The protective effect of solidagenone from Solidago chilensis Meyen in a mouse model of airway inflammation.

Solidagenone is the main active constituent present in Solidago chilensis Meyen which is used in folk medicine to treat pain and inflammatory diseases. This study aimed to evaluate the anti-inflammatory activity of solidagenone in vitro and in a model of allergic airway inflammation. In vitro studies were performed in activated macrophages and lymphocytes. BALB/c mice were sensitized and challenged with ovalbumin and treated with solidagenone orally (30 or 90 mg/kg body weight) or dexamethasone, as a positive control in our in vivo analysis. Supernatant concentrations of nitrite, TNF and IL-1ß, as well as gene expression of pro-inflammatory mediators in macrophages cultures, were reduced after solidagenone treatment, without affecting macrophages viability. Besides, solidagenone significantly decreased T cell proliferation and secretion of IFNγ and IL-2. Th2 cytokine concentrations and inflammatory cell counts, especially eosinophils, in bronchoalveolar lavage fluid were reduced in mice treated with solidagenone. Histopathological evaluation of lung tissue was performed, and morphometrical analyses demonstrated reduction of cellular infiltration and mucus hypersecretion. Altogether, solidagenone presented anti-inflammatory activity in vitro and in vivo in the OVA-induced airway inflammation model, suggesting its promising pharmacological use as an anti-inflammatory agent for allergic hypersensitivity.

Solidagenone from Solidago chilensis Meyen inhibits skin inflammation in experimental models.

Solidagenone (SOL) is a labdane-type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti-inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil-, arachidonic acid (AA)- and phenol-induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glucocorticoid receptor, estradiol-17-ß-dehydrogenase and prostaglandin-E(2)-9-reductase were established using molecular docking. SOL significantly inhibited croton oil-, AA- and phenol-induced ear oedema (P < .001) at doses of 0.1, 0.5 and 1.0 mg/ear. The MPO and NAG activities and TNF-α, IL-6 and NO levels were decreased (P < .001). The histopathological data revealed that inflammatory parameters (oedema thickness, leucocyte infiltration and vasodilatation) were reduced by treatment with SOL at doses of 0.1, 0.5 and 1.0 mg/ear. The docking study showed that SOL interacts with COX-1 and prostaglandin-E(2)-9-reductase through hydrogen bonding, inhibiting these enzymes. These results indicate that SOL may be a promising compound for the treatment of cutaneous inflammatory disorders and has potential as a topical anti-inflammatory agent.

Racemic 3,4-dihydro-4-naphthyl-naphthalen-1(2H)-ones from Juglans regia flowers.

Three previously undescribed (±)-3,4-dihydro-4-naphthyl-naphthalen-1(2H)-one derivatives were isolated from Juglans regia flowers. Elucidation of the 2D structures of these first-reported compounds was completed via regular spectroscopic methods. The assignment of racemic nature of these compounds was achieved using the examination of their chiral HPLC profiles. (±)-2,3-Dihydro-4',8,8'-trihydroxy-(1,1'-binaphthalen)-4(1H)-one, (±)-2,3-dihydro-4',5,8,8'-tetrahydroxy-(1,1'-binaphthalen)-4(1H)-one, and (±)-2,3-dihydro-1',5,5',8-tetrahydroxy-(1,2'-binaphthalen)-4(1H)-one were the structures of these racemic compounds, all taking on central chirality. The resolution of all the racemic compounds was conducted and achieved using a chiral HPLC procedure. The absolute configurations of the three isolated pairs of enantiomers were assigned via time-dependent density functional theory calculations from the electronic circular dichroism data. The findings in this paper demonstrated that the relevant biochemical reactions for the construction of these 3,4-dihydro-4-naphthyl-naphthalen-1(2H)-one derivatives in the test plant are nonselective. The (±)-2,3-dihydro-4',8,8'-trihydroxy-(1,1'-binaphthalen)-4(1H)-one showed selective inhibitory activity on tumor cells growth, preliminarily supporting the application of Juglans regia flowers to protect against cancers in a few Chinese folk areas.

