Racemic Norlignans as Diastereoisomers from Ferula sinkiangensis Resins with Antitumor and Wound-Healing Promotion Activities.

Ferulasinkins A-D (1-4), four new norlignans, were isolated from the resins of Ferula sinkiangensis, a medicinal plant of the Apiaceae family. All of them were obtained as racemic mixtures, chiral HPLC was used to produce their (+)- and (-)-antipodes. The structures of these new compounds, including their absolute configurations, were elucidated by spectroscopic and computational methods. This isolation provides new insight into the chemical profiling of F. sinkiangensis resins beyond the well-investigated structure types such as sesquiterpene coumarins and disulfides. Compounds 2a and 3a were found to significantly inhibit the invasion and migration of triple-negative breast cancer (TNBC) cell lines via CCK-8 assay. On the other hand, the wound-healing assay also demonstrated that compounds 4a and 4b could promote the proliferation of human umbilical vein endothelial cells (HUVECs). Notably, the promoting effects of 4a and 4b were observed as more significant versus a positive control using basic fibroblast growth factor (bFGF).

Sinensiols H-J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring.

One new lignan sinensiol H (1) and two new bisnorlignans, sinensiols I and J (2 and 3), along with three known compounds were isolated from the whole plants of Selaginella sinensis. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy as well as high-resolution mass spectrometry. The absolute configuration of 1 was established by ECD calculation. Compounds 2 and 3 represent rare examples of naturally occurring 9,9'-bisnorlignans. All the isolated compounds were assayed for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages.

Nor-Lignans: Occurrence in Plants and Biological Activities-A Review.

In this review article, the occurrence of nor-lignans and their biological activities are explored and described. Nor-lignans have proven to be present in several different families also belonging to chemosystematically distant orders as well as to have many different beneficial pharmacological activities. This review article represents the first one on this argument and is thought to give a first overview on these compounds with the hope that their study may continue and increase, after this.

Formation of Tetrahydrofurano-, Aryltetralin, and Butyrolactone Norlignans through the Epoxidation of 9-Norlignans.

Epoxidation of the C=C double bond in unsaturated norlignans derived from hydroxymatairesinol was studied. The intermediate epoxides were formed in up to quantitative conversions and were readily further transformed into tetrahydrofuran, aryltetralin, and butyrolactone products-in diastereomeric mixtures-through ring-closing reactions and intramolecular couplings. For epoxidation, the classical Prilezhaev reaction, using stoichiometric amounts of meta-chloroperbenzoic acid (mCPBA), was used. As an alternative method, a catalytic system using dimeric molybdenum-complexes [MoO2L]2 with ONO- or ONS-tridentate Schiff base ligands and aqueous tert-butyl hydroperoxide (TBHP) as oxidant was used on the same substrates. Although the epoxidation was quantitative when using the Mo-catalysts, the higher temperatures led to more side-products and lower yields. Kinetic studies were also performed on the Mo-catalyzed reactions.

9-Norlignans: Occurrence, Properties and Their Semisynthetic Preparation from Hydroxymatairesinol.

Lignans, neolignans, norlignans and norneolignans constitute a large class of phenolic natural compounds. 9-Norlignans, here defined to contain a ß⁻ß' bond between the two phenylpropanoid units and to lack carbon number 9 from the parent lignan structure, are the most rarely occurring compounds within this class of natural compounds. We present here an overview of the structure, occurrence and biological activity of thirty-five 9-norlignans reported in the literature to date. In addition, we report the semisynthetic preparation of sixteen 9-norlignans using the natural lignan hydroxymatairesinol obtained from spruce knots, as starting material. 9-Norlignans are shown to exist in different species and to have various biological activities, and they may therefore serve as lead compounds for example for the development of anticancer agents. Hydroxymatairesinol is shown to be a readily available starting material for the preparation of norlignans of the imperanene, vitrofolal and noralashinol family.

Norlignans from Pouzolzia zeylanica var. microphylla and their nitric oxide inhibitory activity.

Five new compounds, pouzolignan F [4-hydroxy-3-(3,5-dihydroxyphenyl)-2-[bis(4-hydroxy-3-methoxyphenyl)methyl]butyl acetate] (1), pouzolignan G [4-hydroxy-3-(3,5-dihydroxyphenyl)-2-[(4-hydroxy-3,5-dimethoxyphenyl)(4-hydroxy-3-methoxyphenyl)methyl]butyl acetate] (2), pouzolignan H [1,4-dihydroxy-3-(3,5-dihydroxyphenyl)-2-[bis(4-hydroxy-3-methoxyphenyl)methyl]butane] (3), pouzolignan I [1,4-dihydroxy-3-(3,5-dihydroxyphenyl)-2-[(4-hydroxy-3,5-dime thoxyphenyl)-(4-hydroxy-3-methoxyphenyl)methyl]butane] (4), and pouzolignan J [1,4-dihydroxy-3-(3,5-dihydroxyphenyl) -2-[(3,4,5-trimethoxyphenyl)(4-hydroxy-3-methoxyphenyl)methyl]butane] (5), along with two known compounds, indolyl-3-carboxylic acid (6) and uracil (7), were isolated from the aerial parts of Pouzolzia zeylanica (L.) Benn. var. microphylla (Wedd.) W.T.Wang. The structures of these compounds were characterized based on spectroscopic methods, including IR, NMR ((1)H-(1)H COSY, HSQC, HMBC, and NOESY), and HR-ESI/TOF-MS experiments. All the new norlignans were assayed for inhibitory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages.

