|Year : 2017 | Volume
| Issue : 3 | Page : 170-176
In vivo evaluation of antipyretic effects of homoeopathic ultrahigh dilutions of Typhoidinum on baker's yeast-induced fever in comparison with Paracetamol
Saeed Ahmad1, Tayyeba Rehman2, Waheed Mumtaz Ababsi2
1 Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Pakistan
2 University College of Conventional Medicine, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Pakistan
|Date of Web Publication||15-Sep-2017|
Office UCCM, Khawja Fareed Campus, Railway Road, The Islamia University of Bahawalpur
Source of Support: None, Conflict of Interest: None
Introduction: Homoeopathy is a widely used, controversial alternative system of medicine. It is assumed that homoeopathic medicines are slower in action and does not work in acute conditions such as ‘fever’. The study aims to estimate the effectiveness of some homoeopathic remedies in fever and to compare their effects with Paracetamol. Materials and Methods: Baker's yeast fever model of rabbits was used in the study. Rabbits were divided into four different groups (n = 6). Rectal temperature was measured before and after fever induction hourly. After fever induction, medicines were administered orally. Paracetamol and Typhoidinum in 200C and 1M potencies were given orally. ANOVA followed by post hoc test was used for statistical analysis of results. The results were considered statistically significant at P ≤ 0.05. Results: Fever was induced in all the rabbits after 4 h of baker's yeast administration. The results of the study revealed the significant effectiveness of Typhoidinum in 200C and 1M potencies in baker's yeast-induced fever (P = 0.05). Typhoidinum in both potencies showed less significant results as compared to Paracetamol. However, all the medicines’ effects were significant compared to the negative control. Conclusion: Typhoidinum 200C and 1M worked against baker's yeast-induced fever. However, the results were slower and less significant than Paracetamol that might be due to lack of similarity of remedy picture and disease picture.
Keywords: Antipyretic, Homoeopathic ultrahigh dilutions, Typhoidinum
|How to cite this article:|
Ahmad S, Rehman T, Ababsi WM. In vivo evaluation of antipyretic effects of homoeopathic ultrahigh dilutions of Typhoidinum on baker's yeast-induced fever in comparison with Paracetamol. Indian J Res Homoeopathy 2017;11:170-6
|How to cite this URL:|
Ahmad S, Rehman T, Ababsi WM. In vivo evaluation of antipyretic effects of homoeopathic ultrahigh dilutions of Typhoidinum on baker's yeast-induced fever in comparison with Paracetamol. Indian J Res Homoeopathy [serial online] 2017 [cited 2019 Dec 13];11:170-6. Available from: http://www.ijrh.org/text.asp?2017/11/3/170/214842
| Introduction|| |
Fever is a complex physiologic process that is characterised by elevated body temperature above the normal range, associated with increased pulse, aches, chills, tissue destructions, restlessness and other symptoms. Fever can be caused by many factors including factors effecting the temperature regulating centre, bacterial diseases, any abnormality in the brain as brain tumours and many environmental conditions such as heat stroke., The primary manifestation of fever is an elevation of body temperature, usually by 1°C–4°C. In fact, fever is not a disease, but it is the symptom of other pathological state and the immune response of the body that attempt to neutralise microbial infection in the body. Increased temperature led to the disturbance of the human physiology and is responsible for patient discomfort. There are various antipyretics to control fever such as Paracetamol. It reduces fever in multiple species including rabbits, but it has certain side effects, such as asthma, hepatotoxicity and hypertension.,, Thus, there is need to find therapeutic alternatives for fever.
Homoeopathy is one of the most popular complementary and alternative systems of medicine.
Homoeopathy is based on similia principle ‘similia similibus curantur’ that means to treat with something that can produce an effect similar to the suffering. Remedy pictures are obtained by administering homoeopathic medicines in non-toxic dilutions to healthy volunteers during homoeopathic drug proving. In Homoeopathy, medicines are selected based on the similarity between remedy picture and disease-specific individual status. Hahnemann often said that the primary method of treatment is to remove the fundamental cause of the disease.
