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Background: Schisandra chinensis is widely applied in the prevention and treatment of asthma in China, but the material basis for the anti-asthmatic effect of S. chinensis is unclear. Our previous studies found that the lignans from S. chinensis can relax tracheal smooth muscle in rats. Schisandrol A (SCA) is a representative monomer of S. chinensis lignans with high content and activity. Purpose: This study was aimed at further exploring the relaxation effect of SCA and its mechanism on the isolated tracheal smooth muscle of rats through tracheal perfusion experiments. Materials and Methods: The isolated rat tracheal ring was precontracted with acetylcholine (ACh). Then, the impact of SCA on the tension of precontracted tracheal ring was studied. Verapamil (L-type calcium channel blocker) and four potassium channel blockers, including glibenclamide, tetraethylamine, 4-aminopyridine (4-AP), and barium chloride (BaCl2), as well as propranolol (β-adrenergic receptor antagonist), were respectively used to precontract the tracheal ring for investigation. Results: SCA could dose-dependently reduce the ACh-induced contraction of the tracheal ring, and the verapamil and 4-AP could weaken this effect, while BaCl2, glibenclamide, tetraethylamine, and propranolol did not show this effect. Conclusion: SCA can significantly relax the effect of tracheal smooth muscle of rats, and the underlying mechanism might be involved in the blocking of L-type Ca2+ channels and activating the voltage-dependent potassium channels (KV). [ABSTRACT FROM AUTHOR]

Background: Schisandra chinensis (S. chinensis) is a drug commonly used in the clinical treatment of cardiovascular diseases in Traditional Chinese Medicine. However, the specific components and mechanisms of its action are still unclear. We screened six kinds of lignans from S. chinensis with high content and found that schisandrol A and schisantherin A had a strong vasorelaxant effect. The purpose of this study was to investigate the relaxation and underlying mechanism of schisandrol A in the isolated thoracic aorta of rats. Materials and Methods: Isolated rat endothelium-intact and endothelium-removed thoracic aorta strips were pre-constricted with phenylephrine (PE), and the relaxation of schisandrol A on the strips was observed. Then, the mechanism was explored by pre-incubating the strips with nitric oxide synthetase inhibitor Nɷ-nitro-l-arginine methyl ester (L-NAME), cyclooxygenase inhibitor (indomethacin), potassium channel blockers 4-aminopyridine (4-AP), barium chloride (BaCl2), tetraethylamine (TEA), and glibenclamide, respectively, and changing the calcium concentration in the bath. In addition, expressions of endothelial nitric oxide synthetase (eNOS) mRNA and protein in rat thoracic aorta were detected. Results: Schisandrol A induced both endothelium-dependent and endothelium-independent relaxation of isolated thoracic aorta strips of rats, and the mechanism might be related to promoting the synthesis of NO, inhibiting Ca2+ release from the sarcoplasmic reticulum, and blocking the Ca2+ channels. Conclusion: These discoveries may provide a theoretical basis for the traditional application of S. chinensis to treat cardiovascular disease. [ABSTRACT FROM AUTHOR]

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage. [ABSTRACT FROM AUTHOR]

