Lignan Compounds Research Articles

Lignan-rich extract from Cinnamomum camphora leaf attenuates metabolic syndrome by modulating glycolipid metabolism and gut microbiota in T2DM mice

BackgroundType 2 diabetes mellitus (T2DM) is a serious metabolic syndrome with high mortality and disability rates globally, which usually caused by unhealthy dietary patterns. Cinnamomum camphora leaf is a traditional Chinese medicinal herb used for attenuating hyperglycemia and digestive disorder, and high level of lignans has been found in C. camphora leaf. PurposeThis study aimed to examine the chemical composition of lignans extracted from C. camphora leaf (LCCL), and illustrate its therapeutic effect and mechanism on T2DM and its concomitant glycolipid metabolic disorder. MethodsThe components of LCCL were separated and purified by silica gel and macroporous adsorption resin, and were distinguished through LC/MS and NMR. The antioxidant activity of LCCL was determined by free radical scavenging assay in vitro; the hypoglycemic and hypolipidemic abilities were evaluated by α-glucosidase, α-amylase and pancreatic lipase inhibition trials, respectively. T2DM model mice were established by high-sugar and high-fat (HSHF) feed together with streptozotocin (STZ) infection, and then grouped to assess the effect of LCCL treatment. Hematoxylin-eosin (H&E), Periodic Acid-Schiff (PAS) and oil red O staining were employed to analyze the histopathology. qRT-PCR assay, 16S rRNA analysis, and western blot were conducted to illuminate the anti-diabetic mechanism of LCCL. Results6 sesamin lignans were identifed from LCCL. The in vitro assays showed strong inhibitive abilities of LCCL with low IC50 on DPPH (33.68 ± 0.54 μg/ml),O2− (39.25 ± 0.61 μg/ml), OH• (45.72 ± 0.72 μg/ml), α-glucosidase (0.82 ± 0.14 mg/ml), α-amylase (0.86 ± 0.11 mg/ml) and pancreatic lipase (0.91 ± 0.12 mg/ml). LCCL treatment (100, 200 and 400 g kg-1mg kg-1) gradually decreased the fasting blood glucose (FBG) and fasting insulin (FINS), improved the glucose and insulin tolerance, down-regulated the homeostasis model assessment insulin resistance (HOMA-IR) indexes, alleviated the hepatic inflammatory response and oxidative stress, promoted the glycogen storage and depleted the fat accumulation in the liver. Besides, LCCL administration alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner, that significantly increased biodiversity, altered the composition of gut microbiota and increased the proportion of Lactobacillus. ConclusionThe lignan-rich extract of C. camphor leaf (LCCL), containing at least 6 lignans compounds, displayed promising antioxidant, hypoglycemic and hypolipidemic activities. The treatment of LCCL alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner. These finding suggested that LCCL should be further investigated to develop its complementary therapeutic effect on T2DM.

Screening of promising chemotherapeutic candidates from plants against human adult T-cell leukaemia/lymphoma (IX): active principles from Juniperus rigida

During the screening of novel chemotherapeutic candidates from plants against adult T-cell leukaemia/lymphoma (ATL), we found that extracts of plants in the Solanaceae, Annonaceae, Apocynaceae, and Rutaceae families showed anti-proliferative activity in the MT-1 and MT-2 cell lines. We have isolated active compounds from these plants in the present research because Cupressaceae plants showed potent anti-proliferative activity in the cell lines. We attempted to isolate the active compounds from the leaves of Juniperus rigida. Using activity-guided fractionation, we isolated 22 compounds, including seven terpenoids, three aromatic compounds, two iridoids, five lignans, and five biflavonoids. The anti-proliferative activities of five diterpenoids were moderate, and those of two biflavonoids were stronger. A lignan (compound 13) showed the strongest activity. These compounds are promising candidates for the treatment of ATL.

Liriodendrin stimulates proliferation and milk protein synthesis of mammary epithelial cells via the PI3K-DDX18 signaling.

