Folium Sennae Research Articles

Elaeagnus angustifolia L. fruit alleviates diarrhea via regulating intestinal microbiota and short chain fatty acids

Fruits of Elaeagnus angustifolia L. have been used as Uyghur medicine due to the properties of treating spleen and stomach weakness, indigestion, enteritis, diarrhea, lung heat, and cough. However, the anti-diarrhea mechanism was still not clear. This study explored the mechanism of E. angustifolia fruit alleviated diarrhea from the perspective of gut microbiota. Diarrhea model was established with Folium sennae in mice. Then, the levels of diarrhea rate and diarrhea index of mice were evaluated. Hematoxylin eosin (HE) staining was employed to detect pathological sections of colon tissue. 16S rRNA sequencing analysis was researched to confirm the gut microbiota in mice. Diversity and differential analysis were adopted to analyze the intestinal microflora. Furthermore, Gas chromatography-quadrupole time-of-flight tandem mass spectrometry (GC-Q-TOF-MS) was used to detect the concentrations of short chain fatty acids (SCFAs) in intestine. The high-dose group (3.2 g/kg) of E. angustifolia fruit could significantly reduce the diarrhea rate and diarrhea index of mice caused by Folium sennae (p < 0.01). We also found that E. angustifolia fruit enhanced the diversity of gut microbiota while ameliorating diarrhea. Alpha diversity revealed that the microbial composition of E. angustifolia fruit group tended to be more similar to that of the CON group (no significant difference at p < 0.05). E. angustifolia fruit also induced structural changes of gut microbiota in mice. In addition, the concentrations of SCFAs increased after administration of E. angustifolia fruit. This study demonstrated that E. angustifolia fruit could ameliorate diarrhea by regulating the composition and abundance of intestinal microbiota, together with the levels of SCFAs.

Decreasing of Trimethylamine N-Oxide by Cecal Microbiota and Choline-Trimethylamine Lyase are Associated with Sishen Pill on Diarrhea with Kidney-Yang Deficiency Syndrome.

Sishen Pill (SSP) is a traditional Chinese medicine prescription commonly used to treat diarrhea with kidney-yang deficiency syndrome. The aim was to investigate the underlying mechanisms of SSP's therapeutic effects, providing experimental evidence for its mechanism of action. A mouse model of diarrhea with kidney-yang deficiency syndrome was induced using adenine combined with Folium sennae. After successful model replication, SSP decoction was administered. CutC activity, TMAO, IL-6, TNF-α levels, and cecal content microbiota were measured. SSP significantly improved the general behavioral characteristics of diarrhea mice, and reduced CutC activity, TMAO and IL-6 levels. Sequencing results indicated significant changes at the phylum and genus levels. Correlation analysis revealed a positive correlation between CutC activity and Faecalibaculum (p<0.05) and Chryseobacterium (p<0.05), and a significant negative correlation with Prevotellaceae UCG-001, Rikenella (p<0.05), Acinetobacter (p<0.05), Parasutterella (p<0.05), and Lacticaseibacillus (p<0.05). TNF-α levels showed a significant negative correlation with Lacticaseibacillus (p<0.05), Prevotellaceae UCG-001 (p<0.01), Parasutterella (p<0.05), and Candidatus Saccharimonas (p<0.05). IL-6 levels exhibited a significant negative correlation with Rikenella (p<0.05), Acinetobacter (p<0.05), Prevotellaceae UCG-001 (p<0.05), Lacticaseibacillus (p<0.01), and Parasutterella (p<0.05), and a significant positive correlation with Faecalibaculum (p<0.05), Chryseobacterium (p<0.01), and A2. Serum TMAO levels showed a significant positive correlation with Faecalibaculum (p<0.05) and Chryseobacterium (p<0.01), and hepatic TMAO levels exhibited a significant positive correlation with Chryseobacterium (p<0.05). SSP significantly alleviated the symptoms of diarrhea with kidney-yang deficiency syndrome by modulating the cecal microbiota, downregulating CutC activity, and reducing TMAO and inflammatory factor levels. The cecal microbiota-CutC-TMAO-inflammatory cytokine axis may be a key mechanism underlying the therapeutic effects of SSP.

