Fruit and seed structure in the ANA-grade angiosperms: Ancestral traits and specializations.

PREMISE: The representatives of the ANA-grade angiosperms demonstrate a diverse pattern of morphological characters, but their apocarpous gynoecium (except in Nymphaeaceae), composed of at least partly ascidiate carpels, the four-nucleate and four-celled female gametophyte, and the diploid endosperm (except in Amborella) are inferred to be plesiomorphies. Since the structure of fruits in Austrobaileyales is under-investigated, this research aims to fill this gap in these data, describing the carpological characters of ANA-grade taxa, and potentially illuminating the ancestral fruit and seed types of angiosperms. METHODS: The pericarp and seed coat anatomy was studied with light microscopy. The character optimization was carried out using WinClada software. RESULTS: The fruits of Austrobaileya, Trimenia, Kadsura, and Schisandra are determined to be apocarpous berries of the Schisandra type, with a parenchymatous pericarp and mesotestal (Austrobaileya) or exomesotestal seeds (other genera). Most inferred scenarios of fruit evolution indicate that the apocarpous berry is either the most probable plesiomorphic fruit type of all angiosperms, or that of all angiosperms except Amborellaceae. This inference suggests the early origin of the berry in fruit evolution. The plesiomorphic seed type of angiosperms according to reconstructed scenarios of seed type evolution was either a seed lacking a sclerenchymatous layer or an exotestal seed. CONCLUSIONS: The current research indicates that an apocarpous berry, and not a follicle, is a probable plesiomorphic character of the ANA-grade taxa and of angiosperms as a whole.

[Research progress on chemical constituents from Kadsura genus and its pharmacological activities and clinical application].

The 29 plant species in the Kadsura genus of the Schisandraceae family are mainly distributed in eastern and southeas-tern Asia. Ten species of plants in this genus are distributed in China, some of which are folk medicinal plants with activating blood circulation, relieving pain, dispelling wind, and dehumidifying effects. Their main constituents are lignans and triterpenes. The current pharmacology and clinical studies have shown that their extracts and constituents have anti-rheumatoid arthritis, liver protection, antioxidation, anti-inflammatory, and other biological activities. The rheumatologic and liver diseases can also be treated with the plants in the clinic. The new chemical constituents reported in the last decade(2012 to date) from the plants of Kadsura genus in China, as well as their pharmacological effects and clinical applications in recent years were reviewed, so as to provide a theoretical basis for further research on the genus.

Dibenzocyclooctadiene lignans from the family Schisandraceae: A review of phytochemistry, structure-activity relationship, and hepatoprotective effects.

Liver injury is a common pathological process characterized by massive degeneration and abnormal death of liver cells. With increase in dead cells and necrosis, liver injury eventually leads to nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and even hepatocellular carcinoma (HCC). Consequently, it is necessary to treat liver injury and to prevent its progression. The drug Bicylol is widely employed in China to treat chronic hepatitis B virus (HBV) and has therapeutic potential for liver injury. It is the derivative of dibenzocyclooctadiene lignans extracted from Schisandra chinensis (SC). The Schisandraceae family is a rich source of dibenzocyclooctadiene lignans, which possesses potential liver protective activity. This study aimed to comprehensively summarize the phytochemistry, structure-activity relationship and molecular mechanisms underlying the liver protective activities of dibenzocyclooctadiene lignans from the Schisandraceae family. Here, we had discussed the analysis of absorption or permeation properties of 358 compounds based on Lipinski's rule of five. So far, 358 dibenzocyclooctadiene lignans have been reported, with 37 of them exhibited hepatoprotective effects. The molecular mechanism of the active compounds mainly involves antioxidative stress, anti-inflammation and autophagy through Kelch-like ECH-associating protein 1/nuclear factor erythroid 2 related factor 2/antioxidant response element (Keap1/Nrf2/ARE), nuclear factor kappa B (NF-кB), and transforming growth factor ß (TGF-ß)/Smad 2/3 signaling pathways. This review is expected to provide scientific ideas for future research related to developing and utilizing the dibenzocyclooctadiene lignans from Schisandraceae family.

Chromatographic and Biological Screening of Chosen Species of Schisandraceae Family: Schisandra chinensis, S. rubriflora, S. sphenanthera, S. henryi and Kadsura japonica.

