Lignan contents of Schisandra chinensis (Turcz.) Baill. from different origins-A new model for evaluating the content of prominent components of Chinese herbs.

BACKGROUND: As a traditional Chinese herbal medicine, Schisandra chinensis exhibits various effects such as liver protection, blood sugar regulation, blood lipid regulation, immune function regulation, antidepressant activity, etc. However, because of its intricate composition, diverse origins, and medicinal effects depending on complex compound groups, there are differences in the lignan composition of S. chinensis from different origins. Therefore, it is currently difficult to evaluate the quality of medicinal materials from plants of different origins using a single qualitative quality control index. PURPOSE: This paper aims to investigate the potential relationship between the lignan components of S. chinensis from different origins and to establish stable assessment indices for determining the lignan content of S. chinensis from multiple perspectives. METHODS: In this study, we collected S. chinensis samples of seven major origins in China, and randomly sampled 6-9 batches of each origin for a total of 60 batches. The lignan content was determined by HPLC, and its distribution law of the ratio of each lignan component of S. chinensis to Schisandrol A content was analyzed. Combining network pharmacology and differential analysis between samples, the stable and effective substances used as quality markers were determined. RESULTS: There were some correlations among the lignan contents of S. chinensis, some correlations between schisandrin A and other lignans of S. chinensis could be determined. The ratio of each component to the indicator component schisandrol A was evenly distributed and reflected the lignan content of S. chinensis to some extent. Four substances (schisandrol A, schisandrol B, schisantherin A, and schisandrin C) were determined by network pharmacology combined with the analysis results of HCA, PCA and PLS-DA to further optimize the model. They displayed a strong connection with the core target, a large contribution rate to the principal components, and a stable content in each batch of samples, suggesting that these components may be the main active substances of S. chinensis lignans. Therefore, they could be used as main indicators evaluating the advantages and disadvantages of S. chinensis by examining the consistency of component proportions. CONCLUSION: This method can intuitively evaluate the content of main lignans in S. chinensis. This quality assessment model is an exploration of the multi-component comprehensive evaluation system of S. chinensis, providing a new concept for the quality evaluation system of Chinese herbal medicines.

(-)-Asarinin alleviates gastric precancerous lesions by promoting mitochondrial ROS accumulation and inhibiting the STAT3 signaling pathway.

BACKGROUND: (-)-Asarinin (Asarinin) is the primary component in the extract of the herb Asarum sieboldii Miq. It possesses various functions, including pain relief, anti-viral and anti-tuberculous bacilli effects, and inhibition of tumor growth. Gastric precancerous lesion (GPL) is a common but potentially carcinogenic chronic gastrointestinal disease, and its progression can lead to gastric dysfunction and cancer development. However, the protective effects of asarinin against GPL and the underlying mechanisms remain unexplored. METHODS: A premalignant cell model (methylnitronitrosoguanidine-induced malignant transformation of human gastric epithelial cell strain, MC cells) and a GPL animal model were established and then were treated with asarinin. The cytotoxic effect of asarinin was assessed using a CCK8 assay. Detection of intracellular reactive oxygen species (ROS) using DCFH-DA. Apoptosis in MC cells was evaluated using an annexin V-FITC/PI assay. We performed western blot analysis and immunohistochemistry (IHC) to analyze relevant markers, investigating the in vitro and in vivo therapeutic effects of asarinin on GPL and its intrinsic mechanisms. RESULTS: Our findings showed that asarinin inhibited MC cell proliferation, enhanced intracellular ROS levels, and induced cell apoptosis. Further investigations revealed that the pharmacological effects of asarinin on MC cells were blocked by the ROS scavenger N-acetylcysteine. IHC revealed a significant upregulation of phospho-signal transducer and activator of transcription 3 (p-STAT3) protein expression in human GPL tissues. In vitro, asarinin exerted its pro-apoptotic effects in MC cells by modulating the STAT3 signaling pathway. Agonists of STAT3 were able to abolish the effects of asarinin on MC cells. In vivo, asarinin induced ROS accumulation and inhibited the STAT3 pathway in gastric mucosa of mice, thereby halting and even reversing the development of GPL. CONCLUSION: Asarinin induces apoptosis and delays the progression of GPL by promoting mitochondrial ROS production, decreasing mitochondrial membrane potential (MMP), and inhibiting the STAT3 pathway.