Typhoidinum is a nosode (homoeopathic remedy prepared from diseased products) prepared from Salmonella typhi. It is useful for fever with numbness all along right side, with impaired hearing in the right ear, slight nausea, vertigo and numbness that is worse from lying down and better in sitting position. General amelioration from lying down. There is no appetite and no thirst. Typhoidinum is proved to be antiviral medicine in one study. Homoeopathic medicines in potencies of 100C to 1M of Typhoidinum, Tuberculinum, Hydrophobinum, Nux vomica and Malandrinum completely inhibit chicken embryo DNA virus-induced pock-like lesions. The effects were found to be significant compared to controls.
'Baker's yeast-induced fever model’ is a commonly used method of fever induction. In the experimental studies, baker's yeast (Saccharomyces cerevisiae) causes fever in animals in large doses (intraperetoneally or subcutaneous)., It causes high-grade fever in a very short period. Some studies have shown that S. cerevisiae and constituents of its cell wall, such as mannans, cause fever that is accompanied by an increase in the plasma levels of tumour necrosis factor-a, interleukin-1b and interferon-c.,
The study aimed to evaluate:
- The effectiveness of Typhoidinum (ultrahigh dilutions) in baker's yeast-induced fever
- The effectiveness of Typhoidinum (ultrahigh dilutions) in comparison with standard antipyretic ‘ Paracetamol’.
| Materials and Methods|| |
Medicines, reagent and apparatus
Typhoidinum 1M and 200C (Dr. Willmar Schwabe, GmbH and Co., KG, Germany), Paracetamol GlaxoSmithKline, Pakistan, Limited, baker yeast (Rossmoor food products, Karachi, Pakistan), Digital Thermometer (Medisign MANA and CO., Pakistan) were used.
Adult healthy rabbits of local strain were purchased from the market. The weight of rabbits ranged from 1 to 1.5 kg, and both male and female rabbits were included in the study. The study was carried in rabbits as they are not aggressive and comes under the purview of local Ethical Committee. Moreover, rabbits were selected because they develop fever more easily than rats.
All the animals stayed in the air-conditioned animal house situated in Khawaja Fareed Campus, in the Faculty of Pharmacy and Alternative Medicine, the Islamia University of Bahawalpur [Figure 1]. They were fed on standard diet ad libitum. They were acclimatised to animal house conditions 7 days before the start of the experiment. They were also habituated to handling, temperature measurement procedure and injection stress. The study was approved by the Pharmacy Research Ethics Committee, Faculty of Pharmacy and Alternative Medicine, the Islamia University of Bahawalpur, Pakistan, through Notification number ‘88-2015/PREC’.
Animals were grouped into four groups and each group contained six rabbits. The dosage of baker's yeast as well as Paracetamol was adjusted according to weight of each rabbit. Rectal temperature of rabbits was checked with digital thermometer. Fever-inducing agent was prepared according to method of Tomazetti et al. Commercially available baker's yeast (S. cerevisiae) was suspended in normal saline and was injected intraperitoneally at the dosage of 135 mg/kg/10 ml to induce fever. Rectal temperature was checked after 4 h of yeast injection. Temperature raise ≥0.5°F–1.5°F was considered as ‘induced fever’. Group I was negative control and received 90% succussed alcohol (vehicle of used homoeopathic medicines). Group 2 was standard control and received Paracetamol 150 mg/kg orally. Groups 3 and 4 received Typhoidinum 1M and 200C, respectively. A few drops of homoeopathic medicines in 5 cc distilled water were administered orally to rabbits of respective groups. Minimum dose of ultrahigh dilutions was administered to avoid medicinal aggravation. Negative control group received few drops of succussed alcohol in 5 cc distilled water orally. Rectal temperature of rabbits was again checked after administration of medicines hourly.
