Intestinal absorption mechanism of rotundic acid: Involvement of P-gp and OATP2B1.

Ethnopharmacological Relevance: Ilicis Rotundae Cortex (IRC), the dried barks of Ilex rotunda Thunb. (Aquifoliaceae), has been used for the prevention or treatment of colds, tonsillitis, dysentery, and gastrointestinal diseases in folk medicine due to its antibacterial and anti-inflammatory effects. However, there is no report about the intestinal absorption of major compounds that support traditional usage.

Influence of verapamil on the pharmacokinetics of rotundic acid in rats and its potential mechanism.

Context: Rotundic acid (RA), a plant-derived pentacyclic triterpene acid, has been reported to possess extensive pharmacological activities. The poor bioavailability limits its further development and potential clinic application.

Objective: To clarify the potential mechanism for poor oral bioavailability.

Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription.

Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising (CYH) and (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3.

Effects of liquorice on pharmacokinetics of aconitine in rats.

Aconite alkaloids are the main bioactive ingredients existing in , for instance aconitine (AC), which exhibit potent analgesic, antirheumatic and other pharmacological effects. In this study, effects of long-term treatment with liquorice on pharmacokinetics of AC in rats were investigated. Pharmacokinetics of AC after oral administration of AC at 1.

Potential detoxification effect of active ingredients in liquorice by upregulating efflux transporter.

Background: As one of most widely used herbal medicine, liquorice exhibits diverse pharmacological activities, for instance, analgesic, antitussive, antiarrhythmic, anti-inflammatory, and immune regulation. Additionally, detoxification effects were observed in combination of liquorice with other herbal drugs. The mechanism of detoxification of liquorice has been extensively investigated through material basis and interference with CYPs though, investigations of its effect on transporters were very limited, according to the literature.

The effect of polymorphism of uric acid transporters on uric acid transport.

The abnormal metabolism of uric acid results in many disease such as chronic kidney disease, hyperuricemia, nephrolithiasis, gout, hypertension, vascular disease and so on. Serum uric acid levels are maintained by the balance between production and elimination. There are many factors that maintain the balance of serum uric acid.

[The in vitro inhibition and induction of cytochrome P450 activities by bentysrepinine: a novel candidate of anti-hepatitis B virus drug].

Bentysrepinine (Y101), a derivative of phenyalanine dipeptide, has a novel mechanism in the treatment of hepatitis B virus (HBV) infection with a good anti-HBV effect. In the present study, a fluorometric-based high throughput method using cytochrome P450 (CYP) screening kit was adopted to evaluate in vitro inhibition potential of Y101 on CYP isoenzymes by calculating remaining enzyme activities and inhibitory potential (IC(50) values) using the determined values of fluorescence intensity. The result showed that Y101 exhibited little activity in the inhibition of CYP1A2, CYP3A4, CYP2C9, CYP2C19 and CYP2D6 (IC(50) > 100 μmol·L(-1)).

[The in vitro transport mechanism of bentysrepinine: a novel anti-hepatitis B virus drug candidate].

Bentysrepinine (Y101), a derivative of phenylalanine dipeptide, is a novel drug candidate for the treatment of hepatitis B virus (HBV) infection. Our previous preclinical pharmacokinetic study showed that its in vivo absorption and distribution characteristics were probably related to transmembrane transport after Y101 was administered intragastically in rats. In this study, Caco-2 and MDCK-MDR1 cell models were used to investigate interactions between Y101 and P-gp through the apparent permeation coefficient (P(app)) and efflux ratio (RE); the results showed that Y101 was a substrate of P-gp.

The Targeted-liposome Delivery System of Antitumor Drugs.

The liposome delivery system has been intensively explored as novel drug delivery system (DDS) for antitumor drugs, due to its safety, selective cytotoxicity, long circulation and slow elimination in blood, which is favorable for cancer therapy. The liposome-based chemotherapeutics are used to treat a variety of cancers to enhance the therapeutic index of antitumor drugs. Here, the author reviewed the important targets for cancer therapy and the pharmacokinetic behavior of liposomal drugs in vivo, as well as the application of the targeting liposomal system in cancer therapy.

Aspartate-modified doxorubicin on its N-terminal increases drug accumulation in LAT1-overexpressing tumors.

L-type amino acid transporter 1 (LAT1), overexpressed on the membrane of various tumor cells, is a potential target for tumor-targeting therapy. This study aimed to develop a LAT1-mediated chemotherapeutic agent. We screened doxorubicin modified by seven different large neutral amino acids.

[Induction, purification and antifungal activity of beta-1, 3-glucanase from wheat leaves].

Treatment with mercuric chloride (0.01%), salicylic acid (10.0 mg/mL) or riboflavin (1 mmol/L) induced the beta-1, 3-glucanase activity in all the three wheat varieties i.

catena-Poly[[di-mu-chloro-bis[(triphenylphosphine)silver(I)]]-mu-2-aminopyrimidine-kappa 2N1:N3].

In the title supramolecular complex, [Ag(2)Cl(2)(C(4)H(5)N(3))(C(18)H(15)P)(2)](n), a one-dimensional chain is formed by dimeric [Ag(2)Cl(2)(PPh(3))(2)] units bridged by 2-aminopyrimidine moieties. The Ag atoms are four-coordinate, with an AgCl(2)NP core. A crystallographic inversion centre is located in the centre of the Ag(2)Cl(2) chelate ring, while the crystallographic twofold axis bisects the 2-aminopyrimidine ligand.