HPLC and TLC profiling was carried out for leaf and fruit extracts of five Schisandraceae species: Schisandra chinensis, S. rubriflora, S. spehenanthera, S. henryi and Kadsura japonica. HPLC measurements confirmed presence of lignans and phenolic compounds in fruits and leaves of all tested species. The most abundant in lignans was S. chinensis fruit extract in which 15 compounds were detected (e. g.: schisandrol A, schisanhenol, γ-schisandrin, gomisin N). The effect-directed detection, i. e., TLC-direct bioautography against Bacillus subtilis, showed exceptionally high activity for S. chinensis and S. rubriflora fruit extracts. On the other hand, TLC-DB enzyme tests (α-glucosidase, lipase, tyrosinase and acetylcholinesterase (AChE) inhibition assays) showed that all fruit and leaf extracts have ability to inhibit the above-mentioned enzymes (except for the K. japonica fruit). The leaf extracts showed much stronger antioxidant activity than the fruit ones, which were assessed and compared using both TLC-direct bioautography and spectrophotometric measurements based on ABTS, DPPH and FRAP tests.

Dimethylbutyrylated Dibenzocyclooctadiene Lignans from the Fruits of Schisandra cauliflora Inhibit NO Production in LPS-Activated RAW264.7 Cells.

From the fruits of Schisandra cauliflora, five new dimethylbutyrylated dibenzocyclooctadiene lignans, named schisandracaurins A-E, were isolated using separation and chromatographic techniques. Their structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. The schisandracaurins A-E potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC50 values from 21.4 to 30.3 µM.

Schisanwilsonins H and I, two new dibenzocyclooctane lignans from the fruits of Schisandra wilsoniana.

Two new dibenzocyclooctane lignans, schisanwilsonins H (1) and I (2), together with eight known compounds gomisin J (3), wulignan A1 (4), gomisin S (5), tigloylgomisin P (6), gomisin O (7), (-)-gomisin K1 (8), rubschisantherin (9) and wuweizisu C (10) were isolated from the 95% ethanol extract of the fruits of Schisandra wilsoniana. 7 exhibited anti-HBV activity with potency against HBsAg and HBeAg secretion by 37.1% and 32.6%, respectively, at 50 µg/ml. 10 exhibited anti-HIV activity with EC50 and therapeutic index (TI) values of 2.10 µg/ml and 11.98, respectively.

Heilaohuacid G, a new triterpenoid from Kadsura coccinea inhibits proliferation, induces apoptosis, and ameliorates inflammation in RA-FLS and RAW 264.7 cells via suppressing NF-𝜠B pathway.

Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC50 value of 8.16 ± 0.47 µM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model.

Cytotoxic lanostane triterpenoids from the ethanol extract of Schisandra viridis.

Three new lanostane triterpenoids, designated as 6-hydroxyl schiglausin A (1), 29-hydroxyl schiglausin D (2), and 6-hydroxyl schiglausin G (3), were isolated from the ethanol extract of the stems of Schisandra viridis. Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic activities. As a result, compound 1 exhibited cytotoxic activities for all six tested human lung cancer cell lines with IC50 values less than 10 µM.

Dibenzocyclooctadiene lignans from Kadsura coccinea alleviate APAP-induced hepatotoxicity via oxidative stress inhibition and activating the Nrf2 pathway in vitro.

Phytochemical investigation on the roots of Kadsura coccinea led to the isolation five previously unknown dibenzocyclooctadiene lignans, named heilaohusuins A-E (1-5). Their structures determined by NMR spectroscopy, HR-ESI-MS, and ECD spectra. Hepatoprotection effects of a series of dibenzocyclooctadiene derivatives (1-68) were investigated against acetaminophen (APAP) induced HepG2 cells. Compounds 2, 10, 13, 21, 32, 41, 46, and 49 showed remarkable protective effects, increasing the viabilities to > 52.2% (bicyclol, 52.1 ± 1.3%) at 10 µM. The structure-activity relationships (SAR) for hepatoprotective activity were summarized, according to the activity results of dibenzocyclooctadiene derivatives. Furthermore, we found that one new dibenzocyclooctadiene lignan heilaohusuin B attenuates hepatotoxicity, the mechanism might be closely correlated with oxidative stress inhibition via activating the Nrf2 pathway.

New Cadinane Sesquiterpenes from the Stems of Kadsura heteroclita.

As part of our continual efforts to exploit 'Tujia Ethnomedicine' for their pharmacophoric functionalities, we herein investigated Kadsura heteroclita collected from a deep Wulin mountain area in northern Hunan province. The current study resulted in the isolation of three new sesquiterpenes: 6α,9α,15-trihydroxycadinan-4-en-3-one (1), (+)-3,11,12-trihydroxycalamenene (2), (-)-3,10,11,12-tetrahydroxy-calamenene (3), along with four known sesquiterpenes (4-7), and a cytochalasin H (8). Their chemical structures were elucidated by 1D-, and 2D-NMR spectroscopy, and HRESI-MS, CD spectrometry. The antioxidant, and cytotoxic activities of the compounds were evaluated. Compound 8 exhibited a strong antioxidant effect with an IC50 value of 3.67 µM on isolated human polymorphonuclear cells or neutrophils.