TMAO is involved in kidney-yang deficiency syndrome diarrhea by mediating the “gut-kidney axis”

BackgroundTrimethylamine-N-oxide (TMAO) is a harmful metabolite dependent on the intestinal microbiota and excreted through the kidneys. According to numerous investigations, rich circulation concentrations of TMAO have been linked to kidney and gastrointestinal disorders. Through the “gut-kidney axis” mediated by TMAO, this research attempted to clarify the microbiological causes of kidney-yang deficiency syndrome diarrhea. MethodsAdenine and Folium Sennae were used to create a mouse model of kidney-yang deficiency syndrome diarrhea. 16S rRNA sequencing was used to identify the traits of the intestinal mucosal microbiota. ELISA was used to assess TMAO, transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β), and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). Kidney tissue fibrosis was evaluated using Masson's trichrome staining, and immunohistochemical labeling was used to investigate the protein expression of occludin and Zonula Occludens-1(ZO-1) in small intestine tissue. Microbial activity was determined by using fluorescein diacetate (FDA) hydrolysis spectrophotometry. ResultsTMAO showed a positive correlation with NLRP3, IL-1β and TGF-β1, all of which exhibited substantial increases (P < 0.05). Significant renal fibrosis and decreased ZO-1 and occludin expression in small intestine tissues were detected in the model group. The sequencing results revealed alterations in both α and β diversities of small intestinal mucosal microbiota. Elevated TMAO concentrations were potentially associated with increasing Firmicutes/Bacteroidota (F/B) ratios, Streptococcus, Pseudomonas and unclassified Clostridia UCG 014, but with decreasing Rothia and RB41 abundances. ConclusionThis study establishes a link between intestinal microbiota dysbiosis and elevated TMAO concentrations. TMAO can activate inflammatory responses and cytokines, contributing to kidney-yang deficiency syndrome diarrhea via the “gut-kidney axis”. Moreover, TMAO may coincide with disruptions in the intestinal barrier and renal fibrosis. Dysfunction of the “gut-kidney axis” further elevates TMAO levels, perpetuating a vicious cycle.

Multi-bionic strategy combined with surface for anti-fouling

More and more bio-inspired methods are used to obtain anti-fouling surfaces, in which the structure plays a pivotal role in bionic coatings. It is a trend to prepare dynamic anti-fouling surfaces to improve the anti-fouling performance of the surface and synthesis the large-scale surface. Therefore, based on the special multilevel structure of Folium Sennae, the Folium Sennae-inspired surface was prepared and modified by the active molecule from Folium Sennae here (GFSF-x, AGFSF-y). Based on the excellent anti-fouling of Folium Sennae-inspired surfaces, a series of arrayed dynamic surfaces with structure-controlling liquid behavior were prepared (VMxFy). Among them, AGFSF-5 shows an excellent anti-fouling performance, whose anti-diatom attachment rate is as high as 97.8 %. The arrayed-structured coatings (MxFy) exhibit an ability to hinder the adhesion of plaque in mussel adhesion experiments. In addition, the inhibition attachment rate of diatoms of AGMPF-4 (MxFy was subjected to optimal concentration assembly) is 83.7 %, while it is 99.5 % of VMxFy. Besides, the liquid grows dynamically along the arrayed structure, and the height of VMNF-4 increased from 15.12 to 206.26 μm. The bio-inspired surfaces based on the two methods here show outstanding anti-fouling ability, in particular, the arrayed-structured surface controlling liquid behavior. This study provides a new idea for the construction of dynamic structural surfaces and shows the practical application potential due to its ability to large-scale surface texture.

Sishen Pill inhibits intestinal inflammation in diarrhea mice via regulating kidney-intestinal bacteria-metabolic pathway.

