Figure 5 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Effects of B. animalis subsp. lactis LKM512 on intestinal peristalsis of mice administered sennoside after kanamycin treatment. (A) Picture of the intestinal tract. The activity of intestinal peristalsis was expressed as the distance travelled by the charcoal powder from the end of the ileum (i.e. the base of the caecum or start of the colon) to the top of the charcoal powder, measured using a ruler. (B) Comparison of the length of charcoal powder from the end of the ileum. This value was significantly longer in LKM512-adminstered mice (n = 5) than in the control (n = 5) (p,0.05), modified Wilcoxon signedrank test). Error bars show the standard error of the mean. doi:10.1371/journal.pone.0031700.g005
Source publication
While there are a variety of identifiable causes of constipation, even idiopathic constipation has different possible mechanisms. Sennosides, the main laxative constituents of Daio, an ancient Kampo medicine, are prodrugs that are converted to an active principle, rheinanthrone, by intestinal microbiota. In this study, we aimed to determine the sen...
Contexts in source publication
Context 1
... study was performed using LKM512, because the laxative ability of LKM10070 was too strong in the sennoside hydrolysis test. An example of this test is shown in Figure 5. In almost all pairs, the distance travelled by the charcoal powder was greater in LKM512-treated mice than in the controls (n = 5), similar to that shown in Figure 5A. ...
Context 2
... example of this test is shown in Figure 5. In almost all pairs, the distance travelled by the charcoal powder was greater in LKM512-treated mice than in the controls (n = 5), similar to that shown in Figure 5A. The distance travelled by the charcoal powder from the end of the ileum in LKM512-treated mice was significantly longer than that of control (p,0.05) ( Figure 5B). ...
Context 3
... almost all pairs, the distance travelled by the charcoal powder was greater in LKM512-treated mice than in the controls (n = 5), similar to that shown in Figure 5A. The distance travelled by the charcoal powder from the end of the ileum in LKM512-treated mice was significantly longer than that of control (p,0.05) ( Figure 5B). ...
Citations
... The metabolism and potential bioconversion of these compounds begin within the gut, mediated by the gut microbiome (Wang et al., 2021). Mastumoto et al. demonstrated the ability of selected lactic acid bacteria to deglycosylate sennosides in vivo in mice which led to increased intestinal motility (Matsumoto et al., 2012) and such microbial conversion of compounds such as sennosides to the aglycone anthraquinone form appears to be necessary to induce the laxative effect of these compounds (Hardcastle and Wilkins, 1970;Zu et al., 2018;Zhao et al., 2022;Zhang et al., 2023) whereupon the active compounds stimulate motility and draw fluid into the colon (Portalatin and Winstead, 2012). ...
... Another bifidobacterial species which decreased in the SSE incubations was Bifidobacterium pseudocatenulatum. Interestingly, a strain of B. pseudocatenulatum, was shown to be extremely effective at sennoside deglycosylation (Matsumoto et al., 2012). Like other Bifidobacterium sp. it is well adapted to the human gut because it possesses carbohydrate active enzymes (CAZymes) including endo-1,4-b-xylanase (Watanabe et al., 2021) and bglucosidase which is also key in the transformation and activation of sennosides. ...
The genus Senna contains globally distributed plant species of which the leaves, roots, and seeds have multiple traditional medicinal and nutritional uses. Notable chemical compounds derived from Senna spp. include sennosides and emodin which have been tested for antimicrobial effects in addition to their known laxative functions. However, studies of the effects of the combined chemical components on intact human gut microbiome communities are lacking. This study evaluated the effects of Juemingzi (Senna sp.) extract on the human gut microbiome using SIFR® (Systemic Intestinal Fermentation Research) technology. After a 48-hour human fecal incubation, we measured total bacterial cell density and fermentation products including pH, gas production and concentrations of short chain fatty acids (SCFAs). The initial and post-incubation microbial community structure and functional potential were characterized using shotgun metagenomic sequencing. Juemingzi (Senna seed) extracts displayed strong, taxon-specific anti-microbial effects as indicated by significant reductions in cell density (40%) and intra-sample community diversity. Members of the Bacteroidota were nearly eliminated over the 48-hour incubation. While generally part of a healthy gut microbiome, specific species of Bacteroides can be pathogenic. The active persistence of the members of the Enterobacteriaceae and selected Actinomycetota despite the reduction in overall cell numbers was demonstrated by increased fermentative outputs including high concentrations of gas and acetate with correspondingly reduced pH. These large-scale shifts in microbial community structure indicate the need for further evaluation of dosages and potential administration with prebiotic or synbiotic supplements. Overall, the very specific effects of these extracts may offer the potential for targeted antimicrobial uses or as a tool in the targeted remodeling of the gut microbiome.
