Glucocorticoids-based prodrug design:Current strategies and research progress

Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs.

Combination treatment with telitacicept,mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy:A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A(IgA)antibody production by inhibiting the activity of B lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL),thereby decreasing IgA deposition in the glomeruli and local inflammatory response.This ultimately protects the kidneys from damage.This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy.CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment.Pathologically,she exhibited focal proliferative glomerulonephritis.Treatment with angiotensin II receptor blocker,hormones,and mycophenolate mofetil did not lead to a significant improvement in her condition.However,upon the addition of telitacicept,the patient’s renal function recovered and her proteinuria rapidly reduced.Hormones were swiftly tapered and discontinued,with no occurrence of severe infections or related complications.CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.

Association analysis of BclI with benign lymphoepithelial lesions of the lacrimal gland and glucocorticoids resistance

AIM:To evaluate the relationship between gene polymorphism(BclI,ER22/23EK,N363S)and the occurrence,progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion(LGBLEL).METHODS:Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism(SNP)genotypes.The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin(HE)and Masson staining analysis.The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed.The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids(GCs)sensitivity.RESULTS:There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity(P>0.05);BclI GC genotype was closely related to GCs resistance(P=0.03)as is the minor allele C(P=0.0017).The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis(P<0.05),especially for GCs-dependent patients(P<0.0001).Meta-analysis showed that BclI was not significantly associated with GCs responsiveness.CONCLUSION:The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression.The results may guide the clinical treatment strategy for the LGBLEL patients.

Occurrences of Glucocorticoids in Aquatic Environment and Their Removal during Wastewater Treatment

Glucocorticoids(GCs) are a group of endocrine-disrupting compounds(EDCs) frequently prescribed against various medical conditions.Recently,GCs have been shown to be effective in managing septic shock in patients infected with the 2019 novel coronavirus(COVID-19).Due to colossal consumption and potential risks to aquatic organisms,GCs have immensely attracted the focus of the scientific research community as a water pollutant.Therefore,the aim of this paper is to review the current knowledge on the occurrence of various GCs in the aquatic environment and their removal during wastewater treatment.A variety of GCs are ubiquitous in surface water,hospital wastewater,and sewage water worldwide.And the minimum concentration in volume is below 0.01 ng/L,and the maximum one is 10 000 ng/L,and enter the environment through hospital and urban wastewater discharging.Compared with natural GCs,higher risks to aquatic environments could be induced by synthetic GCs.The current activated sludge processes used in wastewater treatment plants(WWTPs) are not fully effective in eliminating GCs,some of which may further increase the risk of GC in the environment.In comparison with the aerobic process in WWTPs,the anaerobic and anoxic processes were found to be more efficient for GC degradation.Of the studied GCs,fluticasone propionate,clobetasol propionate,fluocinolone acetonide,and triamcinolone acetonide need more attention due to their low removal efficiencies and strong toxicity.Among the advanced treatment processes,reverse osmosis,ultraviolet irradiation,CaO_(2),and plasma could achieve significant GC activity removal while micro/ultra-filtration,chlorination,and ozonation were less efficient.

The effect of intravenous high-dose glucocorticoids and orbital decompression surgery on sight-threatening thyroid-associated ophthalmopathy

AIM: To report the effects of intravenous high-dose glucocorticoids(iv GC) and orbital decompression(OD) surgery for treatment of sight-threatening thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective review of medical records from patients with sight-threatening TAO [definite or highly suspected dysthyroid optic neuropathy(DON)] treated with iv GC(60 cases) and OD(25 cases) was conducted at the Zhongshan Ophthalmic Center between January 2001 and January 2009. Patients were initially treated with iv GC(iv GC group). If no significant improvement in visual function was obtained, they then received OD surgery(OD group). The pre-versus post-treatment efficacies of either iv GC or OD in these patients were assessed using several indices, including visual acuity, intraocular pressure, ocular alignment, ocular motility, and exophthalmos. RESULTS: Nighty-one eyes had definite DON while 79 were considered to have highly suspected DON. In the iv GC group, 51 individuals(85.0%) eventually demonstrated normal vision, while 10 patients(16.7%) demonstrated a reduction in deviation(P<0.01), and 35 cases(58.3%) showed slight improvements in ocular motility(P<0.01). In OD group, visual acuity improved in 24 cases(96.0%, P<0.01) and all patients showed varying reductions of exophthalmos(mean: 4.35±1.13 mm, P<0.01). Eight cases(32.0%) experienced an 8-15 PD reduction of deviation and ocular motility improved in 12 cases(48.0%), while 3 patients(12.0%) developed new-onset strabismus with diplopia post-surgically(P<0.01). Patients were followed up at an average of 1.55±1.07 y. CONCLUSION: Both iv GC and OD show good therapeutic efficacy in the treatment of sight-threatening TAO. Thepresence of extremely poor eyesight(≥0.5 log MAR) was corrected in some patients with iv GC alone, thus sparing these patients from subsequent OD surgery. In patients who were refractory to steroids, subsequent OD surgery often provided satisfactory outcomes, however, new-onset strabismus with diplopia was observed in 12.0% of these cases.

