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Three new lanostane triterpenoids ( 1-3 ) along with two new amides fatty compounds ( 4-5 ) were isolated from the ethyl acetate extract of a culture of the endophytic fungus Alternaria sp. gx-2. Their structures were identified by 1D and 2D NMR spectral data and HRESIMS. Compounds 1-12 were evaluated for their anti-inflammatory and tyrosinase inhibition activities. The isolated compounds did not show inhibitory activities at a concentration of 100 μM against tyrosinase, while under the concentration of 10 μM, the release of lactate dehydrogenase (LDH) inhibition rate of compound 1 was 54.45%, indicating that compound 1 had moderate anti-inflammatory activity on the activation of NLRP3 inflammasome.

As a successful anti-tumor drug target, the family of histone deacetylases (HDACs) is also a critical player in immune response, making the research of anti-inflammatory HDAC inhibitors an attractive new focus. In this report, triterpenoids nigranoic acid (NA) and manwuweizic acid (MA) were identified as HDAC inhibitors through docking-based virtual screening and enzymatic activity assay. A series of derivatives of NA and MA were synthesized and assessed for their biological effects. As a result, hydroxamic acid derivatives of NA and MA showed moderately increased activity for HDAC1/2/4/6 inhibition (the lowest IC 50 against HDAC1 is 1.14 μM), with no activity against HDAC8. In J774A.1 macrophage, compound 1-3, 13 and 17-19 demonstrated inhibitory activity against lactate dehydrogenase (LDH) and IL-1β production, without affecting cell viability. Compound 19 increased the histone acetylation level in J774A.1 cells, as well as inhibited IL-1β maturation and caspase-1 cleavage. These results indicated that compound 19 blocks the activation of NLRP3 inflammasome, probably related to HDAC inhibition. This work provided a natural scaffold for developing low-cytotoxic and anti-inflammatory HDAC inhibitors, as well as a class of tool molecules for studying the relationship between HDACs and NLRP3 activation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids, cathayanalactones A-F (1-6), together with seven analogues (7-13). Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses. Compounds 1, 2, 3, 7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Four new dolabellane-type diterpene alkaloids, glandulamines A - D (1:  - 4: ), together with twelve known compounds (5:  - 16: ), were isolated from the seeds of Nigella glandulifera using repeated column chromatography and semipreparative HPLC. The structures of 1:  - 16: were elucidated based on NMR data analysis, HRMS experiments and other spectroscopic interpretations. The absolute configuration of 5: was determined by single-crystal X-ray diffraction data for the first time. Compounds 10: and 12: showed human dihydroorotate dehydrogenase inhibitory activity with IC 50 values of 61.1 ± 5.3 and 45.9 ± 3.0 µM, respectively. Molecular docking of the active compound 12: and positive control teriflunomide on the inhibitor-binding site of human dihydroorotate dehydrogenase was subsequently performed to visualize the interaction pattern. In addition, compounds 8: and 10: exhibited inhibitory effects against lipopolysaccharide-induced nitric oxide production with inhibition rates of 61 and 41%, respectively, at the concentration of 10 µM. Compounds 9: and 12: showed cytotoxic activities with cell viability varying from 29 ~ 57% at 100 µM against T98G, U87, U251, and GL261 glioma cancer cell lines. These data provide new insights on the pharmacologically active compounds of this plant widely used in folk medicine., Competing Interests: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Eight new highly oxygenated lanostane triterpenes, gibbosic acids A-H (1-8), along with three known ones (9-11), were isolated from the fruiting body of Ganoderma gibbosum. The structures of new isolates were assigned by NMR and HRESIMS experiments. The absolute configurations of 1 were further confirmed by single crystal X-ray diffraction data and computational ECD methods. Immunoregulatory effect and anti-inflammatory activities of these compounds were screened in murine lymphocyte proliferation assay and in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages, respectively. Compound 2 exhibited immunostimulatory effect both in lymphocyte proliferation assay without any induction and ConA-induced mitogenic activity of T-lymphocyte, and the proportion of lymphocyte proliferation at the concentration of 0.1μM are 20.01% and 21.40%, respectively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A growing body of evidence suggests the anti-inflammatory and antitumor effects of parthenolide (PAR). Here we show that PAR treatment inhibits the initiation of experimental autoimmune neuritis (EAN), suppresses the production of TNF-α, IFN-γ, IL-1β and IL-17, and decreases Th1 and Th17 cells at early time point. However, such anti-inflammatory effect vanishes later and PAR impedes the recovery of EAN in late phase, which is accompanied with inhibited apoptosis of inflammatory cells. Our results indicate that PAR plays dual roles in EAN and it is not proper to be applied in autoimmune diseases of nervous system., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36–3.44 μM. [ABSTRACT FROM AUTHOR]