... Due to poor intestinal absorption, the main component of rhubarb, sennoside, only has a modest impact on diarrhea. Sennoside is degraded by the b-D-glucosidase produced by the bacteria Bifidobacteria, resulting in the creation of sennoside glycoside (rheinanthrone), which causes diarrhea (Matsumoto et al., 2012). Moreover, Intestinal bacteria convert rhapontin into rhapontigenin, which has more potent antithrombotic and antiallergic properties than its parent substance. ...
... Due to poor intestinal absorption, the main component of rhubarb, sennoside, only has a modest impact on diarrhea. Sennoside is degraded by the b-D-glucosidase produced by the bacteria Bifidobacteria, resulting in the creation of sennoside glycoside (rheinanthrone), which causes diarrhea (Matsumoto et al., 2012). Moreover, Intestinal bacteria convert rhapontin into rhapontigenin, which has more potent antithrombotic and antiallergic properties than its parent substance. ...
The gut microbiome is the community of healthy, and infectious organisms in the gut and its interaction in the host gut intestine (GI) environment. The balance of microbial richness with beneficial microbes is very important to perform healthy body functions like digesting food, controlling metabolism, and precise immune function. Alternately, this microbial dysbiosis occurs due to changes in the physiochemical condition, substrate avidity, and drugs. Moreover, various categories of diet such as "plant-based", "animal-based", "western", "mediterranean", and various drugs (antibiotic and common drugs) also contribute to maintaining microbial flora inside the gut. The imbalance (dysbiosis) in the microbiota of the GI tract can cause several disorders (such as diabetes, obesity, cancer, inflammation, and so on). Recently, the major interest is to use prebiotic, probiotic, postbiotic, and herbal supplements to balance such microbial community in the GI tract. But, there has still a large gap in understanding the microbiome function, and its relation to the host diet, drugs, and herbal supplements to maintain the healthy life of the host. So, the present review is about the updates on the microbiome concerns related to diet, drug, and herbal supplements, and also gives research evidence to improve our daily habits regarding diet, drugs, and herbal supplements. Because our regular dietary plan and traditional herbal supplements can improve our health by balancing the bacteria in our gut.
... It is well-documented that Bifidobacterium spp. (Matsumoto et al., 2012), Bacillus spp. , and Lactobacillus spp. ...
... Pace et al., 2015) play a pivotal role in promoting digestion and enhancing intestinal peristalsis. The declining of these bacteria would deteriorate gastrointestinal tract function and lead to constipation Lu et al., 2019;Matsumoto et al., 2012). On the other aspect, the enrichment of opportunistic pathogens such as Klebsiella pneumoniae and Enterobacter cloacae may promote the occurrence of diarrhea (Lu et al., 2020;Magwira et al., 2021). ...
Ethnopharmacological relevance:
The meridian (GuiJing) theory is a unique theory of traditional Chinese medicine (TCM) which has been guiding the clinical practice of TCM for thousands of years, but physiological foundation of TCM's meridian remains to be clarified. Recent investigations have marked gut microbiota as a key mediator for the pharmacological effects of various TCMs. However, most studies focus on the response of gut microbes to a single drug or formula, the interactive effects of different drugs on gut microbiota are scarcely investigated.
