Anti-inflammatory Activity Of Compounds Research Articles

A new alkaloid and two organic acids from Portulaca oleracea L. and their bioactivities

A new alkaloid, identified as 1-benzyl-2-nitroso-1,2,3,4-tetrahydroisoquinoline-6,7-diol, named oleraisoquinoline (1), and five organic acids and two esters, identified as 5-(hydroxymethyl)furan-2-carboxylic acid (2), 1H-pyrrole-2,5-dicarboxylic acid (3), (7E,10E)-octadeca-7,10-dienoic acid (4), (10E,13E)-octadeca-10,13-dienoic acid (5), (7E,10E)-hexadeca-7,10-dienoic acid (6), methyl tridecanoate (7) and methyl (9E,12E)-octadeca-9,12-dienoate (8), were isolated from Portulaca oleracea L., among which compounds 2 and 4‒7 were isolated for the first time. Moreover, the anti-inflammatory activities of compounds 1‒3 were studied, especially, compound 1 presented good inhibitory effects on the production of inflammatory factors IL-1β and TNF-α.

Total Syntheses and Anti-inflammatory Evaluations of Pongamosides A-C, Natural Furanoflavonoid Glucosides from Fruit of Pongamia pinnata (L.) Pierre.

The syntheses of three natural furanoflavonoid glucosides, including two flavone glucosides, pongamosides A (1) and B (2), and a flavonol glucoside, pongamoside C (3), were achieved for the first time in 9-15 steps from commercially available materials in overall yields ranging from 2.9% to 29%. The synthetic sequence featured a NaH-promoted BK-VK rearrangement and acid-catalyzed intramolecular cyclization to furnish the furanoflavonoid aglycone. Meanwhile, phase-transfer-catalyzed glycosylation and Schmidt's trichloroacetimidate procedure were employed to establish the pivotal O-glycosidic linkage. The anti-inflammatory activities of compounds 1-3, as well as their aglycones 5a, 5b, and 23, were determined against NO production in the LPS-stimulated RAW264.7 cells. The results indicated that the O-glycosylation may reduce the anti-inflammatory activity of furanoflavonoid in vitro.

A Review of the Biological Activities of Heterocyclic Compounds Comprising Oxadiazole Moieties.

The oxadiazole core is considered a privileged moiety in many medicinal chemistry applications. The oxadiazole class includes 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, and 1,2,5-oxadiazole. Compounds bearing an oxadiazole ring show a wide range of biological activities, such as anticancer, antibacterial, anti-inflammatory, anti-malarial, and insecticidal properties. Among oxadiazoles, the 1,3,4-oxadiazole has been the most widely explored moiety in medicinal chemistry research. This review is primarily focused on the anticancer, antibacterial, and anti-inflammatory activities of compounds containing 1,2,4-oxadiazole, 1,3,4-oxadiazole and 1,2,5-oxadiazole reported in the last five years.

Total Synthesis and Anti-Inflammatory Activity of Velutone F

Velutone F (1), a natural bioactive chalcone isolated from Millettia velutina Dunn, possesses significant anti-inflammatory activity. In this study, we have accomplished the total synthesis of velutone F (1), along with its analogues 2 and 3, from a common starting material cyclohexandione in 5 to 7 steps. The anti-inflammatory activities of compounds 1 to 3 were determined against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and all of them exhibited different levels of anti-inflammatory activity.

Two Alkaloids From Delphinium brunonianum Royle, Their Anti-inflammatory and Anti-oxidative Stress Activity via NF-κB Signaling Pathway.

In this study, we isolated and identified four compounds in Delphinium brunonianum Royle, and they were Delbrunine (1), 4-O-α-D-Glucosyl benzoic acid (2), Kaempferol 3-O-β-D-glucopyranoside 7-O-α-L-rhamnopyranoside (3) and Eldeline (4). Furthermore, the anti-inflammatory activity of these compounds was screened in RAW264.7 cells. The results showed that the anti-inflammatory activities of compounds 2 and 3 were weak, and 1, 4 had good anti-inflammatory activity. The macrophage inflammation model was established by lipopolysaccharide (LPS). Then, the anti-inflammatory activity was evaluated by ELISA kits, qRT-PCR experiment and western blot experiment. And the anti-oxidative stress activity was assessed by flow cytometry. The results showed that compounds 1, 4 could significantly inhibit the elevation of inflammatory factors nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and also had obvious inhibitory effects on the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). In addition, compounds 1 and 4 could effectively inhibit the overexpression of reactive oxygen species (ROS) in RAW264.7 cells that activated by LPS. These results indicated that compounds 1 and 4 may exert anti-inflammatory and anti-oxidative stress effects through the NF-κB signaling pathway.

