Biomaterial-based combinatorial approach of aescin-comprised zein-coated gelatin nanoparticles alleviates synovial inflammation in experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mostly affects joints. Although RA therapy has made significant progress, difficulties including extensive medication metabolism and its quick clearance result in its inadequate bioavailability. The anti-inflammatory effect of zein was reported with other medications, but it has certain limitations. There are reports on the anti-oxidant and anti-inflammatory effect of aescin, which exhibits low bioavailability for the treatment of rheumatoid arthritis. Also, the combinatorial effect of zein with other effective drug delivery systems is still under investigation for the treatment of experimental collagen-induced rheumatoid arthritis. The focus of this study was to formulate and define the characteristics of zein-coated gelatin nanoparticles encapsulated with aescin (Ze@Aes-GNPs) and to assess and contrast the therapeutic effectiveness of Ze@Aes-GNPs towards collagen-induced RA in Wistar rats. Nanoprecipitation and the layer-by-layer coating process were used to fabricate Ze@Aes-GNPs and their hydrodynamic diameter was determined to be 182 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to further validate the size, shape, and surface morphology of Ze@Aes-GNPs. When tested against foreskin fibroblasts (BJ), these nanoparticles demonstrated significantly high cytocompatibility. Both Aes and Ze@Aes-GNPs were effective in treating arthritis, as shown by the decreased edoema, erythema, and swelling of the joints, between which Ze@Aes-GNPs were more effective. Further, it was demonstrated that Aes and Ze@Aes-GNPs reduced the levels of oxidative stress (articular elastase, lipid peroxidation, catalase, superoxide dismutase and nitric oxide) and inflammatory indicators (TNF-α, IL-1ß and myeloperoxidase). The histopathology findings further demonstrated that Ze@Aes-GNPs considerably reduced the infiltration of inflammatory cells at the ankle joint cartilage compared to Aes. Additionally, immunohistochemistry examination showed that treatment with Ze@Aes-GNPs suppressed the expression of pro-inflammatory markers (COX-2 and IL-6) while increasing the expression of SOD1. In summary, the experiments indicated that Aes and Ze@Aes-GNPs lowered the severity of arthritis, and critically, Ze@Aes-GNPs showed better effectiveness in comparison to Aes. This suppression of oxidative stress and inflammation was likely driven by Aes and Ze@Aes-GNPs.

Aesculus hippocastanum extract and the main bioactive constituent ß-escin as antivirals agents against coronaviruses, including SARS-CoV-2.

Respiratory viruses can cause life-threatening illnesses. The focus of treatment is on supportive therapies and direct antivirals. However, antivirals may cause resistance by exerting selective pressure. Modulating the host response has emerged as a viable therapeutic approach for treating respiratory infections. Additionally, considering the probable future respiratory virus outbreaks emphasizes the need for broad-spectrum therapies to be prepared for the next pandemics. One of the principal bioactive constituents found in the seed extract of Aesculus hippocastanum L. (AH) is ß-escin. The clinical therapeutic role of ß-escin and AH has been associated with their anti-inflammatory effects. Regarding their mechanism of action, we and others have shown that ß-escin and AH affect NF-κB signaling. Furthermore, we have reported the virucidal and broad-spectrum antiviral properties of ß-escin and AH against enveloped viruses such as RSV, in vitro and in vivo. In this study, we demonstrate that ß-escin and AH have antiviral and virucidal activities against SARS-CoV-2 and CCoV, revealing broad-spectrum antiviral activity against coronaviruses. Likewise, they exhibited NF-κB and cytokine modulating activities in epithelial and macrophage cell lines infected with coronaviruses in vitro. Hence, ß-escin and AH are promising broad-spectrum antiviral, immunomodulatory, and virucidal drugs against coronaviruses and respiratory viruses, including SARS-CoV-2.

A Combination of ß-Aescin and Newly Synthesized Alkylamidobetaines as Modern Components Eradicating the Biofilms of Multidrug-Resistant Clinical Strains of Candida glabrata.