Intravenous glucocorticoids therapy in the treatment of Graves’ ophthalmopathy: a systematic review and Meta-analysis

AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids(IVGC) as first-line treatment for Graves’ ophthalmopathy(GO).METHODS: A systematic review and Meta-analysis of randomized clinical trials(RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score(CAS), and adverse events.RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence(one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio(RR) 7.50, 95% confidence interval(CI) 1.14 to 49.26]. Moderate quality evidence(four trials) support appreciable benefit of IVGC in response compared with oral glucocorticoids(OGC), with of RR being 1.51(95%CI 1.25 to 1.83). There was low quality evidence(one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response(RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lowerresponse compared to participants using rituximab(RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil(MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF(RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence(one trial) showed that participants with dysthyroid optic neuropathy(DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression(RR 3.33, 95%CI 0.51 to 21.89).CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON.

Effects of glucocorticoids on the growth and chemosensitivity of carcinoma cells are heterogeneous and require high concentration of functional glucocorticoid receptors

AIM： To determine how glucocorticoids （GCs） may affect the growth and chemosensitivity of common carcinoma cells. METHODS： The effect of dexamethasone （DEX） on growth and chemosensitivity was assessed in 14 carcinoma cell lines. The function of GC receptors （GR） was assessed by MMTV reporter assay. Overexpression of GR was done by in vitro transfection and expression of a GR-expressing vector. Immunohistochemical stain of tissues and ceils were done by PA1-511A, an anti-GR monodonal antibody. RESULTS： DEX inhibited cell growth of four （MCF-7, MCF- 7/MXR1, MCF-7/TPT300, and HeLa）, increased cisplatin cytoxicity of one （SiHa）, and decreased dsplatin cytotoxicity of two （H460 and Hep3B） cell lines. The GR content of the seven cell lines affected by DEX was significantly higher than those of the seven cell lines unaffected by DEX （5.2±2.5×10^4 sites/cell vs1.3±1.4×10^4 sites/cell, P= 0.005）. Only two DEX-unresponsive cell lines {NPC-TW01 and NPC- TW04） oontained high GR amounts in the range （1.9-8.1×10^4 sites/cell） of the seven DEX-responsive cell lines. The GR function of NPC-TW01 and NPC-TW04, however, was foundto be impaired. The importance of high cellular amount of GR in mediating DEX susceptibility of the cells was further exemplified by GR dose-dependent drug resistance to cisplatin of AGS, a cell line with low GR content and was unaffected by DEX before transfection of GR-expressing vector. Immunohistochemical studies of human cancer tissues showed that 5 of the 45 （11.1%） breast cancer and 43 of the 85 （50.6%） non-small cell lung cancer had high GR contents at the ranges of the GC-responsive carcinoma cell lines. CONCLUSION： The growth and chemosensitivity of human carcinomas with high GR contents may be affected by GC. However, in light of the heterogeneous and even contradictive effects of GC on these cells, routine examination of GR contents of human carcinoma tissues may not be clinically useful until other markers that help predict the ultimate effect of GC on individual patients are identified.

Central serous chorioretinopathy:from glucocorticoids to light intensity

Central serous chorioretinopathy （CSC） is characterized by a localized accumulation of subretinal fluid and an idiopathic focal leakage from choroidal vessels. The exact pathogenesis of CSC, however, still remains obscure. In this paper, we hypothesized that CSC may result from a response of choroidal vessels to an acute increase in the environmental light intensity leading to a focal leakage from the choroidal vessels. High levels of glucocorticoids, in our proposed model, may cause persistence rather than initiation of the focal leakage, probably by suppressing the synthesis of collagen and extracellular matrix components and inhibiting fibroblastic activity.

