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Karajibani M, Montazerifar F, Eslahi H, Yarmand S, Miri M, Naghizadeh M. The Effect of Hydroalcoholic Extract of Senna (Cassia Angustifolia Vahl.) on Lipid Profiles in Hyperlipidemic Rats. JNFS 2023; 8 (1) :1-8
URL: http://jnfs.ssu.ac.ir/article-1-438-en.html
Health Promotion Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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The Effect of Hydroalcoholic Extract of Senna (Cassia Angustifolia Vahl.) on Lipid Profiles in Hyperlipidemic Rats

Mansour Karajibani; PhD*1,3, Farzaneh Montazerifar; PhD2,3, Hadi Eslahi; MSc3, Sazin Yarmand; MSc3,4,
Mahdiyyeh Miri; BSc3,4 &
Mehrdad Naghizadeh; MSc3
1 Health Promotion Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; 2 Pregnancy Health Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; 3 Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran; 4 Student Research Committee, School of Medicine. Zahedan University of Medical Sciences, Zahedan, Iran.
ARTICLE INFO ABSTRACT
ORIGINAL  ARTICLE
Background: Abnormality in metabolism of lipids and hyperlipidemia is a risk factor for atherosclerosis which is the major cause of cardiovascular diseases (CVDs). Several herbal drugs are used for the treatment of dyslipidemia. The present study investigates the effects of hydroalcoholic extracts of Senna extract on serum lipid profile among hyperlipidemic rats. Methods: Forty eight male Wistar rats were randomly divided into 6 groups of 8 animals, including group 1) normal pellet diet (control), group 2) high fat diet (HFD), group, 3) HFD with 100 mg/kg Senna extract treatment, group 4) HFD with 200 mg/kg Senna extract treatment, group 5) 100 mg/kg pure Senna extract, and group 6) 200 mg/kg pure Senna extract. All the dietary regimens and Senna extract treatments were continued for 30 days. At the end of the experiment, blood samples collected from heart of rats and the lipid profile levels were measured. Results: The results indicated that short-term treatment by hydroalcoholic of Senna extract produced a significant reduction in the level of cholesterol, triglyceride, and LDL-C (P < 0.05), as well as an increase in HDL-C. The body weight in the HFD group was significantly higher than the other groups (P < 0.05). Conclusion: Prescription of hydroalcoholic extracts of Senna is effective in the treatment of hyperlipidemia, and can inhibit the weight gain induced by HFD in rats. Some of these effects could be attributed to antioxidants activities, biological and pharmaceutical properties and other protective properties of the Senna extract requiring further investigations.

Keywords: Senna extract; Hyperlipidemia; Rat
Article history:
Received:27 Jun 2021
Revised: 28 Jul 2021
Accepted:16 Aug 2021
*Corresponding author:
mkarajibani@yahoo.com
Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Postal code: 43181-98168-43175
Tel: +98 915 3414358

Introduction
Consumption of a high fat diet (HFD) causes increased lipid accumulation and contributes to various metabolic diseases, such as obesity, hyperlipidemia, atherosclerosis, cardiovascular disease, type 2 diabetes mellitus, and nonalcoholic fatty liver disease (NAFLD) (Bharathi et al., 2018, Hashem and Alazouny, 2016, Soleimani et al., 2016, Zawawi and Ismail, 2018).
Cardiovascular diseases (CVDs) are considered the leading cause of death worldwide, and rapid epidemiological transmission of these diseases has been shown over the past two decades (Ho et al., 2018). Obesity, lack of physical activity, smoking, and abnormal lipid profile have been recognized as the major risk factors for CVDs (Mozaffarian et al., 2016).  The main cause of CVDs is atherosclerosis, which is due to the etiologic and pathologic factors that contribute to the increase in blood lipids (Carr et al., 2019). Low density lipoprotein (LDL-C) is the major atherogenic lipoprotein particle in the circulation, and LDL-C is a key risk factor for CVDs. On the other hand, it has been reported that there is a reverse relationship between serum high density lipoprotein (HDL-C) and CVDs (Kosmas et al., 2018). Abnormality in metabolism of lipids has a main role in atherosclerosis and Chronic Heart Disease (CHD).
