|Year : 2019 | Volume
| Issue : 1 | Page : 22-36
Homoeopathic drug proving of Mangolia grandiflora: A randomised double blind placebo-controlled trial
Goutam Rakshit1, AK Vichitra2, Rajpal Singh1, Amulya Ratna Sahoo3, Sujata Kumari Choudhury4, Vinay Kumar Singh1
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Dr. D. P. Rastogi Central Research Institute (H), Noida, Uttar Pradesh, India
3 Drug Proving Unit, Extension unit of Regional Research Institute (H), Puri at Dr. A. C. Homoeopathic Medical College and Hospital, Bhubaneswar, Odisha, India
4 Regional Research Institute of Homoeopathy, Puri, Odisha, India
|Date of Submission||27-Jun-2018|
|Date of Acceptance||28-Feb-2019|
|Date of Web Publication||29-Mar-2019|
Dr. Sujata Kumari Choudhury
Regional Research Institute of Homoeopathy, Puri - 752 001, Odisha
Source of Support: None, Conflict of Interest: None
Objective: This study was carried out to elicit the pathogenetic response of the drug Magnolia grandiflora in homoeopathic potencies on apparently healthy human beings. Materials and Methods: Drug Magnolia grandiflora was proved by the Central Council for Research in Homoeopathy (CCRH) through a double-blind placebo-controlled method. The study was conducted at three centres. The drug was proved in two potencies (6C and 30C) on 48 apparently healthy volunteers who were selected after conducting pre-trial medical examinations by the medical specialists and routine laboratory investigations. In the first phase, volunteers were given 56 doses (4 doses per day for 14 days) of placebo. In the next two phases, 56 doses (4 doses per day for 14 days) of each potency or placebo were consumed. Out of 48 provers, 32 were given the actual drug and 16 were given placebo. The symptoms generated during the trial period were noted by the volunteers and elaborated by the proving masters. The data obtained from all the three centres were compiled at the Proving-Cum-Data Processing Cell at CCRH headquarters after decoding. Results: Out of the 32 provers who were on the actual drug trial, 21 manifested symptoms. The drug was able to produce symptoms in each potency in most of the parts of the body. Conclusion: New and proved pathogenetic responses elicited during the proving trial expand the scope of use of the drug Magnolia grandiflora and will benefit the research scholars and clinicians. These symptoms will carry more value when verified clinically.
Keywords: Drug proving, homoeopathic pathogenetic trial, Homoeopathy, Magnolia grandiflora, pathogenetic effect
|How to cite this article:|
Rakshit G, Vichitra A K, Singh R, Sahoo AR, Choudhury SK, Singh VK. Homoeopathic drug proving of Mangolia grandiflora: A randomised double blind placebo-controlled trial. Indian J Res Homoeopathy 2019;13:22-36
|How to cite this URL:|
Rakshit G, Vichitra A K, Singh R, Sahoo AR, Choudhury SK, Singh VK. Homoeopathic drug proving of Mangolia grandiflora: A randomised double blind placebo-controlled trial. Indian J Res Homoeopathy [serial online] 2019 [cited 2019 Apr 24];13:22-36. Available from: http://www.ijrh.org/text.asp?2019/13/1/22/255268
| Introduction|| |
Magnolia grandiflora is a tree widely distributed throughout the mid-Atlantic and southeastern United States. This species has been the object of exhaustive phytochemical research because of its long history of folk-medicinal usage and has yielded a variety of natural products, including alkaloids, terpenoids, lignin glycosides and biphenyles. Some of these compounds show activity/toxicity in various animal-based bioassays. However, despite the common observation that virtually no plant will grow beneath a magnolia tree, suggesting an allelopathic effect, none of the isolates appears to have been tested for phytotoxic properties.
