Kadiyala Gopi1, K Anbarasu1, Kadali Renu1, S Jayanthi1, B S Vishwanath2, Gurunathan Jayaraman3. 1. School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu 632 014, India. 2. Department of Biochemistry, University of Mysore, Mysuru, Karnataka, India. 3. School of Bio Sciences and Technology, VIT University, Vellore, Tamil Nadu 632 014, India. Electronic address: gjayaraman@vit.ac.in.
Abstract
BACKGROUND: The plant Euphorbia hirta is widely used against snake envenomations in rural areas and it was proved to be effective in animal models. Therefore, the scientific validation of its phytoconstituents for their antiophidian activity is aimed in the present study. METHODS: E. hirta extract was subjected to bioactivity guided fractionation and the fractions that inhibited different enzyme activities of Naja naja venom in vitro was structurally characterized using UV, FT-IR, LC-MS and NMR spectroscopy. Edema, hemorrhage and lethality inhibition activity of the compound were studied in mice model. In addition, molecular docking and molecular dynamic simulations were also performed in silico. RESULTS: The bioactive fraction was identified as Quercetin-3-O-α-rhamnoside (QR, 448.38 Da). In vitro experiments indicated that protease, phospholipase-A(2), hemolytic activity and hemorrhage inducing activity of the venom were inhibited completely at a ratio of 1:20 (venom: QR) w/w. At the same concentration, the edema ratio was drastically reduced from 187% to 107%. Significant inhibition (93%) of hyaluronidase activity was also observed at a slightly higher concentration of QR (1:50). Further, in in vivo analysis, QR significantly prolonged the survival time of mice injected with snake venom. CONCLUSION: For the first time Quercetin-3-O-α-rhamnoside, isolated from E. hirta, has been shown to exhibit anti-snake venom activity against Naja naja venom induced toxicity. GENERAL SIGNIFICANCE: Exploring such multifunctional lead molecules with anti-venom activity would help in developing complementary medicine for snakebite treatments especially in rural areas where anti-snake venom is not readily available.
BACKGROUND: The plant Euphorbia hirta is widely used against snake envenomations in rural areas and it was proved to be effective in animal models. Therefore, the scientific validation of its phytoconstituents for their antiophidian activity is aimed in the present study. METHODS:E. hirta extract was subjected to bioactivity guided fractionation and the fractions that inhibited different enzyme activities of Naja naja venom in vitro was structurally characterized using UV, FT-IR, LC-MS and NMR spectroscopy. Edema, hemorrhage and lethality inhibition activity of the compound were studied in mice model. In addition, molecular docking and molecular dynamic simulations were also performed in silico. RESULTS: The bioactive fraction was identified as Quercetin-3-O-α-rhamnoside (QR, 448.38 Da). In vitro experiments indicated that protease, phospholipase-A(2), hemolytic activity and hemorrhage inducing activity of the venom were inhibited completely at a ratio of 1:20 (venom: QR) w/w. At the same concentration, the edema ratio was drastically reduced from 187% to 107%. Significant inhibition (93%) of hyaluronidase activity was also observed at a slightly higher concentration of QR (1:50). Further, in in vivo analysis, QR significantly prolonged the survival time of mice injected with snake venom. CONCLUSION: For the first time Quercetin-3-O-α-rhamnoside, isolated from E. hirta, has been shown to exhibit anti-snake venom activity against Naja naja venom induced toxicity. GENERAL SIGNIFICANCE: Exploring such multifunctional lead molecules with anti-venom activity would help in developing complementary medicine for snakebite treatments especially in rural areas where anti-snake venom is not readily available.
Authors: Asenate A X Adrião; Aline O Dos Santos; Emilly J S P de Lima; Jéssica B Maciel; Weider H P Paz; Felipe M A da Silva; Manuela B Pucca; Ana M Moura-da-Silva; Wuelton M Monteiro; Marco A Sartim; Hector H F Koolen Journal: Front Immunol Date: 2022-05-09 Impact factor: 8.786
Authors: Doroty Mesquita Dourado; Rosemary Matias; Baldomero Antonio Kato da Silva; Fiorela Faria Milanesi; Mayra Duarte Martello; Carlos Henrique Marques Dos Santos; Claudia Andréa Lima Cardoso; Willians Fernando Vieira; Maria Alice da Cruz-Höfling Journal: Photochem Photobiol Sci Date: 2021-08-02 Impact factor: 3.982