A diverse range of symbiotic gut bacteria codevelops with the host and is considered a metabolic “organ” that not only facilitates harvesting of nutrients from the dietary components but also ...produces a class of metabolites. Many metabolites of gut microbes have an important impact on host health. For example, an inventory of metabolic intermediates derived from bacterial protein fermentation may affect host physiology and pathophysiology. Additionally, gut microbiota can convert cholesterol to bile acids and further into secondary bile acids which can conversely modulate microbial community. Moreover, new research identifies that microbes synthesize vitamins for us in the colon. Here, we will review data implicating a major class of bacterial metabolites through breaking down dietary fiber we cannot process, short-chain fatty acids (SCFAs), as crucial executors of alteration of immune mechanisms, regulation of metabolic homeostasis, and neuroprotective effects to combat disease and improve health.
Scutellariae radix (
Scutellaria baicalensis
Georgi, SR) and coptidis rhizoma (
Coptis chinensis
Franch, CR) are both widely used traditional Chinese medicines and have been used together to treat ...T2DM with synergistic effects in the clinical practices for thousands of years, but their combination mechanism is not clear. Accumulating evidences have implicated gut microbiota as important targets for the therapy of T2DM. Thus, this study aimed to unravel the cooperation mechanism of SR and CR on the amelioration of T2DM based on the systematic analysis of metagenome and metabolome of gut microbiota. Bacterial communities were analyzed based on high-throughput 16S rRNA gene sequencing. Furthermore, ultra high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze variations of microbial metabolites in feces and the contents of short chain fatty acids (SCFAs) in the cecum were determined by a gaschromatography-flame ionization detector (GC-FID). 16S rRNA gene sequencing results revealed that T2DM rats treated with SR, CR, and the combination of SR and CR (SC) exhibited changes in the composition of the gut microbiota. The SCFAs-producing bacteria such as
Bacteroidales S24-7 group_norank
,
Eubacterium nodatum group
,
Parasutterella
,
Prevotellaceae UCG-001
,
Ruminiclostridium
, and
Ruminiclostridium 9
in T2DM rats were notably enriched after treatment with SR, CR, and their combination. In contrast, secondary bile acid-producing bacteria such as
Escherichia-Shigella
strongly decreased in numbers. The perturbance of metabolic profiling in T2DM rats was obviously improved after treatment, exhibiting a lower level of secondary bile acids and a numerical increase of microbially derived SCFAs. Moreover, the correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. The findings indicated that the crosstalk between microbiota-derived metabolites and the host played an important role in the progress of T2DM and might provide a novel insight regarding gut microbiota and its metabolites as potential new targets of traditional Chinese medicines. Furthermore, this work also suggested that the integration of various omics methods and bioinformatics made a useful template for drug mechanism research.
Rhubarb, a traditional herb, has been used in clinical practice for hundreds of years to cure constipation, but its mechanism is still not clear enough. Currently, growing evidence suggests that ...intestinal flora might be a potential target for the treatment of constipation. Thus, the aim of this study was to clarify the laxative effect of rhubarb via systematically analyzing the metagenome and metabolome of the gut microbiota. In this study, the laxative effects of rhubarb were investigated by loperamide-induced constipation in rats. The gut microbiota was determined by high-throughput sequencing of 16S rRNA gene. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for fecal metabolomics analysis. The data showed that rhubarb could significantly shorten gastrointestinal transit time, increase fecal water content and defecation frequency, improve gastrointestinal hormone disruption, and protect the colon mucus layer. Analysis of 16S rRNA gene sequencing indicated that rhubarb could improve the disorder of intestinal microbiota in constipated rats. For example, beneficial bacteria such as
Ligilactobacillus
,
Limosilalactobacillus
, and
Prevotellaceae UCG-001
were remarkably increased, and pathogens such as
Escherichia-Shigella
were significantly decreased after rhubarb treatment. Additionally, the fecal metabolic profiles of constipated rats were improved by rhubarb. After rhubarb treatment, metabolites such as chenodeoxycholic acid, cholic acid, prostaglandin F2α, and α-linolenic acid were markedly increased in constipation rats; in contrast, the metabolites such as lithocholic acid, calcidiol, and 10-hydroxystearic acid were notably reduced in constipation rats. Moreover, correlation analysis indicated a close relationship between intestinal flora, fecal metabolites, and biochemical indices associated with constipation. In conclusion, the amelioration of rhubarb in constipation might modulate the intestinal microflora and its metabolism. Moreover, the application of fecal metabolomics could provide a new strategy to uncover the mechanism of herbal medicines.