In a study, the therapeutic potential of magnolia extract (BL153) was explored for treating obesity-associated kidney damage in a high fat-diet (HFD)-induced mouse model. The results showed that inflammatory markers (tumour necrosis factor-α and plasminogen activator inhibitor-1) and oxidative stress markers (3-nitrotyrosine and 4-hydroxy-2-nonenal) were all significantly increased in the kidney of HFD-fed mice compared to mice fed with a low-fat diet (LFD). Additionally, proteinuria and renal structure changes in HFD-fed mice were much more severe than those in LFD-fed mice.
Another study was conducted to investigate the antimelanogenic and antioxidant properties of Magnolia grandiflora L. flower extract. In that study Magnolia grandiflora flower extract showed antioxidant properties and potential dermatological effects against melanin production in B16F10 melanoma cells. This was the first report about the effect of Magnolia grandiflora L. flower extract on melanin production. It was found that Magnolia grandiflora L. flower extract inhibited melanin synthesis significantly in a dose-dependent pattern. Besides, Magnolia grandiflora L. flower extract also expressed antioxidant activities.
A study on ‘Apoptosis induced by Magnolia Grandiflora extract in chlorambucil-resistant B-chronic lymphocytic leukemia tested the ability of M. grandiflora extracts to induce the apoptosis of B-chronic lymphocytic leukaemia (B-CLL) cells in vitro, and results showed the apoptotic properties of Magnolia on B-CLL cells. The evidence suggested a potentially effective repertoire for B-CLL treatment. This herb extract might have promising therapeutic strategies in treating B-CLL or other haematological diseases resistant to alkylating agents in clinical practice.
Another study depicted the presence of different phytoconstituents such as alkaloids, carbohydrates, flavonoids, glycosides, gums and mucilage, phenolics, phlobatannins, reducing sugars, saponins, steroids, tannins and terpenoids in leaves and seeds. These chemical compounds are likely to be responsible for medicinal significance of this plant.
Anti-tumor activity of 50% ethanol bark extract of Magnolia grandiflora Linn. was evaluated against tumours induced in mice using dimethyl benzanthracene and 3-methyl cholanthrene. The activity was assessed using the ability of the plant extract in reducing tumour weight, tumour volume and lung weight. The cytotoxic/cytostatic activity of the plant extract on human cancer cell line Bu25Tk− cells was also evaluated using 3-(3,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay.
Keeping in view the above therapeutic activities of the Magnolia grandiflora, an effort had been taken to explore the homoeopathic pathogenicity of the potentised drug extract on healthy human volunteers.
- Botanical name: Magnolia grandiflora
- Family: Magnoliaceae
- Common name: Magnolia, Southern magnolia
- Hindi: Him Champa.
Magnolia grandiflora was described by Carl Linnaeus. The genus Magnolia was named by Carl Linnaeus in honour of Pierre Magnol, who was the physician of King Louis XIV of France and was the director of a botanical garden at Montpellier.Magnolia grandiflora is relatively common and is native to North America. It occurs from North Carolina to Florida and Texas. Although its native range is along the coastal plain, it can be seen as an ornamental tree throughout much of the Southeast, inland as far as the foothills of the Appalachian Mountains. Magnolia grandiflora is evergreen, so it drops foliage throughout the year, leaving piles of leathery leaf litter underneath its branches, stunting the growth of other plants and trees. Its trunk is typically straight and erect with spreading branches that form a dense, broadly pyramidal crown. It has large, thick, leathery dark green leaves which are up to 10” long. In the spring, they have a golden-to-rust colour on their undersides. The large evergreen trees may grow up to 90 feet tall, and the fragrant white blossoms that have smooth, almost velvet-looking petals are 8–12” across. The snow-white flowers are huge and cup shaped when young. The fruits are of reddish-brown cone-like structures, 2–4 in long, with bright red kidney-shaped seeds that hang from little threads when fully mature in the autumn [Figure 1]. In the USA, the magnolia is used as a street tree, a free-standing specimen, a framing tree or a shade tree. In most parts of India, magnolias are grown only in select well-maintained gardens. In Manipur, magnolias are commonly grown with the Manipuri name ‘Ootahmbal’ meaning ‘tree lotus’ – flowers are used as offering to God.