Glucocorticoids and prostate cancer treatment： friend or foe？

Glucocorticoids have been used in the treatment of prostate cancer to slow disease progression, improve pain control and offset side effects of chemo- and hormonal therapy. However, they may also have the potential to drive prostate cancer growth via mutated androgen receptors or glucocorticoid receptors （GRs）. In this review we examine historical and contemporary use of glucocorticoids in the treatment of prostate cancer, review potential mechanisms by which they may inhibit or drive prostate cancer growth, and describe potential means of defining their contribution to the biology of prostate cancer.

Endogenous Glucocorticoids and Bone

While the adverse effects of glucocorticoids on bone are well described, positive effects of glucocorticoids on the differentiation of osteoblasts are also observed. These paradoxical effects of glucocorticoids are dose dependent. At both physiologicaland supraphysiological levels of glucocorticoids, osteoblasts and osteocytes are the major glucocorticoid target cells. However, the response of the osteoblasts to each of these is quite distinct. At physiology levels, glucocorticoids direct mesenchymal progenitor cells to differentiate towards osteoblasts and thus increase bone formation in a positive way. In contrast with ageing, the excess production of glucocorticoids, at both systemic and intracellular levels, appear to impact on osteoblast and osteocytes in a negative way in a similar fashion to that seen with therapeutic glucocorticoids. This review will focus on therole of glucocorticoids in normal bone physiology, with particular emphasis on the mechanism by which endogenous glucocorticoids impact on bone and its constituent cells.

Efficacy Analysis of Glucocorticoids in the Treatment of Allergic Purpura in Tibetan Children

Background: Henoch Schonlein Purpura (HSP) is a common immune-related allergic disease in children. It is very important to understand the clinical features of this disease for doctors. Objective: To explore the clinical efficacy of glucocorticoids in the treatment of HSP in Tibetan children at high altitude, and to analyze the possible causes of HSP in children at high altitude. The risk factors of the disease provide a reference for the treatment of HSP in children in high altitude areas. Methods: Selecting January 2015 to November 2020, 88 children diagnosed with Henoch-Schonlein Purpura in the outpatient and inpatient departments of the People’s Hospital of Bomi County, Tibet Autonomous Region were the subjects of the study. Its gender, age of onset, season of onset, predisposing factors, allergy history, first symptoms, clinical manifestations, laboratory examinations, etc., perform retrospective analysis. Results: Among 88 children with allergic purpura, 55 were boys, accounting for 62.5%, and 33 were girls, accounting for 37.5%. Men have more cases than women. All have clinical manifestations of purpura of the skin, among which 35 cases have obvious triggers, of which the above there were 26 cases of respiratory infections, 6 cases of dietary factors, and 3 cases of contact with allergic substances. Simple skin type: 18 cases, accounting for 20.45%;Abdominal type: 6 cases, accounting for 6.82%;2 male cases, accounting for 33.33%;4 female cases, accounting for 66.67%;Articular type: 8 cases, accounting for 33.33%;Renal type: 2 cases, accounting for 2.27%;54 cases of mixed type, accounting for 61.36%. After glucocorticoids, the rashes disappeared, no any adverse reactions. Conclusion: Allergic purpura in children is more common in school-age children, and upper respiratory tract infection is the main predisposing factor. Skin purpura is the main clinical manifestation, often associated with lower extremity joint swelling and pain. There is no significant difference in the efficacy and course of the disease between intravenous and oral treatment. Therefore, clinicians should strictly grasp the indications of glucocorticoids to reduce the occurrence of complications.