Six new monacolin analogs from red yeast rice.

Six novel monacolin analogs, monacolins V1-V6 (1-6), together with seven known ones (7-13), were isolated from the ethyl acetate extract of red yeast rice. Their structures and absolute configurations were determined by spectroscopic methods, especially 2D NMR (1H-1HCOSY, HSQC, HMBC, and NOESY/ROESY) and CD spectroscopic analyses as well as chemical derivation. Monacolins V2 (2) and V3 (3) represent the first examples of monacolins with 3-hydroxybutyrate substitute. The anti-inflammatory inhibitory activities against the lipopolysaccharide (LPS) induced NO production in BV-2 cells as well as antioxidant activities against rat liver microsomal lipid peroxidation were evaluated.

Biological activity of Dittrichia viscosa (L.) Greuter extracts against adult Sitophilus granarius (L.) (Coleoptera, Curculionidae) and identification of active compounds.

Dittrichia viscosa (L.) Greuter, a perennial weed of the Mediterranean area, was reported to be source of active substances. Here, by means of both ingestion and contact assays, the biological activity of three different extracts (n-hexane, methanol, and distilled water) of D. viscosa aerial part has been evaluated against Sitophilus granarius (L.) adults, an important pest of stored grains. Ingestion assays showed negligible mortality and food deterrence for all the extracts, whereas only a slight reduction of some nutritional parameters (relative growth rate, relative consumption rate, food efficiency conversion) was recorded for water extract. High contact toxicity was found only for the n-hexane extract (24 h median lethal dose LD50 = 53.20 µg/adult). This extract was further subfractioned by silica gel column chromatography and then by thin layer chromatography. Further contact toxicity bioassays highlighted two active subfractions which were analyzed by GC-MS. This revealed the occurrence, in both subfractions, of two major peaks that were identified as α- and γ- costic acid isomers. Moreover, D. viscosa active subfractions, did not cause acetylcholinesterase (AChE) inhibition; therefore, in the light of progressive limitation of compounds acting by this mechanism of action, D. viscosa represents a promising eco-sustainable source of natural products for pest control.

Neuroprotective Secondary Metabolite Produced by an Endophytic Fungus, Neosartorya fischeri JS0553, Isolated from Glehnia littoralis.

Roots of Glehnia littoralis have been used to heal stroke as a traditional medicine. Even though many studies on this plant have been conducted, the secondary metabolites produced by its endophytes and their bioactivities have not been investigated thus far. Therefore, a new meroditerpenoid named sartorypyrone E (1) and eight known compounds (2-9) were isolated from extracts of cultured Neosartorya fischeri JS0553, an endophyte of G. littoralis. The isolated metabolites were identified using spectroscopic methods and chemical reaction, based on a comparison to literature data. Relative and absolute stereochemistries of compound 1 were also elucidated. To identify the protective effects of isolated compounds (1-9) in HT22 cells against glutamate-induced cytotoxicity, we assessed inhibition of cell death, intracellular reactive oxygen species (ROS) accumulation, and calcium ion (Ca2+) influx. Among the isolates, compound 8, identified as fischerin, showed significant neuroprotective activity on glutamate-mediated HT22 cell death through inhibition of ROS, Ca2+ influx, and phosphorylation of mitogen-activated protein kinase, including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38. The results suggested that the metabolites produced by the endophyte N. fischeri JS0553 might be related to the neuroprotective activity of its host plant, G. littoralis.

1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside: A new powerful antioxidant and inhibitor of Aß42 aggregation isolated from the leaves of Lawsonia inermis.

