|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2023 | Volume
: 8
| Issue : 3 | Page : 242-249 |
|
Adjuvant antihypertensive effect of a novel Ayurvedic herbal formulation in fructose-induced albino rat model
Pratibha, Sudipta Kumar Rath, Gaurav Sharma
Department of Dravyaguna, National Institute of Ayurveda (NIA) (Deemed to be University), Jaipur, Rajasthan, India
| Date of Submission | 02-Aug-2022 |
| Date of Acceptance | 03-Feb-2023 |
| Date of Web Publication | 16-Aug-2023 |
Correspondence Address:
Pratibha
Department of Dravyaguna, National Institute of Ayurveda (NIA) (Deemed to be University), Jaipur 302002, Rajasthan
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jdras.jdras_118_22
BACKGROUND: Hypertension is the most common treatable risk factor for cardiovascular disease. Hypertension is a multifactorial clinical condition and thus can be managed in multiple pathways. Management of hypertension with modern antihypertensive medication is not ideally effective due to side effects and adverse effects associated with their long-term use. Thus, a novel Ayurvedic formulation NIA/DG/2015/01 test drug (TD) was designed to address multiple pathway management of hypertension. Further, albeit the simultaneous use of modern and Ayurveda antihypertensive is common, there is no systematic study to evaluate the combined effect and adverse effect of this simultaneous use. This study is aimed to evaluate the antihypertensive activity of a novel Ayurvedic formulation (TD) both as an adjuvant with modern antihypertensive drugs and as a stand-alone drug in fructose-induced hypertensive albino rats. METHODS: TD comprises of the combination of aqueous extract of root of Boerhavia diffusa L., whole plant of Convolvulus prostratus Forssk., rhizome of Nardostachys jatamansi (D. Don) DC., bark of Terminalia arjuna (Roxb. ex DC.) Wight & Arn., and root of Withania somnifera (L.) Dunal. TD was administered 90 mg/kg body weight, P.O. twice a day for 28 days to evaluate its effect in fructose-induced hypertensive rats using the Quinapril as a standard drug. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured on day 7th, 14th, 21st, and 28th day of drug administration by noninvasive BP system for rodents. RESULTS: TD significantly reduced SBP and DBP in comparison to the standard drug Quinapril. (P < 0.001, one-way analysis of variance followed by Turkey’s multiple comparison test and Dunnett’s multiple comparison test). CONCLUSION: Ayurvedic formulation possesses significant antihypertensive activity in fructose-induced hypertensive albino rat model. Keywords: Antihypertensive, Ayurvedic, Boerhavia diffusa, Convolvulus pluricaulis, formulation, fructose, hypertension, Nardostachys jatamansi, Terminalia arjuna, Withania somnifera
How to cite this article:
Pratibha &, Rath SK, Sharma G. Adjuvant antihypertensive effect of a novel Ayurvedic herbal formulation in fructose-induced albino rat model. J Drug Res Ayurvedic Sci 2023;8:242-9 |
How to cite this URL:
Pratibha &, Rath SK, Sharma G. Adjuvant antihypertensive effect of a novel Ayurvedic herbal formulation in fructose-induced albino rat model. J Drug Res Ayurvedic Sci [serial online] 2023 [cited 2023 Sep 23];8:242-9. Available from: http://www.jdrasccras.com/text.asp?2023/8/3/242/383693 |
| Introduction | |  |
Hypertension is characterized by systolic >140 mmHg and diastolic >90 mmHg. Overall prevalence of hypertension was 30.7% and the prevalence among women was 23.7%.[1] Hypertension is a multifactorial disease condition that can be better managed by the holistic approach of Ayurveda, where multicomponent medicinal substances are use. Hypertension can be managed in Ayurveda with herbs having Vata-pitta Shamaka action and having affinity to central nervous system and cardiovascular system. Thus, herbs having antihypertensive, stress-reducing, cardiotonic, diuretic, antidepressant activity, and antioxidant actions are suitable. There is no systematic scientific information about the effect of concurrent use of Ayurvedic and western antihypertensives.
