Effects of schisandra lignans on the absorption of protopanaxadiol-type ginsenosides mediated by P-glycoprotein and protopanaxatriol-type ginsenosides mediated by CYP3A4.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng Radix et Rhizoma (GRR) and Schisandrae Chinensis Fructus (SCF) are frequently used as herb pairs in traditional herbal formulas especially for the synergetic beneficial effects on lung and heart. Shengmai-yin (SMY), a noted formula, was first published in the traditional Chinese medicine classic named Yixue Qiyuan written by Zhang Yuansu in the Jin Dynasty, and has been used for deficiency of both qi and yin, palpitation, shortness of breath and spontaneous sweating. In SMY, GRR, a sovereign herb, plays an essential role in tonifying lung and supplementing qi, and SCF as an adjuvant herb contributes to the effects of nourishing yin and promoting fluid production, both of which are traditionally used as invigorants in China, Korea, Japan, and Russia. However, the underlying compatibility mechanism of GRR-SCF has remained unknown. AIM OF THE STUDY: In order to explore the impact and underlying mechanism of schisandra chinensis extract (SCE) on the absorption of ginsenosides Rb1, Rc, Rb2 and Rd belonging to protopanaxdiol (PPD)-type and ginsenosides Rg1 and Re belonging to protopanaxtriol (PPT)-type, pharmacokinetic studies, molecular docking technique and single-pass intestinal perfusion (SPIP) experiment were conducted. MATERIAL AND METHODS: Preliminarily, pharmacokinetic characteristics of ginseng extract (GE) in the presence and absence of SCE were studied. Thereafter, molecular docking was used to predict whether ginsenosides were P-glycoprotein (P-gp) or cytochrome P450 isoenzyme 3A4 (CYP3A4) substrates. Finally, the effects and underlying mechanism of SCE on the absorption of GE were further investigated by in situ SPIP experiment. RESULTS: Our findings indicated that SCE could increase exposure in vivo and the intestinal absorption of distinct ginsenosides. Additionally, we found that the PPD-type ginsenosides Rb1, Rc, Rb2, and Rd were substrates for P-gp, and the PPT-type ginsenosides Rg1 and Re were substrates for CYP3A4 rather than P-gp. SCE, which has been found with extensive inhibitory effects on P-gp and CYP3A4, could remarkably promote the intestinal absorption of ginsenosides Rg1, Re, Rb1, Rc, Rb2, and Rd, obtaining similar effects comparable with ketoconazole known as a classic dual inhibitor of P-gp and CYP3A4. CONCLUSIONS: The study demonstrated that SCE could improve the absorption of GE, and revealed the underlying compatibility mechanism of GRR and SCF from the perspective of P-gp and CYP3A4-mediated interactions to some extent, which provided a certain scientific reference for the compatibility and clinical practice of GRR-SCF as common herb pairs in traditional prescriptions such as SMY. Moreover, this study also furnished a strategy for improving the oral bioavailability of different types of ginsenosides by drug combinations.

