Solid and liquid state characterization of tetrahydrocurcumin using XRPD, FT-IR, DSC, TGA, LC-MS, GC-MS, and NMR and its biological activities

• Published in: Journal of pharmaceutical analysis Vol. 10; no. 4; pp. 334 - 345
• Main Authors: Trivedi, Mahendra Kumar, Panda, Parthasarathi, Sethi, Kalyan Kumar, Gangwar, Mayank, Mondal, Sambhu Charan, Jana, Snehasis
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.08.2020; Xi'an Jiaotong University, Journal of Pharmaceutical Analysis; Trivedi Global Inc.,Henderson,89052,Nevada,USA%Trivedi Science Research Laboratory Pvt. Ltd.,Thane,(W)-400604,Maharashtra,India; Xi'an Jiaotong University; Elsevier
• Subjects: Anti-inflammatory; Antioxidant; Antioxidants; Catalase; Cell lines; Cell viability; Chemicals; Chromatography; Curcumin; Cytokines; Enzymes; Free radicals; Gas chromatography; Hydrogen bonds; Hydrogen peroxide; Impurities; Inflammation; Interleukin 1; Keto-enol tautomer; Liquid chromatography; Liquid chromatography-mass spectrometry; Macrophage inflammatory protein 1; Macrophages; Mass spectrometry; Mass spectroscopy; Metabolites; Neuroprotection; NMR; Nuclear magnetic resonance; Original; Oxidants; Oxidative stress; Phagocytosis; Physicochemical properties; Scientific imaging; Sensors; Spectroscopic and thermal analysis; Splenocytes; Temperature; Tetrahydrocurcumin; Tumor necrosis factor-α; United States > US; India; Spectroscopic and thermal analysis; Antioxidant; Anti-inflammatory; Liquid chromatography-mass spectrometry; Tetrahydrocurcumin; Keto-enol tautomer
• ISSN: 2095-1779; 2214-0883; 2214-0883
• DOI: 10.1016/j.jpha.2020.02.005

Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin (CUR), an ancient bioactive natural polyphenolic compound. This research article describes both the solid and liquid state characterization of THC using advanced spectroscopic and thermo-analytical techniques. Anti-inflammatory, anti-oxidant, and neuroprotective activities of THC were investigated using in vitro cell lines. Liquid chromatography-mass spectrometry analysis revealed that our sample comprised 95.15% THC, 0.51% tetrahydrodemethoxycurcumin (THDC), 3.40% hexahydrocurcumin, and 0.94% octahydrocurcumin. Gas chromatography-mass spectrometry analysis indicated the presence of 96.68% THC and 3.32% THDC. THC in solution existed as keto-enol tautomers in three different forms at different retention time, but the enol form was found to be dominant, which was also supported by nuclear magnetic resonance analysis. THC was thermally stable up to 335.55 °C. THC exhibited more suppression of cytokines (TNF-α, IL-1β, and MIP-1α) than CUR in a concentration-dependent manner in mouse splenocytes, while NK-cell and phagocytosis activity was increased in macrophages. THC showed a significant reduction of free radicals (LPO) along with improved antioxidant enzymes (SOD and catalase) and increased free radical scavenging activity against ABTS+ radicals in HepG2 cells. THC displayed higher protection capability than CUR from oxidative stress and neuronal damage by improving cell viability against H2O2 induced HepG2 cells and MPP+ induced SH-SY5Y cells, respectively, in a concentration-dependent manner. Thus, a variation of the biological activities of THC might rely on its keto-enol form and the presence of other THC analogs as impurities. The present study could be advantageous for further research on THC for better understanding its physicochemical properties and biological variation. [Display omitted] •Solid and liquid state characterization of THC using advanced analytical techniques.•THC existed in 3 different forms viz. one keto form, two enol forms in solution.•THC was found to be thermally more stable than curcumin.•THC exhibited significant suppression of proinflammatory cytokines, increased NK cells and phagocytosis activities.•THC showed higher total anti-oxidant activity and neuroprotective activity than curcumin.