Jinhong Kang

Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in the treatment of asthma and atopic dermatitis. However, baicalein is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which limits its preclinical and clinical use. In this study, we designed, synthesized, and evaluated baicalein prodrugs that protect the OH group at the 7-position of the A ring in baicalein with the amino acid carbamate functional group. Comprehensive in vitro and in vivo studies identified compound 2 as a baicalein prodrug candidate that improved the plasma exposure of baicalein in mouse animal studies. Our results demonstrated that this prodrug approach could be further adopted to discover oral baicalein prodrugs.

(1S,5R)-4-((E)-3,4-dihydroxy-5-methoxystryryl)-6,6-dimethylbicylco[3.1.1]hept-3-en-2-one (SP-8356) is a novel (1S)-(−)-verbenone derivative that is currently in preclinical development for the treatment of ischemic stroke and atherosclerosis. This report aimed at characterization of the metabolism and pharmacokinetic properties of SP-8356. Following intravenous dose in rats and dogs, plasma concentrations of SP-8356 declined rapidly with high clearance (CL) and short half-life; after oral administration in both species, its plasma levels were below the quantitation limit. Fourteen circulating metabolites, formed by mono-oxygenation, demethylation, glucuronidation, catechol O-methylation, sulfation and oxidation (bioactivation) followed by glutathione (GSH) conjugation, were tentatively identified in both species. Urinary excretion of SP-8356 appeared to be minimal in rats, compared to its metabolites. GSH conjugate of SP-8356 was also formed during incubation with rat liver S9 fraction consistent with oxidative bioactivation; this bioactivation was almost completely inhibited by the cofactors for glucuronidation, sulfation and methylation, indicating that it may be abolished by competing metabolic reactions in the body. The human pharmacokinetics of SP-8356 was predicted to be similar to that of the animals based on the current in vitro metabolic stability results. In summary, rapid phase II metabolism appears to be mainly responsible for its suboptimal pharmacokinetics, such as high CL and low oral absorption. Because of competing metabolic reactions, potential safety risks related to SP-8356 bioactivation may be low.

In the present study, we aimed to develop a novel fermented tea (NFT) product and to evaluate their in vitro antioxidant potential and chemical composition. We found that NFT contained a high level of total phenolic compounds (102.98 mg gallic acid equivalents/g extract) and exhibited diverse antioxidant activities, such as scavenging of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and hydroxyl radicals, as well as reducing power. The total catechins in NFT were comparable to those of Lipton black tea (LBT), but lower than those of Boseong green tea (BGT) or Tieguanyin oolong tea (TOT). Among all catechins tested, epigallocatechin (EGC) and epigallocatechin-3-O-gallate (EGCG) were the predominant compounds in NFT. In particular, the contents of total theaflavins (TFs), theaflavin (TF), theaflavin-3-gallate (TF3G), and theaflavin-3’-gallate (TF3’G) in NFT were significantly higher than that of BGT, TOT, or LBT. NFT had the highest level of total essential amino acid and γ-aminobutyric acid (GABA) compared with BGT, TOT and LBT. Furthermore, the sensory evaluation results showed that NFT had satisfactory color, aroma, taste, and overall acceptability scores. Our results highlight the potential usefulness of this novel fermented tea as a nutraceutical food/ingredient with special functional activities.