[Efficacy and safety of eltrombopag in the treatment of primary immune thrombocytopenia: real-world data from a single medical center].

Objective: This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects. Methods: A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments. Results: Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively (P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively (P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% (P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion: Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Treatment of refractory/relapsed Diamond-Blackfan anaemia with eltrombopag.

Diamond-Blackfan anaemia (DBA) is a rare, inherited bone marrow failure syndrome with a ribosomal defect causing slowed globin chain production with normal haem synthesis, causing an overabundance of reactive iron/haem and erythroid-specific cellular toxicity. Eltrombopag, a non-peptide thrombopoietin receptor agonist, is a potent intracellular iron chelator and induced a robust durable response in an RPS19-mutated DBA patient on another trial. We hypothesized eltrombopag would improve RBC production in DBA patients. We conducted a single-centre, single-arm pilot study (NCT04269889) assessing safety and erythroid response of 6 months of daily, fixed-dose eltrombopag for DBA patients. Fifteen transfusion-dependent (every 3-5 weeks) patients (median age 18 [range 2-56]) were treated. One responder had sustained haemoglobin improvement and >50% reduction in RBC transfusion frequency. Of note, 7/15 (41%) patients required dose reductions or sustained discontinuation of eltrombopag due to asymptomatic thrombocytosis. Despite the low response rate, eltrombopag has now improved erythropoiesis in several patients with DBA with a favourable safety profile. Dosing restrictions due to thrombocytosis may cause insufficient iron chelation to decrease haem production and improve anaemia in most patients. Future work will focus on erythropoiesis dynamics in patients and use of haem synthesis inhibitors without an impact on other haematopoietic lineages.

Eltrombopag treatment in thrombocytopenia following hematopoietic stem cell transplantation: A multicenter real-world experience.

INTRODUCTION: Thrombocytopenia is among the most common complications following hematopoietic stem cell transplantation and is associated with increased mortality and morbidity with no standard treatment yet. In this multicenter and retrospective study, we aim to present our multi-center experience of Eltrombopag treatment in patients with isolated thrombocytopenia following HSCT. MATERIAL-METHOD: A total of 73 patients from 5 centers who underwent autologous or allogeneic stem cell transplantation, had no primary disease relapse, all of whom had neutrophil engraftment, complete chimerism, and who were diagnosed with Prolonged Isolated Thrombocytopenia (PIT) or Secondary Failure Of Platelet Recovery (SFPR) were included in the study. The patients were initiated on Eltrombopag at a dose of 50-150 mg. Complete response was defined as a platelet count >50×109/L for 7 consecutive days with no transfusion support. RESULTS: A total of 50.3% of the patients underwent Autologous and 49.7% Allogeneic Stem Cell Transplantation, 54.8% were diagnosed with PIT, and 45.2% were diagnosed with SFPR, and the treatment with 50-150 mg/day Eltrombopag was initiated on the median day +42. Complete response was achieved in 71.2% of these patients on the median day 23 of the treatment. No significant effects of the initial dose (50-150 mg/day) were detected in the Complete Response in the multivariate analysis on response. An insufficient number of Megakaryocytes in the bone marrow before Eltrombopag treatment was determined as an independent risk factor in determining the response (OR 3.57, 95% CI 1.21-10.55). The overall survival of the patients who did not respond to Eltrombopag was found to be significantly worse than that of patients who responded (p=0.022, HR:2.74, 95% CI 1.12-6.54). CONCLUSION: As a result of the present study, Eltrombopag treatment was found to be effective and safe in thrombocytopenia that develops following hematopoietic stem cell transplantation. It was concluded that its use may be more effective in patients with sufficient bone marrow megakaryocytes before the treatment and an initial dose of 50 mg/day may be appropriate in terms of cost, effectiveness, and toxicity. Large-scale randomized and controlled prospective studies are needed to determine the roles of Eltrombopag treatment in patients with post-transplant PIT and SFPR.

Telmisartan Plus Amlodipine as the Preferred Initial Combination in Newly Diagnosed Indian Patients with Hypertension: An Expert Consensus Statements.

