Synthesis of New Lathyrane Diterpenoid Derivatives from Euphorbia lathyris and Evaluation of Their Anti‐Inflammatory Activities

Euphorbia factor L₃, a lathyrane diterpenoid extracted from Euphorbia lathyris, was found to display good anti‐inflammatory activity with very low cytotoxicity. To find more potent anti‐inflammatory drugs, two series of Euphorbia factor L₃ derivatives with fatty and aromatic acids were designed and synthesized. Among them, lathyrane derivative 5n exhibited most potent inhibition on LPS‐induced NO production in RAW264.7 cells with no obvious cytotoxicity. To determine the key characteristics of Euphorbia factor L₃ derivatives that contribute to anti‐inflammatory activity, we conducted a structure‐activity relationship study of these compounds.     

New Acetophenone Derivatives from Acronychia oligophlebia and Their Anti‐inflammatory and Antioxidant Activities

Seven new acetophenone derivatives (acroliones A – G, 1  –  7 ) and three known ones ( 8  –  10 ) were isolated from the leaves of Acronychia oligophlebia. Their structures were elucidated based on extensive spectroscopic analyses (IR, UV, HR‐ESI‐MS, 1D‐ and 2D‐NMR), X‐ray diffraction and comparison with literature data. The anti‐inflammatory and antioxidant activities of all isolates were evaluated.     

New Constituents from the Low Polar Fraction of the Fruits of Crataegus dahurica and Their Anti‐Inflammatory Activity in RAW264.7 Cells

The fruit of Crataegus dahurica Koehne was used to treat the disease of infantile indigestion and dyspepsia as an ethnic medicine and food. As a continuous work on finding the active constituents from the edible herbs, four new biphenyl derivatives ( 1 – 4 ), together with two known compounds ( 5 and 6 ), were obtained from the petroleum ether fraction of the fruits of C. dahurica. Their structures were determined by the extensive 1D and 2D NMR spectra and HR‐MS spectrometry. Furthermore, the anti‐inflammatory activities of all the isolated compounds were investigated, in which compound 4 showed moderately inhibitory effects on NO production in RAW264.7 cells without inducing cytotoxicity.     

Anti‐Inflammatory Effect of Novel 7‐Substituted Coumarin Derivatives through Inhibition of NF‐κB Signaling Pathway

A series of novel 7‐substituted coumarin derivatives were synthesized and evaluated. Biological screening results obtained by the evaluation of the compounds’ inhibition against LPS‐induced IL‐6 and TNF‐α release in RAW 264.7 cells indicated that most compounds exhibited potent anti‐inflammatory activity. Among them, N‐(3‐methoxybenzyl)‐2‐[(2‐oxo‐2H‐chromen‐7‐yl)oxy]acetamide ( 2d ) showed the best activity. The potential targets of title compound 2d were reversely screened with the molecular modeling software, Discovery Studio 2017 R2. Screening and molecule docking results showed that 2d could bind to the active site (NLS Polypeptide) of NF‐κB p65, and this binding affinity was confirmed by surface plasmon resonance (SPR) analysis. Furthermore, Western blot assay showed that 2d remarkably blocked the NF‐κB signaling pathway in vitro. Collectively, all these findings suggested that compound 2d might be a promising lead compound worthy of further pursuit.     

Two New Prenylated Indole Diterpenoids from Tolypocladium sp. and Their Antimicrobial Activities

Two new prenylated indole diterpenoids, tolypocladins K and L ( 1 and 2 ), together with a known analog terpendole L ( 3 ), were isolated from the solid fermentation culture of a mine soil‐derived fungus Tolypocladium sp. XL115. Their structures and relative configurations were determined by comprehensive spectroscopic data analysis, as well as by comparison of their NMR data with those related known compounds. Compound 3 exhibited remarkable antibacterial activity against Micrococcus luteus with an MIC value of 6.25 μg/mL, and compounds 1 and 3 displayed moderate antifungal activity selectively against tested strains with MIC values of 25–50 μg/mL.     

Varicuothiols A and B,New Fungal Metabolites from Aspergillus versicolor with Anti‐Inflammatory Activities

Chemical examination of a coral‐associated fungus Aspergillus versicolor LZD‐44‐03 resulted in the isolation of two new compounds with the trivial names of varicuothiols A ( 1 ) and B ( 2 ) as a unique scaffold. Their structures were determined through extensive spectroscopic analyses in association with the modified Mosher's method and chemical conversion. Both 1 and 2 exhibited significant inhibition against LPS‐induced RAW24.7 cell proliferation, in association with the down regulation of nitrite production and cytokines (MCP‐1, IL‐6, and TNF‐α).     