A new megastimane sesquiterpenoid from the leaves of Cinnamomum cassia

A new megastimane sesquiterpenoid, cassianol A (1), and five known analogues (2–6) were isolated from the leaves extract of Cinnamomum cassia. Their structures were elucidated by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. All the isolates were isolated from C. cassia for the first time. The anti-inflammatory activities of compounds 1–6 were evaluated against nitric oxide (NO) production in LPS-induced RAW 264.7 mouse macrophages.

Synthesis, in silico, and in vivo anti-inflammatory evaluation of 3β-cinnamoyloxy substituted pregna-4,16-diene-6,20-diones derivatives

Pregnane derivatives have been studied mainly for their 5α-reductase activity. However, the anti-inflammatory activities of such compounds are still poorly explored. In the search for new anti-inflammatory agents, seven new pregnane derivatives 6a-g, with cinnamic acid esters at C-3 were prepared and fully characterized. The anti-inflammatory activity of compounds was assessed in TPA induced mice ear model. From them, compound 6 b was the most active to reduce edema, with an ED50 of 0.017 mg/ear. Also, Molecular Docking and Molecular Dynamics studies were performed to identify a potential molecular target related to the inflammatory process. The in vivo results suggest that 6 b could be a potent anti-inflammatory compound, while in silico studies suggest its interaction with some critical enzymes in the inflammatory response.

Structural Characterization and Assessment of Anti-Inflammatory and Anti-Tyrosinase Activities of Polyphenols from Melastoma normale.

Polyphenols, widely distributed in the genus Melastoma plants, possess extensive cellular protective effects such as anti-inflammatory, anti-tyrosinase, and anti-obesity, which makes it a potential anti-inflammatory drug or enzyme inhibitor. Therefore, the aim of this study is to screen for the anti-inflammatory and enzyme inhibitory activities of compounds from title plant. Using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, the extract of Melastoma normale roots was separated. Four new ellagitannins, Whiskey tannin C (1), 1-O-(4-methoxygalloyl)-6-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (2), 1-O-galloyl-6-O-(3-methoxygalloyl)-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (3), and 1-O-galloyl-6-O-vanilloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (4), along with eight known polyphenols were firstly obtained from this plant. The structures of all isolates were elucidated by HRMS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW2 64.7 cells, we investigated the anti-inflammatory activities of compounds 1–4, unfortunately, none of them exhibit inhibit nitric oxide (NO) production, their IC50 values are all > 50 μM. Anti-tyrosinase activity assays was done by tyrosinase inhibition activity screening model. Compound 1 showed weak tyrosinase inhibitory activity with IC50 values of 426.02 ± 11.31 μM. Compounds 2–4 displayed moderate tyrosinase inhibitory activities with IC50 values in the range of 124.74 ± 3.12–241.41 ± 6.23 μM. The structure–activity relationships indicate that hydroxylation at C-3′, C-4′, and C-3 in the flavones were key to their anti-tyrosinase activities. The successful isolation and structure identification of ellagitannin provide materials for the screening of anti-inflammatory drugs and enzyme inhibitors, and also contribute to the development and utilization of M. normale.

Investigation of anti-inflammatory and antipyretic activity of polymorphic modification of n-(trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1h-2λ6,1-benzothiazine-3-carboxamide derivative in rats

