beta-escin and Inflammation

Saponins are a group of compounds used in clinical practice in the management of several diseases. Escin is a natural mixture of triterpene saponins which mainly consist of several isoforms, in which the α- and β-escin are predominant. β-escin is the major active compound that exerts a therapeutic effect by relieving tissue edema, promoting venous drainage, and reducing inflammation. In this review, we describe the features of its glucocorticoid-like activity that could explain its clinical effects. Using PubMed, Embase Cochrane library and reference lists for articles published until October 01, 2020, we documented that escin is likely able to exert its anti-inflammatory and anti-edematous effects through a glucocorticoid-like activity, but without the development of glucocorticoid-like adverse drug reactions.

Topics: Anti-Inflammatory Agents; Edema; Escin; Humans; Inflammation

This review discusses historical and recent pharmacological and clinical data on the anti-edematous, anti-inflammatory, and venotonic properties of escin (Reparil

Topics: Animals; Anti-Inflammatory Agents; Edema; Escin; Humans; Inflammation; Saphenous Vein; Vasoconstrictor Agents

The use of transdermal therapeutic systems has spread worldwide since they allow effective local drug delivery. In the present study, we investigated the efficacy and safety of a new betamethasone valerate medicated plaster (Betesil®) to manage facial swelling, edema, inflammation, ecchymosis, and hematoma, when applied immediately after a facial rejuvenation procedure.. We applied the plaster to the skin of 20 healthy patients for 12 hours immediately after hyaluronic acid-based procedure performed with the aim of erasing facial wrinkles of perioral and nasolabial folds and improving chin and eye contour. A further 20 patients underwent the same cosmetic procedure, but they were treated with an aescin 10% cream (applied immediately after the procedure, in the evening, and the morning after) and served as control group.. Betesil® application resulted in a significant improvement in swelling/edema/inflammation score, if compared with aescin 10% cream (P < 0.01). As for facial ecchymosis and hematoma around the needle injection track, only two patients in the active treatment group displayed minimal ecchymosis and hematoma. In the control group, two patients presented minimal ecchymosis and three slight hematoma. However, using the ecchymosis/hematoma score, no significant difference between Betesil® and aescin 10% cream groups was observed. Patients' satisfaction was significantly higher among subjects receiving Betesil®, if compared to patients receiving aescin 10% cream (P < 0.01).. The present study supports the use of Betesil® plaster immediately after facial cosmetic procedures in order to safely control swelling, edema, and inflammation.

Topics: Administration, Cutaneous; Adult; Aged; Betamethasone Valerate; Cosmetic Techniques; Edema; Escin; Female; Follow-Up Studies; Glucocorticoids; Humans; Hyaluronic Acid; Inflammation; Male; Middle Aged; Patient Satisfaction; Rejuvenation; Skin Aging; Treatment Outcome

Rheumatoid arthritis is among the most common disabling diseases associated with chronic inflammation. The efficacy of the current therapeutic strategies is limited; therefore, new pharmacological agents and formulation approaches are urgently needed. In this work, we developed a thermosensitive gel incorporating escinosomes, innovative nanovesicles made of escin, stabilized with 10% of tween 20 and loaded with a Carbonic Anhydrase Inhibitor (CAI) bearing a Carbon Monoxide Releasing Moiety (CORM) (i.e., CAI-CORM 1), previously synthesized by some of the authors as a new potent pain-relieving agent. The light scattering analysis of the developed formulation showed optimal physical parameters, while the chromatographic analysis allowed the quantification of the encapsulation efficiency (90.1 ± 5.91 and 91.6 ± 8.46 for CAI-CORM 1 and escin, respectively). The thermosensitive gel, formulated using 23% w/v of poloxamer 407, had a sol-gel transition time of 40 s and good syringeability. Its stability in simulated synovial fluid (SSF) was morphologically evaluated by electron microscopy. Nanovesicles were physically stable in contact with the medium for two weeks, maintaining their original dimensions and spherical shape. The viscosity increased by about 30- to 100-fold with the temperature change from 25 °C to 37 °C. The gel erosion in SSF occurred within 9 h (88.2 ± 0.743%), and the drug's passive diffusion from escinosomes lasted 72 h, allowing a potential sustained therapeutic effect. The efficacy of a single intra-articular injection of the gel containing escinosomes loaded with CAI-CORM 1 (3 mg/mL; 30 μL, CAI-CORM 1 formulation) and the gel containing unloaded escinosomes (30 μL, blank formulation) was evaluated in a rat model of Complete Freund's Adjuvant (CFA)-induced rheumatoid arthritis. CAI-CORM 1 formulation was assessed to counteract mechanical hyperalgesia, spontaneous pain, and motor impairments on days 7 and 14 after treatment. The histological evaluation of the joints stressed the improvement of several morphological parameters in CFA + CAI-CORM 1 formulation-treated rats. In conclusion, the hybrid molecule CAI-CORM 1 formulated in escinosome-based thermosensitive gel could represent a new valid approach for managing rheumatoid arthritis.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Carbonic Anhydrase Inhibitors; Escin; Inflammation; Pain; Rats

