Aiouea padiformis extract exhibits anti-inflammatory effects by inhibiting the ATPase activity of NLRP3.

Inflammation is implicated as a cause in many diseases. Most of the anti-inflammatory agents in use are synthetic and there is an unmet need for natural substance-derived anti-inflammatory agents with minimal side effects. Aiouea padiformis belongs to the Lauraceae family and is primarily found in tropical regions. While some members of the Aiouea genus are known to possess anti-inflammatory properties, the anti-inflammatory properties of Aiouea padiformis extract (AP) have not been investigated. In this study, we aimed to examine the anti-inflammatory function of AP through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and elucidate the underlying mechanisms. Treatment with AP inhibited the secretion of interleukin-1 beta (IL-1ß) mediated by NLRP3 inflammasome in J774A.1 and THP-1 cells without affecting the viability. In addition, AP treatment did not influence NF-κB signaling, potassium efflux, or intracellular reactive oxygen species (ROS) production-all of which are associated with NLRP3 inflammasome activation. However, intriguingly, AP treatment significantly reduced the ATPase activity of NLRP3, leading to the inhibition of ASC oligomerization and speck formation. Consistent with cellular experiments, the anti-inflammatory property of AP in vivo was also evaluated using an LPS-induced inflammation model in zebrafish, demonstrating that AP hinders NLRP3 inflammasome activation.

Anti-Adipogenic Activity of Secondary Metabolites Isolated from Smilax sieboldii Miq. on 3T3-L1 Adipocytes.

Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii (Smilacaceae), we screened methylene chloride (CH2Cl2), ethyl acetate (EtOAc), aqueous-saturated n-butanol, and ethanol (EtOH) extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. The 3T3-L1 cell line with Oil red O staining with the help of fluorometry was used as an indicator of anti-obesity activity. Bioactivity-guided fractionation of the EtOH extract and subsequent phytochemical investigation of the active CH2Cl2- and EtOAc-soluble fractions resulted in the isolation of 19 secondary metabolites (1-19), including a new α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18). The structures of these compounds were characterized using various spectroscopic methods. All the isolated compounds were screened for adipogenesis inhibition at a concentration of 100 µM. Of these, compounds 1, 2, 4-9, 15, and 19 significantly reduced fat accumulation in 3T3-L1 adipocytes, especially compounds 4, 7, 9, and 19, showing 37.05 ± 0.95, 8.60 ± 0.41 15.82 ± 1.23, and 17.73 ± 1.28% lipid content, respectively, at a concentration of 100 µM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial effects regarding the regulation of adipocyte differentiation.

Phytochemical investigation on the aerial parts of Veratrum versicolor f. viride Nakai and their biological activities.

Veratrum spp. have traditionally been used in folk medicine to treat various pathologies. In this study, nine compounds, comprising one simple phenolic compound (1), three stilbenoids (2-4), and five flavonoids (5-9), were isolated from the aerial parts of Veratrum versicolor f. viride Nakai. The structures of these compounds were elucidated by spectroscopic analyses and comparison with reported data. Together, all reported compounds were isolated from V. versicolor f. viride for the first time in the study. Among them, two flavone aglycone tricetins (7 and 9) have never been isolated from the genus Veratrum or the family Melanthiaceae. The ethanol extract and isolated compounds were assessed for their inhibitory effects on elastase, tyrosinase, and melanin synthesis. Compounds 5 and 7 inhibited elastase (IC50: 292.25 ± 14.39 and 800.41 ± 5.86 µM, respectively), whereas compounds 2-5 inhibited tyrosinase with IC50 values in the range of 6.42 ~ 51.19 µM, respectively. In addition, compounds 3-6 and 8 exhibited dose-dependent inhibition (70.4% ~ 91.0%) of melanogenesis at a concentration of 100 µM.

Identification of p-Coumaric Acid and Ethyl p-Coumarate as the Main Phenolic Components of Hemp (Cannabis sativa L.) Roots.

