|
 
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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 6
| Issue : 1 | Page : 4-10 |
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Safety and efficacy of Rudraksha Churna in the treatment of essential hypertension—a single-arm multicentre trial
Vinod Bihari Kumawat1, Babita Yadav2, Ashwathykutty Vijayan2, Avinash Jain2, Jeuti Rani Das3, Bhagwan Sahai Sharma2, Shruti Khanduri2, Rakesh Rana2, Richa Singhal2, Thugutla Maheshwar2, Narayanam Srikanth2, Kartar Singh Dhiman2
1 M.S. Regional Ayurveda Research Institute for Endocrine Disorders, Jaipur, India
2 Central Council for Research in Ayurvedic Sciences, New Delhi, India
3 Regional Ayurveda Research Institute, Itanagar, Arunachal Pradesh, India
| Date of Submission | 19-Aug-2021 |
| Date of Acceptance | 09-May-2022 |
| Date of Web Publication | 04-Aug-2022 |
Correspondence Address:
Dr. Ashwathykutty Vijayan
Central Council for Research in Ayurvedic Sciences Headquarter, Jawahar Lal Nehru Bhartiya Chikitsa Avum Homeopathy Anusandhan Bhavan, No. 61–65, Institutional Area, Opp. ‘D’ Block, Janakpuri, New Delhi 110058
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jras.jras_50_21
BACKGROUND: Essential hypertension (EHTN) is one of the most prevalent lifestyle disorders globally. In Ayurveda, the powdered seed of Elaeocarpus ganitrus Roxb. ex G.Don [Rudraksha Churna (RC)] is indicated for headache, the most common symptom of EHTN. Pharmacological studies on an aqueous extract of E. ganitrus have shown that it can be used to treat anxiety and EHTN. However, no research has been done on the therapeutic efficacy of RC in the treatment of EHTN. Therefore, the present study was designed to evaluate the safety and efficacy of RC in the treatment of EHTN. MATERIALS AND METHODS: The multicentre single arm trial was conducted at the Regional Ayurveda Research Institutes at Jaipur and Itanagar. A total of 150 individuals who met the screening criteria were enrolled in the trial after obtaining written informed consent. The participants were administered two 500 mg capsules of RC twice daily (2 g daily) with water for 12 weeks. The outcome measures were reduction in blood pressure, improvement in Hamilton Anxiety Rating Scale Score (HAM-A), SF-36-Health Survey Questionnaire (HSQ), visual analog scale for headache, anxiety, dizziness, tinnitus, fatigue, and amelioration in clinical parameters at every 14-day interval during the trial period of 98 days comprising 84 days of treatment and 14 days of follow-up. RESULTS: The results showed a significant decrease in mean systolic and diastolic blood pressure (P < 0.001). Significant relief (P < 0.001) was also observed in outcome measures such as headache, anxiety, dizziness, fatigue, shortness of breath, palpitation, HAM-A, and HSQ score. Safety parameters such as liver function tests and renal function tests were within the reference range during the study, indicating the therapeutic safety of RC. CONCLUSION: EHTN and its symptoms can be managed with RC. However, double-blind RCTs with adequate sample size may be planned to validate the findings of this study before generalizing the study results. Keywords: Essential hypertension, Rudraksha Churna, safety, efficacy
How to cite this article:
Kumawat VB, Yadav B, Vijayan A, Jain A, Das JR, Sharma BS, Khanduri S, Rana R, Singhal R, Maheshwar T, Srikanth N, Dhiman KS. Safety and efficacy of Rudraksha Churna in the treatment of essential hypertension—a single-arm multicentre trial. J Res Ayurvedic Sci 2022;6:4-10 |
How to cite this URL:
Kumawat VB, Yadav B, Vijayan A, Jain A, Das JR, Sharma BS, Khanduri S, Rana R, Singhal R, Maheshwar T, Srikanth N, Dhiman KS. Safety and efficacy of Rudraksha Churna in the treatment of essential hypertension—a single-arm multicentre trial. J Res Ayurvedic Sci [serial online] 2022 [cited 2023 Mar 25];6:4-10. Available from: http://www.jrasccras.com/text.asp?2022/6/1/4/353412 |
| Introduction | |  |
In India, hypertension (HTN) has recently established itself as a leading cause of death.[1] Several research studies have shown that the prevalence of HTN in India has risen over time.[2] According to Kearney et al. report, India’s HTN burden will nearly double by 2025, from 118 million in 2000 to 213.5 million.[3] HTN is a severe public health burden on India’s cardiovascular health and healthcare systems, accounting for 57% and 24% of deaths from stroke and coronary heart disease, respectively.[4],[5] According to the WHO, HTN is one of the leading causes of death globally.[6]
