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Journal of Stress Physiology & Biochemistry, Vol. 7 No. 1 2011, pp. 66-78 ISSN 1997-0838 Original Text Copyright © 2011 by Anoop Austin, Elsie, Thirugnanasambantham
ORIGINAL ARTICLE
EVALUATING THE CLINICAL EFFICACY OF A POLYHERBAL FORMULATION AROGH PLUS ON STRESS
- A RANDOMISED CLINICAL STUDY
Anoop Austin1, Elsie C.S.2 and Thirugnanasambantham P.2
1 Rumi Herbals R & D centre, 40/41, Spartan Avenue, Mugappair East, Chennai India
2 Rohini Holistic Health Centre, 40/41, Spartan Avenue, Mugappair East, Chennai India
1 For correspondence and reprints: E-mail : anoopaustin@gmail. com
Received February 3, 2010
Background : Stress is a common entity, widely spoken about among the working population, for which a safe and effective remedy is needed.
Purpose of the study : To evaluate the clinical effectiveness of Arogh plus a polyherbal formulation, towards stress relieving properties in a randomized clinical trial in volunteers.
Results : Ten volunteers from Marketing field, evaluated to be under stress, completed the full course. All were clinically evaluated based upon symptoms, anthropometric evaluation, hematological, diabetic and serum cortisol and urine profile. All the parameters were evaluated during 0 day, 15th day, 30th day and on 45th day after stopping the drug internally. Three grams of Arogh plus was given twice daily for a period of 30 days was found to decrease symptoms due to stress and the benefits was reinforced by way of significant reduction in serum cortisol with a reduction of 36.99 % within a month.
Conclusion :Arogh plus is an effective formulation in relieving stress and improving the quality of life.
Key words: Arogh Plus /Polyherbal / Stress / Cortisol / Anxiety
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ORIGINAL ARTICLE
EVALUATING THE CLINICAL EFFICACY OF A POLYHERBAL FORMULATION AROGH PLUS ON STRESS
- A RANDOMISED CLINICAL STUDY
Anoop Austin1, Elsie C.S.2 and Thirugnanasambantham P.2
1 Rumi Herbals R & D centre, 40/41, Spartan Avenue, Mugappair East, Chennai India
2 Rohini Holistic Health Centre, 40/41, Spartan Avenue, Mugappair East, Chennai India
1 For correspondence and reprints: E-mail : anoopaustin@ gmail. com
Received February 3, 2010
Background : Stress is a common entity, widely spoken about among the working population, for which a safe and effective remedy is needed.
Purpose of the study : To evaluate the clinical effectiveness of Arogh plus a polyherbal formulation, towards stress relieving properties in a randomized clinical trial in volunteers.
Results : Ten volunteers from Marketing field, evaluated to be under stress, completed the full course. All were clinically evaluated based upon symptoms, anthropometric evaluation, hematological, diabetic and serum cortisol and urine profile. All the parameters were evaluated during 0 day, 15th day, 30th day and on 45th day after stopping the drug internally. Three grams of Arogh plus was given twice daily for a period of 30 days was found to decrease symptoms due to stress and the benefits was reinforced by way of significant reduction in serum cortisol with a reduction of 36.99 % within a month.
Conclusion :Arogh plus is an effective formulation in relieving stress and improving the quality of life.
Key words: Arogh Plus /Polyherbal / Stress / Cortisol /Anxiety
Stress was first coined by Hans Selye during to respond appropriately to emotional or physical
1930’s, which referred to the consequence of failure threats, whether actual or imagined. In recent past,
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this has become a commonplace of popular parlance (Selye, 1956). The symptoms commonly include a state of alarm and adrenaline production, short-term resistance as a coping mechanism, and exhaustion, as well as irritability, muscular tension, inability to concentrate and a variety of physiological reactions such as headache and elevated heart rate (Bernard and Krupat, 1994). Sheldon et al. (2007) reported that stress is one of the largest Killer of man today, which is becoming, more accepted as being crucially related to our physical, mental and emotional health, So reducing the stress level can not only protect from diseases but can also enhance our quality of life enormously (Thoits, 2010).