Mounting evidence indicates free radicals as toxic species causing damage to human cells leading to the pathogenesis of many diseases such as neurodegenerative disease. Plant derived antioxidants are considered as promising strategy to prevent free radical toxicity. In this study, the crude extract (CE), 50%MeOH, Petroleum Ether (PE) and Ethyl acetate (EA) fractions of Lawsonia inermis leaves were investigated for their antioxidant activity and their ability to counteract amyloid-ß42 (Aß42) aggregation. Elution of the most bioactive fraction (EA) on silica gel column chromatography led to six sub-fractions. The most active sub-fraction (1) was further resolved on silica gel column chromatography. A new compound with powerful antioxidant and anti-Aß42 aggregation properties was purified and characterised by spectroscopic methods as 1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside (THNG). This finding suggests that the antioxidant and anti-Aß42 aggregation activities of L. inermis leaves are strongly correlated to this compound.

Two new naphthalene glycosides from the seeds of Cassia obtusifolia.

A phytochemical study on the seeds of Cassia obtusifolia was carried out, which finally led to obtain two naphthalenes (1 and 2), two naphthopyrans (3 and 4) and twelve anthraquinones (5-16). The structures of all compounds were established mainly by NMR and MS experiments as well as the necessary chemical evidence. Among them, 1 and 2 (obtusinaphthalensides A and B) were identified to be new naphthalene glycosides.

[A new naphthalene derivative from bulbs of Eleutherine americana].

A new naphthalene derivative and three known compounds were isolated from the petroleum ether extract of the bulbs of Eleutherine americana by using various chromatographic techniques, such as column chromatography over silica gel and semi-preparative HPLC. Their structures were elucidated by spectroscopic date (MS, UV, IR, NMR), which were identified as eleutherol B (1), 4,8-dihydroxy-3-methoxy-1-methylanthraquinone-2-carboxylic acid methyl ester (2), 8-hydroxy-3,4-dimethoxy-1-methylanthraquinone-2-carboxylic acid methyl ester (3), and isoeleutherine (4). Compound 1 is a new compound. The diastolic blood vessels activity of compound 1 and 2 were potent, reaching 82.5% and 85.3% at the concentration of 10 µmol·L⁻¹, which were basically the same as that of the positive drug tanshinone ⅡA.

[A new naphthaldehyde derivative from Comastoma pulmonarium and its anti-tobacco mosaic virus (anti-TMV) activity].

A new naphthaldehyde derivative has been isolated from Comastoma pulmonarium by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compounds was determined as 5-methoxy-2-methyl-7-(2-oxopropyl)naphthalene-1-carbaldehyde(1) by NMR, MS, IR and UV spectra. This compound was also evaluated for its anti-tobacco mosaic virus (anti-TMV) activity. The result showed that it showed high anti-TMV activity with inhibition rate of 32.8%. The inhibition rate is close to that of positive control (ningnanmycin).

New secondary metabolites from the endophytic fungus Fusarium sp. HP-2 isolated from "Qi-Nan" agarwood.

A novel pyrone derivative (1) bearing two fused five-member rings, together with two new naphthalenone derivatives (2, 3), as well as two known compounds (4, 5) were obtained from the endophytic fungus Fusarium sp. HP-2, which was isolated from "Qi-Nan" agarwood. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR, and by HRESIMS spectra, as well as by comparison with the literature. Bioactivity results indicated that compound 3 showed weak acetylcholinesterase inhibitory activity.

Ancistroyafungines A-D, 5,8'- and 5,1'-coupled naphthylisoquinoline alkaloids from a Congolese Ancistrocladus species, with antiausterity activities against human PANC-1 pancreatic cancer cells.

Four new naphthylisoquinoline alkaloids, the 5,8'-coupled ancistroyafungines A-C (1-3) and the 5,1'-linked ancistroyafungine D (4), have been isolated from the stem bark of an as yet unidentified Ancistrocladus (Ancistrocladaceae) liana recently discovered near the village Yafunga, in the North-Central region of the Democratic Republic of the Congo. Likewise obtained were eleven analogs previously identified in related African and Asian Ancistrocladus species, exhibiting five different coupling types, viz., 5,8', 5,1', 7,1', N,6', and N,8'. All of the alkaloids are S-configured at C-3 and possess an oxygen function at C-6 in the isoquinoline portion, and, thus, belong to the subclass of "Ancistrocladaceae-type" alkaloids. This finding is geo- and chemotaxonomically remarkable, since - apart from one other Ancistrocladus species from the Central Congo Basin - only Southeast Asian and East African Ancistrocladaceae are known to exclusively produce naphthylisoquinolines with these structural features. Moreover, the alkaloid pattern of this Congolese liana clearly demarcates this plant from all other Ancistrocladus taxa that have so far been botanically described, which suggests that it might represent a new species or subspecies. The new ancistroyafungines display strong preferential cytotoxic activities towards human PANC-1 pancreatic cancer cells in nutrient-deprived medium, without showing toxicity in normal, nutrient-rich conditions.

