Efficacy of Pippalī (Fruits of Piper longum Linn.) in Grahaṇīroga: A Prospective Open label Clinical Trial

Nath, Mahajon, Kumar Mandal, Sengupta, and Chattopadhyay: Efficacy of Pippalī (Fruits of Piper longum Linn.) in Grahaṇīroga: A Prospective Open label Clinical Trial

Authors

INTRODUCTION

In the current era, the diseases allied to Anna vahaand Purīṣavahasrota (~gastrointestinal tract) are commonly found in clinical practice. Among of them Grahaṇīrogais one of the most important disorders. This disease occurs due to the distorted function of Agni (~digestive fire). Various scholars have opined that function of Agni (~digestive fire) can be evaluated through the analysis of gastric juice and different enzymes at Gastro intestinal level.[1] All of them are accountable for the physiological function of digestion, absorption and metabolism. Altered function of the enzymes secreted from Gastro intestinal tract is responsible for foundation of Gastro intestinal disorders. Agni (~digestive fire) is seated at the spectacle of Grahaṇī (the organ hold down the descending progress of the undigested food particles until it is exclusively digested.) which is situated above the umbilical region. The system Grahaṇīis supported and nurtured by the potency of Agni. Improper function of Agni put across the pathological condition like Vidāha (~The condition where a part of food particle become digested, whereas the other part remain in undigested condition which ultimately budges upwards and downwards in gastro-intestinal tract and produce burning sensation). The Pakva (~digested) and Apakva (~undigested) food particles moves downwards and ultimately manifests Grahaṇīroga.[2] In other words, Agnicooks any material located over it i.e. in Āmāśaya or stomach.[3] Till the food is digested, the organ Grahaṇī helps in its withholding in the upper part (stomach), and after digestion, the food is released to the intestinal tract through the sides of Grahaṇī. This liberate of processed foodstuff takes place from the left side of the Grahaṇī because both the Grahaṇī and Guda (~rectum including anus) are located in the left side of the stomach. Both Āma (~unprocessed) and Pakva (~digested) food products come out with the fecal material. When it is vitiated due to weakness of Agni, only Apakva (~undigested) food is perpetually voided and therefore formed several sign and symptoms of Grahaṇīroga.[4] To mitigate the pathogenesis of Grahaṇīroga, fruit powder of Pippalī was administered in this study. The drug Pippalī , botanically identified as Piper longum Linn. is a well known drug in Āyurveda mentioned by ancient classics and frequently practiced for the condition of Agnimāndya (~poor digestive power).[5] Hence the present study aimed to clinically evaluate the efficacy of Pippalī to improve the symptoms of Grahaṇīroga.

MATERIALS AND METHODS

Selection of the patients

Forty patients were selected from OPD and IPD of Institute of Post Graduate Ayurvedic Education and Research at Shyamadas Vaidya Shastra Pith strictly based on the fixed inclusion and exclusion criteria of the study.

Study design

Prospective open label clinical trial was chosen.

Inclusion criteria

  1. Patient belonged to the age group of 16 years and above up to below 70 years.[6]

  2. Patients primarily diagnosed as classical Grahaṇīrogawith no other history of medications.

  3. Patients presenting with cardinal symptoms Muhurvaddhaṃ Muhurdravammalam (frequently loose motion and constipation)[7] and macroscopically presenting undigested vegetable particles in stool.

  4. Patients satisfied the maximum classical subjective criteria for Grahaṇīroga.

Exclusion criteria

  1. Patients those who were not willing to include themselves in the study.

  2. Patients were suffering from any other major systemic disorders like Hepatic Failure, Renal Failure, Cardiac Disorder, Diabetes Mellitus, Malignancy and Thyroid Disorders etc.

  3. Patients presenting the Asādhyalakṣaṇa (~symptoms indicating the poor prognosis).[8]

  4. Patients were receiving any other supplementary therapy.

Subjective parameters of Grahaṇīroga[9]

Patients those who were presenting cardinal symptoms of Grahaṇīroga associated with maximum numbers of the following subjective parameters were included in the study.

