Phytochemical Characterization and Systemic Exposure of Bioactive Metabolites of the Aqueous Extracts of Ficus thonningii Blume (Moraceae) on Albino Wistar Rats

Ficus thonningii (Blume) is considered as a herbal plant with well documented biological activity in the management of several diseases in the tropics. However, there is a gap of information on its safety and proof of efficacy in evidence-based medicine. The objective of this study was to characterize the bioactive metabolites of the hydro-ethanolic extract of the stem bark of Ficus. thonningii and in vivo evaluation of the systemic exposure of the bioactive metabolite. Phytochemical screening was done using standard extraction techniques, and test according to methods adopted from Sofowora and collaborators. Quantitative analysis was done using spectrophotometer of plant extract with different reference standards. Analysis of the animals' plasma following administration of the extract was used to investigate systemic exposure to confirmed the presence of absence of metabolites in systemic circulation. This work shows that F. thonningii (Blume) stem bark hydro-ethanolic extract contains polyphenols, saponins, alkaloids, flavonoids, catechic tannins, gallic tannins, coumarins, quinones, phlobatannins. This study shows that the hydro-ethanolic extract of F. thonningii contains total phenolic content of 192,27 ± 3,40 mgEQ/MS g gallic acid and total flavonoid content of 103,59 ± 15,72 mgEQ/MS quercetin. This study shows that the secondary metabolites in the hydro-ethanolic extract of the stem bark of F. thonningii (Blume) were not detected in plasma and not bioavailable.

Research progress on the interactions between gut bacterial β-glucuronidases and Chinese herbal medicines / 药学学报

In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.

Exantema intertriginoso y flexural simétrico por fármacos: presentación de un caso / Symmetrical drug-related intertriginous and flexural exanthema: a case report

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a benign, self-limited, immune-mediated, symmetric erythematous rash involving the buttocks and other intertriginous/flexural areas, observed after systemic exposure to a drug in an individual with or without prior sensitization. We present a 70-year old patient, who presented SDRIFE after the administration of piperacillin-tazobactam which improved rapidly after its suspension.

El exantema intertriginoso y flexural simétrico relacionado con fármacos (SDRIFE, por su sigla en inglés) es una erupción eritematosa simétrica, inmunomediada, benigna y autolimitada, que compromete glúteos y otras áreas intertriginosas, flexurales o ambas, y que se observa luego de la exposición sistémica a un fármaco en un individuo con sensibilización previa o sin ella. Se comenta el caso clínico de un paciente de 70 años de edad, que presentó SDRIFE posterior a la administración de piperacilina-tazobactam y que mejoró rápidamente luego de su suspensión.

Multi-compound pharmacokinetic research on Chinese herbal medicines: identifying potentially therapeutic compounds and characterizing their disposition and pharmacokinetics / 药学学报

Chinese traditional medicine has provided, since ancient times, a basis for health care and medicine to the Chinese nation and for China's national stability. Identification of the constituents responsible for therapeutic and undesired effects of Chinese herbal medicines is a type of key research facilitating the modernization of these medicines. For a complex Chinese herbal medicine, multi-compound pharmacokinetic research is a useful approach to identifying its constituents that are bioavailable (in their unchanged and/or metabolized forms) at loci responsible for the medicine's therapeutic action and to characterizing the compounds' disposition and pharmacokinetics related to the action. In addition, such pharmacokinetic research is also useful for identifying herbal compounds associated with the medicine's adverse effects and drug-drug interaction potential. Over the past decade, great advances have been achieved in the theory, methodology, associated techniques, and their application of such multi-compound pharmacokinetic research, which has become an emerging field in pharmacokinetics. In this perspective, we elaborate on the methodology, technical requirements, and key analytical techniques of multi-compound pharmacokinetic research on Chinese herbal medicines, describe research examples regarding investigation of pharmacokinetics and disposition of a class of bioactive herbal constituents (ginsenosides of Panax notoginseng root) and pharmacokinetics-based identification of potential therapeutic compounds from a dosed Chinese herbal medicine (LianhuaQingwen capsule), and discuss follow-up development for the multi-compound pharmacokinetic research.

Potential health benefits of resveratrol: a pharmacokinetics-caused conundrum / 中国临床药理学与治疗学

Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) was first identified from white hellebore (Veratrum grandiflorum) root and began to attract interest when its presence in red wine and cardiovascular activities were reported, leading to speculation of its contribution to the 'French paradox'. Besides the cardiovascular protection, potential health benefits of resveratrol include calorie restriction-like effects, cancer prevention and adjunctive therapy, and neuroprotection. In order to achieve translational applications of these potential benefits, pharmacokinetic research was performed for plasma pharmacokinetics and related disposition of orally dosed resveratrol. This paper summarizes the known human pharmacokinetic characteristics of resveratrol after oral administration and various attempts to improve its systemic exposure level from the perspectives of systemic exposure and in vivo process. However, available pharmacokinetic data of resveratrol has raised conundrums that limit translating potential benefits to clinics: (1) differences between the unchanged resveratrol used in bioactivity studies and its major circulating forms (i.e., metabolites) after dosing; (2) resveratrol's test concentrations used to exert in vitro bioactivities related to the benefits significantly higher than the compound's clinically achievable concentrations; (3) resveratrol's concentrations achievable (estimated from the pharmacokinetics) from doses used to produce in vivo efficacy significantly lower than the effective concentrations found in studies of related action mechanism (suggesting unreliability of test mechanism). In the last part of this review, we provide recommendations for future pharmacokinetic investigations of resveratrol, including a more systematic investigation of systemic exposure to resveratrol metabolites, their access to in vivo loci responsible for the benefits, and their disposition in target cells; an investigation of colon-luminal exposure to resveratrol and its metabolites for accessing colonic microbiota; and a multi-compound pharmacokinetic investigation of red wine.