The role of immune cells in different stages of atherosclerosis.

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of immune cells in the intima of arteries. Experimental and clinical evidence shows that both innate and adaptive immunity orchestrate the progression of atherosclerosis. The heterogeneous nature of immune cells within atherosclerosis lesions is important. Studies utilizing high-dimensional mass spectrometry and single-cell RNA sequencing of leukocytes from atherosclerotic lesions show the diversity and adaptability of these immune cell subtypes. Their migration, compositional changes, phenotypic alterations, and adaptive responses are key features throughout atherosclerosis progression. Understanding how these immune cells and their subtypes affect atherogenesis would help to develop novel therapeutic approaches that control atherosclerosis progression. Precise targeting of specific immune system components involved in atherosclerosis, rather than broad suppression of the immune system with anti-inflammatory agents, can more accurately regulate the progress of atherosclerosis with fewer side effects. In this review, we cover the most recent advances in the field of atherosclerosis to understand the role of various immune cells on its development. We focus on the complex network of immune cells and the interaction between the innate immune system and adaptive immune system.

TRPV3 regulates Breast Cancer Cell Proliferation and Apoptosis by EGFR/AKT pathway.

Breast cancer (BC) is one of the most common cancer types worldwide and the first cause of cancer-related deaths in women. Transient receptor potential vanillin 3 (TRPV3) has been preliminarily discovered to play an important role in various cancers, including BC. Here, we explored the effect of TRPV3 on breast cancer cells and its potential mechanism. TRPV3 level was measured in BC tissue and adjacent noncancerous breast tissue using real-time RT-PCR and Western blot. Wound healing was used to detect cell migration. MTT and EDU were detected cell proliferation. TUNEL and Caspase-3 activity were used to detect cell apoptosis. We found that TRPV3 expression significantly increased in both human BC tissues and breast cells line. TRPV3 siRNA (TRPV3 inhibition) dramatically suppressed cell migration and proliferation, promoted the apoptosis, and decreased [Ca2+]i; whereas Carvacrol (TRPV3 agonist) has opposite effect in MCF-7 cells. We validated EGFR (Epidermal growth factor receptor) is a direct target protein of TRPV3. Mechanism studies have shown that Carvacrol increased phosphorylation levels of EGFR and AKT, and were decreased by suppression of TRPV3. Moreover, Erlotinib (EGFR inhibitor) and LY294002 (PI3K inhibitor) diminished Carvacrol induced cell migration and proliferation, promoted cell apoptosis, and increased [Ca2+]i in Carvacrol group. Our results collectively suggest that TRPV3 siRNA inhibits migration and proliferation, and promoted apoptosis in breast cancer cells by EGFR/AKT pathway. These findings indicate that TRPV3 may represent a novel therapeutic strategy for breast cancer.

Bee venom acupuncture and herbal medicine for hand eczema: Two case reports and an in vivo study.

INTRODUCTION: Eczema and contact dermatitis are relatively common, non-life-threatening disease, but can reduce the patient's quality-of-life when it becomes chronic. This study describes two cases of bee venom acupuncture (BVA) and herbal medicine (San Wu Huangqin decoction; SWH) co-treatment for hand eczema and contact dermatitis, then confirms the effect of the combination therapy in an in vivo model of eczema. CASE PRESENTATION: A 56-year-old female (case 1) and a 33-year-old male (case 2) presented to the clinic with symptoms of itching and erythema (case 1), and scaliness (case 2) on both hands. Both were diagnosed with hand eczema and contact dermatitis based on examination of the erythema and scaliness. They were treated with BVA and SWH for three months. The lesions were healed and had not recurred after 1 and 3 years of follow-up. A mouse study was conducted by repeated application of 2,4-dinitrochlorobenzene (DNCB) to induce eczema-like contact dermatitis in Balb/c mice. In a DNCB-induced eczema-like contact dermatitis model, BVA and SWH co-administration synergistically improved clinical symptoms seen in eczema. Also, they improved histological changes of the skin, suppressed immune cell infiltration, and decreased inflammatory cytokines and immunoglobulin E in the serum. CONCLUSION: This study suggests BVA and SWH could be an alternative treatment for eczema and contact dermatitis.

Recent advances in extracellular vesicles for therapeutic cargo delivery.