New 4,5‐seco‐20(10→5)‐abeo‐Abietane Diterpenoids with Anti‐Inflammatory Activity from Isodon lophanthoides var. graciliflorus (Benth.) H.Hara

Three new 4,5‐seco‐20(10→5)‐abeo‐abietane diterpenoids, 16‐hydroxysalvilenone ( 1 ), 15‐hydroxysalprionin ( 2 ), and 11β,15‐dihydroxysalprionin‐12‐one ( 3 ), and nine known abietane diterpenoids, 4 – 12 , along with one known sempervirane diterpenoid, hispidanol A ( 13 ), were isolated from the aerial parts of Isodon lophanthoides var. graciliflorus. The structures of compounds 1 – 3 were determined on the basis of spectroscopic methods including extensive analysis of NMR and mass spectroscopic data. All diterpenoids were tested for their TNF‐α inhibitory effects on LPS‐induced RAW264.7 cells. Compound 9 (16‐acetoxyhorminone) was the most potent with an IC₅₀ value of 3.97±0.70 μm .     

Biphenyl‐Type Neolignan Derivatives from the Twigs of Magnolia denudata and Their Anti‐Inflammatory Activity

Two new biphenyl‐type neolignan derivatives, 2‐[2‐(hydroxymethyl)‐1‐benzofuran‐5‐yl]‐4‐(prop‐2‐en‐1‐yl)phenol ( 1 ) and 2′‐ethoxy‐5,5′‐di(prop‐2‐en‐1‐yl)biphenyl‐2‐ol ( 2 ), were isolated from the twigs of Magnolia denudata, together with six known compounds ( 3 – 8 ). The structures of 1 and 2 were determined through extensive 1D‐ and 2D‐NMR and mass‐spectrometric analyses. Magnolol ( 6 ) and honokiol ( 7 ) exhibited potent inhibition (IC₅₀ values=4.4±0.2 and 0.71±0.13 μg/ml, resp.) of O$\rm{{_{2}^{{^\cdot} -}}}$ generation by human nutrophils in response to N‐formyl‐L ‐methionyl‐L ‐leucyl‐L ‐phenylalanine/cytochalasin B (fMLP/CB). In addition, 2‐[2‐(hydroxymethyl)‐1‐benzofuran‐5‐yl]‐4‐(prop‐2‐en‐1‐yl)phenol ( 1 ), 2′‐ethoxy‐5,5′‐di(prop‐2‐en‐1‐yl)biphenyl‐2‐ol ( 2 ), magnolol ( 6 ), and vanillic acid ( 8 ) inhibited fMLP/CB‐induced elastase release with IC₅₀ values=6.4±1.5, 2.4±0.4, 1.5±0.2, and 4.8±0.5 μg/ml, respectively.     

Extracts and Steroids from the Edible Mushroom Hypholoma lateritium Exhibit Anti‐Inflammatory Properties by Inhibition of COX‐2 and Activation of Nrf2

Hypholoma lateritium is an edible macrofungus with a common distribution in Europe, North America, and the Far East. The aim of this study was to investigate the potential anti‐inflammatory effects of H. lateritium extracts and its isolated steroids: fasciculic acid B, fasciculol E, fasciculol C, lanosta‐7,9(11)‐diene‐12β,21α‐epoxy‐2α,3β,24β,25‐tetraol, fasciculol F, and demethylincisterol A2. Organic (hexane, chloroform and 50 % methanol) and water extracts of H. lateritium were subjected to in vitro assays to determine pro‐inflammatory protein levels, such as cyclooxygenase‐2 (COX‐2), cytosolic prostaglandin E2 synthase (cPGES), and antioxidant nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2). Fungal extracts demonstrated significant activities on pro‐inflammatory protein levels with minor differences among the activities of the fractions of different polarities. All the compounds proved to exert notable inhibitory properties on COX‐2 and were capable to stimulate the Nrf2 pathway. Fungal extracts and the compounds exerted no cytotoxic activities on RAW 264.7 cells.     

