|Year : 2015 | Volume
| Issue : 1 | Page : 61-66
|Effects of Salacia oblonga on cardiovascular risk factors in chronic kidney disease patients: A prospective study
Rana Gopal Singh1, Surendra Singh Rathore1, Imtiyaz Ahmad Wani1, Usha2, Aruna Agrawal3, Govind Prasad Dubey3
1 Nephrology Department, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
2 Pathology Department, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
3 Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
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|Date of Web Publication||8-Jan-2015|
| Abstract|| |
The present study is aimed to evaluate the effect of the herbal drug Salacia oblonga on reduction of cardiovascular risk factors in patients with chronic kidney disease (CKD). Sixty patients were randomized in four groups; group A1 = non-diabetic CKD given trial drug Salacia oblonga for six months, group A 2 = non-diabetic CKD intended to receive placebo, group B1 = diabetic CKD treated with Salacia oblonga for six months and group B 2 = diabetic CKD patients intended to receive placebo. Estimation of renal function tests including blood urea, serum creatinine and creatinine clearance was performed at baseline and after that at monthly intervals. Lipid profile, interleukin-6 (IL-6) and C-reactive protein (CRP) were measured at baseline and were repeated at three months and six months. After six months of treatment, Salacia oblonga could reduce the triglyceride levels by 23.66% (P = 0.008) in non-diabetic and by 17.45% (P = 0.01) in diabetic CKD patients. In comparison with placebo, both non-diabetic and diabetic CKD patients treated with Salacia oblonga showed significant reduction in CRP levels (P = 0.002 and 0.03, respectively), while significant reduction in IL-6 (P-value = 0.0003) and serum cholesterol levels (P-value = 0.0001) was seen only in diabetic CKD patients treated with Salacia oblonga. Stabilization of creatinine clearance with Salacia oblonga was observed in both non-diabetic (P = 0.05) and diabetic CKD (P = 0.04) patients in comparison with placebo. Salacia oblonga has significant beneficial effects on lipid profile and markers of inflammation and endothelial dysfunction in CKD patients. Salacia oblonga also seems to have a reno-protective effect, as reflected by stabilization of creatinine clearance at six months in this study.
|How to cite this article:|
Singh RG, Rathore SS, Wani IA, Usha, Agrawal A, Dubey GP. Effects of Salacia oblonga on cardiovascular risk factors in chronic kidney disease patients: A prospective study. Saudi J Kidney Dis Transpl 2015;26:61-6
|How to cite this URL:|
Singh RG, Rathore SS, Wani IA, Usha, Agrawal A, Dubey GP. Effects of Salacia oblonga on cardiovascular risk factors in chronic kidney disease patients: A prospective study. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2019 Dec 12];26:61-6. Available from: http://www.sjkdt.org/text.asp?2015/26/1/61/148736
| Introduction|| |
Cardiovascular disease is the leading cause of death in patient with chronic kidney disease (CKD). The adjusted annual mortality rate in CKD patients with cardiovascular disease is reported to vary between 70 and 145 per 1000 patient years, which is almost double than that seen in patients without CKD.  Renal insufficiency is now considered the strongest risk factor for adverse cardiovascular outcome. ,
Apart from traditional risk factors, some CKDspecific non-traditional risk factors such as endothelial dysfunction, inflammation, oxidative stress, accumulation of asymmetric dimethyl arginine, abnormal divalent ion metabolism, advanced glycation products, hyperhomocysteinemia and hypoalbuminemia play an important role in the causation of cardiovascular disease in patients with kidney disease. ,, CKD patients have high levels of markers of endothelial dysfunction, inflammation and oxidative stress, which include Von-Willibrand factor, interleukin-6 (IL-6), tumor necrosis factorα (TNF-α), C-reactive protein (CRP), adhesion molecules and fibrinogen. ,,,,,,
In the present study, we analyzed the effects of the herbal drug Salacia oblonga on CRP, IL-6, and lipid profile in diabetic and non-diabetic CKD patients. Salacia oblonga is a small tree or climbing shrub found in the rain forests of the Western Ghats from Konkan, the Southern ghats of Kerala and some areas of Tamil Nadu in India. It reduces post-prandial hyperglycemia and insulinemia because of its α-glucosidase inhibitory effect. ,,,, Studies in experimental animals have demonstrated that Salacia oblonga has anti-inflammatory and lipid-lowering properties. ,, With this background, we undertook this pilot study to explore the effect of Salacia oblonga on various cardiovascular risk factors.
