Solid and liquid state characterization of tetrahydrocurcumin using XRPD, FT-IR, DSC, TGA, LC-MS, GC-MS, and NMR and its biological activities / 药物分析学报

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 charac-terization 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 ℃. 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 scav-enging 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.

Comparative Effects of Curcumin and Tetrahydrocurcumin on Dextran Sulfate Sodium-induced Colitis and Inflammatory Signaling in Mice

BACKGROUND: Curcumin, a yellow ingredient of turmeric (Curcuma longa Linn, Zingiberaceae), has long been used in traditional folk medicine in the management of inflammatory disorders. Although curcumin has been reported to inhibit experimentally-induced colitis and carcinogenesis, the underlying molecular mechanisms remain largely unresolved. METHODS: Murine colitis was induced by dextran sulfate sodium (DSS) which mimics inflammatory bowel disease. Curcumin or tetrahydrocurcumin was given orally (0.1 or 0.25 mmol/kg body weight daily) for 7 days before and together with DSS administration (3% in tap water). Collected colon tissue was used for histologic and biochemical analyses. RESULTS: Administration of curcumin significantly attenuated the severity of DSS-induced colitis and the activation of NF-κB and STAT3 as well as expression of COX-2 and inducible nitric oxide synthase. In contrast to curcumin, its non-electrophilic analogue, tetrahydrocurcumin has much weaker inhibitory effects. CONCLUSIONS: Intragastric administration of curcumin inhibited the experimentally induced murine colitis, which was associated with inhibition of pro-inflammatory signaling mediated by NF-κB and STAT3.

Effect tetrahydrocurcumin-solid dispersion on KK-Ay mice / 中国药学杂志

OBJECTIVE: To study the effects tetrahydrocurcumin-solid dispersion on KK-AY mice. METHODS: C 57/6 J mice were used as controls, KK-Ay mice were randomly divided into model group, tetrahydrocurcumin-solid dispersion groups(100, 50, 15 mg · kg-1) and rosiglitazone group(2.67 mg · kg-1), gavage for 35 d, mouse weight, fasting blood glucose, oral glucose tolerance, serum insulin and blood lipid indexes were detected. RESULTS: The weight mice tetrahydrocurcumin-solid dispersion group (100 mg · kg-1) on twenty-first days administration began to decrease, and maintained at a low level during the administration; tetrahydrocurcumin-solid dispersion in each dose group showed impaired fasting blood glucose lowering from the fourteenth day after the administration began, and maintained at a low level during the administration, tetrahydrocurcumin-solid dispersion in each dose group can decrease postprandial blood glucose and AUC value; tetrahydrocurcumin-solid dispersion in each dose group can decrease the value TC, LDL-C, increase the insulin sensitivity index, tetrahydrocurcumin-solid dispersion in each dose group glycosylated serum protein values were decreased, while only in the 100 mg · kg-1 group was statistical significant differences compared with the model group. CONCLUSION: Tetrahydrocurcumin-solid dispersion, which can effectively reduce the blood glucose levels KK-AY mice, and has good effect on glucose metabolism, lipid metabolism. The mechanism action may be related to the increase insulin sensitivity.

Scavenging potential of reactive oxygen species by Tetra-hydrocurcumin.

In this study, the scavenging response of tetrahydrocurcumin (THC) was evaluated by using series of in vitro models of chemicals compared with standard antioxidant Trolox and curcumin. The THC exhibited its radical scavenging effect in concentration dependent manner on super oxide, hydroxyl radicals, ferric ions, 1,1-diphenyl, 2-picryl hydrazyl (DPPH) and 2,2- azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS). The THC was also evaluated for its inhibitory response on membrane lipid peroxidation by thiobarbituric acid reactive substances (TBARS) using rat liver homogenate. The present study shows that THC is a good antioxidant compared to the standard antioxidant, Trolox. Although, THC is less active than curcumin in many models, the increased superoxide scavenging and decreased ability to reduce ferric ions offers interesting advantages over curcumin. The THC was also effective in preventing membrane lipid peroxidation induced by FeSO4/ascorbate in concentration dependent manner.

Downregulation of p-ERK1/2 and p-AKT expression by curcumin and tetrahydrocurcumin in hepatocellular carcinoma-induced tumors in nude mice.

Background: Curcumin (CUR) and tetrahydrocurcumin (THC) inhibits tumor angiogenesis. It is suggested that tumor progress may be related to the pathway of extracellular signal-regulated kinase 1/2 (ERK1/2) and serine/ threonine kinase AKT, but the mechanism remains unclear. Objective: Investigate the effects of CUR and THC on the expression of ERK1/2 and AKT in hepatocellula carcinoma (HepG2)-induced tumors in nude mice. Methods: The curcuminoid mixture was obtained from the rhizomes of Curcuma longa, which was subjected to silica gel column chromatography to afford CUR as the major constituent. THC was prepared by hydrogenation of curcumin with palladium on charcoal as a catalyst. HepG2-implanted nude mice model was used to study of angiogenesis and tumor progression. Expressions of phospho-ERK1/2 (p-ERK1/2) and phopho-AKT (p-AKT) in HepG2-implated tissue were measured by immunohistochemistry. Tumor area, area of expression and expression ratio of pERK1/2 and p-AKT were determined. Results: Increases in p-ERK1/2 and p-AKT expression in HepG2 group was related to changes in tumor growth in control, CUR, and THC groups. THC-treatment could attenuate the p-ERK1/2, p-AKT expression, tumor area, and ratio of expression in HepG2-implanted nude mice significantly, compared to CUR-treatment. Conclusion: HepG2-induced tumor progression may be inhibited by THC in part through the inhibition of mitogen-activated protein kinase (MEK)/ERK and phosphoinositide 3-kinase (PI3K)/AKT.