INTRODUCTION: Hypertension (HTN) remains one of the most important risk factors for cardiovascular (CV) diseases and a leading cause of mortality worldwide. Despite improvement in detection and treatment, poor blood pressure (BP) control rates are observed globally. The situation in India is alarming with only 22.5% of patients maintaining their BP under control. Initiating early and effective treatment for HTN helps control BP within normal limits and reduces associated health risks. In India, currently, there are no guidelines on the choice of dual combination treatment that can be considered an initial treatment for newly diagnosed HTN patients to achieve effective BP control and reduce CV risks. OBJECTIVE: To provide consensus recommendations for preferred initial combinations in newly diagnosed Indian patients with HTN. METHODOLOGY: A core group of 100 experts with HTN expertise conceptualized and formulated the four key questions based on answerability, effectiveness, potential for translation to clinical practice, novelty, and potential impact on the healthcare burden. A mix of Delphi and Child Health and Nutrition Research Initiative (CHNRI) methods was adopted for acceptance or refusal of recommendations. Likert scale 1-9 was used for scoring. A score of ≥7 was considered "statement accepted," >6.50 "near to acceptance" and <6.50 "not accepted." A vote of ≥7 by at least two-thirds of the experts (66.66%) was mandatory for acceptance of the recommendation. CONCLUSION: Combination therapy could be necessary for a majority of newly diagnosed Indian patients for effective BP control. It can manage HTN with better clinical outcomes. Based on mean rating scores from experts, telmisartan plus amlodipine can be considered the preferred initial combination in the management of newly diagnosed Indian patients with HTN to achieve better BP control and improve CV outcomes.

Eltrombopag for Post-Transplant Poor Graft Function in East Asian Patients.

Poor graft function (PGF) is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. Eltrombopag has shown multilineage responses in patients with refractory severe aplastic anemia, supporting the idea that it may improve cytopenia in patients with PGF. This retrospective, single center analysis included 8 Korean patients receiving eltrombopag for PGF. Median interval between transplant and eltrombopag treatment was 73 days, and the median duration treatment was 3.5 weeks. With median maximum daily dose of 50 mg, the time to best response was 93 days. Median hemoglobin increased from 8.2 g/dL to 10.9 g/dL, platelet from 18.5 × 109/L to 54 × 109/L, and absolute neutrophil count from 1.25 × 109/L to 3.32 × 109/L. In conclusion, eltrombopag is a good option for PGF in Korean patients, even at a lower dose compared to western patients.

Safety and efficacy of MIKE-1 in patients with advanced pancreatic cancer: a study protocol for an open-label phase I/II investigator-initiated clinical trial based on a drug repositioning approach that reprograms the tumour stroma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are an important component of the tumour microenvironment. Recent studies revealed CAFs are heterogeneous and CAF subset(s) that suppress cancer progression (cancer-restraining CAFs [rCAFs]) must exist in addition to well-characterised cancer-promoting CAFs (pCAFs). However, the identity and specific markers of rCAFs are not yet reported. We recently identified Meflin as a specific marker of rCAFs in pancreatic and colon cancers. Our studies revealed that rCAFs may represent proliferating resident fibroblasts. Interestingly, a lineage tracing experiment showed Meflin-positive rCAFs differentiate into α-smooth muscle actin-positive and Meflin-negative CAFs, which are generally hypothesised as pCAFs, during cancer progression. Using a pharmacological approach, we identified AM80, a synthetic unnatural retinoid, as a reagent that effectively converts Meflin-negative pCAFs to Meflin-positive rCAFs. We aimed to investigate the efficacy of a combination of AM80 and gemcitabine (GEM) and nab-paclitaxel (nab-PTX) in patients with advanced pancreatic cancer. METHODS: The phase I part is a 3 + 3 design, open-label, and dose-finding study. The dose-limiting toxicity (DLT) of these combination therapies would be evaluated for 4 weeks. After the DLT evaluation period, if no disease progression is noted based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or if the patient has no intolerable toxicity, administration of AM80 with GEM and nab-PTX would be continued for up to 24 weeks. The phase II part is an open-label, single-arm study. The maximum tolerated dose (MTD) of AM80 with GEM and nab-PTX, determined in phase I, would be administered until intolerable toxicity or disease progression occurs, up to a maximum of 24 weeks, to confirm efficacy and safety. The primary endpoints are frequency of DLT and MTD of AM80 with GEM and nab-PTX in the phase I part and response rate based on the RECIST in the phase II part. Given the historical control data, we hope that the response rate will be over 23% in phase II. DISCUSSION: Strategies to convert pCAFs into rCAFs have been developed in recent years. We hypothesised that AM80 would be a promising enhancer of chemosensitivity and drug distribution through CAF conversion in the stroma. TRIAL REGISTRATION: Clinicaltrial.gov: NCT05064618 , registered on 1 October 2021. jRCT: jRCT2041210056 , registered on 27 August 2021.

