Lactobacillus Casei-fermented Amomum Xanthioides Mitigates non-alcoholic fatty liver disease in a high-fat diet mice model.

Non-alcoholic fatty liver disease (NAFLD) is a substantial global health issue owing to its high prevalence and the lack of effective therapies. Fermentation of medicinal herbs has always been considered a feasible strategy for enhancing efficacy in treating various ailments. This study aimed to investigate the potential benefits of the Lactobacillus casei-fermented Amomum xanthioides (LAX) on NAFLD in a high-fat diet model. HFD-fed C57BL6/j mice were administered with 200 mg/kg of LAX or unfermented Amomum xanthioides (AX) or 100 mg/kg of metformin for 6 weeks from the 4th week. The 10-week HFD-induced alterations of hepatic lipid accumulation and hepatic inflammation were significantly attenuated by LAX dominantly (more than AX or metformin), which evidenced by pathohistological findings, lipid contents, inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 6 and IL-1ß, oxidative parameters such as reactive oxygen species (ROS) and malondialdehyde (MDA), and molecular changes reversely between lipogenic proteins such as glycerol-3-phosphate acyltransferase (GPAM) and sterol regulatory element-binding protein (SREBP)- 1, and lipolytic proteins including peroxisome proliferator-activated receptor (PPAR-α) and AMP-activated kinase (AMPK)-α in the liver tissues. In addition, the abnormal serum lipid parameters (triglyceride, total cholesterol and LDL-cholesterol) notably ameliorated by LAX. In conclusion, these findings support the potential of LAX as a promising plant-derived remedy for NAFLD.

A Mixture of Cervus elaphus sibiricus and Glycine max (L.) Merrill Inhibits Ovariectomy-Induced Bone Loss Via Regulation of Osteogenic Molecules in a Mouse Model.

Osteoporosis is a metabolic skeletal disease characterized by lowered bone mineral density and quality, which lead to an increased risk of fracture. The aim of this study was to evaluate the anti-osteoporosis effects of a mixture (called BPX) of Cervus elaphus sibiricus and Glycine max (L.) Merrill and its underlying mechanisms using an ovariectomized (OVX) mouse model. BALB/c female mice (7 weeks old) were ovariectomized. From 12 weeks of ovariectomy, mice were administered BPX (600 mg/kg) mixed in a chow diet for 20 weeks. Changes in bone mineral density (BMD) and bone volume (BV), histological findings, osteogenic markers in serum, and bone formation-related molecules were analyzed. Ovariectomy notably decreased the BMD and BV scores, while these were significantly attenuated by BPX treatment in the whole body, femur, and tibia. These anti-osteoporosis effects of BPX were supported by the histological findings for bone microstructure from H&E staining, increased activity of alkaline phosphatase (ALP), but a lowered activity of tartrate-resistant acid phosphatase (TRAP) in the femur, along with other parameters in the serum, including TRAP, calcium (Ca), osteocalcin (OC), and ALP. These pharmacological actions of BPX were explained by the regulation of key molecules in the bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) pathways. The present results provide experimental evidence for the clinical relevance and pharmaceutical potential of BPX as a candidate for anti-osteoporosis treatment, especially under postmenopausal conditions.

Ginseng Sprouts Attenuate Mortality and Systemic Inflammation by Modulating TLR4/NF-κB Signaling in an LPS-Induced Mouse Model of Sepsis.

