Morusin as a Drug Candidate: Opportunities, Limitations, and the Path Toward Clinical Translation

Hany N Azzam¹Ahmed Eldessouki²Kareem A Attallah³Mohamed A. Sadek⁴Yara M Aboulmagd¹Menna Mahmoud¹Mohamed I. Fahmy⁵Riham El-Shiekh⁴Rania M. Kamal⁴Hazim O. Khalifa^6*

• ¹Heliopolis University, Cairo, Egypt
• ²Ahram Canadian University, 6th of October City, Egypt
• ³Egyptian Ministry of Health and Population, Damietta, Egypt
• ⁴Cairo University, Giza, Egypt
• ⁵Misr University for Science and Technology, 6th of October City, Egypt
• ⁶United Arab Emirates University College of Agriculture and Veterinary Medicine, Al Ain, United Arab Emirates

Prenylflavonoids are widespread in plants, which are considered valuable sources of natural polyphenolic compounds with isoprenyl groups, including flavones, flavanones, chalcones and aurones. Among the notable prenylated flavonoids, morusin-a prenylated flavone isolated from the bark of white mulberry, has garnered attention for its multifaceted biological activities. Extensive research has demonstrated that morusin exhibits pronounced analgesic, antioxidant, anti-inflammatory, bone repair, antitumor, cardioprotective, neuroprotective, hepatoprotective, antidiabetic, and antimicrobial effects. The enhanced lipophilicity imparted by prenylation is believed to facilitate greater cellular membrane interaction, contributing to the superior bioactivity of these compounds compared to their non-prenylated derivatives. Unlike previous reviews that mainly emphasize morusin's bioactivities, this article critically addresses its pharmacokinetic limitations, translational challenges, and safety concerns, offering a more integrated perspective on its path toward clinical application. This review aims to get current insights into the health-promoting effects of morusin, thereby informing the development of novel plant-derived pharmaceuticals and nutraceuticals within the prenylflavonoid category.