Tranquilizers, antidepressants and anti-anxiety medications are widely prescribed in stress management (Anonymous, 2000), but the incidence of toxicity and dependence has limited the therapeutic usage of those drugs (Moncrieff et al., 2010). Herbal formulations have been in use for many years not only in Asian countries but also globally for human well-being. The herbal formulations claimed to enhance physical endurance; mental functions and non-specific resistance of the body have been reported to possess anti-stressor (Archana and Namasivayam, 1999) and “adaptogenic” properties (Saggu et al., 2007), as well as the ability to affect the hypothalamic-pituitary-adrenal axis (Al-Qarawi et al., 2002). The potential utility of safer and cheaper herbal medicines as antistress agents have been reported as they can withstand stress without altering the physiological functions of the body (Naik et al., 2006). Various herbs like Asparagus racemosus, Bacopa monnieri, Centella asiatica, Emblica officinalis, Hypericum perforatum, Matricaria recutita, Mentha piperita, Nepeta cataria, Ocimum sanctum, Passiflora incarnate, Piper methysticum, P. longum Tribulus terrestris, Valeriana officinalis
and Withania somnifera are claimed to have immunomodulatory, adaptogenic and anabolic effects along with the ability to improve vital energy (Naik et al., 2006; Bansal and Yadav, 2010). Though herbal medicines are known to act synergistically in combination (Toews and Bylund, 2005), only limited work has been carried out on poly herbal formulation for Stress. With this basis this study was initiated.
Arogh plus, is one such herbal Instant formulation manufactured by Rumi Herbals Pvt. Ltd, Chennai, containing Nelumbo nucifera, Hibiscus rosa-sinensis, Rosa alba, Terminalia chebula, Hemidesmus indicus, Glycyrrhiza glabra, Zingiber officinale, Quercus infectoria and Eclipta alba. Detailed studies have revealed its therapeutic efficacy on hypercholesteremia (Anoop Austin et al., 2006; Ganesh et al., 2006; Asokan et al., 2010), arthritis (Mohan et al., 2009), Stress and anxiety (Balaraman et al., 2007), Myocardial infraction (Suchalatha and Shyamala Devi, 2004) and Oxidative stress (Suchalatha et al., 2004). With this basis, a randomized clinical trial was carried out on the formulation, to evaluate its clinical efficacy, by way of evaluating their performance, Physical and mental characteristics, and blood and hormonal investigation to have an better insight and understanding its effectiveness in volunteers under stressful situation.
Materials and Methods:
Arogh Plus, an Ayurvedic polyherbal formulation, gifted by M/s. Rumi Herbals Pvt. Ltd., Chennai was subjected for a detailed randomized clinical trial at Rohini Holistic Health Centre, Chennai during the period of July to September 2010. A detailed clinical protocol was prepared and was approved by the Institutional Human Ethics committee. The study was carried out on the
volunteers, who were working in marketing field for more than five years. After receiving their consent, they were explained about the entire study and, after acceptance, they were included for the study. The study was organized for a period of 30 days and those who completed the study were only included for evaluation.
The volunteers evolved to be under stress who were included in this study, administered 3 gm of powder (1 Sachet full) twice daily, morning and evening, dissolved in warm water for a period 30 days. Any specific diet schedule was not prescribed to the volunteers. All volunteers involved in the study were thoroughly screened on 0 day, 15 th day and 30th day. After completion of the study period on 45th day all volunteers were again subjected to all parameters again.