Currently, several chemical drugs, such as lovastatin, cholestyramine, and clofibrate are used for the treatment of dyslipidemia. Although the consumption of these drugs may improve dyslipidemia, these drugs are associated with numerous side effects, such as the occurrence of myopathy, rhabdomyolysis, hepatic disorders, muscle tenderness, and digestive problems (Mathur and Kusum Devi, 2016). To improve the lipid profile and blood pressure, dietary modifications are safer and more cost-effective than medical strategies (Kafeshani et al., 2015, Khosravi-Boroujeni et al., 2013, Sahebkar et al., 2016). Several studies have revealed that the consumption of natural substitutes are therapeutically effective, while they have fewer side effects (Hasani-Ranjbar et al., 2010, Wharton et al., 2020).
It is extensively accepted that compliance to a heathier diet leads to positive health outcomes, but recent evidence has shown that nutraceutical compounds have been more widely employed for the adjuvant treatment of dyslipidemia due to their attributed phytotherapic properties, deemed as safe and useful (Ghorbani, 2013, Guo et al., 2014). Medicinal plants are important sources of biologically active natural products which due to their curative properties have been studied for many years (Ahmed et al., 2015, Ahmed et al., 2014). Antioxidant activities of herbal medicines are active in decreasing the toxicities of other medications (Karimi et al., 2015).
Senna (Cassia angustifolia Vahl.)  is a traditional therapeutic plant belong to the family of Caesalpiniaceae and has been emerged from Saudi Arabia, Egypt, and Yemen (Ahmed et al., 2016). It is full of antioxidant and is known to have strong antioxidant activity. It has many biological and pharmaceutical properties, such as antidiabetic, anti-hyperlipidemic, anticancer, and anti-inflammatory ones. Previous studies have shown that flavonoids are one of Senna effective compounds in the prevention or treatment of antihyperlipidemic (Jani and Goswami, 2019, Raut and Karuppayil, 2014). On this basis, the aim of the current study is to investigate the effects of hydroalcoholic extracts of Senna on levels of lipid profile among hyperlipidemic rats.
Materials and Methods
Animal experiments: The current study was conducted on 48 adult male Wistar rats (body weight 200-220 g). The animals were housed in separate cages (2 rats per cage), under the controlled condition of temperature (22 ± 2 °C), humidity (15-20%), and 12:12 h dark/light cycle with free access to food and water adlibitum. The inclusion criteria included male rats and no disease, and the exclusion criteria were as follows: underweight, disease, and bleeding.
Animals were divided into six groups including 1) Normal pellet diet (control), 2) HFD, 3) HFD with 100 mg/kg Senna extract treatment (HFD+100), 4) HFD with 200 mg/kg Senna extract treatment (HFD+200), 5) 100 mg/kg Senna extract (100 mg Ex), and 6) 200 mg/kg Senna extract (200 mg Ex). Each group comprised of eight animals. All the dietary regimens and Senna extract treatments (the alcoholic extract of Senna oral emulsion through gavage over 30 day) were continued for 30 days. The rats were weighed at the beginning and end of the study by digital scales.
Preparation of HFD: In order to provide an HFD, 20 g of pure cholesterol (Sigma corp.) solved in 5 ml olive oil were added to usual pallet diet (1 kg of normal rat diet) for rats (Zarei et al., 2013). Afterwards, the mixture was kept under suitable condition in different portions as the rats’ food. The base chow (3.05 kcal/g digestible energy) contained 23.1% protein, 64.4% carbohydrate, 4.8% fat (soybean oil), 0.3% vitamins, and 7.7% minerals (Behparvar Company, Tehran, Iran).
Preparation of Cassia angustifolia Vahl extract: For preparation of the alcoholic extract of Cassia angustifolia Vahl, Standard methods of extraction were utilized. Cassia angustifolia Vahl was cleaned, dried, powdered, and eventually poured into a covered glass container and was mixed with ethanol alcohol 97%. The mixture was permitted to mix well for 72 hours. After that, it was first filtered and then centrifuged. The resultant mixture was placed in a warm bath to allow the complete evaporation of its alcohol (Zarei et al., 2013).
