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The Role of Plant-Based Natural Compounds in Inflammation
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Marcela Dvorakova, Premysl Landa, Lenka Langhansova
Similar 5-LOX inhibitory activity was observed for the quinone embelin, obtained from the fruit extract of Embelia ribes Burm. F (Figure 22.7C). Embelin was found to remarkably inhibit 5-LOX with an IC50 = 70 nM in a cell-free assay, which was superior to the activity of Zileuton (IC50 = 760 nM). Embelin acted as a reversible inhibitor of 5-LOX. In cell-based assay, embelin inhibited 5-LOX (IC50 = 0.8 µM to 2.0 µM) at a similar level as Zileuton (IC50 = 1.2 µM). In addition, embelin inhibited mPGES-1 with an IC50 of 0.2 µM in a cell-based assay. On the other hand, embelin failed to inhibit COXs below 10 µM (Schaible et al., 2013).
Embelia ribes (False Black Pepper) and Gymnema sylvestre (Sugar Destroyer)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Chandrabose Selvaraj, Chandrabose Yogeswari, Sanjeev Kumar Singh
Bioactive constituents found in E. ribes include vilangin, which is often extracted from the dried ripened fruits of the plant (Latha, 2007). Berries of E. ribes were also found to contain a variety of phytoconstituents, including tannin, resin, alkaloid, phenolic acid, vanillic acid, and o-coumaric acid (Haq et al., 2005). E. ribes seeds yielded the bioactive compounds embelinol, embeliaribyl ester, embeliol, and the fruits were found to contains 4.33% of bioactive compound embelin (Indrayan et al., 2005). Others such as 2-hydroxy-4-undecyl-3-6-benzoquinone, quercetin, embalate, and fatty acids were found in E. ribas in addition to those mentioned previously (Lin et al., 2006). Seeds are rich in inorganic metals, like Ca, Zn, Mn, Cr, K, and C, as well as steroids, cardiac glycosides, and anthraquinone compounds (Tambekar et al., 2009; McErlean and Moody, 2007). In the root region, it has several nitrogen-containing compounds 3-alkyl1, 4-benzoquinone derivative, 4-benzoquinone, gomphilactone derivatives, 5, 6-dihydroxy-7-tridecyl-3- [4-tridecyl-3-hydroxy-5-oxo-2(5H)-furylidene]-2-oxo 3(2H)-benzofuran, daucosterol, and sitosterol (Raja et al., 2005; Dang et al., 2014). Aerial parts of the plant have novel embeliphenol A and embelanide, which are bioactive compounds. The most active bioactive compounds of the E. ribes are represented in Figure 6.3.Represents the important bioactive molecule present in Embelia ribes.
Increasing the Sensitivity of Adipocytes and Skeletal Muscle Cells to Insulin
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
The seeds of Embelia ribes Burm.f. contain embelin (Figure 4.3), which given orally at a dose of 25 mg/kg/day for 15 days to Wistar rats intoxicated with carbon tetrachloride lowered serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase activities, and total bilirubin.67 At the hepatic level, this benzoquinone increased the activity of superoxide dismutase, catalase, and glutathione peroxidase. It also increased glutathione content; lowered hepatic lipoperoxydation; and improved hepatic cytoarchitecture.67 Naik et al. provided evidence that embelin given at a dose of 50 mg/kg/day orally for 3 days to Wistar rats poisoned, with streptozotocin reduced glycemia by 42%.68 Embelin reduced serum tumor necrosis-α and interleukin-6 by 60% and 40%, respectively, and improved hepatic glutathione, superoxide dismutase, and catalase.68 The plasma lipid profile of rodents treated by embelin evidenced a decrease of cholesterol from 187.7 to 111 mg/dL, triglycerides from 173.1 to 108 mg/dL, very low-density lipoprotein from 34.6 to 21.3 mg/dL and low-density lipoprotein from 126.9 to 59.7 mg/dL.68 This alkylresorcinol had no effect on the glycemia of normoglycemic rodents fed with normal diet implying an increase of peripheral glucose uptake.68 In a parallel study, embelin given orally to streptozotocin high fat-induced type 2 diabetic Wistar rats (fasting blood glucose >250 mg/dL) at a dose of 50 mg/kg/day for 28 days had no effect on body weight and lowered glycemia from 305.1 to 138.6 mg/dL (normal: 139.6 mg/dL; rosiglitazone 10 mg/kg/day: 134.2 mg/dL).69 This aryl-1,4-benzoquinone lowered plasma insulin from 28.5 to 