Sishen Pill (SSP) has good efficacy in diarrhea with deficiency kidney-yang syndrome (DKYS), but the mechanism of efficacy involving intestinal microecology has not been elucidated. This study investigated the mechanism of SSP in regulating intestinal microecology in diarrhea with DKYS. Adenine combined with Folium sennae was used to construct a mouse model of diarrhea with DKYS and administered with SSP. The behavioral changes and characteristics of gut content microbiota and short-chain fatty acids (SCFAs) of mice were analyzed to explore the potential association between the characteristic bacteria, SCFAs, intestinal inflammatory and kidney function-related indicators. After SSP intervention, the body weight and anal temperature of diarrhea with DKYS gradually recovered and approached the normal level. Lactobacillus johnsonii was significantly enriched, and propionic, butyric, isobutyric and isovaleric acids were elevated. Serum creatinine (Cr), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) levels of the mice were reduced, while serum blood urea nitrogen (BUN) and secretory immunoglobulin A (sIgA) in the colonic tissues were increased. Moreover, there were correlations between L. johnsonii, SCFAs, intestinal inflammatory, and kidney function. SSP might suppress the intestinal inflammation by regulating the "L. johnsonii-propionic acid" pathway, thus achieving the effect of treating diarrhea with DKYS.

The lack of PPARα exacerbated the progression of non-alcoholic steatohepatitis in mice with spleen deficiency syndrome by triggering an inflammatory response.

In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.

Dysfunction of cecal microbiota and CutC activity in mice mediating diarrhea with kidney-yang deficiency syndrome.

Previous studies have indicated that diarrhea with kidney-yang deficiency syndrome leads to a disorder of small intestine contents and mucosal microbiota. However, the relationship of TMA-lyase (CutC) activity and TMAO with diarrhea with kidney-yang deficiency syndrome remains unexplored. Therefore, this study explores the relationship between cecal microbiota and choline TMA-lyase (CutC) activity, as well as the correlation between trimethylamine oxide (TMAO), inflammatory index, and CutC activity. Twenty SPF-grade male KM mice were randomly divided into the normal group (CN) and the diarrhea model group (CD). Diarrhea mouse models were established by adenine combined with Folium sennae administration. CutC activity, TMAO, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were detected, and the cecal content microbiota was sequenced. After 14 days, diarrhea occurred in the CD group. Compared with the CN group, there was no significant change in the activity of CutC in the small intestine of the CD group, while the activity of CutC in the cecum was significantly increased, and the levels of TMAO, IL-6, and TNF-α showed a significant increase. The Chao1 index, Observed_species index, Shannon index, and Simpson index all exhibited a decreasing trend. The main changes at the bacterial genus level were Alistipes, Enterorhabdus, Desulfovibrio, Bacteroides, Candidatus_Saccharimonas, and [Ruminococcus]_torques_group. The results of LEfSe analysis, random forest analysis and ROC curve analysis revealed Paludicola, Blautia, Negativibacillus, Paraprevotella, Harryflintia, Candidatus_Soleaferrea, Anaerotruncus, Oscillibacter, Colidextribacter, [Ruminococcus]_torques_group, and Bacteroides as characteristic bacteria in the CD group. Correlation analysis showed a significant negative correlation between cecal CutC activity and Ligilactobacillus, and a significant positive correlation with Negativibacillus and Paludicola. The level of TMAO was significantly positively correlated with CutC activity and IL-6. Diarrhea with kidney-yang deficiency syndrome significantly affects the physiological status, digestive enzyme activity, CutC activity, TMAO levels, and inflammatory response in mice. Additionally, there are changes in the composition and function of cecal microbiota, indicating an important impact of diarrhea with kidney-yang deficiency syndrome on the host intestinal microbiota balance. The occurrence of diarrhea with kidney-yang deficiency syndrome may be associated with dysbiosis of intestinal microbiota, increased CutC activity, elevated TMAO levels, and heightened inflammatory factor levels.

Effective degradation of anthraquinones in Folium Sennae with Monascus fermentation for toxicity reduce and efficacy enhancement

Folium Sennae are widely used around the world, mainly in purging and removal of endogenous active substances, such as anthraquinone and its derivatives. However, the potential toxicity of anthraquinones to the liver, kidney, and intestinal limits the application of Folium Sennae. In this study, we aimed at safe regulation of Folium Sennae to degrade anthraquinones, boosting medicinal properties and reducing toxicity and potency with Monascus fermentation. Monascus strains H1102 for Folium Sennae fermentation were selected as the initial strain which was capable of producing high yields of functional pigment and low yields of hazardous citrinin. The anthraquinone degradation rate reached 41.2%, with 212.2 U mL−1 of the pigment and approximately 0.038 mg L−1 of the citrinin under optimal fermentation conditions followed by response surface streamlining, which met the requirements of reducing toxicity, increasing efficiency of Monascus fermented Folium Sennae. Furthermore, the Monascus/Folium Sennae culture had no observable toxic effect on HK-2 and L-02 cells in vitro and further inhibited cell apoptosis and necrosis. Overall, our results showed that Monascus fermentation could provide an alternative strategy for toxicity reduction of herbal medicines as well as efficacy enhancement.