Sesamin-mediated high expression of BECN2 ameliorates cartilage endplate degeneration by reducing autophagy and inflammation.

Lumbar disc degeneration (LDD) is a prevalent clinical spinal disease characterized by the calcification and degeneration of the cartilage endplate (CEP), which significantly reduces nutrient supply to the intervertebral disc. Traditional Chinese medicine offers a conservative and effective approach for treating LDD. We aimed to investigate the molecular mechanisms underlying the therapeutic effects of Sesamin in LDD treatment. Transcriptome sequencing was used to analyze the effect of Sesamin on LPS-induced ATDC5. We explored the role of BECN2, a target gene of Sesamin, in attenuating LPS-induced degeneration of ATDC5 cells. Our results revealed the identification of 117 differentially expressed genes (DEGs), with 54 up-regulated and 63 down-regulated genes. Notably, Sesamin significantly increased the expression of BECN2 in LPS-induced ATDC5 cell degeneration. Overexpressed BECN2 enhanced cell viability and inhibited cell apoptosis in LPS-induced ATDC5 cells, while BECN2 knockdown reduced cell viability and increased apoptosis. Furthermore, BECN2 played a crucial role in attenuating chondrocyte degeneration by modulating autophagy and inflammation. Specifically, BECN2 suppressed autophagy by reducing the expression of ATG14, VPS34, and GASP1, and alleviated the inflammatory response by decreasing the expression of inflammasome proteins NLRP3, NLRC4, NLRP1, and AIM2. In vivo experiments further supported the beneficial effects of Sesamin in mitigating LDD. This study provides novel insights into the potential molecular mechanism of Sesamin in treating LDD, highlighting its ability to mediate autophagy and inflammation inhibition via targeting the BECN2. This study provides a new therapeutic strategy for the treatment of LDD, as well as a potential molecular target for LDD.

Schisantherin A protects hepatocyte via upregulating DDAH1 to ameliorate liver fibrosis in mice.

BACKGROUND: Hepatic fibrosis is the pivotal determinant in the progression of chronic liver diseases towards cirrhosis or advanced stages. Studies have shown that Schisantherin A (Sin A), the primary active compound from Schizandra chinensis (Turcz.) Baill., exhibits anti-hepatic fibrosis effects. However, the mechanism of Sin A in liver fibrosis remain unclear. PURPOSE: To examine the effects and underlying mechanism of Sin A on hepatic fibrosis. STUDY DESIGN AND METHODS: The effects and mechanism of Sin A were investigated using liver fibrosis mouse models induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN), as well as H2O2-induced hepatocyte injury in vitro. RESULTS: Sin A treatment ameliorated hepatocyte injury, inflammation, hepatic sinusoidal capillarization, and hepatic fibrosis in both CCl4-induced and DMN-induced mice. Sin A effectively reversed the reduction of DDAH1 expression, the p-eNOS/eNOS ratio and NO generation and attenuated the elevation of hepatic ADMA level induced by CCl4 and DMN. Knockdown of DDAH1 in hepatocytes not only triggered hepatocyte damage, but it also counteracted the effect of Sin A on protecting hepatocytes in vitro. CONCLUSION: Our findings indicate that Sin A ameliorates liver fibrosis by upregulating DDAH1 to protect against hepatocyte injury. These results provide compelling evidence for Sin A treatment in liver fibrosis.

Evaluation the effect of dietary vitamin E, sesamin and thymoquinone bioactive compounds on immunological response, intestinal traits and MUC-2 gene expression in broiler Japanese quails (Coturnix japonica).

