Paeonol attenuates nonalcoholic steatohepatitis by regulating intestinal flora and AhR/NLRP3/Caspase-1 metabolic pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) is a common metabolic liver injury disease that is closely associated with obesity and metabolic disorders. Paeonol, an active ingredient found in Moutan Cortex, a traditional Chinese medicine which exhibits significant therapeutic effect on liver protection, has shown promising effects in treating liver diseases, particularly NASH. However, the specific intervention mechanism of paeonol on NASH is still unknown. AIM OF THE STUDY: Our objective is to elucidate the pharmacological mechanism of paeonol in intervening NASH at the in vivo level, focusing on the impact on intestinal flora, tryptophan-related targeted metabolome, and related Aryl hydrocarbon receptor (AhR) pathways. MATERIALS AND METHODS: Here, we explored the intervention effect of paeonol on NASH by utilizing the NASH mouse model. The Illumina highthroughput sequencing technology was preformed to determine the differences of gut microbiota of model and paeonol treatment group. The concentration of Indoleacetic acid is determined by ELISA. The intervention effect of NASH mouse and AhR/NLRP3/Caspase-1 metabolic pathway is analyzed by HE staining, oil red O staining, Immunohistochemistry, Immunofluorescence, Western blot and qRT-PCR assays. Fecal microbiota transplantation experiment also was performed to verify the intervention effect of paeonol on NASH by affecting gut microbiota. RESULTS: Firstly, we discovered that paeonol effectively reduced liver pathology and blood lipid levels in NASH mice, thereby intervening in the progression of NASH. Subsequently, through 16S meta-analysis, we identified that paeonol can effectively regulate the composition of intestinal flora in NASH mice, transforming it to resemble that of normal mice. Specifically, paeonol decreased the abundance of certain Gram-negative tryptophan-metabolizing bacteria. Moreover, we discovered that paeonol significantly increased the levels of metabolites Indoleacetic acid, subsequently enhancing the expression of AhR-related pathway proteins. This led to the inhibition of the NOD-like receptor protein 3 (NLRP3) inflammasome production and inflammation generation in NASH. Lastly, we verified the efficacy of paeonol in intervening NASH by conducting fecal microbiota transplantation experiments, which confirmed its role in promoting the AhR/NLRP3/cysteinyl aspartate specific proteinase (Caspase-1) pathway. CONCLUSIONS: Our findings suggest that paeonol can increase the production of Indoleacetic acid by regulating the gut flora, and promote the AhR/NLRP3/Caspase-1 metabolic pathway to intervene NASH.

Ginseng fermentation solution affects the gut microbiota in zebrafish with alcoholic liver disease via PI3K/Akt pathway.

BACKGROUND: Ginsenosides have received increased amounts of attention due to their ability to modulate the intestinal flora, which may subsequently alleviate alcoholic liver disease (ALD). The effects of ginseng fermentation solution (GFS) on the gut microbiota and metabolism in ALD patients have not been explored. PURPOSE: This research aimed to explore the regulatory effect of GFS on ALD both in vitro and in vivo. METHOD: This study assessed the anti-ALD efficacy of GFS using an LO2 cell model and a zebrafish model. Untargeted metabolomics was used for differentially abundant metabolite analysis, and high-throughput 16S rRNA sequencing was used to examine the effect of GFS on ALD. RESULTS: The LO2 cell line experiments demonstrated that GFS effectively mitigated alcohol-induced oxidative stress and reduced apoptosis by upregulating PI3K and Bcl-2 expression and decreasing the levels of malondialdehyde, total cholesterol, and triglycerides. In zebrafish, GFS improved morphological and physiological parameters and diminished oxidative stress-induced ALD. Meanwhile, the results from Western blotting indicated that GFS enhanced the expression of PI3K, Akt, and Bcl-2 proteins while reducing Bax protein expression, thereby ameliorating the ALD model in zebrafish. Metabolomics data revealed significant changes in a total of 46 potential biomarkers. Among them, metabolites such as prostaglandin F2 alpha belong to arachidonic acid metabolism. In addition, GFS also partly reversed the imbalance of gut microbiota composition caused by alcohol. At the genus level, alcohol consumption elevated the presence of Flectobacillus, Curvibacter, among others, and diminished Elizabethkingia within the intestinal microbes of zebrafish. Conversely, GFS reversed these effects, notably enhancing the abundance of Proteobacteria and Archaea. Correlation analyses further indicated a significant negative correlation between prostaglandin F2 alpha, 11,14,15-THETA, Taurocholic acid and Curvibacter. CONCLUSION: This study highlights a novel mechanism by which GFS modulates anti-ALD activity through the PI3K/Akt signalling pathway by influencing the intestinal flora-metabolite axis. These results indicate the potential of GFS as a functional food for ALD treatment via modulation of the gut flora.

