Combining network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification to examine the efficacy and immunoregulation mechanism of FHB granules on vitiligo.

Background: Fufang Honghua Buji (FHB) granules, have proven efficacy against vitiligo in long-term clinical practice. However, its major active chemical components and molecular mechanisms of action remain unknown. The purpose of this study was to confirm the molecular mechanism of FHB's therapeutic effect on vitiligo utilizing network pharmacology, molecular docking, and molecular dynamics simulation prediction, as well as experimental verification. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and HERB databases were used to obtain the chemical composition and action targets of FHB. Online Mendelian Inheritance in Man (OMIM), DrugBank, DisGeNET, GeneCards, and Therapeutic Target Database (TTD) databases were applied to screen for vitiligo-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed through the Matascape database. Molecular docking and dynamics simulation methods were for the analysis of the binding sites and binding energies between the FHB's active components and the targets. Finally, a vitiligo mouse model was created, and the therapeutic effect and molecular mechanism of action of FHB were validated using enzyme linked immunosorbent assay (ELISA), western blot (WB), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, hematoxylin-eosin staining (HE) and blood biochemical assays were conducted to assess the biosafety of FHB. Result: The screening of chemical composition and targets suggested that 94 genetic targets of FHB were associated with vitiligo. The bioinformatics analysis suggested that luteolin, quercetin, and wogonin may be major active components, and nuclear factor-kappa B p65 subunit (RELA), signal transducer, and activator of transcription (STAT) 3 and RAC-alpha serine/threonine-protein kinase (AKT) 1 may be potential targets of FHB-vitiligo therapy. Molecular docking and dynamics simulation further demonstrated that luteolin, quercetin, and wogonin all bound best to STAT3. Through experimental verification, FHB has been demonstrated to alleviate the pathogenic characteristics of vitiligo mice, suppress the JAK-STAT signaling pathway, reduce inflammation, and increase melanogenesis. The in vivo safety evaluation experiments also demonstrated the non-toxicity of FHB. Conclusions: FHB exerts anti-inflammatory and melanogenesis-promoting effects via the effect of multi-component on multi-target, among which the JAK-STAT pathway is a validated FHB-vitiligo target, providing new ideas and clues for the development of vitiligo therapy.

Functional Axis of PDE5/cGMP Mediates Timosaponin-AIII-Elicited Growth Suppression of Glioblastoma U87MG Cells.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.

Effect and mechanism of longkui yinxiao soup in treating psoriasis in mice.

Objective: Longkui Yinxiao Soup is a traditional Chinese medicine formula used to treat psoriasis for decades. Although Longkui Yinxiao Soup showed promising efficacy in clinical practice, the regulatory mechanisms of Longkui Yinxiao Soup remain elusive. This study aimed to explore the underlying mechanisms of Longkui Yinxiao Soup in a psoriasis-like mouse model. Methods: Longkui Yinxiao Soup was quality controlled by determining the contents of imperatorin and rhoifolin using high-performance liquid chromatography. The imiquimod-induced psoriasis-like mouse model was used to study the therapeutic effect and mechanism of Longkui Yinxiao Soup. The histopathological skin changes were observed by hematoxylin and eosin staining; the infiltration of proliferating proteins, proliferating cell nuclear antigen and Ki67, in skin tissues were observed by immunohistochemical analysis; and the inflammatory factors such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-23, and IL-17 in serum were detected using enzyme-linked immunosorbent assay. RNA sequencing and bioinformatic analysis were used to predict the mechanism of LYS against psoriasis. mRNA expressions of p38, extracellular regulated protein kinases (ERK), mitogen-activated protein kinase 3 (MEK3), mitogen-activated protein kinase 6 (MEK6), RAP1 GTPase activating protein (Rap1gap), and Rap1 were determined using real-time quantitative polymerase chain reaction. The expression levels of proteins related to Rap1-mitogen-activated protein kinase signaling pathways were measured by Western blotting. Results: A quality-control method for Longkui Yinxiao Soup was successfully established using imperatorin and rhoifolin as content determination indexes. Longkui Yinxiao Soup significantly ameliorated the psoriatic symptoms in mice. The serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17 were decreased, and the expression levels of antigen identified by monoclonal antibody Ki67 (Ki67) and PCNA in skin tissues were downregulated. Moreover, the inhibition of Rap1-MAPK signaling pathways by Longkui Yinxiao Soup was detected. Conclusion: This study confirmed the antipsoriatic activity of Longkui Yinxiao Soup in psoriasis-like mice. This might be due to the inhibition of inflammatory factor secretion, keratinocyte proliferation, and the Rap1-MAPK signal pathway.