Annotation. Polymorphism among biologically active substances is an extremely important factor that modifies the therapeutic properties of pharmaceutical substances and dosage forms, significantly affects the parameters of their biological activity and pharmacokinetics. Chemical synthesis among the derivatives of 4-R-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylic acids gave the leader compound N-(4-trifluoromethylphenyl)-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, the crystalline polymorph of which in the form of plates has a pronounced analgesic activity. The aim of the study was to investigate the anti-inflammatory activity of compound B by its effect on various components of the inflammatory reaction, as well as the antipyretic effect of this compound in rats. The anti-alterative activity was determined on the model of planar skin wounds, the antiproliferative effect - on the model of cotton granuloma, the anti-exudative effect - on the model of toxic pulmonary edema in rats. The antipyretic effect was studied in a model of milk fever in rats. The study was performed on 91 white male Wistar rats. Statistical processing of the obtained results was performed using the program "STATISTICA 6.1" by methods of variation statistics using parametric and nonparametric methods. The results showed that the polymorphic compound B has anti-inflammatory activity on all components of the inflammatory reaction - alteration, exudation and proliferation. In terms of efficacy in the model of experimental inflammation, this substance is superior to meloxicam, as its ED50 when administered orally is 5.2 mg/kg, while the reference drug - 9.1 mg/kg. Compound B exhibits a pronounced antipyretic effect in a rat fever model. Therefore, the polymorphic modification of the carboxamide derivative in the form of plates is promising for further research in order to create on its basis a drug with analgesic, anti-inflammatory and antipyretic properties.

Structural Elucidation of Garcipaucinones A and B From Garcinia paucinervis Using Quantum Chemical Calculations.

Two tocotrienol derivatives, garcipaucinones A (1) and B (2), and a biosynthetically related known analogue (3) were isolated from the fruit of Garcinia paucinervis. Their structures including absolute configurations were unequivocally determined by spectroscopic methods complemented with electronic circular dichroism (ECD) calculations and gauge-independent atomic orbital (GIAO) NMR calculations. Compounds 1 and 2 are the first naturally occurring tocotrienol derivatives with a 3,10-dioxatricyclo-[7.3.1.02,7]tridecane skeleton incorporating an unusual γ-pyrone motif. A reasonable biosynthetic pathway for formation of the two compounds is proposed. The antiproliferative and anti-inflammatory activities of compounds 1 and 2 were also evaluated.

Polygokingiasides A and B: Two New Spirostane Glycosides From the Roots of Polygonatum kingianum With Nitric Oxide Inhibitory Activity

Two new spirostane glycosides, named polygokingiaside A (1) and polygokingiaside B (2), and 6 known spirostane glycosides, (25 R)-26- O-( β-d-glucopyranosyl)-furost-5-en-3 β,22 α,26-triol 3- O-β-d-glucopyranosyl-(1→4)- β-d-galactopyranoside (3), (25 S)-26- O-( β-d-glucopyranosyl)-furost-5-en-3 β,22 α,26-triol 3- O-β-d-glucopyranosyl-(1→2)- β-d-glucopyranosyl-(1→4)- β-d-galactopyranoside (4), (25 R)-26- O-( β-d-glucopyranosyl)-furost-5-en-3 β,22 α,26-triol 3- O-β-d-glucopyranosyl-(1→2)- β-d-glucopyranosyl-(1→4)- β-d-galactopyranoside (5), (23 S,25 R)-spirostan-5-en-3 β,23-dihydroxy-12-one-3- O-β-d-glucopyranosyl-(1→2)- β-d-glucopyranosyl-(1→4)- β-d-galactopyranoside (6), (24 S,25 R)-spirostan-5-en-3 β,24-dihydroxy-12-one-3- O-β-d-glucopyranosyl-(1→2)- β-d-glucopyranosyl-(1→4)- β-d-galactopyranoside (7), and (25 R)-spirostan-5-en-3 β-hydroxy-12-one-3- O-β-d-glucopyranosyl-(1→4)- β-d-galactopyranoside (8), were isolated from the roots of Polygonatum kingianum Collett & Hemsl. (Asparagaceae). Their structures were determined by extensive analysis of high-resolution electron spray ionization mass spectrometry and nuclear magnetic resonance spectral data, as well as by comparison of the spectral data with those reported in the literature. Anti-inflammatory activity of compounds 1-8 was evaluated by their inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. At a concentration of 20 µM, compounds 1-8 exhibited a modest inhibitory effect on NO production in LPS-stimulated RAW246.7 cells with inhibitory values ranging from 9.5 ± 0.8% to 33.8 ± 2.1%.