Biochemical analysis: On the final day, the blood samples collected from heart of rats, and total cholesterol (TC), triglyceride (TG), and HDL-C serum levels were measured by commercial kits (Pars Azmoon, Tehran, Iran). LDL-C was calculated according to the Friedewald formula (Friedewald et al., 1972).
Ethical considerations: The experimental protocols were approved by the ethical committee of Zahedan University of Medical Sciences, Iran (IR.ZAUMS.REC.2018.340).
Data analysis: Statistical analysis was performed with SPSS 16.0 using one-way ANOVA followed by the Tukey post hoc test. The results were expressed as Mean ± SEM, and P-value < 0.05 was significantly considered.
Results
The mean weight of the rats in the six groups was not significantly different at the beginning of the study (P > 0.05) (Figure 1). At the end of study, the mean weight of the HFD group was significantly higher than control group (P < 0.001). However, the consumption of Senna extract, especially in HFD+200 group led a significant reduction in body weight (P < 0.01). Moreover, body weight significantly decreased in the 100 mg and 200 mg extract groups compared to HFD group (P < 0.01).
The mean cholesterol level showed a significant difference between the studied groups. A significant increase was observed in cholesterol in the HFD group compared to the control group (Figure 2). However, consumption of Cassia angustifolia Vahl extract, except for HFD+100 group (P > 0.05), significantly reduced the cholesterol level among hyperlipidemic rats (P < 0.05).
The mean triglyceride level had a significant increase in HFD group compared to the control group (Figure 3). Also, the administration of Senna extract significantly decreased the amount of triglyceride (especially in 200 extract group) (P < 0.05).
The mean LDL-C level indicated that the consumption of HFD caused a significant increase in LDL-C level compared to the control group (P < 0.05, Figure 4). The consumption of Senna extract can significantly decrease LDL-C level in hyperlipidemic animals (P < 0.05).
It was observed that the HDL-C levels in the HFD group were lower than the control group. There was an increase in HDL-C level in rats consuming Senna extract compared to HFD group, but this difference was not significant (P > 0.05, Figure 5).
















Discussion
The results of the present study showed that HFD consumption increases TC, TG, and LDL-C and decreases HDL-C levels. Administration of Senna extract with HFD prevents changes in fat profiles, which indicates its preventive effects. On the other hand, administration of Senna extract alone improves fat profiles more effectively. The study by Gadanya and Muhammad expressed that the use of aqueous extract of Senna reduces the levels of TC, TG, and LDL-C, which is consistent with the results obtained in the present study (Gadanya and Muhammad, 2018). The results of a study by Nanumala et al. showed that the use of Senna extract significantly reduces the level of blood lipids in Triton 100 X-induced hyperlipidemia (Nanumala et al., 2014).
Although several studies have shown the beneficial effect of Senna in treating hyperlipidemia (Gupta et al., 2011, Habtemariam, 2013), the antihyperlipidemic principles of Senna have not been identified.