Efficacy and safety of glucocorticoids in the treatment of community-acquired pneumonia: A meta-analysis of randomized controlled trials

BACKGROUND: Community-acquired pneumonia(CAP) is pneumonia acquired infectiously from normal social contact as opposed to being acquired during hospitalization. CAP is a leading cause of illness and death. This review aims to determine the efficacy and safety of glucocorticoids in the treatment of community-acquired pneumonia(CAP).DATA SOURCES: We searched randomized controlled trials(RCTs) from Pubmed, EMBASE, Cochrane Library, Chinese Journal Full-text Database, and Chinese Biomedical Literature Database to obtain the information by using steroids, glucocorticoids, cortisol, corticosteroids, community-acquired pneumonia and CAP as key words. The quality of RCTs was evaluated. A Meta-analysis was made using Rev Man 5.0 provided by the Cochrance Collaboration.RESULTS: Seven RCTs involving 944 patients were included in the meta-analysis. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in standard treatment group(WMD=–1.70, 95%CI 2.01–1.39, Z=10.81, P<0.00001). No statistically significant differences were found in the mortality rate(RR=0.77,95%CI 0.46–1.27, Z=1.03, P=0.30), the mean length of hospital stay in ICU(WMD=1.17, 95%CI 1.68–4.02, Z=0.81, P=0.42), the incidence of super infection(RR=1.32, 95%CI 0.66–2.63, Z=0.79, P=0.43), the incidence of hyperglycemia(RR=1.84, 95%CI 0.76–4.41, Z=1.36, P=0.17), the incidence of upper gastrointestinal bleeding(RR=1.98, 95%CI 0.37–10.59, Z=0.80, P=0.42) between the standard treatment group and the glucocorticoids treatment group.CONCLUSIONS: The use of glucocorticoids in patients with community-acquired pneumonia can significantly shorten the duration of illness and have a favorable safety profile. However, it could not reduce the overall mortality.

Glucocorticoids and nervous system plasticity

Glucocorticoid and glucocorticoid receptor（GC/GR） interactions alter numerous aspects of neuronal function. These consequences（e.g., anti-inflammatory vs. pro-inflammatory） can vary depending on the duration of GC exposure or central nervous system（CNS） injury model. In this review we discuss how GC/GR interactions impact neuronal recovery after a central or peripheral nerve injury and discuss how GC exposure duration can produce divergent CNS neuronal growth responses. Finally we consider how new findings on gender specific immune cell responses after a nerve injury could intersect with GC/GR interactions to impact pain processing.

Escin enhances anti-rheumatoid arthritis effects of low dose glucocorticoids through up-regulation of glucocorticoid receptor

OBJECTIVE To investigate the anti-rheumatoid arthritis(RA)effect of Escin combined with low dose of GCs(dexameth⁃asone,Dex)and its underlying mechanism.METHODS Adjuvant-induced rheumatoid arthritis rats and LPS-injured RAW 264.7 were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro.In vivo experiment:rats were randomly divided into model group(AIA),dexamethasone high dose(Dex,0.2 mg·kg^-1)group,dexamethasone low dose(Dex,0.05 mg·kg^-1)group,Escin 10 mg·kg^-1 group,Dex 0.05+Escin group,10 rats in each group,another 10 were used as normal control group.The vehicle and the corresponding drug were administered intragastrically(ig)daily for 14 d.In vitro experiment:LPS was used to stimulate RAW 264.7 macrophages for inflammatory models,which were divided into control group,LPS group,Dex with high dose(50 nmol·L^-1)group,and Dex with low dose(12.5 nmol·L^-1)group.In the Escin 10μmol·L^-1 group and the Dex+Escin(12.5 nmol·L^-1+10μmol·L^-1)group,the corresponding drugs were added to each well.After 2 h,LPS was added to induce inflammation.RESULTS Escin combined with low dose Dex significantly decreased arthritic index,serum IL-6 and TNF-α,improved paw swelling,and ameliorated the joint pathology immune organ pathology significantly.Gene chip results revealed that Nr3c1(GR)altered significantly.And that GR activation by Escin and low dose Dex was confirmed both in vivo and in vitro.Furthermore,Escin combined with low dose Dex also significant increase GR mRNA expression.However,when suppression of GR by its specific inhibitor,the anti-RA effect of Escin combined with low dose Dex was abolished.CONCLUSION Escin combined with Dex reduces the dose of Dex,and exerts significant anti-RA effects,which could also reduce the adverse effects of Dex.This combination might be attributed to GR activation.This study might provide a new combination drugs for the treatment of RA.

Application of LC–MS/MS for quantitative analysis of glucocorticoids and stimulants in biological fuids

Liquid chromatography tandem mass chromatography （LC-MS/MS） is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches （column packing materials, column length and mobile phase） as well as different acquisition modes （SIM, MRM） for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.