Two new compounds, including a norsesquiterpenoid, annuionone H (1), and a quassinoid, picraqualide G (2), along with eleven known compounds (3–13), were isolated from the twigs and leaves of Picrasma quassioides. Comprehensive spectroscopic analyses and NMR calculation with DP4+ analysis were used to identify their structures. Moreover, of all these compounds, compound 4 showed a week inhibition rate in the anti-inflammatory screening results against mouse macrophage J774A.1 cell. [ABSTRACT FROM AUTHOR]

Salidroside, an active constituent from the root of Rhodiola rosea L., has multiple pharmacological effects, such as anti-cancer, anti-inflammatory and anti-oxidative properties, etc. However, its protective effect on bone tissue via regulating calcium homeostasis is yet to be determined. This study was performed to investigate if salidroside could protect against bone injuries induced by estrogen deficiency or hyperglycemia through modulating calcium homeostasis. Ovariectomized (OVX) mice and diabetic mice were treated with salidroside (20 mg/kg) for 6 weeks. Safranin O staining and micro-CT were performed on the distal metaphysis of femur. The calcium content in serum, urine and femur was measured, and the mRNA and protein expressions of regulators in kidney were determined by PCR and immunoblotting, respectively. Treatment with salidroside increased bone calcium level and decreased urinary calcium excretion, consequently attenuating the deteriorations of trabecular bone in both OVX mice and diabetic mice. 25-Hydroxyvitamin D-24 hydroxylase expression was down-regulated and vitamin D receptor expression was up-regulated in kidney of both OVX mice and diabetic mice upon to salidroside treatment, which also inhibited the ovariectomy-induced decrease in expression of renal transcellular calcium transporters and the diabetes-induced enhancement in renal calcium-sensing receptor (CaSR) expression. Taken together, salidroside exerted osteoprotective effects by improving calcium homeostasis via regulating vitamin D metabolism and transcellular calcium transporters as well as modulating CaSR expression in kidney. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seeds (GSPE) in the treatment of ulcerative colitis (UC). Rats were intragastrically administered different doses of GSPE (100, 200, and 400 mg/kg) per day for 7 days after UC was twice-induced by intracolonic injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS)dissolved in 50% ethanol. Sulfasalazine (SASP) at 200 mg/kg was used as a positive control drug. Macroscopic and microscopic damage scores and changes in weight/length ratio (mg/mm) of colon segments were analyzed. The levels of malonyldialdehyde (MDA), interleukin (IL)-1β, IL-2, IL-4, and myeloperoxidase (MPO) activity in the colon tissues and MPO activity in the serum were all measured by biochemical methods or double antibody sandwich ELISA methods. Compared with the TNBS control group, GSPE treatment facilitated recovery of pathologic changes in the colon after insult with TNBS, as demonstrated by increased body weight (p < 0.01) and decreased colonic weight/length ratio (p < 0.01); GSPE also notably reduced the colonic macroscopic and microscopic damage scores (p < 0.01). The MPO activity in colon