Senna is one of the medicinal plants that has a long history of use in traditional medicine and in recent years is also available as an industrial product and as a laxative. Mucilage is one of the compounds in Senna. These compounds are water-soluble substances that swell and bulk by absorbing large volumes of water and form a protective layer on the gastric and intestinal membranes. It has been also mentioned that mucilages reduce cholesterol and blood sugar levels. In the present study, treatment of hyperlipidemic animals with 200 mg/kg of hydroalcoholic extracts of Senna produced a significant decrease in total cholesterol, triglyceride, and LDL-C. This is in line with the previous studies (Ayinla et al., 2011, Maryam et al., 2015, Nirmala et al., 2008).  It seems that the hypolipidemic effect of Senna Cassia angustifolia can be due to the presence of some phytochemical compounds, including alkaloids, flavonoids, and saponins in the Senna extract (Ayinla et al., 2011). All these compounds, especially alkaloids, are known to reduce serum lipid level in animals. In general, herbs used in traditional medicine and their compounds, including dietary fiber, vitamins, flavonoids, sterols, and other antioxidant compounds can play a role in inhibiting LDL-C oxidation and free radical scavenging. It also improves the body's metabolic disorders by affecting the immune system. Flavonoids effect on lipid metabolism in the body reduces the activity of HMG-CoA reductase in the liver. It is also observed that, flavonoids can inhibit LDL-C oxidation by several mechanisms, including 1) scavenging of free radicals; 2) chelating of metal ions and reducing the metals capacity to generate free radicals; 3) sparing of vitamin E and carotenoids in the LDL-C particle, thus protecting LDL-C from oxidation, and this will reduce the risk of CVD (Fuhrman and Aviram, 2001).
The consumption of HFD in rats reduced HDL-C levels compared to the control group. However, this decrease was not statistically significant and intake of the extract had no effect on serum HDL-C levels in the groups. On the other hand, the results of the present study showed that HFD increased blood LDL-C levels in rats, and the appearance of Senna leaf extract in a dose-dependent manner significantly reduced blood LDL-C levels. However, the administration of this extract in groups receiving normal diet had an effect on blood LDL-C levels. Dyslipidemia is a chronic disease caused by metabolic disorders and various factors.
The data also showed that the body weight in the HFD group was significantly higher than the other groups, which may be due to the high calorie intake in this group. The HFD can reflect that calorie intake was high compared to the control group.
Regarding the suggestion that increased food intake enhances serum lipid profile, and according to the results of the study by Jani et al., Senna extract has a significant role in reducing body weight of animals (Jani and Goswami, 2019). Hypercholesterolemia as the main risk factor for atherosclerosis and atherosclerosis is the major cause of heart diseases and stroke. The results indicated that the hydroalcoholic extract of Senna herbal, in addition to having considerable hypolipidemic effects in HFD rats, can lead to weight loss. It is worth mentioning that due to the limited cost and space for keeping rats, the sample size was estimated based on facilities and statistical methods.
Conclusion
Prescription of hydroalcoholic extracts of Senna is effective in the treatment of hyperlipidemia and it also can inhibit the weight gain induced by HFD in rats. It was observed that it increases triglyceride, cholesterol, LDL-C, and decreases HDL-C concentrations due to intake of HFD. Nevertheless, further studies are required to determine the mechanism of these effects. Some of these advantages could be attributed to antioxidants activities, biological and pharmaceutical properties, and other protective properties of Senna extract.
Authors’ contributions
Karajibani M contributed and design of research, drafted and final revised the manuscript; Eslahi H, Yarmand S, Miri M, and Naghizadeh M performed experiments and prepared tools and facilities for field study; Montazerifar F performed statically analysis, drafted and final revised the manuscript. All authors read and approved the final draft of manuscript.
Acknowledgments
This article is taken from research project number 8248: on February 13, 2017. It has been approved and supported by Deputy of Research of Zahedan University of Medical Sciences. The authors are grateful to Research Vice Chancellor of Zahedan University of Medical Sciences for financial support.
Conflict of interests
The authors declare that there is no conflict of interest.
References
Ahmed N, et al. 2015. Ethnopharmacological relevance of indigenous medicinal plants from district Bahawalnagar, Punjab, Pakistan. Journal of ethnopharmacology. 175: 109-123.
Ahmed N, et al. 2014. Ethnomedicinal knowledge and relative importance of indigenous medicinal plants of Cholistan desert, Punjab Province, Pakistan. Journal of ethnopharmacology. 155 (2): 1263-1275.
Ahmed SI, et al. 2016. Pharmacologically active flavonoids from the anticancer, antioxidant and antimicrobial extracts of Cassia angustifolia Vahl. BMC complementary and alternative medicine. 16 (1): 1-9.
