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Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: A pilot prospective study

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In the traditional system of medicine in India Ashwagandha powder and Sidh Makardhwaj have been used for the treatment of rheumatoid arthritis. However, safety and efficacy of this treatment have not been evaluated. Therefore, the present study was carried out to evaluate the efficacy and safety of Ayurvedic treatment (Ashwagandha powder and Sidh Makardhwaj) in patients with rheumatoid arthritis. One hundred and twenty five patients with joint pain were screened at an Ayurvedic hospital in New Delhi, India. Eighty six patients satisfied inclusion criteria and were included in the study. Detailed medical history and physical examination were recorded. Patients took 5g of Ashwagandha powder twice a day for three weeks with lukewarm water or milk. Sidh Makardhwaj (100 mg) with honey was administered daily for the next four weeks. The follow up of patients was carried out every two weeks. The primary efficacy end point was based on American College of Rheumatology (ACR) 20 response. Secondary end points were ACR50, ACR70 responses, change from baseline in disease activity score (DAS) 28 score and ACR parameters. Safety assessments were hepatic function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and ß2 microglobulin], renal function (urea and creatinine and NGAL) tests and urine mercury level. The study was completed by 90.7 per cent (78/86) patients. Patients with moderate and high disease activity were 57.7 per cent (45/78) and 42.3 per cent (33/78), respectively. All patients were tested positive for rheumatoid factor and increased ESR level. Ashwagandha and Sidh Makardhwaj treatment decreased RA factor. A significant change in post-treatment scores of tender joint counts, swollen joint counts, physician global assessment score, patient global assessment score, pain assessment score, patient self assessed disability index score and ESR level were observed as compared to baseline scores. ACR20 response was observed in 56.4 per cent (44/78) patients (American College of Rheumatology criteria) and moderate response in 39.74 per cent (31/78) patients [European League Against Rheumatism (EULAR) criteria]. Ayurvedic treatment for seven weeks in rheumatoid arthritis patients showed normal kidney and liver function tests. However, increased urinary mercury levels were was observed after treatment. The findings of the present study suggest that this Ayurvedic treatment (Ashwagandha powder and Sidh Makardhwaj) has a potential to be used for the treatment of rheumatoid arthritis. However, due to small sample size, short duration, non randomization and lack of a control group as study limitations, further studies need to be done to confirm these findings.
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Indian J Med Res. 2015 Jan; 141(1): 100–106. PMCID: PMC4405924
Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder &
Sidh Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study
Gajendra Kumar, Amita Srivastava, Surinder Kumar Sharma, T. Divakara Rao, and Yogendra Kumar Gupta
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
Department of AYUSH, Ministry of Health & Family Welfare, Government of India, New Delhi, India
CGHS Ayurvedic Hospital, New Delhi, India
Reprint requests: Dr Y.K. Gupta, Professor & Head, Department of Pharmacology, All India Institute of Medical Sciences Ansari Nagar, New
Delhi 110 029, India e-mail: yk.ykgupta@gmail.com
Received 2012 Jun 11
Copyright : © Indian Journal of Medical Research
This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background & objectives:
In the traditional system of medicine in India Ashwagandha powder and Sidh Makardhwaj have been used
for the treatment of rheumatoid arthritis. However, safety and efficacy of this treatment have not been
evaluated. Therefore, the present study was carried out to evaluate the efficacy and safety of Ayurvedic
treatment (Ashwagandha powder and Sidh Makardhwaj) in patients with rheumatoid arthritis.
Methods:
One hundred and twenty five patients with joint pain were screened at an Ayurvedic hospital in New Delhi,
India. Eighty six patients satisfied inclusion criteria and were included in the study. Detailed medical
history and physical examination were recorded. Patients took 5g of Ashwagandha powder twice a day for
three weeks with lukewarm water or milk. Sidh Makardhwaj (100 mg) with honey was administered daily
for the next four weeks. The follow up of patients was carried out every two weeks. The primary efficacy
end point was based on American College of Rheumatology (ACR) 20 response. Secondary end points
were ACR50, ACR70 responses, change from baseline in disease activity score (DAS) 28 score and ACR
parameters. Safety assessments were hepatic function [alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and ß2 microglobulin], renal function (urea
and creatinine and NGAL) tests and urine mercury level.
