**6.4 Cardiovascular protection**

For decades, investigation on the health-promoting effects of Asian diet has been revealed that *Ocimum* oil consumption is a key factor in the cardiovascular protection found in Asian origin [115]. It is well established that the healthful properties of *Ocimum basilicum* L. oil depend largely on its Cardiac glycosides and catecholamines content [116]. But, many arguments prove that in *Ocimum* oil there are little bioactive components, much than Cardiac glycosides and catecholamines, effective for its cardiovascular protective properties: among them, the ethanolic fraction of *Ocimum* oil, and in specific omega-3 fatty acids have proved antioxidant, anti-platelet aggregation, vasodilatory, and anti-inflammatory effects, all engaged in this health beneficial action [117–119].

Oxidation of LDL cholesterol is one of the key steps in the induction of atherosclerotic lesions by increasing damage to the arterial side through several processes, including growth factor and chemotactic protein expression, inflammation, and build up local macrophages [120, 121] have indicated that ethanolic leaf extract of *Ocimum basilicum* L. oil strongly inhibits copper sulfate-induced oxidation of LDL, as a result of the step of different indicators of lipid oxidation [phospholipids (PL), cholesterol ester (CE), triacylglycerol (TG)].

Although the contraction of plasmatic cholesterol and LDL is the primary technique regulating the antiatherogenic activity of *Ocimum basilicum* L. extract, other implements are further identified [121]. It is well settled that local leukocyte and monocyte recruitment into the vessel wall is initial walk-in atherogenesis. This fact takes combined with the statement in the endothelial cells of adhesion fragments such as intercellular adhesion fragment-1 (ICAM-1) and vascular adhesion fragment-1 (VCAM-1). Aqueous extract of *Ocimum gratissimum* L. showed the capacity to reduce LPS-stimulated expression of BEAS-2B cell in human lung epithelial cells inhibiting its mRNA levels. Moreover, Li et al. [122], investigating the action of distillate and residue fractions of basil essential oil (viz. estragole, methyl eugenol, linoleic acid, α-cadinol, and α-bergamotene) in-a Raw 264.7 cells line, have demonstrated that residue fractions prevents the expression of gene and suppressed the production of cytokines (TNF-a, IL-b, IL-6) in LPS-induced Raw264.7 cells, which contribute to treating various disorders caused by extreme oxidative stress.

### **6.5 Anti-inflammatory**

The inflammatory response involves long been compartmentalized into multiple attributes commonly termed redness, heat, pain, and edema. Inflammatory injuries lead to the discharge of a variety of fundamental mediators, cytokines, and chemokines that balance cellular infiltration that consequentially brings about resolving inflammatory response and restoration of tissue scrupulosity. However, immutable inflammatory stimuli or dysregulation of mechanisms of the resolution phase can lead to chronic inflammation [123, 124].

*Ocimum* extracts contain numerous constituents which could have antiinflammatory effects. The anti-inflammatory effects of *Ocimum* oil phenolics, in RAW 264.7 macrophage cells have been described by Aye et al. [125]. When added to murine macrophages stimulated with bacterial lipopolysaccharide (LPS), *Ocimum* oil phenolics did not cause cytotoxicity in RAW 264.7 macrophage cells in vitro, as evaluated by a significant increase in the production of nitric oxide [125]. Additionally, NO is a significant inflammatory mediator generated by NOS (neuronal, inducible, and endothelial) under physiological and pathophysiological conditions [126]. It further serves as a crucial mediator during the inflammatory process. Enhanced NO production and iNOS expression contributes to the great cytotoxic function of LPS stimulated macrophages [127]. Thus, the reduction in NO production indicates the anti-inflammatory activities of the treatment in the cells. However, *Ocimum basilicum* L. ethyl acetate extract and butanol extract inhibited the growth of normal RAW 264.7 macrophage cells [128]. Also, *Ocimum basilicum* L. crude methanolic extract suppressed the induction of iNOS and the subsequent production of NO in LPS-stimulated RAW 264.7 macrophage cells [129, 130]. To test the anti-inflammatory activity of the *Ocimum basilicum* L. methanolic extracts has been determined by PBMC (peripheral blood mononuclear cells) in mitogenic lymphocyte proliferative assay, methanolic extracts enhanced the functional activity of these immune-competent cells, as evaluated by a significant inhibitory effects of methanolic leaf extracts, PHA activated PBMC proliferation could be suggestive of suppression of T cell proliferation [130]. This effect arose from its pivotal role in

