Major Lignan Research Articles

Comparison of Metabolic Profiles of Fruits of Arctium lappa, Arctium minus, and Arctium tomentosum

Metabolites of the edible and medicinal plant Arctium have been shown to possess beneficial activities. The phytochemical profile of Arctium lappa is well-explored and its fruits are known to contain mainly lignans, fatty acids, and sterols. But the fruits of other Arctium species have not been thoroughly investigated. Therefore, this study compares the metabolic profiles of the fruits of A. lappa, Arctium tomentosum, and Arctium minus. Targeted metabolomics led to the putative identification of 53 metabolites in the fruit extracts, the majority of these being lignans and fatty acids. Quantification of the major lignans showed that the year of collection had a significant effect on the lignan content. Furthermore, A. lappa fruits contained lesser amounts of arctigenin but greater amounts of arctigenin glycoside than A. minus fruits. Regarding the profile of fatty acids, A. minus fruits differed from the others in the presence of linolelaidic acid.Graphical

Sesamin and sesamolin potentially inhibit adipogenesis through downregulating the peroxisome proliferator-activated receptor γ protein expression and activity in 3T3-L1 cells

Sesamin and sesamolin are major sesame lignans that have demonstrated anti-inflammatory, anticancer, and neuroprotective properties and potential benefits in the liver, cardiovascular diseases, and metabolic syndrome. However, despite previous research on their antiobesity effects and underlying mechanisms, a comprehensive investigation of these aspects is still lacking. In this study, we evaluated the regulatory effects of 20 to 80 µM sesamin and sesamolin on adipogenesis in vitro using 3T3-L1 cells as a model cell line. We hypothesized that the lignans would inhibit adipogenic differentiation in 3T3-L1 cells through the regulation of peroxisome proliferator-activated receptor γ (PPARγ). Our data indicate that sesamin and sesamolin inhibited the adipogenic differentiation of 3T3-L1 cells by dose-dependently decreasing lipid accumulation and triglyceride formation. Sesamin and sesamolin reduced the mRNA and protein expression of the adipogenesis-related transcription factors, PPARγ and CCAAT/enhancer-binding protein α, leading to the dose-dependent downregulations of their downstream targets, fatty acid binding protein 4, hormone-sensitive lipase, lipoprotein lipase, and glucose transporter 4. In addition, glucose uptake was dose-dependently attenuated by sesamin and sesamolin in both differentiated 3T3-L1 cells and HepG2 cells. Interestingly, our results suggested that sesamin and sesamolin might directly bind to PPARγ to inhibit its transcriptional activity. Finally, sesamin and sesamolin decreased the phosphorylation of 3 mitogen-activated protein kinase signaling components in differentiated 3T3-L1 cells. Taken together, our findings suggest that sesamin and sesamolin may exhibit antiobesity effects by potentially downregulating PPARγ and its downstream genes through the mitogen-activated protein kinase signaling pathway, offering important insights into the molecular mechanisms underlying the potential antiobesity effects of sesamin and sesamolin.

α-Glucosidase Inhibitors from Cold-Pressed Black Sesame (Sesamum indicum) Meal: Characterization of New Furofuran Lignans, Kinetic Study, and In Vitro Gastrointestinal Digestion.

Black sesame (Sesamum indicum) meal is an agricultural waste obtained after oil extraction. It is used as a key protein source in animal feed. Previous investigations have indicated that its health benefits, such as antidiabetic activity, are mainly due to its high lignan content. In the present study, we applied α-glucosidase inhibitory guided isolation to identify the active components responsible for the above claim. Twenty-nine compounds, mostly lignans, were isolated and identified, of which five (2-3, 12-13, and 28) were newly isolated. Of the isolated compounds, 20 and 21 were the most potent inhibitors, retarding enzyme function in noncompetitive and uncompetitive manners. Structure-activity relationship analysis suggested that the number of phenolic hydroxyl groups in the structures was significantly related to the inhibitory effect against α-glucosidase. A gastrointestinal digestion study of the major lignan sesaminol triglucoside (STG, 9) suggested that the transformation of dioxymethylene and glucoside moieties gradually began in the late process, thus enhancing the α-glucosidase inhibitory effect.

How does UV-B radiation influence the photosynthesis and secondary metabolism of Schisandra chinensis leaves?