This study was designed to assess the role of a novel Ayurvedic formulation test drug (TD) (NIA/DG/2015/01). Textual evidences are available regarding single ingredients of this formulation. Ingredients have predominantly tridoshashamaka, hridya, medhya, manasdoshahara, and mutrala properties that are effective in treating hypertension. This formulation comprising aqueous extract of the five herbs, which have already been reported to have hypotensive or antihypertensive effect individually and act through different mechanisms, both along with Quinapril 10 mg/kg/day, P.O. and stand-alone management in hypertension in fructose-induced albino rat model. Acute oral toxicity study of TD (NIA/DG/2015/01) showed no mortality up to 2000 mg/kg dose in the Wistar albino rats.[2]
The study aimed to develop a novel broad-spectrum Ayurvedic antihypertensive formulation both as an adjuvant and stand-alone drug.
| Materials and Methods | | |
Test drug—Raw material
The raw material, that is, bark of Terminalia arjuna (Roxb. ex DC.) Wight & Arn., whole plant of Convolvulus prostratus Forssk., root of Boerhavia diffusa L., and root of Withania somnifera (L.) Dunal. were collected by the research team from their respective original sources and the same were botanically authenticated from in B.S.I., Jodhpur (Rajasthan), letter no. BSI/AZRC/1.12014/Tech./2016-17-(PI.Id.)/497, dated October 14, 2016. Another raw material rhizome of Nardostachys jatamansi (D. Don) DC. was procured from a commercial source and was authenticated at herbarium section, Department of Botany, Rajasthan University, Jaipur, Rajasthan, India [Authentication no. (RUBL 211624)] [Figure 1].
Test drug—Preparation
Dried plant material was grounded separately, and 20 g powder of each drug (in equal ratio) was mixes and extracted with 2000 mL of water using Soxhlet apparatus (Hot extraction method) for 72 h. The obtained extract was concentrated by evaporating the solvent totally in a water bath. The thick and sticky paste thus obtained was stored in airtight container at room temperature to be used as test drug.
Experimental study
Fructose induces hypertensive albino rat model was used for this study.
Ethical clearance
The experimental study was conducted subsequent to getting due approval from its Institutional Animal Ethical Committee vide CPCSEA Approval No: 1737/PO/RC/14/CPCSEA, IAEC No: IBIR/CPCSEA/IAEC/2015/2/3 dated on 15/09/2015.
Animals
Thirty Wistar albino rats of either sex, weighing around 70–140 g, were procured from Institute of Biomedical and Industrial Research, Jaipur, Rajasthan, India. Animals were fed with a standard chow diet. All animals were kept under a controlled light/dark cycle each of 12 h, temperature (22 ± 2°C), and humidity (50%–60%) with free access to food and water ad libitum.
Drugs and reagents
Fructose (Hi media), Quinapril, and all the chemicals used in the experiments were of standard quality.
Fructose-induced hypertension
Hypertension was induced by feeding the rats for 15 days a fructose diet standard rat chow, containing 66% fructose, 12% fat, and 22% protein. In addition, rats were acclimatized to the procedure of blood pressure measurement at 13.00 h daily for 15 days.[3]
After 15 days of test drug, standard drug and carboxy methyl cellulose (CMC) solution were administered orally with the help of oral feeding tube for 28 days, and blood pressure was measured in every 7 days using the tail-cuff method (noninvasive BP system) and at the 28th day blood samples were collected from orbital puncture for analysis of HDL and serum triglycerides.
Group design
The experiment was conducted by designing five following groups [Table 1].
Dose administration
The Test drug and standard drug were suspended in the 1% w/v CMC solution (vehicle) in distilled water and administered orally using an oral feeding tube. The parameters studied included blood pressure SBP, DBP, and lipid profile.
Data collection and statistical analysis
The observed data were recorded and presented in tabular format. All the results are represented in terms of mean ± standard error of the mean (SEM) analyzed by one-way ANOVA followed by Tukey’s multiple comparison test and Dunnett’s multiple comparison test that were applied to check the level of significance using GraphPad Prism software. P < 0.05 was considered a statistically significant activity.