Exosomes, which are nanosized vesicles secreted by cells, are attracting increasing interest in the field of biomedical research due to their unique properties, including biocompatibility, cargo loading capacity, and deep tissue penetration. They serve as natural signaling agents in intercellular communication, and their inherent ability to carry proteins, lipids, and nucleic acids endows them with remarkable therapeutic potential. Thus, exosomes can be exploited for diverse therapeutic applications, including chemotherapy, gene therapy, and photothermal therapy. Moreover, their capacity for homotypic targeting and self-recognition provides opportunities for personalized medicine. Despite their advantages as novel therapeutic agents, there are several challenges in optimizing cargo loading efficiency and structural stability and in defining exosome origins. Future research should include the development of large-scale, quality-controllable production methods, the refinement of drug loading strategies, and extensive in vivo studies and clinical trials. Despite the unresolved difficulties, the use of exosomes as efficient, stable, and safe therapeutic delivery systems is an interesting area in biomedical research. Therefore, this review describes exosomes and summarizes cutting-edge studies published in high-impact journals that have introduced novel or enhanced therapeutic effects using exosomes as a drug delivery system in the past 2 years. We provide an informative overview of the current state of exosome research, highlighting the unique properties and therapeutic applications of exosomes. We also emphasize challenges and future directions, underscoring the importance of addressing key issues in the field. With this review, we encourage researchers to further develop exosome-based drugs for clinical application, as such drugs may be among the most promising next-generation therapeutics.

Antinociceptive Effect of Dendrobii caulis in Paclitaxel-Induced Neuropathic Pain in Mice.

Paclitaxel-induced neuropathic pain (PINP) is a serious adverse effect of chemotherapy. Dendrobii caulis (D. caulis) is a new food source used as herbal medicine in east Asia. We examined the antinociceptive effects of D. caulis extract on PINP and clarified the mechanism of action of transient receptor potential vanilloid 1 receptor (TRPV1) in the spinal cord. PINP was induced in male mice using multiple intraperitoneal injections of paclitaxel (total dose, 8 mg/kg). PINP was maintained from D10 to D21 when assessed for cold and mechanical allodynia. Oral administration of 300 and 500 mg/kg D. caulis relieved cold and mechanical allodynia. In addition, TRPV1 in the paclitaxel group showed increased gene and protein expression, whereas the D. caulis 300 and 500 mg/kg groups showed a significant decrease. Among various substances in D. caulis, vicenin-2 was quantified by high-performance liquid chromatography, and its administration (10 mg/kg, i.p.) showed antinociceptive effects similar to those of D. caulis 500 mg/kg. Administration of the TRPV1 antagonist capsazepine also showed antinociceptive effects similar to those of D. caulis, and D. caulis is thought to exhibit antinociceptive effects on PINP by modulating the spinal TRPV1.

Natural Antioxidants in Obesity and Related Diseases.

Obesity is a chronic complex disease defined by excessive adiposity that impairs health [...].

Antidiabetic Effect of Fermented Mesembryanthemum crystallinum L. in db/db Mice Involves Regulation of PI3K-Akt Pathway.

Type 2 diabetes (T2D) is a serious health issue with increasing incidences worldwide. However, current medications have limitations due to side effects such as decreased appetite, stomach pain, diarrhea, and extreme tiredness. Here, we report the effect of fermented ice plant (FMC) in the T2M mouse model of db/db mice. FMC showed a greater inhibition of lipid accumulation compared to unfermented ice plant extract. Two-week oral administration with FMC inhibited body weight gain, lowered fasting blood glucose, and improved glucose tolerance. Serum parameters related to T2D including insulin, glycosylated hemoglobin, adiponectin, and cholesterols were improved as well. Histological analysis confirmed the protective effect of FMC on pancreas and liver destruction. FMC treatment significantly increased the expression and phosphorylation of IRS-1, PI3K, and AKT. Additionally, AMP-activated protein kinase phosphorylation and nuclear factor erythroid 2-related factor 2 were also increased in the liver tissues of db/db mice treated with FMC. Overall, our results indicate the anti-diabetic effect of FMC; therefore, we suggest that FMC may be useful as a therapeutic agent for T2D.

DANGER Signals Activate G -Protein Receptor Kinases Suppressing Neutrophil Function and Predisposing to Infection After Tissue Trauma.