Macrophage Membrane-Derived Biomimetic Nanoparticles for Treatment of Cytokine Release Syndrome.

Cytokine release syndrome (CRS) is a severe complication of infectious diseases like Coronavirus disease 2019 (COVID-19) that cause serious damage to public health. Currently, supportive therapy is still the main therapeutic strategy exists for CRS treatment. Here, we show the potential of macrophage membrane-derived biomimetic nanoparticles for CRS treatment. By fusing macrophage membrane on the surface of the PLGA nano core, we constructed biomimetic nanoparticles that inherited the membrane receptors from the "parental" macrophages, enabling the neutralization of CRS-related cytokines. We compared three types of macrophage membranes to screen out more effective biomimetic nanoparticles for CRS treatment. Our results show that M0 macrophage membrane-derived biomimetic nanoparticles could neutralize pro-inflammatory cytokines involved in CRS to the greatest extent and reduce organ damage in a mouse model.

Suppression of top-down influence decreases neuronal excitability and contrast sensitivity in the V1 cortex of cat.

How top-down influence affects neuronal activity and information encoding in the primary visual cortex (V1) remains elusive. This study examined changes of neuronal excitability and contrast sensitivity in cat V1 cortex after top-down influence of area 7 (A7) was modulated by transcranial direct current stimulation (tDCS). The neuronal excitability in V1 cortex was evaluated by visually evoked field potentials (VEPs), and contrast sensitivity (CS) was assessed by the inverse of threshold contrast of neurons in response to visual stimuli at different performance accuracy. We found that the amplitude of VEPs in V1 cortex lowered after top-down influence suppression with cathode-tDCS in A7, whereas VEPs in V1 did not change after sham-tDCS in A7 and nonvisual cortical area 5 (A5) or cathode-tDCS in A5 and lesioned A7. Moreover, the mean CS of V1 neurons decreased after cathode-tDCS but not sham-tDCS in A7, which could recover after tDCS effect vanished. Comparisons of neuronal contrast-response functions showed that cathode-tDCS increased the stimulus contrast required to generate the half-maximum response, with a weakly-correlated reduction in maximum response but not baseline response. Therefore, top-down influence of A7 enhanced neuronal excitability in V1 cortex and improved neuronal contrast sensitivity by both contrast gain and response gain.

Top-down influence affects the response adaptation of V1 neurons in cats.

The visual system lowers its perceptual sensitivity to a prolonged presentation of the same visual signal. This brain plasticity, called visual adaptation, is generally attributed to the response adaptation of neurons in the visual cortex. Although well-studied in the neurons of the primary visual cortex (V1), the contribution of high-level visual cortical regions to the response adaptation of V1 neurons is unclear. In the present study, we measured the response adaptation strength of V1 neurons before and after the top-down influence of the area 21a (A21a), a higher-order visual cortex homologous to the primate V4 area, was modulated with a noninvasive tool of transcranial direct current stimulation (tDCS). Our results showed that the response adaptation of V1 neurons enhanced significantly after applying anode (a-) tDCS in A21a when compared with that before a-tDCS, whereas the response adaptation of V1 neurons weakened after cathode (c-) tDCS relative to before c-tDCS in A21a. By contrast, sham (s-) tDCS in A21a had no significant impact on the response adaptation of V1 neurons. Further analysis indicated that a-tDCS in A21a significantly increased both the initial response (IR) of V1 neurons to the first several (five) trails of visual stimulation and the plateau response (PR) to the prolonged visual stimulation; the increase in PR was lower than in IR, which caused an enhancement in response adaptation. Conversely, c-tDCS significantly decreased both IR and PR of V1 neurons; the reduction in PR was smaller than in IR, which resulted in a weakness in response adaptation. Furthermore, the tDCS-induced changes of V1 neurons in response and response adaptation could recover after tDCS effect vanished, but did not occur after the neuronal activity in A21a was silenced by electrolytic lesions. These results suggest that the top-down influence of A21a may alter the response adaptation of V1 neurons through activation of local inhibitory circuitry, which enhances network inhibition in the V1 area upon an increased top-down input, weakens inhibition upon a decreased top-down input, and thus maintains homeostasis of V1 neurons in response to the long-presenting visual signals.

Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer.

PURPOSE: The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells. MATERIALS AND METHODS: An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models. RESULTS: The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs. CONCLUSION: PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.