Two New AChE Inhibitors Isolated from Li Folk Herb Heilaohu "Kadsura coccinea" Stems.

Two new triterpenoids, named kadsuricoccins A and B, together with three known ones, were isolated from the Li folk herb Heilaohu, the stems of Kadsura coccinea (Lem.) A. C. Smith, which was used for food and as a healthy supplement. Their structures were elucidated by comprehensive analyses of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. To search healthy components, an acetylcholinesterase (AChE) inhibitory activity test by Ellman's Method was conducted, kadsuricoccins A and B showed activity with the AChE inhibit index (AII) up to 68.96% ± 0.19% and 57.8% ± 0.11% at 94 nM (compared with positive control tacrine AII 79.80% ± 0.20%, 9.4 nM), respectively.

Cytotoxic lanostane triterpenoids from the stems of Schisandra glaucescens.

Phytochemical investigation on the stems of Schisandra glaucescens resulted into the isolation of three new lanostane triterpenoids, 12-hydroxyschiglausin B (1), 12-hydroxykadsuphilactone B (2), and 20R-hydroxyschinalactone C (3). Structural elucidation of all the compounds was accomplished by spectral methods. The isolated compounds were tested in vitro for cytotoxic activities. As a result, triterpenoids 1 and 2 showed cytotoxic activities for all six tested tumor cell lines with IC50 values less than 15 µM.

Renchangianins F and G: two new sesquiterpenoids from Kadsura renchangiana.

Phytochemical investigation on the stems of Kadsura renchangiana led to the isolation of two new sesquiterpenoids, renchangianins F and G (1 and 2). Their structures were elucidated by spectroscopic methods, including 2D NMR techniques. The in vitro cytotoxic activities of the isolates were studied against HepG2, A549, and LN229 cancer cell lines.

Highly oxygenated triterpenoids from the roots of Schisandra chinensis and their anti-inflammatory activities.

A new highly oxygenated triterpenoid, schinchinenlactone D (1), and three known compounds (2-4) were isolated from the roots of Schisandra chinensis. Their structures were determined by combining the spectroscopic analysis with the theoretical computations. The anti-inflammatory activities of compounds 1-4 were evaluated, and compound 3 exhibits the most significant activity in the inhibition of NO production with an IC50 value of 10.6 µM.

Effect of pinoresinol-lariciresinol reductases on biosynthesis of lignans with substrate selectivity in Schisandra chinensis.

Schisandra lignans are the main bioactive compounds found in Schisandra chinensis fruits, such as schisandrol lignans and schisandrin lignans, which play important roles in organ protection or other clinical roles. Pinoresinol-lariciresinol reductase (PLR) plays a pivotal role in plant lignan biosynthesis, however, limited research has been conducted on S. chinensis PLR to date. This study identified five genes as ScPLR, successfully cloned their coding sequences, and elucidated their catalytic capabilities. ScPLR3-5 could recognize both pinoresinol and lariciresinol as substrates, and convert them into lariciresinol and secoisolariciresinol, respectively, while ScPLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. Transcript-metabolite correlation analysis indicated that ScPLR2 exhibited unique properties that differed from the other members. Molecular docking and site-directed mutagenesis revealed that Phe271 and Leu40 in the substrate binding motif were crucial for the catalytic activity of ScPLR2. This study serves as a foundation for understanding the essential enzymes involved in schisandra lignan biosynthesis.

Characterization of the complete chloroplast genome sequence of Schisandra propinqua subsp. sinensis (Oliv.) R.M.K.Saunders 1997 (Schisandraceae).

Schisandra propinqua subsp. sinensis (Oliv.) R.M.K. Saunders 1997, a woody vine plant esteemed for its medicinal properties, has garnered attention in botanical research. In this study, we elucidated the complete chloroplast genome sequence of S. propinqua. The genome spans 145,562 bp and comprises a large single-copy (LSC) region of 94,164 bp, a small single-copy region of 18,294 bp (SSC), and a pair of inverted repeats (IR) of 16,552 bp. Notably, S. propinqua exhibits an overall GC content of 36.2%. Annotation revealed a total of 116 genes, encompassing 81 protein-coding genes, 27 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis unveiled a close relationship among Schisandraceae, indicating the evolutionary proximity. This comprehensive genomic dataset provides valuable insights into the genetic makeup and evolutionary dynamics within the Schisandra genus.