The current trend in microbiological research aimed at limiting the development of biofilms of multidrug-resistant microorganisms is increasingly towards the search for possible synergistic effects between various compounds. This work presents a combination of a naturally occurring compound, ß-aescin, newly synthesized alkylamidobetaines (AABs) with a general structure-CnTMDAB, and antifungal drugs. The research we conducted consists of several stages. The first stage concerns determining biological activity (antifungal) against selected multidrug-resistant strains of Candida glabrata (C. glabrata) with the highest ability to form biofilms. The second stage of this study determined the activity of ß-aescin combinations with antifungal compounds and alkylamidobetaines. In the next stage of this study, the ability to eradicate a biofilm on the polystyrene surface of the combination of ß-aescin with alkylamidobetaines was examined. It has been shown that the combination of ß-aescin and alkylamidobetaine can firmly remove biofilms and reduce their viability. The last stage of this research was to determine the safety regarding the cytotoxicity of both ß-aescin and alkylamidobetaines. Previous studies on the fibroblast cell line have shown that C9 alkylamidobetaine can be safely used as a component of anti-biofilm compounds. This research increases the level of knowledge about the practical possibilities of using anti-biofilm compounds in combined therapies against C. glabrata.

ß-escin activates ALDH and prevents cigarette smoke-induced cell death.

BACKGROUND: The tobacco use is one of the biggest public health threats worldwide. Cigarette smoke contains over 7000 chemicals among other aldehydes, regarded as priority toxicants. ß-escin (a mixture of triterpenoid saponins extracted from the Aesculus hippocastanum. L) is a potent activator of aldehyde dehydrogenase (ALDH) - an enzyme catalyzing oxidation of aldehydes to non-toxic carboxylic acids. PURPOSE: The aim of this study was to evaluate the effect of ß-escin on ALDH activity, ALDH isoforms mRNA expression and cytotoxicity in nasal epithelial cells exposed to cigarette smoke extract (CSE). METHODS: Nasal epithelial cells from healthy non-smokers were treated with ß-escin (1 µM) and exposed to 5% CSE. After 6- or 24-hours of stimulation cell viability, DNA damage, ALDH activity and mRNA expression of ALDH isoforms were examined. RESULTS: 24 h ß-escin stimulation revised CSE induced cytotoxicity and DNA damage. Cells cultured with ß-escin or exposed to CSE responded with strong increase in ALDH activity. This effect was more pronounced in cultures treated with combination of ß-escin and CSE. The strongest stimulatory effect on ALDH isoform mRNA expression was observed in cells cultured simultaneously with ß-escin and CSE: at 6 h for ALDH1A1 and ALDH3A1, and at 24 h for ALDH1A3, ALDH3A2, ALDH3B1, and ALDH18A1. Combined ß-escin and CSE treatment prevented the CSE-induced inhibition of ALDH2 expression at 24 h. CONCLUSIONS: ß-escin is an effective ALDH stimulatory and cytoprotective agent and might be useful in the prevention or supportive treatment of tobacco smoke-related diseases.

