Ameliorating effects of Orostachys japonica against high-fat diet-induced obesity and gut dysbiosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonica (rock pine) has been used as a folk remedy to treat inflammation, hepatitis, and cancer in East Asia. AIM OF THE STUDY: The aim of this study was to investigate the effect of rock pine extract (RPE) on high-fat diet-induced obesity in mice and to examine its effects on gut dysbiosis. MATERIALS AND METHODS: The characteristic compound of RPE, kaempferol-3-O-rutinoside, was quantified using high-performance liquid chromatography. The prebiotic potential of RPE was evaluated by assessing the prebiotic activity score obtained using four prebiotic strains and high-fat (HF)-induced obesity C57BL/6 mice model. Analysis included examining the lipid metabolism and inflammatory proteins and evaluating the changes in gut permeability and metabolites to elucidate the potential signaling pathways involved. RESULTS: In vitro, RPE enhanced the proliferation of beneficial probiotic strains, including Lactiplantibacillus and Bifidobacterium. HF-induced model showed that the administration of 100 mg/kg/day of RPE for 8 weeks significantly (p < 0.05) reduced the body weight, serum lipid levels, and insulin resistance, which were associated with notable changes in lipid metabolism and inflammation-related markers. CONCLUSIONS: Our results demonstrate that rock pine consumption could mitigate obesity and metabolic endotoxemia in HF-fed mice through enhancing intestinal environment.

Anti-Obesity and Anti-Diabetic Effects of Ostericum koreanum (Ganghwal) Extract.

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.

Orostachys malacophylla (pall.) fisch extracts alleviate intestinal inflammation in Drosophila.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. AIM OF THE STUDY: We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. MATERIALS AND METHODS: Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. RESULTS: We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. CONCLUSIONS: In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.

Echeveria Pallida: Inhibiting Adhesion of Fibroblasts From Pterygium and Neutrophil Extracellular Traps Production.

Context: Pterygium, meaty eyes, is a disease that produces a triangular, conjunctival-epithelial, neovascularized overgrowth covering the cornea, which can cause vision loss. Histological characterization of Pterygium reveals the presence of proliferating fibroblasts (FBs) that remodel the extracellular matrix, with infiltration of immune cells, causing chronic inflammation. The fresh juice of Echeveria pallida E. Walther (Crassulaceae), mechanically extracted from the leaves, can be used to lubricate the eyes and remove Pterygium, even in advanced, degenerative ocular disease. Objective: This study aimed to explore the healing mechanisms of an ethanolic extract of E. pallida on pterygium-derived FBs, lymphocytes, and neutrophils. Design: The research team designed an in-vitro study. Primary cultures of FBs were obtained from fresh, surgical pterygium tissues, and neutrophils and mononuclear cells were purified from the peripheral blood of healthy donors. Intervention: An ethanolic extract of E. pallida was evaluated at 30, 50, 80, 100, 200, and 300 µg/mL-the intervention groups-for viability and proliferation of FBs and lymphocytes. The study included a negative control with no extract, and a positive control, Mitomycin C (MMC), used as a FB proliferation inhibitor and anti-inflammatory. Because some reports have suggested that DMSO at low concentrations can stimulate or inhibit lymphocyte proliferation depending on the cell type, the study also included a DMSO control. Outcome Measures: The measures included an analysis of E. pallida's effects on the proliferation and viability of FBs, the proliferation of human lymphocytes, and human neutrophil extracellular traps (NETs) production. NETs were induced using biochemical and microbiological stimuli-phorbol myristate acetate (PMA), hypochlorous acid (HOCl), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans-through fluorescence microscopy. Results: The ethanolic extract didn't affect the viability or proliferation of pterygium-derived FBs and human blood lymphocytes, but it showed significant inhibitory activity, from 100 µg/mL, on FB adhesion and the production of NETs. Conclusion: The study found scientific evidence that supports the effects of an extract of the medicinal plant E. pallida in inhibiting the adhesion of FBs derived from human pterygium and NET production.

Purification, Structural Characterization, and Anti-Inflammatory Effects of a Novel Polysaccharide Isolated from Orostachys fimbriata.

The present study elucidated the structural characteristics and anti-inflammatory activity of a novel polysaccharide isolated from Orostachys fimbriata, which is a traditional Chinese medicinal plant. O. fimbriata polysaccharide (OFP) was extracted and subsequently purified by chromatography using a DEAE cellulose-52 and Sephadex G-75 column. The molecular weight was determined as 6.2 kDa. HPGPC and monosaccharide composition analysis revealed a homogeneous polysaccharide containing only Glc. Chromatography and spectral analysis showed that the possible chemical structure consisted of →4)-α-Glcp-(1→ and a small quantity of →4,6)-ß-Glcp-(1→ in the main chain and →6)-ß-Glcp-(1→, α-Glcp-(1→, and ß-Glcp-(1→ in the side chain. Morphological analysis using scanning electron microscopy (SEM) and atomic force microscopy (AFM) indicated that OFP had a multi-branched structure, and the sugar chain molecules of polysaccharide appeared aggregated. OFP was found to exhibit anti-inflammatory activity by reducing the secretion of inflammatory factors in RAW264.7 cells and by decreasing the extent of xylene-induced ear swelling in mice.

Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems.

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer's disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses ß-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

ESI-MS/MS Analysis of Phenolic Compounds from Aeonium arboreum Leaf Extracts and Evaluation of their Antioxidant and Antimicrobial Activities.