Hemp (Cannabis sativa L.) contains a variety of secondary metabolites, including cannabinoids, such as psychoactive (-)-trans-Δ9-tetrahydrocannabinol. The present study was conducted to identify the major phenolic components contained in hemp root, which has been relatively under-researched compared to other parts of hemp. The aqueous ethanol extract of hemp roots was fractionated into methylene chloride (MC), ethyl acetate (EA), and water (WT) fractions, and high-performance liquid chromatography with photodiode array detection (HPLC-DAD) analysis was performed. The main ultraviolet (UV)-absorbing phenolic compound contained in the EA fraction was identified as p-coumaric acid by comparing the retention time and UV absorption spectrum with a standard. Silica gel column chromatography was performed to isolate a hydrophobic derivative of p-coumaric acid contained in the MC fraction. Nuclear magnetic resonance (NMR) analysis identified the isolated compound as ethyl p-coumarate. For comparative purposes, ethyl p-coumarate was also chemically synthesized by the esterification reaction of p-coumaric acid. The content of p-coumaric acid and ethyl p-coumarate in the total extract of hemp root was estimated to be 2.61 mg g-1 and 6.47 mg g-1, respectively, by HPLC-DAD analysis. These values correspond to 84 mg Kg-1 dry root and 216 mg Kg-1 dry root, respectively. In conclusion, this study identified p-coumaric acid and ethyl p-coumarate as the main phenolic compounds contained in the hemp roots.

Lotus Seed Green Embryo Extract and a Purified Glycosyloxyflavone Constituent, Narcissoside, Activate TRPV1 Channels in Dorsal Root Ganglion Sensory Neurons.

Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbinis [PN]) green embryo extract. However, the specific bioactive components and associated molecular mechanisms remain largely unknown. This study aimed to identify the ion channel-activating mechanisms of PN extracts. Using fluorometric imaging and patch-clamp recordings, PN extracts were screened for calcium channel activation in dorsal root ganglion (DRG) neurons. The TRPV1 channels in DRG neurons were strongly activated by the PN extract (mean amplitude of 131 ± 45 pA at 200 µg/mL) and its purified glycosyloxyflavone narcissoside (401 ± 271 pA at 100 µM). Serial treatment with a 200 µg/mL PN extract in TRPV1-overexpressing HEK293T cells induced robust desensitization to 10 ± 10% of the initial current amplitude. Thus, we propose that the PN extract and narcissoside function as TRPV1 agonists. This new finding may advance our knowledge regarding the traditional and scientific functions of PN in human health and disease.

Diterpenoids and phenolic analogues from the roots of Aralia continentalis.

Two new compounds, including a nor-pimarane diterpenoid (continentanol, 1) and a phenolic derivative (aralianic acid, 2), along with the known diterpenoids (3-11), polyacetylenes (12-15), phenolic components (16-28), and phytosterols (29 and 30), were isolated from roots of Aralia continentalis. The structures of the new compounds were established by spectroscopic data interpretation, particularly HRESIMS, 1 D and 2 D NMR data including HSQC and HMBC. Also, those of the known compounds were identified by spectral comparison with those of the reported values.[Formula: see text].

A novel role for α-viniferin in suppressing angiogenesis by blocking the VEGFR-2/p70S6K signaling pathway.

Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases.

Combretum quadrangulare Extract Attenuates Atopic Dermatitis-Like Skin Lesions through Modulation of MAPK Signaling in BALB/c Mice.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare (C. quadrangulare) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Coixlachryside B: a new benzoxazinoid glycoside from the roots of Coix lachryma-jobi var. ma-yuen (Gramineae).

Coix lachryma-jobi L. var. ma-yuen has been a source of food and traditional folk medicine in some parts of Asia for thousands of years; however, the roots of this plant have not been phytochemically investigated. Herein, we report the isolation of a new benzoxazinoid glycoside, coixlachryside B (1), along with ten known compounds (2-11), from the roots of C. lachryma-jobi var. ma-yuen using a variety of chromatographic methods. Among the known compounds, the absolute configuration of compound 4 was determined. The structures of all compounds were elucidated by interpreting NMR spectroscopic data, and experimental and calculated electronic circular dichroism spectra.

Anti-Obesity Activity of Saringosterol Isolated from Sargassum muticum (Yendo) Fensholt Extract in 3T3-L1 Cells.