tissues and serum of rats treated with GSPE was significantly lower than that in the TNBS control group. The MDA and IL-1β levels of colon tissues were also decreased in GSPE groups. The intestinal antiinflammatory effect of GSPE was accompanied by a significant improvement of IL-2 and IL-4 levels in the colon tissues of rats in the high-dose GSPE group (p < 0.05). Compared with the SASP group, GSPE groups had no significant difference in the therapeutic effect (p > 0.05). GSPE exerts a beneficial antiinflammatory effect in the acute phase of TNBS-induced colitis in rats by downregulating some of the mediators involved in the intestinal inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, decreasing production of proinflammatory cytokines IL-1β, and increasing production of antiinflammatory cytokines IL-2 and IL-4. Pour examiner l’effet thérapeutique et le mécanisme des proanthocyanidines extraites des graines de raisin (GSPE) chez des rats souffrant de colite ulcéreuse (CU) induite par l’acide 2,4,6-trinitrobenzène sulfonique (TNBS), on leu a administré différentes doses de GSPE (100, 200 et 400 mg/kg) par voie intragastrique, tous les jours pendant 7 jours, après que la CU a été induite deux fois par l’injection intracolique de TNBS dissous dans de l’éthanol 50 %. La sulfasalazine (200 mg/kg, SASP) a servi de médicament témoin positif. Puis les rats ont été sacrifiés. Les scores des lésions microscopiques et macroscopiques, et les modifications de la relation poids/longueur (mg/mm) des segments de côlon ont été analysés. Les taux de malonyldyaldéhyde (MDA), interleukine-1β (IL-1β), interleukine-2 (IL-2), interleukine-4 (IL-4) et l’activité de la myéloperoxydase (MPO) dans les tissus coliques ainsi que l’activité MPO dans le sérum ont tous été mesurés par des méthodes biochimiques et des tests ELISA sandwich. Comparativement a ce qui a été observé chez le groupe témoin TNBS, le traitement avec les GSPE a facilité la régression des modifications pathologiques induites par le TNBS, comme démontré par une augmentation de poids (p < 0,01), une diminution de la relation poids/longueur (p < 0,01) colique et une réduction considérable des scores microscopiques et macroscopiques du côlon (p < 0,01). L’activité MPO dans les tissus coliques et le sérum des rats traités avec les GSPE a été nettement plus faible que celle du groupe témoin TNBS. Les taux de MDA et d’IL-1β dans les tissus coliques ont aussi diminué chez les groupes GSPE. L’effet anti-inflammatoire intestinal des GSPE a été accompagné d’une augmentation significative des taux d’IL-2 et d’IL-4 dans les tissus coliques des rats du groupe GSPE 400 mg/kg (p < 0,05). Comparativement au groupe SASP, les groupes GSPE n’ont pas montré de différence significative dans l’effet thérapeutique (p > 0,05). Les GSPE ont un effet antiinflammatoire bénéfique dans la phase aiguë de la colite induite par le TNBS, en diminuant un certain nombre de médiateurs impliqués dans la réponse inflammatoire intestinale, en inhibant l’infiltration cellulaire inflammatoire, les dommages oxydatifs, en favorisant la réparation du tissu lésé pour diminuer le stress oxydatif colique, en diminuant la production des cytokines proinflammatoires IL-1β et en augmentant celle d [ABSTRACT FROM AUTHOR]