Potential for the development of Taraxacum mongolicum aqueous extract as a phytogenic feed additive for poultry.

Introduction: Taraxacum mongolicum (TM) is a kind of medicinal and edible homologous plant which is included in the catalogue of feed raw materials in China. It is rich in polyphenols, flavonoids, polysaccharides and other active substances, and shows many benefits to livestock, poultry and aquatic products. The study aimed to assess the potential of TM aqueous extract (TMAE) as a substitute for poultry AGPs. Methods: A total of 240 one-day-old Arbor Acker broilers were randomly assigned to four groups and fed a basal diet (Con) supplemented with 500, 1000, and 2000 mg/kg TMAE (Low, Medium, and High groups). The growth performance of the broilers was measured on day 21 and day 42. At the end of the trial, the researchers measured slaughter performance and collected serum, liver, spleen, ileum, and intestinal contents to investigate the effects of TMAE on serum biochemistry, antioxidant capacity, immune function, organ coefficient, intestinal morphology, flora composition, and short-chain fatty acids (SCFAs). Results: The results showed that broilers treated with TMAE had a significantly higher average daily gain from 22 to 42 days old compared to the Con group. Various doses of TMAE resulted in different levels of improvement in serum chemistry. High doses increased serum alkaline phosphatase and decreased creatinine. TMAE also increased the antioxidant capacity of serum, liver, and ileum in broilers. Additionally, middle and high doses of TMAE enhanced the innate immune function of the liver (IL-10) and ileum (Occludin) in broilers. Compared to the control group, the TMAE treatment group exhibited an increase in the ratio of villi length to villi crypt in the duodenum. TMAE increased the abundance of beneficial bacteria, such as Alistipes and Lactobacillus, while reducing the accumulation of harmful bacteria, such as Colidextracter and Sellimonas. The cecum's SCFAs content increased with a medium dose of TMAE. Supplementing broiler diets with TMAE at varying doses enhanced growth performance and overall health. The most significant benefits were observed at a dose of 1000 mg/kg, including improved serum biochemical parameters, intestinal morphology, antioxidant capacity of the liver and ileum, immune function of the liver and ileum, and increased SCFAs content. Lactobacillus aviarius, norank_f_norank_o__Clostridia_UCG-014, and Flavonifractor are potentially dominant members of the intestinal microflora. Conclusion: In conclusion, TMAE is a promising poultry feed additive and 1000 mg/kg is an effective reference dose.

Curcumin alleviates cecal oxidative injury in diquat-induced broilers by regulating the Nrf2/ARE pathway and microflora.

This study evaluated the alleviative effect of curcumin (CUR) on the diquat (DQ)-induced cecal injury in broilers. A total of 320 one-day-old Cobb broilers were selected and randomly divided into 4 treatments, namely control, DQ, CUR 100, and CUR150 groups. The control and DQ groups were fed a basal diet, while the CUR 100 and CUR150 groups were fed the basal diet supplemented with 100 and 150 mg/kg CUR, respectively. Each group had 8 replicates, with 10 broilers per replicate. On day 21 of the experiment, 1 broiler was selected from each replicate and intraperitoneally injected 20 mg/kg body weight of DQ for DQ, CUR 100, and CUR 150 groups. Broilers in control group received equivalent volume of saline. Broilers were euthanized 48h postinjection for tissue sampling. The results showed that DQ injection could cause oxidative stress and inflammatory reactions in the cecum, affecting the fatty acid production and flora structure, thus leading to cecum damage. Compared with the DQ group, the activity of superoxide dismutase, the level of interleukin 10, acetic acid, and total volatile fatty, and the abundance of nuclear factor E2-related factor 2, copper and zinc superoxide dismutase and catalase mRNA in the cecal mucosa of broilers in the CUR group increased significantly (P < 0.05). However, the levels of malondialdehyd, reactive oxygen species, tumor necrosis factor-alpha, and the expression of cysteine-aspartic acid protease-3 and tumor necrosis factor-alpha decreased significantly (P < 0.05) in the CUR group. In addition, CUR treatment alleviated the damage to the cecum and restored the flora structure, and Lactobacillus and Lactobacillaceae promoted the alleviative effect of CUR on DQ. In summary, CUR could alleviate the cecal injury caused by DQ-induced oxidative damage and inflammatory reactions by regulating the Nrf2-ARE signaling pathway and intestinal flora, thus protecting the cecum.