Correlation Between Kidney Function and Intestinal Biological Characteristics of Adenine and Folium SennaeInduced Diarrhea Model in Mice.

This study investigated the correlation among kidney function, intestinal enzyme activities, and microbial activity of adenine and Folium sennae-induced diarrhea model in mice, which provided a basis for clinical treatment of kidney-intestinal correlation. We performed different doses of adenine combined with Folium sennae intragastric administration to establish the animal model of diarrhea. We assessed thymus and spleen indexes, serum creatinine, urea nitrogen and uric acid contents, intestinal contents and mucosal enzyme activities, and microbial activity. After modeling, mice presented increased serum creatinine and decreased urea nitrogen. Uric acid showed different changes in the different model groups. The thymus index in the model mice was trending downward, whereas the spleen index was the opposite. Moreover, model mice induced a non-significant increase in xylanase activity of the intestinal contents and mucosa compared to the control performance. Sucrase content of the intestinal contents increased considerably in the model groups but decreased in the intestinal mucosa. Lactase and amylase induced different trends in the different modeling methods. As well, the microbial activity of intestinal contents increased significantly, while that of intestinal mucosa decreased. Adenine combined with Folium sennae successfully replicated diarrhea in mice models. Using 50 mg/ (kg/day) adenine for 14 days in combination with 10 g/(kg/day) Folium sennae decoction for 7 days caused kidney function injury in diarrhea mice. In addition, kidney function injury was accompanied by changing in intestinal functional enzyme activity and microbial activity.

Deep-fried Atractylodes lancea rhizome alleviates spleen deficiency diarrhea–induced short-chain fatty acid metabolic disorder in mice by remodeling the intestinal flora

Ethnopharmacological relevanceAtractylodes lancea (Thunb.) DC. is a Chinese herb that has been commonly used to treat spleen-deficiency diarrhea (SDD) in China for over a thousand years. However, the underlying mechanism of its antidiarrheal activity is not fully understood. Aim of the studyThe antidiarrheal effects of the ethanol extract of deep-fried A. lancea rhizome (EEDAR) due to spleen deficiency induced by folium sennae (SE) were determined on the regulation of the short-chain fatty acid (SCFA) metabonomics induced by the intestinal flora. Materials and methodsThe effects of EEDAR on a SE-induced mouse model of SDD were evaluated by monitoring the animal weight, fecal water content, diarrhea-grade rating, goblet cell loss, and pathological changes in the colon. The expression of inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10), aquaporins (AQP3, AQP4, and AQP8), and tight junction markers (ZO-1, occludin, claudin-1) in colon tissues were determined using quantitative polymerase chain reaction and western blotting. SCFA metabonomics in the feces of mice treated with EEDAR was evaluated using gas chromatography–mass spectrometry. Furthermore, 16S rDNA sequencing was used to determine the effect of EEDAR on the intestinal flora of SDD mice, and fecal microbiota transplantation (FMT) was used to confirm whether the intestinal flora was essential for the anti-SDD effect of EEDAR. ResultsTreatment with EEDAR significantly improved the symptoms of mice with SDD by inhibiting the loss of colonic cup cells, alleviating colitis, and promoting the expression of AQPs and tight junction markers. More importantly, the effect of EEDAR on the increase of SCFA content in mice with SDD was closely related to the gut microbiota composition. EEDAR intervention did not significantly improve intestinal inflammation or the barrier of germ-free SDD mice, but FMT was effective. ConclusionEEDAR alleviated SE-induced SDD in mice, as well as the induced SCFA disorder by regulating the imbalance of the intestinal microbiota.

Gut-Kidney Impairment Process of Adenine Combined with Folium sennae-Induced Diarrhea: Association with Interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and Acetic Acid, Inflammation, and Kidney Function.