Synthesis and characterization of Zr(IV) doped immobilized cross-linked chitosan/perlite composite for acid orange II adsorption.

To enhance the adsorption capacity of chitosan for acid orange II (AOII) adsorption, a novel adsorbent, zirconium(IV) doped immobilized cross-linked chitosan/perlite (Zr(IV)-CS-PT) composite was synthesized and characterized. Batch studies were conducted to analyze the effect of different parameters on AOII adsorption, such as Zr (IV) loading amount, pH, adsorbent dosage and temperature. Also, kinetic data revealed that AOII adsorption was well described by pseudo-second order kinetic model. Langmuir adsorption isotherm model was best described the isotherm data and maximum adsorption capacity was found 476.2 mg/g at natural pH. The thermodynamic data showed that the AOII adsorption occurred spontaneously and endothermic nature. Desorption and recycle experiments showed that after six cycle the adsorption efficiency was decreased from 95.6% to 90.1%, which shows the Zr(IV)-CS-PT is a reusable, cost-effective and high adsorption capacity adsorbent.

1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside delays amyloid-ß42 aggregation and reduces amyloid cytotoxicity.

Presently, misfolding and aggregation of amyloid-ß42 (Aß42 ) are considered early events in Alzheimer's disease (AD) pathogenesis. The use of natural products to inhibit the aggregation process and to protect cells from cytotoxicity of early aggregate grown at the onset of the aggregation path is one of the promising strategies against AD. Recently, we have purified a new powerful antioxidant and inhibitor of Aß42 aggregation from the leaves of Lawsonia inermis. The new compound was identified as a new Lawsoniaside; 1,2,4-trihydroxynaphthalene-2-O-ß-D-glucopyranoside (THNG). Herein, we show that THNG interferes with Aß42 aggregation, inhibits its conformational change to a ß-sheet-rich structure, decreases its polymerization into large fibrillar species, reduces oxidative stress, and aggregate cytotoxicity. These results indicate that THNG has great potential as a neuroprotective and therapeutic agent against AD. © 2018 BioFactors, 44(3):272-280, 2018.

Evaluation of raw nepodin extraction from Rumex japonicus and R. obtusifolius and their DNA polymorphisms.

Nepodin, found in the roots of Rumex japonicus Houtt. (Polygonaceae), inhibits osteoclast differentiation and has an antidiabetic effect. We propose nepodin as an ingredient of new functional foods or as a drug candidate for reducing the risk of reduced locomotion resulting from diseases such as osteoporosis. Although there are no previous reports of R. obtusifolius L., which is found throughout Japan, having roots containing nepodin, we found nepodin in the roots of this species. Therefore, R. obtusifolius as well as R. japonicus was considered a candidate raw material for nepodin extraction. We also discuss the suitability of R. japonicus and R. obtusifolius as sources of raw nepodin for cultivation on the Ryukyu Islands. In this study, all specimens on the Ryukyu Islands were identified as R. japonicus. Conversely, all specimens on mainland Japan were R. obtusifolius. The DNA sequence of the chloroplast trnL-trnF intergenic spacer region and partial nuclear internal transcribed spacer was consistent with the identification of R. japonicus and R. obtusifolius by morphological characteristics of the perianth segments. Therefore, to avoid erroneous identification and misuse of the plant species used for extraction of raw materials, it is preferable to develop DNA markers for these two regions. The content of nepodin varied from undetectable to 0.34% of the fresh weight (%FW) in R. japonicus and from undetectable to 0.21%FW in R. obtusifolius. From a pharmacological perspective, as plants that might be suitable as raw materials for nepodin extraction, it became clear that both R. japonicus and R. obtusifolius can be used with the same expected extraction efficiency. Based on our findings, R. obtusifolius could not be confirmed as inhabiting the Ryukyu Islands. For this reason, to conserve the endemic genetic characteristics of the Ryukyu Islands and to prevent genetic pollution by R. obtusifolius, only R. japonicus should be cultivated on the Ryukyu Islands.