Equivalent evaluation and biological ingredients of Syringa pinnatifolia against acute myocardial ischemia in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The peeled roots, stems, and twigs of Syringa pinnatifolia Hemsl., known as Shan-Chen-Xiang (SCX) in Chinese, has the traditional effects such as anti-Khii, clearing heat and relieving pain. It has been clinically applied for the treatment of heart failure and mental abnormalities, and gradually replaced agarwood in Mongolian medicine. AIM OF STUDY: The present study aims to evaluate whether the key subfraction C (C), a half composition in mass of total ethanol extract (T) of SCX, exerts an equivalent effect against acute myocardial ischemia (AMI) compared to fraction I (I), and what was the potential pharmacologically active constituents of SCX. MATERIALS AND METHODS: Cardiac function, serum marker enzymes, and myocardial tissue pathology of infarcted mice with ligation of the anterior descending (LAD) branch of the left coronary artery were used to evaluate the anti-AMI effect of C and its equivalent potency to that of I. LCMS-IT-TOF was used to identify the main constituents in C and C-. The new and known compounds were isolated from C by a combination of mass spectrometry and bioactivity-guided fractionation methods, and structures were elucidated by extensive spectroscopic and chemical methods, including calculated 13C NMR data, calculated electronic circular dichroism, and single-crystal X-ray crystallography. The protective effect of isolates against oxidative injury induced by H2O2 in H9c2 cells was evaluated according to a previously reported protocol. RESULTS: The results of cardiac function, serum marker enzymes and myocardial tissue pathology observations (fosinopril as a positive drug) suggested that C (40 mg/kg, orally administered once a day for 7 days) possessed the anti-AMI effect and was equivalent to that of I, while C- did not show the positive effect. Then, 32 lignans were isolated from C, including the majors (8R,8'R,9S)-4,4'-dihydroxy-3,3',9-trimethoxy-9,9'-epoxylignan (24) and (8R,8'R,9R)-4,4'-dihydroxy-3,3',9-trimethoxy-9,9'-epoxylignan (25), which were confirmed by HPLC and LC-MS characterization. Among them, 15 ones were previously undescribed, including a pair of enantiomers (6a/6b), and 11 ones (1, 2, 6a/6b, 8, 10, 12, 16, 17, 24, and 25) exhibited protective effect against oxidative injury to H9c2 cells at different concentrations (ranged from 0.156 to 80 µM). CONCLUSION: C (40 mg/kg) exerts cardioprotective effect in mice, which was equivalent to that of I and T. Lignans, including both representative compounds (24, 25) and other undescribed molecules with low content, significantly contribute to the anti-AMI effect of SCX. However, the anti-AMI property assessment of SCX should not exclude the contribution from the representative sesquiterpenoid ZER. Hence, the exploration of the final potential substances in SCX requires further investigation.

Macelignan prevents colorectal cancer metastasis by inhibiting M2 macrophage polarization.

BACKGROUND: Colorectal cancer (CRC) metastasis is a complicated process that not only involves tumor cells but also the effects of M2 type tumor-associated macrophages, a key component of the tumor microenvironment (TME), act a crucial role in cancer metastasis. Macelignan, an orally active lignan isolated from Myristica fragrans, possesses various beneficial biological activities, including anti-cancer effects, but its effect on macrophage polarization in the TME remains unknown. PURPOSE: To evaluate the inhibitory potency and prospective mechanism of macelignan on M2 polarization of macrophages and CRC metastasis. METHODS: The polarization and specific mechanism of M1 and M2 macrophage regulated by macelignan were determined by western blot, flow cytometry, immunofluorescence and network pharmacology. In vitro and in vivo function assays were performed to investigate the roles of macelignan in CRC metastasis. RESULTS: Macelignan efficiently inhibited IL-4/13-induced polarization of M2 macrophages by suppressing the PI3K/AKT pathway in a reactive oxygen species (ROS)-dependent manner. The proportion of CD206+ M2 macrophages was elevated in patients with CRC liver metastasis. Furthermore, macelignan inhibited M2 macrophage-mediated metastasis of CRC cells in vitro and in vivo. Mechanistically, macelignan reduced secretion of IL-1ß from M2 macrophages, which in turn blocked NF-κB p65 nuclear translocation and inhibited metastasis. CONCLUSION: Macelignan suppressed macrophage M2 polarization via ROS-mediated PI3K/AKT signaling pathway, thus preventing IL-1ß/NF-κB-dependent CRC metastasis. In the present study, we reveal a previously unrecognized mechanism of macelignan in the prevention of CRC metastasis and demonstrate its effectively and safely therapeutic potential in CRC treatment.