Results:
The study was completed by 90.7 per cent (78/86) patients. Patients with moderate and high disease
activity were 57.7 per cent (45/78) and 42.3 per cent (33/78), respectively. All patients were tested positive
for rheumatoid factor and increased ESR level. Ashwagandha and Sidh Makardhwaj treatment decreased
RA factor. A significant change in post-treatment scores of tender joint counts, swollen joint counts,
physician global assessment score, patient global assessment score, pain assessment score, patient self
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assessed disability index score and ESR level were observed as compared to baseline scores. ACR20
response was observed in 56.4 per cent (44/78) patients (American College of Rheumatology criteria) and
moderate response in 39.74 per cent (31/78) patients [European League Against Rheumatism (EULAR)
criteria]. Ayurvedic treatment for seven weeks in rheumatoid arthritis patients showed normal kidney and
liver function tests. However, increased urinary mercury levels were was observed after treatment.
Interpretation & conclusions:
The findings of the present study suggest that this Ayurvedic treatment (Ashwagandha powder and Sidh
Makardhwaj) has a potential to be used for the treatment of rheumatoid arthritis. However, due to small
sample size, short duration, non randomization and lack of a control group as study limitations, further
studies need to be done to confirm these findings.
Keywords: Ashwagandha powder (Withania somnifera), clinical trial, efficacy, rheumatoid arthritis,
safety, Sidh Makardhwaj
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, progressive disease. The prevalence of
rheumatoid arthritis has been reported to be 0.75 per cent in Indian population . The disease is more
common in women than in men and occurs between the ages of 40 and 60 yr . It leads to irreversible joint
damage and systemic complications, and is associated with substantial morbidity and increased
mortality . Patients with active RA suffer from significant decline in functional capacity and 40 per cent
become work disabled within five years from onset of symptoms . Direct and indirect costs are also
enormous .
The goals of RA management are to control pain and swelling, delay disease progression, minimize
disability and improve quality of life. Non steroidal anti-inflammatory drugs (NSAIDs) have both
analgesic and anti-inflammatory properties but do not change disease outcomes and side effects are
gastrointestinal ulcers (15-20% of patients), ulcer with bleeding and perforations (2-4% of patients over 70
yr of age) . Glucocorticoids have greater action on joint pain than NSAIDs but have numerous side effects
including adrenal suppression, ulcers and osteoporosis . Disease modifying antirheumatic drugs
(DMARDs) reduce the progression of joint erosion but they have slow onsets and no analgesic activity.
Methotrexate has been shown to cause pulmonary complications .
Ayurveda is a widely practiced system of traditional medicine in India. It has been shown that 60-90 per
cent of persons with arthritis use complementary and alternative medicine (CAM) . Stress is widely
recognized as an important risk factor in the aetiology of inflammatory rheumatic diseases . Withania
somnifera (Ashwagandha) exhibits anti-inflammatory, anti-tumour, anti-stress, antioxidant,
immunomodulatory, haematopoietic and rejuvenating properties . Thamaraiselvi et al have shown
Ashwagandha powder to be effective in patients with RA. Sidh Makardhwaj is a formulation mentioned in
Ayurvedic Formulary of India . It is a sublimed product made from pure mercury, sulphur and gold. It is
used in rheumatoid arthritis, and neurological disorders, as rasayana for vigour and longevity of life .
Though Ashwagandha and Sidh Makardhwaj have been used in the treatment of patients with RA for many
decades, their safety and efficacy have not been evaluated. The present study was, therefore, undertaken to
evaluate the efficacy and safety of Ayurvedic treatment i.e. Ashwagandha and Sidh Makardhwaj in patients
with RA.
Material & Methods
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The present study was a prospective, open-label, non-randomized, outpatient-based, single centered drug
trial conducted in the department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New
Delhi. It was conducted during October 2009 to December 2010 after obtaining approval from the Institute
Ethics Committee. The study was registered with Clinical Trial Registry of India, (CTRI- 2009 000699).