Considering traditional Chinese medicine as adjunct therapy in the management of chronic constipation by regulating intestinal flora.

Chronic constipation is one of the most common gastrointestinal disorders worldwide. Due to changes in diet, lifestyle, and the aging population, the incidence of chronic constipation has increased year by year. It has had an impact on daily life and poses a considerable economic burden. Nowadays, many patients with chronic constipation try to seek help from complementary and alternative therapies, and traditional Chinese medicine (TCM) is often their choice. The intestinal flora play an important role in the pathogenesis of constipation by affecting the body's metabolism, secretion, and immunity. Regulating the intestinal flora and optimizing its composition might become an important prevention and treatment for chronic constipation. TCM has unique advantages in regulating the imbalance of intestinal flora, and its curative effect is precise. Therefore, we reviewed the relationship between intestinal flora and chronic constipation as well as advances in research on TCM as adjunct therapy in the management of chronic constipation by regulating intestinal flora. Some single Chinese herbs and their active ingredients (e.g., Rheum palmatum, Radix Astragalus, and Cistanche deserticola), some traditional herbal formulations (e.g., Jichuan decoction, Zengye decoction, and Zhizhu decoction) and some Chinese patent medicines (e.g., Maren pills and Shouhui Tongbian capsules) that are commonly used to treat chronic constipation by regulating intestinal flora are highlighted and summarized. Moreover, some external forms of TCM, and especially acupuncture, have also been found to improve intestinal movement and alleviate constipation symptoms by regulating intestinal flora. We hope this review can contribute to an understanding of TCM as an adjunct therapy for chronic constipation and that it can provide useful information for the development of more effective constipation therapies.

Effects of Polymannuronic Acid on the Intestinal Microbiota in Mice after Long-Term Intragastric Administration.

Polymannuronic acid (PM) is an alginate oligosaccharide derived from brown algae with a characterized structure and excellent biological activities. Herein, mice were given different doses of PM through 30-day-long-term intragastric administration, and the contents of the jejunum, ileum, and colon were analyzed by 16S rRNA gene sequencing technology for microbial diversity, and relevant experiments were verified according to the analysis results so as to comprehensively evaluate the effects of PM on the intestinal flora. The PM (400 mg/kg and 100 mg/kg) could regulate the microflora balance at the phylum level and increase the microflora richness in the jejunum, ileum, and colon of the mice. The PM could induce more strains that are negatively correlated with Escherichia, thereby reducing the relative abundance of Escherichia. Analysis of bacterial function showed that high and low doses of PM could promote lipid metabolism in the bacterial communities. Moreover, the PM could reduce serum total cholesterol and cholesterol ester levels in a concentration-dependent manner. High-dose PM could lead to colonic intestinal inflammation by increasing the relative abundance of multiple bacterial groups in the jejunum, ileum, and colon. Moreover, high-dose PM could increase lipopolysaccharide-binding protein and interleukin-1ß levels. Therefore, the dose of PM plays an important role in its efficacy, and its biological activity is dosedifferent.

Chinese herbal decoction, Yi-Qi-Jian-Pi formula exerts anti-hepatic fibrosis effects in mouse models of CCl4-induced liver fibrosis.