Wunorlactones A-G, seven undescribed 7/8/5 and 7/8/3 carbon skeleton schinortriterpenoids from the stems and leaves of Schisandra chinensis, and their neuroprotective activities.

Schisandra chinensis is an important traditional Chinese medicine and its main bioactive components are lignans and schinortriterpenoids (SNTs). The aim of this study was to explore the biologically rich SNTs from the stem and leaves of S. chinensis (SCSL). Here, seven previously undescribed 7/8/5 and 7/8/3 carbon skeleton SNTs (1-7) were reported. Their structures were determined by NMR, UV, MS, ECD, and X-ray diffraction analyses, and the neuroprotective activities of these compounds on corticosterone-induced PC12 cell injury were evaluated. The results showed that 1, 5, and 7 (25 µM) had neuroprotective effects, and the cell viability was increased by 20.07%, 14.24%, and 15.14% (positive control: 30.64%), respectively. These findings increased the number of described SNTs in SCSL, and the neuroprotective activities of all compounds indicated their potential application in neurodegenerative diseases.

Three new schinortriterpenoids from the leaves of Schisandra chinensis (Turcz.) Baill.

Three undescribed schinortriterpenoids, schinensilactones D-F (1-3), together with five known ones, namely, wuweizidilactone A (4), wuweizidilactone C (5), wuweizidilactone F (6), wuweizidilactone J (7) and wuweizidilactone N (8), were isolated from the leaves of Schisandra chinensis (Turcz.) Baill. The structures of new compounds were established by analysis of their spectroscopic data including MS, IR, 1D- and 2D-NMR spectra. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD) spectra. All compounds were evaluated for their neuroprotective effects against H2O2-induced injury in human neuroblastoma SH-SY5Y cell lines. Cell viability was remarkably reduced to 52.33% in H2O2-treated cells. Compounds 5-7 exhibited moderate neuroprotective activities at 50 µM, with cell viability of 64.84%, 67.34% and 63.73%, respectively.

One undescribed glycoside benzofuran derivative and a new p-hydroxybenzoate glycoside from the leaves of Illicium dunnianum Tutcher.

One undescribed benzofuran derivative (illiciumphenolicacid A, 1) and one new phenolic glycoside (illiciumphenolicacid B, 2), together with six known compounds (3-8) were isolated from the leaves of Illicium dunnianum Tutcher. Their structures were elucidated by detailed spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR). In addition, we determined the α-glucosidase inhibitory activity of the isolates in vitro using spectrophotometric methods. Compared with the positive control acarbose (IC50 306.2 ± 4.1 µM), compounds 1-8 were shown to be moderate potential α-glucosidase inhibitory activity with IC50 values in the range 380-655 µM.

Schisandraceae triterpenoids: A review of phytochemistry, bioactivities and synthesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Schisandraceae family have a rich and medicinal history dating back to ancient times. Many of them are used as folk medicine in the treatment of chronic coughs, asthma, nocturnal emission, spontaneous sweating, night sweats, palpitation, insomnia and thirst. AIM OF THE REVIEW: The current review is carried out on triterpenoids from the Schisandraceae family, aiming to comprehensively summarize their phytochemistry, pharmacology and synthesis and provide new insights to the chemical and pharmacological study and rational utilization on medicinal plants of the Schisandarceae family. MATERIALS AND METHODS: The information was searched from the scientific literature published from June 2014 to November 2021 on the online databases (including PubMed, CNKI, Elsevier, SciFinder and Web of Science) and other bibliography (e.g. the Chinese Pharmacopoeia, 2020 edition, Chinese herbal books). The scientific literature related to phytochemistry, pharmacology, biological activites and synthesis of triterpenoids from the Schisandraceae family was gathered. RESULTS: From June 2014 to November 2021, there were approximately 211 novel triterpenoids isolated and identified from 18 species of the Schisandraceae family. These compounds exhibit tremendous diversity in their structures, and some of them possess promising pharmacological activities, including anti-viral, anti-tumor, anti-inflammatory, hepatoprotective, immunosuppressive activities and neuroprotective effects. In the attempt to synthesize active compounds, the total synthesis of 13 schinortriterpenoids belonging to five structural types was successfully completed. CONCLUSIONS: Studies of triterpenoids from the Schisandraceae family are well documented in this review (from June 2014 to November 2021), and it is also well acknowledged that they are valuable resources with medicinal efficacy. However, relevant pharmacological studies are limited to in vitro tests, and data from in vivo studies and toxicology are lacking or unavailable. Fortunately, there is growing interest in the synthesis of active compounds, which should serve as an approach for accessing active compounds to develop in vivo or toxicity studies, with a view of clarifying their in vitro and vivo mechanisms for more effective and safe natural drugs.