Anti-inflammatory activity of novel (5Z)-3-(2-(2-oxo-2H-chromen-4-yloxy)ethyl)-5-benzylidenethiazolidine-2,4‑dione derivatives: An approach to microwave synthesis

Abstract Compounds of oxygen, nitrogen and sulfur containing heterocycles are recognized as important lead compounds in medicinal chemistry. An efficient and rapid synthesis of novel coumarin-thiazolidine-2,4‑dione derivatives (3a-3j) were synthesized by microwave as well as conventional methods. The newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and Mass spectral studies. The newly synthesized molecules were screened for their anti-inflammatory activity. In vitro study reveals that, compound (3 g) shows significant strong anti-inflammatory broad spectrum activity. Anti-inflammatory activity of compound (3 g) has shown excellent activity with IC50 value of 46.62 µg/mL.

A New Phenylethanoid Glycoside From the Leaves of Rosmarinus officinalis With Nitric Oxide Inhibitory Activity

A new phenylethanoid glycoside, named rosmacinalis (1), and 6x known compounds {2-phenylethyl O-α-L-rhamnopyranosyl-(1‴→6″)- O-β-D-glucopyranoside (2), clinopodiolide C (3), rosmanol (4), 7 α-methoxyrosmanol (5) 7 β-methoxyrosmanol (6) and carnosol (7)} were isolated from the leaves of Rosmarinus officinalis. Their structures were determined by extensive analysis of high-resolution electron spray ionization mass spectrum and nuclear magnetic resonance spectral data, as well as by comparison of the spectral data with those reported in the literature. Anti-inflammatory activity of compounds 1‐7 was evaluated by their inhibition of NO production in lipopolysaccharide-stimulated RAW 264.7 cells. At a concentration of 100 µM, compounds 1 and 2 exhibited inhibitory rates of 47.1% ± 2.2% and 44.5% ± 1.3%, respectively, while compounds 3‐7 showed a cytotoxic effect. After dilution to a concentration of 20 µM, except compound 7, compounds 1‐6 did not show a cytotoxic effect. Their NO inhibitory rates ranged from 14.2% ± 1.3% to 31.1% ± 1.9%.

An Efficient Directly Conversion of the Ethyl p-Methoxycinnamate into N,N-dimethyl-p-Methoxycinnamamide and study the structure-activity relationship on anti-inflammatory activity

Ethyl p-methoxycinnamate (EPMC) (1) is a major natural ester found in the rhizome of Kaempferia galanga and has been reported to have anti-inflammatory activity. Some of the structural modification of this compound has been carried out in order to study the structure-activity relationship on its anti-inflammatory activity. In the present study, we report a new, simple and efficient procedure in the conversion of the ethyl p-methoxycinnamate into N,N-dimethyl-p-methoxycinnamamide (5) and then study the structure-activity relationship on its anti-inflammatory activity. The reaction was carried out through a microwave-assisted direct amidation between (EPMC) (1) with dimethylformamide (DMF) in the basic condition. The mixture was irradiated by using unmodified microwave-oven at 300 W for 1 minute to obtain compound (5) in 88.8% yields. The extensive analysis of the GCMS and NMR data supported that the product of synthesis is N,N-dimethyl-p-methoxycinnamamide (5). Evaluation of the anti-inflammatory activity of compound 5 by using anti-denaturation of heat bovine serum albumin (BSA) assay indicated that N,N-dimethyl-p-methoxycinnamamide (5) still have anti-denaturation activity. Compound 5 has an amide functional group which is more slowly hydrolyzed if compared to 1. Hence, the reaction has successfully produced a more stable compound which still has anti-inflammatory activity

Anti-inflammatory and Cytotoxic Lignans from Potentilla anserina

Two undescribed lignans (7′R,8′R,8S)-4,4′,5,9,9′-pentahydroxy-3,3′,8-trimethoxy-2,7′-cyclolignan (1) and (8S,7′S,8′S)-4-[(4-hydroxy-3-methoxyphenyl)-methyl]-4-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyltetrahydrofuran (2) were isolated from Potentilla anserina L., Rosaceae, together with three known lignans, (+)-cycloolivil (3), (+)-lyoniresinol (4), and (+)-cycloolivil-6-O-β-D-glucopyranoside (5), which were reported for the first time from Potentilla spp. Their structures were determined on the basis of various spectroscopic methods (1D and 2D NMR, MS) and by comparison with the published NMR data. In addition, the absolute configurations of 1 and 2 were confirmed by comparison of the experimental and calculated electronic circular dichroism data. Furthermore, the anti-inflammatory activities of compounds 1–5 were assayed on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, and their cytotoxic activities to lung adenocarcinoma A549 tumor cell line were evaluated. It was found that compounds 2, 3, and 5 showed moderate anti-inflammatory and cytotoxic activities.