| Results | | |
Antihypertensive activity
No significant changes in blood pressure were observed in Group A (−ve control) in all observations [Table 2] and [Table 3]; [Graph 1] and [Graph 2]. Test drugs showed a significant reduction in both DBP and SBP on 7th day (18.26%, 5.29%, respectively) and 14th day (5.29%, 6.98%, respectively), but highly significant reduction in BP was observed in this group on 21th and 28th day [Table 4].  | Table 4: Showing differences in BP in Group B (test drug) w.r.t days of drug administration
Click here to view |
Test drug reduced BP in a highly significant (P < 0.001) manner from 7th day onward till 28th day [Table 5]. In the standard control group, both DBP and SBP were reduced highly significantly (P < 0.001) from 7th day till 28th day [Table 6] and [Table 7]. In Group D, the adjuvant effect was seen only till the 7th day by significantly reducing the BP better than Group B, but on the 14th day (DBP) and 21st day (SBP) onward, that is, when the reduction of BP comes back to normal level with the test drug, no added benefits could be observed by adding the standard control [Table 8] and [Table 9]. | Table 5: Showing differences in BP in Group B (test drug) w.r.t Group A (−ve control)
Click here to view |
 | Table 6: Showing differences in DBP in Group B (test drug) vs. Group C (+ve control) w.r.t. Group A (−ve control)
Click here to view |
 | Table 7: Showing differences in SBP in Group B (test drug) vs. Group C (+ve control) w.r.t. Group A (−ve control)
Click here to view |
 | Table 8: Showing differences in DBP in Group B (test drug) vs. Group D (adjuvant) w.r.t. Group A (−ve control)
Click here to view |
 | Table 9: Showing differences in SBP in Group B (test drug) vs. Group D (adjuvant) w.r.t. Group A (−ve control)
Click here to view |
| Discussion | | |
Fructose-induced model is a metabolic pathway-type animal model for hypertension. This is a very commonly used model for hypertension. In animals, high-fructose diets have been used for decades to generate hypertension and insulin-resistance models.[4] Studies to date show that the mechanisms by which excess fructose increases BP fall into three broad categories: increased salt absorption, endothelial dysfunction, and chronic stimulation of the sympathetic nervous system.[5] Tran et al.[6] and Hwang et al.[7] reported that the SBP of rats fed a 66% fructose diet for 2 weeks rose from 124 to 145 mmHg, paving the way for dozens of studies investigating the mechanisms of fructose-induced hypertension. High-fructose feeding plays a role on endothelial dysfunction, nitric oxide, renin angiotensin system, sympathetic nervous system, oxidative stress, and uric acid. High-fructose diet upregulate sodium and chloride transporters therefore resulting in salt overload and increased blood pressure.[8]
In this study, Ayurvedic formulation NIA/D/2015/01 has shown significant reduction in systolic and diastolic BP in fructose-induced rat model.
The study was conducted in five Groups comprising Group A—animals received no medication but were given 1% CMC solution, Group B (test drug)—animals received aqueous extract of formulation 90 mg/kg body wt. twice daily, Group C (standard control)—animals received Quinapril 10 mg/kg/day orally, Group D (adjuvant therapy)—animals received test drug with Quinapril with a constant dose, and Group E (adjuvant with reducing dose of standard control) received constant dose of test drug but standard control drug reduced in 1/4th tapering dose for 1 week and then reduced gradually. The test drug and other drugs were administered orally for 28 days. The observations were recorded on 0, 7, 14, 21, 28, and 35th day, and parameters like blood pressure and lipid profile were analyzed.
As could be seen in observation, the test drug (Group B) showed significant reduction in both DBP and SBP on 7th day (18.26% and 5.29%, respectively) and 14th day (5.29% and 6.98%, respectively). But highly significant reduction in both DBP and SBP was observed in this group on 21th and 28th day. As can be seen from the table, it is also observed that after withdrawal of the test drug the BP went back to the levels on BP on 0 day. So it can be said that the test drug reduced hypertension on 7th and 14th day itself, but the BP obtained normal levels after 21st onward [Table 4].
Thus, it can be suggested that the test drug on its own can manage hypertension, and the results could be expected from 21st day onward. But on withdrawal of the test drug, the BP rose back to the levels at it was before intervention. Therefore, it seems that the effects are maintained till the drug is administered, but the effects are not sustainable after withdrawal.
As could be observed [Table 5], it is seen that the test drug reduced both DBP and SBP in a highly significant manner from 7th day onward till 28th day as compared to the negative control.
