HORSE CHESTNUT

Horse chestnut supplements deliver escin compounds that are mostly established for ability to alleviate early stages of chronic venous insufficiency (“spider veins”). Some clinical evidence also shows improved recovery in connection with surgery, and at least one trial is ongoing with post-operative knee recovery. Identified mechanisms in these settings point to escin’s promising anti-cancer potential, particularly through inhibition of angiogenesis and metastatic spread. The central role of NF-κB pathway inhibition in both vascular health and cancer growth and spread may lead to further traction in clinical trials.

Most remarkable to date are escins positive effects on patient outcomes in advanced thyroid cancers, including potent suppression of biomarkers used to track disease activity such as TSH. Some compelling pre-clinical data has also emerged in its anti-metastatic activity for ovarian cancer, driving some increased interest from researchers. Its highly likely escin based supplements would have some degree of anti-metastatic action due to the positive effects on blood vessel performance. Given the well established effects on vascular health, lab studies that show potent activity might be interesting. Pre-clinical studies show reduced progression for instance of melanoma, osteosarcoma as well as ovarian cancer and more.

TYPICAL ABSORPTION LEVELS

High

EXAMPLES OF IMPROVED OUTCOMES

YES
ANALYSIS

PRE-DIAGNOSIS OR PREVENTION

PENDING

Highlighted Studies

In conclusion, our current study showed Escin is efficient and well tolerated in patients with advanced thyroid cancer. Based on the safety, and pharmacokinetic and efficacy profiles of our study, it was concluded that Escin 0.6 mg/kg/day i.v. for 9 days was tolerable. Furthermore, Escin significantly reduced the serum levels of TSH, TgAb, Tg, and calcitonin related to thyroid cancer progression and recurrence and prolonged the PFS and OS for patients with advanced thyroid cancer

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Indeed, tumour load was very efficiently reduced (>94%) in mice treated with beta-escin when compared with control mice in the prevention and intervention treatment studies. Beta-escin (Venastat) is a natural mixture of triterpenoid saponins (horse chestnut) that has previously been shown to improve chronic venous insufficiency. In addition, it sensitizes cells in culture to gemcitabine chemotherapy and inhibits NF-κB signalling. It is conceivable that beta-escin, which is highly effectiv...

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Our results demonstrate that in endothelial cells β-escin potently induces cholesterol synthesis which is rapidly followed with marked fall in actin cytoskeleton integrity. The concomitant changes in cell functioning result in a significantly diminished responses to TNF-α stimulation. These include reduced migration, alleviated endothelial monolayer permeability, and inhibition of NFκB signal transduction leading to down-expression of TNF-α—induced effector proteins. Moreover, the study...

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Moreover, p38 mitogen-activated protein kinases (MAPKs) and reactive oxygen species (ROS) were activated by escin. A p38 MAPK inhibitor partially attenuated the autophagy and apoptosis triggered by escin, but a ROS scavenger showed a greater inhibitory effect. Finally, the therapeutic efficacy of escin against osteosarcoma was demonstrated in an orthotopic model. Overall, escin counteracted osteosarcoma by inducing autophagy and apoptosis via the activation of the ROS/p38 MAPK signalling path...