Ten human volunteers diagnosed to be under stress were selected, for this present randomized study. All patients selected for this study were interrogated and a detailed history was recorded in the prescribed case history sheet. The individual who have symptoms of stress disorders with or without raised serum cortisol levels, were subjected to clinical trial. Out of 12 volunteers selected, 10 completed the full treatment schedule (i.e., 30 days) and they were only taken for the full evaluation in this study. The clinical pattern (Fait et al., 2006) were studied in all 10 cases for incidence of age, sex (male & female), religion, occupation, economic status, educational status, social status and symptoms of stress disorders following the incidence of blood cortisol (Mattingly et al., 1989) and routine examination of Blood, Stool and Urine (Burtis et al., 2006) were carried out, in addition, to the observation, of subjective features. Clinical symptoms viz., Anorexia, Apprehension, Breathlessness, Constipation, Diarrhea, Disinterest
of life, Dizziness, Fatigue, Frequency of micturation, Headache, Hopelessness/Helplessness, Inability to work, Insomnia, Lack of concentration, Lack of self confidence, Loss of libido, Loss of weight, Pain-chest/Abdomen, Recurrent thought for death /suicide, Slowing of thinking, Slowing of speed, Skin rashes /ulcer, Sweating and Tremor were analysed during each visit on 0 day, 15th day, 30th day and after 45th day in all the volunteers (Fait et al., 2006). The observations made out of the investigations, are statistically expressed as the means ± standard error of the means (S.E.M.) and statistical analysis was carried out using student’s t-test (O'Mahony and Michael, 1986).
Results:
The present study consists of total 10 volunteers, who have symptoms of stress disorders and completed the full course of treatment schedule (i.e. 30 days). Though we had registered 12 cases for the present study, only 10 volunteers (5 male and 5 female) completed the full course of treatment, and they only were included in the complete study. So the clinical pattern will be discussed with the observations and investigation carried out with those ten cases, only.
The volunteers involved in the present study ranged within the age group of 20 to 60. 1 male (10 %) and 4 females (40 %) were between 21 to 30 years age, 1 male (10 %) between 31-40 and 1 (10 %)female between 41-50 age group and 3 (30 %) males between 51 - 60 age group participated in the study. Out of the 10 volunteers, 5 were males (50 %) and the remaining were females (50 %). Their occupation status revealed that all were working and the 5 females (50 %) involved in the study were housewives, with their economic status revealing 1 male (10 %) in low income and 3 males (30 %) and
5 females (50 %) in middle class group and 1 male (10 %) in high class group.
The volunteers involved in the study were from Urban area and 1 male (10 %) and 1 female (10 %) completed Higher Secondary education, 2 male (20 %) and 3 females (30 %) completed their graduation, 1 male (10 %) and 1 female (10 %) completed their post graduation and 1 male (10 %) completed his doctorate. The volunteers involved in the study were all non vegetarians. The nature of work among the volunteers differed to an extent, where, 2 males (20 %) and 1 female (10 %) had sedentary work style, 2 males (20 %) and 2 females (20 %) had moderate and active work culture and 1 male (10 %) and 2 females (20 %) were striving hard in their work nature. Among the group 1 female (10 %) was unmarried and remaining 5 males (50 %) and 4 females (40 %) were married.
The observations pertaining to clinical symptoms and their observations before and after the treatment were found to be interesting with respect to the degree of reduction in symptoms, which are well elicited in Table 1. From this it is interesting to observe that more than 70 % of relief was observed in symptoms like apprehension, breathlessness, constipation, disinterest of life, frequency of micturition, headache, insomnia, lack of concentration, lack of self confidence, suicidal tendency, slowing of thinking, and tremor. More than 50 % of relief was observed in symptoms like dizziness, fatigue, hopelessness/helplessness, inability to work, slowing of speed and sweating. In other symptoms, the relief found was less than 50 %.