The genus Balanophora J. R. Forst. & G. Forst. - Its use in traditional medicine, phytochemistry, and pharmacology: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Natural products, particularly medicinal plants, have been utilized in traditional medicine for millennia to treat various diseases. The genus Balanophora (Balanophoraceae) consists of 23 accepted species. These species are the most controversial flowering plants, with highly reduced morphologies and are found parasitizing on the roots of their host. They have been used in traditional medicine as a remedy for stomach pain, detumescence, uterine prolapse, wounds, syphilis, gonorrhea, treating injuries from falls, and other conditions. However, there is no review of this genus on its traditional uses, phytochemistry, and pharmacology. AIM: The present narrative review discusses the scientific data supporting the traditional uses of Balanophora species. The available information on its botanical properties, traditional uses, chemical contents, pharmacological activities, and toxicity was summarized to help comprehend current research and offer a foundation for future research. MATERIALS AND METHODS: The materials used in combining data on the genus Balanophora comprises online sources such as Web of Science, Google Scholar, Science Direct, and Chinese National Knowledge Infrastructure (CNKI) for Chinese-related materials. World Flora online was used in validating the scientific names of this genus while ChemBio Draw Ultra Version 22.2 software was employed in drawing the phytochemical compounds. RESULTS: Nine Balanophora species including B. harlandii, B. japonica, B. polyandra, B. fungosa, B. fungosa subsp. indica, B. laxiflora, B. abbreviata, B. tobiracola, and B. involucrata have been documented as vital sources of traditional medicines in different parts of Asia. A total of 159 secondary metabolites have been isolated and identified from the ten species of this genus comprising tannins, flavonoids, sterols, lignans, chalcones, terpenes, and phenylpropanoids. Among these compounds, tannins, lignans, terpenoids, chalcones and phenolic acids contribute to the pharmacological activities of the species in this genus with several biological activities both in vitro and in vivo such as anti-inflammatory, anti-oxidant, hypoglycemic activity, cytotoxicity, anti-microbial, melanin synthesis etc. CONCLUSION: This review summarizes the available literature on the traditional uses, pharmacological properties, and phytoconstituents of Balanophora species indicating that they contain fascinating chemical compounds with diverse biological activities. The traditional uses of the species in this genus have been confirmed by scientific data such as antimicrobial, hemostatic effect, gastroprotective activity and others. However, many species in this genus are yet unknown in terms of their botanical uses, chemical composition and biological activities. Thus, more research into the scientific connections between traditional medicinal uses and pharmacological activities, mode of action of the isolated bioactive constituents, and toxicity of other Balanophora species is needed to determine their efficacy and therapeutic potential for safe clinical application.

Sesamol: A lignan in sesame seeds with potent anti-inflammatory and immunomodulatory properties.

Inflammation is associated with the development and progression of a plethora of diseases including joint, metabolic, neurological, hepatic, and renal disorders. Sesamol, derived from the seeds of Sesamum indicum L., has received considerable attention due to its well-documented multipotent phytotherapeutic effects, including its anti-inflammatory and immunomodulatory properties. However, to date, no comprehensive review has been established to highlight or summarize the anti-inflammatory and immunomodulatory properties of sesamol. Herein, we aim to address this gap in the literature by presenting a thorough review encapsulating evidence surrounding the range of inflammatory mediators and cytokines shown to be targeted by sesamol in modulating its anti-inflammatory actions against a range of inflammatory disorders. Additionally, evidence highlighting the role that sesamol has in modulating components of adaptive immunity including cellular immune responses and Th1/Th2 balance is underscored. Moreover, the molecular mechanisms and the signaling pathways underlying such effects are also highlighted. Findings indicate that this seemingly potent lignan mediates its anti-inflammatory actions, at least in part, via suppression of various pro-inflammatory cytokines like IL-1ß and TNFα, and downregulation of a multitude of signaling pathways including NF-κB and MAPK. In conclusion, we anticipate that sesamol may be employed in future therapeutic regimens to aid in more effective drug development to alleviate immune-related and inflammatory conditions.

Effects of Combining Docosahexaenoic Acid and Eicosapentaenoic Acid with Sesame Lignan on Vascular Endothelial Function.

Vascular endothelial cells produce vasoactive substances, such as nitric oxide (NO), to regulate vascular relaxation and contraction. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) enhance NO production in endothelial cells, and sesamin, a sesame lignan contained in sesame seeds, also promotes NO production. This study examined DHA, EPA, and sesamin's combined effects since it was expected that combining them would further enhance NO production in endothelial cells. Using a human umbilical vein endothelial cell (HUVEC), the NO amount secreted in the culture supernatant was analyzed. Sesamin metabolite (SC1) was used in the experiments because it is a major metabolite in human blood after sesamin absorption. When cells were treated with DHA or EPA alone, they increased NO production in a concentration-dependent manner, whereas no change in NO production was observed for SC1. NO production increased when DHA and EPA were treated in combination with SC1, although the low DHA and EPA concentrations showed no difference in NO production. In the concentrations in which the combined effect was observed, SC1 activated eNOS via calcium signaling, whereas DHA and EPA activated eNOS via alterations in the membrane lipid environment. The combined effect of the two pathways was considered to have enhanced the eNOS activity. These results suggested that combining DHA, EPA, and sesamin might improve vascular endothelial function.