Eltrombopag in the treatment of patients with persistent thrombocytopenia after haploidentical peripheral blood stem cell transplantation: a single-center experience.

Persistent thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of bleeding and poor survival. The exact pathogenesis underlying PT remains unclear, and its management is difficult. Here we conducted a retrospective study to evaluate the efficacy and safety of eltrombopag (EPAG) in 34 patients with PT after allo-HSCT. Seven patients suffered from prolonged isolated thrombocytopenia (PIT), and 27 had secondary failure of platelet recovery (SFPR). For most patients, the initial dose was 25 mg or 50 mg daily, then adjusted to the maximum dose of 50-100 mg per day according to the response of platelet recovery and toleration of patients. The cumulative incidence (CI) of platelet recovery to at least 20 × 109/L and 50 × 109/L without transfusion support for at least 7 days was 72.1% and 60.7%, respectively. Nineteen (86.4%) of 22 responders were able to taper off the medication; furthermore, the platelet counts remained stable 1 month after withdrawal of EPAG. Although two patients discontinued EPAG during treatment due to headache and nausea, no patients developed grade 3 or 4 toxicities. Hypoplasia of bone marrow and decreased megakaryocytes (MKs) were found to be risk factors for overall response (OR) and complete response (CR) in multivariate analysis, respectively. Overall, our results indicated that EPAG can be used in the treatment of PT and that continuous exposure to EPAG may not be necessary.

Eltrombopag Add-on Treatment in a Child With Fanconi Aplastic Anemia Awaiting Hematopoietic Stem Cell Transplantation.

Fanconi aplastic anemia (FAA) is a rare inherited bone marrow failure disorder characterized by congenital defects and pancytopenia. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with FAA due to the risk of cancer and pancytopenia. Blood transfusions are the best supportive therapy. Oxymetholone (5 mg/kg daily) is most commonly used; however, it is not curative. Extensive transfusions should be avoided because of alloimmunization and graft-versus-host disease because they have poor outcomes in patients with HSCT. This is a case report of a 5-year-old Syrian male patient with FAA, who was successfully treated with eltrombopag (50 mg daily) in conjunction with oxymetholone (5 mg/kg daily). The patient required platelet transfusions despite oxymetholone therapy and there was no suitable donor for HSCT. After the addition of eltrombopag therapy, platelet transfusions were no longer required. Eltrombopag can be effectively used as a bridge to HSCT in patients with FAA.

The gelling properties of Dillenia indica mucilage in benzyl benzoate emulgel formulations

Abstract The objective of the study was to evaluate the gelling properties of Dillenia indica mucilage in benzyl benzoate emulgel formulation. Mucilage was extracted from the fruits of Dillenia indica using established methods and characterized by rheology and swelling. Emulsion (F1) was prepared using the continental emulsification method. Gelling agents (2 %w /v) were prepared by dispersing in distilled water with constant stirring at a moderate speed using a magnetic stirrer. F1 was added to the gel (0-75 %w /w) to obtain emulgel formulations and evaluated using viscosity, globule size, pH, release profiles and kinetic modeling. Data were expressed as mean ± SD, and similarity factor (f2) was used to compare all formulations. Formulation viscosity was significantly higher with carbopol than with Dillenia; globule sizes increased with concentration of gelling agents, and pH reduced as the concentration of Dillenia increased. All formulations showed controlled release properties with t80 ranging between 114 and 660 min. The release was governed by Korsmeyer-Peppas model. Formulation F5 prepared with 50 % Dillenia showed highest similarity to F4 prepared with 75 %w /w carbopol. Dillenia indica demonstrated acceptable gelling properties comparable with that of carbopol and could be improved for use in emulgel formulations.

Treatment of difficult-to-treat-dermatophytosis: results of a randomized, double-blind, placebo-controlled study.