Background: Yi-Qi-Jian-Pi Formula (YQJPF) is a herbal medicine that is used to treat patients with liver failure. However, scientific evidence supporting the treatment of hepatic fibrosis with YQJPF has not been forthcoming. The present study aimed to determine the mechanisms underlying the anti-fibrotic effects of YQJPF in mouse models of hepatic fibrosis. Methods: Mice were randomly assigned to control, hepatic fibrosis model, silymarin (positive treated), and low-, medium- and high-dose YQJPF (7.5, 15, and 30 g/kg, respectively) groups. Liver function, inflammatory cytokines, and oxygen stress were analyzed using ELISA kits. Sections were histopathologically stained with hematoxylin-eosin, Masson trichrome, and Sirius red. Macrophage polarization was measured by flow cytometry and immunofluorescence. Potential targets of YQJPF against hepatic fibrosis were analyzed by network pharmacology of Chinese herbal compound and the effects of YQJPF on the transforming growth factor-beta (TGF-ß)/Suppressor of Mothers against Decapentaplegic family member 3 (Smad3) signaling pathway were assessed using qRT-PCR and immunohistochemical staining. Finally, metagenomics and LC-MS/MS were used to detect the intestinal flora and metabolites of the mice, and an in-depth correlation analysis was performed by spearman correlation analysis. The data were compared by one-way ANOVA and least significant differences (LSDs) or ANOVA-Dunnett's T3 method used when no homogeneity was detected. Results: We induced hepatic fibrosis using CCl4 to establish mouse models and found that YQJPF dose-dependently increased body weight, improved liver function, and reversed hepatic fibrosis. Elevated levels of the pro-inflammatory factors IL-1ß, IL-6, and TNF-α in the model mice were substantially decreased by YQJPF, particularly at the highest dose. Levels of serum malondialdehyde and superoxide dismutase (SOD) activity were elevated and reduced, respectively. The malondialdehyde concentration decreased and SOD activity increased in the high-dose group. M1 polarized macrophages (CD86) in the mouse models were significantly decreased and M2 polarization was mildly decreased without significance. However, high-dose YQJPF increased the numbers of M2 macrophages and inhibited TGF-ß/Smad3 signaling. Metagenomic and non-targeted metabolomics detection results showed that YQJPF could regulate intestinal homeostasis, and Spearman correlation analysis showed that the abundance of Calditerrivibrio_nitroreducens was significantly negatively correlated with 18ß-glycyrrhetinic acid. It is suggested that Calditerrivibrio_nitroreducens may reduce the anti-fibrosis effect of licorice and other Chinese herbs by digesting 18ß-glycyrrhetinic acid. Conclusions: YQJPF can reverse liver fibrosis by inhibiting inflammation, suppressing oxidative stress, regulating the immunological response initiated by macrophages, inhibiting TGF-ß/Smad3 signaling and regulating intestinal flora homeostasis. Therefore, YQJPF may be included in clinical regimens to treat hepatic fibrosis.

Effects of moxibustion at "Zusanli" (ST 36) on oxidative stress and intestinal flora in aging rats. / 艾灸"足三里"å¯¹è¡°è€å¤§é¼ æ°§åŒ–åº”æ¿€å’Œè‚ é“èŒç¾¤çš„å½±å“.

OBJECTIVES: To observe the effects of moxibustion at "Zusanli"(ST 36)on oxidative stress and intestinal flora in subacute aging rats, and to explore the possible mechanism of moxibustion in delaying aging. METHODS: Thirty SD rats were randomly divided into a blank group, a model group and a Zusanli group, with 10 rats in each group. Subacute aging model was established by intraperitoneal injection of D-galactose at dosage of 500 mg/kg in the model group and the Zusanli group, once a day for 42 days. In the Zusanli group, moxibustion was applied at bilateral "Zusanli" (ST 36) , once a day, 3 moxa cones at each acupoint, for consecutive 28 days. After intervention, the serum levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA; the intestinal flora was detected by 16S rRNA sequencing technique in each group. RESULTS: Compared with the blank group, the serum level of SOD was decreased (P<0.01), the serum level of MDA was increased (P<0.01) in the model group. Compared with the model group, the serum level of SOD was increased (P<0.01), the serum level of MDA was decreased (P<0.01) in the Zusanli group. Compared with the blank group, Chao1 and Shannon indexes were decreased in the model group (P<0.01, P<0.05). Compared with the model group, Chao1 and Shannon indexes were increased in the Zusanli group (P<0.01, P<0.05). Compared with the blank group, the relative abundance of Firmicutes, Treponema_2 and Lachnospiraceae_NK4A136_group was increased (P<0.05, P<0.01), while the relative abundance of Prevotellaceae_UCG-003 and the relative abundance ratio of Bacteroidetes and Firmicutes (B/F value) were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the relative abundance of Firmicutes and Treponema_2 was decreased (P<0.01), while the relative abundance of Bacteroidetes, Lactobacillus, Prevotellaceae_UCG-003 and B/F value were increased (P<0.05, P<0.01) in the Zusanli group. CONCLUSIONS: Moxibustion at "Zusanli"(ST 36)can effectively improve the level of oxidative stress, regulate the constitution of intestinal flora, maintain the microecological balance of intestinal flora in aging rats, and thus play a role in delaying aging.

Astragaloside IV Alleviates Doxorubicin-Induced Cardiotoxicity by Inhibiting Cardiomyocyte Pyroptosis through the SIRT1/NLRP3 Pathway.

Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug used to treat a wide spectrum of tumors. However, its clinical application is limited due to cardiotoxic side effects. Astragaloside IV (AS IV), one of the major compounds present in aqueous extracts of Astragalus membranaceus, possesses potent cardiovascular protective properties, but the underlying molecular mechanisms are unclear. Thus, the aim of this study was to investigate the effect of AS IV on DOX-induced cardiotoxicity (DIC). Our findings revealed that DOX induced pyroptosis through the caspase-1/gasdermin D (GSDMD) and caspase-3/gasdermin E (GSDME) pathways. AS IV treatment significantly improved the cardiac function and alleviated myocardial injury in DOX-exposed mice by regulating intestinal flora and inhibiting pyroptosis; markedly suppressed the levels of cleaved caspase-1, N-GSDMD, cleaved caspase-3, and N-GSDME; and reversed DOX-induced downregulation of silent information regulator 1 (SIRT1) and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mice. The SIRT1 inhibitor EX527 significantly blocked the protective effects of AS IV. Collectively, our results suggest that AS IV protects against DIC by inhibiting pyroptosis through the SIRT1/NLRP3 pathway.