OBJECTIVE: Injured tissue predisposes the subject to local and systemic infection. We studied injury-induced immune dysfunction seeking novel means to reverse such predisposition. BACKGROUND: Injury mobilizes primitive "DANGER signals" [danger-associated molecular patterns (DAMPs)] activating innate immunocyte (neutrophils, PMN) signaling and function. Mitochondrial formyl peptides activate G -protein coupled receptors (GPCR) like formyl peptide receptor-1. Mitochondrial DNA and heme activate toll-like receptors (TLR9 and TLR2/4). GPCR kinases (GRKs) can regulate GPCR activation. METHODS: We studied human and mouse PMN signaling elicited by mitochondrial DAMPs (GPCR surface expression; protein phosphorylation, or acetylation; Ca 2+ flux) and antimicrobial functions [cytoskeletal reorganization, chemotaxis (CTX), phagocytosis, bacterial killing] in cellular systems and clinical injury samples. Predicted rescue therapies were assessed in cell systems and mouse injury-dependent pneumonia models. RESULTS: Mitochondrial formyl peptides activate GRK2, internalizing GPCRs and suppressing CTX. Mitochondrial DNA suppresses CTX, phagocytosis, and killing through TLR9 through a novel noncanonical mechanism that lacks GPCR endocytosis. Heme also activates GRK2. GRK2 inhibitors like paroxetine restore functions. GRK2 activation through TLR9 prevented actin reorganization, implicating histone deacetylases (HDACs). Actin polymerization, CTX, bacterial phagocytosis, and killing were also rescued, therefore, by the HDAC inhibitor valproate. Trauma repository PMN showed GRK2 activation and cortactin deacetylation, which varied with severity and was most marked in patients developing infections. Either GRK2 or HDAC inhibition prevented loss of mouse lung bacterial clearance, but only the combination rescued clearance when given postinjury. CONCLUSIONS: Tissue injury-derived DAMPs suppress antimicrobial immunity through canonical GRK2 activation and a novel TLR-activated GRK2-pathway impairing cytoskeletal organization. Simultaneous GRK2/HDAC inhibition rescues susceptibility to infection after tissue injury.

The Role of Natural Products in the Improvement of Cancer-Associated Cachexia.

The enormous library of natural products and herbal medicine prescriptions presents endless research avenues. However, the lack of research evidence and trials on cancer-induced cachexia limit the therapeutic potential of natural products. Cancer-induced cachexia is a systemic wasting syndrome characterized by continuous body weight loss with skeletal muscle and adipose tissue atrophy. Cancer cachexia is a problem in itself and reduces the quality of life by lessening the treatment efficacy of anticancer drugs. This review summarizes single natural product extracts for cancer-induced cachexia, not compounds derived from natural products and herbal medicine prescriptions. This article also discusses the effect of natural products on cachexia induced by anticancer drugs and the role of AMPK in cancer-induced cachexia. The article included the mice model used in each experiment to encourage researchers to utilize animal models for research on cancer-induced cachexia in the future.

Ponciri Fructus Immatarus Sensitizes the Apoptotic Effect of Hyperthermia Treatment in AGS Gastric Cancer Cells through ROS-Dependent HSP Suppression.

Gastric cancer has been associated with a high incidence and mortality, accompanied by a poor prognosis. Given the limited therapeutic options to treat gastric cancer, alternative treatments need to be urgently developed. Hyperthermia therapy is a potentially effective and safe treatment option for cancer; however, certain limitations need to be addressed. We applied 43 °C hyperthermia to AGS gastric cancer cells combined with Ponciri Fructus Immaturus (PF) to establish their synergistic effects. Co-treatment with PF and hyperthermia synergistically suppressed AGS cell proliferation by inducing extrinsic and intrinsic apoptotic pathways. Additionally, PF and hyperthermia suppressed factors related to metastasis. Cell cycle arrest was determined by flow cytometry, revealing that co-treatment induced arrest at the G2/M phase. As reactive oxygen species (ROS) are critical in hyperthermia therapy, we next examined changes in ROS generation. Co-treatment with PF and hyperthermia increased ROS levels, and apoptotic induction mediated by this combination was partially dependent on ROS generation. Furthermore, heat shock factor 1 and heat shock proteins (HSPs) were notably suppressed following co-treatment with PF and hyperthermia. The HSP-regulating effect was also dependent on ROS generation. Overall, these findings suggest that co-treatment with PF and hyperthermia could afford a promising anticancer therapy for gastric cancer.

Immune-Enhancing Effect of Sargassum horneri on Cyclophosphamide-Induced Immunosuppression in BALB/c Mice and Primary Cultured Splenocytes.