Escin is an active ingredient used in the treatment of phlebitis. However, the pharmacological mechanism of escin remains largely unclear. Here, we aimed to determine the molecular basis for the therapeutic effect of escin. Human umbilical vein endothelial cells (HUVECs) were subjected to shear-stress assays with or without escin. Intracellular Ca

Topics: Animals; Escin; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Ion Channels; Mice; Mice, Knockout; NF-kappa B

Myocardial infarction (MI) is a serious heart health problem in the world with a high mortality rate. Our study is mainly aimed at validating the antioxidative stress and antiapoptotic effects of escin in a H. H9c2 cells were divided into control group, H. We found that the level of reactive oxygen species (ROS) in the H. These results indicated that escin inhibits H

Topics: Apoptosis; Cardiovascular Agents; Cells, Cultured; Escin; Humans; Hydrogen Peroxide; Inflammation; Myocytes, Cardiac; NF-kappaB-Inducing Kinase; Oxidants; Oxidative Stress; Protein Serine-Threonine Kinases; Signal Transduction

Obesity is characterized by excess fat accumulation and closely associated with insulin resistance and type 2 diabetes. We aimed at exploring the potential effect and mechanism of escin for the treatment of obesity using network pharmacology, and to verify the effect of escin on obese mice.. Escin targets were predicted by DrugBank and SwissTarget database. Potential targets for the treatment of obesity were identified based on the DisGeNET database. Comparative analysis was used to investigate the overlapping genes between escin targets and obesity treatment-related targets. Using STRING database and Cytoscape to analyze interactions among overlapping genes, hub genes were identified. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted in DAVID. High-fat diet (HFD) -induced obese mice were used to observe the anti-obesity effects of escin. The body weight, relevant biochemical markers and HE staining of fat and liver tissues were determined after escin was administered for 18 weeks.. We screened 53 overlapping genes for escin and obesity. The mechanism of intervention of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4). The screening and enrichment analysis revealed that the treatment of obesity using escin primarily involved 10 GO enriched terms and 13 related pathways. In vivo, escin can reduce the body weight of obese mice induced by HFD and improve lipid metabolism through lowering triglycerides (TG), total cholesterol (TC), and density lipoprotein (LDL) levels and increasing high density lipoprotein (HDL) levels and decreasing leptin level and increasing adiponectin (ADPN) level. Escin can regulate glucose metabolism caused by obesity through decreasing fasting glucose, postprandial blood glucose and regulating the level of insulin. These obese mice induced by HFD displayed the increased insulin resistance that was associated with the increased inflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Escin may antagonize the increase of MCP-1 and partially antagonize the low-grade inflammation caused by obesity. From the morphological changes of fat and liver tissues stained by HE stain, escin could decrease the size of adipocytes and improve liver necrosis and fatty degeneration in obese mice fed by HFD.. The network pharmacology of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4), 10 GO enriched terms and 13 related pathways. In vivo, escin can be potentially used to prevent or treat obesity through reducing the weight, improving glucose and lipid metabolism, partially antagonizing the low-grade inflammation, and improved insulin resistance.

Topics: Animals; Cyclooxygenase 2; Cytochrome P-450 CYP3A; Diabetes Mellitus, Type 2; Diet, High-Fat; Escin; Glucose; I-kappa B Kinase; Inflammation; Insulin Resistance; Matrix Metalloproteinase 9; Mice; Mice, Obese; Obesity; TOR Serine-Threonine Kinases

Topics: Acute Lung Injury; Animals; Escin; Inflammation; Interleukin-1beta; Interleukin-6; Lipid Peroxidation; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred C57BL; Random Allocation; Tumor Necrosis Factor-alpha

