PMID- 29730557 OWN - NLM STAT- MEDLINE DCOM- 20181012 LR - 20181012 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 60 DP - 2018 Jul TI - Immunomodulatory effects of Tinospora crispa extract and its major compounds on the immune functions of RAW 264.7 macrophages. PG - 141-151 LID - S1567-5769(18)30197-8 [pii] LID - 10.1016/j.intimp.2018.04.046 [doi] AB - The in vivo immunomodulatory activities of Tinospora crispa have been reported but its molecular mechanisms underlying its immunomodulatory properties remains obscure and the active constituents contributing to the activities have not been identified. The present study was aimed to investigate the immunomodulatory effects of T. crispa extract (TCE) and its chemical constituents on RAW 264.7 macrophages. Six known compounds including magnoflorine and syringin were isolated by various chromatographic techniques from TCE and their structures were determined spectroscopically. A validated HPLC method was used to quantify magnoflorine and syringin in the extract. The immunomodulatory effects of TCE and its isolated compounds on chemotaxis, phagocytosis, production of inflammatory mediators including reactive oxygen species (ROS), nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines which include tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and monocyte chemoattractant protein-1 (MCP-1) on macrophages were assessed. TCE increased the chemotaxis and phagocytic activity of macrophages and significantly enhanced the production of ROS, NO and pro-inflammatory cytokines. All alkaloids isolated, specifically magnoflorine showed remarkable inducing effects on the chemotaxis, phagocytic activity, ROS and NO productions and the secretions of IL-1beta, TNF-alpha, IL6, PGE2 and MCP-1. In contrast, syringin potently reduced the chemotaxis, phagocytic activity, ROS and NO productions and secretions of IL-1beta, TNF-alpha, IL6, PGE2 and MCP-1. TCE showed strong immunostimulant effects on various components of the immune system and these activities were possibly contributed mainly by the alkaloids specifically magnoflorine. TCE has potential to be developed as an effective natural immunostimulant for improvement of immune-related disorders. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Ahmad, Waqas AU - Ahmad W AD - School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11700 Gelugor, Penang, Malaysia. FAU - Jantan, Ibrahim AU - Jantan I AD - Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. Electronic address: profibj@gmail.com. FAU - Kumolosasi, Endang AU - Kumolosasi E AD - Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. FAU - Haque, Md Areeful AU - Haque MA AD - Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. FAU - Bukhari, Syed Nasir Abbas AU - Bukhari SNA AD - Pharmaceutical Chemistry Department, College of Pharmacy, Jouf University, Aljouf, Sakaka 2014, Saudi Arabia. LA - eng PT - Journal Article DEP - 20180503 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Cytokines) RN - 0 (Immunologic Factors) RN - 0 (Phytochemicals) RN - 0 (Plant Extracts) RN - 0 (Reactive Oxygen Species) RN - 31C4KY9ESH (Nitric Oxide) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Animals MH - Cell Movement/drug effects MH - Cell Survival/drug effects MH - Cytokines/metabolism MH - Dinoprostone/metabolism MH - Immunologic Factors/analysis/*pharmacology MH - Macrophages/*drug effects/metabolism/physiology MH - Mice MH - Nitric Oxide/metabolism MH - Phagocytosis/drug effects MH - Phytochemicals/analysis/pharmacology MH - Plant Extracts/analysis/*pharmacology MH - Plant Stems MH - RAW 264.7 Cells MH - Reactive Oxygen Species/metabolism MH - *Tinospora OTO - NOTNLM OT - Immunostimulant effects OT - Magnoflorine OT - Phagocytosis OT - Pro-inflammatory cytokines OT - RAW 264.7 cells OT - Tinospora crispa EDAT- 2018/05/08 06:00 MHDA- 2018/10/13 06:00 CRDT- 2018/05/07 06:00 PHST- 2018/02/19 00:00 [received] PHST- 2018/04/25 00:00 [revised] PHST- 2018/04/27 00:00 [accepted] PHST- 2018/05/08 06:00 [pubmed] PHST- 2018/10/13 06:00 [medline] PHST- 2018/05/07 06:00 [entrez] AID - S1567-5769(18)30197-8 [pii] AID - 10.1016/j.intimp.2018.04.046 [doi] PST - ppublish SO - Int Immunopharmacol. 2018 Jul;60:141-151. doi: 10.1016/j.intimp.2018.04.046. Epub 2018 May 3.