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https://onlinelibrary.wiley.com/doi/10.1002/cam4.10314.5 After low term follow-up, we compared the progression-free survival (PFS) and overall survival (OS) between the 120 patients from cohort 2 who have received the Escin treatment and the 30 patients from cohort 1 who have received placebo. As shown in Figure 2, significant prolongation of PFS and OS was observed for patients receiving Escin compared with placebo. The median PFS was 2.44 years in the Escin-treated group comparing with 1.04 years in placebo group. The median OS was also significantly improved from 3.73 years (placebo group) to 7.6 years (Escin-treated group).To our knowledge, this is the first clinic study of Escin with thyroid cancer patients. Escin showed striking effects on prolonging the progression-free survival and overall survival in our current patients. This kind of antitumor effect is consistent with other in vitro and in vivo nude mice studies showing Escin has antitumor effects on lung cancer 20, breast cancer 21, liver cancer 31, pancreas cancer 32, and colon cancer 33. The dosage of Escin in our current was 0.6 mg/kg/day i.v. for 9 days. In our study, there are only two patients (6%) developed grade 3 side effects, one occurred Anemia, another showed ALT elevations. While after symptomatic treatment, both patients accomplished 9-day Escin treatment
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003230.pub4/full2Overall, the trials suggested an improvement in the symptoms of leg pain, oedema and pruritus with horse chestnut seed extract when taken as capsules over two to 16 weeks. Six placebo‐controlled studies (543 participants) reported a clear reduction of leg pain when the herbal extract was compared with placebo. Similar results were reported for oedema, leg volume, leg circumference and pruritis.Overall, there appeared to be an improvement in CVI related signs and symptoms with HCSE compared with placebo. Leg pain was assessed in seven placebo‐controlled trials. Six reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups, while another reported a statistically significant improvement compared with baseline. One trial suggested a weighted mean difference (WMD) of 42.4 mm
https://researchoutput.csu.edu.au/ws/portalfiles/portal/8733014/PrepubPID12118.pdf2Horsechestnut complex has the potential to accelerate lymphatic drainage in the normal population. A multi-centre randomised controlled trial is required to evaluate the clinical benefits of horsechestnut complex in managing lymphoedema in breast cancer survivors.There has also been some suggestion that horsechestnut complex may encourage lymphangiogenesis. In this case, the 1.6% improvement noted in this pilot investigation might be expected to progressively increase over a period of several years as the lymphatics progressively build and repair.
https://ir.swu.ac.th/xmlui/handle/123456789/171841.5However, log-rank test analysis revealed that A group had a slightly more rapid recovery from POST than P group (0.0013 vs. 0.0007 case/person-minute, p=0.03). Side effects and analgesics consumption did not differ between groups. Conclusion: Single 40 mg oral dose of aescin preoperatively, compare to placebo, did not reduce the incidence or severity of POST in the first 24 postoperative hours. Aescin, however, hastened the speed of recovery of POST compare to placebo with statistical significancePatients in A group (n=58) received aescin (Reparil®) 40 mg orally 2 to 6 hours prior to surgery and P group (n=59) received placebo. Anesthesia care was identical and under blinded staff anesthesiologist's discretion. The presence/absence of POST, numerical pain score of POST, adverse events and cumulative analgesics consumption were recorded postoperatively at 30, 60 minutes, 2, 4, and 24 hours.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.01643651Our results demonstrate that in endothelial cells β-escin potently induces cholesterol synthesis which is rapidly followed with marked fall in actin cytoskeleton integrity. The concomitant changes in cell functioning result in a significantly diminished responses to TNF-α stimulation. These include reduced migration, alleviated endothelial monolayer permeability, and inhibition of NFκB signal transduction leading to down-expression of TNF-α—induced effector proteins. Moreover, the study provides evidence for novel therapeutic potential of β-escin beyond the current vascular indications.In summary, the global analysis of β-escin effects on endothelial cells suggests that the β-escin induced perturbation in cholesterol homeostasis may be considered as the triggering event in a cascade of cellular responses leading to cytoskeletal disarrangements followed by a decreased NFκB activation and down-expression of TNF-α—induced effector proteins. defining mechanisms of pharmacological effectiveness of the drug. Our results indicate that the vascular anti-inflammatory mechanism of β-escin involves disturbances in cholesterol homeostasis leading to cytoskeletal perturbations followed by decreased NFκB activation. Moreover, our data provide evidence for novel therapeutic potential of β-escin beyond current vascular indications.