[A new naphthalene derivative from Aloe vera and its antibacterial activity].

A new naphthalene derivative has been isolated from Aloe vera by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC. The new compound was determined as 3-hydroxy-1-(1,7-dihydroxy-3,6-dimethoxynaphthalen-2-yl)propan-1-one (1). In the biological activity assay, compound 1 disglayed prominent antibacterial activity with a MIC90 value of (48±4) mg•L⁻¹ for methicillin resistant Staphylococcus aureus (MRSA) strain which was stronger than that of the positive control levofloxacin with a MIC90 value (58±5) mg•L⁻¹.

[A new napthalenone from roots of Rumex nepalensis].

A new napthalenone, rumexone A (1), was isolated from the roots of Rumex nepalensis. The structure of 1 was elucidated by extensive spectroscopic analyses, including 1D and 2D NMR spectra and MS data. Its cytotoxic effect was evaluated using four clinically relevant human cancer cell lines, gastric carcinoma SGC7901, breast carcinoma MDA-MB-231, lung carcinoma A549, and hepatocellular carcinoma HepG2.

Hepatoprotective naphthalene diglucoside from Neanotis wightiana aerial parts.

BACKGROUND: Neanotis wightiana (Wall. ex Wight & Arn) W.H. Lewis has been used in traditional medicine in India for the treatment of liver disorders. In fact, this plant is frequently used by the local people of Tripura for the treatment of liver disorder problems. In previous study on this plant we have isolated a hepatoprotective saponin, neanoside A. PURPOSE: Evaluation of in vivo hepatoprotective effects of isolated compounds from N. wightiana aerial parts on serum hepatic-biomarkers in CCl4- induced hepatotoxicity in rats to validate the traditional use of the plant. STUDY DESIGN: This study was designed to isolate more hepatoprotective compounds from N. wightiana aerial parts and evaluate their in vivo hepatoprotective activity in animal model. METHODS: The phytochemicals from the polar n-butanol fraction of methanolic extract of N. wightiana aerial parts were isolated by repeated column chromatography over Diaion HP-20 and silica gel. Among the isolated three compounds, two were known triterpenoids, ursolic acid and oleanolic acid. The new compound was named neanoside B and its structure was established as naphthalene diglucoside 1 on the basis of extensive spectroscopic (including 2D NMR) analysis. Furthermore, the hepatoprotective activity of 1 was evaluated on CCl4 -induced hepatic injured rats by oral administration at three doses (5, 10 mg and 20 mg/kg) for 7 d and the assay of serum hepatic injury marker enzymes, SGPT, SGOT, ALP and bilirubin contents and histopathological changes of injured liver tissue after 7 d The herbal hepatoprotective drug, silymarin (100 mg/kg) was as positive control. RESULTS: The structure of the new compound, neanoside B (1) was elucidated as 1,4-dihydroxy-2-(methoxymethyl)naphthalen-3-yl-methyl-3-ß-d-glucopyranosyl-(1→6)-ß-d-glucopyranoside on the basis of extensive spectroscopic (including 2D-NMR) and chemical studies. The compound 1 exhibited significant in vivo hepatoprotective effect at the tested doses of 5, 10 and 20 mg/kg bw in CCl4-induced hepatotoxicity in rats. In a dose-dependent manner, 1 normalized the elevated levels of hepatic injury marker enzymes, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin and ameliorated the damage of liver tissue by reducing the necrosis and vacuoles. Possibly compound 1 ameliorated the hepatic damage in hepatotoxic rats by improving the antioxidant status. The higher dose (20 mg/kg) showed more hepatoprotective effect by reducing the elevated levels of SGPT, SGOT, ALP and bilirubin content to 388.5 ± 2.156, 160.7 ± 3.00, 198.6 ± 4.562 and 0.652 ± 0.036 IU/ml, respectively, compared to the levels in the control group (583.2 ± 6.922, 324.6 ± 4.711, 263.9 ± 4.939 and 1.533 ± 0.042 IU/ml, respectively) and the effect was comparable to that of the positive control silymarin (100 mg/kg bw) (389.4 ± 6.348, 167.9 ± 4.289, 203.3 ± 4.448 and 0.816 ± 0.030 IU/ml, respectively). CONCLUSIONS: This study indicated that isolated neanoside B (1) from Neanotis wightiana could be a potential drug in liver disorders. Further study in pharmacokinetics and long-term toxicity of compound 1 is requested for its clinical setting as effective drug in liver disorders.