| Methods and Materials|| |
This was a randomized, prospective, singleblinded, placebo-controlled study. Adult (>18 years) non-diabetic and diabetic CKD patients with serum creatinine >1.5 mg/dL but < 5 mg/ dL were enrolled in the study. Patients with acute renal failure and patients receiving angiotensin-converting enzyme (ACE) inhibittors or angiotensin receptor blockers (ARBs) were excluded. Non-diabetic and diabetic patients were randomly assigned to four groups: Group A 1 = non-diabetic CKD patients randomized to receive trial drug Salacia oblonga, group A 2 = non-diabetic CKD patients randomized to receive placebo, group B 1 = diabetic CKD patients given trial drug Salacia oblonga and group B 2 = diabetic CKD patients intended to be treated with placebo. The study protocol was approved by the local ethical committee and all patients gave informed consent. Diabetic and non-diabetic patients were studied separately because there are some essential differences in diabetic and non-diabetic kidney diseases, like early onset of symptoms and rapid progression of kidney disease in diabetic CKD; moreover, endothelial dysfunction and lipid abnormalities are more commonly seen in diabetic patients than in their non-diabetic counterparts.
Initially, 67 patients were enrolled in study and, during the study period, four patients were lost to follow-up, two patients developed rapid deterioration of kidney function and one patient died due to intracerebral hemorrhage. Sixty patients completed the follow-up period of six months, 15 in each group. Detailed history and examination was performed at baseline and at monthly intervals for six months. Patients were given antihypertensive drugs to achieve target blood pressure; however, ACE inhibitors and ARBs were not prescribed. Diabetic patients continued to receive usual care. Patients in groups A 1 and B 1 received Salacia oblonga 1000 mg twice daily whereas patients in groups A 2 and B 2 received placebo. At the start of the study and at monthly intervals, blood urea, serum creatinine and creatinine clearance (using the Cockcroft and Gault formula) were measured. Lipid profile, which included serum cholesterol, serum triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), as well as IL-6 and CRP levels were measured at the start of the study and were repeated at three months and six months of follow-up.
Data were analyzed using SPSS software version 16 for windows. Categorical data were analyzed by Fisher's exact test while unpaired student's t tests were used for inter-group analysis of continuous data. P-value of less than 0.05 was taken as the point of significance.
| Results|| |
Data from 60 patients who completed six months of follow-up were analyzed. Group A 1 patients were compared with group A 2 and group B 1 patients were compared with group B 2 . The baseline demographic, clinical and laboratory characteristics of both non-diabetic and diabetic CKD cases (planned for trial drug) were similar to the respective controls (placebo groups), and are shown in [Table 1] and [Table 2], respectively. The study parameters after six months of treatment with Salacia oblonga or placebo, in non-diabetic and diabetic CKD patients, are shown in [Table 3] and [Table 4], respectively.
|Table 1: Baseline demographic and laboratory parameters of study population of non diabetic CKD patients, randomized to receive Salacia oblonga (group A1) or placebo (group A2).|
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|Table 2: Baseline demographic and laboratory parameters of the study population of diabetic CKD patients planned for Salacia oblonga therapy (group B1) or placebo (group B2).|
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|Table 3: Study parameters at 6 months in non-diabetic CKD patients following treatment with Salacia oblonga (group A1), in comparison with placebo (group A2).|
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|Table 4: Study parameters at 6 months in diabetic CKD patients following treatment with Salacia oblonga (group B1) in comparison with placebo (group B2).|
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Effect on renal functions
There was stabilization of creatinine clearance in patients treated with Salacia oblonga in both non-diabetic and diabetic CKD patients. Creatinine clearance in groups A 1 and A 2 at baseline were comparable, being 31.20 ± 10.42 and 27.46 ± 8.54 mL/min, respectively, and, at six months, creatinine clearance in the Salacia oblonga group was 28.37 ± 10.06 mL/min, whereas it declined to 21.13 ± 9.22 mL/min in the placebo group [Table 3]. This difference was statistically significant (P-value = 0.05). Similar beneficial results were obtained in diabetic patients in group B 1 as compared with group B 2 (P-value = 0.04) [Table 4]. Thus, Salacia oblonga-treated patients had better preservation of renal functions at six months.
