Artemisia argyi ethanol extract ameliorates nonalcoholic steatohepatitis-induced liver fibrosis by modulating gut microbiota and hepatic signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear. AIM: This study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model. METHODS: Male C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-ß-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways. RESULTS: Treatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC. CONCLUSION: The AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis.

Osteogenic Effects of the Diospyros lotus L. Leaf Extract on MC3T3-E1 Pre-Osteoblasts and Ovariectomized Mice via BMP2/4 and TGF ß Pathways.

Osteoporosis, a disease defined by the primary bone strength due to a low bone mineral density, is a bone disorder associated with increased mortality in the older adult population. Osteoporosis is mainly treated via hormone replacement therapy, bisphosphates, and anti-bone resorption agents. However, these agents exert severe side effects, necessitating the development of novel therapeutic agents. Many studies are focusing on osteogenic agents as they increase the bone density, which is essential for osteoporosis treatment. Here, we aimed to investigate the effects of Diospyros lotus L. leaf extract (DLE) and its components on osteoporosis in MC3T3-E1 pre-osteoblasts and ovariectomized mice and to elucidate the underlying related pathways. DLE enhanced the differentiation of MC3T3-E1 pre-osteoblasts, with a 1.5-fold elevation in ALP activity, and increased the levels of osteogenic molecules, RUNX family transcription factor 2, and osterix. This alteration resulted from the activation of bone morphogenic protein 2/4 (BMP2/4) and transformation of growth factor ß (TGF ß) pathways. In ovariectomized mice, DLE suppressed the decrease in bone mineral density by 50% and improved the expression of other bone markers, which was confirmed by the 3~40-fold increase in osteogenic proteins and mRNA expression levels in bone marrow cells. The three major compounds identified in DLE exhibited osteogenic and estrogenic activities with their aglycones, as previously reported. Among the major compounds, myricitrin alone was not as strong as whole DLE with all its constituents. The osteogenic activity of DLE was partially suppressed by the inhibitor of estrogen signaling, indicating that the estrogenic activity of DLE participated in its osteogenic activity. Overall, DLE suppresses osteoporosis by inducing osteoblast differentiation.

Saposhnikovia divaricata root and its major components ameliorate inflammation and altered gut microbial diversity and compositions in DSS-induced colitis.

Background: The root of Saposhnikovia divaricata (Turcz.) Schischk is a well-known traditional medicinal plant, containing various bioactive compounds with anti-inflammatory, antioxidant, and analgesic properties. However, no scientific studies have validated its clinical use as an anti-inflammatory agent against inflammatory bowel disease (IBD). This study aimed to investigate whether the root extract of S. divaricata ameliorates IBD and induces gut microbial alteration, using a RAW 264.7 cell line and a DSS-induced colitis mouse model. Methods: To investigate the anti-inflammatory effects and alleviation of IBD, using a methanol extract of Saposhnikovia divaricata (Turcz.) Schischk. root (MESD), RAW 264.7, murine macrophages and a dextran sodium sulfate (DSS)-induced colitis mouse model were employed. 16S rRNA gene sequencing was conducted to determine the alterations in the gut microbiota of mice with DSS-induced colitis. Results: MESD significantly decreased nitric oxide (NO) and inflammatory cytokine levels in lipopolysaccharide (LPS)-induced RAW 264.7 cells in vitro. Oral administration of MESD reduced the expression of inflammatory cytokines in the colons of mice with DSS-induced colitis. Additionally, MESD inhibited the abundance of Clostridium sensu stricto 1 and enhanced the predicted functional pathways, including l-glutamate degradation VIII (to propanoic acid). Seven compounds with anti-inflammatory properties were isolated from the MESD. Among them, 3'-O-acetylhamaudol and 3'-O-angeloylhamaudol exhibited strong anti-inflammatory effects in vitro. Conclusion: Overall, MESD may be a potential natural product for the treatment of IBD by lowering inflammatory cytokine levels and altering gut microbiota composition.