Sesamin: A Promising Therapeutic Agent for Ameliorating Symptoms of Diabetes.

Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin's efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.

Analysis of Volatile Components in Dried Fruits and Branch Exudates of Schisandra chinensis with Different Fruit Colors Using GC-IMS Technology.

To investigate the volatile components of Schisandra chinensis (Turcz.) Bail (commonly known as northern Schisandra) of different colors and to explore their similarities and differences, to identify the main flavor substances in the volatile components of the branch exudates of northern schisandra, and finally to establish a fingerprint map of the volatile components of the dried fruits and branch exudates of northern Schisandra of different colors, we used GC-IMS technology to analyze the volatile components of the dried fruits and branch exudates of three different colors of northern Schisandra and established a fingerprint spectra. The results showed that a total of 60 different volatile chemical components were identified in the branch exudates and dried fruits of Schisandra. The components of germplasm resources with different fruit colors were significantly different. The ion mobility spectrum and OPLS-DA results showed that white and yellow fruits were more similar compared to red fruits. The volatile components in dried fruits were significantly higher than those in branch exudates. After VIP (variable importance in projection) screening, 41 key volatile substances in dried fruits and 30 key volatile substances in branch exudates were obtained. After screening by odor activity value (OAV), there were 24 volatile components greater than 1 in both dried fruits and branch exudates. The most important contributing volatile substance was 3-methyl-butanal, and the most important contributing volatile substance in white fruit was (E)-2-hexenal.

Affinity character analysis of magnolol and honokiol based on stepwise frontal analysis coupled with cell membrane chromatography.

Magnolol and honokiol have been reported to exhibit anti-cancer activity. However, few studies are in relation to the interaction of magnolol/honokiol with vascular endothelial growth factor 2 (VEGFR2). In this study, a membrane chromatography method based on VEGFR2 was established for the interaction characteristic analysis between drug and receptor. The selectivity, repeatability and stability of the chromatographic model were evaluated using drugs acting on different receptors. The affinity between VEGFR2 and magnolol/honokiol was verified by cell membrane chromatography. The binding sites of magnolol/honokiol and VEGFR2 were analyzed by zonal elution. Especially, the dissociation equilibrium constants (Kd) of magnolol/honokiol and VEGFR2 were measured by zonal elution and stepwise frontal analysis respectively. In addition, the actions of magnolol/honokiol on VEGFR2 were analyzed by stepwise frontal analysis at different temperatures. The results showed that the binding sites of magnolol and honokiol on VEGFR2 were different from sorafenib, indicating that magnolol and honokiol could be used as competitive agents for self-competitive displacement experiment. The Kd values (order of magnitude) of magnolol/honokiol with VEGFR2 measured by stepwise frontal analysis were consistent with the zonal elution results. Honokiol binds VEGFR2 with higher affinity than magnolol. The main forces that stabilize the interactions of honokiol with VEGFR2 are hydrogen bonds and van der Waal's forces, and the main force of magnolol is electrostatic forces. These discoveries could assist in the prediction of drug activity and understanding for the underlying mechanism.

The What and Who of Dietary Lignans in Human Health: Special Attention to Estrogen Effects and Safety Evaluation.

Lignans are a group of phenolic compounds found in plant-based diets. The human body can obtain lignans through diet, which are then metabolized into enterolignans. The enterolignans have been linked to several health benefits, including anticancer, anti-inflammatory, antioxidant effects, and estrogen effects. This review explores the relationship between the estrogenic effects of lignans and health. This review not only considers the estrogen-like activity of lignans but also discusses the safe dosage of lignans at different life stages. In addition, this review also identified other types of bioactive compounds that can act synergistically with lignans to promote health. Studies have shown that lignan administration during pregnancy and lactation reduces the risk of breast cancer in offspring. Further studies are needed to investigate the estrogenic safety effects of lignan on pregnant women and children. Whether lignans combine with other nutrients in complex food substrates to produce synergistic effects remains to be investigated. This review provides a basis for future studies on the safe dose of lignan and recommended dietary intake of lignan. We believe that the acquired as discussed here has implications for developing dietary therapies that can promote host nutrition and modulate estrogenic diseases.