The current study was performed to determine the effect of dietary vitamin E, sesamin and thymoquinone bioactive lignans derived from sesame and black seed on immunological response, intestinal traits and Mucin2 gene expression in broiler quails. Three hundred and fifty (one days-old) quails were allotted to seven dietary treatments with five replicates as an experimental randomized design study. Treatments were basal diet as a control, control +100 and +200 mg of vitamin E, sesamin and thymoquinone per each kg of diet respectively. At 35 d of age, two quails from each pen were chosen, weighted, slaughtered, eviscerated and lymphoid organ relative weights were measured. Anti-body titers against Newcastle disease (ND), Sheep red blood cell (SRBC), and infectious bronchitis virus (IBV) and Avian influenza (AI) vaccination were determined. The serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum antioxidant activates such as superoxide dismutase (SOD),glutathione peroxidase(GPX), catalase (CAT) and total antioxidant capacity (TAC) were examined. The cell mediated immunity by dinitrochlorobenzene (DNCB) and phytohemagglutinin (PHA) challenges were assessed. The microflora populations of ileum, morphological traits of jejunum and mucin2 gene expression were analyzed. Data showed that the lymphoid organ (thymus, spleen and Bursa) relative weights and antibody titer against HI, AI, SRBC and IB vaccination were increased compared to the control (p ≤ 0.05). Serum activities of ALP, ALT and AST were decreased under influences of dietary treatments (p ≤ 0.05). The serum antioxidant activates of GPX,SOD,CAT and TAC were increased and Increasing in mean skin thickness after DNCB challenge and decrease wing web swelling response to PHA mitojen injection were observed (p ≤ 0.05). Salmonella enterica, E-coli and Coliforms colonies were decrease and Lactobacillus colonies increased instead (p ≤ 0.05). The villus height and surface, crypt depth and goblet cells density were increased compared to the control (p ≤ 0.05). The expression of MUC2 gene increased under influnces of vitamin E, sesamin and thymoquinone supplemented diets (p ≤ 0.05).

Protection of schisantherin A against dictamnine-induced hepatotoxicity: Pharmacokinetic insights.

Dictamnine (DIC), as the most abundant furoquinoline alkaloid ingredient of the herbal medicine Cortex Dictamni (CD), can induce severe liver injury. A previous study found that DIC-induced liver injury was initiated by cytochrome P4503A (CYP3A)-mediated metabolic activation and subsequent formation of adducts with cellular proteins. Schisantherin A (SchA) is the major lignan component of the herbal medicine Schisandra chinensis (SC). SC is frequently combined with CD used in numerous Chinese medicinal formulas for the treatment of eczema and urticaria. Furthermore, SC could protect against CD-induced hepatotoxicity. The objective of the study was to investigate the protective effect of SchA on DIC-induced hepatotoxicity based on pharmacokinetic interactions. The studies found that SchA exerted a protective effect on DIC-induced hepatotoxicity in a dose-dependent manner. Pharmacokinetic studies showed that pretreatment with SchA enhanced the area under concentration-time curve (AUC) and maximal concentration (Cmax ) values of DIC in the serum and liver tissue of mice, indicating that SchA could augment the accumulation of DIC in the circulation. In vitro metabolism assays with mouse liver microsomes (MLMs) showed that SchA reduced the production of DIC-glutathione (GSH) conjugate. In addition, SchA significantly reduced the excretion of DIC-GSH conjugate in the urine of mice and relieved hepatic GSH depletion induced by DIC. These results suggested that SchA could inhibit the metabolic activation of DIC in vitro and in vivo. In summary, our findings showed that the observed pharmacokinetic interactions might be attributable to the inhibition of the metabolism of DIC by SchA, which might be responsible for the protection of SchA against DIC-induced hepatotoxicity. Therefore, the development of a standardized combination of DIC and SchA may protect patients from DIC-induced liver injury.

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.

A comprehensive review of the bioactive components of sesame seeds and their impact on bone health issues in postmenopausal women.

Sesame seeds perform many therapeutic functions against several health issues especially those related to bones because they possess a rich content of calcium, vitamins, proteins, oil, and carbohydrates. Using the PubMed, ScienceDirect, and Google Scholar databases, we performed a comprehensive search of the literature from 2013 to date on reports related to sesame seeds and their bioactive ingredients. Sesamin, sesamol, sesamolin, and sesamol are the major bioactive lignans found in sesame seeds. Our comprehensive review of the literature revealed the protective role of sesame seeds towards bone health in postmenopausal osteoporosis. It was observed that sesame seeds have a positive impact on postmenopausal women experiencing bone-related problems, i.e. osteoporosis and arthritis. Therefore, this review is focused on exploring the effect of sesame seeds on bone mineralization in women experiencing menopause. Furthermore, to aid balancing the hormones in women after their disturbance by the postmenopausal phase, we highlight the effect of the daily intake of sesame seeds in women. Finally, we conclude that the supplementation of sesame seeds in a regular diet shows a positive impact on the bone health of post-menopausal osteoporosis.