Ṥuktapāka (~sour eructation), Kharāṅgatā (~roughness), Āsyaśoṣa (~dryness of mouth), Kaṅṭhaśoṣa (~dryness of throat), Kṣudhā (~loss of appetite), Tṛṣṇā (~feeling of thirst), Timira(~loss of vision), Karṇayoḥsvanaḥ (~persisting sounds on ear), Pārśvaūruvaṅkṣaṇagrīvāruka (~pain in flank, chest, groin and neck region), Visūcikā (~loose motion and vomiting with sever pricking pain), Hṛdpidā (~cardiac pain), Gṛddhiḥsarvarasānāṃ (~desire for all tastes), Mana Sadana (~depression), Jīrṇe- jīryati ca ādhmānaṃ Bhuktesvāsthyamupaiti (~after ingestion of food patient feel well but after digestion and during digestion urges of flatulence), Cirādduḥkhaṃdravaṃśuṣkaṃtanuāmaśabdaphenavatvarca (~sometimes hard and sometimes frothy stool with minimum quantity), Kāsa (~cough with sound like broken bronze pot.), Ajīrṇa (~indigestion), Nīla-Pītābhaṃpītābhaḥsāryatedravam (~altered color of stool), Pūtiamlaudgāra (~foul smelling belching), Bhinnaāmaśleṣmasaṃsṛṣṭa guru varcapravartanam (~ill formed stool with mucus), Akṛśasyāpidaurbalya (~despite lack of emaciation feels weak in sedentary work).

Objective parameters of Grahaṇīroga

Several studies has concluded that function of Agni (~digestive fire) can be evaluated through the analysis of gastric juice and different enzymes at Gastro intestinal level because physiologically Agni is responsible factor for digestion, absorption and metabolism. Based on this, following laboratorial parameters were observed.

  1. Examination of Stool for Routine Examination and Microscopic Examination (occult blood)

  2. Biochemical tests:

  1. L.F.T (Liver Function Test) with G.G.T (Gamma Glutamyl Transpeptidase)

  2. Serum amylase

  3. Serum Lipase

Administration of drug

The patients were treated with two gms fruit powder of Pippalī with plain water in two divided doses per day, provided in between two meals, for a period of one month. All the patients were examined to evaluate the subjective and objective parameters after 7days, 15 days and 30 days of administration of test drug. The efficacy of the stipulated drug on Grahaṇīroga was evaluated based on statistical analysis.

Assessment of subjective parameters for Grahaṇīroga

Subjective parameters mentioned in the classical Ayurveda texts were evaluated by the preliminary approach of arbitrary grading system. Appropriate literary meanings of each particular symptom were encompassed after methodical discussion with subjective experts to make the arbitrary grading (Table 2). An assessment scale was framed to assess the rate of improvement. At the end of management, the consequence in analysis of percentage of relief was classified under the subsequent headings (Table 1).

Statistical analysis

Effect test drug was evaluated by Statistical method ‘Paired t-test’.

Table 1

Assessment of percentage of relief and remarks

Percentage of reliefRemark
100% improvement of subjective parameters.Complete remission
>75%-100% improvement of subjective parameters.Marked improvement
>50%-75% improvement of subjective parameters.Moderate improvement
>25%-50% improvement of subjective parameters.Mild improvement
Equal or <25% improvement of subjective parameters.No improvement
Table 2