Xijier Qiaolongbatu,1,* Wenjuan Zhao,1,* Xucong Huang,2,3,* Feng Qian,1 Xinyi Yang,1 Jiaqi Wu,2 Cui Ma,2 Han Qu,1,2 Li Wang,3 Guorong Fan,2 Zhenghua Wu2 1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3School of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua Wu; Guorong Fan, Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-133-0177-7863 ; +86-21-36123711, Email zhenghua.wu@shgh.cn; fanguorong@sjtu.edu.cnBackground: Schisandrol A (Sch A) is the main active ingredient of Schisandra chinensis (Turcz.) Baill. Our previous study showed that Sch A has anti-pulmonary fibrosis (PF) activity, but its metabolic-related mechanisms of action are not clear.Methods: Here, we explored the therapeutic mechanisms of Sch A on PF by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) metabolomics approach and network analysis. The metabolites of Sch A in mice (bleomycin + Sch A high-dose group) plasma were identified based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS).Results: 32 metabolites were detected reversed to normal level after treating bleomycin (BLM)-induced PF mice with Sch A. The 32 biomarkers were enriched in energy metabolism and several amino acid metabolisms, which was the first report on the therapeutic effects of Sch A on PF through rescuing the disordered energy metabolism. The UPLC-Q-TOF/MS analysis identified 17 possible metabolites (including isomers) of Sch A in mice plasma. Network analysis revealed that Sch A and 17 metabolites were related to 269 genes, and 1109 disease genes were related to PF. The construction of the Sch A/metabolites-target-PF network identified a total of 79 intersection genes and the TGF-β signaling pathway was determined to be the main signaling pathway related to the treatment of PF by Sch A. The integrated approach involving metabolomics and network analysis revealed that the TGF-β 1-ID3-creatine pathway, TGF-β 1-VIM-carnosine pathway were two of the possible pathways Sch A regulated to modulate metabolic disorders, especially energy metabolism, and the metabolite of Sch A M5 was identified as a most likely active metabolite.Conclusion: The results suggested the feasibility of combining metabolomics and network analysis to reflect the effects of Sch A on the biological network and the metabolic state of PF and to evaluate the drug efficacy of Sch A and its related mechanisms.Graphical Abstract: Keywords: schisandrol A, pulmonary fibrosis, mechanism of action, network analysis, metabonomics

Lignan schisandrol A (SolA) is known to have antioxidant and anti‐inflammatory effects. However, the impact of SolA on obesity is poorly understood. To test the hypothesis that SolA has anti‐obesity effects, C57BL/6J mice were fed a high‐fat diet with or without SolA (0.006%, w/w) for 16 weeks. SolA decreased visceral fat mass (10%) by increasing energy expenditure and upregulating white adipose tissue thermogenic genes mRNA expression. Furthermore, SolA upregulated adipose Lpl mRNA expression and decreased plasma free fatty acid (FFA), triglyceride (TG), apolipoprotein (apo) B, aspartate aminotransferase levels and TG/HDL‐cholesterol and apoB/apoA1 ratios as well as hepatic lipid droplets. Increased hepatic β‐oxidation and fecal FFA and TG levels were observed in the SolA‐supplemented mice, suggesting an association of its lipid‐lowering effect with increased hepatic β‐oxidation, fecal fat excretion and adipose Lpl. Conclusionally, this study provides evidence on the protective effects of SolA against adiposity, dyslipidemia and nonalcoholic fatty liver disease in obese mice. [ABSTRACT FROM AUTHOR]

Diabetes have been shown to cause progressive neuronal injury with pain and numbness via advanced glycation end-products (AGEs)-induced neuronal cell apoptosis; however, the valuable drug targets for diabetic neuropathy have been poorly reported so far. In this study, we discovered a natural small-molecule schisandrol A (SolA) with significant protective effect against AGEs-induced neuronal cell apoptosis. ATP6V0D1, a major subunit of vacuolar-type ATPase (V-ATPase) in lysosome was identified as a crucial cellular target of SolA. Moreover, SolA allosterically mediated ATP6V0D1 conformation via targeting a unique cysteine 335 residue to activate V-ATPase-dependent lysosomal acidification. Interestingly, SolA-induced lysosome pH downregulation resulted in a mitochondrial–lysosomal crosstalk by selectively promoting mitochondrial BH3-only protein BIM degradation, thereby preserving mitochondrial homeostasis and neuronal cells survival. Collectively, our findings reveal ATP6V0D1 is a valuable pharmacological target for diabetes-associated neuronal injury via controlling lysosomal acidification, and also provide the first small-molecule template allosterically activating V-ATPase for preventing diabetic neuropathy. Schisandrol A is identified as an activator of V-ATPase by targeting ATP6V0D1 subunit, which provides a promising target against diabetic neuropathy. [Display omitted] [ABSTRACT FROM AUTHOR]