https://www.nature.com/articles/aps20171921In conclusion, this study demonstrated that the signaling adaptor p62 reduced escin-induced apoptosis in CRC cells via p62-mediated DNA damage and the ATM/γH2AX pathway. p62-mediated DNA damage may be a potential target for the antitumor effect of escin...Our results showed that escin activated ROS levels (Figure 2A), however, there is no evidence to expound the relationship between escin-induced autophagy and apoptosis. Autophagy is a protective factor against DNA damage, ROS and endoplasmic reticulum stress. In response to escin-induced oxidative stress, intracellular autophagy level was increased by escinSurprisingly, we found that escin apparently increases the autophagy levels in HCT116 and HCT-8 cells (Figure 9A), simultaneously upregulating the expression of p62, which may indicate that RNF168 leads to ubiquitination of DNA repair proteins to recruit them to the sites of DNA damage to repair the damage. In addition, escin apparently increases the levels of cellular ROS and autophagy (Figure 2A, Figure 9A). ROS, which induces autophagy and is also eliminated by autophagy, may be involved in the functions of p62 in escin-induced DNA damage and repair
https://www.mdpi.com/1420-3049/23/1/1971It was found that β-escin exerts inhibitory effect on the basic fibroblast growth factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM angiogenesis in vivo. The inhibition of critical steps of angiogenic process observed with β-escin could be partially explained by suppression of Akt activation in response to bFGF. Moreover, the anti-angiogenic effects of β-escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions in endothelial cells. In conclusion, β-escin affects endothelial cells as a negative mediator of angiogenesis in vitro and in vivo and may therefore be considered as a promising candidate for further research elucidating its underlying mechanism of action.It was reported that β-escin inhibited tumor growth and development not only by its potent anti-proliferative and apoptotic effects against different cancer cell lines but also by the inhibition of angiogenesis [32]. According to this fact, we provided a thorough insight into the cellular and molecular mechanisms of the anti-angiogenic effect of plant-based β-escin both on HUVECs and using CAM assay. We showed that β-escin could modulate in vitro HUVECs migration and proliferation. Consistent with our results, previous report showed a potent inhibitory effect of β-escin on angiogenesis by depressing proliferation and migration, reaching an inhibition at 40 µg/mL [32].
https://pmc.ncbi.nlm.nih.gov/articles/PMC4545433/1In conclusion, escin has potent antiproliferative effects against C6 glioma and A549 cells. These effects are dose and time dependent. Also, escin caused apoptotic effects which were more intensely observed in A549 cells compared to C6 glioma. The most likely mechanisms of action are the arrest of cell cycle and the induction of apoptosis by caspase-3 activation and bax protein expression on A549 cells. This study suggests that escin may be a suitable candidate for tumor treatmentThe results indicated that escin has potent antiproliferative effects against C6 glioma and A549 cells. These effects are both dose and time dependent. Taken together, escin possesses cell cycle arrest on G0/G1 phase and selective apoptotic activity on A549 cells as indicated by increased Annexin V-binding capacity, bax protein expression, caspase-3 activity and morphological changes obtained from micrographs by transmission electron microscopy.
https://onlinelibrary.wiley.com/doi/10.1155/2013/2517521Therefore, we hypothesized that Escin, which is derived from horse chestnut seeds and which had already exhibited anti-inflammatory activities [14] could be used as an effective treatment against pancreatic cancer cells, either when administered alone or in combination with existing treatment protocols. Our in vitro experiments revealed that Escin significantly inhibited the growth of all of the pancreatic cancer cells tested (Panc-1, Mia-Paca, COLO357, and P34) in a dose-dependent manner.Finally, the chemosensitization of pancreatic tumor cells appears to be mediated through the ability of Escin to modify cell-signaling molecules, including cell proliferating proteins, such as cyclin D and members of the NF-κB signaling pathways, as described for resveratrol by Gupta et al. [50] whose in vitro studies found that resveratrol inhibited the proliferation of human PaCa pancreatic cell lines, synergized the apoptotic effects of gemcitabine, and inhibited both the constitutive activation of NF-κB and the expression of Bcl-2, Bcl-xL, COX-2, cyclin D1, MMP-9, and VEGF.