Polygonum multiflorum Thunb. and its processed products have been used in China for centuries due to their multiple beneficial effects to human body. Currently, liver injuries caused by taking P. multiflorum have been reported worldwide, but the potential toxic components and possible mechanism that caused hepatotoxicity remain unclear. It is worth noting that the processing procedure could significantly decrease the toxicity of raw P. multiflorum and the processed products of P. multiflorum are considered to be relatively safe. However, the processing mechanism is still ambiguous, and there is the lack of a scientific approach to control the quality of P. multiflorum praeparata. This study is the first review that summarizes the recently advances (from 2007 to 2017) in the chemical analysis of P. multiflorum, and provides comprehensive information on the quantitative and qualitative analysis of P. multiflorum as well as its related species. In addition, the processing mechanism and quality evaluation of processed P. multiflorum are discussed. Moreover, the toxicity of P. multiflorum is analyzed from the perspectives of exploration of the proposed toxic ingredients, metabolite identification, metabolomics studies and exogenous contaminant determination. Furthermore, trends and perspectives for future research of this medicine are discussed.

The Wnt/β-catenin signaling pathway is an evolutionarily conserved developmental signaling event that plays a critical role in regulating tissue development and maintaining homeostasis, the dysregulation of which contributes to various diseases. Natural products have been widely recognized as a treasure trove of novel drug discovery for millennia, and many clinical drugs are derived from natural small molecules. Mounting evidence has demonstrated that many natural small molecules could inhibit the Wnt/β-catenin pathway, while the efficacy of natural products remains to be determined. Therefore, this paper primarily reviews the targeting mechanism of natural small molecules for aberrant Wnt/β-catenin pathway that is intimately implicated in the pathogenesis of myriad diseases, such as cancers, renal diseases, neurodegenerative diseases and bone disorders. In addition, this review also highlights some natural products that have the potential to halt Wnt/β-catenin pathway, especially for porcupine, the receptors of Wnt ligands, β-catenin and β-catenin-dependent proteins. Additionally, a series of natural small molecules have shown good therapeutic effects against mutations of the Wnt/β-catenin pathway, which may dramatically facilitate the development of natural products in Wnt/β-catenin pathway intervention.

Tubulointerstitial fibrosis is the final common pathway for all kidney diseases leading to chronic kidney disease (CKD). TGF-β/Smad signaling pathway plays a key role in renal fibrosis. Previous studies have revealed that rhubarb extracts attenuated the increase of transforming growth factor-β 1 (TGF-β1) in CKD rats. To gain an in-depth insight into the mechanism of the anti-fibrotic activities of the rhubarb extracts, we investigated the influence of rhubarb extracts on TGF-β/Smad signaling pathway and the influence on metabolome in a rat model of CKD with adenine-induced chronic tubulointerstitial nephropathy. Male Sprague-Dawley rats were divided into four groups, including control, CKD, CKD + petroleum ether extract, CKD + ethyl acetate extract, and CKD + n-butanol extract groups. Kidneys harvested on the week three were evaluated for renal fibrosis, the expression of proteins in TGF-β/Smad signaling pathway and metabolomic study. We found rhubarb extracts suppressed TGF-β/Smad3-mediated renal fibrosis by reducing the TGF-β1, transforming growth factor-β receptor I (TGF-β RI), transforming growth factor-β receptor II (TGF-β RII), Smad2, p-Smad2, Smad3, p-Smad3, and Smad4, meanwhile increased Smad7. In addition, rhubarb extracts mitigated renal injury and dysfunction, and either fully or partially reversed the abnormalities of tissue metabolites. Thus, rebalancing the disorder of TGF-β/Smad signaling and metabolic dysfunction by treatment with rhubarb extracts may represent as an effective therapy for CKD associated with fibrosis.