Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng

Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti-cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The K_m and V_max values of CK were 84.20±21.92 μM and 0.28±0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63±10.48 μM and 0.45±0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03±5.04 μM and 0.68±0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC₅₀ values were 16.00 μM and 9.83 μM, and K_i values were 14.92 μM and 11.42μM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors.     

Identification of an enzymatic activity that hydrolyzes protein-bound ADP-ribose in skeletal muscle

An enzymatic activity present in high-speed supernatant fluids of rat skeletal muscle was found that catalyzes the release of ADP-ribose from ADP-ribosylated-modified lysozyme. The nature of the product was proved by chromatographic studies and proton nuclear magnetic resonance spectroscopy. The enzyme activity is stimulated by Mg2+, dithioerythritol, and flouride. These results and those published earlier (Soman, G., Mickelson, J.R., Louis, C.F., and Graves, D.J. (1984) Biochem. Biophys. Res. Commun. 120, 973-980) show that ADP-ribosylation is a reversible process in skeletal muscle.     

Drought mildly reduces plant dominance in a temperate prairie ecosystem across years

1. Shifts in dominance and species reordering can occur in response to global change. However, it is not clear how altered precipitation and disturbance regimes interact to affect species composition and dominance.
2. We explored community‐level diversity and compositional similarity responses, both across and within years, to a manipulated precipitation gradient and annual clipping in a mixed‐grass prairie in Oklahoma, USA. We imposed seven precipitation treatments (five water exclusion levels [?20%, ?40%, ?60%, ?80%, and ?100%], water addition [+50%], and control [0% change in precipitation]) year‐round from 2016 to 2018 using fixed interception shelters. These treatments were crossed with annual clipping to mimic hay harvest.
3. We found that community‐level responses were influenced by precipitation across time. For instance, plant evenness was enhanced by extreme drought treatments, while plant richness was marginally promoted under increased precipitation.
4. Clipping promoted species gain resulting in greater richness within each experimental year. Across years, clipping effects further reduced the precipitation effects on community‐level responses (richness and evenness) at both extreme drought and added precipitation treatments.
5. Synthesis: Our results highlight the importance of studying interactive drivers of change both within versus across time. For instance, clipping attenuated community‐level responses to a gradient in precipitation, suggesting that management could buffer community‐level responses to drought. However, precipitation effects were mild and likely to accentuate over time to produce further community change.

     

Geometric morphometric analysis of the effect of temperature on wing size and shape in Aedes albopictus

Wing geometry helps to identify mosquito species, even cryptic ones. On the other hand, temperature has a well‐known effect on insect metric properties. Can such effects blur the taxonomic signal embedded in the wing? Two strains of Aedes albopictus (laboratory and field strain) were examined under three different rearing temperatures (26, 30 and 33 °C) using landmark‐ and outline‐based morphometric approaches. The wings of each experimental line were compared with Aedes aegypti. Both approaches indicated similar associations between wing size and temperature. For the laboratory strain, the wing size significantly decreased as the temperature increased. For the field strain, the largest wings were observed at the intermediate temperature. The two morphometric approaches describing shape showed different sensibilities to temperature. For both strains and sexes, the landmark‐based approach disclosed significant wing shape changes with temperature changes. The outline‐based approach showed lesser effects, detecting significant changes only in laboratory females and in field males. Despite the size and shape changes induced by temperature, the two strains of Ae. albopictus were always distinguished from Ae. aegypti. The present study confirms the lability of size. However, it also suggests that, despite environmentally‐induced variation, the architecture of the wing still provides a strong taxonomic signal.