Discovery of 23,24-diols containing ergosterols with anti-neuroinflammatory activity from Penicillium citrinum TJ507.

Citristerones A-E (1-5), five new 23,24-diols containing ergosterols, along with three known analogues, were isolated from the endophytic fungus Penicillium citrinum TJ507 obtained from Hypericum wilsonii N. Robson. Their structures and absolute configurations were determined by NMR, HRESIMS, Snatzke's method, X-ray diffraction analyses and ECD calculation. Subsequently, the anti-neuroinflammatory effects of these isolates were screened using lipopolysaccharide (LPS)-induced BV-2 microglial cells, and citristerone B (2) showed outstanding anti-neuroinflammatory activity, with IC50 value of 0.60 ± 0.04 µM. Moreover, immunofluorescence and western blot analysis suggested that citristerone B not only reduced the release of nitric oxide (NO) and proinflammatory cytokines in LPS-induced BV-2 microglial cells, but also significantly inhibited the expression of TNF-α, iNOS and NF-κB, along with the production of cellular ROS.

Methanolic Extract and Brominated Compound from the Brazilian Marine Sponge Aplysina fulva Are Neuroprotective and Modulate Inflammatory Profile of Microglia.

Neurodegenerative diseases involve neuroinflammation and a loss of neurons, leading to disability and death. Hence, the research into new therapies has been focused on the modulation of the inflammatory response mainly by microglia/macrophages. The extracts and metabolites of marine sponges have been presented as anti-inflammatory. This study evaluated the toxicity of an extract and purified compound from the Brazilian marine sponge Aplysina fulva as well as its neuroprotection against inflammatory damage associated with the modulation of microglia response. PC12 neuronal cells and neonatal rat microglia were treated with the methanolic extract of A. fulva (AF-MeOH, 0.1-200 µg/mL) or with its purified dimethyl ketal of 3,5-dibromoverongiaquinol (AF-H1, 0.1-100 µM). Cytotoxicity was determined by MTT tetrazolium, Trypan blue, and propidium iodide; microglia were also treated with the conditioned medium (CM) from PC12 cells in different conditions. The microglia phenotype was determined by the expression of Iba-1 and CD68. AF-MeOH and AF-H1 were not toxic to PC12 or the microglia. Inflammatory damage with Escherichia coli lipopolysaccharide (LPS, 5 µg/mL) was not observed in the PC12 cells treated with AF-MeOH (1-10 µg/mL) or AF-H1 (1-10 µM). Microglia subjected to the CM from PC12 cells treated with LPS and AF-MeOH or AF-H1 showed the control phenotype-like (multipolar, low-CD68), highlighting the anti-neuroinflammatory and neuroprotective effect of components of this marine sponge.

Anti-neuroinflammatory andrastin-type meroterpenoids from the marine-derived fungus Penicillium chrysogenum HNNU w0032.

A new andrastin-type meroterpenoid penimerodione A (1), and three known analogues (2-4), were isolated from the culture of a marine-derived fungus Penicillium chrysogenum HNNU w0032 by the guidance of MS/MS-based molecular networking. The planar structure of 1 was established by extensive NMR spectroscopic and HRESIMS analyses, and the absolute configuration was elucidated by a single-crystal X-ray diffraction. Compound 1 showed significant inhibitory effect on NO production in LPS-stimulated BV-2 macrophages with an IC50 value of 5.9 ± 0.3 µM. The Western blot result revealed that compound 1 exerted an anti-neuroinflammatory effect via the MAPK signalling pathway.

Bioactive Alkaloids from the Mangrove-Derived Fungus Nigrospora oryzae SYSU-MS0024.

Chemical investigation of marine fungus Nigrospora oryzae SYSU-MS0024 cultured on solid-rice medium led to the isolation of three new alkaloids, including a pair of epimers, nigrosporines A (1) and B (2), and a pair of enantiomers, (+)-nigrosporine C (+)-3, and (-)-nigrosporine C (-)-3, together with eight known compounds (4-11). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses and compared with data in the literature. The absolute configurations of compounds 1-3 were determined by a combination of electronic circular dichroism (ECD) calculations, Mosher's method, and X-ray single-crystal diffraction technique using Cu Kα radiation. In bioassays, compound 2 exhibited moderate inhibition on NO accumulation induced by lipopolysaccharide (LPS) on BV-2 cells in a dose-dependent manner at 20, 50, and 100 µmol/L and without cytotoxicity in a concentration of 100.0 µmol/L. Moreover, compound 2 also showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values of 103.7 µmol/L. Compound 5 exhibited moderate antioxidant activity with EC50 values of 167.0 µmol/L.

