Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity
Dengue is a serious public health concern worldwide, with ∼3 billion people at risk of contracting dengue virus (DENV) infections, with some suffering severe consequences of disease and leading to death. Currently, there is no broad use vaccine or drug available for the prevention or treatment of de...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:a2f36b9d0b3b4046aab203f00ae8f6032021-12-01T13:51:45ZCocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity1664-302X10.3389/fmicb.2021.746110https://doaj.org/article/a2f36b9d0b3b4046aab203f00ae8f6032021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.746110/fullhttps://doaj.org/toc/1664-302XDengue is a serious public health concern worldwide, with ∼3 billion people at risk of contracting dengue virus (DENV) infections, with some suffering severe consequences of disease and leading to death. Currently, there is no broad use vaccine or drug available for the prevention or treatment of dengue, which leaves only anti-mosquito strategies to combat the dengue menace. The present study is an extension of our earlier study aimed at determining the in vitro and in vivo protective effects of a plant-derived phytopharmaceutical drug for the treatment of dengue. In our previous report, we had identified a methanolic extract of aerial parts of Cissampelos pareira to exhibit in vitro and in vivo anti-dengue activity against all the four DENV serotypes. The dried aerial parts of C. pareira supplied by local vendors were often found to be mixed with aerial parts of another plant of the same Menispermaceae family, Cocculus hirsutus, which shares common homology with C. pareira. In the current study, we have found C. hirsutus to have more potent anti-dengue activity as compared with C. pareira. The stem part of C. hirsutus was found to be more potent (∼25 times) than the aerial part (stem and leaf) irrespective of the extraction solvent used, viz., denatured spirit, hydro-alcohol (50:50), and aqueous. Moreover, the anti-dengue activity of stem extract in all the solvents was comparable. Hence, an aqueous extract of the stem of C. hirsutus (AQCH) was selected due to greater regulatory compliance. Five chemical markers, viz., Sinococuline, 20-Hydroxyecdysone, Makisterone-A, Magnoflorine, and Coniferyl alcohol, were identified in fingerprinting analysis. In a test of primary dengue infection in the AG129 mice model, AQCH extract at 25 mg/kg body weight exhibited protection when administered four and three times a day. The AQCH was also protective in the secondary DENV-infected AG129 mice model at 25 mg/kg/dose when administered four and three times a day. Additionally, the AQCH extract reduced serum viremia and small intestinal pathologies, viz., viral load, pro-inflammatory cytokines, and vascular leakage. Based on these findings, we have undertaken the potential preclinical development of C. hirsutus-based phytopharmaceutical, which could be studied further for its clinical development for treating dengue.Rahul ShuklaRavi Kant RajpootAnkur PoddarRicha AhujaHemalatha BeesettiRajgokul K. ShanmugamShivam ChaturvediKaushal NayyarDeepika SinghVenugopal SingamaneniPrasoon GuptaAjai Prakash GuptaSumeet GairolaPankaj KumarY. S. BediTapesh JainBhupendra VashishtaRavindra PatilHarish MadanSumit MadanRinku KalraRuchi SoodRam A. VishwakarmaD. Srinivasa ReddyAltaf A. LalUpasana AroraNavin KhannaFrontiers Media S.A.articledenguephytopharmaceuticalCissampelos pareiraCocculus hirsutusAG129 micevascular leakageMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021) |
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dengue phytopharmaceutical Cissampelos pareira Cocculus hirsutus AG129 mice vascular leakage Microbiology QR1-502 |
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dengue phytopharmaceutical Cissampelos pareira Cocculus hirsutus AG129 mice vascular leakage Microbiology QR1-502 Rahul Shukla Ravi Kant Rajpoot Ankur Poddar Richa Ahuja Hemalatha Beesetti Rajgokul K. Shanmugam Shivam Chaturvedi Kaushal Nayyar Deepika Singh Venugopal Singamaneni Prasoon Gupta Ajai Prakash Gupta Sumeet Gairola Pankaj Kumar Y. S. Bedi Tapesh Jain Bhupendra Vashishta Ravindra Patil Harish Madan Sumit Madan Rinku Kalra Ruchi Sood Ram A. Vishwakarma D. Srinivasa Reddy Altaf A. Lal Upasana Arora Navin Khanna Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity |
| description |
Dengue is a serious public health concern worldwide, with ∼3 billion people at risk of contracting dengue virus (DENV) infections, with some suffering severe consequences of disease and leading to death. Currently, there is no broad use vaccine or drug available for the prevention or treatment of dengue, which leaves only anti-mosquito strategies to combat the dengue menace. The present study is an extension of our earlier study aimed at determining the in vitro and in vivo protective effects of a plant-derived phytopharmaceutical drug for the treatment of dengue. In our previous report, we had identified a methanolic extract of aerial parts of Cissampelos pareira to exhibit in vitro and in vivo anti-dengue activity against all the four DENV serotypes. The dried aerial parts of C. pareira supplied by local vendors were often found to be mixed with aerial parts of another plant of the same Menispermaceae family, Cocculus hirsutus, which shares common homology with C. pareira. In the current study, we have found C. hirsutus to have more potent anti-dengue activity as compared with C. pareira. The stem part of C. hirsutus was found to be more potent (∼25 times) than the aerial part (stem and leaf) irrespective of the extraction solvent used, viz., denatured spirit, hydro-alcohol (50:50), and aqueous. Moreover, the anti-dengue activity of stem extract in all the solvents was comparable. Hence, an aqueous extract of the stem of C. hirsutus (AQCH) was selected due to greater regulatory compliance. Five chemical markers, viz., Sinococuline, 20-Hydroxyecdysone, Makisterone-A, Magnoflorine, and Coniferyl alcohol, were identified in fingerprinting analysis. In a test of primary dengue infection in the AG129 mice model, AQCH extract at 25 mg/kg body weight exhibited protection when administered four and three times a day. The AQCH was also protective in the secondary DENV-infected AG129 mice model at 25 mg/kg/dose when administered four and three times a day. Additionally, the AQCH extract reduced serum viremia and small intestinal pathologies, viz., viral load, pro-inflammatory cytokines, and vascular leakage. Based on these findings, we have undertaken the potential preclinical development of C. hirsutus-based phytopharmaceutical, which could be studied further for its clinical development for treating dengue. |
| format |
article |
| author |
Rahul Shukla Ravi Kant Rajpoot Ankur Poddar Richa Ahuja Hemalatha Beesetti Rajgokul K. Shanmugam Shivam Chaturvedi Kaushal Nayyar Deepika Singh Venugopal Singamaneni Prasoon Gupta Ajai Prakash Gupta Sumeet Gairola Pankaj Kumar Y. S. Bedi Tapesh Jain Bhupendra Vashishta Ravindra Patil Harish Madan Sumit Madan Rinku Kalra Ruchi Sood Ram A. Vishwakarma D. Srinivasa Reddy Altaf A. Lal Upasana Arora Navin Khanna |
| author_facet |
Rahul Shukla Ravi Kant Rajpoot Ankur Poddar Richa Ahuja Hemalatha Beesetti Rajgokul K. Shanmugam Shivam Chaturvedi Kaushal Nayyar Deepika Singh Venugopal Singamaneni Prasoon Gupta Ajai Prakash Gupta Sumeet Gairola Pankaj Kumar Y. S. Bedi Tapesh Jain Bhupendra Vashishta Ravindra Patil Harish Madan Sumit Madan Rinku Kalra Ruchi Sood Ram A. Vishwakarma D. Srinivasa Reddy Altaf A. Lal Upasana Arora Navin Khanna |
| author_sort |
Rahul Shukla |
| title |
Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity |
| title_short |
Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity |
| title_full |
Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity |
| title_fullStr |
Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity |
| title_full_unstemmed |
Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity |
| title_sort |
cocculus hirsutus-derived phytopharmaceutical drug has potent anti-dengue activity |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/a2f36b9d0b3b4046aab203f00ae8f603 |
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