Background: Extensive evidence suggests that gut microbiota may interact with the kidneys and play central roles in the pathogenesis of disease. However, the association of gut microbiota-kidneys in diarrhea remains unclear. Methods: A diarrhea mouse model was constructed by combining adenine with Folium sennae. We analyzed the characteristics of the gut content microbiota and short chain fatty acids (SCFAs); and explored the potential link between gut content microbiota, SCFAs, intestinal inflammatory response and kidney function. Results: Characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens were enriched in the gut contents of mice. The productions of SCFAs were remarkably inhibited. Model mice presented an increased trend of creatinine (Cr), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), a decreased trend of blood urea nitrogen (BUN) and secretory immunoglobulin A (SIgA). The pathological analysis proved obvious damage to the kidney structure. Lactobacillus intestinalis and Bacteroides acidifaciens exisited in the correlations with acetic acid, intestinal inflammatory response and kidney function. Conclusions: Adenine combined with Folium sennae-induced diarrhea, altered the structure and function of the gut content microbiota in mice, causing the enrichment of the characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens. The interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and acetic acid, intestinal inflammation, and kidney function might be involved in the process of gut-kidney impairment in adenine, combined with Folium sennae-induced diarrhea.

Diarrhea with deficiency kidney-yang syndrome caused by adenine combined with Folium senna was associated with gut mucosal microbiota.

The present study aims to study and analyze the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Ten male mice were randomly divided into the control group and the model group. Diarrhea mice model with deficiency kidney-yang syndrome was established by adenine combined with Folium sennae. The kidney structure was observed by hematoxylin-eosin (HE) staining. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA). The characteristics of gut mucosal microbiota were analyzed by performing third-generation high-throughput sequencing. The results showed that the model mice exhibit obvious structural damage to the kidney. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels showed a decreased trend in the model group. The diversity and community structure of the gut mucosal microbiota improved in the model group. Dominant bacteria like Candidatus Arthromitus, Muribaculum, and Lactobacillus reuteri varied significantly at different taxonomic levels. The characteristic bacteria like Bacteroides, Erysipelatoclostridium, Anaerotignum, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii were enriched in the model group. A correlation analysis described that Erysipelatoclostridium was positively correlated with Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels, while Anaerotignum exhibited an opposite trend. Together, adenine combined with Folium sennae damaged the structure of the kidney, affected energy metabolism, and caused disorders of gut mucosal microbiota in mice. Bacteroides, Erysipelatoclostridium, and Anaerotignum showed significant inhibition or promotion effects on energy metabolism. Besides, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii might be the characteristic species of gut mucosal microbiota responsible for causing diarrhea with deficiency kidney-yang syndrome.

Orally Administered Xylo-Oligosaccharides (XOS) Ameliorates Diarrhea Symptoms in Mice via Intestinal Barrier Improvement and Gut Microbiota Modulation.

Xylo-oligosaccharides (XOS) has a bidirectional regulatory effect, and can be fermented by gut microbiota. This study aims to investigate how XOS alleviates Folium Sennae extracts induced diarrhea in mice. KM mice are given different concentration XOS for 3 weeks, and then Folium Sennae (Senna alexandrinaMill) extracts solutions (0.8gmL-1 ) are given to establish diarrhea model. The results show that doses of XOS at 0.25mgg-1 BW day-1 and higher could alleviate diarrhea symptoms by decreasing the disease activity indexes, down-regulating pro-inflammatory factors, up-regulating anti-inflammatory factor, and suppressing the intestinal permeability in colon tissues. XOS also regulates the composition of gut microbiota via increasing the abundance Prevotellaceae, Ruminococcus, and Bifidobacterium. The results suggest that the dietary supplementation XOS could be a more effective choice to prevent and alleviate diarrhea.