Essential hypertension (EHTN) is a condition of raised blood pressure without any major systemic illness. EHTN is characterized by increased BP [systolic BP (SBP) ≥ 140 mmHg and diastolic BP (DBP) ≥ 90 mmHg] and may be associated with one or more symptoms such as headache, anxiety, dizziness, tinnitus, confusion, fatigue, shortness of breath, nausea, palpitation, etc.[5] Single or combination of diuretic, antihypertensive, and anxiolytic drugs is the standard line of treatment for the management of EHTN.[7] In Ayurveda, there are some herbs and formulations that possess diuretic, antihypertensive, and anxiolytic actions. In other words, it can be said that Ayurveda interventions can also manage EHTN. Rudraksha Churna [(RC) (powder of seed of Elaeocarpus ganitrus Roxb. ex G.Don)] is an herbal powder mentioned in Raja Nighantu and indicated for headache and alleviation of Kapha and Vata Dosha.[8] Its seeds are considered anxiolytic.[8] A pharmacological study on aqueous extract of RC in renal adrenaline- and nicotine-induced HTN has shown significant antihypertensive activity.[9] RC is also found to be effective in treating depression and Parkinson’s disease.[10] Analgesic, anti-inflammatory, antioxidant, antianxiety, and antidiabetic activities of the extract of RC are the additional beneficial actions reported in several research studies.[8],[9],[10],[11]
In view of Ayurveda pharmacological concepts, RC possesses palliative action on Vata Dosha. Blood circulation is a function of Vyana Vayu (a subtype of Vata Dosha), and the vitiation of Vyan Vayu may result in blood circulation-related diseases such as EHTN. RC is a Vata Dosha palliative, anxiolytic, and antioxidant; hence, it may be able to manage EHTN. It can be deduced that the antihypertensive potential of RC reported in animal studies requires further validation by conducting clinical trials. In view of the supportive background evidence from preclinical studies and the traditional knowledge base from Ayurveda treatises, the present clinical study was planned to evaluate RC's safety and antihypertensive efficacy RC's in the treatment of EHTN.
Objectives
The study's primary objective was to evaluate the role of RC in the treatment of EHTN. The secondary objective was to evaluate the safety profile of RC through its effect on hematological parameters, especially liver (LFT) and kidney function tests.
| Materials and Methods | | |
Trial design
This was a single-arm prospective interventional study.
Study site
The study was carried out at two peripheral institutes of the Central Council for Research in Ayurvedic Sciences (CCRAS), Ministry of Ayush, viz, Ayurveda Central Research Institute, Jaipur, and Ayurveda Regional Research Institute, Itanagar. The study was done after obtaining approval from the Institutional Ethics Committee. The study was conducted in accordance with WHO—Good Clinical Practices Guidelines. This study was also registered in the Clinical Trial Registry of India (CTRI/2014/08/004814).
Study participants
A total of 150 participants (75 from each study site) who fulfilled the screening criteria were enrolled for the trial after obtaining written informed consent.
Inclusion criteria
Patients of either sex, aged between 18 and 50 years, diagnosed with EHTN (SBP ≥ 140 and <160 mmHg; DBP > 90 and < 99 mmHg), HTN stage 1 (as per JNC VII report, 2004), and willing to participate in the study were included in the trial.
Exclusion criteria
Patients diagnosed with coronary artery disease; patients who have a past history of atrial fibrillation, acute coronary syndrome, myocardial infarction, stroke or severe arrhythmia in the last 6 months; symptomatic patients with clinical evidence of heart failure, secondary HTN; patients with concurrent serious hepatic dysfunction (defined as aspartate aminotransferase and/or alanine aminotransferase >3 times of the upper normal limit) or renal dysfunction (defined as serum creatinine > 1.2 mg/dL), uncontrolled pulmonary dysfunction (bronchial asthma and chronic obstructive pulmonary disease), or other concurrent severe disease; patients with diabetes mellitus [blood sugar (fasting) > 126 mg/dL and/or (2 h pp) > 200 mg/dL]; women who are pregnant or lactating; patients on steroids, oral contraceptive pills, or oestrogen replacement therapy; alcohol and/or substance abuse; serum triglycerides ≥ 250 mg/dL; patients with evidence of malignancy; patients suffering from major systemic illness necessitating long-term treatment (rheumatoid arthritis, psycho-neuro-endocrinal disorders, etc.); patients having a history of hypersensitivity to the trial drug; patients who have participated or completed any clinical trial within last 6 months; patients with any other condition that the investigator may think may jeopardise the study were excluded from the clinical trial.
