Alleviating the Intestinal Absorption of Rhein in Rhubarb through Herb Compatibility in Tiaowei Chengqi Tang in Caco-2 Cells

Tiaowei Chengqi Tang (TWCQT) is composed of rhubarb, processed liquorice, and Natrii Sulfas, which is used as a purgative in traditional Chinese medicine (TCM). This study focused on the intestinal absorption of rhein in disassembly of the TWCQT extracts through the Caco-2 cell monolayer model to explicate the possible detoxification mechanism of herb-herb compatibility in TWCQT. The results showed that the intestinal absorption of rhein occurred through active diffusion, and rhein might be composed of breast cancer resistance protein (BCRP) substrates. The extract of processed liquorice increased the exclusion rate and reduced intracellular uptake of rhein. The consistent results observed in TWCQT further implied that processed liquorice in TWCQT could suppress the absorption of rhein across the Caco-2 cell monolayer. It has therefore been concluded that the active ingredients of processed liquorice may play a critical role in reducing the intestinal absorption of rhein to alleviate the toxicity of rhubarb in TWCQT. Because of BCRP’s involvement in rhein transport, we conjectured that some components in processed liquorice could inhibit the transport of rhein, possibly by mediating BCRP. These results would provide new insight into this ancient drug combination in toxicity reduction and clinical use

Antidepressant-Like Effects of Cistanche tubulosa Extract on Chronic Unpredictable Stress Rats Through Restoration of Gut Microbiota Homeostasis

Growing evidence shows that neuropsychiatric disorders, such as depression, are linked with gut microbiome through the gut–brain axis. Cistanches Herba is well known for the treatment of “kidney-yang” deficiency in traditional Chinese medicine (TCM), and has been used for treatment of neurodegenerative diseases in recent years. In this study, chronic unpredictable stress (CUS)-induced depression model was established to explore the impact of Cistanche tubulosa extract (CTE) on behavioral tests, monoamine neurotransmitters and neurotrophic factors in hippocampus and colon, gut microbiota composition, and short-chain fatty acids (SCFAs) production. Moreover, correlation analysis was used to evaluate the functional relationship between altered gut microbiota, changed neurotransmitters and neurotrophins in hippocampus and colon, and disturbed concentration of SCFAs. CTE significantly improved depression-like behaviors in rats under CUS. Brain level of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) expression in CUS rats were restored by CTE. The relative abundance of gut microbiota and the concentrations of acetate and hexanoic acid could also be modulated by CTE treatment. We further showed that the application of CTE in CUS rats led to strong correlation among disrupted gut microbiota composition, hippocampus neurotransmitter levels, and production of neuroactive metabolite SCFAs. Altogether, these results identify CTE as a potential treatment for depressive symptoms by restoring homeostasis of gut microbiota for microbiota–gut–brain axis disorders, opening new avenues in the field of neuropsychopharmacology

Functional Gene-Guided Discovery of Type II Polyketides from Culturable Actinomycetes Associated with Soft Coral <em>Scleronephthya</em> sp

<div><p>Compared with the actinomycetes in stone corals, the phylogenetic diversity of soft coral-associated culturable actinomycetes is essentially unexplored. Meanwhile, the knowledge of the natural products from coral-associated actinomycetes is very limited. In this study, thirty-two strains were isolated from the tissue of the soft coral <em>Scleronephthya</em> sp. in the East China Sea, which were grouped into eight genera by 16S rDNA phylogenetic analysis: <em>Micromonospora</em>, <em>Gordonia</em>, <em>Mycobacterium</em>, <em>Nocardioides</em>, <em>Streptomyces</em>, <em>Cellulomonas</em>, <em>Dietzia</em> and <em>Rhodococcus</em>. 6 <em>Micromonospora</em> strains and 4 <em>Streptomyces</em> strains were found to be with the potential for producing aromatic polyketides based on the analysis of KS_α (ketoacyl-synthase) gene in the PKS II (type II polyketides synthase) gene cluster. Among the 6 <em>Micromonospora</em> strains, angucycline cyclase gene was amplified in 2 strains (A5-1 and A6-2), suggesting their potential in synthesizing angucyclines <em>e.g.</em> jadomycin. Under the guidance of functional gene prediction, one jadomycin B analogue (7b, 13-dihydro-7-O-methyl jadomycin B) was detected in the fermentation broth of <em>Micromonospora</em> sp. strain A5-1. This study highlights the phylogenetically diverse culturable actinomycetes associated with the tissue of soft coral <em>Scleronephthya</em> sp. and the potential of coral-derived actinomycetes especially <em>Micromonospora</em> in producing aromatic polyketides.</p> </div

Neighbor-joining phylogenetic tree based on 16S rRNA gene sequence (<i>ca</i>.1,400 bp) of actinomycetes from the tissue of soft coral <i>Scleronephthya</i> sp.

<p>The sequences obtained in this work are marked by black dot. The number is the percentage indicating the level of boot strap support, based on a neighbor-joining analysis of 1,000 resampled data sets. The scale bar represents 0.02 substitutions per nucleotide position.</p

HPLC of the EtOAc extract of <i>Micromonospora</i> sp. strain A5-1 fermentation broth (UV spectra of selected peaks at t_R 5.22 min show similar absorption as jadomycins).

<p>HPLC of the EtOAc extract of <i>Micromonospora</i> sp. strain A5-1 fermentation broth (UV spectra of selected peaks at t_R 5.22 min show similar absorption as jadomycins).</p

Neighbor-joining tree constructed using aligned KS_α domain amino acid sequence (203 amino acid positions) from type II PKSs.

<p>The sequences obtained in this work are marked by black dot. Next to the taxon name, GenBank accession number of KS_α domain amino acid sequence or/and the identified compounds are indicated. Bootstrap values calculated from 1,000 resamplings using neighborjoining are shown at the respective nodes when the calculated values were 50% or greater. The scale bar represents 0.05 substitutions per amino acid position.</p

TIC of the EtOAc extract of <i>Micromonospora</i> sp. strain A5-1 fermentation broth (the peak with t_R at 4.18 min is putative jadomycin analogue).

<p>TIC of the EtOAc extract of <i>Micromonospora</i> sp. strain A5-1 fermentation broth (the peak with t_R at 4.18 min is putative jadomycin analogue).</p