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1 – 15) along with nine (16 – 24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC 50 value of 2.830 μM and compound 12 with the IC 50 value of 0.682 μM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1 β was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation. [Display omitted] • Twenty-four coumarins were isolated from the ethyl acetate fraction of Toddalia asiatica. • Fifteen coumarins that have not been described before. • Two undescribed compounds showed low IC 50 values and could exert effective anti-inflammatory effects. • Compound 12 inhibited pyroptosis in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Four new diterpenoids (1–4) and four known diterpenoids (5–8) were purified from the whole plant of Euphorbia helioscopia L. Compounds 1 and 2 were jathophanes diterpenoids with a 5/12 polycyclic systems, compound 3 was rhamofolane diterpenoid with a 5/10 bicyclic skeleton and compound 4 was a rare class of euphorbia diterpenes featuring an unusual 5/10 fused ring system. Anti-inflammatory activity tests were conducted on the separated compounds, indicating that compound 4 had significant inhibitory effect on NLRP3 inflammasome with an IC 50 value of 7.75 μM. Further, the inhibitory effect of 4 was determined using immunofluorescence assays. [Display omitted] • Four new diterpenoids (1–4) and four known diterpenoids (5 - 8) were purified from the whole plant of Euphorbia helioscopia L. • Compound 3 was rhamofolane diterpenoid with a 5/10 bicyclic skeleton and 4 was a rare class of euphorbia diterpenes featuring an unusual 5/10 fused ring system • Compound 4 showed strong activity with IC 50 values of 7.75 μM. Frther, the inhibitory effects of 4 on protein levels were determined using immunofluorescence assays. [ABSTRACT FROM AUTHOR]

Nine previously undescribed clerodane-type diterpenoids (1–9), named caseabalanspenes A-I , along with six know compounds (10–15), were isolated from the twigs and leaves of Casearia velutina. Spectroscopic data (1D and 2D NMR) analysis permitted the definition of their structures and then determination of the molecular formula of the compound by high resolution mass spectrometry (HR-ESI-MS). It is worth noting that compound 7 contains N- heterocycle. Compounds 1–8 were tested the anti-inflammasome activity, and compound 3 exhibited potent activity and decreased LDH level in a dose-dependent manner, with IC 50 values of 2.90 μM. [Display omitted] • Nine undescribed clerodane diterpenoids were isolated from Casearia velutina. • Their structures were determined by 1D, 2D-NMR and HR-ESI-MS analyses. • The structure of compound 7 contains an N-heterocycle. • Compound 3 exhibited NLRP3-inflammasome inhibitory activity with IC 50 values of 2.90 μM. [ABSTRACT FROM AUTHOR]

Eleven undescribed 16,17-dinor-abietane diterpenoids, caseazins A-K (1 − 11), and ten known diterpenoids (12 − 21) were isolated from the twigs and leaves of Casearia kurzii (Flacourtiaceae). Caseazins A-K were the first abietane -type dinorditerpenoids to have been isolated from the plant of Casearia kurzii. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 5 and 10 were established by electronic circular dichroism calculations. Moreover, compounds 2 , 3 , 13 , 14 , and 18 exhibited anti-inflammatory activity with IC 50 values of 0.17, 0.36, 6.55, 1.30, and 4.53 μM, respectively. IL-1β and caspase-1 analyses suggested that compound 14 inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis. Diterpenoids from Casearia kurzii with NLRP3 inflammasome inhibitory activity were reported in this research. [Display omitted] • Eleven undescribed dinorditerpenoids were isolated from Casearia kurzii. • The compound 14 showed potent inhibitory activity against pyroptosis by blocking NLRP3 inflammasome activation. Their structures were established by elucidated by NMR, HRESIMS and ECD analyses. [ABSTRACT FROM AUTHOR]

