3. Marco Teórico
3.7 Emprendimiento
The gastroprotective effects of cardamom and its main aroma constituent viz. 1,8-cineole was established in the following studies. A crude methano-lic extract (TM), essential oil (EO), petroleum ether soluble (PS) and insoluble (PI) fractions of methanolic extract were studied in rats at doses of 100–500, 12.5–50, 12.5–150 and 450 mg/kg, respectively, for their ability to inhibit the gastric lesions induced by aspirin and ethanol. All fractions (TM, EO, PS, PI) significantly inhibited gastric lesions.28
In a separate study the gastroprotective effect of 1,8-cineole (cineole) on ethanol-induced gastric mucosal damage in rats was investigated. 1,8-cineole (50–200 mg/kg), given orally 1 hr before administration of 1 ml of pure ethanol significantly attenuated the ethanol-induced gastric injury.29
Results from yet another investigation confirm the potential value of 1,8-cineole as a dietary flavoring agent in the prevention of gastrointesti-nal ulceration. A marked reduction in gross damage scores and wet Cardamom and Its Active Constituent, 1,8-Cineole 73 b734_Chapter-03.qxd 4/8/2009 3:46 PM Page 73
weights (mg/cm) of colonic segments were evident in animals pretreated but not post-treated with 1,8-cineole following trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.30
Hepatoprotective Effect
Another study was conducted to investigate the effects of 1,8-cineole on the D-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury in mice. Pretreatment with 1,8-cineole (400 mg/kg, p.o.) 60 mins before GalN/LPS, offered complete protection (100%) against the lethal shock. Hepatic necrosis induced by GalN/LPS was also greatly reduced by 1,8-cineole treatment.31
Cardiovascular Effects
The cardiovascular effects of 1,8-cineole were investigated in nor-motensive rats by Lahlou et al.,32 providing the first physiological evidence that i.v. treatment with 1,8-cineole in either anesthetized or conscious rats elicits hypotension, which seems related to an active vascular relaxation.32
Anti-Inflammatory Effect
One study observed a marked anti-inflammatory activity of the oil extracted from commercial Elettaria cardamomum seeds in doses of 175 and 280 ml/kg against acute carrageenan-induced plantar edema in male albino rats.33This anti-inflammatory activity of cardamom is sup-ported by other studies conducted using 1,8-cineole. This active monoterpene component in cardamom oil displays an inhibitory effect on some types of experimental inflammation in rats, e.g. paw edema induced by carrageenan and cotton pellet-induced granuloma. This result when taken together with the other reports that describe the inhibitory effects of cineole on the formation of prostaglandins and cytokines by stimulated monocytes in vitro may provide additional evi-dence for its potential beneficial use in therapy as an anti-inflammatory agent.34
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Analgesic and Anti-Spasmodic Effect
Investigation of analgesic activity has proved that a dose of 233 µl/kg of cardamom oil produced 50% protection against the writhing (stretching syndrome) induced by intraperitoneal administration of a 0.02% solution of p-benzoquinone in mice. In addition, antispasmodic activity has been deter-mined on a rabbit intestine preparation using acetylcholine as agonist.33
Anti-Oxidative Effect
Peroxynitrite, a potent cytotoxic agent, can damage a variety of biomolecules such as proteins, lipids and DNA, and is considered to be one of the major pathological causes of several diseases. Methanolic extracts of eight culinary spices including cardamom were selected in order to search for potential pro-tectors against the actions of peroxynitrite. All of the tested spices exerted some level of protective ability against peroxynitrite-mediated biomolecular damage as determined by these extracts’ ability to attenuate the formation of, respectively, nitrotyrosine in albumin, thiobarbiturate acid-reactive sub-stances (TBARS) in liposome and strand breakages for plasmid DNA.35
In another study conducted by Santos et al., post-treatment with cine-ole was found to significantly reduce myeloperoxidase activity and caused repletion of glutathione in the colonic segments following induc-tion of colitis by trinitrobenzene sulfonic acid (TNBS) in rats.30
The essential oils from cardamom, when fed by gavage in Swiss albino mice, was found to significantly elevate the level of the carcinogen metabolizing enzyme glutathione S-transferase (GST) as well as that of the acid-soluble sulfhydryl.36
This finding is in good agreement with another finding by Bhattacharjee et al.37in which it was reported that aqueous suspension of cardamom was responsible for inducing hepatic and colonic GST activities in azoxymethane (AOM) treated Swiss albino mice.