Single batches of Sidh Makardhwaj (Maharshi Ayurveda Pharmaceutical Pvt. Ltd., India), Ashwagandha
and honey (Dabur, India) were procured for the entire study. Patients of either sex between the age group
of 18 to 60 yr, who were diagnosed with rheumatoid arthritis by the American College of Rheumatology
(ACR) 1987 criteria , able to provide written informed consent were included in the study. Exclusion
criteria were medical history of unstable angina, myocardial infarction, heart failure or stroke within three
months of the study, uncontrolled hypertension (diastolic blood pressure >100 mm Hg), uncontrolled
diabetes mellitus, alanine and aspartate aminotransferases (ALT and AST) > 2 x upper limit of normal,
impaired renal function (creatinine 2.0 mg/dl), pregnancy/lactation, or patients on any other Ayurvedic
drugs during the last 15 days.
The first 125 patients with joint pain were screened in the OPD at CGHS Ayurvedic Hospital, Lodhi Road,
New Delhi during the study period. Eighty six patients satisfied the inclusion criteria and were willing to
participate in the study, signed the informed consent. Detailed medical history, general physical
examination and rheumatologic evaluation were recorded by the designated Ayurvedic physician.
Laboratory tests were carried out as per protocol. Subsequently, all patients were examined by the
physician at every visit during the trial.
Medications: The patients took 5g of Ashwagandha powder twice a day for three weeks with lukewarm
water or milk. Sidh Makardhwaj (100 mg) with honey was administered daily for the next four weeks.
Records of dispensed drugs were maintained in drug inventory form. Concurrent analgesics/NSAIDs in
any form, oral, injectable or topical were not permitted. However, there was facility of rescue treatment
with NSAIDs. Patients who received rescue medications were excluded from the study. Patients were
allowed to continue with their ongoing lifestyle and diet.
Clinical assessment: The primary efficacy end point was the proportion of patients with a 20 per cent
improvement as per ACR criteria (ACR20) response at the end of treatment. ACR 20 is defined as 20
per cent improvement in tender joint counts, swollen joint counts and 20 per cent improvement in 3 of the
5 areas, i.e. physician global assessment score, patient global assessment score, pain assessment score,
patient self assessed disability index score, ESR . Secondary end points included ACR50 and ACR70
responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses
of DAS28/European League Against Rheumatism (EULAR) response , change from baseline in each of
the ACR core set of parameters. Safety assessments included hepatic function [alanine aminotransferase
(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin] and renal function
(urea and creatinine) tests were analyzed separately using individual kit by semi auto analyzer (Mini
techno, USA). Early sensitive marker of liver (ß2 microglobulin) and kidney (NGAL: neutrophil
gelatinase associated lipocalin) were reported as the instructions of the manufacturer of ELISA assay kits
(Logitech India Pvt, Delhi, India) to evaluate the effect of the Ashwagandha and Sidh Makardhwaj
treatment. Urinary mercury level was estimated by ICP-AES (Jobin Horiba, JY 2000-2, France) .
Sample size determination: The sample size was determined by the following specifications: (i) there
would be an 80 per cent power for detecting a change from baseline in the DAS in 28 joints; (ii) 20 per
cent improvement as per ACR criteria (ACR 20) response at fourth week; (iii) the test of the null
hypothesis was conducted at a 2-sided 5 per cent significance level; (iv) acceptable margin of errow will be
5 per cent; and (v) population size of 200 and expected response of 10 per cent. Under these assumptions,
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the required sample size was 75 subjects. However, considering high dropout rate (20%) and lack of
sufficient data from published rheumatoid arthritis drug trials using Ayurvedic medicines, it was then
decided to enrol 90 patients.
Statistical analysis: Chi-square test was applied for patients showing improvement/cure after therapy.
Laboratory measurements were compared with baseline using an analysis of variance.
Results
Efficacy evaluation of Ashwagandha and Sidh Makardhwaj: A total of 90.7 per cent (78/86) patients
adhered to study protocol and completed seven weeks of treatment (three weeks of Ashwagandha powder
followed by four weeks of Sidh Makardhwaj). Eight patients prematurely discontinued due to lack of
efficacy and refusal of continued treatment (2 = due to unknown reason, 2 = shifted to allopathic
medication, 4 = concomitant use of other medication). There were 57.7 per cent (45/78) female and 42.3
per cent (33/78) male subjects and mean ages were 45.7 ± 8.6 (range 19-59) and 49.8 ± 7.9 (range, 25-59)
yr, respectively. At baseline, majority of patients tested positive for rheumatoid factor (RF), its values in
male and female patients were 31.2 ± 3.1 and 50.9 ± 16.1 IU/ml, respectively and post-treatment levels
were 22.1 ± 1.4 and 41.7 ± 14.4 IU/ml. The levels of ESR (erythrocyte sedimentation rate) at baseline in
male and female were 28.8 ± 3.3 and 43.8 ± 16.16.3 mm/h and post-treatment levels were 21.6 ± 1.9 and
35.4 ± 14.3 mm/h, respectively. The results showed significant decrease in post-treatment levels of ESR
and RA factor as compared to baseline levels in male and female (Table I).