Key points
•
Rhubarb could significantly improve gut microbiota disorder in constipation rats.
•
Rhubarb could markedly modulate the fecal metabolite profile of constipated rats.
Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. ...Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as
Clostridium
sensu stricto
1
,
Enterobacter
, and
Escherichia-Shigella
correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including
Blautia
,
Muribaculaceae_norank
,
Prevotellaceae UCG-001
, and
Ruminiclostridium 9
elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and
l
-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.
Key Points
•
The potential mechanism of LZD on the amelioration of UC was firstly investigated.
•
LZD could significantly shape the structure of gut microbiota.
•
LZD could notably modulate the fecal metabolic profiling of UC mice.
Graphical abstract
Momilactones are allelochemicals in rice and moss defense. Momilactone-like compounds are therefore considered important secondary metabolites for plant defense. They may serve as promising lead ...compounds for crop-friendly herbicides as well as antifungal and antibacterial agents. Many of these substances possess potent cytotoxicity property against cancer cell lines as well. The present paper is the first review on these versatile molecules, focusing on the structure, biological activity, chemical synthesis, and biosynthesis of the naturally occurring momilactone-like molecules reported from 1973 to 2017.
Angelica sinensis (Oliv.) Diels is a widely used medicinal plant mainly originated in Gansu, China. Angelica sinensis is greatly demanded in the clinical practice of Chinese medicine due to its broad ...pharmacological activities of hematopoietic and anti-inflammatory properties. But, the percentage of early flowering in Angelica sinensis arrives to 20%~30%, which severely affects its quality and quantity. Here, transcriptome profiling and digital gene expression analysis were applied to study the mechanism of early flowering in Angelica sinensis. A total of 49,183,534 clean reads were obtained and assembled into 68,262 unigenes, and 49,477 unigenes (72.5%) could be annotated to a minimum of one database in the Nr, Nt, Swiss-Pro, GO, COG and KEGG. Taking the above transcriptome data as a reference, digital gene expression result showed that 5,094 genes expression level were significant changed during early flowering. These annotated genes offered much information promoting that the biosynthesis of secondary metabolites pathway, the hormone signal transduction pathway, and the transcription regulation system may be closely related to the early flowering phenomenon of Angelica sinensis. Further expression patterns of key genes contribute to early flowering were analyzed using quantitative real-time PCR. The transcriptome result offered important gene expression information about early flowering in Angelica sinensis.
Platycodin D (PLD) is the major triterpene saponin in the root of Platycodon grandiflorum (Jacq.) with various pharmacological activities. The purpose of the present study was to evaluate the ...protective effects and possible mechanisms of PLD on acute lung injury (ALI) both in vivo and in vitro.