Escin-sorafenib synergy up-regulates LC3-II and p62 to induce apoptosis in hepatocellular carcinoma cells.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common solid cancer and the leading cause of cancer deaths worldwide. Sorafenib is the first drug used to treat HCC but its effectiveness needs to be improved, and it is important to find ways to treat cancer that combine sorafenib with other drugs. Synergistic therapies lower effective drug doses and side effects while enhancing the anticancer effect. PURPOSE: In the present study, the therapeutic potential of sorafenib in combination with escin and its underlying mechanism in targeting liver cancer has been established. STUDY DESIGN/METHODS: The IC50 of sorafenib and escin against HepG2, PLC/PRF5 and Huh7 cell lines were determined using MTT assay. The combination index, dose reduction index, isobologram and concentrations producing synergy were evaluated using the Chou-Talaly algorithm. The sub-effective concentration of sorafenib and escin was selected to analyze cytotoxic synergistic potential. Cellular ROS, mitochondrial membrane potential, annexin V and cell cycle were evaluated using a flow-cytometer, and autophagy biomarkers were determined using western blotting. Moreover, autophagy was knocked down using ATG5 siRNA to confirm its role. A DEN-induced liver cancer rat model was developed to check the synergy of sorafenib and escin. RESULTS: Different concentrations of escin reduced the IC50 of sorafenib in HepG2, PLC/PRF5 and Huh7 cell lines. Chou-Talaly algorithm determined cytotoxic synergistic concentrations of sorafenib and escin in these cell lines. Mechanistically, this combination over-expressed p62 and LC-II, reflecting autophagy block and induced late apoptosis, further reconfirmed by ATG5 knockdown. Sorafenib and escin combination  reduced HCC serum biomarker α-feto protein (α-FP) by 1.5 folds. This combination restricted liver weight, tumor number and size, also, conserved morphological features of liver cells. The combination selectively targeted the G0 /G1 phase of cancer cells. CONCLUSION: Escin and sorafenib combination potentially up-regulates p62 to block autophagy to induce late apoptosis in liver cancer cells.

ß-Escin: An Updated Review of Its Analysis, Pharmacology, Pharmacokinetics, and Toxicity.

[Formula: see text]-Escin is an oleanane-type pentacyclic triterpenoid saponin extracted from the seeds of Aesculus hippocastanum (AH), which is more widely distributed. [Formula: see text]-Escin sodium has been approved by the American FDA for clinical usage. This paper is intended to summarize an updated and comprehensive review of the pharmacological activities, pharmacokinetic properties, toxicity, and analytical methods of [Formula: see text]-escin. Studies have shown that [Formula: see text]-escin has significant antitumor, antiviral, anti-inflammatory, and other activities alongside less adverse effects and higher safety than other compounds. The review shows that the pharmacological effects of [Formula: see text]-escin involve mechanisms such as ATM/[Formula: see text]H2AX, RhoA/Rock, GSK-3[Formula: see text]/[Formula: see text]-Catenin, HER2/HER3/Akt, and PI3K/Akt signaling pathways, and Cyclin A, p21[Formula: see text], survivin, Bcl-2, Mcl-1, Caspases, TGF-[Formula: see text], MMPs, and TNF-[Formula: see text] among other inflammatory factors. [Formula: see text]-Escin has significant cytotoxicity; the use of the chitosan/xanthan gum-based polyelectrolyte complexes PA1 and PC-11 to modify it not only to reduces its toxicity, but also improves its drug efficacy. Because of this, these compounds may become a new research hotspot. [Formula: see text]-Escin in vivo metabolism can be converted by the CYP1A2 enzyme in the intestinal flora to produce [Formula: see text]-escin, deacylated, deglycosylated, and 21[Formula: see text]-[Formula: see text]-crotonoyl-protoescin, and the binding rate of the plasma proteins is higher than 90%. These are mainly metabolized by the liver, kidneys, and other organs, and excreted in the form of urine and feces. The number of reports on the specific mediators of the metabolism of [Formula: see text]-escin and their mechanisms and metabolites is relatively small; furthermore, the results are vague. Therefore, a complete and in-depth exploration of the pharmacokinetic characteristics of [Formula: see text]-escin is needed to provide a more complete and effective theoretical reference for the study of its pharmacodynamic activity.

Molecular regulation of autophagy and suppression of protein kinases by aescin, a triterpenoid saponin impedes lung cancer progression.

Lung cancer is the most common and lethal cancer worldwide, yet there are no adequate and novel medications to control this illness. Previous reports suggested the potential of protein kinases to target lung cancer by regulating autophagy. This study establishes the role of aescin, a triterpenoid saponin, in targeting protein kinases responsible for lung cancer proliferation and mobility. The experimental data revealed that aescin significantly impedes lung cancer cell proliferation by downregulating protein kinases such as AKT, mTOR, MEK, and ERK. Downregulation of AKT-mTOR may promote a string of events inducing cytotoxic autophagy-mediated apoptosis in the presence of aescin. Besides, aescin decreases mobility and invasion by downregulating HIF-1α and VEGF gene expressions. Moreover, it successfully monitors EGFR gene expression, improves lung histology, and regulates biochemical parameters in a pre-clinical DEN-induced lung cancer model. Aescin was observed to be safe and non-toxic in both in silico toxicity predictions and ex vivo erythrocyte fragility assays. Hence, this study elucidates the molecular mechanism of aescin in targeting protein kinases and suggests that it could be a safer and more viable therapeutic agent for lung cancer treatment.