Schisandra chinensis (S. chinensis) extract powder is an important intermediate for the preparation of many prepared medicines and health products. The physicochemical properties of S. chinensis extract powder have been found to vary tremendously and this has been attributed to the long drying time in the traditional drying method. In this study, S. chinensis specimens were authenticated as the dry fruit of S. chinensis (Turcz.) Baill. S. chinensis were extracted twice with 8 L kg−1 (liquid to solid ratio) distilled water. The extracts were mixed and concentrated under reduced pressure to 1.24 g cm−3. Ultrasound‐assisted vacuum drying (UAVD) was employed as a new approach to improve the efficiency in drying S. chinensis extract powder and produce a higher quality product. The effects of drying temperature (70, 80, 90°C), ultrasonic power (40, 120, 200 W), and ultrasonic application time (4, 12, 20 min every 20 min) on the kinetics and quality of S. chinensis extract were investigated and compared with the conventional vacuum drying (CVD). It was shown that, with the increase in drying temperature, ultrasonic power, and time of UAVD, the drying time for S. chinensis extract to reach the equilibrium moisture decreased. The drying time was reduced by more than 25% when utilizing UAVD compared to the CVD method. The effective moisture diffusivity (Deff) values for CVD and UAVD were 3.48 × 10–9 m2·s–1 and 7.41 × 10–9 m2 s–1, respectively, at the drying temperature of 80°C, indicating an increase of 112.93%. It was also found that a Weibull distribution model was suitable for predicting the moisture content of S. chinensis extract (R2 > 0.95). Furthermore, the content of Schisandrol A in the extracts obtained from UAVD was 12.79% higher than that obtained using CVD at 90°C. This demonstrates that UAVD is an efficient drying technique for S. chinensis extract. [ABSTRACT FROM AUTHOR]

Schisandra chinensis (Turcz) Baill ( S. chinensis ) is the key traditional Chinese medicine for the treatment of asthma used by ancient and modern medical practitioners. However, the material basis and the main mechanism of its antiasthmatic effect remain unclear. Our preliminary results showed that schisandrol A (SCA), a representative monomer of Schisandra lignans, had the best relaxation effect on tracheal rings in isolated rats. In this research, a mouse asthma model was prepared by combining ovalbumin (OVA) with Al (OH) 3 for exploring the antiasthmatic action and the underlying mechanism of SCA. The study results demonstrated that SCA improved the behavior of mice with asthma and pathological changes in their lung tissues and airways, decreased serum immunoglobulin E (IgE) and OVA-IgE levels, interleukin-4 (IL-4), IL-5, IL-13, and eotaxin contents, and leukocytes number in bronchoalveolar lavage fluid. SCA downregulated the gene expressions of keratinocyte-derived protein chemokines and ILs and reduced the expressions of phosphorylated IκB kinase α (p-IKKα) and p-nuclear factor kappa-B (NF-κB) proteins in lung tissues. In addition, it was found that SCA could significantly increase T-superoxide dismutase and catalase activities, decrease malondialdehyde content, and elevate p-IκBα, NF-E2-related-factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein expressions. In summary, SCA treatment resulted in a significant improvement in the allergic bronchial asthma in mice, and its mechanisms may involve the regulation of the NF-κB/IκBα pathway to reduce inflammatory response and the Nrf2/HO-1 pathway to improve the body's antioxidant capacity. These results suggest that SCA is a key component of S. chinensis in exerting antiasthmatic effects.