Sepsis leads to multi-organ failure due to aggressive systemic inflammation, which is one of the main causes of death clinically. This study aimed to evaluate whether ginseng sprout extracts (GSE) can rescue sepsis and explore its underlying mechanisms. C57BL/6J male mice (n = 15/group) were pre-administered with GSE (25, 50, and 100 mg/kg, p.o) for 5 days, and a single injection of lipopolysaccharide (LPS, 30 mg/kg, i.p) was administered to construct a sepsis model. Additionally, RAW264.7 cells were treated with LPS with/without GSE/its main components (Rd and Re) to explain the mechanisms corresponding to the animal-derived effects. LPS injection led to the death of all mice within 38 h, while GSE pretreatment delayed the time to death. GSE pretreatment also notably ameliorated LPS-induced systemic inflammation such as histological destruction in both the lung and liver, along with reductions in inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß, in both tissues and serum. Additionally, GSE markedly diminished the drastic secretion of nitric oxide (NO) by suppressing the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) in both tissues. Similar changes in TNF-α, IL-1ß, NO, iNOS, and COX2 were observed in LPS-stimulated RAW264.7 cells, and protein expression data and nuclear translocation assays suggested GSE could modulate LPS-binding protein (LBP), Toll-like receptor 4 (TLR4), and NF-κB. Ginsenoside Rd could be a major active component in GSE that produces the anti-sepsis effects. Our data support that ginseng sprouts could be used as an herbal resource to reduce the risk of sepsis. The corresponding mechanisms may involve TLR4/NF-κB signaling and a potentially active component.

Gut Microbiome: The Interplay of an "Invisible Organ" with Herbal Medicine and Its Derived Compounds in Chronic Metabolic Disorders.

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.

Yeokwisan, a Standardized Herbal Formula, Enhances Gastric Emptying via Modulation of the Ghrelin Pathway in a Loperamide-induced Functional Dyspepsia Mouse Model.

Background: Yeokwisan, a standardized herbal formula, has exhibited clinical benefit for patients suffering from refractory functional dyspepsia (FD) in Korea since 2016. However, data about the mechanism of action of this formula are yet not available. Aim of the study: To evaluate and explore the effects of Yeokwisan on gastric emptying, a major symptom of functional dyspepsia, and its underlying mechanisms of action using a mouse model. Materials and methods: BALB/C mice were pretreated with Yeokwisan (100, 200, and 400 mg/kg, po) or mosapride (3 mg/kg, po) for 5 days and then treated with loperamide (10 mg/kg, ip) after 20 h of fasting. A solution of 0.05% phenol red (500 µL) or diet of 5% charcoal (200 µL) was orally administered, followed by assessment of gastric emptying or intestinal transit. Plasma acyl-ghrelin (ELISA), C-kit (immunofluorescence and western blotting), nNOS (western blotting) and gastric contraction- and ghrelin-related gene/protein expression levels were examined in stomach and small intestine tissues. Results: Loperamide injection substantially delayed gastric emptying, while Yeokwisan pretreatment (especially 200 and 400 mg/kg Yeokwisan) significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of phenol red retained in the stomach (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The levels of plasma acyl-ghrelin and expression of gastric ghrelin-related genes, such as growth hormone secretagogue receptor (GHSR), ghrelin-O-acyltransferase (GOAT), adrenergic receptor ß1 (ADRB1) and somatostatin receptor (SSTR), were significantly normalized (p < 0.05 or 0.01) by Yeokwisan (400 mg/kg). Yeokwisan (400 mg/kg) significantly tempered the loperamide-induced alterations in the c-kit and nNOS levels (p < 0.01) as well as the expression of contraction- and ghrelin-related genes, such as 5-HT4 receptor (5-HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK), in the stomach, but not in the small intestine. Conclusion: The present results showed the clinical relevance of Yeokwisan, in treating FD, especially in promoting gastric emptying but not small intestinal transit. The main mechanisms corresponding to these effects may involve the modulation of the ghrelin pathway and activation of interstitial cells of Cajal in stomach tissue.

Genotoxicity of Water Extract from Bark-Removed Rhus verniciflua Stokes.