- Parts used in Homoeopathy: Extracts of flower
- Potencies used: 6C and 30C.
The objective of this study was to explore the pathogenetic effects of the drug Magnolia grandiflora on apparently healthy human volunteers in homoeopathic potencies.
|Figure 1: Magnolia grandiflora (a)Tree, (b) Bud, (c) Flower, (d) Fruit, (e) Flowering top, (f) Mature fruit just starting to open, (g) mature fruit with seeds opened, (h) seeds|
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| Materials and Methods|| |
The study was a randomised double-blind placebo-controlled trial. The study was conducted according to the Drug Proving Protocol designed by the Central Council for Research in Homoeopathy (CCRH), New Delhi.
Participants and settings
The proving was conducted at the following three centres: Drug Proving Unit, Bhubaneswar; Central Research Institute, Kottayam; and Central Research Institute, Noida, during the year 2010–2011. A total of 48 apparently healthy volunteers from the above mentioned three centres, between the age group of 18 and 45 years, comprising 14 males and 34 females, were enrolled in the study. Before commencing the study, all the provers were screened strictly by the experts and apparently healthy provers between the abovementioned age range.
- Age: Above 18 years of age
- Sex: Both male and female volunteers
- Health status: Experts’ acceptance for certifying that participant is healthy
- Participants must be 2 months free of any homoeopathic remedy with no significant change in the last 3 weeks
- Intelligent enough to record carefully the facts and subjective and objective symptoms generated by the drug during proving.
- Volunteers suffering from any acute or chronic disease
- Volunteers under any kind of medical treatment
- Hysterical or anxious persons (such individuals display a high incidence of ‘Placebo’ effects)
- Persons having a history of allergies, food hypersensitivity, etc
- Women during pregnancy, puerperium and breastfeeding
- Persons with colour blindness
- Persons having addictions to brandy, wine, alcohol, narcotics and tobacco
- Persons who have undergone surgery in the last 2 months
- Hysterical persons, individuals prone to hypersensitivity reactions (such as asthma and allergies), anxiety prone, emotionally disturbed, colour blind, suffering from any chronic disease and pregnant, puerperal and lactating females
- Those with previous homoeopathic treatment in the last 2 months
- Participation in another clinical or proving trial during the last 6 months.
A ‘written informed consent’ from each volunteer was obtained before the beginning of the trial. Pre-trial Medical Examinations and Terminal Medical Examinations (TMEs) of the volunteers were carried out by general physicians, psychiatrists, cardiologists, ophthalmologists, ENT specialists, dermatologists, gynaecologists and radiologists, and their routine laboratory investigations at the centres were done to ascertain their health status. After the recommendation of experts, healthy volunteers were enrolled in this homoeopathic pathogenetic trial programme.
The study was conducted according to the CCRH Drug Proving Protocol; the sample size included 30% of volunteers under control group at each centre. According to that, out of the 48 volunteers, 32 were kept on the actual drug (verum) and 16 were on placebo (control) in all the three phases. All the volunteers were assigned code numbers, and the coded drugs of different potencies (including placebo) were supplied in separate glass phials bearing code numbers of the respective volunteers, keeping both provers and proving masters blind about what provers were consuming (drug or placebo).
Magnolia grandiflora was procured in 6C and 30C potencies from M/s. Dr Willmar Schwabe India Pvt., Ltd., Noida, in 100-mL sealed phials of each dilution. Globules (number 30) were medicated with these attenuations at the Council's headquarter office and sent to drug-proving research units. The phials containing both the drug and placebo were coded.
Placebo was made up of plain globules (number 30) moistened with plain dispensing alcohol and was therefore indistinguishable from the verum.
