PMID- 28196487 OWN - NLM STAT- MEDLINE DCOM- 20170223 LR - 20191210 IS - 1472-6882 (Electronic) IS - 1472-6882 (Linking) VI - 17 IP - 1 DP - 2017 Feb 14 TI - Anti-HSV-2 activity of Terminalia chebula Retz extract and its constituents, chebulagic and chebulinic acids. PG - 110 LID - 10.1186/s12906-017-1620-8 [doi] LID - 110 AB - BACKGROUND: Development of new and effective therapeutics for sexually transmitted herpes simplex virus-2 (HSV-2) infection is important from public health perspective. With an aim to identify natural products from medicinal plants, in the present study, the potential of Terminalia chebula Retz was investigated for its activity against HSV-2. METHODS: Fruits of Terminalia chebula Retz were used to prepare 50% ethanolic extract. In addition, chebulagic acid and chebulinic acid both purified from T. chebula were also used. The extract as well as purified compounds were first used to determine their in vitro cytotoxicity on Vero cells by MTT assay. T. chebula extract, chebulagic acid, chebulinic acid along with acyclovir were subsequently assessed for direct anti-viral activity, and their ability to inhibit attachment and penetration of HSV-2 to the Vero cells. In addition, their anti-HSV-2 activity was also determined by in vitro post-infection plaque reduction assay. RESULTS: Cytotoxicity assay using Vero cells revealed CC(50) = 409.71 +/- 47.70 mug/ml for the extract whereas chebulagic acid and chebulinic acid showed more than 95% cell viability up to 200 mug/ml. The extract from T. chebula (IC(50) = 0.01 +/- 0.0002 mug/ml), chebulagic (IC(50) = 1.41 +/- 0.51 mug/ml) and chebulinic acids (IC(50) = 0.06 +/- 0.002 mug/ml) showed dose dependent potent in vitro direct anti-viral activity against HSV-2. These also effectively prevented the attachment as well as penetration of the HSV-2 to Vero cells. In comparison, acyclovir showed poor direct anti-viral activity and failed to significantly (p > 0.05) prevent the attachment as well as penetration of HSV-2 to Vero cells when tested upto 50 mug/ml. However, in post-infection plaque reduction assay, T. chebula extract, chebulagic and chebulinic acids showed IC(50) values of 50.06 +/- 6.12, 31.84 +/- 2.64, and 8.69 +/- 2.09 mug/ml, respectively, which were much lower than acyclovir (71.80 +/- 19.95 ng/ml). CONCLUSIONS: The results presented herein suggest that T. chebula extract, chebulagic and chebulinic acids have higher direct antiviral activity against HSV-2 and efficacy to inhibit virus attachment and penetration to the host cells as compared to acyclovir. However, acyclovir is more potent to inhibit post-infection virus replication. Hence, T. chebula may be a useful candidate for developing alternative therapy for prevention of sexually transmitted HSV-2 infection. ᅟ. FAU - Kesharwani, Ajay AU - Kesharwani A AD - Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India. AD - Present Address: Anatomy and Cell Biology, Medical Faculty, Saarland University, Homburg, Saar, Germany. FAU - Polachira, Suja Kizhiyedath AU - Polachira SK AD - Corporate R & D Centre, HLL Lifecare Limited, Akkulum, Thiruvananthapuram, Kerala, 695 017, India. FAU - Nair, Reshmi AU - Nair R AD - Corporate R & D Centre, HLL Lifecare Limited, Akkulum, Thiruvananthapuram, Kerala, 695 017, India. FAU - Agarwal, Aakanksha AU - Agarwal A AD - Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India. FAU - Mishra, Nripendra Nath AU - Mishra NN AD - Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India. FAU - Gupta, Satish Kumar AU - Gupta SK AUID- ORCID: 0000-0003-3717-0436 AD - Reproductive Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110 067, India. skgupta@nii.ac.in. LA - eng PT - Journal Article DEP - 20170214 PL - England TA - BMC Complement Altern Med JT - BMC complementary and alternative medicine JID - 101088661 RN - 0 (Antiviral Agents) RN - 0 (Benzopyrans) RN - 0 (Glucosides) RN - 0 (Hydrolyzable Tannins) RN - 0 (Plant Extracts) RN - 18942-26-2 (chebulinic acid) RN - 23094-71-5 (chebulagic acid) RN - X4HES1O11F (Acyclovir) SB - IM MH - Acyclovir/pharmacology/therapeutic use MH - Animals MH - Antiviral Agents/*pharmacology/therapeutic use MH - Benzopyrans/*pharmacology/therapeutic use MH - Chlorocebus aethiops MH - Fruit MH - Glucosides/*pharmacology/therapeutic use MH - Herpes Simplex/drug therapy/*virology MH - Herpesvirus 2, Human/*drug effects MH - Hydrolyzable Tannins/*pharmacology/therapeutic use MH - Inhibitory Concentration 50 MH - Phytotherapy MH - Plant Extracts/*pharmacology/therapeutic use MH - Terminalia/*chemistry MH - Vero Cells MH - Virus Attachment/drug effects MH - Virus Replication/drug effects PMC - PMC5310005 OTO - NOTNLM OT - Anti-HSV-2 activity OT - Attachment assay OT - Penetration assay OT - Post-infection plaque reduction assay OT - Terminalia chebula EDAT- 2017/02/16 06:00 MHDA- 2017/02/24 06:00 PMCR- 2017/02/14 CRDT- 2017/02/16 06:00 PHST- 2016/06/24 00:00 [received] PHST- 2017/02/02 00:00 [accepted] PHST- 2017/02/16 06:00 [entrez] PHST- 2017/02/16 06:00 [pubmed] PHST- 2017/02/24 06:00 [medline] PHST- 2017/02/14 00:00 [pmc-release] AID - 10.1186/s12906-017-1620-8 [pii] AID - 1620 [pii] AID - 10.1186/s12906-017-1620-8 [doi] PST - epublish SO - BMC Complement Altern Med. 2017 Feb 14;17(1):110. doi: 10.1186/s12906-017-1620-8.