[Objective] The aim of this study was to investigate effects of 6 monomers of lignans from Schisandra chinensis on the tension of isolated tracheal smooth muscle of rats and the relaxation mechanism. [Method] Trachea perfusion experiment in vitro was performed for understanding the effects of schisandrol A, schisandrol B, schisandrin A, schisandrin B, schisandrin C and schisantherin A with final concentration of 10-7-10-3 mol/L and 1‰ dimethy sulfoxide (DMSO, control) on tension of isolated tracheal ring under resting state and acetylcholine (ACh) pre-contraction state. The isolated rat tracheal rings were pre-incubated with L-type Ca2+ channel blocker verapamil (10-5 mol/L), (β- adrenoceptor blocker propranolol (10-5 mol/L) and l‰DMSO (control) for 15 tnin, then final concentration of 10-5-10-3 mol/L schisandrol A was added to investigate the effects of verapamil and propranolol on tracheal relaxation of schisandrol A. [Result] Compared with DMSO control group, 6 monomers of S. chinensis lignans at different concentrations had no significant effect on tension of tracheal ring at resting state (PX). 05). Schisandrol A, schisandrol B, schisandrin A and schisandrin B significantly inhibited the tension of tracheal rings pre-contracted with ACh in a dose-dependent manner (P 0. 05). [Conclusion] Schizandrol A, schisandrol B, schisandrin A and schisandrin B can relax isolated tracheal smooth muscle of rats in a dose-dependent manner, and schisandrol A might relate to the blocking of L-type Ca2+ channel. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the estrogen-like effects of gentiopicroside, macelignan, γ-mangostin, and three lignans (schisandrol A, schisandrol B, and schisandrin C), and their possible mechanism of action. Their effects on the proliferation of the estrogen receptor (ER)-positive breast cancer cell line (MCF-7) were evaluated using Ez-Cytox reagents. The expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), AKT, and estrogen receptor α (ERα) was measured by performing Western blot analysis. 17β-estradiol (E2), also known as estradiol, is an estrogen steroid and was used as a positive control. ICI 182,780 (ICI), an ER antagonist, was used to block the ER function. Our results showed that, except for gentiopicroside, all the compounds promoted proliferation of MCF-7 cells, with schisandrol A being the most effective; this effect was better than that of E2 and was mitigated by ICI. Consistently, the expression of ERK, PI3K, AKT, and ERα increased following treatment with schisandrol A; this effect was slightly better than that of E2 and was mitigated by ICI. Taken together, the ERα induction via the PI3K/AKT and ERK signaling pathways may be a potential mechanism underlying the estrogen-like effects of schisandrol A. This study provides an experimental basis for the application of schisandrol A as a phytoestrogen for the prevention of menopausal symptoms.

Schisandrol A possesses pharmacological properties and is used to treat various diseases; however, its effects on osteoarthritis (OA) progression remain unclear. Here, we investigated Schisandrol A as a potential therapeutic agent for OA. In vitro, Schisandrol A effects were confirmed based on the levels of expression of catabolic factors (MMPs, ADAMTS5, and Cox2) induced by IL-1β or Schisandrol A treatment in chondrocytes. In vivo, experimental OA in mice was induced using a destabilized medial meniscus (DMM) surgical model or oral gavage of Schisandrol A in a dose-dependent manner, and demonstrated using histological analysis. In vitro and in vivo analyses demonstrated that Schisandrol A inhibition attenuated osteoarthritic cartilage destruction via the regulation of Mmp3, Mmp13, Adamts5, and Cox2 expression. In the NF-κB signaling pathway, Schisandrol A suppressed the degradation of IκB and the phosphorylation of p65 induced by IL-1β. Overall, and Schisandrol A reduced the expression of catabolic factors by blocking NF-κB signaling and prevented cartilage destruction. Therefore, Schisandrol A attenuated OA progression, and can be used to develop novel OA drug therapies.

[Display omitted] • Schisandrol A improves the morphological characteristics of DILI by APAP in mice. • Schisandrol A alleviates DILI by activating autophagy in the exosome. • Differential miRNA target genes are involved in glycerol phosphate metabolism. • mmu-let-7 family miRNAs are closely related to autophagy. To investigate the bioactive compounds of Schisandrae Chinensis Fructus (SCF) and their mechanisms of action in the treatment of drug-induced liver injury (DILI), specifically Acetaminophen (APAP)-induced DILI. Chemical components in SCF were identified using the UPLC-Q-TOF-MS method. Active components were then screened using HotMap, combined with SCF efficacy results concerning the prevention and treatment of drug-induced liver injury. Its direct target was elucidated using a comprehensive chemical-pharmacodynamic-exosome approach. We identified Schisandrol A, is a lignan component, as a key active compound that improved the symptoms DILI in mouse liver tissue; specifically, reducing oxidative stress and thereby the inflammatory response. To further understand the biological function of miRNAs in mouse liver exosomes, we used TargetScan (v5.0) and Miranda (v3.3a) to predict the target genes of MicroRNAs (miRNAs), where changes in the expression of mmu-let-7 family miRNAs were closely related to autophagy. This revealed differential miRNA target genes that were involved in 20 Kyoto Encyclopedia of Genes and Genomes pathways, including glycerol phosphate metabolism, inositol phosphate metabolism, phospholipase D signaling pathway, Rap1 signaling pathway, and Ras signaling pathway. Schisandrol A alleviated the symptoms of DILI in mice by inhibiting oxidative stress and inflammation, whereas, it alleviated DILI by activating autophagy in the exosomes. [ABSTRACT FROM AUTHOR]