Seven weeks treatment effectiveness was assessed by (i) ACR 20 response; (ii) change in DAS28 (baseline
DAS28 to 4 wk DAS28); (iii) non response, moderate and good response according to the EULAR
response criteria; and (iv) the proportion of patients achieving disease remission (DAS28 < 2.6), according
to the EULAR criteria.
There were significant changes in post-treatment scores of tender joint counts, swollen joint counts,
physician global assessment score, patient global assessment score, pain assessment score, patient self
assessed disability index score and ESR level as compared to baseline scores in male and female patients (
Table I). ACR 20 response was observed in 48.5 per cent (16/33) male and 62.2 per cent (28/45) female
patients.
In our study, DAS28 score in male and female patients at baseline were 5.01±0.36 and 5.12 ± 0.33,
respectively and at post-treatment were 4.29 ± 0.21 and 4.28 ± 0.19 showing significant decrease in
DAS28 score. DAS28 score of higher than 5.1 is indicative of high disease activity, whereas a DAS28
below 3.2 indicates low disease activity . A total of 45 (57.7%) patients were in moderate disease activity
with DAS28 score between 3.2 and 5.1. High disease activity was observed in 42.3 per cent (33/78)
patients with DAS28 score >5.1.
In moderate disease activity, DAS28 improvement over the time in the range of 0.6-1.2 was observed in
55.6 per cent (25/45) patients and <0.6 improvement over the time in DAS28 was observed in 44.4 per
cent (20/45) patients. In high disease activity, >1.2 improvement over the time in DAS28 was observed in
18.2 per cent (6/33) patients and DAS28 improvement over the time in the range of 0.6-1.2 was observed
in 81.8 per cent (27/33) patients. In summary, Sidh Makardhwaj treatment for four weeks in rheumatoid
arthritis patients showed moderated response in 39.74 per cent (31/78) patients.
Safety evaluation of Ashwagandha and Sidh Makardhwaj: There was no significant change in serum levels
of ALT, AST, ALP, bilirubin, urea, creatinine, ß2MG and NGAL at post-treatment as compared to baseline
(Table II). Urinary mercury level increased from 6.9 ± 1.3 to 32.5 ± 2.4 and 8.2 ± 1.6 to 41.7 ± 3.1 µg/l in
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male and female patients, respectively. Mercury levels increased significantly after Ayurvedic treatment as
compared to baseline level.
In our study, significant improvements were observed in patients’ tender joint counts, swollen joint counts,
ESRs, physician's rating of disease activity, physical function and pain. For the ACR20 response, there
was a moderate improvement while ACR50 and ACR70 responses were not observed. In agreement with
earlier reports , Ashwagandha and Sidh Makardhwaj were found to be effective and safe treatment for
patients with RA. Seven weeks after starting Ayurvedic treatment, mean DAS28 scores significantly
decreased in male and female patients. Only 39.74 per cent of the patients were EULAR responders
(moderate). The results of the present study are in concordance with several studies on Ayurvedic
treatment .
Sidh Makardhwaj has been used in the Indian System of Medicine with claimed efficacy and safety .
Ayurvedic physicians often avoid prescribing it as a medicine particularly for longer periods. But there has
always been ambiguity in use of this mercury sulphide containing Ayurvedic medicine and often
associated with the question of toxicity. The US Environmental Protection Agency (EPA) has adopted a
reference dose (RfD) for methyl mercury of 0.1 µg/kg body weight/day . The total mercury content of
Sidh Makardhwaj formulation used in the present study was 35454.2 µg/g. The calculated total ingested
mercury per day was 3545.4 µg (Sidh Makardhwaj dose = 100 mg per day). Thus, in its therapeutic dose,
the per day ingested mercury was many fold higher than the reference dose. It was observed that with this
high concentration of mercury in Sidh Makardhwaj given for 28 days did not cause significant change in
liver and kidney functions of the patients. Urinary mercury levels were significantly increased after
Ayurvedic treatment. Hence, mercury present in Sidh Makardhwaj was slowly eliminated from the body.
