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A phytochemical investigation of the barks of Eucommia ulmoides Oliv. resulted in the isolation of 18 flavonoids (1-18). The new compound, eucommiaflavone (1) was structurally elucidated by various spectroscopic analyses. In particular, Mo2(OAc)4-induced circular dichroism (ICD) analysis was applied to determine the absolute configuration of 1. Furthermore, five flavonoids (4, 9, 11, 13, and 15) revealed significant in vitro hepatoprotective activity against D-galactosamine-induced cytotoxicity in human hepatoma HepG2 cells. [ABSTRACT FROM AUTHOR]

Due to the rapidly increasing global interest in the use of herbs, phytomedicines and other natural products as medical or complementary remedies, concerns about the clinical medication safety have drawn much attention worldwide. Particularly, many natural ingredients exhibit inhibitory effects on cytochrome P450 (CYP) enzymes, which are the most important Phase I metabolism enzymes in liver. CYP2C9 is one of the most abundant CYP enzymes and responsible for the metabolism of over 15% clinical drugs, including oral sulfonylurea hypoglycemics, nonsteroidal anti-inflammatory agents, selective cyclooxygenase-2 inhibitors, antiepileptics, angiotensin II receptor inhibitors and anticoagulants. Diclofenac (4'-hydroxylase) and tolbutamide (methylhydroxylation) are widely used as probe substrates for CYP2C9. To date, numerous natural products have been reported to have the capabilities of inhibiting the catalytic activity of CYP2C9 and further influencing the pharmacokinetic and pharmacodynamic behaviors of drugs that are mainly metabolized by CYP2C9, leading to potential herb-drug interactions. Moreover, some fatal adverse interactions may occur for drugs with a narrow therapeutic window when they are coadministered with a CYP2C9 inhibitor, especially irreversible inactivators. For the purpose of better understanding the interactions of natural products with CYP2C9, we comprehensively reviewed the characteristics of CYP2C9, the natural ingredients that inhibit CYP2C9, the related research approaches and strategies, the types of inhibition and the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Two new isoflavone glucosides, 3′-methoxyneopuerarin A (1) and 3′-methoxyneopuerarin B (2), together with nine known isoflavones including puerarin (3), neopuerarin A (4), neopuerarin B (5), daidzin (6), daidzein (7), 3′-methoxypuerarin (PG-3) (8), puerarin xyloside (9), mirificin (10), 3′-hydroxypuerarin (11) were isolated from the water extraction of the dried roots of Pueraria lobata (Willd.) Ohwi. Their structures were elucidated by the means of spectroscopic and chromatographic analysis methods. All compounds were evaluated for their hepatoprotective activity on HepG2 cells. All of them showed statistically significant hepatoprotective effect. [ABSTRACT FROM AUTHOR]

1.Corydaline, an isoquinoline alkaloid obtained from the rhizomes of Corydalis yanhusuo, exhibits anti-acetylcholinesterase, anti-angiogenic, anti-allergic and gastric-emptying activities. In this study, a rapid and reliable ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) method was developed and employed for the comprehensive study of the metabolites of corydaline in rats. 2.Altogether, 43 metabolites were identified in the plasma (11), bile (9), urine (34) and feces (21) of rats after oral administration of corydaline at a dose of 4.5mg/kg. 3.It was demonstrated that demethylation, hydroxylation, sulfation and glucuronidation were the major metabolic transformation pathways. Among these, two metabolites were identified as tetrahydropalmatine and isocorybulbine, and 33 phase I and phase II products were inferred to be new metabolites arising from the in vivo metabolism of corydaline. 4.Importantly, this research provides scientific and reliable support for full understanding of the metabolic profiles of corydaline and the results could help to elucidate its safety and efficacy. [ABSTRACT FROM AUTHOR]

1. Physalin A is a bioactive withanolide isolated from the natural plantPhysalis alkekengivar.franchetii(Solanaceae), a common traditional Chinese herbal medicine. This study aims to investigate the metabolites of physalin Ain vivo. 2. Two metabolites (M1andM2) were characterized as sulfonate metabolites in the feces obtained from rats treated with physalin A orally at a dose of 15 mg/kg/day for 3 days, by application of a UPLC-Q/TOF-MS method. Furthermore, formation of the two sulfonate metabolites was verified by chemical synthesis and NMR, including1H NMR,13C NMR and two-dimensional NMR. The structures ofM1andM2were identified to be 3α-sulfo-2,25β,27-trihydrophysalin A and 3α,27-disulfo-2,25α-dihydrophysalin A, respectively. 3. In summary, this study indicated that physalin A could be biotransformed to sulfonate metabolites with strong polarity, which contributed to the elimination of physalin A. A rare metabolic pathway has been revealed in this study. [ABSTRACT FROM AUTHOR]

