Curcumin acts as an antioxidant agent because of its phenolic structure. This compound alters serum glutathione and superperoxidase activity, reduces lipid peroxidation [10] and scavenges the reactive oxygen species. As curcumin has both prooxidant and antioxidant properties, it is a superior compound to maintain a physiological homeostasis to prevent diseases [11].

Anti-inflammatory action of curcumin occurs by lowering histamine levels and increasing the production of natural cortisone [8]. It has an anticoagulant action by preventing platelets from clumping together [8].

Most significant role of curcumin is its antitumerogenic and chemopreventive role [5]. Curcumin shows growth inhibitory effect on cell lines of various cancers like those of large intestine and bone, leukemia and oral malignant epithelium (derived from malignant tumor) [11]. In different studies on the cell lines of various cancers, curcumin inhibited proliferation of cells and accumulated cells at G2/M cell cycle [11]. A study on turmeric and oral cancer reported that curcumin taken either in diet or applied locally could significantly reduce DNA adducts [12]. The number of adducted DNA was significantly affected by 0.1% turmeric and 0.03% curcumin supplementation [13]. Most importantly, curcumin effectively repaired the broken DNA strands in the peripheral cells [14]. Curcumin also can deactivate tobacco carcinogens [8]. Pathogenesis of cancer has been associated with various proinflammatory molecules like nuclear factor Kappa (NFκ) B, interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF) [15]. At the molecular level curcumin suppresses tumor promoter transcription factor NFκB and apoptotic protein (AP)-1 [10]. Research demonstrated that it down-regulated the expression of NFκB, cyclooxygenase (COX)-2, and phosphorylated STAT3 in blood mononuclear cells of multiple myeloma patients [5].

Another study done by Gupta et al. [14] on inhibitory activity of curcumin on inhibitor of Kappa B Kinase (IκBK) an enzyme responsible for NFκB activation, the authors found that there was a reduction of IκBK activity in head and neck squamous cell carcinoma (HNSSC).

Curcumin inhibits cell signaling pathways including Akt, NFκB, AP-1 or JNK [16]. Also curcumin up-regulates genes related to cell growth arrest and down-regulates genes related to cancer cell proliferation such as egr-1, cmyc, bcl-X and mutated p53. egr-1, cmyc and bcl-X, and abnormal tumor suppressor gene such as p53 [11]. Gene expression profiling by cDNA array was performed on total RNA extract from curcumin treated and untreated oral epithelial cancer cells. There was fourfold increase in the pro-apoptotic activating transcription factor 3 (ATF3) in the curcumin treated oral epithelial cancer cells [11]. Curcumin also effectively inhibits metastasis by decreasing invasive potential of a carcinogen through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 3 (MEKK3) and p-mitogen-activated protein kinase 12 (MAPK12: ERK3) signaling pathways which inhibit matrix metalloproteinases (MMP)-2 and MMP-9 [17]. It ceases the proliferation of endothelial cells [10] by inhibiting VEGF [17].

Curcumin has a chemopreventive effect on oral precancerous lesions like oral leukoplakia (OL) [11], oral lichen planus (OLP) and oral submucous fibrosis (OSMF) [1018]. A study using OL lesion showed that curcumin reduced the size of a lesion by 10% in the treated 62 patients [11]. In OSMF, curcumin reduces the micronuclei formation in exfoliated mucosal cells and in circulating lymphocytes. This protective effect on micronuclei formation can help to prevent oncotransformation [10]. It can prevent and reduce the formation of fibrosis by acting as an antifibrotic agent in OSMF [9]. Its mode of action is by blocking leukocyte influx and inhibiting the activation of inflammatory cells [10].

Curcumin due to its inhibition on activation of inflammatory cells provides relief to patients with gingivitis and periodontitis [10]. Because of pharmaceutical effect of curcumin, it is now used as a supplement in several countries including the United States, India, Japan, Korea, Thailand, China, Turkey, South Africa, Nepal, and Pakistan [17].

Garlic has an important antineoplastic property. Various studies have shown that consumption of high levels of garlic decreases the risk of colon, stomach cancer and melanomas by inhibiting the growth and proliferation of cancer cells [519]. A previous study demonstrated that water extract of fresh garlic had apoptotic effect on cancerous cells and prevented the inception of oral carcinoma [21]. Another study using 7,12-dimethylbenz[a]anthracene (DMBA) induced buccal pouch cancer model reported that, garlic caused apoptosis of malignant cells [6]. It can act as an anticarcinogenic agent by scavenging the free radicals, increasing gluathione levels, increasing the activities of enzymes such as glutathione Stransferase and catalase, inhibiting cytochrome p450 2E1 enzyme and inducing DNA repair mechanisms; at the same time preventing chromosomal damages [5]. Thus it is an alternative therapeutic agent for primary as well as invasive cancer [21].