Sesamin Attenuates Obesity-Associated Nonalcoholic Steatohepatitis in High-Fat and High-Fructose Diet-Fed Mice.

This study explored the effects of sesamin on nonalcoholic steatohepatitis (NASH). High-fat and high-fructose diet-fed mice supplemented with or without sesamin. The results suggested that sesamin-treated mice lost body weight and fat tissue weight, had lower levels of serum metabolic parameters, and insulin resistance was mitigated. Histological examinations showed that sesamin treatment mitigated the progression of hepatic steatosis, and inflammation. In addition, sesamin enhanced hepatic antioxidant capacity, and decreased the activations of hepatic c-jun N-terminal kinase, inhibitor of kappa B kinase α, and insulin receptor substrate 1 as well as hepatic interleukin-6 and tumor necrosis factor-alpha levels. Further experiments indicated that sesamin treatment downregulated GRP78 and phospho-inositol-requiring enzyme 1 (IRE1) expression, and upregulated x-box binding protein 1 (XBP1) expression in hepatic tissue. The aforementioned results suggest that sesamin alleviates obesity-associated NASH, which might be linked to the effect of sesamin on the regulation of the hepatic endoplasmic reticulum stress-IRE1/XBP1 pathway. Thus, sesamin may be a good food functional ingredient in the treatment of obesity-associated NASH.

A New 1,3-Benzodioxole Compound from Hypecoum erectum and Its Antioxidant Activity.

The purpose of this study was to identify the chemical components in aerial parts of Hypecoum erectum. A new 1,3-benzodioxole derivative, identified as Hypecoumic acid (1), was isolated, together with the three known compounds: protopine (2), coptisine (3), and cryptopine (4). Their structures were identified based on extensive spectroscopic experiments, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectra (HR-ESI-MS), as well as comparison with those reported in the literature. Meanwhile, the in vitro antioxidative activity of all compounds was determined using a DPPH-scavenging assay, and compound 1 (IC50 = 86.3 ± 0.2 µM) was shown to have moderate antioxidative activity.

Structures and antiosteoclastogenic activity of compounds isolated from edible lotus (Nelumbo nucifera Gaertn.) leaves and stems.

One new 1,4-bis-phenyl-1,4-butanedione glycoside (14), one new eudesmane-type sesquiterpenoid (16), and 16 known compounds were isolated from the leaves and stems of Nelumbo nucifera Gaertn. The structures of the isolated compounds were elucidated by interpretation of their 1D and 2D NMR spectroscopic and HRESIMS data. Time-dependent density functional theory calculations and Electronic Circular Dichroism (ECD) spectroscopy was used to determine absolute configurations of the new eudesmane-type sesquiterpenoid (16). All the isolated compounds were examined for their antiosteoclastogenic activity. Preliminarily results of the TRAP staining on RAW 264.7 cells indicated that compounds 1 and 11 possess potential inhibitory effects on RANKL-induced osteoclast formation. Further bioassay investigation was carried out to reveal that compounds 1 and 11 suppressed RANKL-induced osteoclast formation in a concentration-dependent manner with the inhibition up to 55% and 78% at the concentration of 10 µM, respectively. In addition, the structure-activity relationship analysis showed that the 1,3-dioxole substitute and the double bond at C-6a/C-7 in the aporphine skeleton may be responsible for the antiosteoclastogenic activity. The findings provided valuable insights for the discovery and structural modification of aporphine alkaloids as the antiosteoclastogenic lead compounds.

Quantitative HPLC-UV Study of Lignans in Anthriscus sylvestris.