Saringosterol, a steroid isolated from Sargassum muticum, a brown edible alga widely distributed on the seashores of southern and eastern Korea, has been shown to exhibit anti-obesity effect. In this study, we investigated the anti-obesity activity of saringosterol through various experiments. The inhibitory effect of saringosterol on adipogenesis was evaluated via Oil Red O staining in 3T3-L1 preadipocytes. After confirming that saringosterol is not cytotoxic to these cells by using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, the effect of saringosterol on the expression of various adipogenesis-related genes was analyzed via quantitative real-time polymerase chain reaction and western blotting. We demonstrated that saringosterol dose dependently inhibited adipocyte differentiation and expression of adipogenic marker genes such as adipocyte fatty acid-binding protein, adiponectin, resistin, and fatty acid synthase in 3T3-L1 cells. In addition, saringosterol significantly inhibited the mRNA and protein expression of peroxisome proliferator-activated receptor γ and CCAAT enhancer-binding protein α in 3T3-L1 cells. Collectively, these findings indicate that saringosterol isolated from S. muticum exhibits anti-obesity effect by inhibiting the expression of adipogenic transcription factors and marker genes and that it may be developed as a drug to suppress adipogenesis. Copyright © 2017 John Wiley & Sons, Ltd.

Anti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages.

Tribulus terrestris (T. terrestris) has been used as a traditional medicine for the treatment of a variety of diseases, including inflammation, edema and hypertension. The aqueous and ethanol extracts of T. terrestris contain alkaloids, flavonoids, tannins, quinines and phenolic compounds. Tribulusamide D is a compound that has been isolated from the ethanol extract of T. terrestris. The present study investigated the anti­inflammatory effect of tribulusamide D on lipopolysaccharide (LPS)­stimulated RAW 264.7 macrophages. Tribulusamide D inhibited the production of LPS­induced nitric oxide and prostaglandin E2, by reducing the expression of inducible nitric oxide synthase and cyclooxygenase­2 expression, respectively. The expression of these genes associated with inflammation was determined using reverse transcription­polymerase chain reaction and western blot analysis. Furthermore, tribulusamide D reduced the expression of LPS­induced inflammatory cytokines, including interleukin (IL)­6, IL­10 and tumor necrosis factor­α. They were quantified using an enzyme­linked immunosorbent assay. In addition, the present study confirmed that the inhibitory effects of tribulusamide D on the inflammatory response were mediated through inactivation of mitogen­activated protein kinase p38 and inhibition of nuclear localization of nuclear factor­B, which were also determined by western blot analysis. To the best of our knowledge, the current study is the first to demonstrate that tribulusamide D exerts anti­inflammatory activity by altering the expression of inflammatory mediators and cytokines, indicating that tribulusamide D could be developed as a potential therapeutic agent for the treatment of inflammatory disorders.

Salvia plebeia Extract Inhibits Xanthine Oxidase Activity In Vitro and Reduces Serum Uric Acid in an Animal Model of Hyperuricemia.

Hyperuricemia is a clinical condition characterized by an elevated level of serum uric acid and is a key risk factor for the development of gout and metabolic disorders. The existing urate-lowering therapies are often impractical for certain patient populations, providing a rationale to explore new agents with improved safety and efficacy. Here, we discovered that Salvia plebeia extract inhibited the enzyme activity of xanthine oxidase, which is a key enzyme generating uric acid in the liver. In an animal model of hyperuricemia, S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of S. plebeia extract in vivo was supported by the identification of compounds that inhibit xanthine oxidase enzyme activity in vitro. Nepetin, scutellarein, and luteolin contributed significantly to S. plebeia bioactivity in vitro. These compounds showed the highest potency against xanthine oxidase with IC50 values of 2.35, 1.74, and 1.90 µM, respectively, and were present at moderate quantities. These observations serve as a basis for further elaboration of the S. plebeia extracts for the development of new therapeutics for hyperuricemia and related diseases.