Anodal and cathodal tDCS modulate neural activity and selectively affect GABA and glutamate syntheses in the visual cortex of cats.

KEY POINTS: The present study showed that anodal and cathodal transcranial direct current stimulation (tDCS) can respectively increase and decrease the amplitude of visually evoked field potentials in the stimulated visual cortex of cats, with the effect lasting for ∼60-70 min. We directly measured tDCS-induced changes in the concentration of inhibitory and excitatory neurotransmitters in the visual cortex using the enzyme-linked immunosorbent assay method and showed that anodal and cathodal tDCS can selectively decrease the concentration of GABA and glutamate in the stimulated cortical area. Anodal and cathodal tDCS can selectively inhibit the synthesis of GABA and glutamate by suppressing the expression of GABA- and glutamate-synthesizing enzymes, respectively. ABSTRACT: Transcranial direct current stimulation (tDCS) evokes long-lasting neuronal excitability in the target brain region. The underlying neural mechanisms remain poorly understood. The present study examined tDCS-induced alterations in neuronal activities, as well as the concentration and synthesis of GABA and glutamate (GLU), in area 21a (A21a) of cat visual cortex. Our analysis showed that anodal and cathodal tDCS respectively enhanced and suppressed neuronal activities in A21a, as indicated by a significantly increased and decreased amplitude of visually evoked field potentials (VEPs). The tDCS-induced effect lasted for ∼60-70 min. By contrast, sham tDCS had no significant impact on the VEPs in A21a. On the other hand, the concentration of GABA, but not that of GLU, in A21a significantly decreased after anodal tDCS relative to sham tDCS, whereas the concentration of GLU, but not that of GABA, in A21a significantly decreased after cathodal tDCS relative to sham tDCS. Furthermore, the expression of GABA-synthesizing enzymes GAD65 and GAD67 in A21a significantly decreased in terms of both mRNA and protein concentrations after anodal tDCS relative to sham tDCS, whereas that of GLU-synthesizing enzyme glutaminase (GLS) did not change significantly after anodal tDCS. By contrast, both mRNA and protein concentrations of GLS in A21a significantly decreased after cathodal tDCS relative to sham tDCS, whereas those of GAD65/GAD67 showed no significant change after cathodal tDCS. Taken together, these results indicate that anodal and cathodal tDCS may selectively reduce GABA and GLU syntheses and thus respectively enhance and suppress neuronal excitability in the stimulated brain area.

Characterization of Feedback Neurons in the High-Level Visual Cortical Areas That Project Directly to the Primary Visual Cortex in the Cat.

Previous studies indicate that top-down influence plays a critical role in visual information processing and perceptual detection. However, the substrate that carries top-down influence remains poorly understood. Using a combined technique of retrograde neuronal tracing and immunofluorescent double labeling, we characterized the distribution and cell type of feedback neurons in cat's high-level visual cortical areas that send direct connections to the primary visual cortex (V1: area 17). Our results showed: (1) the high-level visual cortex of area 21a at the ventral stream and PMLS area at the dorsal stream have a similar proportion of feedback neurons back projecting to the V1 area, (2) the distribution of feedback neurons in the higher-order visual area 21a and PMLS was significantly denser than in the intermediate visual cortex of area 19 and 18, (3) feedback neurons in all observed high-level visual cortex were found in layer II-III, IV, V, and VI, with a higher proportion in layer II-III, V, and VI than in layer IV, and (4) most feedback neurons were CaMKII-positive excitatory neurons, and few of them were identified as inhibitory GABAergic neurons. These results may argue against the segregation of ventral and dorsal streams during visual information processing, and support "reverse hierarchy theory" or interactive model proposing that recurrent connections between V1 and higher-order visual areas constitute the functional circuits that mediate visual perception. Also, the corticocortical feedback neurons from high-level visual cortical areas to the V1 area are mostly excitatory in nature.

Current Progresses of Functional Nanomaterials for Imaging Diagnosis and Treatment of Melanoma.

Melanoma is a malignant skin tumor that results in poor disease prognosis due to unsuccessful treatment options. During the early stages of tumor progression, surgery is the primary approach that assures a good outcome. However, in the presence of metastasis, melanoma hasbecome almost immedicable, since the tumors can not be removed and the disease recurs easily in a short period of time. However, in recent years, the combination of nanomedicine and chemotherapeutic drugs has offered promising solutions to the treatment of late-stage melanoma. Extensive studies have demonstrated that nanomaterials and their advanced applications can improve the efficacy of traditional chemotherapeutic drugs in order to overcome the disadvantages, such as drug resistance, low drug delivery rate and reduced targeting to the tumor tissue. In the present review, we summarized the latest progress in imaging diagnosis and treatment of melanoma using functional nanomaterials, including polymers, liposomes, metal nanoparticles, magnetic nanoparticles and carbon-based nanoparticles. These nanoparticles are reported widely in melanoma chemotherapy, gene therapy, immunotherapy, photodynamic therapy, and hyperthermia.