Lande in 1927 used aurothioglucose for the first time in the treatment of RA . In another study, Forestier
in 1935 used gold thiopropanol sodium sulphanate in 550 cases of RA with beneficial results. Gold
containing drugs comprise a class of distinctive anti-arthritic agents (DMARDs) used when NSAIDs are
insufficient to treat severe cases of rheumatoid or psoriatic arthritis. The reported remissions of rheumatoid
arthritis was of the order of 30 per cent with gold therapy . Gold content in Sidh Makardhwaj formulation
used in the present study was 29.1 mg/g. The calculated total ingested gold per day was 2.91 mg (Sidh
Makardhwaj dose = 100 mg per day). Thus, the per day ingested gold in Sidh Makardhwaj was in
therapeutic dose.
There were a few limitations of our study. This was a seven week study with a sample size of 78 patients
carried out in a single Ayurvedic hospital at New Delhi. Randomization was not done. Also, there was a
lack of standard therapy group as a control group due to ethical issues.
In conclusion, our findings demonstrated the potential efficacy and safety of Ashwagandha (3 wk) and
Sidh Makardhwaj (4 wk) in the treatment of RA. Ashwagandha and Sidh Makardhwaj should be further
tested in long term randomized placebo controlled trial to establish its clinical use.
Acknowledgment
Authors thank the chief medical officer of CGHS, Ayurvedic hospital, New Delhi, for recruitment of
patients, and the staff of the CGHS, Ayurvedic hospital, New Delhi, for their assistance. Authors
acknowledge the support provided by Drs Sudhir Sarangi and Prafful in improving the quality of
manuscript. The financial support by Central Council for Research in Ayurveda and Sidha (CCRAS),
Department of AYUSH, Ministry of Health and Family Welfare, Government of India, for this research
work is duly acknowledged (F. No. Z31014/04/2009/EMR-CCRAS).
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Figures and Tables
Table I
Clinical features in rheumatoid arthritis patients (male=33, female=45) on Ashwagandha and Sidh
Makardhwaj treatment
Table II
Safety evaluation of liver and kidney of rheumatoid arthritis patients (male=33, female=45) on treatment
with Ashwagandha and Sidh Makardhwaj
Articles from The Indian Journal of Medical Research are provided here courtesy of Medknow Publications
... One meta-analysis, 95 eight RCTs, 128-135 one nonrandomised trial 136 and three single arm studies [137][138][139] assessed plant based interventions for RA. RCTs tested microalgae oil, 128 herbal medicine, 135 pomegranate extract, 129 quercetin 130 132 134 and rose hip powder, 133 reporting no consistent effects on outcomes, including pain, function, disease activity, joint counts and QoL. ...
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Background A EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed. Methods Systematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage). Results In total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression. Conclusion The current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing.
... Similarly, there is a significant number of research on the medicinal use of W. somnifera that show a variety of potential medicinal applications, including memory and cognitive function improvement [17], management of muscle sarcopenia [18], anticancer studies [19 -22], anxiolytic potential [23], stress and anxiety reduction in adults [24], sperm count and motility improving efficacy [25], in arthritis [26], anti-diabetic [27,28], and many more. Along with its beneficial uses, there are also some precautions as well as warnings for its users (https://www.mskcc.org/cancer-care/integrative-medicine/herbs/ashwagandha) ...
Chapter
In the present pandemic, demands for natural herbs and spices have been surprisingly enhanced, and the reason behind enhancements in the demands of these spices and herbs are genuine because they have super immunity boosting capability, and they strengthen the human body against various diseases and pathogenic microbes. In this direction, Withania somnifera, also popularly known as ‘Ashwagandha,’ is one of the popular herbs known for its different medicinal values and various biological functions. This Ayurvedic herb is known for its potential anti-inflammatory properties, fatigue reduction, stress reduction, anticancer properties, and it is also helpful for diabetic patients, arthritis pain, and others. Due to lack of research and scientific evidence, there is no concrete information on the direct medicinal importance and use of this plant, but it has a historical pharmaceutical role in Ayurveda as traditional Indian medicine, and its medicinal impacts have now been proved via various pieces of research. This chapter concisely describes the various recent clinical aspects and pieces of research on this medicinally valuable herb.