Ginseng Glucosyl Oleanolate from Ginsenoside Ro, Exhibited Anti-Liver Cancer Activities via MAPKs and Gut Microbiota In Vitro/Vivo.

Ginseng is widely recognized for its diverse health benefits and serves as a functional food ingredient with global popularity. Ginsenosides with a broad range of pharmacological effects are the most crucial active ingredients in ginseng. This study aimed to derive ginseng glucosyl oleanolate (GGO) from ginsenoside Ro through enzymatic conversion and evaluate its impact on liver cancer in vitro and in vivo. GGO exhibited concentration-dependent HepG2 cell death and markedly inhibited cell proliferation via the MAPK signaling pathway. It also attenuated tumor growth in immunocompromised mice undergoing heterograft transplantation. Furthermore, GGO intervention caused a modulation of gut microbiota composition by specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Enterococcus, etc., and ameliorated SCFA metabolism and colonic inflammation. These findings offer promising evidence for the potential use of GGO as a natural functional food ingredient in the prevention and treatment of cancer.

Review of yeast culture concerning the interactions between gut microbiota and young ruminant animals.

Microorganisms inhabit the gastrointestinal tract of ruminants and regulate body metabolism by maintaining intestinal health. The state of gastrointestinal health is influenced not only by the macro-level factors of optimal development and the physiological structure integrity but also by the delicate equilibrium between the intestinal flora and immune status at the micro-level. Abrupt weaning in young ruminants causes incomplete development of the intestinal tract resulting in an unstable and unformed microbiota. Abrupt weaning also induced damages to the microecological homeostasis of the intestinal tract, resulting in the intestinal infections and diseases, such as diarrhea. Recently, nutritional and functional yeast culture has been researched to tackle these problems. Herein, we summarized current known interactions between intestinal microorganisms and the body of young ruminants, then we discussed the regulatory effects of using yeast culture as a feed supplement. Yeast culture is a microecological preparation that contains yeast, enriched with yeast metabolites and other nutrient-active components, including ß-glucan, mannan, digestive enzymes, amino acids, minerals, vitamins, and some other unknown growth factors. It stimulates the proliferation of intestinal mucosal epithelial cells and the reproduction of intestinal microorganisms by providing special nutrient substrates to support the intestinal function. Additionally, the ß-glucan and mannan effectively stimulate intestinal mucosal immunity, promote immune response, activate macrophages, and increase acid phosphatase levels, thereby improving the body's resistance to several disease. The incorporation of yeast culture into young ruminants' diet significantly alleviated the damage caused by weaning stress to the gastrointestinal tract which also acts an effective strategy to promote the balance of intestinal flora, development of intestinal tissue, and establishment of mucosal immune system. Our review provides a theoretical basis for the application of yeast culture in the diet of young ruminants.

Protective effect of Tao Hong Si Wu Decoction against inflammatory injury caused by intestinal flora disorders in an ischemic stroke mouse model.

BACKGROUND AND AIMS: Recent studies have shown that intestinal flora are involved in the pathological process of ischemic stroke (IS). The potential protective effect of the traditional Chinese prescription, Tao Hong Si Wu Decoction (THSWD), against inflammatory injury after IS and its underlying mechanisms of action were investigated in the current study. METHODS: Fifty SPF(Specefic pathogen Free) male C57 mice were randomly assigned to sham operation, model, THSWD low-dose (6.5 g/kg), medium-dose (13 g/kg) and high-dose (26 g/kg) groups (10 mice per group). Mouse models of transient middle cerebral artery occlusion were prepared via thread embolism. Neurological function score, hematoxylin-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), 16S ribosomal DNA (rDNA) sequencing, quantitative reverse transcription PCR (qRT-PCR) and other methods were employed to elucidate the underlying molecular mechanisms. RESULTS: Notably, THSWD induced a reduction in the neurological function score (P < 0.01) and neuronal injury in brain tissue, increase in protein expression of Claudin-5 and zonula occludens-1 (ZO-1) in brain tissue(P < 0.01), and decrease in serum lipopolysaccharide (LPS)(P < 0.01), diamine oxidase (DAO)(P < 0.01) and D-lactic acid(P < 0.01, P < 0.05) levels to a significant extent. THSWD also inhibited the levels of tumor necrosis factor-α (TNF-α)(P < 0.01) and interleukin - 1ß (IL-1ß)(P < 0.01) in brain tissue, and increased alpha and beta diversity in ischemic stroke mice, along with a certain reversal effect on different microflora. Finally, THSWD inhibited the polarization of microglia cells(P < 0.01) and decreased the protein and gene expression of toll-like receptor-4 (TLR-4)(P < 0.01, P < 0.05) and nuclear factor kappa B (NF-κB)(P < 0.01) in brain tissue. CONCLUSION: Our data indicate that THSWD may interfere with inflammatory response in ischemic stroke by regulating intestinal flora and promoting intestinal barrier repair.