The improvements on objective features like anthropometric evaluation (Table 2), Hematological, Diabetic and Serum Cortisol profile (Table 3) and urine profile (Table 4) revealed many interesting
findings. Anthropometric evaluation revealed that Arogh Plus did not alter the observed parameters like the height, weight, BMI, respiration, pulse, blood pressure and Rapid Eye Movement (REM), within the short span of treatment time. The total count was found to be significantly increased, which reverted after the ingestion period, signifying the improvement of immune system (LaFleur-Brooks,
2008). Among the study group two were Type II diabetics, and were under OHA. Their diabetic control was not significant and that was found to reflect in the borderline in glycated haemoglobin level. Serum cortisol was found to be decreasing during the course of treatment and which are reverted after discontinuing the treatment. The cortisol level was found to be more pronounced in normal individuals where the percentage of decrease was observed to be 36.99 % with a month time, whereas in those 2 diabetic persons the serum cortisol was found to be 9.1 ± 1.7 on 0 day, 7.9 ± 1.43 on 15th day, 7.6 ± 1.55 on 30th day and reverted to 8.2 ± 1.55 after the treatment period suggesting only 16.48 % of reduction on the 30th day, which is more significant from the study. Urine analysis revealed an interesting finding in reducing the deposit level, which needs further evaluation. Further there was no undesired effects observed during the course of study with the drug and revealed the safety of the formulation.
Discussion:
Stress is a common problem which might reflect by way of cognitive, emotional, physical or behavioural changes (Gallo and Matthews, 2003). Stress can result in poor judgement, negative outlook, excessive worrying, moodiness, irritability, agitation, inability to relax, feeling lonely, isolated or depressed, aches and pains, altered bowel habits, nausea, dizziness, chest pain, rapid heartbeat, eating
too much or not enough, sleeping too much or not enough, social withdrawal, procrastination or neglect of responsibilities, increased alcohol, nicotine or drug consumption, and nervous habits such as pacing about or nail-biting (Hawkley and Cacioppo, 2003).
Arogh Plus, a polyherbal formulation was
Table 1. Response of treatment on subjective criteria
evaluated clinically in volunteers working under stressful situation and revealed many interesting finding. Daily intake of the formulation for a period of continuous 30 days was found to decrease the symptoms observed due to stress, which was reduced and their work performance was found to be increased.
Sl. No. Symptoms Number of Patients before treatment Number of Patients after treatment Percentage of relief
1 Anorexia 6 4 33.33
2 Apprehension 9 2 77.78
3 Breathlessness 2 0 100
4 Constipation 2 0 100
5 Diarrhea 0 0 0
6 Disinterest of life 2 0 100
7 Dizziness 3 1 66.67
8 Fatigue 5 2 60
9 Frequency of micturation 3 0 100
10 Headache 4 1 75
11 Hopelessness/Helplessness 2 1 50
12 Inability to work 6 2 66.67
13 Insomnia 1 0 100
14 Lack of concentration 6 1 83.34
15. Lack of self confidence 4 1 75
16. Loss of libido 0 0 0
17. Loss of weight 0 0 0
18. Pain-chest/Abdomen 0 0 0
19. Recurrent thought for death /suicide 1 0 100
20. Slowing of thinking 4 1 75
21. Slowing of speed 3 1 66.67
22. Skin rashes /ulcer 1 0 100
23. Sweating 6 2 66.67
24. Tremor 5 1 80
Clinical features observed from stressed individual, among the 10 volunteers