... Thus, several trials have assessed the efficacy and safety of W. somnifera for various purposes such as treating stress and anxiety, improving vitality or sexual function, strength training, arthritis treatment, and as an adjuvant to antitubercular, anticancer, or antipsychotic medications. [9][10][11][12][13][14][15][16][17][18][19][20] Most of these trials used twice-daily dosages of standard immediate release ashwagandha formulations, which are commonly prescribed in clinical practice. However, till date, the development or use of modified release ashwagandha formulations is not reported. ...
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Background: In this open-label, randomized, balanced, two-treatment, two-sequence, two-period, crossover, single-dose oral comparative pharmacokinetics study, the pharmacokinetics, safety, and tolerability of test product ‘ashwagandha (Withania somnifera)’ root extract sustained release capsule 300 mg (Prolanza™), each containing 15 mg withanolides (administered dose: 2×15 mg) was compared with that of a reference product (organic KSM-66 ashwagandha extract [vegan] capsule, each containing 15 mg withanolides [administered dose: 2×15 mg]).Methods: Total 14 healthy men were randomized to receive either the test or the reference product as a single dose of 2 capsules in sequence, administered under fasting conditions. Plasma concentrations of total withanolides, withanolide A and 12-deoxywithastramonolide were measured using validated liquid chromatography–mass spectroscopy/mass spectroscopy.Results: The test product had higher relative absorption, better relative bioavailability, and longer elimination half-life indicating a sustained-release profile compared to reference. Specifically, the relative bioavailability of the test formulation was 12, 44, and 11 times higher for total withanolides, withanolide A and 12-deoxywithastramonolide, respectively. No adverse events were reported during the study.Conclusions: The sustained-release profile of the test product, compared to reference product, will provide more long-lasting therapeutic effects from a single daily dose (Retrospectively applied on Clinical Trials Registry - India [CTRI]. Application reference number: REF/2020/03/032408). The study reports the unique sustained release formulation of Withania somnifera (Ashwagandha) root extract. The pharmacokinetic study also reports for first time, the successful plasma estimation of withanolide A and 12-deoxywithastraamonolide, the major phytoactives of ashwagandha.
... In a randomized controlled trial conducted among 92 patients of osteoarthritis of knee joint treated with a polyherbal combination containing ashwagandha shown mild and uncommon side-effects and no change in ALT and AST levels [15]. Rheumatoid arthritis was treated by other group with ashwagandha and Sidh Makardhwaj in a prospective pilot study demonstrates that symptoms were improved without any alteration in liver enzymes level [16]. In a study conducted by Choudhary et al, tolerability of ashwagandha was found excellent and remarkable improvements were seen in cognitive parameters as compared to placebo among fifty adults without any sign of hepatotoxicity or ALT/AST elevations [17]. ...
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Adverse drug reporting of herbal drugs is less common as they are generally considered as safe. It is also very common to use self-medication by people in the case of herbal drugs. But many times, mild to severe events have been seen with the use of herbal or ayurvedic medicines. We have reported a case of post-covid patient, who was having complained of headache, body ache, lethargy, backache, generalized weakness and excessive sweating since one weak. Patient had past history of hospitalization due to COVID-19 moderate pneumonia one month back. Patient also had history of type-2 diabetes mellitus, hypertension and dyslipidemia and was taking anti-diabetic and anti-hypertensive medications continuously. Ashwagandha powder (Withania somnifera), Maha yogaraj guggulu (herbal anti-inflammatory) and Syrup Amynity Plus (herbal immune-booster) were prescribed for these complain. Conversely, moderate severity adverse reaction like nausea, vomiting, diarrhea, and abdominal cramps were noted after the intake of suspected drug i.e. ashwagandha powder. Nevertheless, symptoms were relieved after the de-challenge. This shows a temporal relation of the event with the suspected drug. One more possibility of drug-drug interaction in this case cannot be ruled out completely. Causality assessment was done for this adverse event and it was considered as the “probable” category of the adverse event in WHO causality classification.