Neuropharmacological insights into Gardenia jasminoides Ellis: Harnessing therapeutic potential for central nervous system disorders.

BACKGROUND: In China, Gardenia jasminoides Ellis (GJE) has a longstanding history of application. The Ministry of Health has listed it as one of the first pharmaceutical or food resources. In ethnic, traditional, and folk medicine, GJE has been used to treat fever and cold and relieve nervous anxiety. Recent studies have confirmed the significant efficacy of GJE for treating central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder; however, GJE has not been systematically evaluated. PURPOSE: This research systematically summarizes global studies on the use of GJE for treating CNS disorders and explores the potential applications and underlying mechanisms via intestinal flora analysis and network pharmacology, aiming to establish a scientific basis for innovative CNS disorder treatment with GJE. METHODS: The PRISMA guidelines were used, and electronic databases such as the Web of Science, PubMed, and China National Knowledge Infrastructure were searched using the following search terms: "Gardenia jasminoides Ellis" with "central nervous system disease," "neuroprotection," "Alzheimer's disease," "Parkinson's disease," "ischemic stroke," "Epilepsy," and "major depressive disorder." The published literature up to September 2023 was searched to obtain relevant information on the application of GJE for treating CNS disorders. RESULTS: There has been an increase in research on the material formulation and mechanisms of action of GJE for treating CNS disorders, with marked effects on CNS disorder treatment in different countries and regions. We summarized the research results related to the role of GJE in vitro and in vivo via multitargeted interventions in response to the complex mechanisms of action of CNS disorders. CONCLUSION: We systematically reviewed the research progress on traditional treatment for GJE and preclinical mechanisms of CNS disorders and explored the potential of optimizing network pharmacology strategies and intestinal flora analysis to elucidate the mechanisms of action of GJE. The remarkable therapeutic efficacy of GJE, an important resource in traditional medicine, has been well documented in the literature, highlighting its significant medicinal potential.

[Effect and mechanism of Yueju Pills on breast cancer induced by DMBA in rats].

This paper aims to explore the inhibitory effect of Yueju Pills on breast cancer and decipher the underlying mechanism. A total of 92 SPF-grade SD female rats were involved in this study, and 14 of them were randomly selected into control group. The remaining 78 rats were administrated with 7,12-dimethylbenzanthracene(DMBA) by gavage to establish the breast cancer model. The modeled rats were randomized into model, tamoxifen(1.9 mg·kg~(-1)·d~(-1)), and low-and high-dose(17, 34 g·kg~(-1)·d~(-1)) Yueju Pills groups. The mental state, food intake, and activities of the rats were observed daily, and the body weight was measured on alternate days. After 12 weeks of administration, the rats were sacrificed and the tumor weight was measured. The serum estrogen and progeste-rone levels were determined by enzyme-linked immunosorbent assay. The histopathological changes of the breast and tumor were observed by hematoxylin-eosin staining. Western blot was employed to measure the protein levels of glucose transporter 1(GLUT1), lactate dehydrogenase A(LDHA), phosphofructokinase muscle(PFKM), pyruvate kinase isozyme type M2(PKM2), hexokinase 2(HK2), nuclear factor-kappaB(NF-κB), and phosphorylated NF-κB. The intestinal microbiome was examined by 16S rRNA high-throughput sequencing. The results showed that compared with the model group, high and low-dose Yueju Pills showed the tumor inhibition rate of 15.8% and 64.5%, respectively, and the low dose group had stronger inhibitory effect. Compared with the control group, the model group presented elevated the levels of estrogen and progesterone in serum. The administration of Yueju Pills lowered such ele-vation, and the low-dose group showed stronger lowering effect(P<0.05). Compared with the model group, Yueju Pills reduced the glands with increased breast tissue, the degree of breast duct expansion, the number and area of acinar cavity, the secretions, and the layers of mammary epithelial cells. Furthermore, Yueju Pills down-regulated the expression of GLUT1, LDHA, PFKM, PKM2, HK2, and NF-κB(P<0.05) and altered the diversity, composition, structure, and abundance of intestinal flora. The results showed that Yueju Pills could inhibit breast cancer by regulating the secretion of estrogen and progesterone, glycolysis, inflammatory cytokines, and intestinal flora.