Ent-eudesmane sesquiterpenoids with anti-neuroinflammatory activity from the marine-derived fungus Eutypella sp. F0219.

In this study, twenty-three ent-eudesmane sesquiterpenoids (1-23) including fifteen previously undescribed ones, named eutypelides A-O (1-15) were isolated from the marine-derived fungus Eutypella sp. F0219. Their planar structures and relative configurations were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of the previously undescribed compounds were determined by single-crystal X-ray diffraction analyses, modified Mosher's method, and ECD calculations. Structurally, eutypelide A (1) is a rare 1,10-seco-ent-eudesmane, whereas 2-15 are typically ent-eudesmanes with 6/6/-fused bicyclic carbon nucleus. The anti-neuroinflammatory activity of all isolated compounds (1-23) was accessed based on their ability to NO production in LPS-stimulated BV2 microglia cells. Compound 16 emerged as the most potent inhibitor. Further mechanistic investigation revealed that compound 16 modulated the inflammatory response by decreasing the protein levels of iNOS and increasing ARG 1 levels, thereby altering the iNOS/ARG 1 ratio and inhibiting macrophage polarization. qRT-PCR analysis showed that compound 16 reversed the LPS-induced upregulation of pro-inflammatory cytokines, including iNOS, TNF-α, IL-6, and IL-1ß, at both the transcriptional and translational levels. These effects were linked to the inhibition of the NF-κB pathway, a key regulator of inflammation. Our findings suggest that compound 16 may be a potential structure basis for developing neuroinflammation-related disease therapeutic agents.

Abietane-Type Diterpenoids from the Arils of Torreya grandis.

A chemical investigation of the arils of Torreya grandis led to the isolation of seven abietane-type diterpenoids (compounds 1-7) including three previously undescribed compounds, one unreported natural product, and three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds 5 and 6 had significant inhibitory effects on methicillin-resistant Staphylococcus aureus, with MIC values of 100 µM. Moreover, compounds 1, 3, 4, and 7 exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC50 values ranging from 38.4 to 67.9 µM.

Structural identification and anti-neuroinflammatory effects of a pectin-arabinoglucuronogalactan complex, AOPB-1-1, isolated from Asparagus officinalis.

Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-ß-D-Galp-(1→ and →4)-ß-D-Glcp-(1→ residues substituted at the 4-position to the →4)-α-D-GalAp-(1→ residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2 (COX2), nitric oxide synthase (iNOS), TNF-α, IL-6, and interleukin-1ß (IL-1ß) in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.

Natural anti-neuroinflammatory inhibitors in vitro and in vivo from Aglaia odorata.

Fifty compounds including seven undescribed (1, 13, 18-20, 30, 31) and forty-three known (2-12, 14-17, 21-29, 32-50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13-25 were found to possess tertiary amide bonds, with compounds 16, 17, and 19-21 existing detectable cis/trans mixtures in 1H NMR spectrum measured in CDCl3. Specifically, the analysis of the cis-trans isomerization equilibrium of tertiary amides in compounds 19-24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[b]benzofuran derivatives (2-6, 8, 10, 12) could inhibit nitric oxide production at the nanomolar concentration (IC50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413-20670 times greater than that of the positive drug (minocycline, IC50 = 41.34 µM). The cyclopenta[bc]benzopyran derivatives (13-16), diterpenoids (30-35), lignan (40), and flavonoids (45, 47, 49, 50) also demonstrated significant inhibitory activities with IC50 values ranging from 1.74 to 38.44 µM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF-α, IL-1ß, and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response.

Four New Polyprenylated Acylphloroglucinols from Hypericum perforatum L.

Hyperforatums A-D (1-4), four new polyprenylated acylphloroglucinols, together with 13 known compounds were isolated and identified from the aerial parts of Hypericum perforatum L. (St. John's wort). Their structures were confirmed with a comprehensive analysis comprising spectroscopic methods, including 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) calculations. Hyperforatum A featured an unusual chromene-1,4-dione bicyclic system, and hyperforatums B and C were two rare monocyclic PPAPs with five-membered furanone cores. Compound 1 exhibited a moderate inhibition effect on NO production in BV-2 microglial cells stimulated by LPS.