Sesquiterpenoids from Chloranthus henryi and Their Anti‐neuroinflammatory Activities

Five new and seven known mono‐sesquiterpenoids ( 1 – 5 and 6 – 12 , resp.) together with five known lindenane‐type disesquiterpenoids, 13 – 17 , were isolated from the whole plant of Chloranthus henryi. Based on spectroscopic methods, the new structures were established to be (5S,6R,8S,10R)‐6‐hydroxyeudesma‐4(15),7(11)‐diene‐12,8‐olide ( 1 ), 6α‐hydroxyeudesma‐4(15),7(11),8(9)‐triene‐12,8‐olide ( 2 ), 8,12‐epoxy‐1β‐hydroxyeudesma‐4(15),7,11‐trien‐6‐one ( 3 ), 12‐oxochloraniolide A ( 4 ), and (4α)‐8‐hydroxy‐12‐norcardina‐6,8,10‐trien‐11‐one ( 5 ), respectively. Among the isolates, compound 2 , zederone epoxide ( 8 ), spicachlorantin G ( 13 ), chloramultilide A ( 14 ), shizukaol B ( 15 ), and spicachlorantin B ( 17 ) showed significant anti‐neuroinflammatory effects by inhibiting nitric‐oxide (NO) production in lipopolysaccharide (LPS)‐stimulated murine BV‐2 microglial cells with relatively low cytotoxicity.     

Three New Labdane-Type Diterpenoids from the Fruits of Amomum villosum and Their Anti-Inflammatory Activities

Three new labdane-type diterpenoids, calcaratarin E, villosumtriol, and 12-epi-villosumtriol ( 1 – 3 ) were isolated from the fruits of Amomum villosum, along with seven known diterpenoids ( 4 – 10 ). Through comprehensive analysis of chemical evidence and spectral data including UV, 1D and 2D NMR, HR-ESI-MS, IR, and X-ray crystallography, the structures of these novel compounds were successfully determined. Additionally, the inhibitory effects of compounds 2 – 10 on NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells were evaluated. Notably, compound 6 exhibited the most significant inhibitory effect with an IC₅₀ value of 1.74±0.69 μM.     

Antioxidant,Anti‐inflammatory and Cytotoxic Activities of Polyphenols Extracted from Chroogomphus rutilus

Chroogomphus rutilus is a rare fungal species that grows under pine trees and is now widely used as a functional food and pharmaceutical product. However, the chemical constituents and biological activities of Chroogomphus rutilus have been relatively limited. The present study aimed at determining the total polyphenols and flavonoids contents, biological activities and main phenolic compounds of Chroogomphus rutilus from different geographical origins at the stipe and pileus. The results suggested that Chroogomphus rutilus polyphenol extracts revealed a higher antioxidant, anti‐inflammatory, and cytotoxic activities, and there were significant differences between samples from different locations and regions. Correlation analysis showed that the contents of total polyphenols and flavonoids were significantly correlated with antioxidant and anti‐inflammatory activities. However, only the content of total flavonoids was significantly correlated with cytotoxicity, which means that the cytotoxicity of Chroogomphus rutilus polyphenol extracts may be regulated by flavonoids or other compounds. HPLC‐DAD analysis revealed that the main phenolic compound was protocatechuic acid, followed by baicalin, p‐hydroxyphenylacetic acid and p‐hydroxybenzoic acid, but comparing with the pileus extracts, the stipe extracts can be considered as a higher concentration of phenolic compounds. Therefore, antioxidant, anti‐inflammatory and cytotoxic activities of Chroogomphus rutilus polyphenol extracts could be due to the identified compounds. This study investigated a deep knowledge about the constituents and activities of Chroogomphus rutilus and provided the reference for its application in food and pharmaceutical.     

New Flavonoid Glucuronate Esters with Anti‐inflammatory Activities from Scutellaria regeliana

Two new flavonoid glucuronate esters, named scuregeliosides A and B ( 1 and 2 ), as well as three known ones, chrysin‐7‐O‐β‐d ‐glucuronic acid methyl ester ( 3 ), 5,7,4′‐trihydroxyflavone‐8‐O‐β‐d ‐glucuronic acid methyl ester ( 4 ) and apigenin‐7‐O‐β‐d ‐glucuronic acid ethyl ester ( 5 ), were isolated from the ethanolic extract of the whole plant of Scutellaria regeliana. Their chemical structures were elucidated on the basis of comprehensive spectroscopic analyses. Five compounds were screened for anti‐inflammatory activity in vitro. As the results, the inhibition rates of release of β‐glucuronidase from rat polymorphonuclear leukocytes were in the range of 42.2 – 47.1% at a concentration of 10 μm .     