... In a study for acute and subacute toxicity, oral administration of LD50 of Withania somnifera alcoholic extract standardized for Withaferin-A, in Wistar rats in dose greater than 2000 mg/kg body weight did not show any toxicologically significant treatment related changes in clinical observations, ophthalmic examination, body weight gain, feed consumption, clinical pathology evaluation, and organ weight. Hematological and serum chemistry parameters were within the normal limits and there were no treatment related gross or histopathological findings14,15,16 Some pilot studies conducted on efficacy and safety evaluation ofAshwagandha showed normal hepatic functions and renal functions when given for 7 weeks.17 A study on healthy volunteers (12 Male &6Female, age: 18-30 years, and BMI:[19][20][21][22][23][24][25][26][27][28][29][30] had shown normal organ function tests before and after the intervention. ...
Book
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This booklet covers easily available medicinal plant products that have been used in Ayurvedic system of medicine for various indications and have useful properties in respiratory infections and have been also shown to have antiviral, anti-inflammatory, immunomodulatory ands other properties which can be beneficial in such infections.
Chapter
The Chemistry inside Spices and Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field. The book is an extensive 2-part collection of 20 chapters contributed by experts in phytochemistry with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included. Part II continues from the previous part with chapters on the treatment of skin diseases and oral problems. This part focuses on clinically important herbs such as turmeric, fenugreek, ashwagandha (Indian winter cherry), basil, Terminalia chebula (black myrobalan). In terms of phytochemicals, this part presents chapters that cover resveratrol, piperine and circumin.
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Obesity is a significant health concern, as it causes a massive cascade of chronic inflammations and multiple morbidities. Rheumatoid arthritis and osteoarthritis are chronic inflammatory conditions and often manifest as comorbidities of obesity. Adipose tissues serve as a reservoir of energy as well as releasing several inflammatory cytokines (including IL-6, IFN-γ, and TNF-α) that stimulate low-grade chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, diabetes, hypertension, cardiovascular disorders, fatty liver disease, oxidative stress, and chronic kidney diseases. Dietary intake, low physical activity, unhealthy lifestyle, smoking, alcohol consumption, and genetic and environmental factors can influence obesity and arthritis. Current arthritis management using modern medicines produces various adverse reactions. Medicinal plants have been a significant part of traditional medicine, and various plants and phytochemicals have shown effectiveness against arthritis and obesity; however, scientifically, this traditional plant-based treatment option needs validation through proper clinical trials and toxicity tests. In addition, essential oils obtained from aromatic plants are being widely used as for complementary therapy (e.g., aromatherapy, smelling, spicing, and consumption with food) against arthritis and obesity; scientific evidence is necessary to support their effectiveness. This review is an attempt to understand the pathophysiological connections between obesity and arthritis, and describes treatment options derived from medicinal, spice, and aromatic plants. (Full-text link: https://www.mdpi.com/2072-6643/14/5/985)
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With growing popularity of complementary and alternative medicine (CAM) among the individuals with chronic pain and muscular problems, a number of patients with rheumatoid arthritis (RA) show their interest in CAM interventions for disease improvement. Various reports published on CAM are based on animal model of RA however there is often lack of high quality clinical investigations for explaining the success stories of CAM therapies in patients with RA. CAMs having potential to be used for therapy in patients with RA have been identified, however lack of awareness and scepticism of their efficacy has made the patients reluctant to choose these drug less therapies. In this review, we have summarized the existing evidences which suggest promising efficacy of different alternative therapies in managing RA and providing both physical and mental well being to RA patients.
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Honey, a natural food product available abundantly all over the world, has a wide range of pharmacological activities. The search for anti-proliferative agents that reduce cervical cancer is a task of great importance. The objective of this study was to observe the cytotoxic activity of honey from Litchi chinensis and purified honey protein (PHP) on HeLa cells. Initially, protein was isolated from honey using ethanol (60%, v/v) followed by purification using single-step Q-sepharose anion exchange chromatography. Honey (1-10%, v/v) and PHP (0-60 mg/mL) exposure significantly reduced the cancer cell viability, indicating apoptosis in a dose dependent manner. The MTT assay showed the IC50 of honey and PHP to be 3.5 mg/mL and 4.13 ng/mL, respectively. The MMP (Δψm) and TUNEL assay showed more apoptosis under PHP intervention than in honey-treated cells. This in vitro evaluation of the cytotoxicity of honey and PHP against cancer cells provides scientific rationale for an effective anti-proliferative agent and endorses lychee honey and PHP as herbal medicines.