Sanguisorba officinalis L. Ameliorates Hepatic Steatosis and Fibrosis by Modulating Oxidative Stress, Fatty Acid Oxidation, and Gut Microbiota in CDAHFD-Induced Mice.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver diseases and encompasses non-alcoholic steatosis, steatohepatitis, and fibrosis. Sanguisorba officinalis L. (SO) roots have traditionally been used for their antioxidant properties and have beneficial effects on metabolic disorders, including diabetes and obesity. However, its effects on hepatic steatosis and fibrosis remain unclear. In this study, we explored the effects of a 95% ethanolic SO extract (SOEE) on NAFLD and fibrosis in vivo and in vitro. The SOEE was orally administered to C57BL/6J mice fed a choline-deficient, L-amino-acid-defined, high-fat diet for 10 weeks. The SOEE inhibited hepatic steatosis by modulating hepatic malondialdehyde levels and the expression of oxidative stress-associated genes, regulating fatty-acid-oxidation-related genes, and inhibiting the expression of genes that are responsible for fibrosis. The SOEE suppressed the deposition of extracellular matrix hydroxyproline and mRNA expression of fibrosis-associated genes. The SOEE decreased the expression of fibrosis-related genes in vitro by inhibiting SMAD2/3 phosphorylation. Furthermore, the SOEE restored the gut microbial diversity and modulated specific bacterial genera associated with NAFLD and fibrosis. This study suggests that SOEE might be the potential candidate for inhibiting hepatic steatosis and fibrosis by modulating oxidative stress, fatty acid oxidation, and gut microbiota composition.

Artemisia argyi extract alleviates inflammation in a DSS-induced colitis mouse model and enhances immunomodulatory effects in lymphoid tissues.

BACKGROUND: The incidence of inflammatory bowel disease (IBD), an inflammatory disorder of the gastrointestinal system has increased. IBD, characterized by aberrant immune responses against antigens, is thought to be caused by the invasion of enterobacteria. The pathogenesis of IBD is complicated, hence novel effective therapeutic agents are warranted. Therefore, this study evaluates the potential of Artemisia argyi, a medicinal herb, in alleviating IBD. METHODS: The effectiveness of the A. argyi ethanol extract was verified both in vitro and in vivo. Inflammation was induced in RAW 264.7 cells by 1 µg/mL of lipopolysaccharide (LPS) and by 3% dextran sodium sulfate (DSS) in a DSS-induced colitis mouse model. During the ten-day colitis induction, 200 mg/kg of A. argyi ethanol extract was orally administered to the treatment group. Levels of inflammation-related proteins and genes were analyzed in the colon, serum, and lymphoid tissues, i.e., Peyer's patches (PPs) and spleen. The chemical constituent of the A. argyi ethanol extract was identified using an ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS) analysis. RESULTS: A. argyi ethanol extract treatment ameliorated IBD symptoms and reduced the expression of inflammation-related proteins and genes in the colon and serum samples. Furthermore, A. argyi treatment induced the activation of anti-oxidative associated proteins, such as nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1); and the treatment have also inhibited nuclear factor-κB (NF-κB), a central mediator of inflammatory responses. A. argyi enhanced the immunomodulatory effects in the PPs and spleen, which may stem from interleukin-10 (IL-10) upregulation. Chemical analysis identified a total of 28 chemical compounds, several of which have been reported to exert anti-inflammatory effects. CONCLUSIONS: The effectiveness of the A. argyi ethanol extract in alleviating IBD was demonstrated; application of the extract successfully mitigated IBD symptoms, and enhanced immunomodulatory responses in lymphoid tissues. These findings suggest A. argyi as a promising herbal medicine for IBD treatment.

Identification of Chemical Compounds from Artemisia gmelinii using UPLC-QTOF-MS/MS and their Regulatory Effects on Immune Responses in DSS-Induced Colitis Mice.

Artemisia gmelinii Web. ex Stechm. (AG), a popular medicinal herb in Asia, has been used as a common food ingredient in Korea and is traditionally known for its anti-inflammatory properties. Therefore, in this study, we aimed to investigate whether AG relieves IBD, a classic chronic inflammatory disease of the gastrointestinal tract. We identified 35 chemical compounds in AG ethanol extract using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. In mice with DSS-induced IBD, AG administration attenuated the disease activity index and the serum and colonic levels of inflammatory cytokines and chemokines. AG treatment decreased nuclear factor-[Formula: see text]B (NF-[Formula: see text]B) signaling, a key mediator of inflammation, in the mouse colons. Additionally, AG extract enhanced immune responses in lymphoid tissues such as spleen and Peyer's patches. Thus, AG consumption potently ameliorated IBD symptoms and improved immune signaling in lymphoid tissues.