Atractyloside-A ameliorates spleen deficiency diarrhea by interfering with TLR4/MyD88/NF-κB signaling activation and regulating intestinal flora homeostasis

PurposeSpleen deficiency diarrhea (SDD) is one of the most common types of diarrhea and is linked to intestinal barrier dysfunction and intestinal flora disorders. Atractyloside-A (AA) is one of the main components of Atractylodes Lancea(Thunb.) DC., which acts on the gastrointestinal tract and has therapeutic effects on diarrhea. Folium sennae is a medicinal plant inducing diarrhea; thus, it is one of the effective methods to obtain a diarrhea model. However, the mechanism of action of AA in the treatment of SDD induced by Folium sennae is unclear. MethodsThe intestinal thrapeutic effect of AA on SDD in mice was evaluated by colon pathology. RNA sequencing (RNA-seq) was used to analyze the colonic transcriptome profiles. In addition, 16S rDNA sequencing and fecal microbiota transplantation (FMT) were carried out to verify the role of AA in the regulation of the intestinal flora. ResultsThe findings revealed that AA alleviated SDD by ameliorating the pathological symptoms while suppressing intestinal inflammatory responses through the TLR4/MyD88/NF-kB signaling and reversing the impairment of mucin synthesis. Furthermore, AA improved the integrity of the intestinal barrier. RNA-seq identified 436 common DEGs out of 1033 DEGs between SDD and AA, and 1933 DEGs between SDD and Ctrl, which are highly enriched in the NF-κB and TNF pathways. Moreover, AA altered the composition of the intestinal flora and FMT reduced SDD. ConclusionAA exerted a therapeutic effect on SDD through the regulation of the intestinal flora and the inflammation by interfering with the TLR4/MyD88/NF-κB signaling pathway.

Folium Sennae Increased the Bioavailability of Methotrexate through Modulation on MRP 2 and BCRP.

Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC0–2880, AUC720–2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC720–2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP.

Based on Network Pharmacology and Molecular Docking Technology, the Mechanism of Folium Sennae, Aloe Combined with Panax Quinquefolium in Treating Functional Constipation Was Investigated

Based on Network Pharmacology and Molecular Docking Technology, the Mechanism of Folium Sennae, Aloe Combined with Panax Quinquefolium in Treating Functional Constipation Was Investigated

Therapeutic effect of Moringa oleifera leaves on constipation mice based on pharmacodynamics and serum metabonomics

Ethnopharmacological relevanceMoringa oleifera is native to India, and has been introduced to China in recent years. Moringa oleifera leaves (MOL), as Ayurvedic medicine, has efficacy of Pachana karma (digestive) and Virechana karma (purgative). Folium Sennae (FS), Rhubarb (RB), Aloe vera (AV), Hemp seed (HS) are commonly used as laxatives in Traditional Chinese Medicine (TCM), which have different characteristics. However, the intensity of the diarrheal effect of MOL and its mechanism of action are unclear. Aim of the studyThe methods of pharmacology and omics were used to compare the purgative effects of MOL and FS, RB, AV, HS, and their effects on metabolomics, to analyze the purgative characteristics and related mechanisms of MOL. Materials and methodsC57BL/6J mouse model of constipation was established by feeding low-fiber food. Feces parameters and colon pathology were used to evaluate the effect of FS, RB, AV, HS and MOL. And mass spectrometry-based serum metabolomics was performed. The differential metabolites of these herbs in the treatment of constipation were obtained by OPLS-DA analysis. Furthermore, pathway analysis was conducted based on different metabolites. ResultsMoringa leaves can adjust the stool number, wet fecal weight and fecal water content to varying degrees to achieve laxative effects, and recover colon muscle thickness and mucus. Analysis of metabolomics results showed that 71 metabolites from LC-MS datasets between model group and control group were obtained. 29, 12, 44, 29 and 20 metabolites were significantly reversed by FS, RB, AV, HS, MOL compared with model group respectively. According to the metabolic pathways, RB and AV may be clustered into a similar category, and MOL, FS and HS showed similarity of metabolic characteristics. ConclusionThe purgative effect of MOL is inferior to that of FS, and stronger than that of AV, RB and HS. The metabolic pathway for constipation is more similar to that of FS. MOL has a long-lasting and mild effect of laxative, increasing defecation volume and water content of feces, and may become a fewer side effects medicine to treat constipation.