Aim of the study:
In this work, we evaluated the co-regulatory effects of different TCMs on gut microbiota when they were individually combined with Coptis chinensis (HL), and assessed the relationship between gut microbiota and the GuiJing of TCMs.
Materials and methods:
Normal C57BL/6 mice were gavaged with HL extract for 14 days to disrupt the gut microbial community. Simultaneously, animals were treated with different TCMs which all possess antimicrobial activity but belong to different meridians. The gut microbiota was analyzed by full-length 16S rRNA gene amplicon sequencing to get a thorough bacterial profile at the species level.
Results:
Administration of HL dramatically disrupted the gut microbiota and decreased the alpha diversity. Co-administration of different TCMs alleviated the adverse impact of HL on gut microbiota in a meridian-dependent manner. TCMs belonging to Shaoyin meridian moderately shifted the gut microbiota, while TCMs belonging to Taiyin and especially Jueyin meridians remarkably recovered the gut microbial community to the normal status. Decreased Firmicutes (Clostridia and Bacilli) and Actinobacteria (Bifidobacteriales) and increased Proteobacteria (Enterobacteriaceae) were main features of HL-induced gut dysbiosis. TCMs belonging to Shaoyin, Taiyin and Jueyin meridians gradually reversed the abundance of these bacteria to their normal levels. Simultaneously, the promoting effect of HL on beneficial bacteria such as Akkermansia muciniphila and Blautia coccoides was substantially preserved when co-administration of these TCMs, suggesting that co-treatment with these TCMs may reduce the toxicity of HL without deteriorating its beneficial effects.
Conclusion:
Combination of special TCMs may alleviate the adverse effect of HL on gut microbiota while preserving its beneficial actions. Gut microbiota may be a potential biological indicator of the meridian of TCMs.
... For instance, a study comparing two groups of Korean subjects with distinct capabilities for metabolizing compound K showed a marked difference in the compositions of their GM, which explained the inconsistency in the drug potency of Panax ginseng between individuals [116]. Another case is the Rhei Radix medicine used in postoperative patients; these patients are frequently administered antibiotics, which prevents the prodrug from being properly metabolized by the GM, and purgative efficacy was not observed in many cases [117]. Another consideration is the fact that the diversity of the GM varied across ethnicities, which could also influence the efficacy of natural drugs [118]. ...
Resembling a concealed "organ" in a holobiont, trillions of gut microbes play complex roles in the maintenance of homeostasis, including participating in drug metabolism. The conventional opinion is that most of any drug is metabolized by the host and that individual differences are principally due to host genetic factors. However, current evidence indicates that only about 60% of the individual differences in drug metabolism are attributable to host genetics. Although most common chemical drugs regulate the gut microbiota, the gut microbiota is also known to be involved in drug metabolism, like the host. Interestingly, many traditional herbal medicines and derived compounds are biotransformed by gut microbiota, manipulating the compounds' effects. Accordingly , the gut microbiota and its specified metabolic pathways can be deemed a promising target for promoting drug efficacy and safety. However, the evidence regarding causality and the corresponding mechanisms concerning gut microbiota and drug metabolism remains insufficient, especially regarding drugs used to treat metabolic disorders. Therefore, the present review aims to comprehensively summarize the bidirectional roles of gut microbiota in the effects of herbal medicine in metabolic diseases to provide vital clues for guiding the clinical application of precision medicine and personalized drug development.
... Sennoside A, a major component of rhubarb extract, is metabolized into rhein anthrone by β-glucosidase of Bifidobacterium sp. strain SEN (Matsumoto et al., 2012;Kon et al., 2014). Under the action of carboxylesterase (CEs), which are expressed by gut microbes, diester diterpenoid alkaloids (DDAs, such as aconitine) hydrolyze the ester bonds of C-8 and C-14 to produce monoester diterpene alkaloids (MDAs, such as hypaconitine), which are less toxic . ...
... The addition of methyl Hydrolysis of natural products under the action of gut microbes. (A-E) Hydrolysis of hesperidin (Mas-Capdevila et al., 2020), geniposide , aconitine , theasinensin A (Liu Z. et al., 2021), sennoside A or B (Matsumoto et al., 2012). ...
