Teorías del servicio

While the effect of C. fimbriata on appetite suppression has not been elucidated, it has been demonstrated that the perennial herb is capable of inhibiting adipocyte maturation. A study on 3T3-L1 pre-adipocyte cell line samples conducted by Akbarsha et al., (2010) clarified the mechanism of action of the pregnane glycosides. The study showed that pregnane glycosides have anti-adipogenic properties through the inhibition of pre-adipocyte cell division in the early phase of adipogenesis by either the down-regulation of cyclin-dependent kinase (CDK) or inhibition of import cyclin D1-CDK/6 complex into the nucleus, resulting in G1 arrest. Thus, C. fimbriata has the potential to block hyperplastic obesity (Akbarsha et al., 2010). Adipocyte proliferation and differentiation in adipose tissue has been inhibited by pregnane glycosides in other studies (De Leo et al., 2005, Plaza et al., 2005, Cioffi et al., 2006).

A rat study investigating the anti-obesogenic and anti-atherosclerotic properties of C. fimbriata showed that following C. fimbriata administration there was a significant reduction in food intake and prevented weight gain in body weight, liver weight and fat pad mass (Kamalakkannan et al., 2010). Hyperleptinaemia and leptin resistance were eliminated by the plant extract and the accumulation of lipids in the intima of the thoracic aorta was inhibited, which may be mediated by the improvement in plasma lipid profile (Figure 2.8a,b) (Kamalakkannan et al., 2010).

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Figure 2.8a Atherosclerosis in aorta of cafetaria fed rat (108x81mm)

Figure 2.8b Aorta section of rat fed Cafeteria

diet plus C. fimbriata extract (108x81 mm)

The study by Ambadasu et al (2013) also showed that administration of C. fimbriata for 50 days has anti-obesogenic effects. Ambadasu et al (2013) showed that there was a significant reduction in food intake, body weight and blood lipid profile in obese rats treated with C. fimbriata (Ambadasu et al., 2013a). Another study by Ambadasu et al (2013) also demonstrated that 50 days of C. fimbriata administration resulted in appetite suppressing, hypolipidemic and anti-obesogenic effects in rats fed a hypercaloric diet (Ambadasu et al., 2013b).

An animal study conducted by Sudhakara et al (2013) also demonstrated that administration of C. fimbriata for 90 days prevented weight gain and hyperleptinemia (Sudhakara et al., 2014). This study also found that C. fimbriata administration prevented hypertriglyceridemia, hyperglycemia and partially prevented hyperinsulinemia, as well as causing a reduction in oxidative stress and plasma glucose levels (Sudhakara et al., 2014). The reduction of leptin and insulin levels in C. fimbriata treated groups may be attributed to a reduction in fat accumulation in the adipose tissue and to weight loss. It is therefore suggested that C. fimbriata supplementation may be a useful therapeutic target to curtail insulin resistance, oxidative stress and obesity in high fat fed Wistar rats.

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The hypolipidemic activity of C. fimbriata was investigated in another rodent study conducted by Somnath et al (2012). This study found that treatment with C. fimbriata after 15 days significantly reduced total cholesterol and triglycerides in triton induced hyperlipidemic Wistar rats. Furthermore, the atherogenic index was found to be significantly reduced in the

C. fimbriata treated groups (Somnath et al., 2012). The anti-hyperglycemic and lipid lowering activity of C. fimbriata was also investigated in the study by Jagtap et al (2013). This study found a reduction in serum glucose, total cholesterol, triglycerides and LDL cholesterol in dexamethasone induced diabetic Sprague-Dawley rats treated with C. fimbriata

after 11 days of administration (Jagtap et al., 2013). A more recent study conducted by Latha et al (2014) investigated the hepatoprotective and anti-diabetic effects of C. fimbriata in streptatozocin induced diabetic rats. Latha et al (2014) also observed a significant reduction in blood glucose levels in C. fimbriata treated rats. Furthermore, histological examination of the liver and kidney in C. fimbriata treated rats confirmed a protective action of C. fimbriata

as there was a significant recovery of liver and kidney destruction observed. Therefore C. fimbriata may be seen as a therapeutic target for diabetes and its related complications (Latha et al., 2014).