Antiproliferative Activity of Lignans from Olea ferruginea: In Vitro Evidence Supported by Docking Studies.

BACKGROUND: The aim of the current study was to investigate the anticancer potential of bioactive compounds isolated from the leaves of Olea ferruginea (O. ferruginea). Lignans from O. ferruginea were previously described to possess antibacterial, antileishmanial, and antioxidant properties. Nevertheless, the antiproliferative activity of cycloolivil (1), ferruginan (2), and ferruginan A (3) have not been investigated in depth. METHODS: The compounds were isolated from the ethyl acetate fraction of the leaves extract of O. ferruginea. The isolated molecules were evaluated for their anticancer activity against U-87 MG malignant glioma cells. In parallel, molecular docking studies were also performed to investigate the interaction of the compounds with a duplex DNA sequence and epidermal growth factor receptor (EGFR). RESULTS: In vitro tests showed that all three compounds inhibit U-87 MG malignant glioma cell proliferation dose-dependently in the µM range, and ferruginan A (3) was highlighted as the most promising compound of the set. Molecular docking studies showed that the compounds could interfere with double stranded DNA possessing a cisplatin 1,2-d(GpG) intrastrand cross-link and EGFR. CONCLUSIONS: Overall, the findings suggest that the tested compounds from O. ferruginea may represent a starting point for the identification of novel tools to inhibit glioma cell proliferation.

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.

Polyoxygenated cyclohexene derivatives and other constituents of Uvaria rufa stem.

Six undescribed compounds, uvarirufols D and E, (+)-uvarigranol B, (-)-uvarigranol E, 6-acetoxy-5-hydroxy-7-methoxyflavanone and cherrevenaphthalene D, along with twelve known compounds, including polyoxygenated cyclohexenes, flavonoids, and lignans, were isolated from the methanol extract of Uvaria rufa stems. Their structures were elucidated by spectroscopic analyses and the absolute configurations were determined using electronic circular dichroism. Several isolates were evaluated for cytotoxic, antitubercular and anti-inflammatory potentials. (-)-6-Acetylzeylenol showed moderate inhibitory activity against Mycobacterium tuberculosis, with MIC value of 47.10 µg/mL. Cherrevenaphthalene D exhibited weak antimycobacterial activity and potent inhibitory effect on lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells (EC50 = 8.54 µM). 8-Hydroxy-5,7-dimethoxyflavanone displayed moderate level of NO inhibition (EC50 = 43.62 µM) with little cytotoxicity. The polyoxygenated cyclohexenes and lignans were inactive against HCT 116 and 22Rv1 cancer cells (IC50 > 100 µM).

Lignan constituents with α-amylase and α-glucosidase inhibitory activities from the fruits of Viburnum urceolatum.

Eleven previously undescribed lignan constituents, including five 8-O-4' type neolignans, viburnurcosides A-E (1-5), three benzofuran type neolignans, viburnurcosides F-H (6-8), and three tetrahydrofuran type lignans, viburnurcosides I-K (9-11), were isolated from the fruits of Viburnum urceolatum. The structures of all isolates were elucidated by an extensive analysis of the NMR and HRESIMS data. The absolute configurations of these compounds were determined by quantum-chemical electronic circular dichroism calculation and comparison. The sugar units of viburnurcosides A-K were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of monosaccharides. The in vitro enzyme inhibition assay exhibited that viburnurcoside J (10) had the most potent inhibitory activity against α-amylase and α-glucosidase with the IC50 values of 19.75 and 9.14 µM, respectively, which were stronger than those of the positive control acarbose (37.31 and 26.75 µM, respectively). The potential binding modes of viburnurcoside J (10) with α-amylase and α-glucosidase were also analyzed by molecular modeling.

Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship.