[Inhibitory mechanisms of timosaponin Aâ ¢ on proliferation and growth of human glioblastoma cells].

To explore the inhibitory effect of timosaponin AⅢ on the proliferation of human glioblastoma cell line U87MG and investigate its related mechanism. As compared with the model group, the tumor weight was significantly reduced in timosaponin AⅢ-treated group. Timosaponin AⅢinhibited the proliferation of U87MG cell line in a dose-dependent manner. It up-regulated the gene and protein expression levels of p21, meanwhile inhibited the protein expression levels of ß-Catenin, Cyclin D1 and Bcl-2. It also inhibited the translocation of ß-Catenin into nucleus, suppressed the phosphorylation expression of ERK, but increased the phosphorylation expression of p38 and JNK. Combined use of JNK inhibitor SP600125 and p38 inhibitor SB203580 could decrease p21 and increase ß-Catenin protein expressions. Timosaponin AⅢ inhibited the proliferation of human glioblastoma cell line U87MG partly by intervening MAPK and Wnt/ß-Catenin signal pathways.

Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating the IRS-1/PI3K/Akt and AMPK/ACC2 signaling pathways.

AIM: We have shown that rutaecarpine extracted from the dried fruit of Chinese herb Evodia rutaecarpa (Juss) Benth (Wu Zhu Yu) promotes glucose consumption and anti-inflammatory cytokine expression in insulin-resistant primary skeletal muscle cells. In this study we investigated whether rutaecarpine ameliorated the obesity profiles, lipid abnormality, glucose metabolism and insulin resistance in rat model of hyperlipidemia and hyperglycemia. METHODS: Rats fed on a high-fat diet for 8 weeks, followed by injection of streptozotocin (30 mg/kg, ip) to induce hyperlipidemia and hyperglycemia. One week after streptozotocin injection, the fat-fed, streptozotocin-treated rats were orally treated with rutaecarpine (25 mg·kg(-1)·d(-1)) or a positive control drug metformin (250 mg·kg(-1)·d(-1)) for 7 weeks. The body weight, visceral fat, blood lipid profiles and glucose levels, insulin sensitivity were measured. Serum levels of inflammatory cytokines were analyzed. IRS-1 and Akt/PKB phosphorylation, PI3K and NF-κB protein levels in liver tissues were assessed; pathological changes of livers and pancreases were examined. Glucose uptake and AMPK/ACC2 phosphorylation were studied in cultured rat skeletal muscle cells in vitro. RESULTS: Administration of rutaecarpine or metformin significantly decreased obesity, visceral fat accumulation, water consumption, and serum TC, TG and LDL-cholesterol levels in fat-fed, streptozotocin-treated rats. The two drugs also attenuated hyperglycemia and enhanced insulin sensitivity. Moreover, the two drugs significantly decreased NF-κB protein levels in liver tissues and plasma TNF-α, IL-6, CRP and MCP-1 levels, and ameliorated the pathological changes in livers and pancreases. In addition, the two drugs increased PI3K p85 subunit levels and Akt/PKB phosphorylation, but decreased IRS-1 phosphorylation in liver tissues. Treatment of cultured skeletal muscle cells with rutaecarpine (20-180 µmol/L) or metformin (20 µmol/L) promoted the phosphorylation of AMPK and ACC2, and increased glucose uptake. CONCLUSION: Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating IRS-1/PI3K/Akt signaling pathway in liver and AMPK/ACC2 signaling pathway in skeletal muscles.

[Effects of four kinds of Chinese medicine monomer on growth of PANC-1 xenograft tumor and studying of molecular mechanism].

