Isolation of bioactive phytochemicals from Crinum asiaticum L. along with their cytotoxic and TRAIL-resistance abrogating prospect assessment
Sharmin Ahmed Rakhi,
Yasumasa Hara,
Md. Saiful Islam,
Teruhisa Manome,
Safaet Alam,
Nazim Uddin Emon,
Muhammad Abdullah Al-Mansur,
Md. Ruhul Kuddus,
Md. Raihan Sarkar,
Masami Ishibashi,
Firoj Ahmed
Affiliations
Sharmin Ahmed Rakhi
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka, 1000, Bangladesh
Yasumasa Hara
Department of Natural Products Chemistry, Chiba University, Chiba, 260-8675, Japan
Md. Saiful Islam
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka, 1000, Bangladesh; Pharmaceutical Sciences Research Division, BCSIR Laboratories, Dhaka, Bangladesh Council of Scientific and Industrial Research, Dhaka, 1205, Bangladesh
Teruhisa Manome
Department of Natural Products Chemistry, Chiba University, Chiba, 260-8675, Japan
Safaet Alam
Drugs and Toxins Research Division, BCSIR Laboratories Rajshahi, Bangladesh Council of Scientific and Industrial Research, Rajshahi, 6206, Bangladesh; Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka, 1000, Bangladesh
Nazim Uddin Emon
Department of Pharmacy, Faculty of Science and Engineering, International Islamic University Chittagong, Chittagong, 4318, Bangladesh
Muhammad Abdullah Al-Mansur
Institute of National Analytical Research and Service, BCSIR, Dhaka, 1205, Bangladesh
Md. Ruhul Kuddus
Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka, 1000, Bangladesh
Md. Raihan Sarkar
Department of Pharmaceutical Technology, University of Dhaka, Dhaka, 1000, Bangladesh
Masami Ishibashi
Department of Natural Products Chemistry, Chiba University, Chiba, 260-8675, Japan
Firoj Ahmed
Department of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh; Corresponding author.
Crinum asiaticum L. (Amaryllidaceae) is a perennial bulbous herb, locally utilized for possessing multifaceted pharmacological properties including anticancer, immune-stimulating, analgesic, antiviral, antimalarial, antibacterial and antifungal, in addition to its popularity as an aesthetic plant. Separation of MeOH extract of C. asiaticum leaves yielded three known compounds as cycloneolitsol (1), hippeastrine (2) and β-sitosterol (3). Among these, compounds 1 and 2 were subjected to the cytotoxic assay and found that they induced mild effect against HCT116, Huh7 and DU145 cell lines with the IC50 values from 73.76 to 132.53 μM. When tested for TRAIL-resistance abrogating activity, 1 (100 μM) along with TRAIL (100 ng/mL) showed moderate activity in AGS cells producing 25 % more inhibition than the agent alone. Whereas 2 (20 and 30 μM) in combination with TRAIL (100 ng/mL) exhibited strong activity in abrogating TRAIL-resistance and caused 34 % and 36 % more inhibition in AGS cells, respectively. The in-silico studies of compound 2 revealed high docking hits with the TRAIL-associated anti-apoptotic proteins which give a justification for the regulatory interactions to induce such abrogating activity. It is still recommended to conduct further investigations to understand their exact molecular mechanism.