Lignans are plant-derived polyphenolic compounds with a plethora of biological applications. Also, regarded as phytoestrogens, the lignans offer a variety of health benefits of which the anti-cancer effects are the most attractive. Honokiol is a lignan isolated from various parts of trees belonging to the genus Magnolia. The bioactivity of honokiol is attributed to its characteristic physical properties, which include small size and the presence of two phenolic groups that may interact with proteins in cell membranes via hydrophobic interactions, aromatic pi orbital co-valency, and hydrogen bonding. The hydrophobicity of honokiol enables its rapid dissolution in lipids and the crossing of physiological barriers, including the blood-brain barrier and cerebrospinal fluid. These factors contribute towards the high bioavailability of honokiol which further support its candidature in medicinal research. Therefore, the anticancer properties of honokiol are of particular interest as many of the contemporary anticancer drugs suffer from bioavailability drawbacks, which necessitates the identification and development of novel candidate molecules directed as anticancer chemotherapeutics. The antioncogenic profile of honokiol also arises from the regulation of various signalling pathways associated with oncogenesis, arresting of the cell cycle by regulation of cyclic proteins, upregulation of epithelial markers and downregulation of mesenchymal markers leading to the inhibition of epithelial-mesenchymal transition, and preventing the metastasis by restricting cell migration and invasion due to the downregulation of matrix-metalloproteinases. In this review, we discuss the anticancer properties of honokiol.

Tissue-specific transcriptome and metabolome analyses reveal candidate genes for lignan biosynthesis in the medicinal plant Schisandra sphenanthera.

Schisandra sphenanthera is an extremely important medicinal plant, and its main medicinal component is bioactive lignans. The S. sphenanthera fruit is preferred by the majority of consumers, and the root, stem, and leaf are not fully used. To better understand the lignan metabolic pathway, transcriptome and metabolome analyses were performed on the four major tissues of S. sphenanthera. A total of 167,972,229 transcripts and 91,215,760 unigenes with an average length of 752 bp were identified. Tissue-specific gene analysis revealed that the root had the highest abundance of unique unigenes (9703), and the leaves had the lowest (189). Transcription factor analysis showed that MYB-, bHLH- and ERF-transcription factors, which played important roles in the regulation of secondary metabolism, showed rich expression patterns and may be involved in the regulation of processes involved in lignan metabolism. In different tissues, lignans were preferentially enriched in fruit and roots by gene expression profiles related to lignan metabolism and relative lignan compound content. Furthermore, schisandrin B is an important compound in S. sphenanthera. According to weighted gene co-expression network analysis, PAL1, C4H-2, CAD1, CYB8, OMT27, OMT57, MYB18, bHLH3, and bHLH5 can be related to the accumulation of lignans in S. sphenanthera fruit, CCR5, SDH4, CYP8, CYP20, and ERF7 can be related to the accumulation of lignans in S. sphenanthera roots. In this study, transcriptome sequencing and targeted metabolic analysis of lignans will lay a foundation for the further study of their biosynthetic genes.

A comprehensive review on pharmacological, toxicity, and pharmacokinetic properties of phillygenin: Current landscape and future perspectives.

Forsythiae Fructus is a traditional Chinese medicine frequently in clinics. It is extensive in the treatment of various inflammation-related diseases and is renowned as 'the holy medicine of sores'. Phillygenin (C21H24O6, PHI) is a component of lignan that has been extracted from Forsythiae Fructus and exhibits notable biological activity. Modern pharmacological studies have confirmed that PHI demonstrates significant activities in the treatment of various diseases, including inflammatory diseases, liver diseases, cancer, bacterial infection and virus infection. Therefore, this review comprehensively summarizes the pharmacological effects of PHI up to June 2023 by searching PubMed, Web of Science, Science Direct, CNKI, and SciFinder databases. According to the data, PHI shows remarkable anti-inflammatory, antioxidant, hepatoprotective, antitumour, antibacterial, antiviral, immunoregulatory, analgesic, antihypertensive and vasodilatory activities. More importantly, NF-κB, MAPK, PI3K/AKT, P2X7R/NLRP3, Nrf2-ARE, JAK/STAT, Ca2+-calcineurin-TFEB, TGF-ß/Smads, Notch1 and AMPK/ERK/NF-κB signaling pathways are considered as important molecular targets for PHI to exert these pharmacological activities. Studies of its toxicity and pharmacokinetic properties have shown that PHI has very low toxicity, incomplete absorption in vivo and low oral bioavailability. In addition, the physico-chemical properties, new formulations, derivatives and existing challenges and prospects of PHI are also reviewed and discussed in this paper, aiming to provide direction and rationale for the further development and clinical application of PHI.