Table 2. Anthropometric Parameters
Sl. No Anthropometric Parameters 0 day 15 days 30 days 45th day
1 Height 63.8 ± 1.26 63.78 ± 1.26 63.78 ± 1.26 63.78 ± 1.26
2 Weight 68.5 ± 46.8 68.6 ± 4.83 68.05 ± 4.67 68.2 ± 4.59
3 BMI 25.8 ± 1.33 26.02 ± 1.37 25.82± 1.33 25.68± 1.31
4 Pulse rate 74.6 ± 1.8 74.4 ± 1.68 73.6 ± 1.76 73.6 ± 1.76
5 Respiratory rate 18.5 ± 0.44 18.4 ± 0.4 18.4 ± 0.4 18.3 ± 0.4
6 Temperature, 0F 98.4 ± 0 98.4 ± 0 98.4 ± 0 98.4 ± 0
7 Systolic blood Pressure 128.0 ± 2.59 124 ± 3.07 122 ± 2.11 122 ± 1.67
8 Diastolic blood Pressure 84 ± 1.52 82 ± 2.15 80 ± 1.58 80 ± 1.39
9 REM 4.3 ± 0.47 3.5 ± 0.17 3.2 ± 0.13 3.8 ± 0.20
Results are expressed in mean ± SEM, where n = 10, BMI - Body Mass Index, REM - Rapid Eye Movement
Table 3. Hematological, diabetic and serum cortisol profile
Sl. No Parameters 0 day 15 days 30 days 45th day
1 Total Count 8450 ± 361.74 8320 ± 364.17 * 8850 ± 709.81 *** 8480 ± 536.82
2 Differential Count
a Polymorph 56.9 ± 1.61 56.2 ± 1.59 59.6 ± 1.88 58.0 ± 1.39
b Lymphocytes 36.2 ± 1.77 41.2 ± 1.55 37.6 ± 1.94 39 ± 1.32
c Eosinophil 2.7 ± 0.19 2.6 ± 0.27 2.8 ± 0.44 2.8 ± 0.46
d Monocytes 0.2 ± 0 0 ± 0 0 ± 0 0.2 ± 0
3 ESR 16.8 ± 3.6 17.4 ± 3.35 16.7 ± 3.35 16.6 ± 3.61
4 Hb % 13.2 ± 0.44 13.38 ± 0.55 13.54 ± 0.54 13.6 ± 0.55
5 MCV 83.8 ± 1.17 82.79 ± 1.14 83.66 ± 1.14 83.82 ± 1.18
6 MCH 28.3 ± 0.51 28.26 ± 0.57 29.94 ± 0.54 29.76 ± 0.55
7 Sugar (F) 99.4 ± 10.18 92.6 ± 7.31 93.5 ± 7.53 103 ± 10.22
8 Glycated Hb% 5.8 ± 0.25 5.74 ± 0.22 5.89 ± 0.2 5.85 ± 0.25
9 Serum Cortisol 9.3 ± 0.54 6.30 ± 0.22 * 5.86 ± 0.2 * 7.83 ± 0.25
Results are expressed in mean ± SEM, where n = 10,
*p<0.05, ***p<0.001, as compared to control
73 Evaluating the clinical efficacy...
Table 4. Urine analysis
Sl. No Parameters 0 day 15 days 30 days 45th day
1 Albumin NIL NIL NIL NIL
2 Sugar NIL NIL NIL NIL
3 Deposits 3.3 ± 0.18 2.8 ± 0.15 2.0 ± 0.11 1.8 ± 0.11 ***
Results are expressed in mean ± SEM, where n = 10, ***p<0.001, as compared to control NIL - absent
Haematological studied revealed an significant change in the Total count, during the treatment period, which is considered to increase immunity (LaFleur-Brooks, 2008), which needs further studies. But findings have suggested that reverting stress will also improve the immunity and the sense of well being (Avitsur et al, 2006). During exertion, the sympathetic nervous system stimulates splenic contractions, which increase total counts, supporting the claims of reduced stress (Rose and Allen, 1985).
Cortisol is often used as an indicator of stress due to stimulation of the hypothalamic-pituitary-adrenal axis (Roshan et al,, 2010), which is a common physiological response to various stressors. The effect of stress on central nervous system and hypothalamic-pituitary-adrenal axis includes an increase in cortisol, and a disruption in circadian rhythm of cortisol secretion (Roshan et al., 2010). A reduction in cortisol during the study period can be interpreted as a reduction of stress (Stull and Rodiek, 2002) and in turn will increase catecholamine neuro transmitters, such as serotonin and dopamine (Field et al., 2005), which will also help in stress relieving, but needs a detailed evaluation.. Further decreased levels of cortisol, on long-term can prevent neuronal damages (Spiegel et al. , 1999). The difference of lowering the cortisol level in diabetics is due to the metabolic
derangement, which has affected the decrease in cortisol level and it clearly illustrates the poor response in the diabetic group, which is highly warranted.