Rhus verniciflua Stokes (RVS) has been traditionally used as an herbal remedy to support the digestive functions in traditional Korean medicine. Additionally, the pharmacological effects of RVS, including antioxidative, antimicrobial and anticancer activities, have been well-reported. The genotoxicity of RVS, however, is elusive; thus, we evaluated the genotoxicity of RVS without bark (RVX) for safe application as a resource of functional food or a medical drug. To evaluate the genotoxicity of RVX, we used a bacterial reverse mutation test, chromosomal aberration test and comet assay, according to the "Organization for Economic Co-operation and Development" (OECD) guidelines. Briefly, for the reverse mutation test, samples (5000, 1667, 556, 185, 62 and 0 µg/plate of RVX or the positive control) were treated with a precultured strain (TA98, TA100, TA1535, TA1537 or WP2µvrA) with or without the S9 mix, in which RVX partially induced a reverse mutation in four bacterial strains. From the chromosomal aberration test and comet assay, the RVX samples (556, 185, 62, 20 and 0 µg/mL of RVX or the positive control) were treated in a Chinese hamster ovary cell line (CHO-K1 cells) in the conditions of the S9 mix absent or S9 mix present and in Chang liver cells and C2C12 myoblasts, respectively. No chromosomal aberrations in CHO-K1 or DNA damage in Chang liver cells and C2C12 myoblasts was observed. In conclusion, our results suggest the non-genotoxicity of RVX, which would be helpful as a reference for the safe application of bark-removed Rhus verniciflua Stokes as functional raw materials in the food, cosmetics or pharmaceutical fields.

Cynanchum atratum Alleviates Non-Alcoholic Fatty Liver by Balancing Lipogenesis and Fatty Acid Oxidation in a High-Fat, High-Fructose Diet Mice Model.

Cynanchum atratum, a medicinal herb, is traditionally used as an antidote, diuretic, and antipyretic in eastern Asia. The current study aimed to investigate the anti-fatty liver capacity of the ethanol extract of Cynanchum atratum (CAE) using a 10-week high-fat, high-fructose diet mouse model. A six-week treatment of CAE (from the fifth week) significantly attenuated the weights of the body, liver, and mesenteric fat without a change in diet intake. CAE also considerably restored the alterations of serum aminotransferases and free fatty acid, fasting blood glucose, serum and hepatic triglyceride, and total cholesterol, as well as platelet and leukocyte counts. Meanwhile, CAE ameliorated hepatic injury and lipid accumulation, as evidenced by histopathological and immunofluorescence observations. Additionally, CAE significantly lowered the elevation of hepatic TNF-α, the TNF-α/IL-10 ratio, fecal endotoxins, and the abundance of Gram-negative bacteria. Hepatic lipogenesis and ß-oxidation-related proteins and gene expression, including PPAR-α, SREBP-1, SIRT1, FAS, CTP1, etc., were normalized markedly by CAE. In particular, the AMPK, a central regulator of energy metabolism, was phosphorylated by CAE at an even higher rate than metformin. Overall, CAE exerts anti-hepatic steatosis effects by reducing lipogenesis and enhancing fatty acid oxidation. Consequently, Cynanchum atratum is expected to be a promising candidate for treating chronic metabolic diseases.

Combination of Scutellaria baicalensis and Metformin Ameliorates Diet-Induced Metabolic Dysregulation in Mice via the Gut-Liver-Brain Axis.

Scutellaria baicalensis (SB), a herbal medicine, is commonly used to treat metabolic diseases, while Metformin (MF) is a widely used drug for type 2 diabetes. The purpose of this study was to investigate whether co-treatment of SB with MF could produce a potential therapeutic effect on high-fat and high-fructose diet (HFFD)-induced metabolic dysregulation. First, we optimized the dose of SB (100, 200, 400, and 800[Formula: see text]mg/kg) with MF (200[Formula: see text]mg/kg) in HFFD-induced C57BL6J mice. Next, the optimized dose of SB (400[Formula: see text]mg/kg) was co-administered with MF (50, 100, and 200[Formula: see text]mg/kg) in a similar animal model to find the effective combinations of SB and MF. Metabolic markers were determined in serum and tissues using different assays, histology, gene expression, and gut microbial population. The SB and MF co-treatment significantly decreased the body, liver, and VAT weights. The outcome of OGTT was improved, and the fasting insulin, HbA1c, TG, TC, LDL-c, AST, and ALT were decreased, while HDL-c was significantly increased. Histological analyses revealed maintained the integrity of liver, adipose tissue, and intestine prevented lipid accumulation in the liver and intestine and combated neuronal damage in the brain. Importantly, controlled the expression of PPAR[Formula: see text], and IL-6 genes in the liver, and expression of BDNF, Glut1, Glut3, and Glut4 genes in the brain. Treatment-specific gut microbial segregation was observed in the PCA chart. Our findings indicate that SB and MF co-treatment is an effective therapeutic approach for HFFD-induced metabolic dysregulation which is operated through the gut-liver-brain axis.

