Devyani Awari1*, Deorao Awari2, Sagar Wankhede1, Rajendra Ganjiwale2, Lalit Rathi2,
1Datta Meghe College of Pharmacy, Datta Meghe Institute of Medical Sciences (DU),
Wardha - 442004, Maharashtra, India.
2Institute of Pharmaceutical Education and Research, Borgaon Meghe, Wardha - 442001, Maharashtra, India.
*Corresponding Author E-mail: devawari@rediffmail.com
ABSTRACT:
Despite significant advances in high throughput assays, the current state of drug discovery and development is facing an insurmountable challenge. For this reason, new methods for drug research are urgently needed. Ayurveda was used by almost 70% of Indians. The systematic and research-based search and investigation of native plants for beneficial and therapeutic effects should be modified. For this clarification, new scenarios and approaches were developed and developed Ayurvedic epidemiology, observational studies, and reverse pharmacological methods have produced remarkable achievements, indications, and components for a wide variety of diseases and conditions. The potential phytobase entity will appear in future scaffolds for medicinal chemists to increase potency while reducing toxicity. Many native medicinal herbs have been shown to be effective. Mucuna pruriens eggs are effective in treating Parkinson's disease, the Nycthanthes plant arbor-tritis is effective in treating malaria, and Phyllanthus amarus is used in treating hepatitis. Reverse pharmacology is used by several groups around the world for drug development of new formulations, chemicals, and baits.
KEYWORDS: Reverse Pharmacology, Traditional Medicine, Hits, Lead molecule, Drug Discovery.
1. INTRODUCTION:
1.1 Concept of Reverse Pharmacology:
Based on Ayurvedic knowledge, the fundamentals of reverse pharmacology were Reverse Pharmacology (RP) is a science of integrating documented experience hits into leads through transdisciplinary exploratory studies and further development of drug candidates through experimental research1. Reverse pharmacology is a discipline of harmonizing the catalog of clinical existence and practical experience through exploratory transdisciplinary studies, as well as developing these connections to drug candidates through vigorous, robust animal studies and subjective clinical research. This validation focuses on safety and efficacy2,3 Rauwolfia serpentine is a vegetable source from which an alkaloid was isolated. Reserpine was a great discovery that was invented with the approach of reverse pharmacology4.
The plant's antihypertensive sedatives were confirmed by Indian chemists Sen and Bose in 19315. Occasional and exclusive side effects, such as depression, extrapyramidal complaints, gynecomastia and another after-effect that was also observed by Ciba Geigy while working on the herb, reserpine as an effective antihypertensive drug of first choice (antihypertensive alkaloid), which was introduced for commercial products6. The antiulcer activity of the bark of Caesalpinia pulcherrima L. has been reported in Ayurveda and, using its knowledge, a study by Takawale, Mute et. in 20117. Probably used for the first time comprehensively for targeted, accelerated research into active substances8,9,10. At the Poddar Ayurveda Hospital in Mumbai. Reverse pharmacology (RP), practiced for several years. The Indian Council of Medical Research and the Indian state CSIR (Council for Scientific and Industrial Research) did some promising work two to three decades ago as part of a jointly conducted combined drug research program. A memory enhancer developed by the Central Drug Research Institute is also available on the market. It is obtained from Bacopa monnieri and the availability of real raw materials is a limiting factor2.
A drug used to treat Prurien seeds' Parkinson's disease is another example of the reverse pharmacological approach. Zandopa, which is made from a locally sourced resource, synthetic L-DOPA formulations can be replaced with Zandopa in patients who adhere to its dosage regimen manufactured by Zandu, a commercial product that is standardized, safe, effective and economical holds11. Initially, no carpet discovery tool was available in the industry, so academics is the only source for drug discovery using reverse pharmacology. A result of extensive efforts by academics leads to successful product development and understanding of the molecular mechanism. To fill this gap, the Indian government is taking the initiative and bringing together industry experts and academics under the joint platform of the New Millennium Indian Technology Leadership Initiative (NMITLI). The government oversees this program from its inception through to the development of a specific drug to treat diseases such as psoriasis, osteoarthritis (OA), hepatitis, and diabetes2,12.