Inhibitory effect of ß-escin on Zika virus infection through the interruption of viral binding, replication, and stability.

ß-Escin is a mixture of triterpenoid saponins extracted from horse chestnut seeds that have diverse pharmacological activities, including anti-inflammation, anti-edematous, venotonic, and antiviral effects. In the clinical setting, ß-escin is primarily used to treat venous insufficiency and blunt trauma injuries. The anti-Zika virus (ZIKV) activity of ß-escin has not been explored. This study investigated the antiviral efficacy of ß-escin on ZIKV and dengue virus (DENV) in vitro and then elucidated the underlying mechanism. The inhibitory effects of ß-escin on viral RNA synthesis, protein levels, and infection ability were determined using qRT-PCR, Western blotting, and immunofluorescence assays, respectively. To further characterize how ß-escin interferes with the viral life cycle, the time-of-addition experiment was performed. An inactivation assay was performed to determine whether ß-escin affects ZIKV virion stability. To broaden these findings, the antiviral effects of ß-escin on different DENV serotypes were assessed using dose-inhibition and time-of-addition assays. The results showed that ß-escin exhibits anti-ZIKV activity by decreasing viral RNA levels, protein expression, progeny yield, and virion stability. ß-Escin inhibited ZIKV infection by disrupting viral binding and replication. Furthermore, ß-escin demonstrated antiviral activities against four DENV serotypes in a Vero cell model and prophylactic protection against ZIKV and DENV infections.

Escin suppresses immune cell infiltration and selectively modulates Nrf2/HO-1, TNF-α/JNK, and IL-22/STAT3 signaling pathways in concanavalin A-induced autoimmune hepatitis in mice.

The current study aims to investigate the possible protective effect of escin, the active constituent of a natural mixture of triterpene saponin glycoside, against immune-mediated hepatitis driven by concanavalin A (Con A) and to elucidate its possible underlying mechanisms. Adult male mice were administered Con A (15 mg/kg, intravenously) for 8 h. In the treated groups, mice were pretreated with escin daily (10 mg/kg in CMC, orally) for 4 days before Con A intoxication. In addition, escin was administered in a group to examine its effect on normal mice. Our results showed that escin inhibited Con A-induced elevation in liver enzymes (ALT, AST, and LDH) and curbed the Con A-induced hepatocyte necrosis and apoptosis together with abrogating the death pathway, JNK. Coincidentally, escin has shown a reduction in neutrophil, CD4+ T cell, and monocyte infiltration into the liver. In addition, escin modulated the cellular oxidant status by compensating for the Con A-depleted expression of the transcription factor Nrf2 and the stress protein hemeoxygenase-1. These effects were in good agreement with the restraining effect of escin on Con A-instigated overexpression of NF-κB and the pro-inflammatory cytokines TNF-α and IL-17A. Interestingly, Con A provoked the cellular protective pathway IL-22/STAT3, which was revoked by the escin pretreatment. In conclusion, escin shows extended antioxidant, anti-inflammatory, antinecrotic, and anti-apoptotic effects against Con A-induced immune-mediated hepatitis. These effects may collectively be via suppressing immune cell infiltration into the liver and selective modulation of Nrf2/HO-1, TNF-α/NF-κB, TNF-α/JNK, and IL-22/STAT3 signaling pathways.

Effects of Escin on Oxidative Stress and Apoptosis of H9c2 Cells Induced by H2O2.

