Multi-omics approaches for in-depth understanding of therapeutic mechanism for Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is extensively utilized in clinical practice due to its therapeutic and preventative treatments for various diseases. With the development of high-throughput sequencing and systems biology, TCM research was transformed from traditional experiment-based approaches to a combination of experiment-based and omics-based approaches. Numerous academics have explored the therapeutic mechanism of TCM formula by omics approaches, shifting TCM research from the "one-target, one-drug" to "multi-targets, multi-components" paradigm, which has greatly boosted the digitalization and internationalization of TCM. In this review, we concentrated on multi-omics approaches in principles and applications to gain a better understanding of TCM formulas against various diseases from several aspects. We first summarized frequently used TCM quality assessment methods, and suggested that incorporating both chemical and biological ingredients analytical methods could lead to a more comprehensive assessment of TCM. Secondly, we emphasized the significance of multi-omics approaches in deciphering the therapeutic mechanism of TCM formulas. Thirdly, we focused on TCM network analysis, which plays a vital role in TCM-diseases interaction, and serves for new drug discovery. Finally, as an essential source for storing multi-omics data, we evaluated and compared several TCM databases in terms of completeness and reliability. In summary, multi-omics approaches have infiltrated many aspects of TCM research. With the accumulation of omics data and data-mining resources, deeper understandings of the therapeutic mechanism of TCM have been acquired or will be gained in the future.

Limosilactobacillus fermentum-fermented ginseng improved antibiotic-induced diarrhoea and the gut microbiota profiles of rats.

AIMS: This study investigated the efficacy of Limosilactobacillus fermentum-fermented ginseng for improving colitis and the gut microbiota profiles in rats and explored the benefits of the L. fermentum fermentation process to ginseng. METHODS AND RESULTS: Ginseng polysaccharide and ginsenoside from fermented ginseng were analysed by UV and HPLC. Antibiotic-fed rats were treated with fermented ginseng and a L. fermentum-ginseng mixture. Histopathology- and immune-related factors (TNF-α, IL-1ß, IL-6 and IL-10) of the colon were assayed by using pathological sections and ELISA. After treatment, fermented ginseng relieved the symptoms of antibiotic-induced diarrhoea and colon inflammation, and the expression of colon immune factors returned to normal. The gut microbial communities were identified by 16S rRNA gene sequencing. The results showed that the alterations in the gut microbiota returned to normal. In addition, the gut microbiota changes were correlated with immune factor expression after treatment. The fermented ginseng had better biological functions than a L. fermentum-ginseng mixture. CONCLUSIONS: Fermented ginseng can relieve diarrhoea and colon inflammation and restore the gut microbiota to its original state. The process of L. fermentum fermentation can expand the therapeutic use of ginseng. SIGNIFICANCE AND IMPACT OF THE STUDY: This research suggested the potential function of fermented ginseng to relieve diarrhoea and recover the gut microbiota to a normal level and explored the benefits of the Limosilactobacillus fermentum fermentation process to ginseng.

Paecilomyces cicadae-fermented Radix astragali ameliorate diabetic nephropathy in mice by modulating the gut microbiota.

The occurrence and development of diabetic nephropathy (DN) are closely related to gut microbiota. Paecilomyces cicadae is a medicinal and edible fungus. Radix astragali is a therapeutic material for unifying Chinese Qi. They can delay the occurrence and development of kidney disease. In recent years, solid-state fermentation of edible fungi and traditional Chinese medicine has become a hot issue.Hypothesis/Gap Statement. We assumed that solid-state fermentation products of R. astragali and Paecilomyces cicadidae (RPF) could ameliorate diabetic nephropathy and modulate gut microbiota composition. We aimed to study the function and mechanism of the RPF for ameliorating DN in mice. We investigated the effect of the potential roles of RPF in DN mice and interaction between DN and gut microbiota using animal experiments and gut microbiota measurements. We found that RPF dramatically reduced urine protein, serum creatinine and blood urea nitrogen in DN mice. Furthermore, RPF ameliorated the physiological condition of DN mice by regulating the abundance of intestinal microbiota such as Ruminococcaceae_UCG-014, Allobaculum, Unclassified_f__Lachnospiraceae Alloprevotella and Bacteroides. RPF can ameliorate diabetic nephropathy and modulate gut microbiota composition.