Aqueous extract of Sargentodoxa cuneata alleviates ulcerative colitis and its associated liver injuries in mice through the modulation of intestinal flora and related metabolites.

Background: Ulcerative colitis (UC) is a refractory disease worldwide. Liver injury can be found clinically with UC, and now, it is found that gut dysbiosis is an important mechanism in the pathogenesis of UC. Sargentodoxa cuneata has been used as a traditional Chinese medicine and is commonly used clinically for the treatment of UC. The main objective of this study was to investigate the intrinsic mechanisms of Sargentodoxa cuneata in the treatment of UC and its associated liver injuries from the perspective of intestinal flora and related metabolites. Methods: Ultra-performance liquid chromatography-mass spectrometry was used to identify the components in the aqueous extract of Sargentodoxa cuneata (AESc). Mice with UC induced by dextran sulfate sodium were used to study the effects of AESc on UC and its associated liver injuries. Furthermore, 16S rRNA gene sequencing and analysis were performed on intestinal contents, and correlation analysis of intestinal flora with short-chain fatty acids (SCFAs) and organic acids was performed. Results: A total of 114 compounds were identified in AESc. AESc improved disease activity index scores, liver index, and colon length in mice with UC and had a good protective effect on intestine and liver injuries. Moreover, the administration of AESc regulated gut microbiota dysbiosis and the levels of a few SCFAs and organic acids in mice with UC. In addition, the correlation analysis results showed that the Megamonas and Bifidobacterium were the key intestinal flora related to the levels of differential SCFAs and organic acids in mice with UC after AESc intervention. Conclusion: AESc has a good protective effect on UC and UC related liver injuries. Modulation of the intestinal flora and its metabolites (SCFAs and a few organic acids) is an important pathway for AESc in the treatment of UC and also provides a rationale for the clinical use of Sargentodoxa cuneata in the treatment of UC.

Ginseng-derived nanoparticles alleviate inflammatory bowel disease via the TLR4/MAPK and p62/Nrf2/Keap1 pathways.

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy.

Mechanism of action of vinegared Cornu Cervi Degelatinatum in suppressing spleen kidney yang deficient ulcerative colitis through NCK2-JNK pathway.

As a traditional Chinese herbal medicine, Cornu Cervi Degelatinatum (CCD) has the effect of warming the kidney to support yang, astringing, and stopping bleeding, and is used for spleen kidney yang deficient (SKYD). This experiment was to investigate the therapeutic effects of different processes of CCD on SKYD type ulcerative colitis (UC) rats and to explore its impact on the intestinal flora of rats. METHODS: ELISA was used to study the anti-inflammatory activity of Cornu Cervi Degelatinatum processed with water (WCCD) and Cornu Cervi Degelatinatum processed with vinegar (VCCD). 16SrRNA and transcriptome sequencing were used to detect the composition of rat intestinal flora and gene expression; RT-PCR and Western blot were used to verify the role of WCCD and VCCD in treating UC. RESULTS: WCCD and VCCD have therapeutic effects on UC, could reduce tissue damage. VCCD performed better in improving Bacteroidetes/Firmicutes ratios and species evenness and abundance; performed better in increasing the quantity of lactobacillus. VCCD simultaneously inhibit the intestinal inflammatory response through NCK2, PAK4, and JNK signaling pathways. CONCLUSIONS: WCCD and VCCD play a therapeutic role in UC by regulating the proportion of different flora in the intestinal flora. VCCD regulates the intestinal flora and inflammatory response by interfering with the NCK2, PAK4 and JNK signaling pathways.

Selenium- and/or Zinc-Enriched Egg Diet Improves Oxidative Damage and Regulates Gut Microbiota in D-Gal-Induced Aging Mice.