New lignans and their biological activities.

Lignans, which are widely distributed in higher plants, represent a vast and rather diverse group of phenylpropane derivatives. They have attracted considerable attention due to their pharmacological activities. Some of the lignans have been developed approved therapeutics, and others are considered as lead structures for new drugs. This article is based on our previous review of lignans discovered in the period 2000-2004, and it provides a comprehensive compilation of the 354 new naturally occurring lignans obtained from 61 plant families between 2005 and 2011. We classified five main types according to their structural features, and provided the details of their sources, some typical structures, and diverse biological activities. A tabular compilation of the novel lignans by species is presented at the end. A total of 144 references were considered for this review.

New nor-lignans from the leaves of styrax annamensis guillaumin.

Phytochemical study of the leaves of Styrax annamensis Guillaumin resulted in the isolation of a new natural product egonol-3''-sulphate (1), and two new derivatives egonol-3-methyl-D-galactopyranoside (2) and 7-methoxy-2-(3',4'-methylenedioxyphenyl)-benzofuran-5-carboxamide (3). Their chemical structures were -elucidated by spectroscopic data. Compounds 1 and 3 significantly established a great role for the chemotaxonomic aspect. Compound 1 showed cytotoxicity against four cancer cell lines KB, HepG2, Lu, and MCF7 with the IC50 values of 84.90-101.69 µg/mL, and exhibited acetylcholinesterase (AChE) inhibitory activity with the IC50 value of 97.08 µg/mL.

Biological activities of organic extracts and specialized metabolites from different parts of Cryptomeria japonica (Cupressaceae) - A critical review.

Forest operations and wood industry generate large amounts of residues that are discarded in the field and cause environmental pollution. However, these biomass residues are still raw materials to obtain value-added products, such as essential oils, organic/aqueous extracts and resins that are among the great natural sources of bioactive metabolites. Thus, in recent years, the scientific community is giving special attention to their valorization. To date, different uses of biomass residues have been proposed, such as a source of renewable energy, fertilizers, animal feed and bioactive molecules. In this context, Cryptomeria japonica biomass residues (e.g., bark and its exudate, heartwood, sapwood, leaves, cones and roots) represent a source of diverse specialized metabolites (e.g., sesqui-, di-, tri- and sesquarterpenes, flavonoids, lignans and norlignans) with potential application in different fields, particularly in the agrochemical, food, cosmeceutical, pharmaceutical, phytomedicine and esthetic, due to their valuable multi-bioactivities determined over the last decades. Thus, this review provides an overview of the reported biological activities of organic extracts/fractions and their specialized metabolites obtained from different parts of C. japonica, in order to encourage the alternative uses of C. japonica wastes/byproducts, and implement a sustainable and circular bioeconomy.

Norlignans and phenolics from genus Curculigo protect corticosterone-injured neuroblastoma cells SH-SY5Y by inhibiting endoplasmic reticulum stress-mitochondria pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of genus Curculigo are divided into the Section Curculigo and the Section Capitulata, which are mainly distributed in southeastern and southwestern China. Various ancient chinese books record that these plants were used as an important herb for tonifying kidney yang. Traditional Chinese medicine often draws on this property to treat depression syndrome. Thus genus Curculigo has potential for the treatment of neurodegenerative diseases (ND). The study showed that phenolics were the main characteristic components of plants in the Section Curculigo, represented by orcinol glucoside and curculigoside; the norlignans, with Ph-C5-Ph as the basic backbone, were the main characteristic components of the Section Capitulata. However, there is a lack of sufficient scientific evidence as to whether these two types of ingredients have neuroprotective effects. AIM OF THE STUDY: To determine the neuroprotective effects of phenolics and norlignans in genus Curculigo on human neuroblastoma cells SH-SY5Y. To discuss their structure-activity relationship and screen for compounds with high activity and neuroprotective effects. To reveal that the amelioration of endoplasmic reticulum (ER) stress by two classes of compounds is mediated by the PERK/eIF2α/ATF4 pathway. MATERIALS AND METHODS: The cytotoxicity of 17 compounds was assayed by MTT. SH-SY5Y cells were damaged by corticosterone (Cort) (200 µM) for 24 h and then co-administered with 17 compounds (0.1-100 µM) and Cort (200 µM) for 24 h. Cell survival was determined by MTT assay. Apoptosis rate, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels were detected using flow cytometry. Intracellular Ca2+ levels were detected using a fluorescent probe. Cellular mitochondrial and ER damage was observed using transmission electron microscopy (TEM). ER stress and apoptotic pathway-related proteins (BiP, CHOP, cleaved caspase-3, cleaved caspase-9, Bax/Bcl-2), and the expression level of PERK/eIF2α/ATF4 pathway was measured via western blot (WB). RESULTS: The experimental data showed that Cort treatment of SH-SY5Y cells resulted in decreased cell survival and increased apoptosis, mitochondrial depolarization, ROS, and intracellular Ca2+ levels. The co-action of 17 compounds and Cort for a period of time significantly increased cell survival. Compounds 3, 7, 12, 13 also reduced apoptosis rate, mitochondrial depolarization, ROS and intracellular Ca2+ levels in the subsequent experiments. In addition, TEM observed that Cort caused mitochondrial and ER damage, and the damage was improved after treatment. WB analysis obtained that Cort increased the expression of apoptotic and ER stress-related proteins and activated pathway expression. However, in the presence of compounds 3, 7, 12, 13, the expression of BiP, CHOP, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 was significantly reduced, and the phosphorylation of PERK and eIF2α and the expression of ATF4 were inhibited. CONCLUSION: This study found that one phenolic (3) and three norlignans (7, 12, 13) from genus Curculigo have significant neuroprotective effects. The results of the structure-activity relationship indicated that the glucosyl polymeric norlignans and the phenolics with benzoic acid as the parent nucleus were more active. The neuroprotective effect of three norlignans is the latest discovery. This finding has important research value in the field of prevention and treatment of neurodegenerative diseases.

