Search

Orostachys japonicus is a popular traditional medicinal herb used in Asian countries. This study is focused on evaluating its role in lipid and glucose metabolism in cell and animal models to establish the plant as an anti-obesity and antidiabetic herb. A butanol fraction of O. japonicus was used in the study. The lipid production was evaluated by the Oil Red O technique while the expression of adipogenic markers by Western blotting and RT-PCR using 3T3-L1 preadipocyte. The effect on glucose uptake activity was evaluated in C2C12 myoblast cells. The animal study was carried out in C57BL mice to evaluate anti-obesity activity using the high-fat diet model. The evaluation of serum lipid, blood glucose, adipogenic and fibrosis markers in the liver, and fat deposition in the liver and adipose tissue (by histology) of mice was conducted. Butanol fraction of O. japonicus significantly inhibited the lipid production in the 3T3-L1 cells and reduced the expression of PPARγ, C/EBPα, SREBP-1c and aP2. It enhanced glucose uptake in insulin-resistant C2C12 myoblast cells. It reduced body weight, triglycerides, and blood glucose in the obese mice. It significantly inhibited lipid accumulation in the liver and adipose tissue of obese mice along with suppression of expression of adipogenic and fibrosis markers in the liver. In summary, supporting the previous results, this study helped to establish the potent anti-obesity, antidiabetic, and liver-protecting effect of the butanol fraction of O. japonicus .

Acne vulgaris is a common skin disease characterized by increased sebum production, inflammation, and Cutibacterium acnes (CA: formerly Propionibacterium acnes ) hyperproliferation in pilosebaceous follicles. This study evaluated the efficacy of FRO, a formula composed of fermented Rhus verniciflua Stokes and Orostachys japonicus , against acne pathogenesis via antimicrobial assessment and an in vitro analysis. Stimulated model cells treated with hormones, CA, or lipopolysaccharide (LPS) were designed based on the characteristics of acne pathogenesis, including inflammation and sebum hypersecretion. High-performance liquid chromatography, disc diffusion, MTS, and western blotting assays were used to examine potential anti-acne effects. FRO was determined to contain phenolics such as gallic acid, fisetin, quercetin, and kaempferol. FRO exerted antimicrobial activity against CA and inhibited reactive oxygen species production that was otherwise increased by LPS or CA in HaCaT cells. Additionally, FRO exerted anti-inflammatory effects by inhibiting iNOS, TNF-α, IL-6, p-STAT-3, and p-NF-κB, which were previously upregulated by LPS or CA in THP-1 and HaCaT cells. FRO inhibited lipogenesis induced by steroid hormones and CA by decreasing FAS and SREBP-1 levels in sebocytes. Additionally, FRO down-regulated the androgen receptor, 5α-reductase, SREBP-1, and FAS levels, which were upregulated by steroid hormone in LNCaP cells. Taken together, our findings suggest that FRO alleviates acne by inhibiting the growth of CA, inflammation, and excess sebum and could be used for functional cosmetics or acne treatments.

Orostachys japonicus ( O. japonicus ) was extracted with ethanol (EtOH) and sequentially separated with organic solvents, including n-hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (BuOH), and water (H 2 O). All the fractions were confirmed for anti-inflammatory activity in an inflammatory condition. The DCM fraction showed the highest anti-inflammatory ability. Here, we examined the effect of DCM fraction and investigated the intracellular signaling pathways in LPS-stimulated RAW 264.7 macrophage cells. The DCM fraction significantly inhibited the mRNA levels of pro-inflammatory mediators and cytokines including iNOS, COX-2, IL-1β, IL-2, IL-6, and IP-10 in LPS-stimulated cells. Also, the treatment of DCM fraction excellently reduced the expression of the proteins of AP-1 (phospho-c-Jun and phospho-c-Fos) and phospho-IRF3 as transcription factors. As a result, it suppressed LPS-induced inflammatory mediator and cytokines via inhibition of transcription factors. In conclusion, our data demonstrated that DCM fraction has a strong anti-inflammatory activity that improves the inflammatory state., Competing Interests: The author declares no conflict of interest., (© 2020 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)

The risk of atopic dermatitis (AD)-like skin lesions has increased due to the elevated levels of allergens worldwide. Natural-origin agents, which are effective and safe, show promise for the prevention and treatment of inflammatory conditions. Orostachys japonicus (OJ) A. Berger is an ingredient of traditional herbal medicines for fever, gingivitis, and cancer in Korea, China, and Japan. However, the effect of OJ on AD-like skin lesions is unknown. Therefore, we investigated the effect of OJ ethanol extract (OJEE) on AD-like skin symptoms in mice and cells. OJEE reduced the 2,4-dinitrochlorobenzene-induced AD severity, serum levels of IgE and TARC, and mRNA levels of TARC, TNF-α, and IL-4 in NC/Nga mice. Histopathological analysis showed that OJEE reduced the thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in ear tissue. Furthermore, OJEE suppressed the TNF-α/IFN-γ-increased TARC mRNA level by inhibiting NF-κB and STAT1 activation in HaCaT cells. Taken together, our findings show that OJEE reduced the risk of AD-like skin symptoms by decreasing TARC expression via inhibiting NF-κB and STAT1 activation in skin keratinocytes and thus shows promise as an alternative therapy for AD-like skin lesions., Competing Interests: Conflict of interestThe authors declare no competing financial interest., (© Korean Society of Toxicology 2019.)