Antileukemic ancistrobenomine B and related 5,1'-coupled naphthylisoquinoline alkaloids from the Chinese liana Ancistrocladus tectorius.

A striking feature of the metabolite pattern of the Southeast Asian liana Ancistrocladus tectorius (Ancistrocladaceae) is the predominance of 5,1'-coupled naphthylisoquinoline alkaloids. About 20 alkaloids of this coupling type have so far been discovered in this plant species. Here, we report on the isolation of four new 5,1'-linked naphthylisoquinolines from the twigs and stems of A. tectorius. Two of them, the ancistrobenomines B (5) and C (6), belong to the very rare group of alkaloids with a fully dehydrogenated isoquinoline portion. Likewise unusual for naphthylisoquinoline alkaloids is the presence of a hydroxymethylene group at C-3. Within the large class of meanwhile ca. 180 such natural products, this structural peculiarity had so far been known only from two other representatives isolated from the Malaysian species A. benomensis, and from one single naphthalene-devoid 3-hydroxymethyleneisoquinoline from A. tectorius. Seven further 5,1'-linked alkaloids, previously isolated from related Asian and African Ancistrocladus species, have now been identified for the first time in A. tectorius. Their structural elucidation was achieved by spectroscopic analysis including HRESIMS, 1D and 2D NMR, and by chemical (oxidative degradation) and chiroptical (electronic circular dichroism) methods. Ancistrobenomine B (5) exhibited moderate effects against Plasmodium falciparum and Trypanosoma brucei rhodesiense in vitro, and it was found to display strong cytotoxic activities against drug-sensitive acute lymphoblastic CCRF-CEM leukemia cells and their multidrug-resistant subline, CEM/ADR5000.

2-Phenylnaphthalenes and a polyoxygenated cyclohexene from the stem and root extracts of Uvaria cherrevensis (Annonaceae).

Three new 2-phenylnaphthalene derivatives, cherrevenaphthalenes A-C (1-3), and a new polyoxygenated cyclohexene derivative, (-)-uvaribonol F (4) together with six known compounds, 5-10, were isolated from the stem and root extracts of Uvaria cherrevensis (Annonaceae). The structures of all isolated compounds were elucidated by spectroscopic analysis. The structures of 3 and 4 were further confirmed by single crystal X-ray diffraction methods. Compound 2 exhibited modest antiplasmodial activity against the P. falciparum stains TM4/8.2 and K1CB1 with IC50 values of 18.8±3.63 and 23.4±4.08µM, respectively, and weak cytotoxicity to a Vero cell line. Furthermore, compound 4 displayed cytotoxic activity against a KB cell line with an IC50 value of 22.1±0.42µM but was non-cytotoxic to the Vero cell line. Compound 5 revealed stronger cytotoxicity towards the KB cell line, with an IC50 value of 5.05±0.86µM and was nearly equally cytotoxic to the Vero cell line.