Ulmus davidiana Nakai induces apoptosis and autophagy on non-small cell lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus davidiana Nakai (UDN) is frequently used in the treatment of cancer in traditional oriental medicine. Although several reports indicate that UDN has inhibitory effects in some cancers, there has been no report on the inhibitory effects of UDN via both autophagy and apoptosis. MATERIALS AND METHODS: Cytotoxicity induced by UDN in human non-small cell lung cancer (NSCLC) H-1299 and H-460 cell lines was evaluated using the 2, 3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay and trypan blue exclusion assay. Induction of apoptosis was also investigated using Hoechst staining and annexin-V binding assay and was confirmed with western blot analysis. Induction of autophagy was investigated through observation of autophagy vacuoles under inverted phase-contrast microscopy and was confirmed by observing the formation of autophagy vacuoles under a fluorescence microscope using monodansylcadaverine (MDC) staining and western blot analysis. The in vivo anti-tumorigenic effect of UDN was investigated in an athymic nude mouse xenograft model using H-1299 NSCLC cells. RESULTS: UDN exhibited a marked inhibitory effect on cell growth in H-1299 and H-460 human NSCLC cell lines in a dose- and time-dependent manner in vitro and in vivo. It induced not only apoptosis, but also autophagy in both H-1299 and H-460 cells in a dose-dependent manner. UDN-mediated autophagy led to the accumulation of autophagosome, resulting in apoptosis induction and cell death. CONCLUSIONS: From our current knowledge, we are the first to demonstrate that UDN has the potential to induce both autophagy and apoptosis in H-1299 and H-460 human NSCLC cell lines. We suggest that UDN can be considered a potential candidate for lung cancer-specific chemotherapy with efficacy as a cytotoxic agent.

Caragasinin C: a new oligostilbene from the roots of Caragana sinica.

A new oligostilbene, caragasinin C (1), and seven known compounds, betulinic acid (2), 4-hydroxybenzaldehyde (3), (‒)-medicarpin (4), wistin (5), (2E,4S)-4-hydroxy-2-nonenoic acid (6), pallidol (7), and (+)-α-viniferin (8), were isolated from the roots of Caragana sinica. The structure of caragasinin C was established on the basis of spectroscopic techniques, including HRESIMS, 1D and 2D-NMR.

Quassinoids isolated from Brucea javanica inhibit pepper mottle virus in pepper.

A green fluorescent protein (GFP)-tagged pepper mottle virus (PepMoV) based leaf-disc method and systemic host method were developed to identify antiviral agents. Preliminary experiments using a PepMoV-GFP based leaf-disc method led to the isolation of five quassinoids, including brusatol (1), bruceantin (2), brucein A (3), bruceantinol (4), and brucein B (5), from the CH3OH extract of Brucea javanica. All isolated compounds exhibited inactivation effects in systemic host plants, and compounds 3 and 4 were potent, with a minimum inhibitory concentration of 10µM. Furthermore, compound 3 was found to have a protective effect at the tested concentration of 40µM.

Antiinflammatory Effects of Functionally Active Compounds Isolated from Aged Black Garlic.

The antiinflammatory effects of functionally active compounds isolated from aged black garlic (AGE-1 and AGE-2) were investigated using a lipopolysaccharide-induced inflammatory response model. To examine the potential antiinflammatory properties of AGE-1 and AGE-2, cell viability as well as nitric oxide, prostaglandin E2, and pro-inflammatory cytokine [interleukin-6 (IL-6), TNF-α, and IL-1ß] levels were measured. The mRNA and protein expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were detected by reverse transcription polymerase chain reaction and western blotting. The results indicated that AGE-1 and AGE-2 were not cytotoxic to macrophages. Nitric oxide and prostaglandin E2 levels decreased significantly with increasing concentration of AGE-1 (IC50 = 29.6 and 1.41 µg/mL, respectively), but not AGE-2. The secretion of IL-6, TNF-α, and IL-1ß was also suppressed by AGE-1 in a dose-dependent manner, and inducible nitric oxide synthase and cyclooxygenase-2 mRNA, and protein expression decreased with AGE-1 treatment. Furthermore, AGE-1 attenuated the phosphorylation of the extracellular signal-regulated kinase, p38, and c-Jun terminal kinase in lipopolysaccharide-induced RAW264.7 cells. These results suggested that compound AGE-1 may have significant effects on inflammatory factors and could potentially be used as an antiinflammatory therapeutic agent. Copyright © 2016 John Wiley & Sons, Ltd.

A New Neolignan from Coix lachryma-jobi var. mayuen.