Targeted therapy at the molecular level is important for pancreatic cancer treatment. This study looked over the anticancer activity of Orostachys japonicus in a human pancreatic cancer cell line, PANC-1. An ethyl acetate fraction containing quercetin, kaempferol, and flavonol glycosides from O. japonicus (OJE) exhibited significant anticancer activity against the PANC-1. OJE activated caspase-3, caspase-8, and caspase-9, leading to the induction of both intrinsic and extrinsic apoptosis pathways. It also inhibited cyclin D1, cyclin B1, and cyclin-dependent kinase 4, representing cell cycle arrest at both G1/S and G2/M phases. In addition, OJE phosphorylated MAPKs such as p38, JNK, and ERK, which are important upstream signaling factors in apoptosis and arrest of cell cycle inducing system. In conclusion, OJE effectively exerted antipancreatic cancer activity via induction of apoptosis directed by both intrinsic and extrinsic pathways and arrest of cell cycle regulated at both G1/S and G2/M stages, which is activated by MAPKs, p38, JNK, and ERK., Competing Interests: The authors declare no conflict of interest., (© 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)

In this study, Orostachys japonicus was extracted with ethyl alcohol and fractionated by a serial of organic solvents. The ethyl acetate fraction was found to be the most effective among the tested five fractions. High-performance liquid chromatography and mass spectrometry analysis of the ethyl acetate fraction presented epicatechin gallate, quercetin-3-O-glucoside, and kaempferol-3-O-rutinoside. Treatment with O. japonicus inhibited reactive oxygen species (ROS) generation and lipid accumulation during adipogenesis. The gene expression of enzymes involved in the antioxidant system increased in O. japonicus-treated cells. messeanger RNA (mRNA) and protein expression of the pro-oxidant enzymes such as nicotinamide adenine dinucleotide phosphate hydrogen oxidase4 and glucose-6-phosphate dehydrogenase suppressed in O. japonicus-treated cells. O. japonicus also inhibited the mRNA and protein levels of adipogenic transcription factors (including proliferator activated receptor-γ and CCAAT/enhancer-binding protein-α) and their target gene (adipocyte protein 2). These results suggest that O. japonicus inhibits adipogenesis by controlling pro-/anti-oxidant enzyme responses and adipogenic transcription factors. PRACTICAL APPLICATIONS: ROS generation is markedly related to the pathogenesis and development of metabolic disorders. Treatment with O. japonicus inhibited ROS generation and lipid accumulation during adipogenesis. This result indicates that O. japonicus inhibit adipogenesis by controlling pro-/anti-oxidant enzyme responses and adipogenic mediators., (© 2019 Wiley Periodicals, Inc.)

Orostachys japonicus ( O. japonicus ) is utilized as a traditional medicine for patients with various diseases. This study investigated the effect of the ethyl acetate fraction from O. japonicus extract (OJE) on the growth inhibition of OVCAR-3 human ovarian cancer cells demonstrated to inhibit cell growth and arrest the cell cycle in OVCAR-3 cells by blocking the sub-G1 phase and decreasing cyclin E1/CDK2 expression. Cell cycle arrest was connected to the increased expression of the cell cycle regulating factors p53 and p21. Apoptosis was initiated through the intrinsic pathway by up-regulating the expression of the Bcl-2/Bax ratio and down-regulating the expression of pro-caspase-3. Furthermore, OJE treatment elicited p-p38 activation and p-ERK1/2 inhibition. In conclusion, our results demonstrated that OJE reduced the growth of OVCAR-3 human ovarian cancer cells mediated by arrest of the cell cycle and regulation of MAPK signaling pathways.

The hypolipidemic and hypoglycemic effects of two dietary dosages (0.1% and 0.5%) of water and 80% ethanol extracts from hot-air dried Orostachys japonicus A. Berger were evaluated in the serum and organ tissues of streptozotocin-induced diabetic rats. The STZ-induced diabetic groups supplemented with the O. japonicus extracts showed significantly higher body weight compared to a diabetic control group at the end of experiment. The extracts exhibited substantial hypoglycemic effects by significant reductions of fasting blood glucose levels at all time points tested compared to the initial stage before treatment of the extracts. Declines of serum and hepatic triglyceride levels were greater than declines of total cholesterol in the groups treated with the 0.5% O. japonicus extract (DBW2 and DBE2) when compared to the DBC group. Hepatic glycogen content was higher in the groups treated with O. japonicus extract, while lipid peroxide content was decreased in these treated groups compared to the DBC group. Hepatic antioxidant activity was significantly increased in the groups supplemented with the O. japonicus ethanol extract. The hypolipidemic and hypoglycemic effects of the O. japonicus ethanol extract were significantly greater than the effects of the water extract. Based on this study, it seems that O. japonicus ethanol extract, due to its higher phenolic and flavonoid components than the water extract, may control blood glucose and alleviate hyperlipidemia in diabetes.