Methodology of proving
The study was completed in three phases. Each phase consisted of 56 doses of coded drugs/placebo.
- Phase I: It is the placebo phase. It is useful in generating prover's response to placebo and therefore, symptoms generated by the prover in this stage act as control for subsequent phases
- Phase II: In the 2nd phase, the proving was conducted with 6C potency
- Phase III: In the 3rd phase, the proving was conducted with 30C potency.
Procedure of proving
The volunteers were instructed to take 4–6 globules of a particular potency of the codes drug, four times a day, dry on the tongue, and also instructed to note down the details of their feelings/changes in the mind and body, after taking the coded drug/placebo in ‘Prover's Day Book Proforma’ daily.
- If no sign(s)/symptoms(s) appeared: The volunteers were instructed to note down as ‘No Symptom’ with date and time of intake of the respective dose of the drug/placebo
- If sign(s)/symptoms(s) appeared: The volunteers were asked to stop taking the drug/placebo as soon as he/she felt any change or any sign(s) and/or symptoms(s) developed during the trial. The volunteer noted down the sequence of the appearance of new sign(s) and/or symptoms(s), their progress and the number of doses after which each sign or symptom appears with date, time of onset and duration for which it persisted. The intake of drug remained suspended till the sign(s) and/or symptoms(s) totally disappeared. Any change in the normal routine of the prover with respect to daily habits pertaining to diet, living conditions, etc., and any treatment taken were also noted in the Prover's Day Book Proforma.
After the disappearance of sign(s) and/or symptom(s) developed by the drug, the volunteers were instructed to wait for a further period of 7 days before taking the remaining doses of that potency following the same dose schedule as stated above. In case of further appearance of new sign(s) and/or symptom(s), the same procedure as stated above was followed till the consumption of 56 doses of that potency by the volunteer. If the volunteer was experiencing the same symptom(s) what he/she had already shown, he/she was asked to stop the current quota and to switch over to the next quota after a washout period of 14 days.
Each prover was interrogated by the Proving Master about the appearance of new sign(s) and/or symptom(s) or progress of symptoms and noted down those in ‘Symptoms Elaboration Proforma’ with respect to the appearance and disappearance of symptoms, their location, sensation/character, modalities, concomitants, extension of symptoms, causation, clinicopathological findings and other treatment taken.
Before commencing the administration of subsequent potencies (subsequent phase) of the drug, the volunteers remained on a washout/rest period (it should be a symptom-free period between the two phases of drug proving in which a volunteer does not take drug) for 14 days and started taking the next potency in the same procedure as mentioned above, till completion of 56 doses. The same procedure was followed for the 3rd phase.
Each volunteer was interrogated by the Proving Master to verify the sign(s) and/or symptom(s) recorded by the volunteers. The symptoms recorded in ‘Prover's Day Book Proforma’ were verified by the Proving Master and completed through further interrogation with the volunteers with respect to their location/sensation/modalities/concomitants, if any, in ‘Symptoms Elaboration Proforma'.
During the course of proving, the volunteers were referred to specific laboratory investigation(s) to rule out any pathological cause for the appearance of new sign(s) and/or symptom(s). In this regard the opinions of experts were also obtained to establish any correlations between the subjective and objective changes where ever needed.
After completion of the trial of all potencies, the volunteers underwent TME. On completion of all the respective phases of the proving programme, the compilation of data recorded in ‘Prover's Day Book Proforma', ‘Symptoms Elaboration Proforma', ‘Pathological Report Sheets’ and ‘TME sheets’ was done at the Council's headquarters by the Drug Proving-cum-Data Processing Cell. After decoding, the sign(s) and/or symptom(s) produced by the volunteers of the verum group were separated from those produced by the volunteers kept on placebo. The sign(s) and/or symptom(s) which were common to both the groups, i.e., placebo as well as drug groups, were not taken into consideration while compiling the pathogenecity of the proved drug.