INTRODUCTION: Difficult-to-treat dermatophytosis is an emerging public health problem in Sri Lanka. Safe, effective and affordable treatment is needed to solve this problem. Therefore this study has assessed the effectiveness and safety of modified Whitfield ointment applied twice daily with oral griseofulvin 500 mg daily given over 8 weeks in patients with difficult-to-treat dermatophytosis. METHODOLOGY: A randomized, double-blind, within-patient-placebo-controlled trial was conducted in patients with clinico- mycologically (history, physical examination, direct light microscopy examination of scales in potassium hydroxide mount) confirmed difficult-to-treat dermatophytosis. Lesions were randomized to receive modified Whitfield ointment (5% benzoic acid and 5% salicylic acid) or emulsifying ointment. All patients were given oral griseofulvin 500mg once daily. The outcome measures were clinical assessment of disease severity, the total surface area of the lesions and the patient's perception of the disease severity at baseline and every two weeks up to a maximum of 8 weeks. RESULTS: Thirty patients completed the study. At two weeks, there was a statistically significant improvement in modified Whitfield ointment arm in the clinical assessment of disease severity and the patients' perception. There was a 7.59% reduction in the surface area of lesions in modified Whitfield ointment arm and a 5.83% increase in the surface area of lesions in the emulsifying ointment arm at two weeks. The difference between the two arms in surface area changes was not statistically significant (p = 0.107, df = 29). CONCLUSIONS: A combination of modified Whitfield ointment with griseofulvin is significantly effective, safe and affordable option for treating difficult-to-treat dermatophytosis in the tropics.

Effects of low-dose insulin or a soluble guanylate cyclase activator on lower urinary tract dysfunction in streptozotocin-induced diabetic rats.

AIMS: To examine the effects of low-dose insulin or a soluble guanylate cyclase activator (sGC) on lower urinary tract dysfunction (LUTD) in rats with diabetes mellitus (DM). MAIN METHODS: Female Sprague-Dawley rats were divided into non-DM control (N), DM induced by streptozotocin (65 mg/kg), with low-dose insulin (DI), DM with vehicle (D), and DM with sGC (GC) groups. In GC group, BAY 60-2770 (1 mg/kg/day) was orally administered in 6-8 weeks after DM. Voiding assay at 2, 4, and 8 weeks after DM, cystometry, and urethral pressure recordings at 8 weeks of DM were performed. mRNA levels of NO-related markers and cGMP protein levels in the urethra, and ischemia and inflammation markers in the bladder were evaluated by RT-PCR. KEY FINDINGS: Moderate levels of high blood glucose were maintained in Group DI versus Group D. The 24-h voided volume was significantly higher in Group D versus Groups N and DI. Non-voiding contractions were significantly greater, and voiding efficiency and urethral pressure reduction were significantly lower in Group D versus Groups N, DI, and GC. Urethral cGMP levels were significantly lower in Group D versus Groups N and GC. mRNA levels of PDE5 in the urethra and ischemia and inflammation markers in the bladder increased in Group D versus Group N or DI was reduced after sGC treatment. SIGNIFICANCE: DI rats with a lesser degree of bladder and urethral dysfunction might be useful as a slow-progressive DM model. sGC activation could be an effective treatment of LUTD in DM.

Accelerative action of topical piperonylic acid on mice full thickness wound by modulating inflammation and collagen deposition.

Epidermal growth factor (EGF) promotes cell growth, proliferation, and survival in numerous tissues. Piperonylic acid, a metabolite present in peppers (Piper nigrum L. and Piper longum L.), can bind to the epidermal growth factor receptor (EGFR) and induce an intracellular signaling cascade leading to the transcription of genes responsible for these actions, especially in keratinocytes. These cells are fundamental in maintaining cutaneous homeostasis and are the first to be damaged in the case of a wound. Thus, we hypothesized that piperonylic acid improves wound healing. C57BL6/J male mice were submitted to dorsal skin wounds caused by a 6 mm punch and treated topically with piperonylic acid or vehicle. The wounds were evaluated macro- and microscopically, and tissue samples were collected for immunofluorescence and real-time PCR analyses on days 6, 9 and 19 post-injury. Topical piperonylic acid improved wound healing from day 6 post-injury until closure. This phenomenon apparently occurred through EGFR activation. In addition, piperonylic acid modulated the gene expression of interleukin (Il)-6, il-1ß, tumor necrosis factor (Tnf)-α, il-10, monocyte chemoattractant protein (Mcp)-1 and insulin-like growth factor (Igf)-1, which are important for the healing process. By day 19 post-injury, the new tissue showed greater deposition of type I collagen and a morphology closer to intact skin, with more dermal papillae and hair follicles. We conclude that piperonylic acid may be a viable option for the treatment of skin wounds.