[Effect of acupuncture at "reflection points" of the affected side on the peripheral facial paralysis in acute phase].

OBJECTIVE: To explore the effect of acupuncture at the "reflection points" of affected side on the peripheral facial paralysis in acute phase. METHODS: Ninety patients with peripheral facial paralysis in acute phase were randomly divided into a reflection group (group A), a conventional acupuncture group (group B) and a physiotherapy group (group C), 30 cases in each group. The same basic medication were given in all three groups. In the group A, acupuncture at "reflection points" of the affected side and local acupoints in acute phase, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group B, acupuncture at Yifeng (TE 17) of the affected side in acute phase and local acupoints, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group C, ultrashort wave on Yifeng (TE 17) of the affected side in acute phase was applied, and the treatment in the stationary phase and the recovery phase was the same as the group B. The treatment was given once every day, 5 times as one course for 4 courses. The House-Brackmann (H-B) grading scale, facial disability index scale, the symptom and physical score integral scale were used to score before and after treatment, and the clinical effects of the three groups were compared. RESULTS: After treatment, the functional grade of H-B facial nerve was better than that before treatment in the three groups (P<0.01). There was no significant difference among the three groups after treatment (P>0.05). After treatment, the course of treatment required to reflect the healing in the group A was shorter than that in the group B and the group C (P<0.01); the body function scores and social function scores in the three groups were better than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). The scores of symptoms and signs in the three groups were lower than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). H-B facial nerve function grading scale and facial disability index (FDI) scale were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B and 46.7% (14/30) in the group C, the curative rate in the group A was better than the other two groups (P<0.05). The curative and markedly effective rate in the group A was 83.3% (25/30), 70.0% (21/30) in the group B and 63.3% (19/30) in the group C, the curative and markedly effective rate in the group A was better than the other two groups (P<0.05). The scores of symptoms and signs were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B, and 46.7% (14/30) in the group C. The curative rate in the group A was better than the other two groups (P<0.05). CONCLUSION: Compared with general acupuncture and physiotherapy, acupuncture at the "reflection points" of the affected side on the peripheral facial paralysis in acute phase could shorten the course of treatment and improve the curative effect.

A Controlled Fermented Samjunghwan Herbal Formula Ameliorates Non-alcoholic Hepatosteatosis in HepG2 Cells and OLETF Rats.

Hepatosteatosis (HS), a clinical feature of fatty liver with the excessive intracellular accumulation of triglyceride in hepatocytes, is manifested by perturbation of the maintenance of liver lipid homeostasis. Samjunghwan (SJH) is an herbal formula used mostly in Korean traditional medicine that is effective against a number of metabolic diseases, including obesity. Herbal drugs, enriched with numerous bioactive substances, possess health-protective benefits. Meanwhile, fermented herbal products enriched with probiotics are known to improve metabolic processes. Additionally, current lines of evidence indicate that probiotics-derived metabolites, termed as postbiotics, produce the same beneficial effects as their precursors. Herein, the anti-HS effects of 5-weeks naturally fermented SJH (FSJH) was investigated with FSJH-mixed chow diet in vivo using Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats as animal models of HS and controls, respectively. In parallel, the anti-HS effects of postbiotic-metabolites of three bacterial strains [Lactobacillus brevis (LBB), Lactococcus lactis (LCL) and Lactobacillus plantarum (LBP)] isolated from FSJH were also evaluated in vitro using the FFAs-induced HepG2 cells. Feeding OLETF rats with FSJH-diet effectively reduced body, liver, and visceral adipose tissue (VAT) weights, produced marked hypolipidemic effects on serum and hepatic lipid parameters, decreased serum AST and ALT levels, and upregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR gene expressions levels. Additionally, exposure of FFAs-induced HepG2 cells to postbiotic metabolic media (PMM) of bacterial strains also produced marked hypolipidemic effects on intracellular lipid contents and significantly unregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR genes expressions levels. Overall, our results indicate that FSJH enriched with fermented metabolites could be an effective anti-HS formulation.