OBJECTIVE: 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 H2O2-induced cardiomyocyte injury model. METHODS: H9c2 cells were divided into control group, H2O2 treatment group, and H2O2+escin group. We studied the effect of escin on H9c2 cells and its mechanism by flow cytometry, real-time PCR, CCK-8 assay and Western blot. Cell morphology was observed by cell staining and optical microscopy. RESULTS: We found that the level of reactive oxygen species (ROS) in the H2O2 treatment group was significantly elevated, while the high level of ROS was significantly reversed after treatment with escin. The protein levels of SOD1, SOD2, Bcl-2, and IκB-α in the H2O2 treatment group were significantly decreased compared with the H2O2+escin group, and the Bax, TNF-α, IL-1ß, p65, and IκKα protein expressions were greatly higher than those in the H2O2+escin group. And the results of PCR were also consistent with those. TUNEL-positive cells also decreased significantly when treated with escin. Flow cytometry showed that the percentage of apoptotic cells decreased greatly after treatment of escin. Through IL-1ß immunofluorescence, the fluorescence intensity of the H2O2 treatment group was greatly higher compared with that of the control group, but escin reversed this effect. CONCLUSIONS: These results indicated that escin inhibits H2O2-induced H9c2 cell apoptosis, oxidative stress, and inflammatory responses via the NF-κB signaling pathway.

Escin attenuates oxidative damage, apoptosis and lipid peroxidation in a model of cyclophosphamide-induced liver damage.

To investigate the effects of escin (ES) on acute damage induced by alkylating agent, experimental rats were injected with cyclophosphamide (CPM) to cause liver damage. The animals were divided into four groups: Control Group, CPM (200 mg/kg), ES (10 mg/kg), CPM, and ES Groups. Immunohistopathological, hepatic histopathological, and biochemical changes were analyzed. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), malondyaldehyde (MDA), glutathion (GSH), total oxidant status (TOS) and total antioxidant status (TAS) in serum were all determined. Serum and immunohistopathology analysis revealed that MDA, ALT, AST, LDH, TOC and OSI, caspase-3 and Bax levels had increased while GSH, TAC, Bcl- 2 and OSI levels decreased in CPM Group when compared to Control Group. These findings appear to account for the severe damage detected. In the CPM + ES treated group, positive improvements were found in biochemical parameters as well as in cell-death and tissue-related damage parameters.The results show that ES considerably protects the rat liver against CPM-induced hepatotoxicity thanks to because of its anti-oxidant and anti-apoptotic properties.

Escin Sodium Improves the Prognosis of Acute Pancreatitis via Promoting Cell Apoptosis by Suppression of the ERK/STAT3 Signaling Pathway.

Acute pancreatitis (AP), an inflammatory disorder of the pancreas, can cause systemic inflammatory responses. Escin Sodium (ES), a natural mixture of triterpene saponins extracted from the dry ripe fruit of Fructus Aesculi or horse chestnut crude, has been demonstrated to have antiedematous, anti-inflammatory, and antiexudative effects. We here aim to investigate the effects of ES pretreatment on AP in vivo and in vitro and explore its potential molecular mechanism. In the present study, we demonstrated that ES pretreatment could apparently decrease amylase and lipase, downregulate inflammatory cytokines, and attenuate pancreatic damage. Additionally, the increased expression of apoptotic-related proteins and the results of flow cytometry demonstrated the effects of ES on promoting apoptosis in acinar cells. Moreover, ES could enhance mitochondrial membrane potential (MMP, ΔΨm) and reactive oxygen species (ROS) level and reduce intracellular calcium concentration, which are closely related to mitochondrial-mediated death. The effect of ES pretreatment on acinar cell apoptosis was furtherly confirmed by the regulatory pathway of the ERK/STAT3 axis. These results suggest that ES attenuates the severity of AP by enhancing cell apoptosis via suppressing the ERK/STAT3 signaling pathway. These findings provide evidence for ES which is treated as a novel and potent therapeutic for the treatment of AP.

Escin inhibits angiogenesis by suppressing interleukin­8 and vascular endothelial growth factor production by blocking nuclear factor­κB activation in pancreatic cancer cell lines.