Natural products have been extensively applied in clinical practice, characterized by multi-component and multi-target, many pharmacodynamic substances, complex action mechanisms, and various physiological activities. For the oral administration of natural products, the gut microbiota and clinical efficacy are closely related, but this relationship remains unclear. Gut microbes play an important role in the transformation and utilization of natural products caused by the diversity of enzyme systems. Effective components such as flavonoids, alkaloids, lignans, and phenols cannot be metabolized directly through human digestive enzymes but can be transformed by enzymes produced by gut microorganisms and then utilized. Therefore, the focus is paid to the metabolism of natural products through the gut microbiota. In the present study, we systematically reviewed the studies about gut microbiota and their effect on the biotransformation of various components of natural products and highlighted the involved common bacteria, reaction types, pharmacological actions, and research methods. This study aims to provide theoretical support for the clinical application in the prevention and treatment of diseases and provide new ideas for studying natural products based on gut biotransformation.
... Chinese herbal medicine dreg has many polysaccharides that are not easily decomposed by digestive enzymes, and probiotics can use abundant enzymes to convert this polysaccharide into easy-to-use small-molecule carbohydrates. Therefore, the dregs of Chinese herbal medicine can provide nutrients for the growth and metabolism of probiotics, thereby improving the resource utilization rate of the dregs of Chinese herbal medicine (ADDM Network Surveillance investigators, 2014; Guo et al., 2014;Li et al., 2018;Matsumoto et al., 2012). The fermentation of medicinal dregs through probiotics has a positive effect on environmental protection and medicinal material saving. ...
Objectives
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that often occurs in children and seriously affects daily life. In recent years, many studies have shown that intestinal microbial imbalance and intestinal-brain dysfunction may be the critical mechanism for the formation of ASD. This article reviews the changes in the gut microbiota of patients and their impact mechanisms, and the current mechanisms of probiotic and traditional Chinese medicine therapies.
Methods
A review of contemporary peer-reviewed studies. Pubmed and Cnki were the databases used to identify the studies.
Results
The majority of the reviewed studies demonstrated that changes in the gut microbiota can directly or indirectly induce ASD by affecting the immune system, nervous system, and endocrine system. Probiotics can improve brain function by affecting the vagus nerve, and improve metabolism by regulating the expression of neuroendocrine hormones. According to the Chinese medicine theory, there are three leading causes of ASD such as deficiency of kidney essence, stagnation of liver qi, and malnutrition of heart spirit.
Conclusions
The fermentation of Chinese herbal medicine and probiotics can be further studied and may become a new type of treatment for ASD in the future.
... 8) For example, sennosides were hydrolyzed by Bifidobacterium species to promote intestinal peristalsis in mice. 9) When a crude drug is ingested, the glycosides in the crude drug are hydrolyzed by intestinal bacteria in the digestive tract and metabolized in the liver, resulting in the manifestation of its pharmacological activities in the body. Three pairs of glucosides and their aglycones in the roots and stolons of Glycyrrhiza uralensis were compared with regard to their ability to suppress NO production in hepatocytes. ...
Many constituents of crude drugs in Japanese Kampo formulas are thought to function as pro-drugs, whose pharmacological activity is manifested after oral administration. Proteins and peptides in crude drugs may be digested and metabolized in the digestive tract and liver. However, few studies have reported the pharmacological activity of peptides in crude drugs. Here, we applied an analysis using LC–tandem mass spectrometry (LC-MS/MS) to identify the compounds derived from six crude drugs that are assumed to have anti-inflammatory effects. To simulate in vivo protease digestion, each water-soluble fraction of the crude drug extracts was treated with proteases, including endoproteinases and exopeptidases. Amines in the resultant digests were modified by 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate and analyzed using LC-MS/MS, which demonstrated the presence of four decarboxylated amino acids (primary amines). In the digest of the hydrophilic fraction of the fruit of Ziziphus jujuba Miller var. inermis Rehder (Taiso), isobutylamine, isoamylamine, and 2-methylbutylamine were identified, which may be derived from valinyl, leucinyl, and isoleucinyl residues, respectively. Additionally, tyramine possibly derived from tyrosyl residues was identified in the digests of all the crude drugs. In primary cultured rat hepatocytes treated with interleukin-1β, all these decarboxylated amino acids suppressed the production of nitric oxide, a proinflammatory mediator. Our approach, i.e., in vitro protease digestion and LC-MS/MS analysis, suggests that decarboxylated amino acids may be formed in vivo from peptides and may be responsible for the anti-inflammatory effect of crude drugs included in Kampo medicine.