Study interventions
RC powder was filled in 500 mg capsules and was given with potable water in the dose of two capsules (1 g) twice daily, i.e., 2 g per day. The duration of the treatment was 12 weeks. The formulation was procured from good manufacturing practice-certified Ayurveda drug manufacturer. Patients were also given guidance regarding Pathya–Apathya (Do’s and Don’ts) as per the disease condition and the physiological constitution of the patient [Table 1].[12]
Study procedure
Assessment criteria
On the day of enrollment, details such as patient’s demographic information, family history, medical history, particularly related to blood pressure (assessment of objective parameters such as blood pressure, pulse pressure, mean arterial pressure, and pulse rate), Hamilton Anxiety Rating Scale (HAM-A) score, Short Form Survey 36 (SF-36)-Health Survey Score, visual analog scale (VAS) for headache, the presence of symptoms such as anxiety, dizziness, tinnitus, fatigue, shortness of breath, nausea, increased sweating, abnormal sleep, palpitation, blurred vision, and generalized weakness were noted. Subsequent visits were planned at an interval of 2 weeks [14th day (visit 2), 28th day (visit 3), 42nd day (visit 4), 56th day (visit 5), 70th day (visit 6), and 84th day (visit 7)]. Assessments of the patients were done, and study medications were given at each subsequent visit till 84th day. After 2 weeks of 84th day visit, a follow-up without medication was done.
Data of the study participants were documented in case report forms (CRFs) and electronic formats (e-formats) prepared in MS Excel with data validation checks to ensure correct data entry. The e-formats and Xerox of the CRFs along with the laboratory investigation reports of the study participants were assessed at the monitoring center on weekly basis for clinical trial monitoring.
Outcomes
The primary outcome measure was change in mean sitting SBP and DBP from baseline. The secondary outcome measures were change in HAM-A score, SF-36-Health Survey Score, VAS for headache, anxiety, dizziness, tinnitus, fatigue, shortness of breath, nausea, increased sweating, abnormal sleep, palpitation, blurred vision, and generalized weakness.
Sample size
The sample size for the study has been calculated expecting a change of at least 10 mmHg after treatment in SBP. With a standard deviation of 25 mmHg and with 80% power and 95% confidence interval, the sample size was calculated as 62. Adding a dropout rate of 25%, the sample size was assumed as 75 for each centre. Since the study was planned at two centres, so, a total sample size of 150 was finalized.
Statistical analysis
The qualitative data on baseline characteristics of the participants have been presented as n(%). The data on continuous parameters have been analyzed using paired sample t-test. A P value of <0.05 has been considered significant. Analysis has been done using STATA 16.1.
| Results | | |
Data of 100 participants (62 males and 38 females) were used for final analysis. Fifty patients from the trial did not turn up for even a single follow-up even after repeated reminders; thus, the dropout rate was 33.33. Maximum participants (30%) were aged 46-52 years and were married (96%). The majority of the participants were literate and the socioeconomic condition was good (above the poverty line) in 74.7% of participants. Maximum numbers of participants (40%) were performing desk job. 61% of the participants were residing in an urban area [Table 2].
Statistically significant results were observed on subjective parameters such as headache, anxiety, dizziness, fatigue, confusion, shortness of breath, nausea, palpitation, and blurred vision (P ≤ 0.001). Other subjective parameters such as tinnitus, increased sweating, and abnormal sleep also showed statistically significant decrease (P ≤ 0.05) [Table 3]. The mean SBP at the baseline was 148.10 (7.227), which was reduced to 130.00 (8.234) on day 84. And the mean DBP at baseline was 92.90 (4.543), which was reduced to 84.16 (5.083) on day 84 (P < 0.001) [Table 4]. In secondary outcomes, HAM-A score mean at the baseline was 7.01 (3.986), and on 84th day, it was 3.19 (2.087) which was statistically significant (P < 0.001). Significant results were found in all the domains of SF-36-Health Survey Score such as physical functioning, role limitations due to physical health, limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, and general health (P ≤ 0.05) [Table 5].