Pancreatic cancer (PaCa) is one of the most aggressive types of cancer. Thus, the development of new and more effective therapies is urgently required. Escin, a pentacyclic triterpenoid from the horse chestnut, has been reported to exhibit antitumor potential by reducing cell proliferation and blocking the nuclear factor­κB (NF­κB) signaling pathway in several types of cancer. Our previous study reported that NF­κB enhanced the secretion of interleukin (IL)­8 and vascular endothelial growth factor (VEGF), thereby inducing angiogenesis in PaCa cell lines. In the present study, it was examined whether escin inhibited angiogenesis by blocking NF­κB activation in PaCa. It was initially confirmed that escin, at concentrations >10 µM, significantly inhibited the proliferation of several PaCa cell lines. Next, using immunocytochemical staining, it was found that escin inhibited the nuclear translocation of NF­κB. Furthermore, ELISA confirmed that NF­κB activity in the escin­treated PaCa cells was significantly inhibited and reverse transcription­quantitative PCR showed that the mRNA expression levels of tumor necrosis factor­α­induced IL­8 and VEGF were significantly suppressed following escin treatment in the PaCa cell lines. ELISA also showed that escin decreased the secretion of IL­8 and VEGF from the PaCa cells. Furthermore, tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escin­treated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the secretion of IL­8 and VEGF by blocking NF­κB activity in PaCa. In conclusion, escin could be used as a novel molecular therapy for PaCa.

Ameliorative effects of escin on neuropathic pain induced by chronic constriction injury of sciatic nerve.

ETHNOPHARMACOLOGY RELEVANCE: Escin is a natural mixture of triterpene saponins extracted from the seeds of Aesculus wilsonii Rehd. And has been reported to possess the therapeutic effects against neuropathic pain (NP). However, the underlying mechanisms remain unclear. AIM OF THE STUDY: The present study aimed to investigate the therapeutic effects and explore the underlying mechanisms of escin on rats of NP induced by chronic constriction injury (CCI) of sciatic nerve. MATERIALS AND METHODS: Rats were treated with escin (7, 14, and 28 mg/kg, i. g.) daily from the third day after the surgery (day 0) for consecutive 14 days. Regular behavior and thermal threshold were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of inflammatory factors and biochemical factors in dorsal root ganglion (DRG). Inflammatory pain responses and nerve injuries were induced by the CCI model. Tonic pain model and acute inflammatory model induced by formalin or carrageenan were established to evaluated the pharmacological effects of escin on acute inflammatory pain. Corresponding behaviors were monitored and relevant gene expression such as c-fos, mu opioid receptor (MOR) and KCNK1 were detected by qRT-PCR. Investigate the neuroprotective effects of escin on PC12 cell injury induced by lipopolysaccharide (LPS). Cell morphology was observed under inverted microscope and neuroprotective effect of escin on cell activity was assessed by MTT assay. RESULTS: Escin could widen thermal threshold, downregulate the concentration of inflammatory factors like tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, suppress the gene expression of toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), decrease the level of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) remarkably. In addition, escin significantly lowered the duration of licking, numbers of flinches and increase in paw edema, showing great therapeutic effects on inflammatory pain responses. Moreover, the activity of injured PC12 cells was significantly improved after escin administrated. CONCLUSION: Escin exerted the ameliorative effects on NP induced by CCI which may be related to downregulating the release of pro-inflammatory cytokines, suppressing TLR-4/NF-κB signal pathway, thereafter decreasing the level of GFAP and NGF.

Attenuation of Cardiac Autonomic Neuropathy by Escin in Diabetic Rats.