Wild chervil (Anthriscus sylvestris) is a wild-growing plant from the Apiaceae family, used as a food in Europe and eastern Asia. Due to its high content of lignans known to possess anti-inflammatory, antiproliferative, antiviral and other activities, it represents a potential functional food. However, quantitative data on lignans are still scarce and limited to deoxypodophyllotoxin, nemerosin and yatein. In this paper, a newly developed and validated reverse-phase HPLC-UV method was used to evaluate the content of 14 lignans in both aerial parts and roots of A. sylvestris. The most abundant root components were found to be deoxypodophyllotoxin (2.0-42.8 mg/g), nemerosin (2.0-23.4 mg/g), yatein (1.1-18.5 mg/g), podophyllotoxone (0.7-20.5 mg/g), guaiadequiol (0.8-8.3 mg/g) and dimethylmatairesinol (0.1-5.2 mg/g). Despite the high intra-population variability, a general trend of an increased lignan content during plant development could be observed in the root samples, whereas an opposite trend was observed in the herb samples. A validation study indicated that some of the investigated compounds-7-oxoaryltetralins and dibenzylbutyrolactones-have low stability and require cold storage in the dark. Furthermore, dibenzylbutyrolactones were confirmed to undergo a fast cis-trans isomerization; therefore, only the total content of these isomers should be reported.

Schisantherin D from Schisandra chinensis (Turcz.) Baill. exhibits anti-liver fibrosis capacity via modulating ETBR involved signaling, an in vitro and in vivo study.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-ß1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-ß/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

A multidimensional strategy for uncovering comprehensive quality markers of Schisandra chinensis (Turcz.) Baill based on pharmacodynamics and chemical properties.

BACKGROUND: Quality control of Traditional Chinese Medicines (TCMs) has improved greatly, but there is still a lack of a convincing quality evaluation system for TCMs. Developing quality control markers of TCMs based on pharmacodynamics instead of content has been an attractive approach. However, on account of neglecting phytochemistry attributes of TCMs, part of effective markers might be short of specificity and inconvenient for detecting in production manufacture, which is adverse to control the quality of TCMs systematically. PURPOSE: To build a novel and multidimensional quality assessment approach for TCMs based on pharmacodynamics and chemical properties. METHODS: Schisandra chinensis (Turcz.) Baill (S. chinensis) was used as an example and a rat depression model was built by using a chronic unpredictable mild stress procedure. For identifying the antidepressive components of S. chinensis, we elucidated its antidepressant mechanism in first-step by using quantitative RT-PCR and immunoblotting techniques. And accordingly, correlation analysis between ingredients in vivo with target proteins and anti-inflammation experiments in vitro were carried out. On the other hand, HPLC fingerprint combinations with diverse chemometrics methods were applied to analyze 14 preparations of S. chinensis to obtain its characteristic chemical information. Finally, we ascertained the quality control markers of S. chinensis by integrating the efficacious and characteristic constituents. RESULTS: Our research indicated that S. chinensis treated depression by relieving disordered monoaminergic system and ameliorating neuroinflammation. Five effective substances (schisandrol A, schisandrin A, gomisin N, schisandrin B, and schisandrin C) were screened out according to their potential anti-depression efficacy. Besides, 21 common ingredients and 4 representative constituents of S. chinensis were identified by chemical analysis, whereas only 2 characteristic quantitative markers (schisandrol A, schisandrol B) were ultimately ascertained based on previous studies. CONCLUSION: 6 components, schisandrol A, schisandrin A, gomisin N, schisandrin B, schisandrin C, and schisandrol B, possessed efficacy, measurability, and specificity, were selected as the comprehensive markers for quality control of S. chinensis. We proposed a multidimensional strategy for identifying comprehensive quality markers for TCMs in this study.

In vivo, in vitro and Molecular Modelling Analysis of Isoquercetin, Roseoside, Coreximine, Anonaine, and Arianacin Molecules.