Schisandra chinensis (Trucz.) is a medicinal plant with a rich profile of physiologically active substances, including lignans. The levels of these substances can be affected by external factors such as light exposure, temperature, and humidity. The current study aimed to explore the impacts of UV-B radiation on the photosynthetic properties and biochemical parameters as well as the contents of major lignans and phenolic compounds in two-year-old S. chinensis plants. The results revealed that exposure to UV-B radiation (10.0 μW cm−2, 30 min per day) did not cause any significant changes in the photosynthetic properties of S. chinensis plants until the 7th or 15th days of treatment. However, a significant reduction in photosynthetic capacity was observed after 30 days of UV-B exposure. The contents of photosynthetic pigments including chlorophyll a, b, total chlorophyll, and carotenoid decreased under UV-B treatment. Besides, we found that the highest level of lignan synthesis, a major bioactive compound in S. chinensis, occurred after seven days of UV-B treatment. However, lignan levels gradually decreased over time, with most individual lignans either having similar or lower contents than the control at 30 days. Furthermore, a comprehensive analysis of 35 phenolic compounds present in S. chinensis leaves showed that quercetin, isoquercetin, and 4-hydroxycinnamic acid were critical phenolic compounds responsible for moderating the plant's response to ultraviolet stress. Consistent with the trend of lignan content, these phenolic compounds exhibited the highest levels after seven days of UV-B treatment and gradually decreased over time. Our findings demonstrate that an appropriate dose of UV-B exposure can stimulate the synthesis of bioactive compounds such as lignans and phenolics via activation of the phenylpropanoid pathway in S. chinensis, enhancing its medicinal value.

Optimizing conditions for the recovery of lignans from sesame cake using three green extraction methods: Microwave-, ultrasound- and accelerated-assisted solvent extraction

Lignans, a group of polyphenolic low molecular weight bioactive compounds with health benefits, are major constituents of sesame cake (SC), a by-product derived from sesame oil processing. The utilization of this by-product in the food or nutraceutical industries could explore its valorization route in compliance with sustainability and circular economy principles. This study aimed to investigate the impact of different environmental-friendly processing approaches such as ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and accelerated solvent extraction (ASE) for lignans extraction from SC using central composite design (CCD) with response surface methodology (RSM). Sesaminol triglucoside (SETRI) and sesaminol diglucoside (SEDI) were identified and quantified as the major lignan glucosides in SC. Ethanol/water mixture was selected as ‘green’ solvent for all extraction methods. The influence of ethanol concentration (X1), extraction time (X2), temperature (X3) and solid-to-solvent (SS) ratio or solid weight (X4) on extraction yield (EY), SETRI and SEDI contents for each technique was examined. The developed models exhibited a high degree of desirability (> 0.72) with determined optimal levels of extraction parameters as follows: X1 = 71%, X2 = 10 min, X3 = 50 °C, X4 = 1.50 g/20 mL for UAE; X1 = 80%, X2 = 5 min, X3 = 50 °C, X4 = 0.85 g/20 mL for MAE; X1 = 80%, X2 = 20 min, X3 = 65 °C, X4 = 2 g for ASE. Under these optimal conditions, the experimental values for EY, SETRI and SEDI contents in SC extracts were: 8.28%, 105.98 mg/g and 16.93 mg/g, respectively for UAE; 8.75%, 105.41 mg/g and 18.76 mg/g, respectively for MAE; 9.34%, 108.00 mg/g and 18.34 mg/g, respectively for ASE. The ANOVA analysis from the RSM were fitted with quadratic models yielding acceptable R2 (> 0.87), adjusted R2 (> 0.77), predicted R2 (> 0.74), and nonsignificant lack-of-fit (p > 0.05) values. Ethanol concentration and solid-to-solvent ratio were the most influencing factors affecting lignans extraction. Although ASE was found as the most suitable method for extracting lignans from SC, from an industrial viewpoint, UAE could be a more affordable technique due to advances in ultrasonic processing devices for large scale applications.

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.

Identification of the Microbial Transformation Products of Secoisolariciresinol Using an Untargeted Metabolomics Approach and Evaluation of the Osteogenic Activities of the Metabolites.

Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

Sesamin lacks zebrafish embryotoxicity but exhibits evidence of anti-angiogenesis, anti-oxidant and anti-inflammatory activities

Sesamin, the major lignan in sesame seeds (Sesamum indicum L.), is known to have several pharmaceutical activities. However, its toxicological profile is still limited, especially regarding embryotoxicity. This study aimed to evaluate the developmental toxicity of sesamin in zebrafish embryos. After 72 h exposure, sesamin did not affect the survival and hatching rates, nor did it cause malformation in zebrafish embryos. Cardiotoxicity was also evaluated by monitoring embryo heartbeats and erythrocyte staining using o-dianisidine. The results showed that sesamin did not affect heart morphology, heart rate, or cardiac output in zebrafish embryos. The present study also evaluated sesamin's anti-angiogenesis, antioxidant and anti-inflammation activities. Sesamin significantly decreased the sub-intestinal vessel plexus as revealed by alkaline phosphatase staining indicating the compound exhibited anti-angiogenesis activity. For the antioxidant and anti-inflammatory assays, oxidative stress and inflammation in zebrafish embryos were induced by hydrogen peroxide and lipopolysaccharide, respectively. The reactive oxygen species (ROS) and nitric oxide (NO) production were detected using a fluorescent dye. Sesamin significantly decreased ROS and NO production in zebrafish embryos. In addition, the transcription examination by qRT-PCR of oxidative- and inflammation-related genes showed that sesamin affected the genes in a manner that correlated with results from the efficacy assays. In conclusion, the present study revealed that sesamin did not cause embryotoxicity and cardiotoxicity in zebrafish embryos. In addition, it exhibited evidence of anti-angiogenesis, antioxidant and anti-inflammatory activities.

Pharmacological and Nutritional Benefits of Flaxseed’s (Linum usitatissimum Linn.) Biocomponents

Abstract: Linum usitatissimum (Linn.), Commonly known as flaxseed or flaxseed, belongs to the family Linaceae. Flaxseed is a crop of blue flowers that produce small, flat seeds of golden yellow to reddish-brown color. It is a native of the Mediterranean and West Asia. Due to its health benefits associated with the high content of linolenic acid (ALA), flaxseed has played a major role in diet and research. The ALA is an essential omega-3-fatty acid, and also due to its presence a major lignan, i.e. secoisolaricyrcinol diglucoside (SDG). There is also a wide range of uses of flaxseed oil in skin health, anticoagulants, anticancer, ulcer treatment, muscle growth, and weight loss. The nutritional composition of flaxseed is about 30% carbohydrate, 18% protein, and 39% fat. Flaxseed contains most carbohydrates in the form of fiber and contains more than 45% omega-3 fatty acids. It also contains dietary fibers, proteins and polyunsaturated fatty acids. All the ingredients possess different health benefits. Although plant resources are the key ingredient in drug discovery, the popularity of flaxseed always fascinate scientists, the number of articles giving information about the chemical components of flaxseed and its potential clinical use is very little. This review provides a systematic summary of the research completed over the past decade and provides an up-to-date summary of the various bioactive and outlines the relationship between the nutritional and pharmacological use of chemical ingredients and its flaxseed.

Abstract MP36: Long-Term Dietary Lignan Intake and Weight Change: Results From Three Prospective Cohort Studies

Objectives: Studies suggest that endogenous estrogen may be involved in regulating body weight. Dietary lignans can act as estrogen receptor agonists and may be beneficial for weight control. We prospectively examined the association between changes in dietary lignan intake with weight change. Methods: We analyzed data from 124,875 men and women in the Nurses’ Health Study (1986-2010), Nurses’ Health Study II (1991-2011), and the Health Professionals Follow-up Study (1986-2010). We calculated 4-year changes in total lignan intake as well as in four major individual lignans (matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol) using data from a semi-quantitative food frequency questionnaire. Participants reported their height and weight at baseline and updated their current weight every 2 years thereafter, from which we calculated 4-year changes in weight as the primary study outcome. We used multivariable generalized linear regression models to examine the association between 4-year changes in lignan intake with 4-year weight changes over the same period, and these models were adjusted for age, baseline BMI in each period, and relevant lifestyle factors. Results: Each 1-standard deviation (SD) increase in total lignan intake was associated with a 4-year weight change of -0.36 lbs (95% confidence interval [CI] -0.40 to -0.33 lbs; P for trend <0.0001). This inverse association persisted among all four individual lignans, although the magnitude of this association was the strongest for lariciresinol (-0.63 lbs [95% CI, -0.67 to -0.59 lbs]; P for trend <0.0001) (Figure) . The observed associations were stronger among certain subgroups, including those with BMI ≥25 kg/m 2 , below-median diet quality, or below-median physical activity level. Conclusions: Increases in dietary lignan intake were associated with less weight gain over the same 4-year period. Our findings support existing dietary recommendations to consume a healthy plant-based diet.