Association of Serum Glucocorticoids with Various Blood Pressure Indices in Patients with Dysglycemia and Hypertension:the Henan Rural Cohort Study

Objective To our knowledge, no definitive conclusion has been reached regarding the relationship between glucocorticoids and hypertension. Here, we aimed to explore the characteristics of glucocorticoids in participants with dysglycemia and hypertension, and to analyze their association with blood pressure indicators.Methods The participants of this study were from the Henan Rural Cohort study. A total of 1,688 patients 18–79 years of age were included in the matched case control study after application of the inclusion and exclusion criteria. Statistical methods were used to analyze the association between glucocorticoids and various indices of blood pressure, through approaches such as logistic regression analysis, trend tests, linear regression, and restricted cubic regression.Results The study population consisted of 552 patients with dysglycemia and hypertension(32.7%).The patients with co-morbidities had higher levels of serum cortisol(P = 0.009) and deoxycortisol(P <0.001). The adjusted odds ratios(and 95% confidence intervals) for dysglycemia with hypertension were1.55(1.18, 2.04) for the highest tertile of Ln-cortisol compared with the lowest tertile. Additionally, the highest Ln-deoxycortisol levels were associated with increased prevalence of dysglycemia with hypertension by 159%(95% confidence interval: 122%, 207%).Conclusions Serum deoxycortisol was positively correlated with systolic blood pressure, pulse pressure, mean arterial pressure, mean blood pressure, and mean proportional arterial pressure.Glucocorticoids(deoxycortisol and cortisol) increase the risk of hypertension in people with dysglycemia, particularly in those with T2 DM.

Forskolin augments the effects of glucocorticoids on proliferation and differentiation of a human osteosarcoma cell line by up-regulation of glucocorticoid receptor

The effect of forskolin, an activator of adenylate cyclase, on glucocorticoid-induced modulation of proliferation and differentiation of a human osteosarcoma cell line(HOS-8603) was iniually studied. It was found that forskolin could significantly augment

Glucocorticoids combined with tofacitinib in the treatment of Castleman’s disease:A case report

BACKGROUND Castleman’s disease(CD),also known as vascular follicular lymphadenopathy is a rare proliferative disease of lymphoid tissue of unknown etiology that is clinically classified as unicentric CD(UCD) or multicentric CD(MCD) depending on lymph node involvement.At present,idiopathic MCD(iMCD) is treated with interleukin-6 inhibitors,but some patients have poor clinical outcomes.This paper reports on a case of iMCD that achieved a good therapeutic effect after treatment with glucocorticoids combined with tofacitinib.The relevant data are summarized and reported below.CASE SUMMARY This paper reports on a case of MCD in a 49-year-old female with persistent peritoneal effusion as the first manifestation and combined with multiple lymphadenopathies.Lymph node biopsy showed Castleman’s disease-like changes.The ascites subsided after treatment with glucocorticoids and tofacitinib,indicating that the treatment was effective.CONCLUSION The combination of glucocorticoids with tofacitinib is an effective regimen for the treatment of CD.

Escin may exert a synergistic anti-inflammatory effect with glucocorticoids

Escin is a natural mixture of triterpenoid as- ponin isolated from the seed of the horse chestnut and demonstrates anti-oedematous and anti-inflammatory effects. As yet, the pre-cise mechanisms by which escin exerts its anti- inflammatory effects remain unclear. The data from current studies indicate that the anti-in-flammatory properties of escin were attributed to its ability to reduce the adhesiveness of neu-trophils and the associated release of inflam-matory mediators;its ability to decrease hista-minic and serotoninergic activities;its ability to inhibit phospholipase A2;its ability to decrease nuclear factor-κ B activation and down-regulate the expression of tumor necrosis factor-α. All these effects are similar to glucocorticoids. Mo- reover, escin depends on adrenal glands to ex-ert its anti-inflammatory effects. Also, our recent research showed that the serum corticosterone level in mice did not increase after a 7-day in-travenous injection of escin. The results sup-port the hypothesis that escin may exert a syn-ergistic anti-inflammatory effect with glucocor-ticoids. Confirming this hypothesis will play a role in elucidating the anti-inflammatory mech- anisms of escin.