Structural identification and anti-neuroinflammatory effect of a heteropolysaccharide ATP50-3 from Acorus tatarinowii rhizome.

Acorus tatarinowii, a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF-α, IL-1ß, PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50-3 was obtained from AT50. Structural analysis indicated ATP50-3 consisted of α-L-Araf-(1→, →2)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, α-D-Xylp-(1→, →3,4)-ß-D-Xylp-(1→, →3)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-4-OAc-α-D-Galp-(1→, →3,4,6)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2,3,6)-ß-D-Glcp-(1→, →4,6)-α-D-Manp-(1→, →3,4)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →4)-α-D-GlcpA-(1 â†’ residues and terminated with Xyl and Ara. Additionally, ATP50-3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50-3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.

Chemical constituents from Notopterygium incisum and their anti-neuroinflammatory activity.

Phytochemical research on an extract of Notopterygium incisum yielded fifteen compounds (1-15), including four previously undescribed compounds (10-13). The structures of the unreported compounds were elucidated by spectroscopic and spectrometric data analysis such as 1D and 2D NMR, IR and HR-ESI-MS. Compounds 1-5 and 10-14 were isolated from N. incisum for the first time. 7S⁎,8R⁎-Phenethyl-(7-methoxy-8-isoeugenol)-ferulate (10), 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) are the undescribed ferulic acid derivatives. Additionly, the anti-neuroinflammatory effects of compounds were evaluated in lipopolysaccharide (LPS)-induced BV2 cells. The pharmacological results showed that 6ß,10ß-epoxy-4α-hydroxy-guaiane (6), teuclatriol (7) and 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) inhibited the production and expression of nitric oxide (NO) in the LPS-induced BV2 cells in a concentration-dependent manner. Acorusnol (4), teucladiol (9), 7S⁎,8R⁎-benzyl-(7-methoxy-8-isoeugenol)-ferulate (12) and p-hydroxyphenethyl-(4-benzoy-3-methoxy)-cinnamate (13) only inhibited the release of NO at concentration of 20 µM. Moreover, 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) reduced the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-stimulated BV2 cells. The results demonstrated 7S⁎,8R⁎-p-hydroxyphenethyl-(7-methoxy-8-isoeugenol)-ferulate (11) could be a potential anti-neuroinflammatory agent and is worthy of further study.

Molecular Docking, Synthesis, and Characterization of Furanyl-Pyrazolyl Acetamide and 2,4-Thiazolidinyl-Furan-3-Carboxamide Derivatives as Neuroinflammatory Protective Agents.

Microglia are key immune cells in the brain that maintain homeostasis and defend against immune threats. Targeting the dysfunctional microglia is one of the most promising approaches to inhibit neuroinflammation. In the current study, a diverse series of molecular hybrids were designed and screened through molecular docking against two neuroinflammatory targets, namely HMGB1 (2LY4) and HMGB1 Box A (4QR9) proteins. Based on the outcomes of docking scores fifteen compounds; ten furanyl-pyrazolyl acetamides 11(a-j), and five 2,4-thiazolidinyl-furan-3-carboxamide 15(a-e) derivatives were selected for further synthesis, followed by biological evaluation. The selected compounds, 11(a-j) and 15(a-e) were successfully synthesized with moderate to good yields, and structures were confirmed by IR, NMR, and mass spectra. The in-vitro cytotoxicity was evaluated on microglial cells namely BV-2, N-9, HMO6, leukemic HAP1, and human fibroblast cells. Further western-blot analysis revealed that 11h, 11f, 11c, 11j, 15d, 15c, 15e, and 15b compounds significantly suppressed anti-inflammatory markers such as TNF-α, IL-1, IL-6, and Bcl-2. All derivatives were moderate in potency compared to reference doxorubicin and could potentially act as novel anti-neuroinflammatory agents. This study can act as a beacon for further research in the application of furan-pyrazole and furan-2,4-thiazolidinediones as lead moieties for anti-neuroinflammatory and related diseases.

Structural characterization of a galactoglucomannan with anti-neuroinflammatory activity from Ganoderma lucidum.

