Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch or starch derivatives. They contain six (αCD), seven (βCD), eight (γCD), or more glucopyranose monomers linked via α-1,4-glycosidic bonds. CDs have a truncated cone shape with a hydrophilic outer wall and a less hydrophilic inner wall, the latter forming a more apolar internal cavity. Because of this special architecture, CDs are soluble in water and can simultaneously host lipophilic guest molecules. The major advantage of inclusion into CDs is increased aqueous solubility of such lipophilic substances. Accordingly, we present studies where the complexation of natural compounds such as propolis and dietary plant bioactives (e.g., tocotrienol, pentacyclic triterpenoids, curcumin) with γCD resulted in improved stability, bioavailability, and bioactivity in various laboratory model organisms and in humans. We also address safety aspects that may arise from increased bioavailability of plant extracts or natural compounds owing to CD complexation. When orally administered, α- and βCD—which are inert to intestinal digestion—are fermented by the human intestinal flora, while γCD is almost completely degraded to glucose units by α-amylase. Hence, recent reports indicate that empty γCD supplementation exhibits metabolic activity on its own, which may provide opportunities for new applications.

Kuding tea (KT) is a bitter-tasting herbal tea that has been commonly used in traditional Chinese medicine (TCM). The large-leaved Ku-Ding-Cha (Aquifoliaceae) is composed of its representative species Ilex latifolia Thunb and Ilex kudingcha C.J. Tseng. Because of its potential lipid-lowering, body weight-reducing and blood-glucose-lowering properties, KT has increasingly been recognised for its importance over the past several decades. KT is no longer used only as a beverage, and various extraction methods have been applied to obtain aqueous and ethanolic KT extracts (KTE) or their fractions, which could potentially be used as dietary supplements. The major bioactive components of KT are triterpene saponins and polyphenols, but the composition of KT differs substantially between and among the different KT species. This in turn might affect the physiological effects of KT. KT exhibits antiobesity properties, possibly partly by affecting the intestinal microbiota. In addition, KT may mediate putative antioxidative, anti-inflammatory and anticancer activities. However, there is evidence that high KTE supplementation can adversely affect liver metabolism. The physiological relevance of KT in humans remains rather unclear since the potential health benefits of KT and its constituents reviewed here are mainly derived on the basis of in vitro and animal studies.

Kuding tea (KT) is a traditional Chinese beverage rich in plant bioactives that may exhibit various health benefits. However, little is known about the safety of KT extract (KTE) when consumed long term at high doses as a dietary supplement. Therefore, in this study, we investigated aspects of the safety of KTE. Male C57BL/6 mice were fed a high-fat, high-fructose, Western-type diet (control) supplemented with either 12.88% γ-cyclodextrin (γCD), 7.12% KTE (comprising 0.15% ursolic acid, UA) encapsulated in 12.88% γCD (KTE-γCD), or 0.15% UA over a 6-week experimental period. The dietary treatments did not affect food intake, body weight or body composition. However, treatment with KTE-γCD, but not γCD and UA, increased liver weight and hepatic fat accumulation, which was accompanied by increased hepatic PPARγ and CD36 mRNA levels. KTE-γCD treatment elevated plasma cholesterol and CYP7A1 mRNA and protein levels compared to those in control mice. KTE-γCD substantially increased the mRNA and protein levels of hepatic CYP3A and GSTA1, which are central to the detoxification of drugs and xenobiotics. Furthermore, we observed a moderate elevation in hepatic CYP3A (5-fold change) and GSTA1 (1.7-fold change) mRNA levels in UA-fed mice. In vitro data collected in HepG2 cells indicated a dose-dependent increase in hepatic cytotoxicity in response to KTE treatment, which may have been partly mediated by UA. Overall, the present data may contribute to the safety assessment of KTE and suggest that KTE encapsulated in γCD affects liver fat storage and the hepatic phase I and phase II responses in mice.

Gamma-cyclodextrin (gamma CD) is a cyclic oligosaccharide consisting of eight alpha-(1,4)-linked glucopyranose subunits, which is often used in the food and pharmaceutical industries. However, little is known regarding the metabolic activity of "empty" gamma CD per se. Therefore, in the present study young C57BL/6 male mice received a control diet (CON) or an experimental diet that was supplemented with 12.88% gamma CD exchanged against corn starch. After 6 weeks of treatment, the voluntary wheel running activity was monitored and the muscle strength of mice was measured by employing Kondziela's inverted screen test and forelimb grip strength assay. The gamma CD-treated mice covered a significantly larger distance per night (CON 8.6 km, gamma CD 12.4 km) and were significantly longer active (CON 340 min, gamma CD 437 min). Moreover, gamma CD-treated mice significantly performed better at the inverted screen test indicated by an enhanced Kondziela score (CON 3.10, gamma CD 4.63). These data suggest that dietary gamma CD leads to an increased endurance. We also found a slightly anti-glycemic effect of gamma CD during oral glucose tolerance test. However, our mice from the gamma CD group exhibited no difference in terms of GLUT2 protein level in ileum tissue nor increased muscle glycogen storage. Furthermore, yCD exhibited no DPP-4 inhibitory activity in vitro. By analysing candidate muscle genes and proteins related to endurance and muscle performance we did not observe any differences in terms of Sirt1, Pgc1 alpha, Cpt1b, Mef2c, Myh1 and Myh2 gene expression levels as well as total oxidative phosphorylation (OXPHOS), mtTFA and GLUT4 protein expression levels in skeletal muscle in response to gamma CD. We could not fully establish the exact underlying molecular mechanisms of the fitness improvement by dietary gamma CD which warrants further investigations.