Schisandra chinensis (Chinese starvine) is a popular dietary supplement with a rich history of use in traditional Chinese medicine. Schisandra glabra (bay starvine) is the only North American representative of the genus, and little is known about its history of traditional use, chemistry, and potential biological activity. In this study, we conducted comparative high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis on S. glabra and S. chinensis fruits. Additional characterization of S. glabra was performed by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS). Quantitative analysis of four bioactive marker compounds revealed that S. glabra does not have statistically higher levels of schisandrin A or schisandrol B than S. chinensis. S. glabra has lower levels of schisandrol A and γ-schisandrin. Total phenolic contents of the two species' fruits were not statistically different. S. glabra had higher total tannin content than S. chinensis. We discuss the relevance of this analytical analysis to the study of S. glabra as a potential dietary supplement ingredient and give specific consideration to the conservation challenges involved in commercially developing a regionally threatened species, even in semicultivated conditions. [ABSTRACT FROM AUTHOR]

Curdione is a main active component of curcuma rhizomes (Ezhu), which shows an excellent antithrombotic activity. In this study, the concentration of Curdione in pregnant rats and their offspring brain was determined using ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF-MS) method. The water extraction then alcohol precipitation extract from Ezhu was administered through tail intravenous injection. The pharmacokinetic parameters were analyzed to compare the differences between the blood stasis group rats and normal group rats. Using Schisandrol A as an internal standard, samples were extracted using dichloromethane and isopropanol (90:10, v/v). Calibration plot was linear over the range of 0.5-200μg·mL-1 for Curdione in brain with the lower quantification limit being 0.5μg·mL-1. The recoveries of Curdione and IS from brain were more than 93.31% and 90.90% separately. The RSD for both intra- and inter-day precision were <6.49%, RE were -14.84%~-2.8%. The pharmacokinetic parameters Cmax and AUC among the four kinds of rats had significant difference. The Curdione distributed in rat brain in model group is less than normal group. Ezhu medicine may show the therapeutic effect but not the reproductive toxicity on mother or unborn baby to cure the pregnant women under the adaptive symptoms. [ABSTRACT FROM AUTHOR]

Background: Schisandrol A, a lignan with anticancer effects, is one of the representative components that identifies Schisandra chinensis. Objective: A method for purifying schisandrol A from the stems of S. chinensis was established using an octadecylsilyl (ODS) column combined with preparative high-performance liquid chromatography (HPLC). Materials and Methods: Crude extracts obtained from the stems of S. chinensis using 70% ethanol were separated on an AB-8 macroporous resin column and then eluted with a graded ethanol series. After 70% methanol was used in an ODS column separation, preparative HPLC was used for subsequent purification. The structure was identified by electrospray ionization-mass spectrometry, 1H-nuclear magnetic resonance, and 13C-nuclear magnetic resonance. HepG2 and Bel-7402 hepatocellular carcinoma cell lines were used for toxicological evaluation. Results: 21.4 mg of schisandrol A with a purity of 95.2% were collected. The cytotoxicity of the ODS-purified sample and schisandrol A were significantly stronger than that of a resin-purified sample. Conclusion: Schisandrol A was successfully extracted from the stems of S. chinensis and separated with an ODS column combined with preparative HPLC. The samples obtained during the purification process showed different levels of cytotoxicity on the HepG2 and Bel-7402 hepatocellular carcinoma cell lines. [ABSTRACT FROM AUTHOR]