A Close Look at the Clinical Efficacy of Rho-Associated Protein Kinase Inhibitor Eye Drops for Fuchs Endothelial Corneal Dystrophy.

ABSTRACT: The current understanding on the clinical efficacy of Rho-associated protein kinase (ROCK) inhibitor for treating Fuchs endothelial corneal dystrophy is summarized to clarify whether the "off-label" ROCK-inhibitor eye-drop application are appropriate. ROCK-inhibitor eye drops may eventually be deemed a cutting-edge therapy for Fuchs endothelial corneal dystrophy patients with acute corneal endothelial defect.

Treatment patterns in adults with immune thrombocytopenia before, during and after use of thrombopoietin receptor agonists: a longitudinal prescription database study from Germany.

OBJECTIVE: To assess real-world treatment patterns in patients with immune thrombocytopenia (ITP) who received thrombopoietin receptor agonists (TPO-RAs) in Germany. METHODS: This was a longitudinal, retrospective study using anonymized patient-level data (IQVIA healthcare prescription database, covering 82% of German statutory prescriptions). Eligible patients (aged ≥18 years) had received ≥1 TPO-RA prescription (romiplostim/eltrombopag) from July 2016 to June 2019 (treatment duration ≥30 days). ITP medication use was assessed for 18 months prior to, during and for ≥6 months after TPO-RA treatment. RESULTS: A total of 3553 patients (median age 64 years) were included. Median persistence on TPO-RAs was 12 months (range 1-34). In the periods before, during and after TPO-RA treatment, oral corticosteroids were the most commonly used therapy (64.4%, 43.4% and 36.1% of patients, respectively); median cumulative doses across each period were 2521.9, 2000.0 and 2277.8 mg. The median total duration of corticosteroid use before, during and after TPO-RA therapy was 15, 18 and 32 weeks, respectively. The total median cumulative corticosteroid dose was 6799.7 mg. CONCLUSION: We identified a potential overuse of corticosteroids in patients with ITP in Germany. Earlier use of TPO-RA therapy after a short course of corticosteroids could avoid side effects associated with long-term use.

Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice.

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.

Activation of the Hippocampal LXRß Improves Sleep-Deprived Cognitive Impairment by Inhibiting Neuroinflammation.

Sleep deprivation (SD) leads to cognitive impairment due to neuroinflammation associated with impaired hippocampal neuronal plasticity and memory processes. Liver X receptors (LXRs), including LXRα and LXRß isoforms, are crucial for synaptic plasticity and neuroinflammation. However, the potential roles of LXRs in the pathogenesis of cognitive impairment induced by SD remain unclear. We revealed that SD resulted in LXRß reduction in the hippocampus, which was associated with upregulated expression of high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)/NF-κB p65, and knockdown of hippocampal LXRß by shRNA (shLXRß) led to cognitive impairment. GW3965, a dual agonist for both LXRα and LXRß, ameliorated SD-induced cognitive impairment by inhibiting microglia activation, suppressing HMGB1/TLR4/NF-κB p65 pathway, and ultimately affecting the hippocampal expression of inflammatory cytokines in SD mice. LXRß knockdown by shLXRß abrogated the GW3965-mediated inhibition of the HMGB1/TLR4/NF-κB p65 pathway, therefore, abolishing the cognitive improvement. Moreover, inhibition of HMGB1 by glycyrrhizin (GLY) synergistic promoted GW3965-mediated anti-inflammation in activated microglia after lipopolysaccharide (LPS)/ATP stimulation and facilitated the cognitive improvement after GW administration by activating LXRß. All the data suggested that GW3965 ameliorated impaired cognition in SD mice by suppressing the HMGB1/TLR4/NF-κB p65 pathway followed LXRß activation. This study correlates a deficit of LXRß in cognitive dysfunction in SD associated with HMGB1 inflammatory pathway in hippocampus, and LXRs may serve as a potential therapeutic target for cognitive impairment with anti-inflammation.