Bioassay-guided phytochemistry of Zingiber zerumbet (L.) Smith rhizome extract against dengue virus serotype-2 NS2B/NS3 protease and its anti-pyretic activities / Haslinda Mohd Salleh

Haslinda , Mohd Salleh (2023) Bioassay-guided phytochemistry of Zingiber zerumbet (L.) Smith rhizome extract against dengue virus serotype-2 NS2B/NS3 protease and its anti-pyretic activities / Haslinda Mohd Salleh. PhD thesis, Universiti Malaya.

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Abstract

The bioassay-guided study was conducted on Zingiber zerumbet (L.) Smith (shampoo ginger) to investigate its anti-dengue potential through the inhibition of DENV2 NS2B/ NS3 protease. In this study, the rhizomes of Z. zerumbet were extracted with different polarities of solvents and tested for DENV2 NS2B/NS3 protease inhibition, acute toxicity and anti-pyretic studies. The results showed that the ethyl acetate (EA) extract of Z. zerumbet exhibited potent inhibitory activity against NS2B/NS3 protease with IC50 value of 2.39 ± 0.86 μg/mL. Acute toxicity test indicated that the EA extract is not toxic up to dosage of 5000 mg/kg. In addition, comparison of anti-pyretic activity between the EA extract (125 mg/kg body weight) and aspirin (121) (100 mg/kg body weight) have shown a difference in reduction of the rectal temperature of rats. The EA extract (125 mg/kg body weight) demonstrated faster temperature reduction than aspirin (121) within the first two hours after administration. However, the temperature rose after the 2nd hour of the experiment. On the other hand, aspirin (121) had slower temperature reduction but the temperature reduction was continued until the 4th hour of the experiment. Therefore, the EA extract (125 mg/kg body weight) showed rapid onset of action compared to aspirin (121) but aspirin (121) has longer lasting anti-pyretic effect. Furthermore, two compounds were isolated from the potent EA fraction of Z. zerumbet, namely zerumbone (3) and zerumbone epoxide (56). Zerumbone epoxide (56) exhibited more potent inhibition against DENV2 NS2B/NS3 protease (72.04%) than zerumbone (3) (54.33%). Both compounds were subjected to a molecular docking study. Two hydrogen bonding were observed between the epoxide group of zerumbone epoxide (56) -alkyl interactions of zerumbone epoxide (56) with Tyr150, Tyr161, and His51 were also observed. The binding energy of zerumbone epoxide (56) (-5.60 kcal/mol) was slightly lower than zerumbone (3) (-5.58 kcal/mol). Thus, the molecular docking results are consistent with the anti-protease studies of both compounds. In conclusion, the EA of Z. zerumbet could be a promising candidate for the development of anti-pyretic and antidengue agents.

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