Safety profile
The effect of the study intervention on various safety parameters such as LFT and renal function tests (RFT) was assessed before and after the treatment. Compared to the baseline, there were no statistically significant changes in LFT and RFT after completion of the treatment [Table 6]. No adverse reaction or adverse event was observed throughout the entire trial period. These observations indicate the safety of RC at the studied dose level.
| Discussion | | |
It is crucial to understand the physiological aspects of BP in Ayurveda, which is based on the Tridosha.[13] The Vata Dosha, specifically the Vyana Vata, is located in the heart and is responsible for blood circulation.[14] According to Charaka, Vyana Vata is a component of Vata Dosha, which constantly forces blood out of the heart and distributes it.[15] Therefore it can be interpreted that the mechanism of BP is controlled by Vata (Vyana Vata). Cardiac output and peripheral resistance are the core factors influencing BP.[16] As a result, an increase in cardiac output or peripheral resistance should accompany a rise in BP. [17] Adopting a faulty lifestyle that includes the Apathya indicated in [Table 1], can vitiate Pitta, Rakta (blood), and Vata Dosha (Vyana Vata). According to Sushruta, the blood vitiated by Vata is both Sheeghra gama (fast-moving) and Askandi (hemodilution).[18] The vitiation of Vata–Pitta Dosha and Rakta Dhatu may lead to changes in peripheral resistance. Hemodilution can increase cardiac output[19] and Vata being Ruksha (dry) and Sheeta (cold) in nature may cause stiffness of blood vessels, which increase peripheral vascular resistance leading to HTN.[20],[21]Rudraksha, the trial drug, is having Sheeta Virya and Madhura Vipaka and is known to pacify Vata and Pitta Dosha, which are primary Doshas involved in the pathology of EHTN.[22] Moreover, Rudraksha is a drug indicated in psychiatric diseases, seizures, asthma, arthritis, dizziness and in clinical conditions that are similar to the EHTN.[23],[24],[25] Also, an aqueous extract of E.Ganitru showed antihypertensive activity due to the action on the rennin-angiotensin system.[26] Another study reported that injecting an ethanol extract of E. ganitrus into anesthetized cats resulted in a significant drop in normal blood pressure and entirely reversed adrenaline-induced HTN.[27] Hence, it can be said that the observed improvement in various symptoms in this clinical trial may be due to the correction of the pathological process by the pharmacological action of RC.
Rudraksha beads have been narrated in Ayurveda for treating headache, fever, mental disorders, and for burn and wound healing.[28] According to Dan et al., mental disorders such as depression, anxiety, impulsive eating disorders, and substance use disorders are linked to a diagnosis of HTN.[29] Headache is a commonly known symptom in cases of EHTN. The indication of RC in headache and mental disorders in the classical text of Ayurveda and the available evidence of the effect of RC in central nervous system (CNS) activities such as sedative, tranquillizing, hypnosis potentiation and, antidepressant action support the therapeutic potential of RC in the management of EHTN.[30] Significant reduction in SBP and DBP (<0.001) is suggestive of its antihypertensive action.
RC contains several secondary metabolites such as phenolic compounds, alkaloids, terpenoids, steroids, and saponins.[31] Phenolic compounds have multiple pharmacological actions such as antioxidant, anti-inflammatory, antidepressant, antiallergic, and antidiabetic.[32] Alkaloids present in RC may be related to its antianxiety action.[33] The symptoms such as headache, anxiety, dizziness, confusion, shortness of breath, increased sweating, palpitation, nausea, and blurred vision are physiologically related to each other and the aforementioned actions can act to treat these symptoms. Therefore, based on the significant result obtained in these symptoms after treatment with RC, it can be interpreted that the previously mentioned secondary metabolites and their actions may have been the cause for the effect.
Tinnitus is found in patients suffering from EHTN; however, the association between tinnitus and HTN is uncertain.[34] In the analysis of the effect on tinnitus, significant result has been observed; however, this symptom was present in a less number of patients, and thus, it cannot be claimed that whether the effect is due to physiological recovery or due to drug action. It can be understood that the presence of many phytoconstitutes and CNS-related action in RC may have been a supportive role of RC in restoring tinnitus-related physiology. Symptoms such as fatigue, generalized weakness, and abnormal sleep can be of psychosomatic origin or nutrition related. The nutritional value of the RC was not evaluated; hence, the significant effect observed in the aforementioned symptoms cannot be attributed to RC. However, it can be interpreted that the advised specific Pathya to all the participants may have increased the nutritional status of the body.[35],[36]
Statistically significant results were observed in all the parameters mentioned in HAM-A except in parameter “Pain.” This may be because of the indication of RC is headache and no musculoskeletal pain reliving activity is reported. Thus, the nonsignificance may be an indicative of the necessity for pain-relieving medicines to be administered along with RC in cases where musculoskeletal pain is a substantial complaint in addition to EHTN.
| Conclusion | | |
The results of this clinical study highlight the efficacy of RC in the management of EHTN. However, the study was single arm, and thus comparative efficacy of RC with standard antihypertensive drug may need to be proven to assess whether RC can be used as standard intervention for the management of EHTN.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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