title: Cissampelos pareira Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes.
abstract: BACKGROUND
  Dengue, a mosquito-borne viral disease, poses a significant global public health risk. In tropical countries such as India where periodic dengue outbreaks can be correlated to the high prevalence of the mosquito vector, circulation of all four dengue viruses (DENVs) and the high population density, a drug for dengue is being increasingly recognized as an unmet public health need.
  
  
  RESULTS
  Using the knowledge of traditional Indian medicine, Ayurveda, we developed a systematic bioassay-guided screening approach to explore the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity. Our results show that the alcoholic extract of Cissampelos pariera Linn (Cipa extract) was a potent inhibitor of all four DENVs in cell-based assays, assessed in terms of viral NS1 antigen secretion using ELISA, as well as viral replication, based on plaque assays. Virus yield reduction assays showed that Cipa extract could decrease viral titers by an order of magnitude. The extract conferred statistically significant protection against DENV infection using the AG129 mouse model. A preliminary evaluation of the clinical relevance of Cipa extract showed that it had no adverse effects on platelet counts and RBC viability. In addition to inherent antipyretic activity in Wistar rats, it possessed the ability to down-regulate the production of TNF-α, a cytokine implicated in severe dengue disease. Importantly, it showed no evidence of toxicity in Wistar rats, when administered at doses as high as 2g/Kg body weight for up to 1 week.
  
  
  CONCLUSIONS
  Our findings above, taken in the context of the human safety of Cipa, based on its use in Indian traditional medicine, warrant further work to explore Cipa as a source for the development of an inexpensive herbal formulation for dengue therapy. This may be of practical relevance to a dengue-endemic resource-poor country such as India.
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Sood
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Raut
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Poornima
authors.initials: P
authors.lastname: Tyagi
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Pareek
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Tarani Kanta
authors.initials: TK
authors.lastname: Barman
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Smita
authors.initials: S
authors.lastname: Singhal
authors.affiliation: Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Shirumalla
authors.affiliation: Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kanoje
authors.affiliation: Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Subbarayan
authors.affiliation: Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Ravisankar
authors.initials: R
authors.lastname: Rajerethinam
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Navin
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kanaujia
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Gyanesh
authors.initials: G
authors.lastname: Shukla
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Y K
authors.initials: YK
authors.lastname: Gupta
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Chandra K
authors.initials: CK
authors.lastname: Katiyar
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Bhatnagar
authors.affiliation: Department of Microbiology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India.
authors.forename: Dilip J
authors.initials: DJ
authors.lastname: Upadhyay
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Sathyamangalam
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Navin
authors.initials: N
authors.lastname: Khanna
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001681:Biological Assay; D002460:Cell Line; D031606:Cissampelos / Q000737:chemistry*; D003715:Dengue / Q000188:drug therapy* / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D007194:India; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D065288:Serogroup; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D010936:Plant Extracts