Arbitrary grading of subjective parameters for Grahanī roga

SNSign and symptomsGrade
  01234
1.Ṥuktapāka (Amla pākam = Sour eructation)Sour eructation not occurs.Sour eructation occurs occasionally in 24 hours.Sour eructation occurs after an interval in 24 hours.Sour eructation occurs continuously in 24 hours.Sour eructation occurs continuously more than 24 hours.
2.Kharāṅgatā (Karkaśa śarīratvaṃ, vātena tvaga gata sneha śoṣāt = Roughness) No Roughness.Roughness due to atmosphere.Roughness occurs occasionally.Roughness during touch.Visualized persisting roughness.
3.Kaṇṭha śoṣa, Āsya śoṣa (Dryness of throat and mouth)Dryness of throat and mouth not occurs.Dryness of throat and mouth occurs some times in 24 hours.Dryness of throat and mouth occurs 1 or 2 times in 24 hours.Dryness of throat and mouth occurs after an interval of24 hours.Dryness of throat and mouth occurs all time in 24 hours.
4.Kṣudhā: (Kṣudhāyā abhāvaḥ =Loss of Appetite)Normal Appetite.Loss of Appetite occurs 1 time in 24 hours.Loss of Appetite occurs 2 times in 24 hours.Loss of Appetite occurs 3 times in 24 hours.Loss of Appetite occurs 4 times in 24 hours.
5.Tṛṣṇā (Pipāsa =Punaḥ Punaḥ Pibati = Feeling of thirst).Normal feeling of thirst.Feeling of thirst 7-9 times/ 24 hours, either/ or intake of water 5-7 times / 24 hours with quantity 1.5-2 lit/ 24 hours.Feeling of thirst 9-11 times/ 24 hours, either/ or intake of water 7-9 times / 24 hours with quantity 2-2.5 lit/ 24 hours.Feeling of thirst 11-13 times/ 24 hours, either/ or intake of water 9-11 times / 24 hours with quantity 2.5-3 lit/ 24 hours.Feeling of thirst >13 times/ 24 hours, either/ or intake of water >11 times/ 24 hours with quantity >3 lit/ 24 hours.
6.Timira (Manda dṛṣṭitā = loss of vision.) Vision without glass.Vision with glass.Vision with glass with blunt.Blunt vision with systemic problem.Complete loss of vision.
7.Karṇayoḥsvanaḥ (Karṇau saśabdau = Persisting sounds on ear)Persisting sounds on ear not present.Persisting sounds on ear present occasionally in 24 hours.Persisting sounds on ear present intermittently in 24 hours.Persisting sounds on ear present continuously 24 hours.Persisting sounds on ear present continuously more than 24 hours.
8.Pārśvaūru vaṅkṣaṇa grīvā ruka (Pīḍā sā pārśvadibhiḥ saṁvadhyate =Pain in flank chest groin and neck region).Pain not occurs.Occasionally pain in flank chest groin and neck region occurs in 24 hours.In a particular time pain in flank chest groin and neck region occurs in 24 hours.Intermittently pain in flank chest groin and neck region occurs in 24 hours.Persisting pain in flank chest groin and neck region occurs more than 24 hours.
9.Hṛdpidā (Hṛdayaśulaṃ gauravaṃ ca = Cardiac pain)Mild cardiac pain not occurs.Mild cardiac pain occurs occasionally in 24 hours.Mild cardiac pain occurs 2 to 3 times in 24 hours.Mild cardiac pain persists 24 hours.Mild cardiac pain persists more than 24 hours.
10.Gṛddhiḥ sarvarasānāṁ (Gṛddhiḥ kāṅkhā, sarvarasānāṃ madhurādīnā =Desire for all tastes)Desire for all tastes not occurs.Desire for all tastes occurs occasionally in 24 hours.Desire for all tastes occurs particular time in 24 hours.Desire for all tastes occurs intermittently in 24 hours.Desire for all tastes occurs all time in 24 hours.
11.Mana sadana ( Manoglāniḥ =Depression)No depression.Depression in unfavorable condition.Depression in favorable condition.Intermittent depression.Continuous depression.
12.Kāsa (Bhinna kāṁsya pātravat hata svanaḥ = Cough with sound like broken bronze pot.)Cough with sound like broken bronze pot not occurs 24 hours.Cough with sound like broken bronze pot persists occasionally in 24 hours.Cough with sound like broken bronze pot persists intermittently in 24 hours.Cough with sound like broken bronze pot persists 24 hours.Cough with sound like broken bronze pot persists more than 24 hours.
13.AjῙrṇa (Apakvam = Indigestion)Indigestion not occurs.Persisting indigestion for 6 hours.Persisting indigestion for 12 hours.Persisting indigestion for 24 hours.Persisting indigestion for more than 24 hours.
14.Nīlapītābhaṁpītābhaḥ sāryate dravam (Altered colour of stool).Altered colour of stool not present Altered colour of stool present occasionally in 24 hoursAltered colour of stool present 1 times in 24 hours.Altered colour of stool present continuously in 24 hours.Altered colour of stool present continuously more than 24 hours.
15.Pūti amlaudgāra: (Sa dhūmodgāraḥ =Foul smelling belching).Foul smelling belching not occurs.Foul smelling belching occurs occasionally in 24 hours.Foul smelling belching occurs intermittently in 24 hours.Foul smelling belching occurs continuously 24 hours.Foul smelling belching occurs continuously more than 24 hours.
16.Akṛśasyāpi daurvbalya (Sthūlavato api karmani asamartham =Despite lack of emaciation feels weak in sedentary work).Symptoms absent.Despite lack of emaciation feels weakin hard work.Despite lack of emaciation feels weak in moderate work.Despite lack of emaciation feels weak in mild work.Despite lack of emaciationfeels weak in sedentary work.