Fourteen undescribed seco -type diterpenoids, named nudifloids A-N, together with ten known analogs, were isolated from the leaves of Callicarpa nudiflora. Nudifloids A-N had a characteristic 3,4- seco -labdane-type diterpenoid skeleton, whereas nudifloids A-C and K–N were 3,4- seco -norditerpenoids. Nudifloid A was the first example of a 3,4- seco -12,13,14,15,16-quartnor-labdane diterpenoid, with a seven-membered lactone ring formed through esterification between C-3 and C-11. Nudifloids B and C were a pair of highly modified 3,4- seco -labdane nor-diterpenoid epimers, of which C-2 and C-18 were cyclized together to form a cyclohexene fragment. The structures of these undescribed diterpenoids were established by spectroscopic analysis and reference data. The anti-inflammatory activity of diterpenoids in rich yield was evaluated by analyzing the inhibition of lipopolysaccharide plus nigericin-induced pyroptosis in J774A.1 cells. Nudifloids D and E exhibited prominent anti-NLRP3 inflammasome activity, with IC 50 values of 1.80 and 1.59 μM, respectively. Cell permeability assays revealed that nudifloid D inhibited pyroptosis, which could ameliorate inflammation by blocking the activation of the NLRP3 inflammasome. Guiding by anti-inflammatory activity, fourteen undescribed 3,4- seco -labdane diterpenoids were isolated from the leaves of Callicarpa nudiflora , and evaluated the anti-inflammatory activity of abundant diterpenoids. [Display omitted] • Bioassay-guided isolation of C. nudiflora to obtain twenty-four seco -diterpenoids. • Of which, fourteen undescribed 3,4- seco -labdane diterpenoids were determined. • Nudifloid A exhibits the first example with a seven-numbered lactone ring. • Nudifloids D and E exhibited prominent inflammatory inhibitory activity. [ABSTRACT FROM AUTHOR]

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for anti-inflammatory led to the obtainment of eleven previously undescribed clerodane diterpenoids, named caseatardies A-K (1 − 11), and four known clerodane diterpenoids (12 – 15) from the twigs and leaves of Casearia tardieuae. The structural elucidation of these clerodane diterpenoids was based on 1D and 2D-NMR spectroscopy (COSY, HSQC, HMBC and ROESY) as well as high resolution mass spectrometry (HR-ESI-MS). The relative configurations were defined by ROESY correlations. The anti-inflammatory activity of all the isolated compounds was screened and compound 15 decreased LDH level in a dose-dependent manner, showing IC 50 value of 2.89 μM. [Display omitted] • Eleven new clerodane diterpenoids with conjugated diene side chain at C-9 were isolated from Casearia tardieuae. • The compound 15 showed potent inhibitory activity against pyroptosis by blocking NLRP3 inflammasome activation. • Their structures were established by elucidated by 1D, 2D-NMR and HR-ESI-MS analyses. [ABSTRACT FROM AUTHOR]

Duan Teng Yimu decoction is a Chinese herbal medicine compound with proven therapeutic effects on inflammasome-related diseases, such as rheumatoid arthritis. This decoction consists of three Chinese herbal medicines, including Leonurus japonicus (L. japonicus), which promotes the blood circulation and exhibits detumescence activity, traditionally curing gynecologic and inflammasome diseases. To explore the anti-inflammasome activity and the underlying mechanisms of action of the compounds from L. japonicus. A series of compounds were isolated from L. japonicus. Their anti-inflammasome activities were evaluated in macrophages that were co-stimulated by lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. NLRP3 inflammasome formation and apoptosis speck like containing a CARD (ASC) oligomerization were evaluated by immunofluorescent microscopy and Western blot analysis. The regulation of autophagy after treatment of this compound was also evaluated. Lastly, in vivo activity of Leojaponin was analyzed in a mouse acute gouty arthritis model. Here we show that Leojaponin, a diterpenoid compound from L. japonicus , suppressed lactate dehydrogenase and IL-1β release in Nigericin-stimulated macrophages in a pyroptosis model. Leojaponin inhibits NLRP3 inflammasome activation in both J774A.1 cells and bone marrow-derived macrophages in a dose dependent manner. Moreover, Leojaponin suppressed NLRP3-mediated ASC specks formation and ASC oligomerization. These activities of Leojaponin depend on restoration of autophagy via promoting RAPTOR phosphorylation. Furthermore, Leojaponin ameliorated monosodium urate (MSU)-induced acute gouty arthritis in vivo. Our findings suggest that Leojaponin inhibits NLRP3 inflammasome activation through enhancing autophagy via RAPTOR phosphorylation, thereby highlighting Leojaponin as a potent drug for inflammasome-related diseases. [Display omitted] [ABSTRACT FROM AUTHOR]