Therefore, it could be logically said that the test drug has a significant role in reducing hypertension in fructose-induced hypertensive rat model.
In Group C [Table 6] and [Table 7] that is the standard control group, blood pressure was reduced significantly from 7th day till 28th day. In this group, also upon withdrawal of the drug, the BP increases back to the levels of day 0. The test drug was almost equally effective in reducing DBP and SBP in comparison to that of the standard control. This reduction in BP is highly significant in both the test drug and the standard control, but the standard control showed percentage wise better efficacy than the test drug.
This could be seen when the data were statistically analyzed with keeping Group A as baseline. The difference between the standard control and the test drug with respect to their efficacy on hypertension was found to be highly significant only on the 7th day and significant on the 14th day, but the difference was no significant from 21st day onward. Hence, it is apparent that the test drug reduces hypertension almost at par with the standard control.
In Group D [Table 8] and [Table 9], standard control distinctively and almost immediately reduces BP when given the test drug in order to explore possible better effects of the test drug as an adjuvant. But it was seen that only till 7th day, the effects in Group D were significantly better than Group B. But the differences in activity were found to be no significant (DBP) from 14th day onward and no significant (SBP) from 21st day onward. Therefore, it seems that from 14th day (DBP) and 21st day (SBP) onward, that is, when the reduction of BP comes back to normal level with the test drug, no added benefit could be observed by adding the standard control. It may be suggested that depending upon the clinical condition, the standard control could be given along with the test drug till 2 weeks.
In Group E, it was planned to withdraw the standard control in a phased manner so as to sustainably establish the effects of the test drug. But during the experiment, it was seen that the test drug could restore BP to normal levels by 14th day itself and at a comparable percentage with that of standard control. It was also further observed that the standard control and the test drug did not improve or deteriorate the individual effects when given in combination.
Therefore, as could be seen in [Table 10], the gradual reduction in the dose of standard control when given along with test drug did not show any significant change in their effect on BP. | Table 10: Effect of reduction of dose of +ve control (Group D vs. Group E)
Click here to view |
Lipid profile—No significant changes were observed in serum triglycerides and HDL on day 28 in all groups with respect to Group A [Table 11]. | Table 11: Showing HDL and serum triglycerides (mean ± SEM) in all groups
Click here to view |
| Conclusion | | |
Based on the observations and results recorded in the present research work, it can be suggested that TD was significantly effective in reducing BP in fructose-induced hypertensive rats when given at the 90 mg/kg body wt. twice daily from 14th day onward. The TD could not sustain its effect in reducing BP upon its withdrawal on the 28th day. The standard control, that is, the modern conventional drug, showed no synergistic and additive effect with the TD in reducing BP. Since the TD normalizes BP after 2 weeks, the standard control may be given along with the test drug.
Financial support and sponsorship
The authors are grateful to National Institute of Ayurveda, Deemed to be University, Jaipur (Rajasthan) for providing funding and all necessary facilities to carry out the research work.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Ramakrishnan S, Zachariah G, Gupta K, Shivkumar Rao J, Mohanan PP, Venugopal K, et al. Prevalence of hypertension among Indian adults: Results from the great India blood pressure survey. Indian Heart J 2019;71:309-13.  |
| 2. | Pratibha SG, Sudipta RK. Acute oral toxicity study of polyherbal formulation NIA/DG/2015/01. World J Pharm Sci Technol 2009; ISSN 2581-6217:52-56. |
| 3. | Vogel HG, Vogel WH. Drug Discovery and Evaluation. Berlin Heidelberg Gmbh: Springer-Verlag. |
| 4. | Tran LT, Yuen VG, McNeill JH. The fructose-fed rat: A review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 2009; 332:145-59. |
| 5. | Klein AV, Hosen K. The mechanisms underlying fructose-induced hypertension: A review. J Hypertens 2015;33: 912-20. |
| 6. | Tran LT, Yuen VG, McNeill JH. The fructose-fed rat: A review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 2009;332:145-59. |
| 7. | Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension 1987;10:512-6. |
| 8. | Dai S, McNeill JH. Fructose-induced hypertension in rats is concentration-and duration-dependent. J Pharmacol Toxicol Methods 1995;33:101-7. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]
|
Search Pubmed for