Results obtained by this activity were analysed by Social package of Statistical sciences SPSS version 20.0 software. The test applied for analysis of data was ANOVA followed by post hoc test. ANOVA was used for comparison among groups. Fischer least significant difference post hoc test was applied only if ANOVA was significant. P ≤ 0.05 was taken as statistically significant.
| Results|| |
At the 4th h after yeast administration, temperature of more than 1°F was raised in all the rabbits. The temperature variations in different groups at different hours are as follows.
Effect of vehicle on fever induced by baker's yeast
The negative control group showed a continuous increase of temperature till the 8th h from the time of yeast administration and then showed the progressive decline in temperature. At 0 h, normal mean temperature of the group was 102.6°F. Up till 8th h, a temperature raise of 2.3°F was observed that is started to decline afterward [Figure 2]. Three of the rabbits in negative control group suffered from diarrhoea (greenish watery) and later euthanised in the end of 5th h.
|Figure 2: Antipyretic effects of Typhoidinum 1M, 0 h is the normal baseline temperature reading before fever induction, 4th h reading is temperature-induced reading, 5th–10th h readings are after medicine administration (n = 6 in each group)|
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Effect of Paracetamol on fever induced by baker's yeast
At 4th h of yeast administration, 2.8°F temperature increase was observed. Paracetamol was administered orally at this time, and this group showed the decrease of 2°F temperature in the 1st h of medicine administration (P = 0.002). At the 2nd h of medicine administration, a further decrease of 0.2°F temperature was observed (P < 0.001). In the succeeding 2 h, a slight increase of temperature was seen that was going to normal temperature in the 10th h of the experiment [Figure 2],[Figure 3],[Figure 4],[Figure 5]. All the rabbits survived in this group.
|Figure 3: Comparative effectiveness of Paracetamol and Typhoidinum 1M at the end of experiment|
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|Figure 4: Antipyretic effects of Typhoidinum 200C, 0 h is the normal baseline temperature reading before fever induction, 4th h reading is temperature-induced reading, 5th–10th h readings are after medicine administration|
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|Figure 5: Comparative effectiveness of Paracetamol and Typhoidinum 200C at the end of experiment|
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Effect of Typhoidinum 1M on fever induced by baker's yeast
Typhoidinum 1M group showed an increase of 3°F after 4 h of yeast administration. After medicine administration, a gradual decrease of temperature was observed that became statistically significant (P < 0.05) in 3rd h to onward [Figure 2]. At the end of experiment, both Paracetamol and Typhoidinum 1M showed equal decrease of temperature (P < 0.001) [Figure 3].
Effect of Typhoidinum 200C on fever induced by baker's yeast
Typhoidinum 200C group showed an increase of 2.2°F after 4 h of yeast administration. After medicine administration, a slight non-significant decrease of temperature was observed in first 2 h. In 3rd h temperature decrease became significant (P < 0.05) that was continuous at the end of experiment [Figure 4]. At the end of experiment, both Paracetamol and Typhoidinum 200C showed equal decrease of temperature (P < 0.001) [Figure 5].
| Discussion|| |
Homoeopathy is the widely used complementary and alternative system of medicine. Homoeopathy faces many criticisms, the most common condemnation is about biological activities of homoeopathic ultrahigh dilutions beyond Avogadro's number. The present study examined the effects of Typhoidinum in fever in baker's yeast-induced fever model of rabbits. In the present study, administration of baker's yeast in rabbits causes a significant elevation of temperature in 4 h. Our results matched to earlier studies reporting fever induced by baker's yeast in rats and rabbits.,
Orally administered Paracetamol (150 mg/kg) significantly decreased baker's yeast-induced fever in rabbits. Results are in accordance with other study results.,, Typhoidinum ultrahigh dilutions slowly decreased temperature as compared to Paracetamol; however, results became statistically significant in 3rd h of medicine administration. Antipyretics and non-steroidal anti-inflammatory drugs decreased fever by decreasing inflammation at the peripheral sites in tissue inflammation and within central nervous system thermoregulatory sites. However, homoeopathic medicines has supposed action on the regulation of inflammatory pathological changes as it is perceived as an expression of natural healing dynamics (commonly known as Hahnemann's ‘life force'). Homoeopathic medicines in ultra-high dilutions are safe and have no adverse effects. Large doses of ultrahigh dilutions ingestion showed that nothing happened, they have not the power to cause adverse effects as the conventional drugs.