Schisandra chinensis decoction derived from the book of Waitai Miyao (Tao Wang, Tang dynasty) is often used in the treatment of idiopathic pulmonary fibrosis (IPF), which is included in the Grand Ceremony of Chinese formulae (Huairen Peng, 1994). Schisandrae Chinensis Fructus (Sch) is one of the most important herbs in this formula. According to the "Shennong's Herbal Classicherbal" of the Han Dynasty, Sch has sour taste, warm nature, which has the effect of tonifying qi and curing cough. In addition, according to the "Compendium of Materia Medica" of the Ming Dynasty, Sch is used to treat cough and asthma, which has the effect of moistening the lung and tonifying the kidney. However, the active ingredients of Sch absorption into the plasma and its pharmacological mechanism of treatment for IPF still remained unclear. Our research aimed at identifying the absorbed active ingredients and metabolized of Sch in rat plasma and the mechanism of anti-IPF based on serum pharmacochemistry. First, the rats were divided into control group and Sch group. Sch sample was orally administrated to the rats for seven days. The blood samples were drawn into an Eppendorf tube after the last dosing. The ultrahigh performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the absorption components and metabolites of Sch in rat plasma. Second, the network pharmacology combined with molecular docking analysis was further investigated to illuminate its potential mechanism of treatment for IPF by the biological targets regulating related pathways. Finally, the mechanism of action was verified by experimental in vitro and in vivo. A total of 78 compounds, consist of 13 prototype lignans and 65 metabolites (including isomers) were identified. Network pharmacology study and molecular docking analysis indicated that schisandrol A (L1) play an anti-fibrosis role by regulating the TGF-β signaling pathway. Experimental in vitro and in vivo verified that the schisandrol A could inhibiting pulmonary fibrosis through TGF-β signaling pathway. The effect and mechanism of schisandrol A inhibiting pulmonary fibrosis were reported for the first time. In this study, the absorption active ingredients of Sch in rat plasma were combined with the network pharmacology investigation and experimental in vitro and in vivo to elucidate its biological mechanism of treatment for IPF. The results provided a theoretical support for understanding the bioactive compounds and the pharmacological mechanism of Sch. [Display omitted] • Thirteen prototype lignans of Sch were identified in rat plasma via UPLC-Q-TOF/MS. • Sixty-five metabolites of Sch were identified in rat plasma via UPLC-Q-TOF/MS. • The component-target-disease associations were identified by network pharmacology. • The interaction between targets and compounds were predicted by molecular docking. • Schisandrol A played an anti-fibrosis role by regulating the TGF-β signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC50 values of 32.02μM and 1.39μM, respectively. SCH or GOM at concentrations up to 100μM did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GOM could affect cellular drug metabolism in addition to drug uptake. [Copyright &y& Elsevier]

[Display omitted] • Schisandrol A is a bioactive lignan of Schisandrae Chinensis Fructus. • Schisandrol A plays critical roles in drug-induced liver injury by acetaminophen. • The mechanism is that TNF signaling pathway is regulated. • The oxidative stress, inflammation, P450 enzymes' activities are inhibited. Schisandrae Chinensis Fructus (SCF) was a Traditional Chinese Medicine for protecting liver. However, underlying therapeutic mechanisms of these bioactive lignans from SCF similar hepatoprotective effects against drug-induced liver injury (DILI) by acetaminophen (APAP) are still unclear. This study aims to discover the potential regulation mechanisms of Schisandrol A in the treatment of DILI by APAP. The integrated UPLC-Q-TOF/MS, pharmacodynamic study, histopathological combination with network pharmacology and molecular docking technology were used to explore the potential mechanisms. The results showed that Schisandrol A reduced the level of AST, ALT, MDA, PNP, TNF-α and IL-1β, increased the levels of the GSH against acute liver failure. Additionally, Schisandrol A could improve the morphological characteristics of DILI by APAP in mice with liver tissue. Molecular docking results had showed that Schisandrol A with high scores when docking with COX-2, ALOX5, CYP2E1, CYP2C9, CYP2C19, EGFR SRC, Nrf2, MAPK14 and MAPK8. The study demonstrated that Schisandrol A could play critical roles in DILI by APAP via regulating TNF signaling pathway, inhibiting oxidative stress, inflammation and inhibiting the activities of cytochrome P450 enzymes, which contributed to searching for leading compounds and the development of new drugs for DILI by APAP. [ABSTRACT FROM AUTHOR]