Monascus ruber fermented Panax ginseng ameliorates lipid metabolism disorders and modulate gut microbiota in rats fed a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng Meyer) is rich in a variety of biologically active ingredients, which shows good effect in the treatment of metabolic diseases. Monascus has lipid-lowering activity and one of its metabolites, lovastatin, is widely used in clinical practice. AIM OF THE STUDY: The main purpose of this study was to clarify the effects of fermented Panax ginseng by Monascus ruber (PM) on lipid metabolism and gut microbiota in rats fed a high-fat diet. MATERIALS AND METHODS: SPF Sprague-Dawley rats were randomly divided into 5 groups, the therapeutic effect of PM on HFD-induced obesity, hyperlipidemia, hepatic steatosis, and disordered gut microbiota were determined in rats. RESULTS: PM could attenuate features of obesity in rats, decrease serum TC, LDL-C and IgA levels, increase excretion of bile acids in feces. Hepatic histopathologic analysis revealed that PM decrease lipid accumulation in hepatocytes. Consistently, mRNA expression levels of cholesterol metabolism-related genes were regulated in the livers of HFD-fed rats administered with PM. In addition, PM could enhance the diversity and relative abundance of gut microbiota, reduce the Firmicutes/Bacteroidetes (F/B) ratio, increase significantly the relative abundance of Prevotella_9, and decrease these of Muribaculaceae. CONCLUSIONS: PM could regulate lipid metabolism and the structure of the gut microbiota in the HFD rats. Our findings provide valuable experience for the development of ginseng. PM could be a potentially effective strategy to prevent and treat metabolic diseases and alleviate the gut microbiota disturbance caused by it.

Effects of fermented ginseng on the gut microbiota and immunity of rats with antibiotic-associated diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng Meyer) is a well-known herb in traditional Chinese medicine and has been used to treat many diseases for thousands of years. Recent studies have shown that ginseng is a promising agent for improving the gut microbiota and treating ulcerative colitis. Fermentation is a common process in traditional Chinese medicine making that can be used to enhance efficacy and reduce toxicity. AIM OF THE STUDY: The purpose of the present study was to research the efficacy of ginseng fermented with probiotics (Lactobacillus fermentum) on the gut microbiota and immunity of rats with antibiotic-associated diarrhea (AAD). MATERIALS AND METHODS: SPF Sprague-Dawley rats were randomly divided into eight groups: control group, antibiotic group, natural recovery group, and five groups treated with different doses of fermented ginseng (FG1 to FG5). A model of AAD was established by treating the rats with triple antibiotics, and obvious symptoms of AAD were observed. A histopathological analysis of the colon was performed. The total bacteria in the intestinal microbiota and five types of gut microbes in the feces were detected by quantitative PCR. The expression levels of related immune factors TLR4 and NF-κB in the colon were assayed. RESULTS: An appropriate dose of fermented ginseng (0.5 g/kg/d) relieved some of the symptoms of AAD and colon inflammation and reduced the expression of the immune factors TLR4 and NF-κB in the colon. The alteration of the gut microbiota observed in the rats treated with antibiotics also returned to normal after treatment with fermented ginseng. Moreover, different doses of fermented ginseng exerted different influences on the gut microbiota, and excessively high or low doses of fermented ginseng were disadvantageous for resolving the symptoms of AAD and promoting recovery. CONCLUSIONS: These results demonstrate that fermented ginseng can treat AAD symptoms and colon inflammation and restore the gut microbiota to its original state.

Paecilomyces cicadae-fermented Radix astragali activates podocyte autophagy by attenuating PI3K/AKT/mTOR pathways to protect against diabetic nephropathy in mice.