Ayinla M, et al. 2011. Anti-hyperlipidemic effect of aqueous leaf extract of Ocimum gratissimum in alloxan induced diabetic rats. International journal of medicine and medical sciences. 3 (12): 360-363.
Bharathi V, et al. 2018. Effects of a medicinal plant Macrotyloma uniflorum (Lam.) Verdc. formulation (MUF) on obesity-associated oxidative stress-induced liver injury. Saudi journal of biological sciences. 25 (6): 1115-1121.
Carr SS, Hooper AJ, Sullivan DR & Burnett JR 2019. Non-HDL-cholesterol and apolipoprotein B compared with LDL-cholesterol in atherosclerotic cardiovascular disease risk assessment. Pathology. 51 (2): 148-154.
Friedewald WT, Levy RI & Fredrickson DS 1972. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry. 18 (6): 499-502.
Fuhrman B & Aviram M 2001. Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Current opinion in lipidology. 12 (1): 41-48.
Gadanya A & Muhammad S 2018. Hypolipidemic effect of oral administration of aqueous leaf extract of Senna occidentalis in rats. Nigerian journal of basic and clinical sciences. 15 (1): 68.
Ghorbani A 2013. Phytotherapy for diabetic dyslipidemia: evidence from clinical trials. Clinical lipidology. 8 (3): 311-319.
Guo M, Liu Y, Gao Z-Y & Shi D-z 2014. Chinese herbal medicine on dyslipidemia: progress and perspective. Evidence-based complementary and alternative medicine. 2014.
Gupta S, Sharma SB, Singh UR & Bansal SK 2011. Salutary effect of Cassia auriculata L. leaves on hyperglycemia-induced atherosclerotic environment in streptozotocin rats. Cardiovascular toxicology. 11 (4): 308-315.
Habtemariam S 2013. Antihyperlipidemic components of Cassia auriculata aerial parts: identification through in vitro studies. Phytotherapy research. 27 (1): 152-155.
Hasani-Ranjbar S, et al. 2010. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Current pharmaceutical design. 16 (26): 2935-2947.
Hashem H & Alazouny Z 2016. Does splenectomy modulate high fat diet induced liver injury in male rat?(Histological and biochemical study). British journal of science. 13 (2): 45-58.
Ho JE, et al. 2018. Protein biomarkers of cardiovascular disease and mortality in the community. Journal of the American heart association. 7 (14): e008108.
Jani DK & Goswami S 2019. Effect of Senna and Radish Extracts on Hepatic Function in High Fat Diet Fed and Diabetic Rats. Journal of drug delivery and therapeutics. 9 (3-s): 1164-1167.
Kafeshani O, Sarrafzadegan N, Nouri F & Mohammadifard N 2015. Major dietary patterns in Iranian adolescents: Isfahan healthy heart program, Iran. ARYA atherosclerosis. 11 (Suppl 1): 61.
Karimi A, Majlesi M & Rafieian-Kopaei M 2015. Herbal versus synthetic drugs; beliefs and facts. Journal of nephropharmacology. 4 (1): 27.
Khosravi-Boroujeni H, et al. 2013. White rice consumption and CVD risk factors among Iranian population. Journal of health, population, and nutrition. 31 (2): 252.
Kosmas CE, et al. 2018. High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease. Drugs in context. 7.
Maryam AT, Victor OB & Toyin YM 2015. Effect of ethanolic leaf extract of Senna fistula on some haematological parameters, lipid profile and oxidative stress in alloxan-induced diabetic rats. Nigerian journal of physiological sciences. 30 (1-2): 87-93.
Mathur M & Kusum Devi V 2016. Potential of novel drug delivery strategies for the treatment of hyperlipidemia. Journal of drug targeting. 24 (10): 916-926.
Mozaffarian D, et al. 2016. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 133 (4): e38-e360.
Nanumala SK, Nischal Y, Sarika M & Shravaya S 2014. Hypolipidemic activity of ethanolic extracts of Cassia angustifolia in Triton X 100 induced hyperlipidemia in rats. Asian journal of pharmaceutical and clinical research. 7 (1): 189-191.