Sargassum horneri (SH) is a seaweed that has several features that benefit health. In this study, we investigated the immune-enhancing effect of SH, focusing on the role of spleen-mediated immune functions. Chromatographic analysis of SH identified six types of monosaccharide contents, including mannose, rhamnose glucose, galactose xylose and fucose. SH increased cell proliferation of primary cultured naïve splenocytes treated with or without cyclophosphamide (CPA), an immunosuppression agent. SH also reversed the CPA-induced decrease in Th1 cytokines. In vivo investigation revealed that SH administration can increase the tissue weight of major immune organs, such as the spleen and thymus. A similar effect was observed in CPA-injected immunosuppressed BALB/c mice. SH treatment increased the weight of the spleen and thymus, blood immune cell count and Th1 cytokine expression. Additionally, the YAC-1-targeting activities of natural killer cells, which are important in innate immunity, were upregulated upon SH treatment. Overall, our study demonstrates the immune-enhancing effect of SH, suggesting its potential as a medicinal or therapeutic agent for pathologic conditions involving immunosuppression.

Paeonia lactiflora Pallas extract alleviates antibiotics and DNCB-induced atopic dermatitis symptoms by suppressing inflammation and changing the gut microbiota composition in mice.

Atopic dermatitis (AD) is a highly prevalent inflammatory skin disease worldwide. Recent studies have suggested an important role for association with the gut and skin microbiome axis in AD development. Paeonia lactiflora Pallas extract (PL) is commonly used for the treatment of inflammatory diseases. However, the possible mechanisms by which PL can alleviate AD by regulating the gut microbiota have not been investigated. In this study, we aimed to investigate the therapeutic effects and underlying mechanism of PL in mice with antibiotic cocktail (ABX)-induced AD. The effects of PL were evaluated in bone marrow-derived macrophages (BMDMs) and ABX and dinitrochlorobenzene (DNCB) mouse models. PL suppressed inflammatory cytokine and NO production in LPS-treated BMDMs. Moreover, PL attenuated scoring atopic dermatitis (SCORAD) scores, epidermal thickness, white blood cell counts and the disease activity index (DAI) in ABX-induced AD mice. Meanwhile, PL decreased IL-17A production, induced Foxp3 expression and improved intestinal barrier integrity by especially increasing the expression of tight junction proteins such as ZO-1 and occludin. Additionally, PL partially increased the diversity of the gut microbiota and changed the microbial composition. Our findings suggest that PL may be a potential natural product that can ameliorate atopic dermatitis symptoms by suppressing inflammatory cytokine production, inducing Foxp3 expression, increasing intestinal barrier integrity and changing the gut microbiota composition.

ERRγ Ligand Regulates Adult Neurogenesis and Depression-like Behavior in a LRRK2-G2019S-associated Young Female Mouse Model of Parkinson's Disease.

Adult neurogenesis, a process controlling the proliferation to maturation of newly generated neurons in the post-developmental brain, is associated with various brain functions and pathogenesis of neuropsychological diseases, such as Parkinson's disease (PD) and depression. Because orphan nuclear receptor estrogen-related receptor γ (ERRγ) plays a role in the differentiation of neuronal cells, we investigated whether an ERRγ ligand enhances adult neurogenesis and regulates depressive behavior in a LRRK2-G2019S-associated mouse model of PD. Young female LRRK2-G2019S mice (7-9 weeks old) showed depression-like behavior without dopaminergic neuronal loss in the nigrostriatal pathway nor motor dysfunction. A significant decrease in adult hippocampal neurogenesis was detected in young female LRRK2-G2019S mice, but not in comparable male mice. A synthetic ERRγ ligand, (E)-4-hydroxy-N'-(4-(phenylethynyl)benzylidene)benzohydrazide (HPB2), ameliorated depression-like behavior in young female LRRK2-G2019S mice and enhanced neurogenesis in the hippocampus, as evidenced by increases in the number of bromodeoxyuridine/neuronal nuclei-positive cells and in the intensity and number of doublecortin-positive cells in the hippocampal dentate gyrus (DG). Moreover, HPB2 significantly increased the number of spines and the number and length of dendrites in the DG of young female LRRK2-G2019S mice. Furthermore, HPB2 upregulated brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, one of the important factors regulating neurogenesis, as well as phosphorylated cAMP-response element binding protein-positive cells in the DG of young female LRRK2-G2019S mice. Together, these results suggest ERRγ as a novel therapeutic target for PD-associated depression by modulating adult neurogenesis and BDNF/TrkB signaling.