Liriodendrin is a lignan compound that is involved in a wide variety of physiological functions, however it is unknown whether liriodendrin plays an important role in milk production in the mammary glands. In this study, we explored the role and molecular mechanism of Liriodendrin in milk synthesis of mammary epithelial cells (MECs). Bovine MECs were treated with liriodendrin (0, 0.45, 0.9, 1.35, 1.8, and 2.25mM) for 24 h. Liriodendrin dose-dependently increased cell number, cell cycle transition, and milk protein synthesis, as well as Cyclin D1 and mTOR phosphorylation, with the maximal effects observed at a dose of 1.35mM. Liriodendrin increased the expression of DDX18, which mediated liriodendrin stimulation of Cyclin D1 and mTOR mRNA expression. PI3K inhibition and DDX18 knockdown experiments further confirmed that liriodendrin regulates the mRNA expression of Cyclin D1 and mTOR via the PI3K-DDX18 signaling. Mouse feeding experiment showed that liriodendrin dose-dependently promotes β-casein and DDX18 expression in mouse mammary gland. In this study, DDX18 was found to be a novel positive regulator that plays a role in cell proliferation and synthesis of milk protein. These findings reveal that liriodendrin stimulates proliferation and milk protein synthesis of MECs via the PI3K-DDX18 signaling.

오미자(Schisandra chinensis) 열매의 과육과 씨에서 정유 및 리그난 성분 비교

Fully ripe Omija (Schisandra chinensis Baillon) berry has been used for medicinal and edible purposes for a long time due to its various physiological activities. The seeds of Omija fruit are produced during the processing of the fruit, but are often discarded in the food industry. To increase the utilization of Omija seeds, this study investigated the differences in essential oil and lignan compositions between the pulp and seed. The yield of essential oil in whole berries was 1.33% based on dry weight, 0.91% in the pulp, and 2.65% in the seed, respectively. A total of 62 constituents were identified by GC and GC–MS analysis from the oils of the two parts. The major constituents were sesquiterpenes, such as α-ylangene, cuparene, alloaromadendrene, cis-lanceol, β-himachalene, and nootkatone. The content of these ingredients was higher in the seed than in the pulp. The most abundant lignan compounds in the berry were schizandrin, followed by γ-schizandrin, schizandrin A, and schizandrol B. The content of the four lignans in the seed was significantly higher than in the pulp. The seeds of Omija have higher contents of essential oils and lignan compounds compared to the pulp, making it necessary to explore approaches for utilizing them as food ingredients.

오미자(Schisandra chinensis) 열매의 과육과 씨에서 정유 및 리그난 성분 비교

Fully ripe Omija (Schisandra chinensis Baillon) berry has been used for medicinal and edible purposes for a long time due to its various physiological activities. The seeds of Omija fruit are produced during the processing of the fruit, but are often discarded in the food industry. To increase the utilization of Omija seeds, this study investigated the differences in essential oil and lignan compositions between the pulp and seed. The yield of essential oil in whole berries was 1.33% based on dry weight, 0.91% in the pulp, and 2.65% in the seed, respectively. A total of 62 constituents were identified by GC and GC–MS analysis from the oils of the two parts. The major constituents were sesquiterpenes, such as α-ylangene, cuparene, alloaromadendrene, cis-lanceol, β-himachalene, and nootkatone. The content of these ingredients was higher in the seed than in the pulp. The most abundant lignan compounds in the berry were schizandrin, followed by γ-schizandrin, schizandrin A, and schizandrol B. The content of the four lignans in the seed was significantly higher than in the pulp. The seeds of Omija have higher contents of essential oils and lignan compounds compared to the pulp, making it necessary to explore approaches for utilizing them as food ingredients.