RESULTS AND DISCUSSION

Effect of drug on subjective parameters: Effect of drug on subjective parameters were analyzed (Graph 1).

Effect of drug on objective parameters: Before and after administration of drug the biochemical parameters and examination of stool were performed. In analysis of objective parameters like serum bilirubin, SGPT, SGOT, alkaline phosphatase, prothrombin time, gamma glutamyl transpeptidase, serum amylase, serum lipase; data were found to be statistically insignificant (P>0.05) and significant changes (P<0.001 and P<0.01) were observed in the parameters of serum proteins, serum albumin, serum globulin, albumin globulin ratio. Significant changes were also noticed in physical, microscopical and chemical parameters of stool. After completion of one month, undigested food materials were completely absent.

Assessment of progress: The assessment of progress was first noted at the end of 7th day, 15th day and 30th day i.e. after the course of treatment. An assessment scale was framed to assess the rate of improvement. Result obtained from the study is discussed (Table 1 and Graph 1).

Graph 1

Effect of Pippalī on the subjective parameters of Grahaṇīroga

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To assess the state of Grahaṇīroga initial move towards arbitrary grading system were utilized. Where Grade 4 was considered as maximum severe condition and Grade 0 was considered as the minimum grave condition (table-2). After one month administration of drug marked and moderate improvement was observed. Study showed that the drug is significantly helpful in subjective parameters of Grahaṇīroga (Graph 1). Maximum subjective parameters were to be found statistically significant (P<0.05) except Kharāṅgatā (~roughness), Tṛṣṇā (~feeling of thirst), Timira (~loss of vision), Visūcikā (~loose motion and vomiting with sever pricking pain) where observed ‘p’ value was statistically insignificant (P>0.05). Significant changes of objective parameters were observed on examination of stool. Other parameters were found to be statistically insignificant. At the end of management, the result in view of percentage of relief was classified. Here in no such parameter 100% improvement was observed. Less than 100% to 75% i.e. marked improvement of subjective parameters were observed on the parameters of Śuktapāka (~sour eructation), Visūcikā (~loose motion and vomiting with sever pricking pain), Hṛdpidā (~cardiac pain), Jīrṇe- jīryati ca ādhmānaṃbhuktesvāsthyamupaiti (~after the ingestion of food patient feels well but after digestion and during digestion urge of flatulence). Moderate improvement (≥ 50% - < 75%) was observed on the parameters of Kaṇṭhaśoṣa (~dryness of throat), Āsyaśoṣa (~dryness of mouth), Kṣhudhā(~loss of Appetite), Karṇayoḥsvanaḥ (~persisting sounds on ear), Pārśvaūruvaṇkṣaṇagrīvāruka (~pain in flank chest groin and neck region), Gṛddhiḥsarvarasānāṃ (~desire for all tastes), Mana sadana (~depression), Cirādduḥkhaṃdravaṃśuṣkaṃtanuāmaśabdaphenavatvarca (~sometimes hard and sometimes frothy stool with leastquantity), Kāsa (~cough with sound like broken bronze pot), Ajīrṇa (~indigestion), Nīla-pītābhaṃpītābhaḥsāryatedravam (~altered colour of stool), Pūtiamlaudgāra (~foul smelling belching), Bhinnaāmaśleṣmasaṃsṛṣṭa guru varcapravartanam (~ill formed stool with mucus), Akṛśasyāpidaurbalya (~despite lack of emaciation feels weak in sedentary work) likewise mild improvement (≥25% - <50%) was observed on the parameter of Kharāṇgatā (~roughness), Tṛṣṇā (~feeling of thirst).

The drug Pippalī is a renowned drug in Āyurveda due to its multidimensional exploit. The drug may acts through its Kaṭu rasa (~pungent taste), Laghu (~light), Snigdha (~unctuous), Tīkṣṇaguṇa (~raggedness property), Madhuravipāka (~sweet metabolic transformation) and Anuṣṇavīrya (~medium temperate active potency). [5] All the Dravya (~substances) are constituted by five Mahābhūta (~five basic elements). So, after scrutiny the Pāñcabhautika composition of Pippalī, it was observed that Pippalī have significant ability to alleviate the symptoms of Grahaṇīroga by its Dīpana (~stimulation of digestion), Pācana (~digestion andmetabolism), Rocana (~craving), Lekhana (~scrap), Vṛṁhana (~nourishing) and Śodhana (~purification) Karma (~action). In Āmāvasthā (~unprocessed ingested food materials) the Dīpana (~stimulation of digestive process), Pācana (~absolute digestion), etc. karma and in Pacyamānāvasthā (~during the processing of ingested food materials) Śodhana karma (~action of purification) are meticulous (Fig. 1 and 2).