INTRODUCTION: Annona muricata is a member of the Annonaceae family. This plant has a high concentration of acetogenin, which gives it excellent therapeutic property. Researchers have tested this miraculous herb in breast cancer cells treatment and observed that it could be a source of anti-cancer agents. The proposed study focused on screening the anticancer biological activity of Annona muricata plant by using the in vitro, in vivo, and in silico methods. METHODS: In in vitro analysis, the IC50 was determined on two-dimensional and three-dimensional breast cancer cells. 2D cells were cultured on flat dishes typically made of plastic, while 3D cells were cultured using the hanging drop method. In in vivo analysis, Drosophila melanogaster was preferred, and the LC50 was determined. In in silico analysis, molecular docking studies have been carried out on the different classes of Annona muricata acetogenins against the target proteins. Nearly, five acetogenins were selected from the literature, and docking was performed against human Bcl-2, Bad and Akt-1 proteins. RESULTS: In vitro and in vivo results revealed the IC50 value of 2D MDA-MB-231 cells as 330 µg.mℓ-1, of 2D MCF-7 cells as290 µg.mℓ-1, and of 3D MCF-7 and MDA-MB-231 cells about 0.005 g.mℓ-1; the LC50 value of Drosophila melanogaster was determined as 0.1 g.mℓ-1. In silico results revealed that the docked complex formed by Isoquercetin showed better binding affinity towards target proteins. CONCLUSION: As a result of the analysis, the Annona muricata plant has been observed to be effective against cancer and likely to be a potential drug.

Comparative effects of sesame lignans (sesamin, sesamolin, and sesamol) on oxidative stress and lipid metabolism in steatosis HepG2 cells.

Non-alcoholic fatty liver disease (NAFLD) can be attributed to the imbalance between lipogenesis and lipidolysis in the liver. Sesame lignans (sesamin, sesamolin, and sesamol) are unique bioactive compounds responsible for the nutritional function of sesame oils. However, the preventive effects of three lignans on oxidative stress and lipid metabolism in steatosis HepG2 cells have not been compared. In this study, we investigated the role of sesamin, sesamolin, and sesamol on hepatic lipid accumulation and explored the underlying mechanism via a well-established cell model. The results showed that 3 µg/ml of lignans could decrease the TG/TC contents and alleviate cellular oxidative stress, with an order of the lipid-lowering effect as sesamol > sesamin > sesamolin. The lignan-activated AMPK and PPAR signaling pathways enhanced gene and protein expressions related to fatty acid oxidation, cholesterol efflux, and catabolism. Meanwhile, treatment of the steatosis HepG2 cells with sesamin, sesamolin, and sesamol reduced lipid synthesis and cholesterol uptake, thus lowering intracellular lipogenesis in the process of NAFLD. Our data suggested that sesame lignans can attenuate oxidative stress and regulate lipid metabolism in liver cells, which may be potential therapeutic agents for treating the NAFLD. PRACTICAL APPLICATIONS: The present work demonstrated that sesame lignans can be used for dietary supplements or functional additives with excellent lipid-lowering effects. Furthermore, this study supplied potential molecular mechanisms involved in NAFLD treatment process, and also provided nutritional guidelines for sesame oil evaluation and selection.

The Effects of Sesamin Supplementation on Obesity, Blood Pressure, and Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Aims: Sesamin, the main lignin constituent of sesame, plays a pivotal role in regulating physical state. Some studies have evidenced that the supplementation of sesamin may decrease cardiovascular disease risk. The goal of this systematic review was to summarize evidence of the effects of sesamin supplementation on obesity, blood pressure, and lipid profile in humans by performing a meta-analysis of randomized controlled trials. Data Synthesis: Five databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) were searched electronically from inception to July 2021 to identify randomized controlled trials that assessed the impact of sesamin on obesity, blood pressure, and lipid profile. Weighted mean difference (WMD) and standard deviation (SD) were used to present the major outcomes. Conclusions: Seven trials (n = 212 participants) were included in the overall analysis. Results showed that sesamin supplementation caused a great reduction in TC (WMD: -10.893 mg/dl, 95% CI: -19.745 to -2.041, p = 0.016), LDL-c (WMD: -8.429 mg/dl, 95% CI: -16.086 to -0.771, p = 0.031), and SBP (WMD: -3.662 mmHg, 95% CI: -6.220 to -1.105, p = 0.005), whereas it had no effect on HDL-c, TG, DBP, or weight. Subgroup analysis showed that duration, parallel design, and unhealthy status can affect TC, LDL-c, and SBP evidently. We did not discover a strong link between indicators' changes and duration of supplementation. Sesamin can be used as an obtainable dietary supplement to improve blood pressure and blood lipids, and further as a health product to prevent cardiovascular diseases.