**193**

**6.6 Antidiabetic**

Ocimum *Phytochemicals and Their Potential Impact on Human Health*

immune regulation [131, 132], T cell activation provides a target for pharmacological modulation aimed at achieving clinically useful immune-suppression [133]. Złote et al. [134] studied the capacity of phenolic-rich fraction obtained from the elicited basil leaves to inhibit the activity of two enzymes of inflammatory process (LOX and COX). This research found that a higher LOX and COX inhibition efficiency was positively correlated with the increased contents of rosmarinic, benzoic and *o*-coumaric acids determined after elicitation of basil. This result partially corresponds with the study of [135]. More recently, to gain insight into the mechanism of action and pharmacological value of the anti-inflammatory activity of aqueous and methanolic extracts of *Ocimum basilicum* L. in macrophage (RAW264.7) and human chondrosarcoma (SW1353) cell lines, and human primary chondrocytes to correlate their efficacy in terms of management of osteoarthritis (OA). Raina et al. [136] evaluated aqueous extract of *O. basilicum* L. significantly accustom the production of inflammatory mediators such as NO, PGE2, LTB4, and MMPs increased than the methanolic extract. The regulation of these inflammatory intermediaries is pivotal in OA, as it would have a direct effect on (1) chondrocyte survival, (2) production of proinflammatory cytokines, prostaglandins and leukotrienes, and (3) production of extracellular matrix-degrading enzymes such as MMPs. Due to the significant side-effects related to the use of NSAIDs, the check for natural products that would regulate the inflammatory cascade related to OA, without engaging chondrocyte survival, is extremely important. To investigate the anti-inflammatory effect of *Ocimum basilicum* L. oil, Rodrigues et al. [137] investigated an acute and chronic in vivo test as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was also analyzed by the participation of histamine and arachidonic acid pathways. These researchers found that the *Ocimum basilicum* L. essential oil and estragole significantly reduced paw edema induced by carrageenan and dextran. The smallest quantities of *Ocimum basilicum* L. essential oil (50 mg/kg) and estragole (30 mg/kg) revealed effectiveness in the decrease of paw edema created by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. These dosages were carried out of decrease the assured inflammatory process. The results followed between the *Ocimum basilicum* L. essential oil and estragole determine efficacy in antiinflammatory activity, however, the essential oil is higher efficacious in the acute and chronic anti-inflammatory action. Dextran is a high molecular weight polysaccharide, which differently to carrageenan, induces anaphylactic reactions characterized by extravasation and formation of edema due to mastocyte degranulation with release of histamine and serotonin. Carrageenan induces an inflammatory response through opinion with sulfated polysaccharides, initially encouraging the free of chemical substances which encourage multifactorial facts, mostly concerning the free of substance P, bradykinin, histamine, serotonin, cytokines, and nitric oxide and, subsequently on commodity arise from the arachidonic acid pathway [138].

Diabetes mellitus is a chronic metabolic disorder caused by an absolute or relative lack of insulin and or reduced insulin activity which results in hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism [139, 140]. The hypoglycemic effect of *O. tenuiflorum* L., *O. canum* Sims. and *O. gratissimum* L. in animals with alloxan-induced diabetes was applied to potentiation of glucoseinduced insulin free and parallel increased peripheral uptake of glucose [141, 142]. Successive studies have reported a greater link of antidiabetic deal with the antioxidant effects of *Ocimum* oil. The character played by OS for diabetes complications

*DOI: http://dx.doi.org/10.5772/intechopen.88555*

#### Ocimum *Phytochemicals and Their Potential Impact on Human Health DOI: http://dx.doi.org/10.5772/intechopen.88555*

*Phytochemicals in Human Health*

**6.5 Anti-inflammatory**

lead to chronic inflammation [123, 124].

cholesterol ester (CE), triacylglycerol (TG)].