Hyperthermia Treatment as a Promising Anti-Cancer Strategy: Therapeutic Targets, Perspective Mechanisms and Synergistic Combinations in Experimental Approaches.

Despite recent developments in diagnosis and treatment options, cancer remains one of the most critical threats to health. Several anti-cancer therapies have been identified, but further research is needed to provide more treatment options that are safe and effective for cancer. Hyperthermia (HT) is a promising treatment strategy for cancer because of its safety and cost-effectiveness. This review summarizes studies on the anti-cancer effects of HT and the detailed mechanisms. In addition, combination therapies with anti-cancer drugs or natural products that can effectively overcome the limitations of HT are reviewed because HT may trigger protective events, such as an increase of heat shock proteins (HSPs). In the 115 reports included, the mechanisms related to apoptosis, cell cycle, reactive oxygen species, mitochondrial membrane potential, DNA damage, transcription factors and HSPs were considered important. This review shows that HT is an effective inducer of apoptosis. Moreover, the limitations of HT may be overcome using combined therapy with anti-cancer drugs or natural products. Therefore, appropriate combinations of such agents with HT will exert maximal effects to treat cancer.

Reduced HIF-1α Stability Induced by 6-Gingerol Inhibits Lung Cancer Growth through the Induction of Cell Death.

Lung cancer (LC) is the leading global cause of cancer-related death, and metastasis is a great challenge in LC therapy. Additionally, solid cancer, including lung, prostate, and colon cancer, are characterized by hypoxia. A low-oxygen state is facilitated by the oncogene pathway, which correlates with a poor cancer prognosis. Thus, we need to understand the related mechanisms in solid tumors to improve and develop new anticancer strategies. The experiments herein describe an anticancer mechanism in which heat shock protein 90 (HSP90) stabilizes HIF-1α, a master transcription factor of oxygen homeostasis that has been implicated in the survival, proliferation and malignant progression of cancers. We demonstrate the efficacy of 6-gingerol and the molecular mechanism by which 6-gingerol inhibits LC metastasis in different oxygen environments. Our results showed that cell proliferation was inhibited after 6-gingerol treatment. Additionally, HIF-1α, a transcriptional regulator, was found to be recruited to the hypoxia response element (HRE) of target genes to induce the transcription of a series of target genes, including MMP-9, vimentin and snail. Interestingly, we found that 6-gingerol treatment suppressed activation of the transcription factor HIF-1α by downregulating HSP90 under both normoxic and hypoxic conditions. Furthermore, an experiment in an in vivo xenograft model revealed decreased tumor growth after 6-gingerol treatment. Both in vitro and in vivo analyses showed the inhibition of metastasis through HIF-1α/HSP90 after 6-gingerol treatment. In summary, our study demonstrates that 6-gingerol suppresses proliferation and blocks the nuclear translocation of HIF-1α and activation of the EMT pathway. These data suggest that 6-gingerol is a candidate antimetastatic treatment for LC.

Discovery of new ERRγ agonists regulating dopaminergic neuronal phenotype in SH-SY5Y cells.

The discovery of small molecules that regulate specific neuronal phenotypes is important for the development of new therapeutic candidates for neurological diseases. Estrogen-related receptor γ (ERRγ), an orphan nuclear receptor widely expressed in the central nervous system (CNS), is closely related to the regulation of neuronal metabolism and differentiation. We previously reported that upregulation of ERRγ could enhance dopaminergic neuronal phenotypes in the neuroblastoma cell line, SH-SY5Y. In this study, we designed and synthesized a series of new ERRγ agonists using the X-ray crystal structure of the GSK4716-bound ERRγ complex and known synthetic ligands. Our new ERRγ agonists exhibited increased transcriptional activities of ERRγ. In addition, our molecular docking results supported the experimental findings for ERRγ agonistic activity of the potent analogue, 5d. Importantly, 5d not only enhanced the expression of dopaminergic neuronal-specific molecules, TH and DAT but also activated the relevant signaling events, such as the CREB-mediated signaling pathway. The results of the present study may provide useful clues for the development of novel ERRγ agonists for neurological diseases related to the dopaminergic nervous system.

Platycodin D inhibits autophagy and increases glioblastoma cell death via LDLR upregulation.