Secondary Metabolites and Bioactivities of Aspergillus ochraceopetaliformis Isolated from Anthurium brownii.

Five new polyketides, asperochrapyran (1) and asperochralactones A–D (2–5), along with 12 known polyketides (6–17), were obtained from the fungal strain Aspergillus ochraceopetaliformis. Structures of all isolates were elucidated by their spectroscopic parameters. The relative configurations of the new compounds were deduced by the data of coupling constants and NOESY spectra. The absolute configurations were determined by the comparison of experimental and calculated ECD spectra. Moreover, the plausible biosynthesis pathway of major isolates was proposed as well. Anti-inflammatory activity of compounds 5 and 7–17 were evaluated with human neutrophils in response to the stimulation of formyl-methionyl-leucyl phenylalanine (fMLP). Asperlactone (9), aspyrone (13), and (−)-(3R)-mellein (14) exerted superoxide anion inhibition at 30 ± 9%, 29 ± 9%, and 26 ± 12%, respectively, at 10 μM. The capacities of asperlactone (9), aspilactonol B (10), penicillic acid (12), and (−)-(3R)-mellein (14) in elastase release inhibition were revealed as 25 ± 4%, 38 ± 8%, 25 ± 5%, and 34 ± 9%, respectively, at 10 μM.

Phenylpropanoids from Croton velutinus with cytotoxic, trypanocidal and anti-inflammatory activities

This current study presents the phytochemical analysis of Croton velutinus, describing phenylpropanoids obtained from this species. The fractionation of the roots hexane extract led to the isolation of four new phenylpropanoids derivatives, velutines A–D (1–4) and three known (5–7). Their structures were established based on spectroscopic (1D-2D NMR; HRMS and IR) analysis. Cytotoxic, trypanocidal and anti-inflammatory activities of compounds 1–7 were evaluated. Only compounds 2 and 5 showed cytotoxic activity against cancer cell lines (B16F10, HL-60, HCT116, MCF-7 and HepG2), with IC50 values ranging from 6.8 to 18.3 μM and 11.1 to 18.3 μM, respectively. Compounds 2 and 5 also showed trypanocidal activity against bloodstream trypomastigotes with EC50 values of 9.0 and 9.58 μM, respectively. Finally, the anti-inflammatory potential of these compounds was evaluated on cultures of activated macrophages. All compounds exhibited concentration-dependent suppressive activity on the production of nitrite and IL-1β by macrophages stimulated with LPS and IFN-γ. These results indicate phenylpropanoids esters (2 and 5) from C. velutinus as promising cytotoxic, trypanocidal and anti-inflammatory candidates that warrants further studies.

Clerodane Diterpenoids from Callicarpa hypoleucophylla and Their Anti-Inflammatory Activity

Plants of the genus Callicarpa are known to possess several medicinal effects. The constituents of the Taiwan endemic plant Callicarpa hypoleucophylla have never been studied. Therefore, C. hypoleucophylla was selected for our phytochemical investigation. Two new clerodane-type diterpenoids, named callihypolins A (1) and B (2), along with seven known compounds were isolated from the leaves and twigs of the Lamiaceae plant C. hypoleucophylla and then characterized. The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis, specifically, two-dimension nuclear magnetic resonance (NMR). The anti-inflammatory activity of compounds 1–9 based on the suppression of superoxide anion generation and elastase release was evaluated. Among the isolates, compounds 2–4 showed anti-inflammatory activity (9.52−32.48% inhibition at the concentration 10 μm) by suppressing superoxide anion generation and elastase release. Our findings not only expand the description of the structural diversity of the compounds present in plants of the genus Callicarpa but also highlight the possibility of developing anti-inflammatory agents from Callicarpa endemic species.