Abstract: Variations of medicinal ingredients were qualitatively analyzed in beagle dog plasma after oral administration of the water and ethanol extracts of the decoction, respectively, a compound traditional Chinese herbal medicine for the irritable bowel syndrome (IBS). HPLC analysis was performed using a Waters 996 series HPLC system. The mobile phase was a water/methanol solvent or a water/acetonitrile one. Both retention times of HPLC and data of UV spectrum were used to determine the ingredients in plasma samples. It was found that no desired ingredient was detected in the plasma samples administered with the water extract of the IBS formula at different dosages. However, at least 20 compounds were able to be detected in those treated with the ethanol extract when the detection dosage was 27 times lower than in the water one. Compositions of medicinal ingredients in dog plasma significantly varied upon different solvent extracts of the formula. This presented difficulties or clues in demonstrating the effectiveness of traditional Chinese medicines. [Copyright &y& Elsevier]

Purpose: To determine if five dibenzocyclooctadiene lingnans, a class of naturally occurring compounds from Schisandra chinensis (Turcz.) Baill, have the activities to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR). Methods: The IC50s of four MDR cell lines (K562/Adr, MCF-7/Adr, KBv200, and Bcap37/Adr) toward daunorubicin, vincristine, and paclitaxel in the presence or absence of one of the dibenzocyclooctadiene lingnans were determined by a FACscan assay. The intracellular daunorubicin accumulation in the four MDR cell lines was determined by incubation of cells with daunorubicin (2 μg/ml) in the presence or absence of one of the dibenzocyclooctadiene lingnans by a FACscan assay. The interaction of the five dibenzocyclooctadiene lingnans with P-gp was assayed by their inhibition of 3H-azidopine photoaffinity labeling of P-gp. Results: Among the five lingnans, while schisandrin A and B, and schisantherin A demonstrated strong and comparable activities to reverse the drug resistance and the intracellular drug accumulation in four MDR cell lines, schisandrol A and B showed very limited activities. The poor activities of schisandrol A and B are possibly caused by the hydroxyl groups on the cyclooctadiene ring, because the activities of the molecules resumed when the hydroxyl group was esterified to form a benzoate. Further studies demonstrated that these compounds physically interacted with P-gp. Conclusion: Schisandrin A and B, and schisantherin A are potent P-gp inhibitor and is of potential for future clinical application. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the estrogen-like effects of gentiopicroside, macelignan, γ-mangostin, and three lignans (schisandrol A, schisandrol B, and schisandrin C), and their possible mechanism of action. Their effects on the proliferation of the estrogen receptor (ER)-positive breast cancer cell line (MCF-7) were evaluated using Ez-Cytox reagents. The expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), AKT, and estrogen receptor α (ERα) was measured by performing Western blot analysis. 17β-estradiol (E2), also known as estradiol, is an estrogen steroid and was used as a positive control. ICI 182,780 (ICI), an ER antagonist, was used to block the ER function. Our results showed that, except for gentiopicroside, all the compounds promoted proliferation of MCF-7 cells, with schisandrol A being the most effective; this effect was better than that of E2 and was mitigated by ICI. Consistently, the expression of ERK, PI3K, AKT, and ERα increased following treatment with schisandrol A; this effect was slightly better than that of E2 and was mitigated by ICI. Taken together, the ERα induction via the PI3K/AKT and ERK signaling pathways may be a potential mechanism underlying the estrogen-like effects of schisandrol A. This study provides an experimental basis for the application of schisandrol A as a phytoestrogen for the prevention of menopausal symptoms. [ABSTRACT FROM AUTHOR]