Defensive furofuran lignans localized to the oil cells of Neocinnamomum delavayi and their metabolism by a specialist insect.

Neocinnamomum delavayi (Lauraceae) leaves with abundant oil cells are seldom attacked by insects, but their chemical constituent and biological function remain obscure. Three furofuran lignans, including (+)-eudesmin (3), (+)-magnolin (4), and demethoxyaschantin (5), were identified to be the major specialized metabolites in the oil cells of N. delavayi leaves through laser microdissection coupled with NMR analysis. Compounds 3 and 4 exhibited obvious antifeedant activity against a generalist insect Spodoptera exigua, and their natural contents in the leaves could effectively defend against generalist insects. Intriguingly, three specific metabolites 9-11, the O-demethylation derivates of compounds 3-5, were identified from a native specialist insect Dindica polyphaenaria feeding with N. delavayi leaves, implying an adaptation mechanism of specialist insects to plant defensive compounds. The results revealed a chemical connection between plants and insects, which would contribute to our understanding of plant-insect interaction and insect management.

Frequency of Phytoestrogen Consumption and Symptoms at Midlife among Bangladeshis in Bangladesh and London.

There is a longstanding interest in the relationship between diet and hot flash symptoms during midlife, especially in whether phytoestrogens ease menopausal symptoms. The purpose of this study was to examine hot flashes, night sweats, trouble sleeping, and vaginal dryness in relation to the intake of foods rich in phytoestrogens among Bangladeshi women aged 35 to 59 years who were living either in Sylhet, Bangladesh (n = 157) or as migrants in London (n = 174). Consumption ranges for phytoestrogens were constructed from food frequencies. We hypothesized that diets rich in isoflavones, lignans, and coumestrol would be associated with lower symptom frequencies. However, adjusted logistic regression results showed that with each incremental increase in general phytoestrogen consumption (scale of 0 to 10), the likelihood of hot flashes increased by 1.4%. Each incremental increase in lignan consumption raised the likelihood of hot flashes by 1.6%. In contrast, the odds of vaginal dryness decreased by 2%, with each incremental increase in phytoestrogen and lignan consumption, and by 4%, with each incremental increase in isoflavone consumption. Night sweats and trouble sleeping were not associated with phytoestrogen intake in logistic regressions. Our findings add to the conflicting data on relationships between phytoestrogens and symptoms associated with menopause.

Simultaneous Extraction and Determination of Lignans from Schisandra chinensis (Turcz.) Baill. via Diol-Based Matrix Solid-Phase Dispersion with High-Performance Liquid Chromatography.

The quality of Schisandra chinensis (Turcz.) Baill. (S. chinensis) is principally attributed to lignan compounds. In this paper, a simple and rapid strategy for simultaneous extraction and determination of 10 lignans from S. chinensis was established through matrix solid-phase dispersion (MSPD) assisted by diol-functionalized silica (Diol). The experimental parameters for MSPD extraction were screened using the response surface methodology (RSM). Diol (800 mg) was used as a dispersant and methanol (MeOH, 85%, v/v) as an eluting solvent (10 mL), resulting in a high extraction efficiency. MSPD extraction facilitated the combination of extraction and purification in a single step, which was less time-consuming than and avoided the thermal treatment involved in traditional methods. The simultaneous qualification and quantification of 10 lignans was achieved by combining MSPD and high-performance liquid chromatography (HPLC). The proposed method offered good linearity and a low limit of detection starting from 0.04 (schisandrin C) to 0.43 µg/mL (schisantherin B) for lignans, and the relative standard deviation (RSD, %) values of precision were acceptable, with a maximum value of 1.15% (schisantherin B and schisanhenol). The methodology was successfully utilized to analyze 13 batches of S. chinensis from different cultivated areas of China, which proved its accuracy and practicability in the quantitative analysis of the quality control of S. chinensis.