Chemical constituents from stems and leaves of Artocarpus tonkinensis and their inhibitory effects on proliferation of synovioblasts in vitro

The chemical constituents from the stems and leaves of Artocarpus tonkinensis in Artocarpus of Moraceae were systematically studied by means of silica gel, octadecylsilyl(ODS), and Sephadex LH-20 gel column chromatographies, as well as preparative high-performance liquid chromatography(Pre-HPLC) and a variety of chromatographic separation techniques. The spectral data and physicochemical properties of the compounds were obtained from separation and compared with those of the compounds reported in the literature. As a result, 11 compounds isolated from the 90% ethanol extract of the stems and leaves of A. tonkinensis were identified as artocatonkine(1), 5,6,7,4'-tetramethoxyflavone(2), apigenin-4'-O-β-D-glucoside(3), rayalinol(4), psorachalcone A(5), 4-ketopinoresinol(6), ficusesquilignan B(7), pinnatifidanin AI(8), pinnatifidanin A(9), O-methylmellein(10), and trans-4-hydroxymellein(11). Among these compounds, compound 1 was a new prenylated flavone, and compounds 2-11 were isolated from the plants belonging to the genus Artocarpus for the first time. Furthermore, all compounds 1-11 were evaluated for their anti-rheumatoid arthritis activities, and the MTS method was used to measure their inhibitory effects on the proliferation of synovioblasts in vitro. The results of activity evaluation showed that flavonoid compounds 1-3, 5, and lignan compounds 8 and 9 displayed significant anti-rheumatoid arthritis activities, showing the IC_(50) values in inhibiting the proliferation of synovioblasts MH7A from(6.38±0.06) μmol·L~(-1) to(168.58±0.28)μmol·L~(-1).

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae).

Herpetospermum pedunculosum (Ser.) C. B. Clarke is a traditional Chinese herbal medicine that heavily relies on the lignans found in its dried ripe seeds (Herpetospermum caudigerum), which have antioxidant and hepatoprotective functions. However, little is known regarding the lignan biosynthesis in H. pedunculosum. In this study, we used metabolomic (non-targeted UHPLC-MS/MS) and transcriptome (RNA-Seq) analyses to identify key metabolites and genes (both structural and regulatory) associated with lignan production during the green mature (GM) and yellow mature (YM) stages of H. pedunculosum. The contents of 26 lignan-related metabolites and the expression of 30 genes involved in the lignan pathway differed considerably between the GM and YM stages; most of them were more highly expressed in YM than in GM. UPLC-Q-TOF/MS confirmed that three Herpetospermum-specific lignans (including herpetrione, herpetotriol, and herpetin) were found in YM, but were not detected in GM. In addition, we proposed a lignan biosynthesis pathway for H. pedunculosum based on the fundamental principles of chemistry and biosynthesis. An integrated study of the transcriptome and metabolome identified several transcription factors, including HpGAF1, HpHSFB3, and HpWOX1, that were highly correlated with the metabolism of lignan compounds during seed ripening. Furthermore, functional validation assays revealed that the enzyme 4-Coumarate: CoA ligase (4CL) catalyzes the synthesis of hydroxycinnamate CoA esters. These results will deepen our understanding of seed lignan biosynthesis and establish a theoretical basis for molecular breeding of H. pedunculosum.

Arctigenin induces activated HSCs quiescence via AMPK-PPARγ pathway to ameliorate liver fibrosis in mice

Arctigenin (ATG), a traditional Chinese herbal medicine, is a natural lignan compound extracted from the seeds of burdock (Arctium lappa L, Asteraceae). As a natural product with multiple biological activities, the effect and mechanism of ATG against liver fibrosis are not fully elucidated yet. In current work, we first discovered that ATG could improve CCl4-induced liver injury reflected by lower plasma ALT and AST levels, liver coefficient and pathological scoring of ballooning. Furthermore, it also could reduce the positive areas of Masson, Sirius red and α-SMA staining, inhibit the expression of fibrosis-related genes (Col1a1, Col3a1, Acta2), and decrease the content of hydroxyproline, indicated ATG treatment had benefits in alleviating CCl4-induced liver fibrosis. In vitro, we observed that ATG can inhibit collagen production stimulated by TGF-β1 in LX2 cells. By analysis of the information obtained from SymMap and GeneCards databases and in vitro validation experiments, ATG was proven to be an indirect PPARγ agonist and its effect on collagen production was dependent on PPARγ. Subsequently, we confirmed that ATG activating AMPK was the contributor of its effect on PPARγ and collagen production. Finally, the transformation of activated hepatic stellate cells was determined after treated with ATG, in which ATG treatment could return activated LX2 cells to quiescence because of the elevated quiescent markers and lipid droplets. Our work has highlighted the potential of ATG in the treatment of liver fibrosis and clarified that ATG can activate AMPK/PPARγ pathway to restore the activated hepatic stellate cell to quiescence thereby improving liver fibrosis.