Targeting autophagy is a promising therapeutic approach in cancer therapy. Here, we screened 30 traditional herbal medicines to identify novel autophagy regulators and found that Platycodon grandiflorus (PG) and platycodin D (PD), a triterpenoid saponin from PG, inhibited autophagy in glioblastoma multiforme (GBM) cells. Mechanistically, PD prevented lysosomal degradation and the fusion between autophagosomes and lysosomes by inducing sequestration of free cholesterol in lysosomes. The autophagy inhibitory effect of PD was mimicked by both genetic and pharmacological inhibition of Niemann-Pick C1 (NPC1), which exports low-density lipoprotein (LDL)-derived cholesterol from lysosomes. Moreover, PD promoted the uptake of exogenous LDL cholesterol via upregulation of LDL receptor (LDLR), leading to further accumulation of cholesterol within lysosomes and GBM cell death. Importantly, these phenomena were more pronounced in LDLR-overexpressing GBM cells than in normal astrocytes. Finally, blockade of cholesterol uptake by LDLR knockdown reversed the PD-induced inhibition of autophagy and GBM cell growth. Our study proposes that PD could be a potent anti-GBM drug by disrupting cholesterol trafficking and autophagy.

Plasma and wound fluids from trauma patients suppress neutrophil extracellular respiratory burst.

BACKGROUND: Trauma increases susceptibility to secondary bacterial infections. The events suppressing antimicrobial immunity are unclear. Polymorphonuclear neutrophils (PMNs) migrate toward bacteria using chemotaxis, trap them in extracellular neutrophil extracellular traps, and kill them using respiratory burst (RB). We hypothesized that plasma and wound fluids from trauma patients alter PMN function. METHODS: Volunteer PMNs were incubated in plasma or wound fluids from trauma patients (days 0 and 1, days 2 and 3), and their functions were compared with PMNs incubated in volunteer plasma. Chemotaxis was assessed in transwells. Luminometry assessed total and intracellular RB responses to receptor-dependent and independent stimulants. Neutrophil extracellular trap formation was assessed using elastase assays. The role of tissue necrosis in creating functionally suppressive systemic PMN environments was assessed using a novel pig model where PMNs were incubated in uninjured pig plasma or plasma from pigs undergoing intraperitoneal instillation of liver slurry. RESULTS: Both plasma and wound fluids from trauma patients markedly suppress total PMN RB. Intracellular RB is unchanged, implicating suppression of extracellular RB. Wound fluids are more suppressive than plasma. Biofluids suppressed RB maximally early after injury and their effects decayed with time. Chemotaxis and neutrophil extracellular trap formation were suppressed by biofluids similarly. Lastly, plasma from pigs undergoing abdominal liver slurry instillation suppressed PMN RB, paralleling suppression by human trauma biofluids. CONCLUSION: Trauma plasma and wound fluids suppress RB and other key PMNs antimicrobial functions. Circulating suppressive signals can be derived from injured or necrotic tissue at wound sites, suggesting a key mechanism by which tissue injuries can put the host at risk for infection.

Anmyungambi Decoction Ameliorates Obesity through Activation of Non-Shivering Thermogenesis in Brown and White Adipose Tissues.

Obesity is a burden to global health. Non-shivering thermogenesis of brown adipose tissue (BAT) and white adipose tissue (WAT) is a novel strategy for obesity treatment. Anmyungambi (AMGB) decoction is a multi-herb decoction with clinical anti-obesity effects. Here, we show the effects of AMGB decoction using high-fat diet (HFD)-fed C57BL6/J mice. All four versions of AMGB decoction (100 mg/kg/day, oral gavage for 28 days) suppressed body weight gain and obesity-related blood parameters in the HFD-fed obese mice. They also inhibited adipogenesis and induced lipolysis in inguinal WAT (iWAT). Especially, the AMGB-4 with 2:1:3:3 composition was the most effective; thus, further studies were performed with the AMGB-4 decoction. The AMGB-4 decoction displayed a dose-dependent body weight gain suppression. Serum triglyceride, total cholesterol, and blood glucose decreased as well. In epididymal WAT, iWAT, and BAT, the AMGB-4 decoction increased lipolysis markers. Additionally, the AMGB-4 decoction-fed mice showed an increased non-shivering thermogenic program in BAT and iWAT. Excessive reactive oxygen species (ROS) and suppressed antioxidative factors induced by the HFD feeding were also altered to normal levels by the AMGB-4 decoction treatment. Overall, our study supports the clinical use of AMGB decoction for obesity treatment by studying its mechanisms. AMGB decoction alleviates obesity through the activation of the lipolysis-thermogenesis program and the elimination of pathological ROS in thermogenic adipose tissues.