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Role of Natural Agents in the Management of Diabetes
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Monika Elżbieta Jach, Anna Serefko
Galega officinalis is a leguminous plant, which aerial parts have long been used in traditional and folk medicine to treat diabetes in Chile, Japan as well as Europe (Bailey and Day, 2004; Gunn and Farnsworth, 2013; Rios et al., 2015). This herb consists of two nitrogen guanidine constituents: galegin (syn. galegine) as isoamylene guanidine and hydroxygalegine prevalent in all parts during flowering and forming fruits. These bioactive substances possess pharmacological features as hypoglycemic and galactogenic factors. However, guanidine is excessively toxic for clinical treat; hence, the study focused on galegine, which turned out to be less toxic as an extract of G. officinalis. In the 1920s, the extract was specified as an antidiabetic formulation (Bailey and Day, 2004; Martínez-Larrañaga and Martínez, 2018).
Plant Diversity and Ethnobotanical Perspective of Odisha
Published in Jayanta Kumar Patra, Gitishree Das, Sanjeet Kumar, Hrudayanath Thatoi, Ethnopharmacology and Biodiversity of Medicinal Plants, 2019
Saswati Dash, Ichhamati Pradhan, Suraja Kumar Nayak, Bighneswar Baliyarsingh
Bioactive compounds in plants are complex molecules produced by plants having pharmacological or toxicological effects on humans or other organisms. Phylogenetically, the ability of producing typical bioactive compounds, loosely termed as secondary metabolites, can vary. The secondary bioactive compounds in plants are synthesized non-constitutively but hold important function in plants. For example, flavonoids can protect against free radicals generated during photosynthesis. Terpenoids may attract pollinators or seed dispersers, or inhibit competing plants. Alkaloids usually ward off herbivore animals or insect attacks (phytoalexins). Surveys of plant-derived pure compounds used as drugs conducted by countries with WHO-Traditional Medicine Centers have identified 122 compounds. Of these, 80% were used for the same or related medicinal purposes and were derived from only 94 plant species (Farnsworth et al., 1985). Some notable examples of bioactive compounds in drug formulations are galegine, derived from Galega officinalis L., served as a model for metformin and bisguanidine-type in antidiabetic drugs synthesis and papaverine derived from Papaver somniferum is an active constituent of hypertension drugs like verapamil (Fabricant and Farnsworth, 2001). In addition, the latter plant is the best source of painkillers such as morphine and codeine (Buss et al., 2003), but probably the best examples of ethnomedicine’s role in guiding drug discovery and development is that of the antimalarial drugs, particularly quinine and artemisinin.
Diabetes and Phytopharmaceuticals: Translational Pharmacology Perspective
Published in Vikas Kumar, Addepalli Veeranjaneyulu, Herbs for Diabetes and Neurological Disease Management, 2018
Priyanka Ingle-Jadhav, Trupti Rajkumar Angolkar, Ginpreet Kaur
One of the most widely prescribed anti-diabetic drug, metformin, it history can be traced to use of Galega officinalis Linn—a medieval herbal medicine. Also called as goats rue, the plant was used as a folklore medicine to treat diabetes since 17th century. Studies in 1800 indicated that G. officinalis is rich in guanidine, which was shown to be anti-hyperglycemic in animals. Yet due to its overt toxicity for clinical use, galegine was utilized for further studies. Figure 8.2 depicts the similar structures of these drugs.13 Over the period, there were many modifications and clinical studies involved to understand the efficacy and toxicity of these drugs. In 1957, Jean Sterne published his work on exploration of several biguanides including dimethyl biguanide (metformin) for clinical development and proposed the name “Glucophage” (glucose eater). It was only after 1970s, the use of metformin was in prominence.14 In retrospect, metformin can be traced back to the origin from the plant source.
Application of the Mannich reaction in the structural modification of natural products
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Miao-Xia Pu, Hong-Yan Guo, Zhe-Shan Quan, Xiaoting Li, Qing-Kun Shen
Natural products constitute a treasury for drug development and have always been valuable sources in drug design. Pharmaceutical researchers are often inspired by natural product molecules with specific reactive backbones, reactive groups, and excellent biological activities. For example, khellin from Ammi visnaga (L) Lamk led to the development of chromolyn (in the form of sodium chromoglycate) as a bronchodilator and galegine from Galega officinalis L, which is a model for the synthesis of metformin and other bisguanidine-type antidiabetic drugs1. In addition, data analysis has shown that a considerable number of drugs approved by the Food and Drug Association (FDA) since 1939 contain natural product fragments. The natural product database contains 210,213 natural products. This demonstrates the importance of natural products for drug research. Therefore, the structural modifications of natural products are of great significance.
Current and emerging gluconeogenesis inhibitors for the treatment of Type 2 diabetes
Published in Expert Opinion on Pharmacotherapy, 2021
The first oral hypoglycemic was the herbal medicine Galega officinalis containing galegine, structurally similar to metformin [118]. Metformin was studied in the 1920s but only came into official clinical use in the 1950s. It is the primary initial treatment for type 2 diabetes. Metformin acts at the mitochondrion to decrease glycerol production and change the redox state of the mitochondrial membrane. The mechanisms of metformin inhibition of gluconeogenesis are not fully understood, but evidence points to a direct effect on the mitochondrion and inhibition of the enzyme glycerol 3 phosphate dehydrogenase [65].
Metformin as a potential treatment for COVID-19
Published in Expert Opinion on Pharmacotherapy, 2023
Metformin is derived from galegine, a compound from the plant Galega officinalis, which has been used for centuries in herbal medicine [15,16]. Galegine was noted to be a glucose-lowering agent, but its use has been limited by systemic toxicity [17,18]. Metformin, a synthetic derivative of galegine, was introduced into clinical practice in the 1950s and was not designed to target a particular pathway or disease mechanism [19,20]. Metformin was quickly established as a safe and effective treatment for DM2 [21,22].