20-Hydroxyecdysone, from Plant Extracts to Clinical Use: Therapeutic Potential for the Treatment of Neuromuscular, Cardio-Metabolic and Respiratory Diseases

Abstract

There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin–angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.

Comparison between the Biological Active Compounds in Plants with Adaptogenic Properties (Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus and Panax ginseng)

“…cons ., Diploclisia glaucescens (Blume) Diels, Pfaffia glomerata (Spreng.) Pedersen, Spinacia oleracea L., Polypodium japonicum Makino, and some others [ 62 , 63 , 64 ].…”

“…Since 2020, ecdysterone has been included in the World Anti-doping Agency (WADA) monitoring program [ 65 ]. According to different studies in mammals, ecdysterone has a wide variety of pharmacological effects: anabolic, anti-diabetic, anti-inflammatory, cardioprotective, hypolipidemic and others [ 62 , 66 , 67 , 68 , 69 , 70 ].…”

“…Although the four plants have quite different phytochemical composition ( Table 6 ), the future perspectives for introduction of their specific molecules/ plant extracts as medi-cines are similar [ 12 , 13 , 22 , 23 ]. Most of them could be included in the management of dia-betes, cardiovascular diseases, or used as nootropic agents and hepatoprotectors ( Table 7 ) [ 12 , 18 , 35 , 62 , 67 , 132 ]. Rhaponticum carthamoides is the only plant among these which has the greatest potential to be used as a remedy for improvement physical performance, because of potential ergogenic activity.…”

Insulin-like Growth Factor 2 Promotes Tissue-Specific Cell Growth, Proliferation and Survival during Development of Helicoverpa armigera

“…The 20E also upregulates the expression of Ilp4 and Ilp5 in Aedes aegypti [ 40 ]. The 20E is found in insects and many plants, and has been shown to have possible clinical applications to treat neuromuscular, cardio-metabolic, and respiratory diseases [ 41 ].…”

Plant Secondary Metabolites Used for the Treatment of Diseases and Drug Development

“…A second review shows natural products, alone or in combination with US Food and Drug Administration-approved drugs, used to treat COVID-19, which is a public health emergency of international concern, and lung cancer, a malignant tumour with the highest mortality rate, which has presented significant challenges to both human health and economic development [10]. The third review describes 20-hydroxyecdysone, a polyhydroxylated steroid, and its path from plant extracts to clinical use, mainly showing its therapeutic potential for the treatment of neuromuscular, cardio-metabolic, and respiratory diseases [11]. This review is connected to the fourth one, which names the natural products that "changed society", as, despite the impressive results achieved within the art of synthetic chemistry, natural products or modified natural products still constitute almost half of the drugs used for the treatment of cancer and diseases such as malaria, onchocerciasis (river blindness), and lymphatic filariasis (caused by parasites) [12].…”