Physalis pubescens L. has been used as a traditional folk medicine in China. Comprehensive studies aimed at identifying the bioactive constituents are still lacking. In the course of searching bioactive secondary metabolites from P. pubescens L., phytochemical investigation of the fruits of P. pubescens L. led to the isolation of one new eremophilane glycoside, 1β,3α-dihydroxy-7α-eremophila-911-dien-3-O-[α-L-arabinopyranosyl-(l→6)]-β-D-glucopyranoside (1), and six known glycosides (2–7). Their structures were established via extensive spectroscopic data including 1D and 2D NMR and HRESIMS. Cytotoxic effects against six human cancer cell lines (C4-2B, A375, A375-S2, 786-O, Caki-2, and ACHN) and one human normal hepatic cell line (L02) were evaluated and compounds 1 and 2 exhibited moderate cytotoxicity against C4-2B and A375 cell lines with IC50 values in the range of 6.78–28.3 μM. The study indicates that the fruits of P. pubescens L. have the potential to be used for drug discovery. [ABSTRACT FROM AUTHOR]

Thirteen phenones were obtained from the 70% ethanol extract of Paeonia suffruticosa Andrews. Their structures were determined on the basis of chemical methods and spectral data. Among them, compound 1 was identified as a new compound, and compounds 5 and 13 were obtained from genus Paeonia for the first time. The inhibitory effects of isolated compounds (1–12) on nitric oxide (NO) production in lipopolysaccharide-activated macrophages were evaluated, and NO production was suppressed significantly by compound 7. [ABSTRACT FROM AUTHOR]

Glycyrrhizin (GZ), the main active component of licorice, is a widely used therapeutic in the clinic. Depending on the disease, the treatment may involve a long course of high dose GZ. Another component of licorice, glycyrrhetinic acid (GA), is the main active metabolite of GZ and is thought to be responsible for the majority of the pharmacological properties of GZ. Therefore, GZ and GA are both used for therapeutic purposes. In addition, GZ and GA are also widely used to sweeten and flavor foods. Due to this widespread, multifaceted use of these substances, potential drug interactions with GZ and GA have recently gained attention. Along these lines, this review covers the known effects of GZ and GA on drug-metabolizing enzymes and efflux transporters. We conclude that both GZ and GA may have an effect on the activity of CYPs. For example, GZ may induce CYP3A activity through activation of PXR. Also, GZ and GA may affect glucuronidation in rats and humans. Furthermore, 18β-GA is a potent inhibitor of P-gp, while GZ and GA are inhibitors of MRP1, MRP2 and BCRP. The pharmacokinetics and pharmacodynamics of many medications may be altered when used concurrently with GZ or GA, which is also covered in this review. Overall, GZ, GA or related products should be taken with caution when taken with additional medications due to the possible drug interactions. [ABSTRACT FROM AUTHOR]

abstract 1. Paeonol, a major component of Paeonia suffruticosa Andrews, is used in clinical situations in China as a natural anti-inflammatory agent. The aim of the present study is to investigate the metabolism of paeonol in humans. 2. Six metabolites were isolated from human urine after oral administration of paeonol, and their structures were elucidated as resacetophenone (M1), resacetophenone-2-O-sulfate (M2), 2-hydroxy-4-methoxyacetophenone-5- O-sulfate(M3), 2-hydroxy-4-methoxyacetophenone-5-O-glucopyranuronoside (M4), 2-hydroxyacetophenone-4- O-glucopyranuronoside (M5) and 2,5-dihydroxy-4-methoxyacetophenone(M6) by a series of analyses involving mass spectrometry, 1H NMR, 13C NMR and NOESY spectra. 3. In addition, three more metabolites 2,4-dihydroxyacetophenone-5-O-sulfate (M7), paeonol-2-Oglucopyranuronoside (M8) and paeonol-2-O-sulfate (M9), were identified in human urine by using a UPLC/Q-TOF– MS/MS method. 4. This is the first study of paeonol metabolism in humans. Based on the identified metabolites, possible metabolic pathways of paeonol in humans are proposed. Paeonol is metabolized mainly by hydroxylation and demethylation to give the corresponding phase I metabolites, M1, M6 and 2,4,5-trihydroxyacetophenone, and which then underwent conjugation with glucuronic acid or sulfuric acid to form phase II metabolites, [ABSTRACT FROM AUTHOR]