Eggs, with their high nutritional value, are great carriers for enriching nutrients. In this study, selenium- and/or zinc-enriched eggs (SZE) were obtained and their effects on ameliorating oxidative stress injury, alleviating cognitive impairment, and maintaining intestinal flora balance in a D-gal-induced aging mice model were investigated. As determined by the Y-maze test, SZE restored the learning and memory abilities and increased the Ach level and AChE activity of aging mice (p < 0.05). Meanwhile, supplementation of low-dose SZE increased antioxidant levels and decreased inflammation levels (p < 0.05). High-dose SZE increased anti-inflammatory levels but were less effective than low dose. Additionally, SZE maintained the intestinal flora balance and significantly increased the ratio of Firmicutes and Bacteroidota. Blautia, as a probiotic, was negatively correlated with pro-inflammatory factors and positively correlated with antioxidant levels (p < 0.05). These results suggest that SZE might improve organ damage and cognitive function by attenuating oxidative stress and inflammatory response and maintaining healthy gut flora.

Exploring the relationship between intestinal microbiota and immune checkpoint inhibitors in the treatment of non-small cell lung cancer: insights from the "lung and large intestine stand in exterior-interior relationship" theory.

Objective: This study is aim to discern the Traditional Chinese Medicine (TCM) syndrome classifications relevant to immunotherapy sensitive in non-small cell lung cancer (NSCLC) patients, and to delineate intestinal microbiota biomarkers and impact that wield influence over the efficacy of NSCLC immunotherapy, grounded in the TCM theory of "lung and large intestine stand in exterior-interior relationship." Methods: The study cohort consisted of patients with advanced NSCLC who received treatment at the Oncology Department of Chengdu Fifth People's Hospital. These patients were categorized into distinct TCM syndrome types and subsequently administered immune checkpoint inhibitors (ICIs), specifically PD-1 inhibitors. Stool specimens were collected from patients both prior to and following treatment. To scrutinize the differences in microbial gene sequences and species of the intestinal microbiota, 16S rRNA amplicon sequencing technology was employed. Additionally, peripheral blood samples were collected, and the analysis encompassed the assessment of T lymphocyte subsets and myeloid suppressor cell subsets via flow cytometry. Subsequently, alterations in the immune microenvironment pre- and post-treatment were thoroughly analyzed. Results: The predominant clinical manifestations of advanced NSCLC patients encompassed spleen-lung Qi deficiency syndrome and Qi-Yin deficiency syndrome. Notably, the latter exhibited enhanced responsiveness to ICIs with a discernible amelioration of the immune microenvironment. Following ICIs treatment, significant variations in microbial abundance were identified among the three strains: Clostridia, Lachnospiraceae, and Lachnospirales, with a mutual dependency relationship. In the subset of patients manifesting positive PD-L1 expression and enduring therapeutic benefits, the study recorded marked increases in the ratios of CD3+%, CD4+%, and CD4+/CD8+ within the T lymphocyte subsets. Conversely, reductions were observed in the ratios of CD8%, Treg/CD4+, M-MDSC/MDSC, and G-MDSC/MDSC. Conclusion: The strains Clostridia, Lachnospiraceae, and Lachnospirales emerge as potential biomarkers denoting the composition of the intestinal microbiota in the NSCLC therapy. The immunotherapy efficacy of ICIs markedly accentuates in patients displaying durable treatment benefits and those expressing positive PD-L1.

Radix Bupleuri aqueous extract attenuates MK801-induced schizophrenia-like symptoms in mice: Participation of intestinal flora.

Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function of Radix Bupleuri aqueous extract in SCZ in mouse models. The SCZ mouse model was established by MK-801 injection and feeding of Radix Bupleuri aqueous extract or combined antibiotics. Radix Bupleuri aqueous extract significantly improved the aberrant behaviors and neuronal damage in SCZ mice, upregulated SYP and PSD-95 expression and BDNF levels in hippocampal homogenates, down-regulated DA and 5-HT levels, and suppressed microglial activation in SCZ mice. Moreover, Radix Bupleuri aqueous extract improved the integrity of the intestinal tract barrier. The 16 S rRNA sequencing of feces showed that Radix Bupleuri extract modulated the composition of gut flora. Lactobacillus abundance was decreased in SCZ mice and reversed by Radix Bupleuri aqueous extract administration which exhibited a significant negative correlation with IL-6, IL-1ß, DA, and 5-HT, and a significant positive correlation with BDNF levels in hippocampal tissues. The abundance of Parabacteroides and Alloprevotella was increased in SCZ mice. It was reversed by Radix Bupleuri aqueous extract administration, which exhibited a positive correlation with IL-6, IL-1ß, and 5-HT and a negative correlation with BDNF. In conclusion, Radix Bupleuri aqueous extract attenuates the inflammatory response in hippocampal tissues and modulates neurotransmitter levels, exerting its neuroprotective effect in SCZ. Meanwhile, the alteration of intestinal flora may be involved in this process, which is expected to be an underlying therapeutic option in treating SCZ.