Effect on lipid profile
In group A 1 , cholesterol levels at 0 and six months were 216.0 ± 29.15 and 204.90 ± 44.80 mg/dL, respectively, showing no effect of Salacia oblonga on cholesterol in non-diabetic CKD patients; however, in diabetic CKD patients, cholesterol levels in the Salacia oblonga group (group B 1 ) were reduced from a baseline value of 241.10 ± 38.40 to 209.27 ± 18.40. This reduction was statistically very significant (P-value = 0.0001) as compared with the placebo group in which the levels actually increased. Serum triglyceride level in group A 1 decreased by 23.66%, from a baseline value of 317.03 ± 47.80 to 242.0 ± 51.90 mg/dL after six months of treatment with Salacia oblonga, and the difference was statistically significant as compared with placebo (P = 0.008). In group B 1 , the triglyceride levels at 0 month (334.50 ± 68.59 mg/ dL) were reduced to 276.10 ± 56.90 mg/dL at the sixth month. This 17.45% decline was significant compared with the placebo group (P-value = 0.01), where the triglyceride levels at 0 and six months were 348.0 ± 74.30 and 326.80 ± 49.90 mg/dL, respectively. There was no significant change in serum HDL levels in both non-diabetic and diabetic CKD patients treated with Salacia oblonga or placebo. In non-diabetic patients, the LDL levels did not show a significant change, but in diabetic CKD patients there was a significant reduction of the mean LDL level from a baseline value of 138.60 ± 40.20 to 112.80 ± 25.90 at the end of the study. The results were statistically significant in comparison with placebo (P-value = 0.01).
Effect of Salacia oblonga on markers of inflammation and endothelial dysfunction
At the start of the study, the CRP level in group A 1 was 2.38 ± 0.63 mg/dL, which decreased significantly to 1.76 ± 0.59 mg/dL after six months. In group B 1 , the CRP levels at 0 and six months were 2.78 ± 0.90 and 2.10 ± 0.67 mg/dL, respectively; hence, in both non-diabetic and diabetic CKD patients, the CRP level decreased significantly with Salacia oblonga treatment compared with placebo (Pvalue = 0.002 and 0.03, respectively). The interleukin-6 level in group A 1 did not change significantly, but, in diabetic CKD patients on Salacia oblonga, the interleukin-6 level decreased significantly compared with placebo (P-value = 0.0003).
| Discussion|| |
Cardiac disease is the predominant cause of death in CKD.  Both traditional and non-traditional factors account for a high risk of cardiac disease in CKD patients.  Interventions known to modulate cardiovascular risk include ACE inhibitors, , insulin sensitizers,  hypolipidemic therapy, , anti-oxidants , and folate administration. 
Ismail et al  studied the anti-inflammatory activity of Salacia oblonga root-bark powder in male albino rats and found that the drug has a significant anti-inflammatory activity. Salacia oblonga has been found to have lipid-lowering and anti-oxidative properties as well. , In the present study, Salacia oblonga could reduce the triglyceride levels by 23.66% in nondiabetic and by 17.45% in diabetic CKD patients. These changes were significant compared with placebo. Both serum cholesterol and LDL levels did not change significantly in non-diabetic patients, but were lowered significantly in diabetic CKD patients. HDL cholesterol did not decrease significantly in either diabetic or non-diabetic CKD patients. Thus, it can be concluded that Salacia oblonga has a significant hypolipidemic action, particularly in reducing the triglyceride level, and the drug can be used for this indication.
We also studied the effect of Salacia oblonga on IL-6, a marker of endothelial dysfunction, and CRP, a marker of inflammation. In nondiabetic CKD patients on Salacia oblonga, the IL-6 level did not change significantly compared with placebo, but there was a significant reduction in diabetic CKD patients. This suggests that Salacia oblonga may have a role in modulating endothelial dysfunction in diabetic CKD patients. CRP levels decreased significantly in both groups treated with Salacia oblonga. CRP is an acute phase reactant and marker for inflammation and has been recognized as an important link in the development and progression of atherosclerosis and mortality in CKD. ,, By decreasing the CRP level in CKD patients, Salacia oblonga may have a role in cardiovascular risk reduction.
The main drawbacks of the study include a small number of patients and short follow-up, but, as a pilot study, it has provided new insights into the various beneficial effects of Salacia oblonga. New studies are needed to provide further evidence, particularly on the clinical cardiovascular outcomes.
| Conclusion|| |
In conclusion, Salacia oblonga has significant beneficial effects on multiple cardiovascular risk factors in both diabetic and nondiabetic kidney diseases patients, particularly as a lipid-lowering agent and as a modulator of endothelial dysfunction and inflammation. However, further studies are needed before Salacia oblonga can be recommended for routine use as a cardio-protective drug.
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Dr. Surendra Singh Rathore
Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005
[Table 1], [Table 2], [Table 3], [Table 4]
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