OBJECTIVE: The antitumor effects of icarisid II, timosaponin A-III, neferine and salidroside were studied in PANC-1 xenograft tumor. METHOD: To establish of the nude mice xenograft tumor model, PANC-1 cells were injected. When the tumor major diameter was reached 3-5 mm, the treatment was initiated. The mice were randomized into vehicle control and treatment groups of six animals per each. Chinese medicine monomer was injected intraperitoneally every day. In 23th day, mice were killed once a day, tumor tissue were isolated and weighed and divided into two parts. One part was fixed with formaldehyde for tissue section and immunohistochemistry, the another of tissue was frozen in liquid nitrogen then in - 80 degrees C refrigerator for gene and protein expression analysis. RESULT: In PANC-1 tumor xenograft experiment, compared with model group, timosaponin A-III (1.0 mg x kg (-1)) exerted significant inhibitory effects on tumor growth. Timosaponin A-III suppressed mRNA expressions of VEGF (P < 0.05), reduced protein expressions of VEGF (P < 0.05), activated Caspase-3 protein. Icarisid II, neferine and salidroside had not an excelled antitumor effect. CONCLUSION: Timosaponin A-III exerted an excelled antitumor effect. The antitumor mechanisms include anti-angiogenesis, apoptosis promotion.

[Mitochondrial dysfunction induced by excessive ROS/RNS-metabolic cardiovascular disease and traditional Chinese medicines intervention].

Metabolic cardiovascular disease is a type of disease which almost caused by body carbohydrate and lipid metabolism dysfunction. Type 2 diabetes mellitus is a typical metabolic disease. It not only lead to the insulin resistance but also related to atherosclerosis. Oxidative stress is produced by the reactive oxygen/nitrogen species (ROS/RNS). Oxidative stress and its consequence events play important roles in atherosclerosis (AS). Mitochondria are both sources and targets of reactive oxygen and/or nitrogen species (ROS/RNS), and there is growing evidence that mitochondrial dysfunction may be relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. This review starts with excessive ROS/RNS-induced mitochondrial dysfunction. The authors emphasize the relationship among axis of excessive ROS/RNS-mitochondrial dysfunction-apoptosis-atherosclerosis. They also introduce several traditional Chinese medicines such as Ophiopogon japonicus, butin, Panax ginseng, Pueraria lobata, Solanum lyratum and so on in the treatment of relevant diseases through anti-ROS/RNS mechanism. Moreover, the TCMs also can anti-cancer and anti-fatigue,which show the speciality of TCMs different from the single effect of classical western medicines.

[Diabetes mellitus ulcers treatment with Bletilla striata polysaccharide].

The aim of this study was to evaluate the efficacy of Bletilla striata polysaccharide on diabetes mellitus ulcers. Diabetes mellitus animal model was established by single ip injection of streptozotocin (STZ, 50 mg x kg(-1)) with the criteria of blood glucose > or = 16.7 mmol x L(-1) after 72 h. 4 weeks after STZ injection, each animal received two full thickness incisional wounds (1.8 cm in diameter). The wounds then were divided into B. striata polysaccharide group and PBS group. Wound closure rate, fibroblast (FB) infiltration, hydroxyproline (OHP) content and myeloperoxidase (MPO) levels were examined on day 3, 7, 14, 21 post wound. The treatment of B. striata polysaccharide significantly facilitated diabetes mellitus ulcers healing compared to PBS group. Histological analysis showed that B. striata polysaccharide markedly increased inflammatory cell infiltration in wound area. The herb also strongly evaluation of FB, OHP demonstrated a significantly increased in B. striata polysaccharide group. B. striata polysaccharide group promoted wound closure by means of enhanced inflammatory cell infiltration and re-epithelialization, and the promotion of FB and OHP levels.

[Study on effect of total saponins from Semen Nigellae on inflammatory mediators and ERK/MAPK pathway in stimulated macrophage].

OBJECTIVE: To study the anti-inflammatory mechanism of total saponins from Semen Nigellae (TSSN). METHOD: IFN-gamma plus LPS stimulated RAW 264. 7 macrophage has been used as inflammatory experimental model. Griess reaction for nitric oxide production, FRAP assay for total antioxidant capacity, RT-PCR for mRNA expression and Western blot for protein expression examination were performed. RESULT: TSSN inhibited NO production in a dose-dependent manner. The gene and protein expression of iNOS were also suppressed by the herb extract. TSSN treatment significantly attenuated mRNA of inflammatory mediators such as COX-2, IL-1beta, IL-6 while increased PPAR-gamma gene and protein expression. Furthermore, phosphorylation of ERK (p-ERK) was markedly inhibited by TSSN. CONCLUSION: TSSN suppressed pro-inflammatory mediators such as COX-2, IL-1beta, IL-6 and increased anti-inflammatory mediator PPAR-gamma expression. Meanwhile, TSSN inhibited over production of NO and iNOS expression through ERK/MAPK pathway.