Dose-Dependent Production of Mammalian Lignans in Rats and In Vitro from the Purified Precursor Secoisolariciresinol Diglycoside in Flaxseed

The mammalian lignans enterodiol (ED) and enterolactone (EL) produced from colonic bacterial action on dietary precursors have exhibited anticarcinogenic effects in vitro. The major lignan precursor in flaxseed (a rich source) has been identified as secoisolariciresinol diglycoside (SDG). The purpose of this study was to first isolate SDG and determine whether 1) SDG accounted for all the lignan production from flaxseed; 2) this production was dose-related; and 3) a relationship between in vitro production and in vivo urinary excretion existed. Extraction of flaxseed with dioxane:ethanol (1:1, v/v) followed by chromatographic separations yielded the purified SDG. Rats were fed a high fat diet without/with 2.5, 5 or 10 g/100g ground flaxseed or 1.1, 2.2 or 4.4 µmol SDG/d (equivalent to levels in the respective flaxseed diets) for 4 wk. In vitro lignan production was assessed by fermenting flaxseed or SDG for 24 h with human fecal inoculum. Urinary lignan excretion increased linearly with doses from 0–5% flaxseed and 0–2.2 µmol SDG/d followed by a plateau, indicating a threshold response. When all doses were considered, a curvilinear relationship was observed. A similar trend was seen in vitro for SDG, resulting in a high correlation between in vitro production and in vivo excretion of lignans (r = 0.990, P < 0.02). Thus in vivo response can be predicted with confidence based on in vitro results. Theoretical urinary ED + EL from the SDG present in flaxseed correlated with the actual excretion in flaxseed-fed animals (r = 0.655, P < 0.005). However, urinary ED + EL of SDG-fed rats was only 20% of levels of flaxseed-fed rats, indicating the presence of other precursors or incomplete conversion of SDG to ED and EL.

Pharmacological activities and mechanisms of action of hypophyllanthin: A review.

Hypophyllanthin is a major lignan present in various Phyllanthus species and has been used as one of the bioactive chemical markers for quality control purposes as it contributes to their diverse pharmacological activities. The objective of this study is to compile up-to-date data on the pharmacological actions and mechanisms of hypophyllanthin. This review also includes the extracts of Phyllanthus species whose pharmacological actions have been partially attributed to hypophyllanthin. The scientific findings on the compound are critically analyzed and its potential as a lead molecule for the discovery of drug candidates for the development of therapeutics to treat diverse diseases is highlighted. Data collection was mainly through the exploration of Ovid-MEDLINE, Scopus, Science Direct, and Elsevier databases. Studies conducted in vitro and in vivo showed that hypophyllanthin had potent immunomodulating properties as well as a variety of other pharmacological properties, including anti-inflammatory, hepatoprotective, anti-tumor, anti-allergic, anti-hypertensive, and phytoestrogenic properties. Several mechanisms of action on the effects of hypophyllanthin on the immune system, in cancer and other disease states, were presented to provide some insights into its pharmacological effects. Before being submitted to clinical investigations, additional animal studies utilising different animal models are necessary to analyse its bioavailability, pharmacokinetics, and pharmacodynamic properties, as well as its toxicity, to determine its efficacy and safety. Understanding its potential as a lead molecule for the discovery of therapeutic candidates, particularly for the development of therapies for inflammatory and immune-related disorders, requires an understanding of its pharmacological activities and mechanisms of action. An insight into its pharmacological activities and mechanisms of action will provide an understanding of its potential as a lead compound for the discovery of drug candidates, especially for the development of therapies for inflammatory and immune related diseases.

Schisandrol A and gomisin N from Schisandra chinensis extract improve hypogonadism via anti-oxidative stress in TM3 Leydig cells.

Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency. Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency. S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE. The 2,2-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3β-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17β-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N). These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.

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.

The Ethanol Extract of Syringa oblata Heartwood, a Mongolian Folk Medicine Containing Major Lignans, Exerts Analgesic and Sedative Effects on Mice.