Management of adverse effects
A vial of antidote was sent with each quota to each centre. In this trial, homoeopathic potencies of Camphora were used as antidote as it is mentioned in Allen's Key notes and Boericke's Materia Medica that Camphora can antidote nearly every vegetable medicine. The proving Master gives antidote to the volunteer if symptoms continue for a long time or intensity is much to cause discomfort. The Proving Master is also directed to take the advice of honorary consultants and to get laboratory investigations done, if required. During this trial, no such adverse effects were observed.
| Observation and Discussion|| |
The trial programme comprised 48 provers (14 males and 34 females). From the 48 provers, 32 were kept on verum and 16 were on placebo. From the 32 provers who were kept on verum, 20 provers produced symptoms. The drug was able to produce symptoms in different systems of the body. In this trial, there were no mental symptoms produced (as no prover complained of any sort of mental symptoms or perhaps the mental symptoms could have not been extracted). It is also evident from the observation that the drug also did not produce any symptoms in vision, ear, face, teeth, respiration and skin. A comparative study of the present proving symptoms and the symptoms recorded in the Hand Book of Materia Medica and Therapeutics by T.F. Allen is shown in [Table 1] and [Table 2].
|Table 1: Comparison of the symptoms of Magnolia grandiflora in the present proving and previously recorded in source book Hand book of Materia Medica and homoeopathic therapeutics by T. F. Allen|
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Pathogenetic effects were deduced from the following criteria:
- Comparison of symptoms developed in placebo phase with symptoms during intervention phases (intraprover comparison)
- Comparison of symptoms developed by the provers on control (for all phases) with provers on the actual drug trial (interprover comparison).
Out of 48 provers from three centres, 32 were kept on actual drug and out of these, 20 provers produced symptoms. At the Drug Proving Unit (H), Bhubaneswar, out of 15 provers, 4 provers reported symptoms. At the Central Research Institute (H), Kottayam, out of 15 provers, 7 provers reported symptoms. At the Central Research Institute (H), Noida, out of 18 provers, 9 provers reported symptoms. Ninety-one symptoms were observed in this trial of which 36 symptoms were observed during the 2nd quota drug trial, i.e., by 6C, and 55 were produced during the 3rd quota drug trial, i.e., by 30C. [Figure 2] shows the frequency of symptoms in different systems/organs produced by Magnolia grandiflora. More number of symptoms were produced related to head, rectum and fever in this proving in both 6C and 30C potencies except that fever and vertigo symptoms were produced only by 6C potency. Likewise, symptoms related to urinary organs, female genital organs, eyes, mouth and sleep were produced only by 30C potency.
The incidence of pathogenetic effects per prover is defined as the total number of findings observed in the trial divided by the total number of provers producing the symptoms. In this trial, 91 symptoms were produced by twenty provers. Hence, incidence in this proving trial was 4.55.
The incidence of pathogenetic effects of the trial (claimed % of provers) is the number of provers who had produced symptoms divided by the total number of provers taking medicine, and it was (20/32 × 100) i.e, 62.5%.
The percentage of responsive volunteers is the number of provers producing symptoms in the trial divided by the total number of provers participated in the trial, and it was (20/48 × 100) i.e, 41.67.
| Conclusion|| |
From the pathogenetic effects or symptoms of Magnolia grandiflora produced during this pathogenetic trial, it is evident that this drug from the plant kingdom produced so many symptoms in different systems/organs, so the plant can be used for treating different clinical conditions such as headache, palpitation, menstrual abnormality, rhinitis, rheumatic pains, and myalgia. There are so many other symptoms which are not observed during this proving trial which are already mentioned in source books. The sample size of provers is too small to produce more number of symptoms in different systems/organs. However, whatever symptoms we found during this proving programme may be clinically verified afterwards to validate this.
Financial support and sponsorship
Conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2]