Preclinical Studies III

Study 5

Objective: To study the lipid lowering activity of gugulipid in various animal models.

Methods:
Normal rats: The different oral doses of gugulipid with or without other hypolipidemic agents were administered to normal rats. Some rats received 100 mg/kg body weight of gugulipid for 90 days. Another group received doses of gugulipid and/or clofibrate for 30 days. (fig 10 & 11)

Triton-treated rats: Hyperlipidemic rats were given 200 mg/kg body weight of gugulipid, 200 mg/kg body weight of clofibrate, or 1000mg/kg body weight of nicotinic acid. (fig 12)

Dietery cholesterol -induced hyperlipidemic rats: Hyperlipidemic rats fed a high cholesterol diet received gugulipid for a period of 14 days.

Ethanol-induced hyperlipidemic rats: Gugulipid 200 mg/kg and clofibrate 200 mg/kg were administered to the rats.

Rabbits: Hyperlipidemic rabbits (serum cholesterol levels > 500 mg/dl) received gugulipid 50 mg/kg body weight for eight weeks.

Monkeys: Normal rhesus monkeys were given gugulipid doses of 60 and 120 mg/kg body weight for 90 days.

Results:

Figure 10
Effect of gugulipid on the percentage of cholesterol lowering in normal rats (p<0.01).Serum triglycerides were also reduced by 30% (p < 0.05).

 

Figure 11
Effect of gugulipid and clofibrate on the reduction of serum lipids in normal rats (G = gugulipid and C = clofibrate).

 

Figure 12
Effect of gugulipid, clofibrate, and nicotinic acid on the reduction of serum lipids in triton-treated rats (G = guggulipid, C = clofibrate, N = nicotinic acid).


Gugulipid lowered serum cholesterol and triglyceride levels by 60.5% and 37.7% at day 14 in diet-induced hyperlipidemic rats.

Significant reductions in serum cholesterol and triglycerides (p<0.01) were observed in ethanol-induced hyperlipidemic rats given 200 mg/kg gugulipid. These reductions were 30% more than clofibrate at the same dose.

Administration of 50 mg/kg gugulipid produced significant reductions of 40% in serum cholesterol and 30% in triglycerides in hyperlipidemic rabbits.

Levels of serum cholesterol, triglycerides, LDL, and VLDL were lowered by 20-30%, 15-30%, 50%, and 30%, respectively in gugulipid-treated, normal rhesus monkeys.

Conclusions: Gugulipid was effective in reducing serum lipid levels in rats, rabbits, and monkeys. Its effects were comparable or better than the conventional hypolipidemic agents in some cases.

Study 6

Objective: To study the effect of gugulipid on atheroma formation and regression in hyperlipidemic animal models.

Results: Gugulipid inhibited elevated levels of serum cholesterol and triglycerides (p<0.001) in hyperlipidemic rabbits in 90 days. In addition, it raised HDL and apoproteins by 29% and 21%, respectively. A marked reduction of 50% in atheroma was observed in treated rabbits compared to a 60% increase in atheromatic lesions in untreated rabbits.

Significant reductions in serum cholesterol (p<0.01) and triglycerides (p<0.05) were observed in hyperlipidemic rhesus monkeys that received gugulipid. A regression in atheromatous lesions was also observed.

Conclusions: Gugulipid lowered serum lipids and reduced the formation of atheromatous lesions.

B.Thyroid Stimulating Effects

Study 7

Objective:
To investigate the effects of C. mukul on melatonin-induced hypothyroidism in mice.

Methods: One hundred and eight mice were divided into three groups:

Group I- A dose of 25 mg/100 g body weight of melatonin was administered to the rats intraperitoneally for 8 days. Subgroups were created from Group I. Subgroup 1 received 20 mg/ 100g body weight of C. mukul extract i.p., and subgroup 2 served as controls.

Group II- A dose of melatonin (25 mg/100 g body weight) combined with C. mukul (20 mg/100 g body weight) i.p.

Group III- This group served as normal controls. They only received saline solution.

The thyroid function of the animals was studied by assessing the structural and functional status of the thyroid gland.

Results:

The melatonin-treated group showed significant reductions in thyroid weight and secretions. In contrast, increased thyroid secretions, iodine uptake, and thyroid weights were observed in mice treated with C. mukul extract. A reversal of the symptoms induced by melatonin-induced hypothyroidism were reversed by the combined treatment of melatonin and C. mukul extract. Histological studies revealed that the combined C. mukul extract/melatonin treatment brought about increased follicular cell height compared to the reduced cell height of the mice treated solely with melatonin.

Conclusions: C. mukul stimulates thyroid function and helps to normalize the thyroid lowering activity of melatonin.

Study 8

Objective: To investigate the thyroid stimulating effects of Z-guggulsterone in rats.

Methods: Albino rats received doses of 1 mg/100 g body weight of Z-guggulsterone orally. The animals were sacrificed after specified periods and various biochemical parameters (peroxidase and protease activities of the thyroid and iodine uptake) were measured to determine changes in thyroid activity.

Figure 13
Effect of Z-guggulsterone on thyroid peroxidase activity (measured as in terms of moles o-dianisidine oxidized/minute/mg/tissue).

 

Figure 14
Effect of Z-guggulsterone on thyroid proteolytic activity (measured in terms of g tyrosine liberated /mg thyroid tissue). (n=6)

Figure 15
Effect of Z-guggulsterone on the iodine concentration ratio (measured in terms of counts/g thyroid tissue divided by counts/ml serum). (n=6)



Conclusions: Z-guggulsterone stimulated thyroid activity in rats as evidenced by the significant increases in thyroid function parameters. (n=6)


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