Effect of acupoint catgut embedding on intestinal mucosal epithelial barrier in ulcerative colitis rats

To observe the effect of acupoint catgut embedding on intestinal mucosal epithelial injury, and expression of epithelial tight junction proteins and mRNAs and protein kinase C(PKC) protein (intestinal mucosal epithelial barrier-related molecules) in rats with experimental ulcerative colitis (UC) of "deficiency-stasis" type, so as to explore its mechanisms underlying improvement of UC. Male SD rats were randomly divided into normal control, UC model, medication (sulfasalazine, SASP) and catgut-embedding groups. The "deficiency-stasis" type UC model was established by gavage of adenine (10 mL/kg) for 2 weeks, cold Folium Sennae (10 mL/kg) for 2 weeks, and then enema of mixture solution of 5% trinitro-benzene-sulfonic acid (100 mg/kg) + 50% ethyl alcohol. Rats of the medication group received gavage of SASP. The catgut-embedment was applied to bilateral "Tianshu"(ST23),"Zusanli"(ST36), "Geshu"(BL17), "Pishu"(BL20), "Shenshu"(BL23) and "Dachangshu"(BL25), once every two weeks, 3 times altogether. The body mass was recorded, and histopathological changes of the colon tissues were observed after H.E. staining. The contents of serum D-lactic acid (D-LA), diamine oxidase (DAO) and protein kinase C (PKC) were detected by ELISA. The expression levels of occludin, claudin-8, cingulin and zonulin mRNAs and proteins and PKC protein of the colon tissues were detected by using quantitative real-time PCR and Western blot, separately. Compared with the control group, the body mass and expression levels of colonic occludin, claudin-8 and cingulin mRNAs and proteins were significantly lower (P<0.01), and the colonic mucosa damage index (CMDI) score, contents of serum D-LA, DAO and PKC, as well as the expression levels of zonulin mRNA and protein and PKC protein were significantly higher in the model group (P<0.01). In comparison with the model group, the body mass, and the expression levels of occludin, claudin-8 and cingulin mRNAs and proteins were significantly higher (P<0.05, P<0.01), whereas the CMDI score, expression levels of zonulin mRNA and protein and PKC protein were remarkably lower in both the medication group and acupoint embedding groups (P<0.05,P<0.01). No significant differences were found between the acupoint embedding and medication groups in all the indexes mentioned above (P>0.05). H.E. staining showed markedly swollen, disordered arrangement of intestinal mucosal cells, and hemorrhage with infiltration of inflammatory cells in the colonic tissues after modeling, which was relatively milder in both medication and acupoint embedding groups. Acupoint catgut embedding can reduce colonic tissue injury in UC rats, which may be related to its functions in regulating the expression of intestinal epithelial tight junction proteins and mRNAs and in inhibiting the activation of PKC protein.

Role of tryptophan-metabolizing microbiota in mice diarrhea caused by Folium sennae extracts

BackgroundAlthough reports have provided evidence that diarrhea caused by Folium sennae can result in intestinal microbiota diversity disorder, the intestinal bacterial characteristic and specific mechanism are still unknown. The objective of our study was to investigate the mechanism of diarrhea caused by Folium sennae, which was associated with intestinal bacterial characteristic reshaping and metabolic abnormality.ResultsFor the intervention of Folium sennae extracts, Chao1 index and Shannon index were statistical decreased. The Beta diversity clusters of mice interfered by Folium sennae extracts were distinctly separated from control group. Combining PPI network analysis, cytochrome P450 enzymes metabolism was the main signaling pathway of diarrhea caused by Folium sennae. Moreover, 10 bacterial flora communities had statistical significant difference with Folium sennae intervention: the abundance of Paraprevotella, Streptococcus, Epulopiscium, Sutterella and Mycoplasma increased significantly; and the abundance of Adlercreutzia, Lactobacillus, Dehalobacterium, Dorea and Oscillospira reduced significantly. Seven of the 10 intestinal microbiota communities were related to the synthesis of tryptophan derivatives, which affected the transformation of aminotryptophan into L-tryptophan, leading to abnormal tryptophan metabolism in the host.ConclusionsFolium sennae targeted cytochrome P450 3A4 to alter intestinal bacterial characteristic and intervene the tryptophan metabolism of intestinal microbiota, such as Streptococcus, Sutterella and Dorea, which could be the intestinal microecological mechanism of diarrhea caused by Folium sennae extracts.

Folium Sennae and emodin reverse airway smooth muscle contraction.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.