The drug, which is already in clinical use, is used in reverse pharmacology. This is why reverse pharmacology is an innovative tool for accelerated drug development. The evaluation of drug studies during the exploratory study. To know the mechanistic explanation of clinical studies that were carried out at the same time. The systematic approach is used to treat multi-target diseases in Ayurvedic treatment. Therefore, Ayurvedic treatment is the most promising treatment for treating multi-target diseases. Chronic treatment is required for certain diseases such as diabetes and cardiovascular disease. Herbal combination with modern medicine can lead to serious adverse drug interactions. Therefore, strong evidence is required as a proof of safety13.
In India, most researchers use many plants to study the pharmacological effects of herbal medicines on a disease state. This combination creates the synergistic effect. It is therefore difficult to find out the mechanism of action of a single plant14. The disease state can be a remedy, but the mechanism of action of the medicinal plant is not researched. This is the time to find out the exact mechanism of action of herbal medicines/formulations with the correct application of reverse pharmacology. Most people believe in experience, observation, and traditional medicine to treat the disease. Aside from Ayurvedic treatment, some people rely on other treatment modalities such as Unani, Sidha, and Homeopathy. Herbal medicine is the main component of traditional medicine. The demand for safe and effective herbal treatments to treat chronic disease conditions is increasing day by day1. Many Ayurvedic and Chinese herbs have been shown to be effective in certain chronic disease conditions. This is the reason for the increasing demand for herbal plants in western countries. In western countries these herbal plants are offered as dietary supplements. But it's not approved by the United States Federal Drug Regulation. As part of the label statement, each nutritional supplement bottle states that it is not permitted by the United States Federal Drug Regulation. It is necessary to write such a guide, since dietary supplements can be harmful. According to a survey by the WHO, the World Health Organization, the cost of the global herbal market is set to rise in the future and is expected to rise to around $ 100 billion, but herbal medicine must be evidence-based and statistically proven15.
Reverse pharmacology can discover the potential of herbal medicine and become an innovative tool for drug discovery. With several chronic disease treatments, there is an increasing demand for herbal treatments16,17. Reverse pharmacology is not only used to find out the hidden potential of the new drug, it is also useful in figuring out the new uses of the old drug. Herbal medicine phytochemicals act as scaffolds for modification18.
2. Reverse Pharmacology Phases2,19
Reverse Pharmacology Phases are
2.1. Experience phase:
This phase includes the investigation of the pharmacological effects of traditional herbal medicine, its documentation and logging.
2.2 Exploratory studies:
This step includes the dose determination, drug interaction, drug tolerance as well as in vitro and in vivo studies.
2.3. Experimental Studies:
This phase involves the identification and validation of drug safety and efficacy at multiple levels. The three phases of reverse pharmacology are interrelated. The first phase of reverse pharmacology is the experience base. It gathers the pharmaco-epidemiological information, clinical observation information and case study information. It also gathers information about new uses of old drugs. Reverse Pharmacology acts as a new platform for several disciplines to investigate the pharmacological effects of traditional medicine. It helps to find the new chemical molecule and ultimately a new drug from conventional medicine for the treatment of certain acute and chronic diseases.
3. Current scenario of drug discovery in India11,20,21.
The currently available method of drug discovery is a time consuming process, requires more budget and has less chance of successfully finding new safe and effective drug molecules. Therefore, the number of active ingredient discoveries for the search for the new active ingredient Chemical is decreasing from day to day. The number of approvals for new active ingredients has steadily declined. The World Health Organization also recommended the traditional use of medicine for the treatment of acute and chronic diseases. The pharmaceutical company is constantly on the lookout for new technologies for drug discovery. The currently available drug discovery model indicates that there is no growth rate. The traditional uses of medicine is a new area for drug discovery. Reverse Pharmacology is an innovative tool for researching active component from medicinal plants.
4. The need for reverse pharmacology22,23,24
Most of the world's affected populations have very little access to modern medicine. The use of medicines made from natural resources is the first regimen in rural areas. These people rely on traditional medicines. Synthetic drugs have been linked to the development of resistance. In order to avoid the development of resistance, it is imperative to define novel hits and lead shares. In this era, the reverse pharmacological approach is the innovative tool in the drug discovery process, and the success rate is higher than other tools used for drug discovery.