A new neolignan, named coixide A (1), along with fifteen known compounds, (7R,8S)-3'-demethyl-dehydrodiconiferyl alcohol-3'-O-ß-glucopyranoside (2), (7R,8)-3'-demethyl-9'-butoxy-dehydrodiconiferyl-3'-O-ß-glucopyranoside (3),adenosine (4), 2-O-caffeoyl isocitricacid (5), pseudolaroside A (6), 2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (7), 2-O-ß-glucopyranosyl-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (8), 2-O-ß-glucopyranosyl-4-hydroxy-7- methoxy-2H-1,4-benzoxazin-3(4H)-one (9), 2-O-ß-D-glucopyranosyl-7-hydroxy-2H-1,4-benzoxazin-3(4H)-one (10), p-coumaric acid ethyl ester (11), caffeic acid ethyl ester (12), p-coumaric acid (13), cis-N-p-coumaroyltyramine (14) trans-N-p-coumaroyltyramine (15), and coixol (16) have been isolated from Coix lachryma-jobi var. mayuen. Their chemical structures were elucidated by chemical evidence on the basis of spectroscopic and MS data, and as well as by comparison with those reported.

2,8-Decadiene-1,10-Diol Inhibits Lipopolysaccharide-Induced Inflammatory Responses Through Inactivation of Mitogen-Activated Protein Kinase and Nuclear Factor-κB Signaling Pathway.

Amomum tsao-ko (A. tsao-ko) has been used as a traditional medicine for the treatment of infectious and digestive disorders. In the present study, we report the anti-inflammatory activity and molecular mechanism of 2,8-decadiene-1,10-diol (DDO) isolated from the extract of A. tsao-ko in lipopolysaccharide-stimulated RAW 264.7 cells. DDO treatment inhibited the production of nitric oxide and prostaglandin E2 by downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression, respectively. Moreover, DDO suppressed the production of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. These inhibitory effects of DDO on the expression of inflammatory proteins were found to be mediated through the inactivation of mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase, c-Jun-N-terminal kinase and p38(MAPK), and inhibition of nuclear factor-κB (NF-κB) pathways including degradation of inhibitor of κB-α and nuclear localization of NF-κB. Taken together, these findings demonstrate the pharmacological roles and molecular mechanisms of DDO in regulating inflammatory responses, and suggest further evaluation and development of DDO as a potent therapeutic agent for the treatment of inflammatory disorders.

Neolignan inhibitors of antigen-induced degranulation in RBL-2H3 cells from the needles of Pinus thunbergii.

The ethanolic extract of the needles of Pinus thunbergii was found to suppress antigen mediated degranulation of rat basophilic leukemia (RBL-2H3) cells. A new neolignan glycoside, named pinusthunbergiside A (1), as well as six known neolignan glycosides (2-7) were isolated from the ethanolic extract using bioassay-guided fractionation. Their structures were elucidated by a combination of 1D and 2D NMR, HRESI-MS, and circular dichroism (CD) data. Compounds 2-7 were found for the first time in this plant. The inhibitory effects of isolated constituents on the release of ß-hexosaminidase from RBL-2H3 cells were examined, and compounds 2, 3, 5, and 6 were found to show the inhibitory activity with IC50 values ranging between 52.3 and 75.3 µM.

Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-κB and p38 MAPK signaling pathways.

Microglial cells are the resident macrophages and intrinsic arm of the central nervous system innate immune defense. Microglial cells become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Therefore, regulating microglial activation may have therapeutic benefits that lead to alleviating the progression of inflammatory-mediated neurodegeneration. In the present study, we investigated the effect of glaucocalyxin A (GLA) isolated from Rabdosia japonica on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated primary microglia and BV-2 cells. GLA significantly inhibited LPS-induced production of nitric oxide and reversed the morphological changes in primary microglia. Further, GLA suppressed expression of inducible nitric oxide synthase and cyclooxygenase-2 dose-dependently at the mRNA and protein levels. The production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1ß (IL)-1ß, and IL-6 were inhibited by suppressing their transcriptional activity. Furthermore, GLA suppressed nuclear factor-κB activation by blocking degradation of IκB-α and inhibited the induction of lipocalin-2 expression in LPS-stimulated BV-2 cells. Mechanistic study revealed that the inhibitory effects of GLA were accompanied by blocking the p38 mitogen activated protein kinase signaling pathway in activated microglia. In conclusion, given that microglial activation contributes to the pathogenesis of neurodegenerative diseases, GLA could be developed as a potential therapeutic agent for treating microglia-mediated neuroinflammatory diseases.