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4427252/1This in vitro activity was mirrored by an inhibition of in vivo adhesion, which translated into the formation of fewer metastatic nodules. Indeed, tumour load was very efficiently reduced (>94%) in mice treated with beta-escin when compared with control mice in the prevention and intervention treatment studies. Beta-escin (Venastat) is a natural mixture of triterpenoid saponins (horse chestnut) that has previously been shown to improve chronic venous insufficiency. In addition, it sensitizes cells in culture to gemcitabine chemotherapy and inhibits NF-κB signalling31. It is conceivable that beta-escin, which is highly effective in preventing early OvCa metastasis, may also be useful for the treatment of other cancers that metastasize to the same anatomic sites within the peritoneal cavity, such as gastric, colon and pancreatic cancer.Here we show that a multilayered culture containing primary human fibroblasts, mesothelial cells and extracellular matrix can be adapted into a reliable 384- and 1,536-multi-well HTS assay that reproduces the human ovarian cancer (OvCa) metastatic microenvironment. We validate the identified inhibitors in secondary in vitro and in vivo biological assays using three OvCa cell lines: HeyA8, SKOV3ip1 and Tyk-nu. The active compounds directly inhibit at least two of the three OvCa functions: adhesion, invasion and growth. In vivo, these compounds prevent OvCa adhesion, invasion and metastasis, and improve survival in mouse models
https://www.oncotarget.com/article/8152/text/1Moreover, it reduced the LOXL2 level in MDA-MB-231 cells but not in MCF-7 cells. When MCF-7 cells were stimulated with TNF-α/TGF-β, transfected with LOXL2 or treated with hypoxia, escin Ia down-regulated the level of LOXL2 in MCF-7 cells. Meanwhile, escin Ia suppressed the EMT process in LOXL2-transfected or hypoxia-treated MCF-7 cells. Of interest, escin Ia did not alter the level of HIF-1α in hypoxia-induced MCF-7 cells. In TNBC xenograft mice, the metastasis and EMT of MDA-MB-231 cells were suppressed by escin Ia. In conclusion, escin Ia was the main active ingredient of SFAC for the anti-TNBC metastasis activity, and its action mechanisms involved inhibition of EMT process by down-regulating LOXL2 expression.Escin Ia (4 mg/kg) and BAPN (100 mg/kg) treatments caused down-regulations of LOXL2, vimentin, α-SMA, Snail, Slug, Zeb1, Zeb2 and Twist and up-regulation of E-cadherin at protein and mRNA grades in MDA-MB-231 xenografts mice (Figure 9B–9D). However, escin Ia (2 mg/kg, 4 mg/kg) showed little effect on protein and mRNA expression of HIF-1α in breast tumors of mice (Figure 9B and 9C). Taken together, the findings indicted that escin Ia suppressed the TNBC metastasis by inhibition of EMT process and consequent invasive growth through down-regulating LOXL2.
https://cancerci.biomedcentral.com/articles/10.1186/s12935-022-02713-91Taken together, our findings highlight β-escin as a promising candidate for the treatment of trastuzumab-resistant HER2-positive breast cancers....Importantly, β-escin selectively inhibited malignant cells and was less toxic to normal mammary cells, and no toxic effects were found in liver and kidney function in animals.Attenuation of CSC-related features by β-escin challenge was accompanied by marked reductions in CD44high/CD24low stem-like cells and aldehyde dehydrogenase 1 (ALDH1) activity as well as hindrance of mammosphere formation. β-escin administration also significantly retarded tumor growth and angiogenesis in a trastuzumab-resistant JIMT-1 xenograft model via downregulation of CSC-associated markers and intracellular domain HER2
https://pubs.rsc.org/en/content/articlehtml/2018/ra/c8ra03578d1β-Escin exhibits anticancer effects on a panel of established cancer cells. However, the effects of β-escin on human osteosarcoma (OS) are still unknown. The aim of the present study was to investigate whether β-escin was effective against OS both in vivo and in vitro. Our results showed that β-escin induced dose- and time-dependent effects against MG-63, OS732, U-2OS, HOS and SAOS-2 cell proliferation. β-Escin also exhibited excellent anti-proliferative and pro-apoptotic effects in an established OS xenograft model. Taken together, in this study we found that β-escin inhibits proliferation of human OS cells in vitro and in vivo. Further work showed that β-escin blocked the PI3K/Akt pathway in MG-63 cells and MG-63 xenograft OS model. Our findings suggest that β-escin and cytotoxic drugs may be used together to treat OS patients.