Two New Anti‐Proliferative C18‐Norditerpenes from the Roots of Podocarpus macrophyllus

Activity‐guided fractionation strategy was used to investigate chemical constituents from the roots of Podocarpus macrophyllus. Successfully, two new norditerpenes, 2β‐hydroxymakilactone A ( 1 ) and 3β‐hydroxymakilactone A ( 2 ), along with ten known analogues ( 3  –  12 ) were isolated. The structures of 1 and 2 were elucidated by spectroscopic analysis including 1D‐, 2D‐NMR, and HR‐ESI‐MS data. The previously reported structure of 2,3‐dihydro‐2α‐hydroxypodolide was revised as 2,3‐dihydro‐2β‐hydroxypodolide ( 3 ) by spectroscopic analysis, and was further confirmed by X‐ray crystallographic analysis. Cytotoxic activities of all isolated compounds against five human solid tumour cell lines (AGS, HeLa, MDA‐MB‐231, HepG‐2, and PANC‐1) were evaluated. All of them exhibited anti‐proliferative activities (IC₅₀ = 0.3 – 27 μm ), except for 10 . Compounds 1 , 4 , 5 , 6 , and 8 exhibited potent inhibitory activities with IC₅₀ < 1 μm against HeLa and AGS cells.     

Chemical Composition of Bawei Longzuan Granule and Its Anti‐Arthritic Activity on Collagen‐Induced Arthritis in Rats by Inhibiting Inflammatory Responses

Bawei Longzuan granule (BLG) is a representative Zhuang medicine preparation. The present work aims to characterize the chemical constituents of BLG and evaluate its anti‐arthritic activity. The major chemical constituents of BLG were tentatively identified by ultra‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS), which revealed the presence of some alkaloids (e. g., magnoflorine, sinomenine and nitidine) and flavonoids (e. g., hesperidin, diosmin and sinensetin) that may be partly responsible for the anti‐arthritic effect of BLG. In addition, the collagen‐induced arthritis (CIA) model in rats was induced by intradermal injection of bovine collagen‐II in complete Freund's adjuvant at the base of tail. The CIA rats received oral administration of BLG (1.25, 2.5 and 5 g/kg) for 30 days. Then, various indicators were determined to evaluate its anti‐arthritic activity, including paw swelling, arthritic score, body weight, knee joint pathology, thymus index and spleen index. Additionally, the serum levels of tumor necrosis factor (TNF)‐α, interferon (IFN)‐γ, interleukin (IL)‐1β, IL‐6, IL‐4 and IL‐10 were measured to determine the underlying mechanisms. The results showed that BLG efficiently ameliorated the severity of arthritis in CIA rats by decreasing paw swelling and arthritis score and improving the histological lesions of knee joint. Moreover, the serum levels of several pro‐inflammatory cytokines (i. e., IL‐1β, TNF‐α, IL‐6 and IFN‐γ) were downregulated, whereas two anti‐inflammatory factors (i. e., IL‐4 and IL‐10) were upregulated after BLG administration. These results indicated that BLG possessed promising therapeutic effect on collagen‐induced arthritis by inhibiting inflammatory responses. BLG can be used as a complementary or alternative traditional medicine to treat rheumatoid arthritis.     

Biphenyl Derivatives from the Aerial Parts of Oenanthe javanica and Their COX‐2 Inhibitory Activities

Four new biphenyl derivatives ( 1 – 4 ), along with six known biphenyl derivatives ( 5 – 10 ) were isolated and elucidated by their detailed analyses of spectroscopic data and references from the aerial parts of Oenanthe javanica for the first time. Compounds ( 1 – 10 ) were assayed for their activities about the inhibition of COX‐2 enzyme in vitro for the first time. Compounds 1 , 2 , 4 , and 6 showed inhibitory activities against COX‐2 with IC₅₀ values ranging from 22.18±0.29 to 108.54±0.42 μm .     

Three New Species of Anemone (Ranunculaceae) from Xizang

Three species of the genus Anemone (Ranunculaceae), Amotuoensis, Abrachystema and Ajiachaensis, are described as new from the Xizang Autonomous Region. The diagnostic differences between them and their allies or their specific characteristics are given.