Fullsize Image
... The anthraquinones belong to anthranoid glycosides, for which sennoside A is used as a chemical marker for quality control [4,5]. Being protected by the β-glucoside bond, the anthraquinones can reach the intestines where they are degraded into complex metabolites by enzymes secreted from the intestinal microbiome [6,7]. The purgative action of sennoside A conversion to rheinanthrone in the intestine has previously been explained in terms of Na + /K + transport, water and mucus secretion in the colon [8]. ...
Senna and rhubarb are often used as routine laxatives, but there are differences in mechanism of action and potential side effects. Here, we studied metabolites of senna anthraquinones (SAQ), rhubarb anthraquinones (RAQ) and their chemical marker, sennoside A (SA), in a rat diarrhea model. In in vitro biotransformation experiments, SAQ, RAQ and SA were incubated with rat fecal flora solution and the metabolites produced were analyzed using HPLC. In in vivo studies, the same compounds were investigated for purgation induction, with measurement of histopathology and Aqps gene expression in six organs. The results indicated that SAQ and RAQ had similar principal constituents but could be degraded into different metabolites. A similar profile of Aqps down-regulation for all compounds was seen in the colon, suggesting a similar mechanism of action for purgation. However, in the kidneys and livers of the diarrhea-rats, down-regulation of Aqps was found in the RAQ-rats whereas up-regulation of Aqps was seen in the SAQ-rats. Furthermore, the RAQ-rats showed lower Aqp2 protein expression in the kidneys, whilst the SA-rats and SAQ-rats had higher Aqp2 protein expression in the kidneys. This may have implications for side effects of SAQ or RAQ in patients with chronic kidney or liver diseases.
... HET includes triterpenoid saponins, which undergo deglycosylation in a metabolic pathway related to the microbiome 23 . In our study, the effect of Kampo medicines was promoted by probiotics, as supported by the metabolism of saponin to aglycon, which is mediated by probiotics 24,25 . These reports may explain the additional effects of probiotics on Kampo medicines in the gut environment and immune system. ...
Vancomycin-resistant enterococci (VRE) are prominent causes of nosocomial infections. Japanese traditional (Kampo) medicine promotes intestinal immunity and protects against bacterial infections. We assessed potential differences in the clinical course of VRE-positive patients, based on their characteristics and treatment with Kampo medicines. This retrospective observational study collected data from VRE-positive patients from August 2018 to July 2019 at a tertiary-care hospital in Japan. The data of 122 consecutive VRE-positive inpatients were analyzed. Sixty-nine patients were treated with probiotics, among whom, 18 were further treated with Kampo medicines. Twenty-six of the 122 patients subsequently died. In univariate analyses, subsequent VRE negative conversion significantly reduced the mortality of VRE-detected patients ( p = .0003). Administration of probiotics ( p = .0065) and Kampo medicines with probiotics ( p = .0002), especially of the Kampo medicine hochuekkito ( p = .0014), and a higher serum albumin level positively contributed to the subsequent VRE negative conversion. Multivariate analyses demonstrated that Kampo medicines and body mass index contributed to VRE negative conversion. Hochuekkito shortened the time needed for VRE negative conversion ( p = 0.0485). Administration of Kampo medicines, especially of hochuekkito, in addition to probiotics in VRE patients may promote VRE negative conversion.