Figure 1

Mode of action of Pippalī

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Figure 2

Samprāpti Vighaṭana of Grahaṇī roga

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By virtue of these properties the drug was markedly effective in the symptoms like Śuktapāka (~sour eructation), Visūcikā (~loose motion and vomiting with sever pricking pain), Hṛdpidā (~cardiac pain), Jīrṇe- jīryati ca ādhmānaṃ bhukte svāsthyamupaiti (~after the ingestion of food patient feel well but after digestion and during digestion urge of flatulence) etc.

CONCLUSION

The present study ascertains that succeeding one-month administration of fruit powder of Pippalī (Piper longum Linn.) was significantly effective in improvement of subjective parameters of Grahaṇīroga. Ultimately, marked to moderate intensification was observed in the participants but no marked changes were found in most of the objective parameters of Grahaṇīroga, except in the parameters of Serum Proteins, Serum Albumin, Serum Globulin, Albumin Globulin ratio and physical, microscopical and chemical parameters of stool. Explanation behinds this may be the constraint of study like small sample size, short duration of study and few objective criteria were not found in every selected patient. Further study can undertake with special consideration of these limitations.

GRAPHICAL ABSTRACT

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ABOUT AUTHORS

Dr Rupashri Nath obtained her MD degree from Institute of post graduate ayurvedic education and research at shyamadas vaidya shastra pith,Kolkata in 2015. Presently working as Ph.D. Scholar, PG Department of Roga Nidana and Vikriti Vigyana, National Institute of Ayurveda, Jaipur-302002. She obtained Jivaka award in 2010 from Himalaya drug company for achieving the 1st position in final BAMS under The West Bengal University of Health Sciences and Gold medal in the year 2015 for achieving the 1st position in MD(Ayu-Roga Nidana). She has published many research articles in various indexed journals. RN worked as primary investigator for this study. Made the study design, observation, collection and compilation the data from the field sources.

Dr Bidhan Mahajon obtained his MD degree from VPSV Ayurveda College Kottakkal, Kerala in 2015. Presently working Research Officer (Ayurveda), CCRAS,Ministry of AYUSH Govt. of India and doing Ph.D. in PG Department of Dravyagunavigyana, National Institute of Ayurveda, Jaipur-302002. He obtained Ayurvisharada award in 2010 from Himalaya drug company for achieving the 2nd position in final BAMS under The West Bengal University of Health Sciences. He obtained ICMR junior research fellowship STS-2009. He has published many research articles in various indexed journals. BM contributed for compilation and presentation of the data. Framed the manuscript as corresponding author.

Dr Sisir Kumar Mandal is working as Assistant professor, PG Department of Roga Nidana and Vikriti Vigyana, National Institute of Ayurveda, Jaipur-302002. Obtained his Ph.D. degree from IPGT&RA Gujarat Ayurved University, Jamnagar. He is a practicing Ayurvedic physician and specializes in Ayurvedic management of Skin disorders. He has published many research articles in various indexed journals. SKM contributed for better understanding the conceptual part of the study and helped for organization of subjective and objective parameters.

Dr Apala Sengupta is working as Reader, Department of Roga Nidana and Vikriti Vigyana, IPGAE & R at Shyamadas vaidya shastra pith, Kolkata-700009. India. She obtained her MD and Ph.D. degree from University of Calcutta. ). She has published many research articles in various indexed journals. AS served as guide for this study. Advised for betterment of study and compilation of data.

Dr Abichal Chattopadhyay is working as Reader, Department of Sharira Samhita, IPGAE & R at Shyamadas vaidya shastra pith, Kolkata-700009. India. Obtained his MD and PhD degree from IPGT&RA Gujarat Ayurved University,Jamnagar. He is the present coordinator of Asiatic Society, Kolkata. He is a renowned practicing Ayurvedic physician in Bengal tradition. He has published many research articles in various indexed journals. AC worked as co-investigator for this study. Provided the concept for making the study design and better understanding the fundamental concepts.

Notes

[1] Conflicts of interest CONFLICT OF INTEREST Nil

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