Endothelial dysfunction is involved in the pathogenesis of decompression sickness (DCS) and contributes substantively to subsequent inflammatory responses. Escin, the main active compound in horse chestnut seed extract, is well known for its endothelial protection and anti-inflammatory properties. This study aimed to investigate the potential protection of escin against DCS in rats. Escin was administered orally to adult male rats for 7 d (1.8 mg/kg/day) before a simulated air dive. After decompression, signs of DCS were monitored, and blood and pulmonary tissue were sampled for the detection of endothelia related indices. The incidence and mortality of DCS were postponed and decreased significantly in rats treated with escin compared with those treated with saline (P < 0.05). Escin significantly ameliorated endothelial dysfunction (increased serum E-selectin and ICAM-1 and lung Wet/Dry ratio, decreased serum NO), and oxidative and inflammatory responses (increased serum MDA, MPO, IL-6 and TNF-α) (P < 0.05 or P < 0.01). The results suggest escin has beneficial effects on DCS related to its endothelia-protective properties and might be a drug candidate for DCS prevention and treatment.

Topics: Animals; Antioxidants; Biomarkers; Decompression Sickness; Endothelial Cells; Escin; Inflammation; Male; Malondialdehyde; Protective Agents; Rats, Sprague-Dawley; Superoxide Dismutase

Periodontitis is a chronic inflammatory disease associated with gram-negative subgingival microflora infection. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and anti-edematous effects. This study was designed to investigate the in vitro effects of escin on the inflammatory reaction of human periodontal ligament cells (hPDLs). hPDLs were stimulated with lipopolysaccharide (LPS). The cells were treated with various concentrations of escin. The viability of hPDLs was evaluated using the MTT method. The expression of Toll-like receptor 2 (TLR2) in hPDLs and the levels of IL-1β, TNF-α and IL-6 in the supernatant were measured. Escin significantly attenuated LPS-induced cytotoxicity in a concentration-dependent manner in hPDLs. Treatment with escin partly blocked the expression of TLR2. Escin also lowered the increase of pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) induced by LPS. The present findings show that escin exerts a protective effect against LPS-induced inflammation in hPDLs. It was also shown that escin is a promising medicine for the treatment of periodontitis.

Topics: Adolescent; Anti-Inflammatory Agents; Cells, Cultured; Escin; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Periodontal Ligament; Periodontitis; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha; Young Adult

Escin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut (Aesculus hippocastanum), had been demonstrated to possess anti-edematous and anti-inflammatory effects. The present study was designed to investigate whether escin exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to investigate the anti-inflammatory effects of escin and glucocorticoid alone or combined. The carrageenan-induced paw edema was inhibited only when escin and corticosterone (Cort) were administered together. Co-administration of escin with Cort significantly reduced the volume of exudates and the number of white blood cells of exudates in bilaterally adrenalectomized rats with pleuritis, but treatment with escin or Cort alone at a suboptimal concentration did not show any effect on the pleuritis rats. After the murine macrophagic RAW264.7 cells stimulated by lipopolysaccharide (LPS), they were treated with escin, Cort or escin and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) of cell culture supernatants were analyzed. Escin or Cort markedly reduced the content of NO, TNF-α and IL-1β secreted by LPS-stimulated RAW264.7 macrophage cells. The combination of suboptimal concentrations of escin with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO, TNF-α and IL-1β in LPS-stimulated RAW264.7 macrophage cells. The findings suggest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect.

Topics: Aesculus; Animals; Anti-Inflammatory Agents; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Edema; Escin; Glucocorticoids; Inflammation; Inflammation Mediators; Interleukin-1beta; Lipopolysaccharides; Macrophages; Male; Mice; Nitric Oxide; Pleurisy; Random Allocation; Rats; Tumor Necrosis Factor-alpha

Although Bell's palsy is the most common acute facial paralysis, the cause of it is still unknown. This made the treatment for it remain very limited. Many methods are simply symptomatic treatment. Up to now we have known that Bell's palsy is related to viral infection and the pathomechanism of Bell's palsy involves inflammatory oedema and entrapment neuropathy in the narrow bony facial canal. So treatment plans for Bell's palsy mainly focus on antiviral therapy, relieving inflammatory oedema and accelerating facial nerve recovery. Sodium beta-aescin is derived from horse chestnut and its major constituent is aescigenin which has been approved by China national drug standard. The pharmacologic action of sodium beta-aescin is to relieve tissue oedema, recover vasopermeability and eliminate pressure caused by oedema. Nowadays sodium beta-aescin has been widely used clinically for encephaledema or tumefaction caused by trauma or operation. It also can be used for treating disease of digestive system and increasing intravenous tension and improving microcirculation. Although many papers had been published on the anti-edema effects of sodium beta-aescin, little was known about the effects in treating oedema complicated by Bell's palsy.