The heartwood of Syringa oblata Lindl. (SO) is one of Mongolian folk medicines to treat insomnia and pain, while its pharmacological evaluation and underlying mechanism remain unclear. In this study, the sedative effect of ethanol extract of SO (ESO) was evaluated with the locomotor activity test and the threshold dose of pentobarbital sodium-induced sleep test in mice, and the hot plate test, acetic acid-induced writhing test, and formalin test in mice were used to evaluate its analgesic effect. The underlying mechanism of ESO analgesia was explored by RT-PCR and western blot analysis, which is associated with the regulation of the NF-κB signaling pathway. Besides, the main constituents of ESO were characterized by LC/MS data analysis and comparison with isolated pure compounds. The current findings brought evidence for clinical application and further pharmacological and phytochemical studies on SO.

Exploring the active compounds and potential mechanism of the anti-nonalcoholic fatty liver disease activity of the fraction from Schisandra chinensis fruit extract based on multi-technology integrated network pharmacology

Ethnopharmacological relevanceSchisandra chinensis fruit is a well-known traditional Chinese medicine (TCM) that has been used to treat various liver diseases. Our previous study revealed that its extract is effective against nonalcoholic fatty liver disease (NAFLD). Aim of this studyThis study aimed to elucidate the active components and explore the underlying mechanisms of action of S. chinensis fruit in the treatment of NAFLD. Materials and methodsA HepG2 cell model was used to screen the anti-NAFLD activity of the fraction from S. chinensis fruit extract. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to determine the components of the active fraction. Active compounds, potential targets, and key pathways were predicted for the active fraction treatment of NAFLD using network pharmacology. The anti-NAFLD effects of the active fraction and core active compound 3 were further validated using a high-fat diet (HFD)-induced NAFLD mouse model, intraperitoneal glucose tolerance test (IPGTT), and intraperitoneal insulin tolerance test (IPITT). Related hepatic mRNA expression was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to preliminarily validate the mechanism. ResultsIn vitro experiments showed that the active fraction of S. chinensis fruit ethanol (EtOH) extract was mainly concentrated in the soluble fraction of petroleum ether (PET). Thirty-seven lignans were identified in this active fraction using UPLC-Q-TOF/MS. Network pharmacology studies have indicated that its anti-NAFLD effects lie in three major active lignans (3, 24, and 27) contained in PET, which may regulate the insulin resistance signaling pathway. In vivo experiments demonstrated that PET and core active compound 3 treatment significantly attenuated hepatic steatosis and reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST), insulin, malondialdehyde (MDA), hepatic triglyceride (TG), and total cholesterol (TC) in HFD-induced mice (P < 0.05). Moreover, treatment with PET and compound 3 alleviated glucose tolerance and insulin resistance. These beneficial effects can be achieved by regulating the expression of Pik3ca, Gsk3β, Jnk1, and Tnf-α. ConclusionThis study identified the main active fraction and compounds responsible for the anti-NAFLD activity of S. chinensis fruit. This mechanism may be related to regulation of the resistance pathway.

Siamese, Indian, and Brazilian Rosewoods: A Review on Phytochemistry, Applications, and Pharmacology

For the first time, the current review fully provides information on the phytochemicals, applications, and pharmacological aspects relating to 3 Dalbergia species, Siamese Rosewood ( Dalbergia cochinchinensis Pierre ex Laness.), Indian Rosewood ( D sissoo Roxb.), and Brazilian Rosewood ( D nigra (Vell.) Benth.). Based on chromatographic separation, phytochemical studies on these plants have, to date, resulted in the isolation and structural elucidation of 136 secondary metabolites. Among them, flavonoids and simple phenols are major components, whereas terpenoids, quinones, benzofurans, benzophenols, phytosterols, stilbenes, phthalates, xanthones, and lignans have been also detected. Dalbergia rosewoods are heavy and strong, taking an outstanding polish, and are very suitable for furniture. They are also used as natural dyes, raw materials for removing contaminants from water, and might be a rich resource of essential oils, polysaccharides, and active glycosidase enzymes. Dalbergia crude extracts and their secondary metabolites have a wide range of pharmacological actions, such as anti-inflammatory, anti-oxidative, anti-aging, anti-bacterial, anti-nociceptive, anti-diarrheal, anti-pyretic, gastrointestinal, biocontrol activities, but sexual and anti-osteoporosis activities are the most valuable.

A Comprehensive Review of the Main Lignan Components of Schisandra chinensis (North Wu Wei Zi) and Schisandra sphenanthera (South Wu Wei Zi) and the Lignan-Induced Drug-Drug Interactions Based on the Inhibition of Cytochrome P450 and P-Glycoprotein Activities.