The Root of Atractylodes macrocephala Koidzumi Prevents Obesity and Glucose Intolerance and Increases Energy Metabolism in Mice.

Targeting energy expenditure offers a strategy for treating obesity more effectively and safely. In previous studies, we found that the root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) increased energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on obesity and glucose intolerance by examining energy metabolism in skeletal muscle and brown fat in high-fat diet (HFD) induced obese mice. ARA decreased body weight gain, hepatic lipid levels and serum total cholesterol levels, but did not modify food intake. Fasting serum glucose, serum insulin levels and glucose intolerance were all improved in ARA treated mice. Furthermore, ARA increased peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) expression, and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle tissues, and also prevented skeletal muscle atrophy. In addition, the numbers of brown adipocytes and the expressions of PGC1α and uncoupling protein 1 (UCP1) were elevated in the brown adipose tissues of ARA treated mice. Our results show that ARA can prevent diet-induced obesity and glucose intolerance in C5BL/6 mice and suggests that the mechanism responsible is related to the promotion of energy metabolism in skeletal muscle and brown adipose tissues.

In vivo therapeutic effect of combination treatment with metformin and Scutellaria baicalensis on maintaining bile acid homeostasis.

The radix of Scutellaria baicalensis (SB) is a herb widely used in traditional Chinese medicine to treat metabolic diseases. Several main components, including baicalin and wogonoside, possess anti-dyslipidemia, anti-obesity and anti-diabetic effects. We hypothesized that co-administration of SB extract and metformin exerts a better effect on obesity-induced insulin resistance and lipid metabolism than treatment with metformin alone. We compared the effect of metformin (100 mg/10 mL/kg/day) alone with co-administration of metformin (100 mg/5 mL/kg/day) and SB extract (200 mg/5 mL/kg/day) on Otsuka Long Evans Tokushima Fatty rats, a useful model of type II diabetes with obesity, and used Long-Evans Tokushima Otsuka rats as a control. Weight, fasting glucose, oral glucose tolerance test, intraperitoneal insulin tolerance test, and serum total cholesterol were measured after 12 weeks of drug administration. We observed a synergetic effect of metformin and SB on lowering cholesterol level by excretion of bile acid through feces. We found that this accompanied activation of FXR, CYP7A1 and LDLR genes and repression of HMGCR in the liver. Although there were no significant changes in BSH-active gut microbiota due to high variability, functional prediction with 16S sequences showed increased primary and secondary bile acid biosynthesis in the combination treatment group. Further study is needed to find the specific strains of bacteria which contribute to FXR-related cholesterol and bile acid regulations.

Comparison of electroacupuncture and medical treatment for functional constipation: a systematic review and meta-analysis.

OBJECTIVES: To assess the effectiveness of electroacupuncture (EA) relative to conventional medication in functional constipation (FC). DESIGN: Systematic review and meta-analysis. SETTING: To be included, studies needed to: (1) have been randomised controlled trials; (2) have recruited adult patients diagnosed with FC according to the Rome II/III criteria or the American Gastroenterological Association guideline for chronic FC; and (3) have randomised patients to be treated with EA or anti-constipation medication. We searched Medline, the Cochrane Library and Embase databases for articles published up to 30 June 2016. INTERVENTION: EA or anti-constipation medication. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the change in the number of weekly spontaneous bowel movements. Secondary outcomes were total response rate (or total effective rate), symptom reduction and Cleveland Clinic constipation scores. RESULTS: The pooled results showed significantly more improvement in the frequency of spontaneous bowel movements in the EA treatment group compared with the medicine-treated group (pooled SMD 0.244, 95% CI 0.065 to 0.424, P=0.008). Deep-needling EA was significantly more effective than treatment with medication at increasing the frequency of spontaneous bowel movements (p=0.019). Significantly greater improvement was also seen for total response rates (p=0.018) and reductions in symptom score (p<0.001) in EA-treated patients. CONCLUSIONS: EA was more effective than medication at improving spontaneous bowel movements and total response rate, and reducing the symptoms of FC.

Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid.

Modified SJH alleviates FFAs-induced hepatic steatosis through leptin signaling pathways.

Samjunghwan (SJH) is an herbal formula used in traditional Korean medicine. This prescription has long been used in treatment of aging and lifestyle diseases. The current study showed the effect and mechanisms of anti-hepatic steatosis action of modified SJH (mSJH) in vitro and in vivo. Treatment with mSJH resulted in significantly decreased intracellular lipid accumulation in steatosis-induced cells. Furthermore, mSJH triggered the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase as well as increased the expression of leptin at both protein and gene levels. In addition, C57BL6 mice fed high-fat diet (HFD) showed significant improvements in body, liver weights and fat weights; and serum, hepatic and fecal lipid parameters in response to the treatment with mSJH. Furthermore, mSJH showed favorable effects on the hepatic expression of several genes related to lipid metabolism. Betaine, one of constituents of mSJH exerted fundamental beneficial impact on FFAs-induced cells. However, the beneficial effects of mSJH were diminished upon blocking of leptin signaling by dexamethasone, suggesting the leptin signaling as a key component in mSJH-mediated modulation of lipid homeostasis. Our results suggest that mSJH exerts an anti-hepatic steatosis effect via activation of leptin and associated signaling cascades related to lipid metabolism.

Daesiho-Tang Is an Effective Herbal Formulation in Attenuation of Obesity in Mice through Alteration of Gene Expression and Modulation of Intestinal Microbiota.

BACKGROUND: Obesity has become a major global health challenge due to its increasing prevalence, and the associated health risk. It is the main cause of various metabolic diseases including diabetes, hypertension, cardiovascular disease, stroke and certain forms of cancer. METHODS AND RESULTS: In the present study we evaluated the anti-obesity property of Daesiho-tang (DSHT), an herbal medicine, using high fat diet (HFD)-induced obese mice as a model. Our results showed that DSHT ameliorated body weight gain, decreased total body fat, regulated expression of leptin and adiponectin genes of adipose tissue and exerted an anti-diabetic effect by attenuating fasting glucose level and serum insulin level in HFD-fed animals. In addition, DSHT-treatment significantly reduced total cholesterol (TC), triglycerides (TG) and increased high density lipoprotein-cholesterol (HDL), glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) levels in serum and reduced deposition of fat droplets in liver. DSHT treatment resulted in significantly increased relative abundance of bacteria including Bacteroidetes, Bacteroidetes/Firmicutes ratio, Akkermansia Bifidobacterium., Lactobacillus, and decreased the level of Firmicutes. Using RT2 profiler PCR array, 39 (46%) genes were found to be differentially expressed in HFD-fed mice compared to normal control. However, normal gene expressions were restored in 36 (92%) genes of HFD-fed mice, when co-exposed to DSHT. CONCLUSION/MAJOR FINDINGS: The results of this study demonstrated that DSHT is an effective herbal formulation in attenuation of obesity in HFD-fed mice through alteration of gene expressions and modulation of intestinal microbiota.

CST, an Herbal Formula, Exerts Anti-Obesity Effects through Brain-Gut-Adipose Tissue Axis Modulation in High-Fat Diet Fed Mice.