Simultaneous separation and determination of seven biphenyl cyclooctene lignans in Schisandra chinensis and its preparations by micellar electrokinetic chromatography with dual organic solvent system.

Gomisin is a natural dibenzo cyclooctene lignan, which is mainly derived from the family Magnoliaceae. It has anti-inflammatory, antioxidant, anti-tumor, anti-aging, and hypoglycemic effects. Gomisins play important roles as medicines, nutraceuticals, food additives, and cosmetics. The objective of this study is to establish a micellar electrokinetic chromatography (MEKC) method for simultaneous separation and determination of seven biphenyl cyclooctene lignans (Gomisin D, E, G, H, J, N, and O) in Schisandra chinensis and its preparations. The method was optimized by studying the effects of the main parameters on the separation. The method has been validated and successfully applied to the determination of seven Gomisins in S.chinensis and its preparations. In the separation system, the running buffer was composed of 20 mM Na2HPO4, 8.0 mM sodium dodecyl sulfate (SDS), 11% (v/v) methanol, and 6.0% (v/v) ethanol. A diode array detector was used with a detection wavelength of 230 nm, a separation voltage of 17 kV, and an operating temperature of 25°C. Under this condition, the seven analytes were separated at baseline within 20 min, and a good linear relationship was obtained with correlation coefficient ranging from 0.9919 to 0.9992. The limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N = 10) ranged from 0.8 to 0.9μg/mL and from 2.6 to 3.0μg/mL, respectively. The recovery rate was between 99.1% and 102.5%. The experimental results indicated that this method is suitable for the separation and determination of seven Schisandra biphenyl cyclooctene lignan compounds in real samples. At the same time, it provides an effective reference for the quality control of S.chinensis and its preparations.

Americanin B inhibits pyroptosis in lipopolysaccharide-induced septic encephalopathy mice through targeting NLRP3 protein

BackgroundSepsis is considered as a severe illness due to its high mortality. Sepsis can cause septic encephalopathy, thus leading to brain injury, behavioral and cognitive dysfunction. Pyroptosis is a type of regulated cell death (RCD) and takes a crucial part in occurrence and development of sepsis. Americanin B (AMEB) is a lignan compounds, which is extracted from Vernicia fordii. In our previous study, AMEB could inhibit microglial activation in inflammatory cell model. However, the function of AMEB in septic encephalopathy mice is uncertain. It would be worthwhile to ascertain the role and mechanism of AMEB in sepsis. PurposeCurrent study designs to certify the relationship between pyroptosis and septic encephalopathy, and investigate whether AMEB can restrain NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation and restrict pyroptosis by targeting NLRP3 in septic mice model. Study designC57BL/6 mice were utilized to perform sepsis model in vivo experiments. BV-2 cell lines were used for in vitro experiments. MethodsIn vivo sepsis model was established by lipopolysaccharide (LPS) intraperitoneal injection in male C57BL/6 J mice and in vitro model was exposed by LPS plus ATP in BV-2 cells. The survival rate was monitored on the corresponding days. NLRP3, apoptosis associated Speck-like protein (ASC), caspase-1, GasderminD (GSDMD), interleukin-1β (IL-1β) and interleukin-18 (IL-18) level were detected by western blotting and immunofluorescence analysis. Molecular docking, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) experiments, RNAi transfection and quantitative real-time PCR were applied to confirm the potential target of AMEB. ResultsThe results suggested that AMEB could rise survival percentage and lighten brain injury in LPS-induced sepsis mice. In addition, AMEB could inhibit pyroptosis and the activiation of NLRP3 inflammasome. The inhibiting function of AMEB on the activiation of NLRP3 inflammasome is weakened following si-NLRP3 transfection. Moreover, AMEB exerted anti-pyroptosis effect via targeting NLRP3 protein. ConclusionsOur findings first indicate NLRP3 is an effective druggable target for septic encephalopathy related brain injury, and also provide a candidate-AMEB for the treatment of septic encephalopathy. These emerging findings on AMEB in models of sepsis suggest an innovative approach that may be beneficial in the prevention of septic encephalopathy.