Cardiac autonomic neuropathy (CAN) is a least diagnosed complication of diabetes. Inflammation and oxidative stress play a crucial role in the pathophysiology of cardiomyopathy and neuropathy. Escin has anti-inflammatory activity and antioxidant activity. Hence, the present study was designed to evaluate the effect of escin in the management of CAN. Diabetes was induced in Sprague Dawley rats with streptozotocin (STZ). Diabetic animals were randomized in different groups after 6 weeks. Animals in the diabetic control group received no treatment, while animals in other groups received escin at dose 5, 10, and 20 mg/kg for 4 weeks. One group was kept as normal control. Various parameters like basic hemodynamic parameters, heart rate variability (HRV), oxidative stress parameters, and matrix metalloproteinase 9 (MMP-9) were assessed at the end of study. Escin significantly normalized hemodynamic parameters and HRV as compared to diabetic animals. Escin significantly reduced the malondialdehyde level and significantly increased reduced glutathione, catalase and superoxide dismutase levels in diabetic animals. Escin treatment significantly reduced plasma MMP-9 level in diabetic rats. The improvement in the studied parameters was found mainly with administration of higher doses of escin (10 and 20 mg/kg). The escin treatment mitigates CAN in diabetic rats. The results of study indicate that escin can be useful option for management of CAN.

Molecular docking analyses of Escin as regards cyclophosphamide-induced cardiotoxicity: In vivo and in Silico studies.

This study aims to investigate whether Escin (ES) can protect against Cyclophosphamide (CPM)-induced cardiac damage. The experimental rats were categorized as Control, CPM (200 mg/kg), ES (10 mg/kg), and CPM + ES Groups, each having 6 members. Their heart tissues were stained with Hematoxylin and Eosin and the structural changes were investigated under the light microscope. The biochemical markers of ischemia modified albumin (IMA), creatine kinase (CK-MB), antioxidant activity indicators Catalase (CAT), and superoxide dismutase (SOD) activities were measured using blood samples. Besides, the effects of CPM, ES, and CPM + ES upon CAT and SOD activities were shown via molecular docking studies. In the Single-Dose CPM group, CK-MB and IMA levels significantly increased while SOD and CAT levels significantly decreased. However, the heart tissues were damaged. CK-MB and IMA levels significantly decreased in CP+ ES Group. On the other hand, SOD, and CAT levels significantly increased and reduced the damage remarkably. Our findings showed that ES treatment successfully reduced the toxic effects upon the rats. The conclusion is that ES treatment can help protect the heart tissue against CPM-induced toxicity. Both in-vivo results and molecular modeling studies showed that the negative effects of CPM upon SOD activity were bigger than that of CAT.

Aescin Protects Neuron from Ischemia-Reperfusion Injury via Regulating the PRAS40/mTOR Signaling Pathway.

Ischemic stroke is one of the major causes of disability; widely use of endovascular thrombectomy or intravenous thrombolysis leads to more attention on ischemia-reperfusion injury (I/R injury). Aescin, a natural compound isolated from the seed of the horse chestnut, has been demonstrated anti-inflammatory and antiedematous effects previously. This study was aimed at determining whether aescin could induce protective effects against ischemia-reperfusion injury and exploring the underlying mechanisms in vitro. Primary cultured neurons were subjected to 2 hours of oxygen-glucose deprivation (OGD) followed by 24 hours of simulated reperfusion. Aescin, which worked in a dose-dependent manner, could significantly attenuate neuronal death and reduce lactate dehydrogenase (LDH) release after OGD and simulated reperfusion. Aescin treatment at a concentration of 50 µg/ml provided protection with fewer side effects. Results showed that aescin upregulated the phosphorylation level of PRAS40 and proteins in the mTOR signaling pathway, including S6K and 4E-BP1. However, PRAS40 knockdown or rapamycin treatment was able to undermine and even abolish the protective effects of aescin; meanwhile, the levels of phosphorylation PRAS40 and proteins in the mTOR signaling pathway were obviously decreased. Hence, our study demonstrated that aescin provided neuronal protective effects against I/R injury through the PRAS40/mTOR signaling pathway in vitro. These results might contribute to the potential clinical application of aescin and provide a therapeutic target on subsequent cerebral I/R injury.

Effects of Biosurfactants on Enzymatic Saccharification and Fermentation of Pretreated Softwood.