Nirmala A, Eliza J, Rajalakshmi M, Priya E & Daisy P 2008. Effect of hexane extract of Cassia fistula barks on blood glucose and lipid profile in streptozotocin diabetic rats. International journal of pharmacology. 4 (4): 292-296.
Raut JS & Karuppayil SM 2014. A status review on the medicinal properties of essential oils. Industrial crops and products. 62: 250-264.
Sahebkar A, Simental-Mendia LE, Giorgini P, Ferri C & Grassi D 2016. Lipid profile changes after pomegranate consumption: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine. 23 (11): 1103-1112.
Soleimani D, Paknahad Z, Askari G, Iraj B & Feizi A 2016. Effect of garlic powder consumption on body composition in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. Advanced biomedical research. 5.
Wharton S, Bonder R, Jeffery A & Christensen RA 2020. The safety and effectiveness of commonly-marketed natural supplements for weight loss in populations with obesity: A critical review of the literature from 2006 to 2016. Critical reviews in food science and nutrition. 60 (10): 1614-1630.
Zarei A, et al. 2013. Comparison between the effects of the alcholic extract of Mellissia officinalis and atorvastatin on serum levels of thyroid hormones in hypercholesterolemic male rats. Zahedan journal of research in medical sciences. 15 (8): 6-12.
Zawawi N & Ismail M 2018. Strobilanthes crispus extract reduces respiratory exchange ratio in obese mice fed high fat and low fat diets. Malaysian journal of medical sciences. 25 (6): 46.


 
Type of article: orginal article | Subject: public specific
Received: 2021/06/27 | Published: 2023/02/21 | ePublished: 2023/02/21

References
1. Ahmed N, et al. 2015. Ethnopharmacological relevance of indigenous medicinal plants from district Bahawalnagar, Punjab, Pakistan. Journal of ethnopharmacology. 175: 109-123.
2. Ahmed N, et al. 2014. Ethnomedicinal knowledge and relative importance of indigenous medicinal plants of Cholistan desert, Punjab Province, Pakistan. Journal of ethnopharmacology. 155 (2): 1263-1275.
3. Ahmed SI, et al. 2016. Pharmacologically active flavonoids from the anticancer, antioxidant and antimicrobial extracts of Cassia angustifolia Vahl. BMC complementary and alternative medicine. 16 (1): 1-9.
4. Ayinla M, et al. 2011. Anti-hyperlipidemic effect of aqueous leaf extract of Ocimum gratissimum in alloxan induced diabetic rats. International journal of medicine and medical sciences. 3 (12): 360-363.
5. Bharathi V, et al. 2018. Effects of a medicinal plant Macrotyloma uniflorum (Lam.) Verdc. formulation (MUF) on obesity-associated oxidative stress-induced liver injury. Saudi journal of biological sciences. 25 (6): 1115-1121.
6. Carr SS, Hooper AJ, Sullivan DR & Burnett JR 2019. Non-HDL-cholesterol and apolipoprotein B compared with LDL-cholesterol in atherosclerotic cardiovascular disease risk assessment. Pathology. 51 (2): 148-154.
7. Friedewald WT, Levy RI & Fredrickson DS 1972. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry. 18 (6): 499-502.
8. Fuhrman B & Aviram M 2001. Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Current opinion in lipidology. 12 (1): 41-48.
9. Gadanya A & Muhammad S 2018. Hypolipidemic effect of oral administration of aqueous leaf extract of Senna occidentalis in rats. Nigerian journal of basic and clinical sciences. 15 (1): 68.
10. Ghorbani A 2013. Phytotherapy for diabetic dyslipidemia: evidence from clinical trials. Clinical lipidology. 8 (3): 311-319.
11. Guo M, Liu Y, Gao Z-Y & Shi D-z 2014. Chinese herbal medicine on dyslipidemia: progress and perspective. Evidence-based complementary and alternative medicine. 2014.
12. Gupta S, Sharma SB, Singh UR & Bansal SK 2011. Salutary effect of Cassia auriculata L. leaves on hyperglycemia-induced atherosclerotic environment in streptozotocin rats. Cardiovascular toxicology. 11 (4): 308-315.