It is demonstrated that garlic plaster can be effectively used in the treatment for recurrent oral ulcers (ROU) [22]. Garlic plaster was made and applied to the oral ulcer lesions and the patients were for 1-4 years. The authors found that the complete effective rate was 83.3% while total effective rate was 100%. Garlic exerts a strong antimicrobial activity against gram-positive and gram-negative bacteria, viruses, fungi and parasites. Topical and dietary garlic has been used in the treatment of diseases like dermatologic infections and warts [19].

Strong antioxidant activity of gingirol is due to its superoxide dismutase (SOD) like activity as it can counteract reactive oxygen species; scavenge superoxide anions, hydroxyl, peroxyl and nitric oxide (NO) radicals [125]. Antioxidant property of ginger is used as an antiulcer therapeutic agent [23].

Ginger has a strong anti-inflammatory property by inhibiting arachidonic acid metabolism in the COX and lipoxygenase (LOX) pathways [1]. Several researches have proved that gingerdiones and shogaols can act similar to non-steroidal anti-inflammatory drugs (NSAIDs) [23]. Ginger is an effective agent against the pro-inflammatory cytokines which are secreted at the site of inflammation. It was demonstrated that ginger extract inhibited lipopolysaccharide induced activation of macrophages by inhibiting the pro-inflammatory cytokine and chemokines [26]. Furthermore, it was revealed that ginger extracts were responsible for decrease in proliferation of T cells and thus decrease in production of IL-2 and interferon (IFN)-γ. Usually macrophages act as antigen presenting cell (APC) and thus are responsible for stimulation of T cell proliferation. These activated T cells then release IL-2 and IFN-γ.

Curcumin plays a significant role in the prevention of OSMF by inhibiting myofibroblasts (MF). MFs are responsible for fibrosis by releasing transforming growth factor (TGF)-β. Curcumin inhibits the proliferation of MF and thus inhibits fibrosis. MFs are also responsible for type I and type II collagen formation which was effectively inhibited by curcumin. Curcumin is responsible for cessation of proliferation of MF by arresting the cell cycle at G0/G1 phase and increasing apoptosis [9] through a decrease in Bcl-2/Bax ratio [10]. Ginger inhibits NFκB signaling pathway and thus represses COX-2 expressions [5]. Ginger has a dose dependent cytotoxicity on oral carcinoma cells by activating caspase-3-mediated apoptosis [25].

Ginger also down-regulates NFκB-regulated gene products which reduces release of IL-8 and VEGF which are responsible for angiogenesis [24]. These favorable effects help to prevent tumor growth and metastasis [27]. Gingerols and gingerdiol has a dose dependent antimicrobial effect. Studies demonstrated that they also act as an antiviral and an antifungal agent [2328]. It can also acts as blood thinners by inhibiting platelet thromboxane-B2 (TBX₂) and other production [29]. These properties make it useful for the treatment of tooth ache, as a sialogogue to promote salivation for treating oral candidiasis and herpes simplex virus-1 infection [29].

Studies have proved that honey possesses strong bactericidal and bacteriostatic property. It is mainly effective against gram-positive bacteria such as A pyogenes, S. mutans, S. aureus etc. Honey has shown strong antimicrobial activity because of its low water content and low pH [30]. Other than these, honey contains glucose oxidase which produces hydrogen peroxide which has a strong bactericidal action [30]. Studies demonstrate that ingestion of honey can inhibit the growth of bacteria that causes caries and thus provides a carioprotective effect [30]. It also inhibits the development of dental plaque, gingivitis, and periodontal diseases [31]. Honey has antifungal activity by inhibiting C. albican [3031]. Pichichero et al. [32] studied the role of honey on C. albicans and found that the amylase present in honey increased the osmotic effect in the media by increasing the sugar concentration and consequently inhibited the fungal activity. Honey also shows antiviral activity against herpes labialis and rubella virus. Jungle honey acts as chemotactic inducer for neutrophils.

It also shows strong antioxidant activity by scavenging free radicals and by preventing the formation of free radicals released from the inflamed tissues [31]. Antioxidant property is due to its content of glucose oxidase, catalase, ascorbic acid, flavonoids compounds [31]. Furthermore, honey helps in increasing absorption and activity of some antioxidants like vitamin C (47%), carotene (3%), uric acid (12%), glutathione reductase (7%). The antioxidant activity is responsible for preventing several chronic diseases including cancer [3031].