Anti-Carcinogenic Effect
Bhattacharjee et al. have investigated the anti-carcinogenic effect of car-damom and it was observed that aqueous suspension of carcar-damom Cardamom and Its Active Constituent, 1,8-Cineole 75 b734_Chapter-03.qxd 4/8/2009 3:46 PM Page 75
significantly inhibited aberrant crypt foci (ACF) formation in AOM induced colon carcinogenesis in Swiss albino mice.38 ACF are recog-nized as early preneoplastic lesions of the colon.39 In the study conducted by Bhattacharjee et al. cell proliferation in the colon was found to decrease and apoptosis was found to increase after cardamom treatment. It is well known that the balance between cell proliferation and apoptosis is important in the genesis of colon carcinoma40; this study indicates a good correlation between the ability of the spice to pre-vent AOM induced ACF through reduction in cell proliferation and enhanced apoptosis.
Sengupta et al. has also explored the chemopreventive efficacy of car-damom against DMBA induced and croton oil promoted skin carcinogenesis in Swiss albino mice and has observed a marked decrease in papilloma count after cardamom treatment (unpublished data).
Effect of Cardamom as an Ingredient of Garam Masala
As we know that cardamom is an essential ingredient in the Indian spice mixture garam masala, many studies are being carried out to explore the beneficial health effects, if any, of garam masala. In one investigation, when pregnant mice were given 10 mg and 30 mg of garam masala per day from Days 13–19 of gestation in addition to DMBA (5 mg/day) on Days 15–17 of gestation, the multiple-site tumor incidence declined sig-nificantly in the F1 progeny.41 In another study Singh and Rao assessed the chemopreventive role of garam masala through modulatory impact on the hepatic levels of detoxification enzymes like glutathione S-transferase (GST), cytochrome b5 (cyt. b5) and cytochrome P450 (cyt. P450), and acid soluble sulfhydryl (−SH) content in Swiss albino mice fed garam masala in their diet.42
MOLECULAR TARGETS
The potential of cardamom and its active constituent 1,8-cineole to exhibit such a wide variety of pharmacological properties must be through mod-ulation of specific molecular targets. However, to date only a few studies have been conducted to identify these targets.
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Many investigations have proven that cardamom shows anti-inflammatory activity in vitro and in vivo. Although not fully understood, several action mechanisms are proposed to explain in vivo anti-inflammatory action. One recent study has shown that cardamom expresses its anti-inflammatory activity at least in part by modulation of pro-anti-inflammatory protein expression such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).39 An inhibition of these enzymes by car-damom reduces the production of arachidonic acid (AA), prostaglandins (PG), leukotrienes (LT), and NO, crucial mediators of inflammation.
Thus, the inhibition of these enzymes exerted by cardamom is definitely one of the important cellular mechanisms of anti-inflammation. Tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) are pro-inflamma-tory cytokines produced by macrophages/monocytes during acute inflammation. These are important mediators of intestinal inflammation in inflammatory bowel disease.43,44 Results from experiments characterize 1,8-cineole as a strong inhibitor of TNF-α and IL-1β.31,45As TNF-α is responsible for a diverse range of signaling events within cells
,
leading to necrosis or apoptosis,46inhibition of this molecule may account for a wide range of pharmacological effects exhibited by cadamom and/or 1,8-cineole, including its role in controlling airway mucus hypersecretion, conferring protection against liver injury, and so on.As already mentioned cardamom has traditionally been used for cur-ing ailments such as asthma, bronchitis and diarrhea. It has also been used as an analgesic and as an antispasmodic. It can be tentatively said from experimental evidence that by blocking a single target molecule car-damom performs all these activities. Carcar-damom oil was found to exhibit its inhibitory effect against the contractile response elicited by the neuro-transmitter acetylcholine on rabbit intestine preparation. Acetylcholine (ACh) is the most common neurotransmitter at the parasympathetic nerve ending to induce smooth muscle contractions. In the gastrointestinal tract, ACh is released from the primary excitatory motor neurons and mediates an immediate smooth muscle contraction.47,48 Cholinergic signaling is mediated by the muscarinic ACh receptor expressed on the surface of the smooth muscle cells. As the antispasmodic activity of cardamom oil was investigated using acetylcholine as an agonist, this suggests that car-damom exerts its effect by muscarinic receptor blockade.33
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By blocking muscarinic receptors on airway smooth muscle on sub-mucosal gland cells, anticholinergics have also proved to be of particular value in the treatment of chronic obstructive pulmonary disorder (COPD).49 Parasympathetic nerves provide the dominant autonomic innervation of the airways. Release of acetylcholine from parasympathetic nerves activates postjunctional muscarinic receptors present on airway smooth muscle, submucosal glands and blood vessels, causing bron-choconstriction, mucus secretion and vasodilatation, respectively. The increasing evidence of the role of 1,8-cineole in controlling airway mucus hypersecretion might be by virtue of muscarinic receptor blockage.