The mechanism of hypoglycemic activity of C. fimbriata is yet to be determined. However, as C. fimbriata contains many chemical constituents including pregnane glycosides, flavonoids, megastigmane glycosides, bitter principles and saponins, it may be suggested that these chemical constituents could be responsible for the hypoglycemic activity. A possible mechanism by which this botanical decreases blood glucose is by the potentiation of insulin effect, through either stimulating pancreatic secretion of insulin from β-cells of islets of Langerhans or via enhancing peripheral glucose uptake. This proposed anti-diabetic mechanism of C. fimbriata is similar to that of Caralluma edulis (Wadood et al., 1989). The

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histopathological changes seen in the diabetic group were restored in the C. fimbriata treated rats. Hence, further research into the mechanism of hypoglycemic effects of C. fimbriata

can be undertaken through oral glucose tolerance tests, insulin sensitivity tests, measurement of urinary output and analysis of cytokines (diabetic markers) for instance.

A study conducted by Saivasanthi et al (2011) evaluated the anti-inflammatory effects of C. fimbriata in Wistar rats. Anti-inflammatory activity of C. fimbriata was evaluated by using carrageenan induced paw oedema model of rat (Saivasanthi et al., 2011). The progression of oedema in the paw of the rat after injection of carrageenan is a biphasic event (Vinegar et al., 1969). The initial phase of the oedema has been attributed to the release of histamine and serotonin, the oedema maintained during the plateau phase to kinin like substances and the second accelerating phase of swelling to the release of prostaglandin like substances (Asongalem et al., 2004). Therefore, the inhibition of oedema following C. fimbriata

administration may be attributed to the ability of C. fimbriata to inhibit various chemical mediators of inflammation, such as histamine and 5-HT during the initial phase. It is also postulated that the anti-inflammatory activity of C. fimbriata could be achieved through inhibition of cyclooxygenase, which is involved in the synthesis of inflammatory prostaglandins as it has been demonstrated that C. fimbriata contains flavonoids which are known to possess anti-inflammatory properties (Saivasanthi et al., 2011). Further research into the underlying mechanisms involved in the anti-inflammatory effects of C. fimbriata is needed. In addition, future directions may be focused on the effect of C. fimbriata on metabolic syndrome associated inflammation through analysis of anti-inflammatory and pro- inflammatory cytokines.

There is limited research into the effect of C. fimbriata on humans and therefore it has been of interest to verify these therapeutic claims observed in rodents through human controlled

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clinical studies. A preliminary clinical trial conducted by Kurpad et al., (unpublished) at the St John’s Medical College in Bangalore, India showed significant weight reductions in overweight subjects with C. fimbriata supplementation (Preliminary data). Another preliminary clinical trial conducted by Lawrence et al., (unpublished) in Los Angeles, California, USA also showed a significant reduction in body weight with C. fimbriata

ingestion (Lawrence and Choudhary, 2004).

A human trial evaluating the appetite suppressing effects of C. fimbriata in Indian adults found that the botanical extract (1g/day) appears to suppress appetite and reduce waist circumference in overweight individuals (n = 50) with a BMI greater than 25 kg/m2 over a two month period compared to the placebo group (Kuriyan et al., 2007). However, the experimental group was not significantly different from the placebo group in body weight, BMI, hip circumference and percentage body fat. The adverse effects experienced by 24 % of subjects in the experimental group were minor and restricted to initial mild symptoms of the gastro-intestinal tract which subsided within a week; these included abdominal distension, constipation, flatulence and gastritis.

Kuriyan et al., (2007) also found that hunger levels of participants reduced by 20 % following the administration period, which may account for an 8 % decline in energy intake of the experimental group. However, this could be influenced by under estimation of food intake and/or individual variation. The appetite suppressing effect caused a decrease in energy and fat intake and also a decline in the consumption of less desirable food (Kuriyan et al., 2007). Furthermore, there was no significant change in blood lipid values in the experimental group. As there is only one published human clinical trial that has investigated the effect of C. fimbriata extract on appetite and obesity, there is a need to clarify and further investigate the

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potential beneficial effects of this popular weight loss aid in the treatment of metabolic syndrome.

2.4.3 Citrus sinensis