https://aacrjournals.org/cancerpreventionresearch/article/6/10/1140/50034/1The results presented here suggest that β-escin may provide a significant protective effect against tobacco carcinogen–induced lung tumor formation in female A/J mice. This study is consistent with the earlier observations that support possible antitumorigenic effects of β-escin in in vitro and in vivo models (6–10). Previously, we showed that β-escin, at 250 and 500 ppm in the diet, inhibited colon carcinogen–induced preneoplastic foci in rat colon in a dose-dependent manner (6). Our current results show that β-escin provides significant inhibition (up to 65%, P < 0.0001) of lung adenocarcinoma incidence and decreased tumor volume in a well-established model of lung cancerAdministration of 500 ppm β-escin significantly suppressed lung tumor (adenoma + adenocarcinoma) formation by more than 40% (P < 0.0015) at 20 weeks and by 53.3% (P < 0.0001) at 37 weeks. β-Escin inhibited NNK-induced lung adenocarcinoma formation by 65% (P < 0.001) at 20 weeks and by 53% (P < 0.0001) at 37 weeks. Immunohistochemical analysis revealed that lung tumors from mice exposed to β-escin showed significantly reduced aldehyde dehydrogenase (ALDH)1A1 and phospho-Akt (p-Akt) expression when compared with those in mice fed control diet.
https://www.jacc.org/doi/10.1016/S0735-1097%2821%2902729-7#cestitle301Administration of Escin or HCSE demonstrate tendency to reduce cell death in atherosclerotic lesions. Duramycin uptake was lower by 12.5% (Escin), 12.5% (HCSE) and 37.5% (HCSE + Statin) compared to control. HCSE + statin reduced uptake with >99% probability; Escin (91% reduction probability) and HCSE (88%) alone also reduced duramycin uptake.On comparing gene expression signature pattern of 1309 small molecules to rosuvastatin, using a connectivity mapping, an active ingredient of horse chestnut seed extract (HCSE)- Escin ranked #2 in similarity. Escin, HCSE, or HCSE with atorvastatin were fed to 24 rabbits with 5-mo high-cholesterol diet atherosclerosis model; controls were fed high cholesterol diet only
https://www.spandidos-publications.com/10.3892/or.2021.80061In conclusion, the results from the present study indicated that a low concentration of escin inhibited angiogenesis by reducing the secretion of VEGF and IL-8 by suppressing NF-κB activation in PaCa. As escin did not affect the normal proliferating function of the cells, escin may be a safer and less toxic compound compared with other available treatments, such as gemcitabine. Therefore, escin may have important applications as an effective therapeutic agent for PaCaThus, it was examined whether escin inhibited angiogenesis in human endothelial cells. The EA.hy 926 cell line is an immortalized endothelial cell line that has previously been used to estimate angiogenic potential (51). The results from the present study indicated that culturing EA.hy 926 cells with supernatants from the PaCa cell lines, which may contain VEGF and IL-8, enhanced the angiogenic potential of the EA.hy 926 cells; however, culturing the cells with supernatants from escin-treated PaCa cells, which may contain less VEGF and IL-8, suppressed angiogenic potential
https://www.jstage.jst.go.jp/article/bpb/41/10/41_b18-00251/_html/-char/en1Hence, the purpose of this study is to examine the anti-tumor activities of β-escin using the mouse (B16F10) and human (SK-MEL5) melanoma cell lines, with respect to its regulation of the migration, invasion, and adhesion properties. Here, we report that β-escin decreases cell migration, invasion, and adhesion in melanoma cell lines and that these effects may include the nuclear factor-kappa B/inhibitor of nuclear factor-kappa B (NF-κB/IκB) signaling event. Our findings provide the first insight into the signaling-mediated anti-tumor potential of β-escin, and hence, we strongly suggest that β-escin should be considered as a potential candidate for development as a preventive/therapeutic agent.ased on these observations and our results, it can be inferred that β-escin significantly suppressed the ERK1/2 signaling pathway, thereby enhancing the inhibitory effects of β-escin on cell migration and invasion. It has been reported that NF-κB plays a major role in the immune-inflammatory response, and is associated with numerous skin diseases and skin cancer. Activated NF-κB translocates to the nucleus to bind to the promoter or enhancer regions of specific genes and then induces the expression of relevant genes, including various MMPs.17,18) Expressions of not only NF-κB but also p-I-κB were inhibited by β-escin in a concentration-dependent manner in SK-MEL5 cells
https://www.nature.com/articles/cddis20174881In conclusion, escin can inhibit osteosarcoma cell proliferation by inducing autophagy and apoptosis mediated by the ROS/p38 MAPK signalling pathway (Figure 7). Escin exhibited potent anti-tumour activity in the orthotopic osteosarcoma model. The results of this study provide new insights into the potential efficacy of escin in the treatment of osteosarcoma.Finally, the therapeutic efficacy of escin against osteosarcoma was demonstrated in an orthotopic model. Overall, escin counteracted osteosarcoma by inducing autophagy and apoptosis via the activation of the ROS/p38 MAPK signalling pathway; these findings provide evidence for escin as a novel and potent therapeutic for the treatment of osteosarcoma.

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