Aeonium is a genus of succulents belonging to the Crassulaceae family. Their importance in traditional medicine has stimulated both pharmacological and chemical research. In this study, we optimized extraction, separation, and analytical conditions using a high performance liquid chromatographic method coupled with electrospray ionization mass spectrometry by the negative mode (HPLC-ESI-MS) in order to, for the first time, determine thirty-four compounds from Aeonium arboreum leaves. Twenty-one of them are assigned among which are sixteen flavonoids and five phenolic acids. FRAP, TAC, DPPH, and ABTS•+ radical scavenging were used to evaluate antioxidant activity. The obtained IC50 values ranged from 0.031 to 0.043 mg.mL-1 for DPPH and between 0.048 and 0.09 mg·mL-1 for ABTS•+. Antimicrobial activity was also assessed. The obtained minimum inhibitory concentrations (MIC) of these extracts ranged from 12.5 to 50 µg·mL-1 against Micrococcus luteus, Listeria ivanovii, Staphylococcus aureus, Salmonella enterica, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger, and Fusarium oxysporum, and from 25 to 50 µg·mL-1 against Candida albicans. Therefore, these extracts can be considered as a potential source of biological active compounds.

Anti-cancer effects of the aqueous extract of Orostachys japonica A. Berger on 5-fluorouracil-resistant colorectal cancer via MAPK signalling pathways in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonica A. Berger, also known as Wa-song in Korea, has traditionally been used as a folk medicine, but the potential anti-cancer effects of aqueous extract of Orostachys japonica (OJe) have not yet been thoroughly investigated. AIM OF THE STUDY: To evaluate the anti-cancer effects of OJe, its possible mechanisms of action were investigated in 5-fluorouracil (5-FU) resistant SNU-C5/5-FUR colorectal cancer cells. MATERIALS AND METHODS: The functional compounds of OJe were identified with high performance liquid chromatography. The anti-cancer effects of OJe in SNU-C5/5-FUR cells were investigated by a cell viability assays, flow cytometry analysis, and a subcutaneous xenograft model employing BALB/c-nude mice. Possible signalling pathways were assayed with Western blotting. RESULTS: OJe (250 µg/ml) showed anti-cancer effects in SNU-C5/5-FUR cells, that were mediated via apoptosis as well as cell cycle arrest at the G0/G1 phase. Gallic acid and (-)-epicatechin, the major functional components of OJe, induced cell cycle arrest. OJe treatment (250 mg/kg, p.o.) produced a significant anti-proliferative effect in the xenograft model via decreased ß-catenin/GSK3ß and increased p27 expression. OJe treatment significantly activated ERK and p38 both in vitro and in vivo. CONCLUSIONS: These results suggest that OJe has anti-proliferative effects on 5-FU-resistant colorectal cancer cells via regulation of MAPK signalling pathways.

Effect of Combined K. pinnata and Metformin Preparation on Inflammatory Cytokines in Normal and Diabetic Skeletal Muscle Cells.

Diabetes Mellitus is associated with systemic inflammation and oxidative stress, which may play a central role in the development of diabetic complications. In this study, combined preparations of Kalanchoe pinnata and metformin were investigated to determine the effects on inflammatory activity in human skeletal muscle myoblasts (HSMMs) and human diabetic skeletal muscle myoblasts (DHSMMs). Results showed that combinatorial preparations sustained cell viability for 3 days in both HSMM and DHSMM cells. However, a significant decrease in cellular viability occurred for both cell lines on day 5. Results also indicate that combinatorial preparations of K. pinnata may modulate immune responses by significantly upregulating proinflammatory markers, interleukin (IL) 2, and tumor necrosis factor-alpha, and upregulating the anti-inflammatory marker, IL-10, in HSMM and DHSMM cells. The combined preparations significantly downregulated the anti-inflammatory glycoprotein IL-6 in both diabetic and nondiabetic human skeletal muscle cells. The findings suggest that combined preparations of K. pinnata and metformin might be a potential immune-modulating agent that may promote inflammation and adversely affect the outcome of diabetic patients.

Orostachys japonicus ameliorates acetaminophen-induced acute liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (O. japonicus), referred to as Wa-song in Korea is a traditional and herbal medicine. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of ethanol extract of O. japonicus (OJE) on acetaminophen (N-acetyl-p-aminophenol, APAP) overdose-induced hepatotoxicity have not been determined yet. AIM OF THE STUDY: The present study was aimed to investigate the effects of OJE against APAP-induced acute liver injury (ALI) and explore the underlying mechanisms. MATERIALS AND METHODS: Mice were treated orally with OJE (50, 100, or 200 mg/kg) for seven days before APAP (300 mg/kg) injection. After 12 h of APAP treatment, serum and liver tissues were collected. An in vitro system using primary hepatocytes was also applied in this study. RESULTS: Pretreatment with OJE, especially at a dose of 200 mg/kg, reduced APAP overdose-induced ALI in mice, as evidenced by decreased serum alanine/aspartate aminotransferase levels, histopathological damage, and inflammation. Consistently, OJE pretreatment reduced the gene transcription of cytochrome P450 (CYP) 3A11 and CYP1A2 in livers of mice injected with or without APAP, at least in part, via inactivation of nuclear receptor pregnane X receptor (PXR). Furthermore, the role of PXR in mediating the OJE regulation of CYPs was confirmed in primary hepatocytes, which showed that OJE pretreatment inhibited PXR activity and APAP hepatotoxicity enhanced by pregnenolone 16α-carbonitrile, a mouse agonist of PXR. Besides, the antioxidative activity provided by OJE, involving increases in hepatic glutathione (GSH) content and decreases in malondialdehyde levels, has been shown to exert hepatoprotective effects in normal and injured livers. Moreover, APAP-activated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in mice liver were indirectly inhibited by pretreatment with OJE. CONCLUSIONS: Taken together, our findings showed that OJE attenuated APAP-induced ALI by decreasing APAP-metabolizing enzymes via inactivation of PXR and the restoration of hepatic GSH content. Therefore, OJE could be a promising hepatoprotective agent.