15.6 μU/mL (normal: 16.7 μU/mL; rosiglitazone 10 mg/kg/day: 16.8 μU/mL) evidencing a decrease in insulin resistance.69 This treatment lowered plasma cholesterol by 23.2%, triglycerides by 53.3%, and free fatty acids by 41.3%.69 In oral glucose tolerance test on day 25, embelin lowered 60 minutes peak glycemia at 356.1 to 141.2 mg/dL (normal: 158.6; rosiglitazone 10 mg/kg/day: 143.1 mg/dL).69 Embelin evoked an increased expression of peroxisome proliferator-activated receptor-γ in epididymal adipose tissue and to a much lesser extend in liver and skeletal muscle.69 Embelin in epididymal adipose tissue upregulated phosphoinositide 3-kinase, phosphorylated Akt and glucose transporter-4.69 The glucose lowering effects of thiazolidinedione antidiabetic agents is based on agonist effect on peroxisome proliferator-activated receptor-γ, which induces the expression of glucose transporter-4, the secretion of leptin, adiponectin and tumor necrosis-α, fatty acid-binding protein, fatty acid transport protein, and acyl-CoA-oxidase.70 Furthermore, agonists of peroxisome proliferator-activated receptor-γ improve the sensitivity of adipocyte to insulin resulting in decreased release of nonesterified free fatty acids in the circulation.71
IAP inhibitor, Embelin increases VCAM-1 levels on the endothelium, producing lymphocytic infiltration and antitumor immunity
Published in OncoImmunology, 2020
Kosei Nakajima, Yoshinori Ino, Rie Yamazaki-Itoh, Chie Naito, Mari Shimasaki, Mami Takahashi, Minoru Esaki, Satoshi Nara, Yoji Kishi, Kazuaki Shimada, Nobuyoshi Hiraoka
Recovering the dysfunctional TECs by Embelin occurred at a lower concentration compared to that of the tumor-cell-killing effect. Embelin has been shown to have an antitumor effect on glioma, leukemia, and pancreatic cancers in in vitro assays using cell lines ,22–24 where more than 20–30 µM of Embelin was needed in contrast to the 0.1 µM concentration required for inducing the lymphocyte-trafficking-related adhesion molecules in TECs, as shown in this study. Although Embelin was used at a relatively low dose to avoid its direct tumor-killing effect in the animal model in this study, if a high dose of Embelin is administered, higher antitumor activity is expected through direct tumor killing, vascular normalization, and some additional immunological effects, as described above.
Embelin impairs the accumulation and activation of MDSCs in colitis-associated tumorigenesis
Published in OncoImmunology, 2018
Ting Wu, Chaohui Wang, Weihong Wang, Yuhang Hui, Rongxin Zhang, Liang Qiao, Yun Dai
Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) is a non-peptidic small molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), and its anti-oxidant and anti-inflammatory properties have been reported earlier.29,30 Our previous studies have shown that embelin has potent anti-inflammatory and anti-tumor effects in a CAC model.31–33 Embelin can not only inhibit cancer cell proliferation but also modulate the TME. It decreases the expression and production of pro-inflammatory cytokines and impairs the infiltration and function of tumor-associated macrophage (TAM) in the tumor milieu.33 Our finding suggests that myeloid cells may be a critical target of embelin to achieve its therapeutic benefits in CAC.
Antidepressant-like effects of embelin and its possible mechanisms of action in chronic unpredictable stress-induced mice
Published in Neurological Research, 2018
Bailing Wang, Xiaoqin Chen, Tiantian Zhou, Xiaoying Wang
Embelin (2, 5-dihydroxy-3-undecyl-1, 4-benzoquinone) is the principal active constituent of Embelia ribes Burm belonging to the Myrsinaceae family. Embelin is reported to possess antifertility [15], antidiabetic [16], antibacterial [17], wound healing [18], analgesic, anti-tumor, anti-inflammatory [19,20], and antioxidant [21]. Moreover, the effects of embelin on the central nervious system such as anxiolytic [22], anticonvulsant activities [23], huntington’s disease [24], and hypoxia-ischemia (HI) induced neurological injury [25] have also been reported. Although a report shows embelin probably has a positive effect on depression [26], the roles and underlying mechanisms of embelin on chronic stress-induced depression are still unknown.