According to traditional Chinese medicine theory, Ganoderma lucidum (G. lucidum) presents certain effects for nourishing nerves and calming the mind. G. lucidum polysaccharides (GLPs) have various biological activities; however, the structural characterization and the structure-activity relationship in anti-neuroinflammation of GLPs needs to be further investigated. In this work, the crude polysaccharide GL70 exhibited a remarkable impact on enhancing the spatial learning and memory function, as well as reducing the anxiety symptoms of the lipopolysaccharide (LPS)-induced rat model of Alzheimer's disease (AD). A galactoglucomannan (GLP70-1-2) was isolated from GL70, and characterized by monosaccharide composition, partial acid hydrolysis, methylation, and NMR analysis. The backbone of GLP70-1-2 was →6)-α-D-glcp-(1 â†’ 6)-ß-D-galp-(1 â†’ [6)-ß-D-manp-(1]3 â†’ 4)-α-D-Glcp-(1 â†’ 6)-α-D-glcp-(1 â†’ 2)-ß-D-galp-(1 â†’ [4)-α-D-glcp-(1 â†’ 6)-ß-D-manp-(1 â†’ 2)-ß-D-galp-(1]2 â†’ 6)-ß-D-glcp-(1 â†’ 6)-ß-D-glcp-(1→ with two side chains attached to O-4 of →6)-ß-D-galp-(1→ and O-3 of →6)-ß-D-glcp-(1→, respectively. In addition, GLP70-1-2 exhibited remarkable efficacy in decreasing the level of pro-inflammatory factors in LPS-activated BV2 cells through the TLR4/MyD88/NF-κB pathway. Collectively, GLP70-1-2 exhibited significant anti-neuroinflammatory activity and may have the potential for developing as a drug for AD.

Meroterpenes and prenylated benzoylphloroglucinol from the flowers of Hypericum formosanum.

Formohyperins A-F, previously undescribed meroterpenes, and grandone, a prenylated benzoylphloroglucinol being considered to be one of their biogenetic precursors, were isolated from the flowers of a Hypericaceous plant, Hypericum formosanum Maxim. Detailed spectroscopic analyses showed that formohyperins A-D were meroterpenes with an enolized 3-phenylpropane-1,3-dione moiety. Formohyperins E and F were elucidated as meroterpenes having a 4-benzoyl-5-hydroxycyclopent-4-ene-1,3-dione moiety. Formohyperins A-C and E were optically active, and their absolute configurations were deduced by comparison of the experimental and TDDFT calculated ECD spectra. In contrast, formohyperin D was concluded to be a racemate. Formohyperins A-F and grandone were found to show inhibitory activities against LPS-stimulated IL-1ß production from murine microglial cells with EC50 values of 13.2, 6.6, 8.5, 24.3, 4.1, 10.9, and 3.0 µM, respectively.

The basic chemical substances of total alkaloids of Uncaria rhynchophylla and their anti-neuroinflammatory activities.

To clarify the chemical basis of the total alkaloids of Uncaria rhynchophylla, HPLC-VWD chromatogram of total alkaloids was established. Under its guidance, modern chromatographic and spectroscopic techniques were used to track, isolate and identify the representative principal components. As a result, one new monoterpenoid indole alkaloid, 3S,15S-N4-methoxymethyl-geissoschizine methyl ether (1), together with 20 known alkaloids (2-21), and 5 other known compounds (22-26) were obtained. Meanwhile, sixteen characteristic peaks were identified from the total alkaloids using HPLC analysis. Then, the anti-neuroinflammatory effect of compounds 1-21 was assessed through inhibiting nitric ---oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Among them, compounds 1, 3, 7, 8, 11, 12, 19 and 21 showed potent inhibitory activities with IC50 values of 5.87-76.78 µM.

Unlocking Quercetin's Neuroprotective Potential: A Focus on Bee-Collected Pollen.

In the quest to evade side effects associated with synthetic drugs, mankind is continually exploring natural sources. In recent decades, neurodegenerative disorders (NDDs) have surged dramatically compared to other human diseases. Flavonoids, naturally occurring compounds, have emerged as potential preventers of NDD development. Notably, quercetin and its derivatives demonstrated excellent antioxidant properties in the fight against NDDs. Recognizing bee-collected pollen (BP) as a well-established excellent source of quercetin and its derivatives, this review seeks to consolidate available data on the prevalence of this flavonoid in BP, contingent upon its botanical and geographical origins. It aims to advocate for BP as a superb natural source of "drugs" that could serve as preventative measures against NDDs. Examination of numerous published articles, detailing the phenolic profile of BP, suggests that it can be a great source of quercetin, with an average range of up to 1000 mg/kg. In addition to quercetin, 24 derivatives (with rutin being the most predominant) have been identified. Theoretical calculations, based on the recommended dietary intake for quercetin, indicate that BP can fulfil from 0.1 to over 100 % of the requirement, depending on BP's origin and bioaccessibility/bioavailability during digestion.