The brain, gut, and adipose tissue interact to control metabolic pathways, and impairment in the brain-gut-adipose axis can lead to metabolic disorders, including obesity. Chowiseungcheng-tang (CST), a herbal formulation, is frequently used to treat metabolic disorders. Here, we investigated the anti-obesity effect of CST and its link with brain-gut-adipose axis using C57BL/6J mice as a model. The animals were provided with a normal research diet (NRD) or high-fat diet (HFD) in absence or presence of CST or orlistat (ORL) for 12 weeks. CST had a significant anti-obesity effect on a number of vital metabolic and obesity-related parameters in HFD-fed mice. CST significantly decreased the expression levels of genes encoding obesity-promoting neuropeptides (agouti-related peptide, neuropeptide Y), and increased the mRNA levels of obesity-suppressing neuropeptides (proopiomelanocortin, cocaine-and amphetamine-regulated transcript) in the hypothalamus. CST also effectively decreased the expression level of gene encoding obesity-promoting adipokine (retinol-binding protein-4) and increased the mRNA level of obesity-suppressing adipokine (adiponectin) in visceral adipose tissue (VAT). Additionally, CST altered the gut microbial composition in HFD groups, a phenomenon strongly associated with key metabolic parameters, neuropeptides, and adipokines. Our findings reveal that the anti-obesity impact of CST is mediated through modulation of metabolism-related neuropeptides, adipokines, and gut microbial composition.

Rehmannia glutinosa reduced waist circumferences of Korean obese women possibly through modulation of gut microbiota.

The clinical study reported here was conducted in order to analyze the anti-obesity effect of the steamed root of Rehmannia glutinosa Libosch (Shu Dihuang), a Chinese herbal medicine widely used for the treatment of metabolic diseases. To understand the mechanism(s) underlying the beneficial effects of R. glutinosa, we investigated the changes in gut microbiota after herbal intervention through 16S rRNA gene-based pyrosequencing analyses. Twelve female middle-aged subjects (40-65 years old) with body mass index (BMI) over 25 kg m(-2) were included in this study which involved intake of steamed roots of R. glutinosa for eight weeks. The subjects were visited for anthropometric measurements every two weeks and fecal samples were collected before and after the intervention. All subjects showed a significantly decreased waist circumference following the herbal treatment. The relative abundances of fecal microbiota suggested an association of intake of R. glutinosa with increases in phylum Actinobacteria and genus Bifidobacterium, while phylum Firmicutes and genus Blautia were decreased in response to the herbal treatment. Based on these findings, it is conceivable that a decrease in the waist circumferences after R. glutinosa intake may be related to alteration of intestinal microbiota and the herbal intervention has the potential as a prebiotic.

Flos Lonicera ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota.

BACKGROUND AND AIM: Increasing evidence has indicated a close association of host-gut flora metabolic interaction with obesity. Flos Lonicera, a traditional herbal medicine, is used widely in eastern Asia for the treatment of various disorders. The aim of this study was to evaluate whether unfermented or fermented formulations of Flos Lonicera could exert a beneficial impact to combat obesity and related metabolic endotoxemia. METHODS: Obesity and metabolic endotoxemia were induced separately or together in rats through feeding a eight-week high fat diet either alone (HFD control group) or in combination with a single LPS stimulation (intraperitoneal injection, 0.75 mg/kg) (LPS control group). While, the mechanism of action of the Lonicera formulations was explored in vitro using RAW 264.7 and HCT 116 cell lines as models. RESULTS: In cell-based studies, treatment with both unfermented Flos Lonicera (UFL) and fermented Flos Lonicera (FFL) formulations resulted in suppression of LPS-induced NO production and gene expression of vital proinflammatory cytokines (TNF-α, COX-2, and IL-6) in RAW 264.7 cells, reduced the gene expression of zonula occludens (ZO)-1 and claudin-1, and normalized trans epithelial electric resistance (TEER) and horseradish peroxidase (HRP) flux in LPS-treated HCT-116 cells. In an animal study, treatment of HFD as well as HFD+LPS groups with UFL or FFL resulted in a notable decrease in body and adipose tissue weights, ameliorated total cholesterol, HDL, triglyceride, aspartate transaminase and endotoxin levels in serum, reduced the urinary lactulose/mannitol ratio, and markedly alleviated lipid accumulation in liver. In addition, exposure of HFD as well as HFD+LPS groups with UFL or FFL resulted in significant alteration of the distribution of intestinal flora, especially affecting the population of Akkermansia spp. and ratio of Bacteroidetes and Firmicutes. CONCLUSION: This evidence collectively demonstrates that Flos Lonicera ameliorates obesity and related metabolic endotoxemia via regulating distribution of gut flora and gut permeability.