Schisandrin B enhances embryo competence and potentially mitigates endoplasmic reticulum stress during porcine preimplantation development

Endoplasmic reticulum (ER) stress induced by agents such as tunicamycin (TM) substantially impedes the developmental progression of porcine embryos. Lignan compounds such as Schisandrin B (Sch-B), may have the potential to mitigate this stress. However, there are few studies on the effects of Sch-B on embryo development. To address this research gap, this study evaluates the protective efficacy of Sch-B against TM-induced ER stress during pivotal stages of porcine embryogenesis. Notably, embryos treated with Sch-B exhibited pronounced resistance to TM-induced developmental arrest, particularly at the 4-cell stage, facilitating progression to the 8-cell stage and subsequent blastocyst formation. It was also observed that Sch-B effectively reduced reactive oxygen species (ROS) levels and improved mitochondrial membrane potential (MMP). Furthermore, Sch-B positively influenced the expression of several stress-related genes. These findings highlight the promising role of Sch-B in improving porcine embryo development and mitigating ER stress.

Exploring the diversity of dissolved organic matter (DOM) properties and sources in different functional areas of a typical macrophyte - derived lake combined with optical spectroscopy and FT-ICR MS analysis

Lake Baiyangdian is one of China's largest macrophyte - derived lakes, facing severe challenges related to water quality maintenance and eutrophication prevention. Dissolved organic matter (DOM) was a huge carbon pool and its abundance, property, and transformation played important roles in the biogeochemical cycle and energy flow in lake ecosystems. In this study, Lake Baiyangdian was divided into four distinct areas: Unartificial Area (UA), Village Area (VA), Tourism Area (TA), and Breeding Area (BA). We examined the diversity of DOM properties and sources across these functional areas. Our findings reveal that DOM in this lake is predominantly composed of protein - like substances, as determined by excitation - emission matrix and parallel factor analysis (EEM - PARAFAC). Notably, the exogenous tyrosine-like component C1 showed a stronger presence in VA and BA compared to UA and TA. Ultrahigh - resolution mass spectrometry (FT - ICR MS) unveiled a similar DOM molecular composition pattern across different functional areas due to the high relative abundances of lignan compounds, suggesting that macrophytes significantly influence the material structure of DOM. DOM properties exhibited specific associations with water quality indicators in various functional areas, as indicated by the Mantel test. The connections between DOM properties and NO3N and NH3N were more pronounced in VA and BA than in UA and TA. Our results underscore the viability of using DOM as an indicator for more precise and scientific water quality management.

Sonneralignan A, a new lignan from the fruit of mangrove Sonneratia apetala

A new lignan, sonneralignan A (1), along with two known lignan compounds, (+)-lariciresinol-9-O-β-D-glucopyranoside (2) and (-)isolariciresinol-9-O-β-D-glucopyranoside (3) were isolated from the n-butanol extract of the mangrove Sonneratia apetala fruit. The structures of the compounds were elucidated on the basis of extensive spectral analysis. The evaluation of activity showed that compound 1 exhibited significant anti-aging activity, which extended the mean lifespan of Caenorhabditis elegans by up to 19.13% (p < 0.05) and 55.29% (p < 0.01) under normal and heat stress cultivation conditions, respectively. Molecular docking studies showed that compound 1 was bound to the DNA binding domain of DAF-16 and promoted the conformation of DAF-16, thus strengthening the interaction between the DAF-16 and related DNA. TRP-252, SER-250 and SER-249 of the binding region might be the key amino residues during the interaction.