Sesquiterpenes from Wikstroemia lungtzeensis with anti-neuroinflammatory effects.

An anti-neuroinflammatory activities-guided phytochemical research of Wikstroemia lungtzeensis was performed for the first time. Three undescribed carotane-type sesquiterpenes, excoecafolinols C-E (1-3), and nine known sesquiterpene derivatives were isolated from the effective ethyl acetate extract of W. lungtzeensis. Their structures were determined based on multiple spectroscopic techniques and electronic circular dichroism (ECD) spectra. Furthermore, the anti-neuroinflammatory activities of the identified compounds were evaluated in lipopolysaccharide-stimulated BV-2 cells. Among them, six components (1, 2, 4, 7, 11, 12) exhibited significant inhibitory effects on nitric oxide (NO) production, with IC50 values ranging from 10.48 to 49.41 µM (positive control minocycline, IC50 53.20 µM). Carotane-type sesquiterpenes (1, 2, 4) with high content and significant inhibitory effects, are considered to be major active ingredients of W. lungtzeensis, which might serve as potential therapeutic agents for neurodegenerative diseases.

Hysterolides A-I, dimeric or monomeric sesquiterpene lactones from Parthenium hysterophorus L.

Nine undescribed sesquiterpene lactones, including two pseudoguaianolide dimers (1 and 2), a pseudoguaiac dilactone (3), and six pseudoguaianolides (4-9), along with 13 known analogues (10-22) were isolated from Parthenium hysterophorus. Among them, hysterolide A (1) possesses an unusual carbon skeleton with a unique cyclobutane ring connecting two pseudoguaianolides. Hysterolide C (3) is a sesquiterpene dilactone incorporating a bicyclo[5.1.0]octane core. Spectroscopic analyses, 13C NMR and ECD calculations, and X-ray diffraction elucidated their structures and absolute configurations. Moreover, all the isolates were assayed for their anti-inflammatory activities by inhibiting LPS-induced nitric oxide production in BV-2 microglia cells, wherein, nine compounds displayed significant inhibitory activities with IC50 of 0.52-6.32 µM. Furthermore, the preliminary structure-activity relationship was also established.

Dihydrophenanthro[b]furan derivatives from the tubers of Bletilla striata.

Two pairs of new dihydrophenanthro[b]furan enantiomers blephebibnols G-H (1-2), one new dihydrophenanthro[b]furan derivative blephebibnol I (3), along with four known analogues (4-7), were isolated from the tubers of Bletilla striata. Their structures including the absolute configurations were determined by the combination of spectroscopic data analysis, ECD and NMR calculations. Compounds 1a, 1b, and 2b showed inhibition of NO production in LPS-stimulated BV-2 cells, with IC50 values ranging from 4.11 to 14.65 µM. Further mechanistic study revealed that 1a suppressed the phosphorylation of p65 subunit to regulate the NF-κB signaling pathway. In addition, some compounds displayed selective cytotoxic activities against HCT-116, HepG2, A549, or HGC27 cancer cell lines with IC50 values ranging from 0.1 to 8.23 µM.

Anti-biofilm and anti-inflammatory active diterpene isolated from the fruit of Xylopia benthamii R.E.Fr.

Xylopia benthamii (Annonaceae) is a plant with limited phytochemical and pharmacological evidence. Thus, using LC-MS/MS, we performed exploratory analyses of the fruit extract of X. benthamii, resulting in the tentative identification of alkaloids (1-7) and diterpenes (8-13). Through the application of chromatography techniques with the extract of X. benthamii, two kaurane diterpenes were isolated, xylopinic acid (9) and ent-15-oxo-kaur-16-en-19-oic acid (11). Their structures were established using spectroscopy (NMR 1D/2D) and mass spectrometry. The isolated compounds were submitted to anti-biofilm analysis against Acinetobacter baumannii, anti-neuroinflammatory and cytotoxic activity in BV-2 cells. Compound 11 (201.75 µM) inhibited 35% of bacterial biofilm formation and high anti-inflammatory activity in BV-2 (IC50 = 0.78 µM). In conclusion, the results demonstrated that compound 11 was characterized for the first time with pharmacological potential in the development of new alternatives for studies with neuroinflammatory diseases.