In Homoeopathy, medicines are selected based on the similarity between drug-specific pathogenesis ‘remedy picture’ and disease-specific individual status. Typhoidinum is useful for low-grade fever types such as typhoid with numbness. Baker's yeast caused high-grade fever during the study. Lack of complete similarity between disease condition and remedy picture might be responsible for slow onset of decline in temperature by Typhoidinum ultrahigh dilutions as compared to Paracetamol. Another study with similar protocols reported effectiveness of Aconitum napellus on baker's yeast-induced fever due to similarity of high-grade fever.
The potency should be selected according to disease energy activity (intensity), intense diseases need higher and mild diseases require lower or medium potency. Experimentally induced diseases are short term and high intensity. It is evident from study results that both selected potencies (high potencies) of Typhoidinum have similar effect in reducing temperature.
The specific effects of homoeopathic medicines are of a non-molecular origin, yet provide powerful biological activities that are clinically effective. It has been assumed that highly diluted substances transfer biological activity to cells by electromagnetic fields. Another working hypothesis about homoeopathic ultrahigh dilutions is interactions between the radiation fields of a charged molecule. The electric dipoles of water generate permanent polarisation of water which becomes coherent. It transmits specific information to cell receptors, somewhat like a laser. However, the exact mechanism of action of homoeopathic ultrahigh dilution is not proved yet.
The effects of Typhoidinum ultrahigh dilutions should be evaluated on S. typhi-induced fever as it is the source of medicine administration. It can be hypothesised that medicine will be more effectively work in S. typhi-induced fever. Moreover, it can also be hypothesised that Belladonna and Pyrogenium would be effective remedies in baker's yeast-induced fever on the basis of some similarity of these medicines with baker's yeast-induced fever.
| Conclusion|| |
Homoeopathic medicines worked well when the criteria of similarity met entirely. If disease picture and drug picture have partial similarity, then results are slower or sometimes none. However, there is no ambiguity about the effects of homoeopathic medicines as the study showed positive results on animals. Hence, the effects of homoeopathic medicines are not mere placebos, and in fever, homoeopathic medicines worked as Paracetamol.
We appreciate Khalid Akhtar for animal handling and general support. Moreover, we acknowledge Faculty of Pharmacy and Alternative Medicine for providing animal house and general facilities for the conduction of this study.
Financial support and sponsorship
Conflicts of interest
None decl ared.
| References|| |
Guyton A, Hall J. Metabolism and temperature regulation. Textbook of Medical Physiology. 9th
ed. Philadelphia: W.B. Saunders Co.; 1996. p. 914-5.
Hall J, Guyton A. Body temperature regulation, and fever. Guyton and Hall Text Book of Medical Physiology. 12th
ed. Philadelphia: Saunders Elsevier; 2011. p. 867-77.
Saper CB, Breder CD, Flier JS, Underhill LH. The neurologic basis of fever. N Engl J Med 1994;330:1880-6.
Axelrod YK, Diringer MN. Temperature management in acute neurologic disorders. Neurol Clin 2008;26:585-603, xi.
Toussaint K, Yang XC, Zielinski MA, Reigle KL, Sacavage SD, Nagar S, et al.
What do we (not) know about how paracetamol (acetaminophen) works? J Clin Pharm Ther 2010;35:617-38.
Persky V, Piorkowski J, Hernandez E, Chavez N, Wagner-Cassanova C, Vergara C, et al.
Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life. Ann Allergy Asthma Immunol 2008;101:271-8.
Rebordosa C, Kogevinas M, Sørensen HT, Olsen J. Pre-natal exposure to paracetamol and risk of wheezing and asthma in children: A birth cohort study. Int J Epidemiol 2008;37:583-90.
Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension 2005;46:500-7.