STAT3 Inhibitory Activities of Lignans Isolated from the Stems of Lindera obtusiloba Blume

Lindera obtusiloba Blume has several activities, such as anti-inflammatory, anti-allergic, anti-tumor, anti-wrinkle, and antioxidant activities. Interleukin-6 (IL-6) is a classic pro-inflammatory cytokine that is associated with various functions, such as proliferation, invasion, inflammatory responses and functions within antioxidant defense systems. In this study, we investigated IL-6-induced STAT3 activation of lignan compounds isolated from L. obtusiloba. The structures of the isolated compounds were elucidated via spectroscopic nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI-MS). As a result, seven lignans were identified from L. obtusiloba. All the isolated compounds (1–7) were evaluated for their IL-6-induced STAT3 inhibitory effects in Hep3B cells using a luciferase reporter assay. Of the isolates, compounds 1 and 5 showed inhibitory effects against IL-6-stimulated STAT3 activation. Furthermore, the mRNA expression levels of inflammation-related genes such as CRP, IL-1b, and SOCS3 were significantly reduced by exposure to compounds 1 and 5. The protein levels of p-STAT3 and p-JAK2 in IL-6-induced U266 cells were regulated in the presence of lignans derived from Lindera obtusiloba by Western blot assay. Based on the results, this study of L. obtusiloba demonstrates that the species has promise as a bioactive candidate for the treatment of IL-6-induced STAT3-related disease.

Retracted] Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells

Retracted] Arctigenin, a natural lignan compound, induces G₀/G₁ cell cycle arrest and apoptosis in human glioma cells

Protective effect of arctiin against Toxoplasma gondii HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of cytosolic phospholipase A2 and platelet-activating factor

Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g.HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A2 (cPLA2) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii) on allergic liver injury using T.g.HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii-induced allergic acute liver injury. The results showed that ARC suppressed the T.g.HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g.HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA2, PAF, and interferon-γ. This result suggested that ARC ameliorates T.g.HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g.HSP70-induced allergic liver injury.

Nectandrin B significantly increases the lifespan of Drosophila - Nectandrin B for longevity.

Phytochemicals are increasingly recognized in the field of healthy aging as potential therapeutics against various aging-related diseases. Nutmeg, derived from the Myristica fragrans tree, is an example. Nutmeg has been extensively studied and proven to possess antioxidant properties that protect against aging and alleviate serious diseases such as cancer, heart disease, and liver disease. However, the specific active ingredient in nutmeg responsible for these health benefits has not been identified thus far. In this study, we present evidence that Nectandrin B (NecB), a bioactive lignan compound isolated from nutmeg, significantly extended the lifespan of the fruit fly Drosophila melanogaster by as much as 42.6% compared to the control group. NecB also improved age-related symptoms including locomotive deterioration, body weight gain, eye degeneration, and neurodegeneration in aging D. melanogaster. This result represents the most substantial improvement in lifespan observed in animal experiments to date, suggesting that NecB may hold promise as a potential therapeutic agent for promoting longevity and addressing age-related degeneration.

Anti‑adipogenic effect and underlying mechanism of lignan‑enriched nutmeg extract on 3T3‑L1 preadipocytes.