5. Current State of Reverse Pharmacology in India:
Less than 10% of the herbal products on the world market are really standardized to known active ingredients and strict quality controls are not always scrupulously adhered to. With the increasing diversity and complexity of diseases, the need for the discovery and development of new drugs increases. The currently available drug discovery method is a time consuming process, requires more budget, and has less chance of successfully finding new safe and effective drug molecules21. Because of such a situation, reverse pharmacology can be a more effective alternative approach to drug discovery. Reverse Pharmacology is a science of integrating documented experience hits, into leads through transdisciplinary exploratory studies, and advancing drug candidates through experimental research. In reverse pharmacology, the already established drugs of traditional medicine are scientifically reassessed and the lead compounds are generated, which are further screened to develop a molecule that can be used for a clinical study. RP offers an advantage over traditional drug research as it is a time-saving and economical process.
The Indian government is currently taking many initiatives to promote a multidisciplinary approach to health care. RP has been practiced for a long time, but has not caught on due to a lack of documentation and standardized scientific procedures. But now with the change in scenario and the development of molecules that use RP, it is gaining popularity and we can hope for a paradigm shift in the future in drug discovery22.
6. Outstanding features of reverse pharmacology:
The classical process of drug discovery is extravagant and delayed. Extensive investigation period (10-15 years) and expenditure requirements of more than 1 to 1.5 billion US $. This highly complex technology base and the capital-intensive process have contributed to the achievement of target group-rich and underperforming goals. Reverse pharmacology, on the other hand, is tricky, saves time, and has the fewest barriers and obstacles. Reverse Pharmacology9,12, effectively shortens the duration of drug discovery to around 4-5 years. The new lead molecules can find out with the help of reverse pharmacology. It also helps to determine the mechanism of action of the compound in the various biological systems, the safety, and efficacy of natural herbal medicine.
Existing information about the native medicinal plant is used to discover new molecules from an existing herbal medicinal plant. This type of drug research is known as bedside-to-bench discovery. Validation of safety and efficacy is the most important and starting point26.
7. Contribution of reverse pharmacology to drug discovery:
The breakthrough of reverse pharmacology in India has produced the following indications from indigenous medicinal plants27.
Table 7.1 Discovery of drugs through Reverse Pharmacological Approach
|
Disease |
Plants |
Ayurvedic forms |
Phytoactive |
|
Diabetes mellitus |
P. emblica E. littorale |
Fruits-Chyavanprash Entire plant Ghana |
Gallic acid Swertiamarin |
|
Arthritis |
T. cordifolia S. anacardum |
Amrita bhallatakAvaleha |
Polysaccharide Bhilawanol |
|
Hepatitis |
Multi-ingredients |
Phalaghrita |
Multiple |
|
Psoriasis |
A. Mexicana |
Latex Ghana |
Berberine |
|
NASH |
P. karroa |
Powder |
Picroside 2 |
|
Malaria |
N. arbor-tristis |
Leaves-paste |
Unknown |
|
Pre-cancer Lesions |
C. longa |
Powder |
Curcumin |
8. Scope of Reverse Pharmacology:
It is observed that 75% to 90% of the world's population use traditional herbal medicine because it is readily available, low in cost, and effective28.29 Reverse Pharmacology helps figure out the new uses of existing plants and contribute the new application to traditional healing of the existing medicinal plants. With the help of traditional scientific knowledge and reverse pharmacology tools, a huge database can be generated from the screening of herbal plants30,31. Reverse pharmacology depends mainly on traditional knowledge as it deals with the molecules, not the ethnopharmacological process. It helps to find out the pharmacological effect and the mechanisms of action on the various biological systems at the molecular level. Reverse Pharmacology is a new way to explore traditional and scientific knowledge and ultimately bridges the gap between traditional knowledge and modern science.
9. CONCLUSION:
Reverse pharmacology is a coordinated transdiscipline that will fill the central gaps between chance and research creativity. Together with observational studies/therapeutics, systems biology, pharmacoepidemiology and reverse pharmacology will improve, enlarge, complement and strengthen the discovery process of the new drug. Hopefully reverse pharmacology has reduced the high cost of modern drugs and runaway health budgets. Funding Source (s) No grant received from funding agencies.
10. CONFLICT OF INTEREST:
None.
11. ACKNOWLEDGMENTS:
The authors would like to thank Dr. Sagar Wankhede, Principal, Datta Meghe College of Pharmacy, Datta Meghe Institute of Medical Sciences (DU), Wardha-442004, Maharashtra, India for providing guidance, resources and support.
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Received on 25.11.2021 Modified on 18.02.2022
Accepted on 29.03.2022 © RJPT All right reserved
Research J. Pharm. and Tech 2022; 15(12):5875-5878.
DOI: 10.52711/0974-360X.2022.00991