The enzymatic hydrolysis of cellulose is inhibited by non-productive adsorption of cellulases to lignin, and that is particularly problematic with lignin-rich materials such as softwood. Although conventional surfactants alleviate non-productive adsorption, using biosurfactants in softwood hydrolysis has not been reported. In this study, the effects of four biosurfactants, namely horse-chestnut escin, Pseudomonas aeruginosa rhamnolipid, and saponins from red and white quinoa varieties, on the enzymatic saccharification of steam-pretreated spruce were investigated. The used biosurfactants improved hydrolysis, and the best-performing one was escin, which led to cellulose conversions above 90%, decreased by around two-thirds lignin inhibition of Avicel hydrolysis, and improved hydrolysis of pretreated spruce by 24%. Red quinoa saponins (RQS) addition resulted in cellulose conversions above 80%, which was around 16% higher than without biosurfactants, and it was more effective than adding rhamnolipid or white quinoa saponins. Cellulose conversion improved with the increase in RQS addition up to 6 g/100 g biomass, but no significant changes were observed above that dosage. Although saponins are known to inhibit yeast growth, no inhibition of Saccharomyces cerevisiae fermentation of hydrolysates produced with RQS addition was detected. This study shows the potential of biosurfactants for enhancing the enzymatic hydrolysis of steam-pretreated softwood.

Phytochemical, ethanomedicinal and pharmacological applications of escin from Aesculus hippocastanum L. towards future medicine.

Medicinal plants are used from ancient times for treatment of various ailments. Aesculus hippocastanum (Horse chestnut), is the popular and most valuable tree native to the South East Europe. It's seed extracts and their concentrates contain phytocompounds like flavonoids, polyphenols, triterpenoid saponin glycosides (escin), epicatechin, tannins, kaempferol, esculin, fraxin, carbohydrate, essential fatty acids (linoleic acid), oleic acid and purine bases (adenine and guanine). Due to these vital phyto-constituents, horse chestnut is used in phytomedicine for the prevention and treatment of diverse disorders as in venous congestion in leg ulcers, bruises, arthritis, rheumatism, diarrhoea, phlebitis etc. We collected the pharmacological applications of Aesculus hippocastanum L. extracts and escin as the cheif bioactive compound and their uses in traditionally and clinically for the management of various disorders. This review describes the efficacy of A. hippocastanum L. extracts and their bioactive compounds. So in the furtue this plant may be useful for the alternative treatment measure for various ailments via incorporating either extract or escin into novel delivery systems for improving the social health in future and would provide improved quality of life.

Escin alleviates peripheral neuropathy in streptozotocin induced diabetes in rats.

AIM: Inflammatory cascade and oxidative stress play a central role in diabetic peripheral neuropathy via activation of inflammatory cytokines. Escin has potent antioxidant and anti-inflammatory properties. Hence, the present study was conducted to evaluate the effect of escin on diabetic peripheral neuropathy in streptozotocin (STZ) induced diabetes in rats. MAIN METHODS: Diabetes was induced in rats with streptozotocin (55 mg/kg). The animals with blood glucose above 250 mg/dl were randomized in different groups. Animals were treated with escin at a dose of 5, 10 and 20 mg/kg after six weeks of diabetes induction for the next four weeks. After completion of treatment, various parameters like glucose, thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia and nerve conduction velocities were evaluated. Oxidative stress parameters like malondialdehyde, catalase, reduced glutathione and superoxide dismutase were performed in sciatic nerves. Histopathology study of sciatic nerves was also studied. KEY FINDINGS: Escin treatment significantly reduced plasma glucose, thermal hyperalgesia, mechanical hyperalgesia and mechanical allodynia as compared to diabetic animals. The motor nerve conduction velocity and sensory nerve conduction velocities were significantly improved in diabetic animals treated with escin. Escin significantly normalized oxidative stress parameters. Escin treatment also prevented progression of neuronal damage by reducing demyelination, leukocytic infiltration in sciatic nerves as compared to diabetic animals. SIGNIFICANCE: From the results of study it can be concluded that escin can be a useful option for management of diabetic peripheral neuropathy.