergy and asthma treatment and currently, several studies have found that curcumin has a powerful activity both in vitro and in vivo against asthma. These effects are produced by an inhibition of IL-5, IL-4, IL-2, immunoglobulin (Ig) E2 production and by decreasing the histamine effects in peritoneal mast cells from rats.

Anti Venom Effect

Curcumin was listed as a herbal plant metabolite that can effective against Snake Venom PLA2.[118] Researchers studied the structural relationship between medicinally important herbal compounds such as acalyphin, chlorogenic acid, stigmasterol, curcumin and tectoridin and PLA2 from Russell's viper. The molecular modeling studies revealed favorable interactions with the amino acid residues at the active site of venom PLA2 that could result in the inhibition.[119]

ORAL IMPLICATIONS OF CURCUMIN

Dental Pain

Massaging the aching teeth with roasted, ground turmeric eliminates pain and swelling.

Rinsing the mouth with turmeric water (boil 5g of turmeric powder, 2 cloves and dried leaves of guava in 200g water) gives instant relief.

Dental Plaque Detection System

Dental-Plaque staining agent, which contains turmeric extracts and curcumin, and a light emitting apparatus, which gives out light having a wavelength within a range of 250-500 nm to an object in the oral cavity where the dental plaque staining agent is attached.

Periodontal Problems

Topical application: Applying a paste made from1 tbsp of turmeric with ½ tsp of salt and ½ tsp of mustard oil provides relief from gingivitis and periodontitis. It is recommended to rub the teeth and gums with this paste twice daily.

Mouth Wash: In a study by Waghmare et al, about 100 subjects were randomly selected. Both gingival index and plaque index were recorded at 0, 14, and 21 days.

It was concluded that chlorhexidine gluconate as well as turmeric mouthwash can be effectively used as an adjunct to mechanical plaque control methods in prevention of plaque and gingivitis. Turmeric mouthwash prepared by dissolving 10 mg of curcumin extract in 100 ml of distilled water and 0.005% of flavouring agent peppermint oil with pH adjusted to 4 is found to be as effective as most widely used chlorhexidine mouthwash. Though chlorhexidine gluconate has been found to be more effective when antiplaque property was considered. The effect of turmeric observed may be because of its anti-inflammatory action.

Local Drug Delivery System

In a study conducted by Behal et al., 30 subjects with chronic localized or generalized periodontitis with pocket depth of 5-7 mm were enrolled in a split-mouth study design.

Control sites received Scaling and Root Planing [SRP] alone, while experimental sites received SRP plus 2% whole turmeric gel. Both groups demonstrated statistically significant reduction in plaque index, gingival index, sulcus bleeding index, probing pocket depth, and gain in relative attachment loss. There was a significant reduction in the trypsin-like enzyme activity of “red complex” microorganisms. Greater reduction was observed in all parameters in the experimental group in comparison to those in the control group. Thus, the local drug delivery system containing 2% whole turmeric gel can be used as an adjunct to scaling and root planning.

Subgingival Irrigant

In a study conducted by Suhag et al., periodontal sites were treated on day 0 (baseline) by a single episode of scaling and root planing. Subsequently selected sites were irrigated (triple irrigation regimen) with either saline (0.9%), chlorhexidine (0.2%), curcumin (1%), or served as nonirrigated control sites on day 0 (baseline) immediately following instrumentation. Triple irrigation regimen was repeated for the next 5 consecutive days and on days 15 and 21. Clinical parameters recorded were probing pocket depth (PPD), bleeding on probing (BOP), and redness for 200 sites in 20 patients with chronic periodontitis. The results indicated that the irrigated sites had significant improvement in all parameters as compared with the nonirrigated sites on days 2, 3, 4, and 5. The curcumin group showed significant reduction in BOP (100%) and redness (96%) when compared with the chlorhexidine group and saline group on day 5. However, the difference between groups was not significant at the next recall visits. Mean PPD reduction was significantly greater for the curcumin group than all other groups on all post-treatment days. Thus, 1% curcumin solution can cause better resolution of inflammatory signs than chlorhexidine and saline irrigation as a subgingival irrigant.

Pit and Fissure Sealant

This sealant can be produced from a composition comprising a polymerizable resin system containing acrylic monomer and at least one colorant selected from the group consisting of annatto extract, turmeric extract, and Beta-Apo-8’- Carotenol.

Anticancer Properties

Curcumin has been found to possess anticancer activities because of its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis, and metastasis.

It potentiates the effect of chemotherapy and acts as an enhancer of radiotherapy. Also, it is found to arrest carcinomatous cells in the G2/M phase of cell cycle, in which cells are more susceptible to cytotoxic effects of radiotherapy.

Precancerous lesions

Its role in the treatment of various precancerous conditions like oral submucous fibrosis, leukoplakia, and lichen planus has also been studied. Turmeric extract and turmeric oil have demonstrated oncopreventive activity in in vitro and sensation and pain were reduced and partial reversal in vivo animal experiments. The local symptoms of burning of opening of the mouth was also observed.

CONCLUSION

Curcumin (C21H20O6) has promising ability in the improvement of current medicine for the treatment of various diseases. Safety regarding the use of curcumin make it more interesting since people in India use it orally to cure sore throat. Curcumin has much higher potential of not only the treatment but also the prevention of many diseases as demonstrated by numerous studies. Curcuminoids or derivatives of curcumin are important anticancer and anti-inflammatory agents. However, more studies are required regarding curcumin nano-formulations to find out the effectiveness as well as toxic effects of these particles in small and large concentrations and during different phases of clinical trials. From these studies, it would be possible to compare efficacy of free curcumin and curcumin with its nanoparticles to reveal its effect against cardiovascular diseases and cancer. Most importantly these trials need to be conducted on humans in order to evaluate their effect practically in clinical applications for cancer and other diseases.

CONFLICT OF INTEREST STATEMENT: We declare that we have no conflict of interest.

REFERENCES