In vivo, we used two ALI models, lipopolysaccharide (LPS)-induced ALI and bleomycin (BLE)-induced ALI to evaluate the protective effects and possible mechanisms of PLD. Female BALB/c mice were randomly divided into the following groups: control group, LPS group, LPS plus pre-treatment with dexamethasone (2mg/kg) group, LPS plus pre-treatment with PLD groups (50mg/kg, 100mg/kg), LPS plus post-treatment with dexamethasone (2mg/kg) group, LPS plus post-treatment with PLD groups (50mg/kg, 100mg/kg), BLE group, BLE plus pre-treatment with dexamethasone (2mg/kg) group, BLE plus pre-treatment with PLD groups (50mg/kg, 100mg/kg), BLE plus post-treatment with dexamethasone (2mg/kg) group, and BLE plus post-treatment with PLD groups (50mg/kg, 100mg/kg). PLD was orally administered before or after LPS or BLE challenge with mice. Mice were sacrificed, and lung tissues and bronchoalveolar fluid (BALF) were prepared for further analysis. Our results showed that PLD significantly decreased lung wet-to-dry weight ratio (lung W/D weight ratio), total leukocyte number and neutrophil percentage in the BALF, and myeloperoxidase (MPO) activity of lung in a dose-dependent manner. Besides, cytokine levels, including interleukin (IL)-6, tumor neurosis factor (TNF)-α were also found significantly inhibited in BALF. Furthermore, PLD effectively inhibited the expressions of nuclear factor κB (NF-κB), Caspase-3 and Bax in the lung tissues, as well as restored the expression of Bcl-2 in the lungs and improved the superoxide dismutase (SOD) activity in BALF.
In vitro, we used LPS-challenged cell model to evaluate the protective effects and possible mechanisms of PLD. MLE-12 cells were stimulated with LPS in the presence and absence of PLD. The levels of TNF-α, IL-6 and the expressions of NF-κB, Caspase-3, and Bax were remarkably down-regulated, while the expression of bcl-2 was significantly up-regulated in PLD treatment groups in MLE-12 cells.
These results showed that the administration of PLD improved ALI both in vivo and in vitro, possibly through suppressing apoptosis and inflammation.
•Platycodin D inhibited lung inflammation.•Platycodin D inhibited lung apoptosis.•Platycodin D inhibited LPS-induced lung injury.
Yueju, a Traditional Chinese Medicine formula, exhibited fast-onset antidepressant responses similar to ketamine. This study focused on assessing the rapid and persistent antidepressant efficacy of ...Yueju and ketamine in chronically stressed mice and its association with alternations in prefrontal N-methyl-D-aspartate (NMDA) receptor and mammalian target of rapamycin (mTOR)-related activity. Chronic mild stress (CMS) led to deficits in sucrose preference test (SPT), forced swim test, tail suspension test, and novelty-suppressed feeding test, which were improved differently by acute Yueju or ketamine administration. The improvement in SPT started as soon as 2 hours post Yueju and ketamine but lasted for 6 days only by Yueju. Body weight was regained by Yueju more than ketamine at post-drug administration day (PAD) 6. CMS decreased phosphorylation of the mTOR effectors 4E-BP1 and p70S6K, their upstream regulators ERK and Akt, and downstream targets including synaptic protein GluR1. Yueju or ketamine reversed these changes at PAD 2, but only Yueju reversed phosphor-Akt at PAD 6. CMS selectively and lastingly increased NMDA receptor subunit NR1 expression, which was reversed by ketamine or Yueju at PAD 2 but only by Yueju at PAD 6. These findings suggest that NR1 and Akt/mTOR signaling are important therapeutic targets for depression.
COVID-19 mortality is primarily driven by abnormal alveolar fluid metabolism of the lung, leading to fluid accumulation in the alveolar airspace. This condition is generally referred to as pulmonary ...edema and is a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are multiple potential mechanisms leading to pulmonary edema in severe Coronavirus Disease (COVID-19) patients and understanding of those mechanisms may enable proper management of this condition. Here, we provide a perspective on abnormal lung humoral metabolism of pulmonary edema in COVID-19 patients, review the mechanisms by which pulmonary edema may be induced in COVID-19 patients, and propose putative drug targets that may be of use in treating COVID-19. Among the currently pursued therapeutic strategies against COVID-19, little attention has been paid to abnormal lung humoral metabolism. Perplexingly, successful balance of lung humoral metabolism may lead to the reduction of the number of COVID-19 death limiting the possibility of healthcare services with insufficient capacity to provide ventilator-assisted respiration.
Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this ...study, chryseno2,1-coxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using
Aspergillus terreus
TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1β (IL-1β; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.
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