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Licorice (Gan-Cao in Chinese) is one of the most famous herbal medicines around the world. The fermentation of probiotics and herbs can change the chemical constituents and significantly improve the efficacy. However, it is still unknown whether licorice fermented with probiotics would produce beneficial therapeutic effects. This study aimed to comprehensively analyze the chemical constituents in fermented licorice via quasi-targeted metabolomics, predict the potential efficacy of fermentation products via diverse bioinformatic methods, and further verify the efficacy of fermentation products through in vitro and in vivo experiments. As a result, 1,435 compounds were identified totally. Among them, 424 natural medicinal products were classified with potentially important bioactivities, including 11 anthocyanins, 10 chalcones and dihydrochalcones, 25 flavanones, 45 flavones and flavonols, 117 flavonoids, 34 isoflavonoids, 21 phenols and its derivatives, 20 phenylpropanoids and polyketides, 96 terpenoids and 25 coumarins and derivatives. Interestingly, bioinformatic prediction showed that the targets of some important compounds were related to neurodegeneration, oxidoreductase activity and response to stress. In vitro and in vivo tests further verified that fermented licorice had excellent effects of DPPH clearance, anti-oxidation, anti-neurodegeneration, and anti-stress. Thus, this study would provide a reference method for related research and the development of fermented licorice-related products.

Rehmanniae Radix (RR, the dried tuberous roots of Rehmannia glutinosa (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-related diseases in a class of prescriptions. The oligosaccharides and catalpol in RR have been confirmed to have neuroprotective effects. However, there are few studies on the anti-Alzheimer’s disease (AD) effect of oligosaccharides in Rehmanniae Radix (ORR). The chemical components and pharmacological effects of dried Rehmannia Radix (DRR) and prepared Rehmannia Radix (PRR) are different because of the different processing methods. ORR has neuroprotective potential, such as improving learning and memory in rats. Therefore, this study aimed to prove the importance of oligosaccharides in DRR (ODRR) and PRR (OPRR) for AD based on the Caenorhabditis elegans (C. elegans) model and the different roles of ODRR and OPRR in the treatment of AD. In this study, we used paralysis assays, lifespan and stress resistance assays, bacterial growth curve, developmental and behavioral parameters, and ability of learning and memory to explore the effects of ODRR and OPRR on anti-AD and anti-aging. Furthermore, the accumulation of reactive oxygen species (ROS); deposition of Aβ; and expression of amy-1, sir-2.1, daf-16, sod-3, skn-1, and hsp-16.2 were analyzed to confirm the efficacy of ODRR and OPRR. OPRR was more effective than ODRR in delaying the paralysis, improving learning ability, and prolonging the lifespan of C. elegans. Further mechanism studies showed that the accumulation of ROS, aggregation, and toxicity of Aβ were reduced, suggesting that ORR alleviated Aβ-induced toxicity, in part, through antioxidant activity and Aβ aggregation inhibiting. The expression of amy-1 was downregulated, and sir-2.1, daf-16, sod-3, and hsp-16.2 were upregulated. Thus, ORR could have a possible therapeutic effect on AD by modulating the expression of amy-1, sir-2.1, daf-16, sod-3, and hsp-16.2. Furthermore, ORR promoted the nuclear localization of daf-16 and further increased the expression of sod-3 and hsp-16.2, which significantly contributed to inhibiting the Aβ toxicity and enhancing oxidative stress resistance. In summary, the study provided a new idea for the development of ORR.

Abstract Background Peganum harmala L. is a medicinal herb extensively used in traditional Chinese medicine (TCM). So far, relevant reports on the toxicity of Peganum harmala L. seeds (PHS) are hardly available. Especially, we still know little about the in vivo mechanism for PHS toxicity. This study aims to evaluate the toxicity effects of PHS in Caenorhabditis elegans (C. elegans), investigate the possible mechanism of the toxicity effects of PHS, and provide reference for the pharmacological research of PHS. Methods In the present study, the C. elegans was exposed to 0.25, 0.50, 1.00 mg/mL of PHS in nematode growth medium (NGM) at 22 °C in the presence of food. Lethality, lifespan, growth, reproduction, and locomotion behavior assays were performed to evaluate the toxicity effects of PHS in C. elegans. We then determined the mechanism of the toxicity effect of PHS by quantitative real-time polymerase chain reaction (qRT-PCR), acetylcholinesterase (AChE) activity assay, and oxidative stress resistance assays. The main components of PHS were detected by high performance liquid chromatography (HPLC). Results Compared with the control group, the lethality of C. elegans was significantly increased when they were exposed to the ethanol extract of PHS at 0.25, 0.50 and 1.00 mg/mL (P

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4′-teterahydroxystilbene-2-O-β-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-β-D-glucoside (EG), and physcion-8-O-β-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

Huolisu Oral Liquid (HLS), a well-known traditional Chinese medicine (TCM) prescription, is an over-the-counter drug that is registered and approved by the State Food and Drug Administration (Approval No. Z51020381). HLS has been widely applied in the clinical treatment of cognitive disorders and has effects on delaying aging. The antioxidant effects of HLS are closely related to its antiaging activities, but the underlying mechanisms are unclear. In this study, the potential antioxidant ingredients of HLS were screened based on serum pharmacochemistry and network pharmacology, and the potential mechanisms involved in HLS antioxidant effects were preliminarily explored. Further, the antioxidant effects of HLS were verified by in vivo and in vitro experiments. The results showed that potential antioxidant ingredients could affect the toxic advanced glycation end products-receptor for advanced glycation end products (TAGE-RAGE) signaling, mitogen-activated protein kinase (MAPK) signaling, interleukin (IL)-17 signaling, tumor necrosis factor (TNF) signaling, toll-like receptors (TLRs), cyclic adenosine monophosphate (cAMP) signaling, hypoxia-inducible factor (HIF)-1 signaling, and other related pathways by regulating GAPDH, AKT1, TP53, MAPK1, JUN, and other associated targets. Thus, HLS may reduce inflammation, control the release of inflammatory cytokines, and regulate mitochondrial autophagy and metabolic abnormalities to ultimately play an antioxidant role. This is the first study attempting to construct a multilevel network of “HLS-antioxidant targets” based on serum pharmacochemistry and network pharmacology to explore the relationship between HLS and antioxidation and the molecular mechanisms of antioxidation combined with bioinformatics functional analysis and lays a foundation for further elucidating the antioxidant mechanisms of HLS.