Wu Wei Zi is the dried fruit of Schisandra chinensis (Turcz.) Baill. or Schisandra sphenanthera Rehd. et Wils. (family Magnoliaceae). As a homology of medicine and food, it has been widely used in China for thousands of years, to tonify the kidney, and ameliorate neurological, cardiovascular, liver, and gastrointestinal disorders. As its increasing health benefits and pharmacological value, many literatures have reported that the combination of Wu Wei Zi in patients has led to fluctuations in the blood level of the combined drug. Therefore, it is extremely important to evaluate its safety concern such as drug-drug interactions (DDIs) when patients are under the poly-therapeutic conditions. This review summarized the effects of Wu Wei Zi extract and its major lignan components on cytochrome P450 and P-glycoprotein activities, the change of which could induce metabolic DDIs. Our review also elaborated on the differences of the major lignan components of the two Schisandra species, as well as the absorption, distribution, metabolism, and elimination of the major lignans. In conclusion, these results would enhance our understanding of the DDI mechanisms involving Wu Wei Zi, and may potentially untangle some differing and conflicting results in the future.

Sesame lignans upregulate glutathione S-transferase expression and downregulate microRNA-669c-3p.

Oxidative stress is associated with aging and pathologies such as cardiovascular diseases, Alzheimer’s disease, and cancer. Glutathione S-transferase (GST), a family of detoxification enzymes, plays a crucial role in countering oxidative stress. Therefore, there is a need for the development of physiologically functional foods and agricultural products, which enhance GST activity. Sesamin and episesamin are major lignans in refined sesame oil that exhibit beneficial properties including antioxidative stress effects. A previous study showed that sesamin upregulated GST activity. This study aimed to elucidate the mechanism underlying the GST activity enhancement elicited by sesame lignans. C57BL/6J mice were orally administered 20 mg/kg body weight sesame lignans (sesamin:episesamin=1:1) for 7 days. Oral administration of sesame lignans increased the GST activity in the mouse liver. Furthermore, the lignans upregulated GSTA1, GSTA4, and GSTM4 protein expression. Microarray analysis revealed that sesame lignans changed the expression of various microRNAs (miRNAs) (84 upregulated, 19 downregulated). We also found 16 miRNAs, including miR-669c-3p, that may negatively regulate GST expression among the 19 miRNAs with reduced expression caused by the sesame lignans. miR-669c is reportedly negatively correlated with GST. Additionally, we transfected NMuLi cells with an miR-669c-3p mimic and evaluated the effect of miR-669c-3p on GST mRNA and protein expressions. The results showed that the miR-669c-3p mimic suppressed the mRNA and protein levels of GSTA4 and GSTM4. In conclusion, sesame lignans increased GST protein expression and activity and downregulated miRNAs, including miR-669c-3p, which is a possible suppressor of GST.

Pomegranate, fruit of the desert, a functional food, and a healthy diet

Traditional medicinal plants contain various ranges of chemical contents and they have become popular because of effectiveness, frequently inadequate provision of modern medicine, preferences and cultural beliefs. Pomegranate belongs to the family of Punicaceae, and its various pharmacological activities are due to presence of wide range of bioactive compounds. The current searching was done by the keywords in main indexing systems including PubMed/MEDLINE, Scopus, and Institute for Scientific Web of Science as well as the search engine of Google Scholar. The keywords were traditional medicine, health benefits, pharmaceutical science, pomegranate, punicalin, punicalagin, and ellagitannins. Major polyphenols in peel and juice of pomegranate are flavonoids such as flavonols (catechin, epicatechin, gallocatechin), condensed tannins, phenolic acids such as gallic, ellagic and caffeic, hyrolysable tannins such as ellagitannins and gallotannins. The main organic acids in pomegranate juice are malic and citric, and in seed is fatty acids (punicic). The major alkaloids and lignans in peel are punigratane and isolariciresinol, respectively. Pomegranate fruit has been proven to act against various diseases like cancer, cardiovascular disorders, diabetes, AIDS, Alzheimer’s disease, male infertility, inflammation, coronary heart disease, and aging. The review summarizes the beneficial impacts of pomegranate which is recommended for consumption. Pomegranate is a high potential natural functional food due to its high pharmacological activities as an ancient efficacious natural drug.