Radix astragali, a medicinal material for tonifying Chinese Qi, has widely been used for the treatment of Kidney disease in China and East Asia, especially in reducing the apoptosis of glomerular podocytes. Paecilomyces Cicadidae is a medicinal and edible fungus. In recent years, the application of traditional Chinese medicine (TCM) in solid-state fermentation of edible and medicinal fungi has become a hot issue. Fermentation is a special method to change the properties of TCM. Therefore, the potential roles and molecular mechanisms on podocytes of solid-state fermentation products of Radix astragali and Paecilomyces cicadidae (RPF) in diabetic nephropathy (DN) were studied. In vivo, the effect of RPF and Radix astragali on DN in mice was evaluated by detecting the biochemical indexes of blood and urine, renal function and podocyte integrity. In vitro, the expression of podocyte marker protein, autophagy marker protein and PI3K/AKT/mTOR signaling pathway protein were detected by Western blotting using a high glucose-induced podocyte injury model. The results showed that RPF had a significant alleviative effect on DN mice. RPF can significantly reduce urine protein, serum creatinine, and blood nitrogen urea in DN mice. Morphological analysis showed that RPF could improve kidney structure of DN and reduce the apoptosis of podocytes, and the effect was better than Radix astragali. In vitro results indicated that RPF could enhance autophagy and protect podocytes by inhibiting the PI3K/AKT/mTOR signaling pathway. In summary, RPF has better effect on delaying the development of DN than Radix astragali. RPF enhances autophagy in podocytes and delays DN probably by inhibiting the PI3K/AKT/mTOR signaling pathway.

Analysis of chemical constituents and six compounds in Qu-feng-sheng-shi Granules via HPLC-ESI-Q/TOF-MSn and HPLC-UV technique.

Qu-feng-sheng-shi Granules (QFSSG), a common prescription for the treatment of chronic inflammation and allergic rhinitis, is widely used in the clinic as a traditional Chinese medicine. Chemical analysis and quality control studies of this formulation are relatively limited compared with pharmacological studies. In this study, a high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q/TOF-MSn ) was used to identify the components in this prescription. Next, to quantify six major compounds, an HPLC-UV method was developed and validated. The results showed that 53 compounds were identified based on the MSn data, retention time and previous reports, including 17 coumarins, 14 lignans, 10 chromones, nine phenylethanoid glycosides and three other compounds, were identified or tentatively assigned. Contents of six major bioactive compounds (4'-O-ß-glucopyranosyl-5-O-methylvisamminol, Prim-O-glucosylcimifugin, forsythin, magnolin, imperatorin, isoimperatorin) could be determined by HPLC simultaneously. In addition, the potential anti-inflammatory activity of six major compounds was determined too, and we found that four compounds (4'-O-ß-glucopyranosyl-5-O-methylvisamminol, Prim-O-glucosylcimifugin, forsythin, imperatorin) have a potent nitric oxide inhibitory effect. In conclusion, this work provided comprehensive information on the quality control of QFSSG and evaluated the potential biological activity of the main components in QFSSG, which can contribute to understanding and using it more scientifically.

Multiscale study on the enhancing effect and mechanism of borneolum on transdermal permeation of drugs with different log P values and molecular sizes.

D-borneolum is commonly used as a permeation enhancer in Traditional Chinese Medicine (TCM) formulas for transdermal application. Additionally, two other sources of borneolums were recorded in the 2015 edition of the Chinese Pharmacopoeia (ChP), including L-borneolum and borneolum syntheticum. To guide the selection and application of borneolum, the safety and enhancing effect of three sources of borneolums were investigated on transdermal permeation of compounds with different octanol-water partition coefficient (log P) values and molecular weights (MWs). Both the results of cellular cytotoxicity and in vitro transdermal permeation experiments showed that all three sources of borneolums could be applied in TDDS as permeation enhancers. Moreover, all three sources of borneolums achieved optimal permeation-enhancing performances on transdermal drugs with lower log P values as well as higher MWs. Further study was carried out to elucidate the potential molecular mechanism of borneolum enhancing transdermal drug delivery via transmission electron microscope (TEM) and coarse-grained molecular dynamic (CG-MD) simulation. Borneolum significantly promoted transdermal delivery of drugs via changing the dense morphology of the stratum corneum (SC), disturbing the ordered arrangement of ceramide (CER) and free fatty acid (FFA) molecules in lipid layers, and further increasing the diffusion rate of drugs in the lipid layers.