Nutmeg is the seed derived from Myristica fragrans. Nutmeg seeds contain alkylbenzene derivatives such as myristicin, which are toxic to the human organism, and lignan compounds such as nectandrin B, which possess anti-aging and anti-diabetic properties. However, the anti-adipogenic, prolipolytic and anti-inflammatory effects of lignan-enriched nutmeg extract (LNX) on preadipocytes remain unclear. In the present study, the effects of LNX on lipid accumulation, glycerol release and inflammatory cyclooxygenase-2 (COX-2) expression in differentiated 3T3-L1 preadipocytes were investigated. Oil red O staining demonstrated that treatment with LNX resulted in a concentration-dependent reduction in lipid accumulation in differentiating 3T3-L1 preadipocytes without affecting cell growth. Mechanistically, LNX treatment at 6 µg/ml led to a reduction in phosphorylation levels of signal transducer and activator of transcription 3 (STAT3), whereas it did not influence the peroxisome proliferator-activated receptor gamma (PPAR-γ) and CCAAT enhancer binding protein alpha (C/EBP-α) expression levels during 3T3-L1 preadipocyte differentiation. In addition, LNX treatment at 6 µg/ml led to a decrease in fatty acid synthase (FAS) expression levels on day (D) 2, but not D5 and D8, during preadipocyte differentiation. Treatment with LNX at 6 µg/ml did not affect the expression levels of perilipin A during preadipocyte differentiation. In differentiated 3T3-L1 adipocytes, LNX treatment at 6 µg/ml did not stimulate glycerol release and hormone-sensitive lipase phosphorylation, which are known lipolysis hallmarks. Furthermore, LNX treatment at the doses tested had no effect on tumor necrosis factor alpha-induced COX-2 expression in 3T3-L1 preadipocytes. Collectively, these results demonstrated that LNX has an anti-adipogenic effect on differentiating 3T3-L1 preadipocytes, which is mediated by the downregulation of STAT3 phosphorylation and FAS expression.

Sesamol as a potential candidate for the treatment of hepatic fibrosis, based on its regulation of FXR/LXR axis-mediated inhibition of autophagy through crosstalk between hepatic cells and macrophage

BackgroundSesamol (SEM), a natural lignan compound isolated from sesame, has strong anti-oxidant property, regulating lipid metabolism, decreasing cholesterol and hepatoprotection. However, its anti-hepatic fibrosis effect and mechanisms have not been comprehensively elucidated. Hypothesis/PurposeThis study aims to investigate the anti-hepatic fibrosis of SEM and its underlying mechanisms. MethodC57BL/6 mice with hepatic fibrosis were induced by TAA, then administrated with SEM or curcumin, respectively. HSCs were stimulated by TGF-β or conditioned medium, and then cultured with SEM, GW4064, GW3965, Rapamycin (RA) or 3-methyladenine (3-MA), respectively. Mice with hepatic fibrosis also were administrated with SEM, RA or 3-MA to estimate the effect of SEM on autophagy. ResultsIn vitro, SEM significantly inhibited extracellular matrix deposition, P2 × 7r-NLRP3, and inflammatory cytokines. SEM increased FXR and LXRα/β expressions and decreased MAPLC3α/β and P62 expressions, functioning as 3-MA (autophagy inhibitor). In vivo, SEM reduced serum transaminase, histopathology changes, fibrogenesis, autophagy markers and inflammatory cytokines caused by TAA. LX-2 were activated with conditioned medium from LPS-primed THP-1, which resulted in significant enhance of autophagy markers and inflammatory cytokines and decrease of FXR and LXRα/β expressions. SEM could reverse above these changes and function as 3-MA, GW4064, or GW3965. Deficiency of FXR or LXR attenuated the regulation of SEM on α-SMA, MAPLC3α/β, P62 and IL-1β in activated LX-2. In activated THP-1, deficiency of FXR could decrease the expression of LXR, and vice versa. Deficiency of FXR or LXR in activated MΦ decreased the expressions of FXR and LXR in activated LX-2. Deficiency FXR or LXR in activated MΦ also attenuated the regulation of SEM on α-SMA, MAPLC3α/β, P62, caspase-1 and IL-1β. In vivo, SEM significantly reversed hepatic fibrosis via FXR/LXR and autophagy. ConclusionSEM could regulate hepatic fibrosis by inhibiting fibrogenesis, autophagy and inflammation. FXR/LXR axis-mediated inhibition of autophagy contributed to the regulation of SEM against hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. SEM might be a prospective therapeutic candidate, and its mechanism would be a new direction or strategy for hepatic fibrosis treatment.

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.