Ernst E. The role of complementary and alternative medicine. BMJ 2000;321:1133-5.
Hahnemann S. Organon of Medicine. America, Philadelphia: Boericke & Tafel; 1901. p. 108.
Hahnemann S. Essay on a new principle for ascertaining the curative powers of drugs. Hufelands J 1796;2:295-352.
Hahnemann S. Organon of Medicine. Translated by Boericke W. 6th
ed. New Delhi: B Jain Publishers; 1991. p. 243-53.
Davis EL. An important nosode [Important Nosode]. In: Robert H, editor. Bureau of Materia Medica. Bombay, India: IHA; 1953.
Singh L, Gupta G. Antiviral efficacy of homoeopathic drugs against animal viruses. Br Homeopath J 1985;74:168-74.
Tomazetti J, Avila DS, Ferreira AP, Martins JS, Souza FR, Royer C, et al.
Baker yeast-induced fever in young rats: Characterization and validation of an animal model for antipyretics screening. J Neurosci Methods 2005;147:29-35.
Sultana S, Akhtar N, Asif HM. Phytochemical screening and antipyretic effects of hydro-methanol extract of Melia azedarach
leaves in rabbits. Bangladesh J Pharmacol 2013;8:214-7.
Ataoglu H, Dogan MD, Mustafa F, Akarsu ES. Candida albicans and Saccharomyces cerevisiae
cell wall mannans produce fever in rats: Role of nitric oxide and cytokines. Life Sci 2000;67:2247-56.
Bruguerolle B, Roucoules X. Time-dependent changes in body temperature rhythm induced in rats by brewer's yeast injection. Chronobiol Int 1994;11:180-6.
Mapara M, Thomas BS, Bhat KM. Rabbit as an animal model for experimental research. Dent Res J (Isfahan) 2012;9:111-8.
Morimoto A, Murakami N, Sakata Y, Watanabe T, Yamaguchi K. Functional and structural differences in febrile mechanism between rabbits and rats. J Physiol 1990;427:227-39.
Rao ML, Roy R, Bell IR, Hoover R. The defining role of structure (including epitaxy) in the plausibility of homeopathy. Homeopathy 2007;96:175-82.
Hossain E, Mandal SC, Gupta J. Phytochemical screening and in-vivo
antipyretic activity of the methanol leaf-extract of Bombax malabaricum DC (Bombacaceae
). Trop J Pharm Res 2011;10:1-6.
Ahmad S, Rehman T, Abbasi WM. Effects of homoeopathic ultrahigh dilutions of Aconitum napellus
on Baker's yeast-induced fever in rabbits. J Integr Med 2017;15:209-13.
Abbasi WM, Ahmad S, Perveen S, Rehman T. Preliminary phytochemical analysis and in vivo
evaluation of antipyretic effects of hydromethanolic extract of Cleome scaposa
leaves. J Tradit Complemen Med 2017; [In Press].
Jongchanapong A, Singharachai C, Palanuvej C, Ruangrungsi N, Towiwat P. Antipyretic and antinociceptive effects of Ben-Cha-Lo-Ka-Wi-Chian remedy. J Health Res 2010;24:15-22.
Conforti A, Bellavite P, Bertani S, Chiarotti F, Menniti-Ippolito F, Raschetti R. Rat models of acute inflammation: A randomized controlled study on the effects of homeopathic remedies. BMC Complement Altern Med 2007;7:1.
Dantas F, Rampes H. Do homeopathic medicines provoke adverse effects? A systematic review. Br Homeopath J 2000;89 Suppl 1:S35-8.
Teixeira MZ. Plausibility of the implausible: Is it possible that ultra-high dilutions ‘without biological activity'cause adverse effects. Int J High Dil Res 2013;12:41-3.
Kent JT. Lectures on Homoeopathic Philosophy. India: B. Jain Publishers; 2002. p. 899-905.
Del Giudice E, Preparata G, Vitiello G. Water as a free electric dipole laser. Phys Rev Lett 1988;61:1085-8.
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