The effectiveness of the formulation on Stress can be attributed to its synergestic activity (Toews and Bylund, 2005). Various studies carried out on the ingredients were also found to be strengthening the claims. Compounds 3-O-beta-d-glucopyranoside and Qc 3-O-beta-d-glucuronopyranoside isolated from N. nucifera was responsible for relieving stress (Jung et al., 2008) and H. rosa-sinensis was able to relieve oxidative stress in ischemic reperfusion injury (Nade et al., 2010) and hypotensive (Nade et al., 2009). N. nucifera (Chopra et al., 1969) and Z. officinale (Bone and Gupta, 1997) are found to be cardotonics and hypertensive’s. The vasodilation, positive inotropic, and cardioprotective activity of H. indicus and H. rosa-sinensis were reported by Vinoth et al., (2010). T. chebula has been reported to act directly on the heart muscle (Srivastava et al., 1991), where negative chronotropic, inotropic and hypotensive responses observed might protect the myocardium by decreasing its overload (Vinoth et al., 2010). In support to this observation, previous study carried out on the formulation by Balaraman et al. (2007) also proved the anxiolytic activity of the formulation in albino rats, by virtue of its
diminished serotonergic transmission and decreased duration of catalepsy indicating potentiation of dopaminergic transmission and modified 5-HT and DA mediated behaviour.
The antioxidant, anti inflammatory and free radical scavenging properties of G. glabra (Alam and Gomes, 1998), T. chebula (Aeshbaech et al.,
1994), H. indicus (Chandra et al., 1987), Z. officinale (Sreeramamurthy et al., 1993), E. alba (Kim and Hong, 1996) might synergistically enhance the efficacy of Arogh Plus to scavenge the free radicals, minimize lipid peroxidation, thereby preventing membrane damage and leakage of enzymes. Body functions, including cellular respiration depends on the oxygen supply, which can be attributed by its antioxidant and free radical properties is justified.
The antioxidant effects of H. indicus (Rao, et al., 2005) may be associated with tannins (Hong et al.,
1995), one of the main constituents. Likewise, saponins have also been shown to have beneficial effects on cardiovascular diseases (Matsuura, 2001). Flavonoids produce vasodilation by regulating endothelial nitric oxide (NO) production (Schmitt and Dirsch, 2009) and interaction with ion channels (Akhlaghi and Bandy, 2009). Moreover, flavonoids are known to protect the I/R-induced myocardial injury by their multifaceted properties, such as antioxidant, antiinflammatory, vasodilatory, and antiplatelet aggregation (Akhlaghi and Bandy,
2009). Therefore, it is conceivable that the cardioprotective effect can be related to the combined effects of saponins, tannins, and flavonoids. H. rosa-sinensis has been shown to enhance the endogenous antioxidant activity and protect the heart from isoproterenol-induced injury (Karunakaran et al., 2006). The interpretations made with the ingredient were also in line with the
Austin et al „ „
74
observations made by Suchalatha et al. (2004), where the drug was able to possess inhibition of lipid peroxidation, maintaining the levels of superoxide dismutase and catalase, enhancing the activity of glutathione peroxidase and glutathione-s-transferase, which can scavenge superoxide radicals and prevent free radical formation and lipid peroxidation.
G. glabra present in the formulation is a proven adaptogen (Winston and Maimes, 2007), which is capable of increasing succinate dehydrogenase [SDH] in brain and decreasing brain neurotransmitters like norepinephrine (NE), dopamine (DA), serotonin (5-HT) and acetylcholine (ACh) (Deore and Khadabadi, 2009) and decrease in beta-endorphin level (Gregory and. Kelly, 2001).
The study clearly elucidates that Arogh Plus, as a suggestive drug in treating stress by virtue of its cortisol lowering activity, antioxidant and free radical properties, thereby influencing the neurotransmitters. The limitation of this study is that it has carried out in a small selected group and further detailed investigations, with respect to various neurotransmitters, in a large group and cross over studies will through more light on the effectiveness of the formulation.
Conclusion
Arogh Plus, is found to reduce the stress by virtue of its cortisol lowering activity in a short duration of 30 days, and can be taken to relieve stress and improve their quality of life.
Acknowledgments:
The authors are thankful to M/s. Rumi Herbals Pvt. Ltd., Chennai for supplying the study material and funding to carry out the study.
75 Evaluating the
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