Oxidation of LDL cholesterol is one of the key steps in the induction of atherosclerotic lesions by increasing damage to the arterial side through several processes, including growth factor and chemotactic protein expression, inflammation, and build up local macrophages [120, 121] have indicated that ethanolic leaf extract of *Ocimum basilicum* L. oil strongly inhibits copper sulfate-induced oxidation of LDL, as a result of the step of different indicators of lipid oxidation [phospholipids (PL),

Although the contraction of plasmatic cholesterol and LDL is the primary technique regulating the antiatherogenic activity of *Ocimum basilicum* L. extract, other implements are further identified [121]. It is well settled that local leukocyte and monocyte recruitment into the vessel wall is initial walk-in atherogenesis. This fact takes combined with the statement in the endothelial cells of adhesion fragments such as intercellular adhesion fragment-1 (ICAM-1) and vascular adhesion fragment-1 (VCAM-1). Aqueous extract of *Ocimum gratissimum* L. showed the capacity to reduce LPS-stimulated expression of BEAS-2B cell in human lung epithelial cells inhibiting its mRNA levels. Moreover, Li et al. [122], investigating the action of distillate and residue fractions of basil essential oil (viz. estragole, methyl eugenol, linoleic acid, α-cadinol, and α-bergamotene) in-a Raw 264.7 cells line, have demonstrated that residue fractions prevents the expression of gene and suppressed the production of cytokines (TNF-a, IL-b, IL-6) in LPS-induced Raw264.7 cells, which

contribute to treating various disorders caused by extreme oxidative stress.

*Ocimum* extracts contain numerous constituents which could have antiinflammatory effects. The anti-inflammatory effects of *Ocimum* oil phenolics, in RAW 264.7 macrophage cells have been described by Aye et al. [125]. When added to murine macrophages stimulated with bacterial lipopolysaccharide (LPS), *Ocimum* oil phenolics did not cause cytotoxicity in RAW 264.7 macrophage cells in vitro, as evaluated by a significant increase in the production of nitric oxide [125]. Additionally, NO is a significant inflammatory mediator generated by NOS (neuronal, inducible, and endothelial) under physiological and pathophysiological conditions [126]. It further serves as a crucial mediator during the inflammatory process. Enhanced NO production and iNOS expression contributes to the great cytotoxic function of LPS stimulated macrophages [127]. Thus, the reduction in NO production indicates the anti-inflammatory activities of the treatment in the cells. However, *Ocimum basilicum* L. ethyl acetate extract and butanol extract inhibited the growth of normal RAW 264.7 macrophage cells [128]. Also, *Ocimum basilicum* L. crude methanolic extract suppressed the induction of iNOS and the subsequent production of NO in LPS-stimulated RAW 264.7 macrophage cells [129, 130]. To test the anti-inflammatory activity of the *Ocimum basilicum* L. methanolic extracts has been determined by PBMC (peripheral blood mononuclear cells) in mitogenic lymphocyte proliferative assay, methanolic extracts enhanced the functional activity of these immune-competent cells, as evaluated by a significant inhibitory effects of methanolic leaf extracts, PHA activated PBMC proliferation could be suggestive of suppression of T cell proliferation [130]. This effect arose from its pivotal role in

The inflammatory response involves long been compartmentalized into multiple attributes commonly termed redness, heat, pain, and edema. Inflammatory injuries lead to the discharge of a variety of fundamental mediators, cytokines, and chemokines that balance cellular infiltration that consequentially brings about resolving inflammatory response and restoration of tissue scrupulosity. However, immutable inflammatory stimuli or dysregulation of mechanisms of the resolution phase can

**192**

immune regulation [131, 132], T cell activation provides a target for pharmacological modulation aimed at achieving clinically useful immune-suppression [133].