Effects of tulang honey on OSCC and osteosarcoma were reported [33]. The authors demonstrated that honey has an apoptotic mechanism on OSCC and human ostogenic sarcoma (HOS) cell lines by acting as an antiproliferating agent. It induces apoptosis by up-regulating p53 and by modulating the expression of pro and anti-apoptotic proteins. It is also responsible for activation of caspase-3 pathway because of its phenolic and tryptophan components [29]. It was hypothesized that honey transduced the apoptotic signal via initial depletion of intracellular non-protein thiols, and then consequently reduced the MMP by increasing the ROS generation required for apoptosis [33]. Thus honey acts on cancer cell line by inducing cell-growth arrest by cell cycle blockage at the sub-G1 phase [33].

Previous studies showed that water soluble derivative of honey i.e. propolis and its associated phenolic compounds had antimetastatic effects [303334]. When honey is taken orally it activates the immune system by stimulating antibodies in primary and secondary immune response. It also stimulates inflammatory cytokines production. Manuka honey (jelly type of honey) specifically increases tumor necrosis factor (TNF)-α, IL-1β, IL-6 by stimulating monocytes. Lower immune system is more prone to cancer, thus ingestion of honey can be beneficial for immunocompromized patients [3031]. Polyphenols like chrysin, galangin, quercetin, acacetin, kaempferol, pinocembrin, pinobanksin and apigenin present in honey has a very strong antiproliferative property [34]. Honey also has anti-ulcerogenic as well as anti-lipid effect. It has also been shown to possess anti-inflammatory, anti-atherogenic, anti-thrombotic, immune modulating and analgesic properties [3133]. Honey is useful in preventing and controlling S. aureus infection by its enzymatic production of hydrogen peroxide property. Honey has a stimulatory action on wound repair and regenerative tissues [35]. Study on animal model showed that it has an ability to decrease the number of inflammatory cells and hence can act as an anti-inflammatory agent [36].

Anethole is the chief active constituent of spice fennel. Its chemical name is 1-methoxy-4-(1-propenyl) benzene [5]. Important constituent of anise is anethole ditholethione (ADT) [37].

ADT acts as an antioxidant agent by inhibiting lipid peroxidation and increasing intracellular glutathione and glutathione S transeferase by scavenging hydroxyl radical [38].

Various research on anise showed that it inhibits NO production and hence acts as a very effective antimicrobial agent. It also inhibits lipopolysaccharide-induced NO production [38]. Anethole also acts as an antiviral agent and specifically against aciclovir-resistant herpes simplex virus-1 strains by interrupting the absoprtion of herpes viruses on cell wall [39]. In oral cavity, anise kills odor-causing bacteria and thus so it is a natural herbal remedy for bad breath [40].

Non oxidative mechanism for anticarcinogenic effects of lycopene is through regulation of gap junction communication [44]. Lycopene is a significant anticancer agent by its various mechanisms. Lycopene's ability for quencher of single oxygen is twice as high as β-carotene and ten times higher than vitamin A [4245]. It is a scavenger of free radicals preventing oxidative stress, which causes DNA damage [4245]. Lycopene also inactivates free radicals which are responsible for lipid peroxidation process thus preventing tissue damage [42]. Another anticancer mechanism is the suppression of carcinogen-induced phosphorylation of p53, Rb antioncogenes and stopping the cell division at the G0-G1 cell cycle phase. It acts as an antiproliferative agent by inhibiting insulin like growth factor and thus reduces proliferative capacity of cells. Modulation of immune functions is carried out by regulation of intrathymic T-cell differentiation [44]. It also acts as an antitumor agent by induction of apoptosis and modulation of carcinogen metabolizing enzyme [42].

Various studies demonstrated that lycopene has an effect on diverse oral conditions like OSMF and OL [42]. It has been demonstrated that in OSMF, lycopene inhibited abnormal growth of human abnormal fibroblast, and an up-regulated lymphocyte resistance to stress. It has been proved that lycopene singly or with intralesional steroid injections has positive effect on mouth opening and at the same time can be helpful in alleviation of burning sensation symptoms. Thus lycopene has been claimed to be an effective, safe and reliable drug in OSMF [42].

Studies have demonstrated that it can resolve OL as they have a protective effect on cells against cell damage and progression of dysplasia [42434546], and therefore can be recommended in the treatment regimen of OL.