Cepharanthine: An update of its mode of action, pharmacological properties and medical applications

Abstract

A B S T R A C TBackground: Cepharanthine (CEP) is a drug used in Japan since the 1950s to treat a number of acute and chronic diseases, including treatment of leukopenia, snake bites, xerostomia and alopecia. It is the only approved drug for Human use in the large class of bisbenzylisoquinoline alkaloids. This natural product, mainly isolated from the plant Stephania cephalantha Hayata, exhibits multiple pharmacological properties including anti-oxidative, anti-inflammatory, immuno-regulatory, anti-cancer, anti-viral and anti-parasitic properties. Purpose: The mechanism of action of CEP is multifactorial. The drug exerts membrane effects (modulation of efflux pumps, membrane rigidification) as well as different intracellular and nuclear effects. CEP interferes with several metabolic axes, primarily with the AMP-activated protein kinase (AMPK) and NFκB signaling pathways. In particular, the anti-inflammatory effects of CEP rely on AMPK activation and NFκB inhibition. Conclusion: In this review, the historical discovery and development of CEP are retraced, and the key mediators involved in its mode of action are presented. The past, present, and future of CEP are recapitulated. This review also suggests new opportunities to extend the clinical applications of this well-tolerated old Japanese drug.

Identifying SARS-CoV-2 Entry Inhibitors through Drug Repurposing Screens of SARS-S and MERS-S Pseudotyped Particles

“… 27 Cepharanthine is a natural product used in Japan since the 1950s for treatments of several diseases without major side effects. 28 It has polypharmacology, with anti-inflammatory activity linked to AMPK activation and NFκB inhibition. 28 Cepharanthine has previously reported antiviral activities against HIV, SARS-CoV, HCoV-OC43, human T-lymphotropic virus (HTLV) and hepatitis B virus (HBV).…”

“… 28 It has polypharmacology, with anti-inflammatory activity linked to AMPK activation and NFκB inhibition. 28 Cepharanthine has previously reported antiviral activities against HIV, SARS-CoV, HCoV-OC43, human T-lymphotropic virus (HTLV) and hepatitis B virus (HBV). 29 …”

Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2

“…Currently, there is an ongoing clinical trial using tetrandrine in COVID-19 patients to improve pulmonary function (80). Cepharanthine is reported to have antiinflammatory and immunoregulatory properties and is used to treat a variety of acute and chronic conditions outside of the US (89). Both cepharanthine and tetrandrine were previously shown to have antiviral activity against the human coronavirus OC43 and in recent studies on SARS-CoV-2 in Vero cell screens (13,62,63).…”

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

“…To date, the published literature has focused principally on the alkaloids and extracts of S. tetrandra. The molecules that have received the greatest in-depth study of their pharmacological activity are tetrandrine (Yang et al 2018a;Bhagya and Chandrashekar 2016;Wang et al 2017a;Xing et al 2014;Cai et al 2011), fangchinoline (Desgrouas et al 2014a;Wang et al 2017a;Xing et al 2014) and cepharanthine (Bailly 2019;Wang et al 2017a). Not only are these compounds found in S. tetrandra, but also in other plants known to have medicinal properties (Table 2).…”