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Amavata is described as a difficult to cure (Krichhrasadhya) disease in Ayurveda. Pain in joints with swelling is a cardinal feature of this disease. It can be correlated with rheumatoid arthritis described in modern medical science. In conventional medical science, steroids and some nonsteroidal anti-inflammatory drugs are used for its management, but they cause certain dangerous side effects in the patients. Ayurveda promises an excellent therapy for it. The present clinical trial was conducted with the same objective to provide a safe, economical and effective therapy to the patients of Amavata. The present study was conducted in 73 patients having classical symptoms of Amavata. The patients were given Vardhamana Pippali Rasayana for 15 days. Patients with any other acute or chronic systemic illness or infection were excluded from the study. The observations and results obtained were analyzed statistically applying the "t" test. All the patients experienced up to 50% relief from the signs and symptoms of Amavata after the therapy. The drug might have produced its beneficial effects in the patients of Amavata due to its Agnideepana, Amapachana, Vatashamaka and Rasayana effects in the body. A significant decrease in the erythrocyte sedimentation rate in all the patients was also noticed. All the results obtained were highly significant statistically. Thus, it can be implicated that the Vardhamana Pippali Rasayana has a lot of beneficial effects in the patients of Amavata.
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Amavata (Rheumatoid Arthritis) has been a challenging problem to the medical field. Various treatment protocols are applied in this disease with partial success. In present clinical study, 12 patients of clinically proven Amavata (Rheumatoid Arthritis) were treated with Panchamuladi Kaala Basti to evaluate its efficacy. All clinical Ayurvediya nidanadi parameters and American Rheumatism Association guidelines for Rheumatoid Arthritis were followed. Before treatment and after treatment, analysis was done and results were calculated statistically using paired 't' test. Results obtained are encouraging and indicate the efficacy of Panchamuladi Kaala Basti over Amavata (Rheumatoid arthritis), exploring many aspects of this clinical entity.
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Presents guidelines for the management of rheumatoid arthritis and monitoring of drug therapy.
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The real physicochemical nature of the classical metal preparations, the bhasmas in the Indian Systems of Medicine (ISM) is not very clear. Of late, doubts have been raised as to their utility and suitability as medicine. The bhasmas are in fact products of classical alchemy - inorganic compounds of certain metals and gems in a very fine powdered form, mostly oxides, made in elaborate calcination processes perfected several centuries ago. For most of the metals, methods of bhasma preparation as given in the classical texts differ between themselves in terms of accompaniments and process detail. Correspondingly, the processing of a certain metal lead to bhasmas with different colours. The resultants are considered to be the same medicinal substance with the ascribed indications even though these may differ in composition between them and should ideally be addressing different ailments. In short, there is no standard bhasma of a metal as such. In view of such ambiguity and the risks attendant to their inconsiderate use, there is an urgent need to bring about a standardization of these preparations- process and the end product, as also to resolve the respective indications and strengthen the regime to monitor the manufacturing, and administration of these preparations.
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Objective. Methotrexate has a well-recognized side-effect of acute hypersensitivity pneumonitis. There is concern about whether chronic pulmonary toxicity can occur with methotrexate treatment. Our objective was to compare chest high-resolution computed tomography (HRCT) findings and serial pulmonary function tests in rheumatoid arthritis (RA) patients on methotrexate with findings for a control group of patients with RA who were not being treated with methotrexate. Methods Study patients had an initial chest radiograph, full pulmonary function tests and chest HRCT. Pulmonary function tests were then performed regularly over a 2-yr period. Results. Fifty-five RA patients on methotrexate and 73 control patients with RA were enrolled for the study. Mean dose of methotrexate was 10.7 mg/week (S.D. 2.5 mg/week) and mean duration of treatment at entry into the study was 30 (20) months. Twenty per cent of patients with RA treated with methotrexate had pulmonary fibrosis (PF) on initial HRCT compared with 23% in the control group. When the patients with and without PF were compared, there was no statistical difference in the duration (mean difference -4.18 months. P = 0.237) or dose (mean difference -0.8 mg week P = 0.52) of methotrexate therapy. Mean changes after 2 yr in forced expiratory volume, forced vital capacity, diffusion capacity for carbon monoxide and residual volumes were not different in the methotrexate group compared with the control group. Conclusion. There is no evidence to suggest clinically, from HRCT assessment or serial pulmonary function tests, that low-dose methotrexate is associated with chronic interstitial lung disease.