13. Habtemariam S 2013. Antihyperlipidemic components of Cassia auriculata aerial parts: identification through in vitro studies. Phytotherapy research. 27 (1): 152-155.
14. Hasani-Ranjbar S, et al. 2010. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Current pharmaceutical design. 16 (26): 2935-2947.
15. Hashem H & Alazouny Z 2016. Does splenectomy modulate high fat diet induced liver injury in male rat?(Histological and biochemical study). British journal of science. 13 (2): 45-58.
16. Ho JE, et al. 2018. Protein biomarkers of cardiovascular disease and mortality in the community. Journal of the American heart association. 7 (14): e008108.
17. Jani DK & Goswami S 2019. Effect of Senna and Radish Extracts on Hepatic Function in High Fat Diet Fed and Diabetic Rats. Journal of drug delivery and therapeutics. 9 (3-s): 1164-1167.
18. Kafeshani O, Sarrafzadegan N, Nouri F & Mohammadifard N 2015. Major dietary patterns in Iranian adolescents: Isfahan healthy heart program, Iran. ARYA atherosclerosis. 11 (Suppl 1): 61.
19. Karimi A, Majlesi M & Rafieian-Kopaei M 2015. Herbal versus synthetic drugs; beliefs and facts. Journal of nephropharmacology. 4 (1): 27.
20. Khosravi-Boroujeni H, et al. 2013. White rice consumption and CVD risk factors among Iranian population. Journal of health, population, and nutrition. 31 (2): 252.
21. Kosmas CE, et al. 2018. High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease. Drugs in context. 7.
22. Maryam AT, Victor OB & Toyin YM 2015. Effect of ethanolic leaf extract of Senna fistula on some haematological parameters, lipid profile and oxidative stress in alloxan-induced diabetic rats. Nigerian journal of physiological sciences. 30 (1-2): 87-93.
23. Mathur M & Kusum Devi V 2016. Potential of novel drug delivery strategies for the treatment of hyperlipidemia. Journal of drug targeting. 24 (10): 916-926.
24. Mozaffarian D, et al. 2016. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 133 (4): e38-e360.
25. Nanumala SK, Nischal Y, Sarika M & Shravaya S 2014. Hypolipidemic activity of ethanolic extracts of Cassia angustifolia in Triton X 100 induced hyperlipidemia in rats. Asian journal of pharmaceutical and clinical research. 7 (1): 189-191.
26. Nirmala A, Eliza J, Rajalakshmi M, Priya E & Daisy P 2008. Effect of hexane extract of Cassia fistula barks on blood glucose and lipid profile in streptozotocin diabetic rats. International journal of pharmacology. 4 (4): 292-296.
27. Raut JS & Karuppayil SM 2014. A status review on the medicinal properties of essential oils. Industrial crops and products. 62: 250-264.
28. Sahebkar A, Simental-Mendia LE, Giorgini P, Ferri C & Grassi D 2016. Lipid profile changes after pomegranate consumption: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine. 23 (11): 1103-1112.
29. Soleimani D, Paknahad Z, Askari G, Iraj B & Feizi A 2016. Effect of garlic powder consumption on body composition in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. Advanced biomedical research. 5.
30. Wharton S, Bonder R, Jeffery A & Christensen RA 2020. The safety and effectiveness of commonly-marketed natural supplements for weight loss in populations with obesity: A critical review of the literature from 2006 to 2016. Critical reviews in food science and nutrition. 60 (10): 1614-1630.
31. Zarei A, et al. 2013. Comparison between the effects of the alcholic extract of Mellissia officinalis and atorvastatin on serum levels of thyroid hormones in hypercholesterolemic male rats. Zahedan journal of research in medical sciences. 15 (8): 6-12.
32. Zawawi N & Ismail M 2018. Strobilanthes crispus extract reduces respiratory exchange ratio in obese mice fed high fat and low fat diets. Malaysian journal of medical sciences. 25 (6): 46.

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