PMID- 31947962 OWN - NLM STAT- MEDLINE DCOM- 20200602 LR - 20200602 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 1 DP - 2020 Jan 4 TI - Curcumin Can Decrease Tissue Inflammation and the Severity of HSV-2 Infection in the Female Reproductive Mucosa. LID - 10.3390/ijms21010337 [doi] LID - 337 AB - Herpes Simplex Virus Type 2 (HSV-2) is one of the most prevalent sexually transmitted viruses and is a known risk factor for HIV acquisition in the Female Genital Tract (FGT). Previously, we found that curcumin can block HSV-2 infection and abrogate the production of inflammatory cytokines and chemokines by genital epithelial cells in vitro. In this study, we investigated whether curcumin, encapsulated in nanoparticles and delivered by various in vivo routes, could minimize inflammation and prevent or reduce HSV-2 infection in the FGT. Female mice were pre-treated with curcumin nanoparticles through oral, intraperitoneal and intravaginal routes, and then exposed intravaginally to the tissue inflammation stimulant CpG-oligodeoxynucleotide (ODN). Local intravaginal delivery of curcumin nanoparticles, but not intraperitoneal or oral delivery, reduced CpG-mediated inflammatory histopathology and decreased production of pro-inflammatory cytokines Interleukin (IL)-6, Tumor Necrosis Factor Alpha (TNF-alpha) and Monocyte Chemoattractant Protein-1 (MCP-1) in the FGT. However, curcumin nanoparticles did not demonstrate anti-viral activity nor reduce tissue pathology when administered prior to intravaginal HSV-2 infection. In an alternative approach, intravaginal pre-treatment with crude curcumin or solid dispersion formulations of curcumin demonstrated increased survival and delayed pathology following HSV-2 infection. Our results suggest that curcumin nanoparticle delivery in the vaginal tract could reduce local tissue inflammation. The anti-inflammatory properties of curcumin delivered to the vaginal tract could potentially reduce the severity of HSV-2 infection and decrease the risk of HIV acquisition in the FGT of women. FAU - Vitali, Danielle AU - Vitali D AD - Department of Pathology & Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada. FAU - Bagri, Puja AU - Bagri P AD - Department of Pathology & Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada. FAU - Wessels, Jocelyn M AU - Wessels JM AD - Department of Pathology & Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada. FAU - Arora, Meenakshi AU - Arora M AD - Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USA. FAU - Ganugula, Raghu AU - Ganugula R AD - Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USA. FAU - Parikh, Ankit AU - Parikh A AD - School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5000, Australia. FAU - Mandur, Talveer AU - Mandur T AD - Department of Pathology & Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada. FAU - Felker, Allison AU - Felker A AD - Department of Pathology & Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada. FAU - Garg, Sanjay AU - Garg S AUID- ORCID: 0000-0001-7253-2629 AD - School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5000, Australia. FAU - Kumar, M N V Ravi AU - Kumar MNVR AD - Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University, College Station, TX 77843, USA. FAU - Kaushic, Charu AU - Kaushic C AUID- ORCID: 0000-0002-7088-2569 AD - Department of Pathology & Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada. LA - eng GR - 126019/CAPMC/CIHR/Canada GR - 138657/CAPMC/CIHR/Canada GR - R01EY028169/NH/NIH HHS/United States PT - Journal Article DEP - 20200104 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (CPG-oligonucleotide) RN - 0 (Chemokine CCL2) RN - 0 (Drug Carriers) RN - 0 (Interleukin-6) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Tumor Necrosis Factor-alpha) RN - IT942ZTH98 (Curcumin) SB - IM MH - Administration, Intravaginal MH - Animals MH - Chemokine CCL2/metabolism MH - Curcumin/chemistry/*pharmacology/therapeutic use MH - Drug Carriers/chemistry MH - Epithelial Cells/cytology/metabolism/virology MH - Female MH - Genitalia, Female/cytology/metabolism MH - Herpes Simplex/*pathology/veterinary/virology MH - Herpesvirus 2, Human/physiology MH - Humans MH - Inflammation/chemically induced/*pathology/prevention & control MH - Interleukin-6/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Nanoparticles/chemistry MH - Oligodeoxyribonucleotides/toxicity MH - Severity of Illness Index MH - Tumor Necrosis Factor-alpha/metabolism MH - Vagina/metabolism/pathology PMC - PMC6982333 OTO - NOTNLM OT - CpG OT - HSV-2 OT - curcumin OT - cytokine OT - herpes OT - inflammation OT - nanoparticles OT - pathology COIS- The authors declare no conflict of interest. EDAT- 2020/01/18 06:00 MHDA- 2020/06/03 06:00 PMCR- 2020/01/01 CRDT- 2020/01/18 06:00 PHST- 2019/12/02 00:00 [received] PHST- 2019/12/24 00:00 [revised] PHST- 2019/12/31 00:00 [accepted] PHST- 2020/01/18 06:00 [entrez] PHST- 2020/01/18 06:00 [pubmed] PHST- 2020/06/03 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - ijms21010337 [pii] AID - ijms-21-00337 [pii] AID - 10.3390/ijms21010337 [doi] PST - epublish SO - Int J Mol Sci. 2020 Jan 4;21(1):337. doi: 10.3390/ijms21010337.