Norlignans as potent GLP-1 secretagogues from the fruits of Amomum villosum.

The dried fruit of Amomum villosum (Amomi Fructus) is an important spices and traditional Chinese medicine. In this study, the EtOH extract of Amomi Fructus was revealed with hypoglycemic effects on db/db mice by increasing plasma insulin levels. After extracted with EtOAc, the EtOAc fraction showed increased activity in stimulating glucagon-like peptide-1 (GLP-1) secretion compared with the EtOH extract. In order to clarify the antidiabetic constituents, four undescribed norlignans, amovillosumins A‒D, were isolated from the EtOAc fraction, and the subsequent chiral resolution yielded three pairs of enantiomers. Their structures were determined by extensive spectroscopic data (1D and 2D NMR, HRESIMS, IR, UV and [α]D) and ECD calculations. Amovillosumins A and B significantly stimulated GLP-1 secretion by 375.1% and 222.7% at 25.0 µM, and 166.9% and 62.7% at 12.5 µM, representing a new type of GLP-1 secretagogues.

Artemyrianins A-G from Artemisia myriantha and Their Cytotoxicity Against HepG2 Cells.

Four new sesquiterpenoids, artemyrianins A-D (1-4), and three new norlignans, artemyrianins E-G (5-7), together with five known compounds (8-12), were isolated from the aerial parts of Artemisia myriantha (Asteraceae). The new compounds were established by spectroscopic data analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2 µM.

Inhibitory effects of norlignans isolated from Anemarrhena asphodeloides on degranulation of rat basophilic leukemia- 2H3Cells.

Anemarrhena asphodeloides is known to suppress inflammation and lower various fevers. To determine the active component of A. asphodeloides, ethanol (EtOH) extract of A. asphodeloides rhizomes was fractionized. The compounds isolated from the dichloromethane (CH2Cl2) soluble fraction were identified as 4'-O-methylnyasol (1), nyasol (2), 3″-methoxynyasol (3), 3″-hydroxy-4″-methoxy-4″-dehydroxynyasol (4), 4-hydroxybenzaldehyde (5), and 4-hydroxyacetophenone (6). The four norlignans (1-4) potently inhibited the release of ß-hexosaminidase from immunoglobulin E (IgE)/dinitrophenol-conjugated bovine serum albumin (DNP-BSA)-treated rat basophilic leukemia (RBL)-2H3 and A23187 plus phorbol 12-myristate 13-acetate co-treated isolated rat primary mast cells, as markers of degranulation and histamine release. The intraperitoneal treatment with the EtOH extract significantly suppressed the fetal reaction, and serum histamine release induced by compound 48/80 in mice. These results suggest that the four active norlignan compounds and the EtOH extract of A. asphodeloides may have potential to be developed as medicines for the treatment of allergies by inhibiting the activation of mast cells.

Isolation of cytotoxic compounds from the seeds of Crataegus pinnatifida.

AIM: To study the chemical constituents and bioactivity of the seeds of Crataegus pinnatifida. METHODS: The chemical constituents were isolated and purified by macroporous adsorptive resin D101, silica gel, and ODS column chromatography, and preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods. In addition, the cytotoxic activities of compounds 1-4 were investigated on OPM2 and RPMI-8226 cells. RESULTS: Four compounds were obtained and their structures were identified as (7S, 8S)-4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)ethoxy]-3, 5-dimethoxybenzaldehyde (1), (+)-balanophonin (2), erythro-guaiacylglycerol-ß-coniferyl aldehyde ether (3), buddlenol A (4). CONCLUSION: Compound 1 is a novel norlignan, while compounds 1-4 exhibited marginal inhibition on the proliferation of OPM2 and RPMI-8226 cells.