A comprehensive mechanistic insight into the dietary and estrogenic lignans, arctigenin and sesamin as potential anticarcinogenic and anticancer agents. Current status, challenges, and future perspectives.

A large body of evidence indicates that lignans as polyphenolic compounds are beneficial against life-threatening diseases such as cancer. Plant lignans have the potential to induce cancer cell death and interfere with carcinogenesis, tumor growth, and metastasis. Epidemiological studies have revealed that the intake of lignans is inversely associated with the risk of several cancers. Moreover, numerous experimental studies demonstrate that natural lignans significantly suppress cancer cell proliferation with minimal toxicity against non-transformed cells. Dietary lignans arctigenin and sesamin have been found to have potent antiproliferative activities against various types of human cancer. The purpose of this review is to provide the reader with a deeper understanding of the cellular and molecular mechanisms underlying anticancer effects of arctigenin and sesamin. Our review comprehensively describes the effects of arctigenin and sesamin on the signaling pathways and related molecules involved in cancer cell proliferation and invasion. The findings of present review show that the dietary lignans arctigenin and sesamin seem to be promising carcinopreventive and anticancer agents. These natural lignans can be used as dietary supplements and pharmaceuticals for prevention and treatment of cancer.

Differential effects of biogenic and chemically synthesized silver-nanoparticles application on physiological traits, antioxidative status and californidine content in California poppy (Eschscholzia californica Cham).

Silver nanoparticles (AgNPs) of both biologically and chemically origins trigger various physiological and metabolic processes through interaction with plant cells, exerting positive, negative and inconsequential effects. However, their impacts on plant systems must be critically investigated to guarantee their safe application in food chain. In this study, the effects of chemically synthesized (synthetic) AgNPs (sAgNPs) and biologically synthesized (biogenic) AgNPs (bAgNPs) on physiological and biochemical features of Eschscholzia californica Cham were evaluated at different concentrations (0, 10, 25, 50 and 100 mg L-1). Plants exposed to bAgNPs (at 10 and 25 mg L-1) and sAgNPs (at 10 mg L-1) displayed relatively uniform deposition of AgNPs on leaf surface, however, the higher concentration (100 mg L-1) was accompanied by aggregation of AgNPs, resulting in anatomical and physiological disorders. Foliar application of both AgNPs at lower concentrations resulted in significant (P < 0.01) improve in the content of photosynthetic pigments (chlorophylls a, b, a+b, and carotenoids) and total phenolics over the control in a dose-related manner. Leaf relative water content decreased steadily with increasing both sAgNPs and bAgNPs concentrations-with sAgNPs being more inhibitive. Both types of AgNPs at 100 mg L-1 significantly (P < 0.05) increased electrolyte leakage index, level of lipid peroxidation product (malondialdehyde), and leaf soluble sugar content when compared to controls. No significant difference was found on cell membrane stability index among the plants exposed to bAgNPs and sAgNPs at the lowest concentration over the control. Californidine content was significantly (P < 0.01, by 45.1%) increased upon all the bAgNPs treatments (with a peak at 25 mg L-1) relative to control. The obtained extracts from plants treated with bAgNPs at lower concentrations revealed a significant induction of antioxidant capacity (based on DPPH˙ free radical scavenging and ferrous ions-chelating activities) with lower IC50 values compared to the other treatments. Conclusively, bAgNPs at lower concentrations are potent elicitors of pharmaceutically active compounds biosynthesis, which enhance physiological efficiency of E. californica, but at higher concentrations bAgNPs are equally toxic as sAgNPs.

Screening and verification of CYP3A4 inhibitors from Bushen-Yizhi formula to enhance the bioavailability of osthole in rat plasma.

ETHNOPHARMACOLOGICAL RELEVANCE: With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated. AIM OF THE STUDY: The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported. MATERIALS AND METHODS: Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance. RESULTS: 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro, we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid, 1,2,3,4,6-O-Pentagalloylglucose, Rutin, and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC50 = 0.339 µM), and even better than the clinically used drug (Ket) at the concentration of 5 µM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01). CONCLUSIONS: Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.