Złote et al. [134] studied the capacity of phenolic-rich fraction obtained from the elicited basil leaves to inhibit the activity of two enzymes of inflammatory process (LOX and COX). This research found that a higher LOX and COX inhibition efficiency was positively correlated with the increased contents of rosmarinic, benzoic and *o*-coumaric acids determined after elicitation of basil. This result partially corresponds with the study of [135]. More recently, to gain insight into the mechanism of action and pharmacological value of the anti-inflammatory activity of aqueous and methanolic extracts of *Ocimum basilicum* L. in macrophage (RAW264.7) and human chondrosarcoma (SW1353) cell lines, and human primary chondrocytes to correlate their efficacy in terms of management of osteoarthritis (OA). Raina et al. [136] evaluated aqueous extract of *O. basilicum* L. significantly accustom the production of inflammatory mediators such as NO, PGE2, LTB4, and MMPs increased than the methanolic extract. The regulation of these inflammatory intermediaries is pivotal in OA, as it would have a direct effect on (1) chondrocyte survival, (2) production of proinflammatory cytokines, prostaglandins and leukotrienes, and (3) production of extracellular matrix-degrading enzymes such as MMPs. Due to the significant side-effects related to the use of NSAIDs, the check for natural products that would regulate the inflammatory cascade related to OA, without engaging chondrocyte survival, is extremely important. To investigate the anti-inflammatory effect of *Ocimum basilicum* L. oil, Rodrigues et al. [137] investigated an acute and chronic in vivo test as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was also analyzed by the participation of histamine and arachidonic acid pathways. These researchers found that the *Ocimum basilicum* L. essential oil and estragole significantly reduced paw edema induced by carrageenan and dextran. The smallest quantities of *Ocimum basilicum* L. essential oil (50 mg/kg) and estragole (30 mg/kg) revealed effectiveness in the decrease of paw edema created by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. These dosages were carried out of decrease the assured inflammatory process. The results followed between the *Ocimum basilicum* L. essential oil and estragole determine efficacy in antiinflammatory activity, however, the essential oil is higher efficacious in the acute and chronic anti-inflammatory action. Dextran is a high molecular weight polysaccharide, which differently to carrageenan, induces anaphylactic reactions characterized by extravasation and formation of edema due to mastocyte degranulation with release of histamine and serotonin. Carrageenan induces an inflammatory response through opinion with sulfated polysaccharides, initially encouraging the free of chemical substances which encourage multifactorial facts, mostly concerning the free of substance P, bradykinin, histamine, serotonin, cytokines, and nitric oxide and, subsequently on commodity arise from the arachidonic acid pathway [138].

#### **6.6 Antidiabetic**

Diabetes mellitus is a chronic metabolic disorder caused by an absolute or relative lack of insulin and or reduced insulin activity which results in hyperglycemia and abnormalities in carbohydrate, fat and protein metabolism [139, 140]. The hypoglycemic effect of *O. tenuiflorum* L., *O. canum* Sims. and *O. gratissimum* L. in animals with alloxan-induced diabetes was applied to potentiation of glucoseinduced insulin free and parallel increased peripheral uptake of glucose [141, 142]. Successive studies have reported a greater link of antidiabetic deal with the antioxidant effects of *Ocimum* oil. The character played by OS for diabetes complications

such as retinopathy, nephropathy, and cardiovascular disease are well set up so that dietary antioxidant compounds was fixed to protect from the damages of oxidative stress and free radicals in diabetic cases [143].

In animal experimental designs of alloxan-induced diabetes, both antioxidant and hypoglycemic effects of *O. basilicum* L., *O. tenuiflorum* L., *O. canum* Sims. and *O. gratissimum* L. have been reported. By treating alloxan-diabetic rabbits [141, 142, 144], made a significant decrease in blood glucose levels as corresponded with diabetic control rabbits. Such a hypoglycemic work was related to its powerful antioxidant potentiality: in evidence, in interact, the rabbits studied with *Ocimum* oil showed further a renewal of the levels of malondialdehyde and most of the enzymatic and nonenzymatic endogenous antioxidants [141, 142, 144]. Similar results were achieved in alloxan-diabetic rats: the control, of *Ocimum tenuiflorum*rich extracts showed significant hypoglycemic, hypolipidemic, and antioxidant effects in all the investigated diabetic rats [145, 146]. In an identical empirical design, *O. gratissimum* L. led to a decrease in the sugar level in plasma and a rise in superoxide dismutase, catalase, and glutathione peroxidase activities in liver and kidney. Furthermore, an opposed reaction against hepatic and renal toxicity in diabetic rats was also observed [147, 148]. Furthermore, the effects of *Ocimum sanctum* leaf polyphenols have been investigated also in insulin-secreting pancreatic β-cells, whose OS-induced alterations contribute to the pathogenesis of diabetes [149].