Topics: Bell Palsy; Cardiovascular Agents; Chemistry, Pharmaceutical; Drug Design; Edema; Escin; Facial Paralysis; Humans; Inflammation; Ischemia; Models, Biological; Models, Theoretical; Pharmaceutical Preparations; Sodium

Human vascular endothelial cells (HUVECs) were exposed to CoCl2 as an in vitro model of hypoxia. Expression of VCAM-1 (vascular cell adhesion molecule), reduction of PECAM-1 (platelet endothelial cell adhesion molecule) and cytoskeletal changes without alterations in cell viability were observed. HUVECs were also exposed to Escherichia coli lipopolysaccaride (LPS) as an in vitro model of inflammation: significant IL-6 release was measured. Pre-treatment of HUVECs with aescin prevented, in a concentration-dependent fashion (0.1-1 microM), the action of CoCl2 on VCAM-1 and PECAM-1, also preserving endothelial cell morphology. Furthermore, aescin pre-treatment reduced IL-6 release from LPS-activated vascular endothelium.

Topics: Aesculus; Cell Survival; Cobalt; Dose-Response Relationship, Drug; Endothelium, Vascular; Escherichia coli; Escin; Fruit; Humans; Hypoxia; Inflammation; Interleukin-6; Lipopolysaccharides; Phytotherapy; Plant Extracts; Platelet Endothelial Cell Adhesion Molecule-1; Vascular Cell Adhesion Molecule-1

We investigated the effects of escins Ia, Ib, and IIb isolated from horse chestnut, the seeds of Aesculus hippocastanum L., and desacylescins I and II obtained by alkaline hydrolysis of escins on acute inflammation in animals (p.o.). Escins Ia, Ib, IIa, and IIb (50-200 mg/kg) inhibited the increase of vascular permeability induced by both acetic acid in mice and histamine in rats. Escins Ib, IIa, and IIb (50-200 mg/kg) also inhibited that induced by serotonin in rats, but escin Ia didn't. Escins Ia, Ib, IIa, and IIb (200 mg/kg) inhibited the hind paw edema induced by carrageenin at the first phase in rats. Escin Ia (200 mg/kg) and escins Ib, IIa, and IIb (50-200 mg/kg) inhibited the scratching behavior induced by compound 48/80 in mice, but escin Ia was weakest. Desacylescins I and II (200 mg/kg) showed no effect. With regard to the relationship between their chemical structures and activities, the acyl groups in escins were essential. Escins Ib, IIa, and IIb with either the 21-angeloyl group or the 2'-O-xylopyranosyl moiety showed more potent activities than escin Ia which had both the 21-tigloyl group and the 2'-O-glucopyranosyl moiety.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Capillary Permeability; Edema; Escin; Inflammation; Male; Mice; Rats; Rats, Wistar; Seeds; Structure-Activity Relationship

In order to complete previous results of the efficacy of the horse chestnut saponin escin, its activity was tested on two further models of inflammation: the rat serous peritonitis provoked by i.p. injection of formalin solution, and the rat serous pleurisy provoked by intrapleural injection of Evans Blue/carrageenan. The results showed escin to be an anti-exudative substance with regard to its exudation inhibitory effect determined by the reduction of exudative fluid. As to peritonitis the diminution of protein permeation into the abdominal cavity was determined: with increasing doses escin tended to prevent more efficiently the diffusion of small molecules than the permeation of large molecules. The hypothesis that escin has an effect on the vascular walls in the sense of a "sealing" effect on the capillaries was tested on the following model: the permeability of the plasma-lymph barrier of the hind leg of the rabbit was enhanced by injection of bradykinin. Escin antagonised the bradykinin effect dose-dependently determined by the depression of the raised lymph-flow by about 70%.

Topics: Animals; Aspirin; Bradykinin; Dose-Response Relationship, Drug; Escin; Exudates and Transudates; Female; Hydrocortisone; Inflammation; Male; Peritonitis; Phenylbutazone; Pleurisy; Rabbits; Rats; Saponins; Time Factors

Topics: Adrenal Cortex Hormones; Adrenal Glands; Adrenalectomy; Aesculus; Animals; Anti-Inflammatory Agents; Ascorbic Acid; Biomedical Research; Cholesterol; Edema; Escin; Guinea Pigs; Hypophysectomy; Inflammation; Lipid Metabolism; Metabolism; Pharmacology; Pituitary Gland; Rats; Research; Saponins; Tryptophan