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Common Medicines from Herbs, Minerals and Animal Sources
Published in Mehwish Iqbal, Complementary and Alternative Medicinal Approaches for Enhancing Immunity, 2023
One of its examples includes alkaloid reserpine, separated from Indian snakeroot, also recognised as Rauwolfia serpentina, which was a significant invention made by utilising the approach of reverse pharmacology. In 1931, the Indian chemists persuasively showed the tranquillising and antihypertensive activities of the plant. They also noticed distinctive adverse effects, such as gynaecomastia, depression, extrapyramidal syndrome and a number of adverse effects (Patwardhan et al., 2015a). In 1949, Rustom Jal Vakil, who evolved cardiology in India, conducted a trial of Indian snakeroot on subjects with primary hypertension, which documented a drop in diastolic and systolic blood pressure (Vakil, 1949). It took many years to describe the mechanisms of these adverse effects. This determined attempt gave rise to a turning point for new drugs such as prolactin-inhibiting agents, antidepressants and medicines for Parkinson's disease (Svensson, 1980). One more example of reverse pharmacology is a medicine prepared from the seeds of Mucuna pruriens for the management of Parkinson's disease (Manyam et al., 2004; Vaidya et al., 1978).
Natural Medicines
Published in Dilip Ghosh, Pulok K. Mukherjee, Natural Medicines, 2019
Ashok Vaidya, Hiteshi Dhami-Shah, Shobha Udipi
There are two nuances of the term ‘reverse pharmacology’: one meaning is the path of pharmacology from the bedside observations to bench experiments, and the second is the quest for drug-like molecules (endogenous or extrinsic) that dock with human macromolecules as receptors or enzymes. For the present chapter, our focus is on the first meaning of RP (Raut et al. 2016). RP can be pursued in three stages. First, the experiential stage covers robust documentation, by meticulous records, of clinical and laboratory observations of the effects of standardised natural drugs of traditional medicine. Second, the exploratory stage includes studies for safety, efficacy, interactions and dose-range finding in patients with defined therapeutic targets, besides paraclinical studies in relevant in vitro and in vivo models to evaluate pharmacological activities. The third stage consists of experimental studies, basic and clinical, at several levels of biological organisation, to investigate and identify the pharmacological correlates of the safety and efficacy of the NM. The RP path is economical, fast-track and productive (Figure 26.1). The scope of RP extends also to the unveiling of the molecular mechanisms of action and the use of active phytomolecules as scaffolds for synthetically modified novel candidates of NM (Patwardhan et al. 2008).
Antimicrobial Properties of Traditional Medicinal Plants: Status and Potential
Published in Megh R. Goyal, Durgesh Nandini Chauhan, Plant- and Marine-Based Phytochemicals for Human Health, 2018
V. Duraipandiyan, T. William Raja, Naif Abdullah Al-Dhabi, Ignacimuthu Savarimuthu
“Reverse pharmacology” is an innovative approach that mixes living traditional knowledge such as Ayurveda with modern technology, providing better and safer lead drug candidates. In this process, safety is the starting point and markers of efficacy are used for validation purposes. This approach has been utilized in the process of preclinical and clinical research.38 Practical guidelines for plant-based “drug” development have been framed by the Food and Drug Administration (FDA), as well as other agencies, to cure existing diseases in the world.16 The importance of TMs has recently been recognized. TMs include 25,000–75,000 plant species that are used to treat various diseases, including microbial diseases and several products are accepted for commercial purposes.1 Plant-based drugs and traditional herbal formulations can be used to fight against infectious pathogens, effectively killing microorganisms, and inhibiting their growth. Thus, they are helpful for improving human health.
Where lies the future of Ayurveda-inspired drug discovery?
Published in Expert Opinion on Drug Discovery, 2023
The Ayurveda-inspired drug discovery can follow a reverse pharmacology approach from ‘clinics-to-laboratories’ rather than the conventional ‘laboratory-to-clinics’ process. Reverse pharmacology is an approach that integrates reported clinical experiences and experiential observations into leads, through trans-disciplinary exploratory studies. These leads can then be further developed into drug candidates through robust preclinical and clinical studies. In this process, quality and safety is of primary importance, and efficacy is validated using conventional outcome measures [8]. Scientists have identified several bioactive compounds from medicinal plants described in Ayurveda. Examples of these include: Rauwolfia alkaloids for treating hypertension; psoralens for vitiligo; guggulsterons as hypolipidemic agents; Mucuna pruriens for Parkinson’s disease; piperidines as enhancers of bioavailability; baccosides in mental retention; picrosides for hepatic protection; phyllanthins as antivirals; berberine, curcumin for controlling infections, inflammation, and cancer; shatavarins and withanolides as adjuvants and immunomodulators [9].
How to rekindle drug discovery process through integrative therapeutic targeting?
Published in Expert Opinion on Drug Discovery, 2018
Ashok Vaidya, Anuradha Roy, Rathnam Chaguturu
In recent years, the novel bedside hits and leads in therapeutics have emerged as opportunities for drug discovery through repurposing and reverse pharmacology (RP) approaches. Clinician pharmacologists in modern medicine, Vaidya scientists in Ayurveda and practitioners of TCM can be major stakeholders and collaborators in drug discovery, by sharing their bedside novel hints, hits and leads of therapeutic interventions. These natural remedies work at multiple targets and at different levels of biological organization. Natural drugs have again emerged on the global stage, after the 2015 Nobel Prize awarded to William Campbell, Satoshi Omura, and Youyou Tu for their discovery of avermectins and artemisinin, respectively. In the words of Ben Shen, we are witnessing a new golden age of natural product drug discovery, in that natural products possess enormous structural and chemical diversity that cannot be matched by any synthetic libraries of small molecules and continue to inspire novel discoveries in chemistry, biology, and medicine [21].
A comprehensive review of recent studies on pharmacokinetics of traditional Chinese medicines (2014–2017) and perspectives
Published in Drug Metabolism Reviews, 2018
Peiying Shi, Xinhua Lin, Hong Yao
Recently, Hao et al. (2014) proposed a novel concept of ‘reverse PK’ in drug discovery from NMs, including TCMs in some extent. In contrast to ‘classical PK’, which are designated to determine the drug metabolism and pharmacokinetics (DMPK) characteristics of a given chemical drugs with validated targets, in the concept of ‘reverse PK’, DMPK properties of NMs and the association with well-documented pharmacological efficacies can be exploited to assess the possible targeting tissues/organs/systems/receptors of NMs. With this information, relevant pharmacodynamics in vitro models could be selected to discover active components, facilitate mechanism-of-action and target studies, and reverse pharmacology-guided drug discovery. In addition, Hao et al. (2014) elucidated how might the ‘reverse PK’ help development of NMs (or TCMs) from four aspects, which were ‘Identification of physiologically relevant targets/mechanisms’, ‘Illumination of gut microbiota as important mediators or potential targets of NMs’, ‘Discovery of new chemical entities and multiple-component, multiple-target combinatory drugs from NMs’, and ‘Pharmacokinetic compatibility-guided drug discovery’, respectively. Thus, ‘reverse PK’ has great significance in innovating NMs-guided drug discovery and in inspiring new therapeutic targeting strategies for complex diseases and chronic diseases. We also believe that the new concept of ‘reverse PK’ can be well applied to TCMs, and to improve the discovery of both single ingredient and multiple-component modern drugs from TCMs.