Синтез похідних бензенсульфонамідів і вивчення їхньої спорідненості до циклооксигенази-2 методом молекулярного докінгу

Відповідно до сучасних уявлень, інгібіцію циклооксигенази-2 (ЦОГ-2) розглядають як один з важливих механізмів протизапальної активності нестероїдних протизапальних препаратів (НПЗП). Тому пошук нових НПЗП, селективних до ЦОГ-2, є дуже актуальним завданням. Мета дослідження – синтезувати й оцінити потенційну спорідненість до ЦОГ-2 похідних 4-аміноN-(4,5,6,7-тетрагідро-3Н-азепін-2-їл)-бензенсульфонаміду порівняно з целекоксибом (ЦК) – відомим селективним інгібітором ЦОГ-2 на етапі первинного молекулярного докінгу. Кип’ятінням еквімолярних кількостей 2-метокси-3,4,5,6-тетрагідро-7H-азепіну та 4-амінобензенсульфонаміду в толуолі синтезовано 4-аміно-N-(4,5,6,7-тетрагідро-3Н-азепін-2-їл)-бензенсульфонамід. Подальшим модифікуванням кінцевої аміногрупи синтезовані відповідні ацил-(4 а­с) і ароїл- похідні (5 d­h). Визначено, що всі сполуки показують хороші значення вільної енергії зв’язування з сайтами ЦОГ-2. Проте базова молекула 3 і сполуки 4 a­c займають положення в ніші, що є характерною для ЦК. Їхня мінімальна вільна енергія зв’язування знаходиться в межах від -8,6 ккал/моль до -9,3 ккал/моль, що дає підставу досліджувати ці сполуки як потенційні інгібітори ЦОГ-2. Експериментальну верифікацію прогнозу протизапальної та аналгезуючої активності похідних бензолсульфонаміду було проведено на прикладі найактивнішої сполуки 4 а з використанням білих мишей і щурів. Протизапальну активність сполуки 4 а досліджували на моделі карагенанового набряку, а антиноцицептивну дію на моделі вісцерального болю та больової реакції, індукованої карагенаном. Порівняльні дослідження сполуки 4 а з ЦК дозволяють передбачити, що один з механізмів протизапальної дії похідних 4-аміно-N-(4,5,6,7-тетрагідро-3Н-азепін-2-їл)-бензен сульфонамідів може бути реалізований шляхом взаємодії з ЦОГ-2. Отримані дані є свідченням перспективності пошуку активних сполук з властивостями інгібіторів ЦОГ-2 у зазначеному хімічному ряду.

Inhibitory Functions of Novel Compounds from Dioscorea batatas Decne Peel on HMGB1-mediated Septic Responses

Inhibition of high mobility group box 1 (HMGB1) signaling and restoration of endothelial integrity are emerging as promising therapeutic strategies for managing severe vascular inflammatory diseases. Dioscorea batatas Decne (DBD, Chinese yam), a perennial plant which belongs to Dioscoreaceae, is widely cultivated across Korea, Japan, China, and other tropical and subtropical regions, and both the aerial parts and roots of this plant are used for food and medicinal purposes. Here, we determined the effects of the two phenanthrene compounds from DBD peel, 2,7-dihydroxy-4,6-dimethoxyphenanthrene (1) and 6,7-dihydroxy-2,4-dimethoxyphenanthrene (2), on HMGB1-mediated septic responses and survival rate in cecal ligation and puncture (CLP)-induced septic model. The anti-inflammatory activities of compounds 1 and 2 were monitored by lipopolysaccharide (LPS)- or CLP-induced release of HMGB1. The anti-septic activities of compounds 1 and 2 were determined by measuring permeability, leukocyte adhesion and migration, and pro-inflammatory protein activation in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice. Compounds 1 and 2 inhibited HMGB1 release and downregulated HMGB1-mediated inflammatory responses in HUVECs. Compounds 1 and 2 also inhibited HMGB1-induced hyperpermeability and leukocyte migration in mice. Additionally, treatment with compounds 1 and 2 reduced CLP-induced HMGB1 release and sepsis-related mortality and pulmonary damage in vivo. Our results indicate that the compounds 1 and 2 are potential therapeutic agents for treating severe vascular inflammatory diseases via HMGB1 signaling pathway inhibition.