Schisandra chinensis ( S. chinensis ) extract powder is an important intermediate for the preparation of many prepared medicines and health products. The physicochemical properties of S. chinensis extract powder have been found to vary tremendously and this has been attributed to the long drying time in the traditional drying method. In this study, S. chinensis specimens were authenticated as the dry fruit of S. chinensis (Turcz.) Baill. S. chinensis were extracted twice with 8 L kg -1 (liquid to solid ratio) distilled water. The extracts were mixed and concentrated under reduced pressure to 1.24 g cm -3 . Ultrasound-assisted vacuum drying (UAVD) was employed as a new approach to improve the efficiency in drying S. chinensis extract powder and produce a higher quality product. The effects of drying temperature (70, 80, 90°C), ultrasonic power (40, 120, 200 W), and ultrasonic application time (4, 12, 20 min every 20 min) on the kinetics and quality of S. chinensis extract were investigated and compared with the conventional vacuum drying (CVD). It was shown that, with the increase in drying temperature, ultrasonic power, and time of UAVD, the drying time for S. chinensis extract to reach the equilibrium moisture decreased. The drying time was reduced by more than 25% when utilizing UAVD compared to the CVD method. The effective moisture diffusivity ( D eff ) values for CVD and UAVD were 3.48 × 10 -9  m 2 ·s -1 and 7.41 × 10 -9  m 2  s -1 , respectively, at the drying temperature of 80°C, indicating an increase of 112.93%. It was also found that a Weibull distribution model was suitable for predicting the moisture content of S. chinensis  > 0.95). Furthermore, the content of Schisandrol A in the extracts obtained from UAVD was 12.79% higher than that obtained using CVD at 90°C. This demonstrates that UAVD is an efficient drying technique for R 2  > 0.95). Furthermore, the content of Schisandrol A in the extracts obtained from UAVD was 12.79% higher than that obtained using CVD at 90°C. This demonstrates that UAVD is an efficient drying technique for S. chinensis extract., Competing Interests: The author declares no conflict of interests., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Schisandrol A possesses pharmacological properties and is used to treat various diseases; however, its effects on osteoarthritis (OA) progression remain unclear. Here, we investigated Schisandrol A as a potential therapeutic agent for OA. In vitro, Schisandrol A effects were confirmed based on the levels of expression of catabolic factors (MMPs, ADAMTS5, and Cox2) induced by IL-1β or Schisandrol A treatment in chondrocytes. In vivo, experimental OA in mice was induced using a destabilized medial meniscus (DMM) surgical model or oral gavage of Schisandrol A in a dose-dependent manner, and demonstrated using histological analysis. In vitro and in vivo analyses demonstrated that Schisandrol A inhibition attenuated osteoarthritic cartilage destruction via the regulation of Mmp3, Mmp13, Adamts5, and Cox2 expression. In the NF-κB signaling pathway, Schisandrol A suppressed the degradation of IκB and the phosphorylation of p65 induced by IL-1β. Overall, and Schisandrol A reduced the expression of catabolic factors by blocking NF-κB signaling and prevented cartilage destruction. Therefore, Schisandrol A attenuated OA progression, and can be used to develop novel OA drug therapies. [ABSTRACT FROM AUTHOR]

Parkinson's disease is the second most common neurodegenerative disease. Its main pathological feature is the substantial nigra-striatum dopaminergic neuronal dysfunction, which causes insufficient release of DA, induces motor symptoms, and is accompanied by nonmotor symptoms. Schisandrol A belongs to lignan components and has anti-inflammatory, antioxidant and neuroprotective effects. In this experiment, we injected 6-OHDA into medial forebrain bundle of C57BL/6J male mice to establish the model. The motor function of mice was examined by open field test and pole test, the depression-like behavior of mice was examined by sucrose preference test and the memory function was examined by Y maze. We found that schisandrol A (20 mg/kg/d) could significantly improve the motor symptoms, and alleviate the depression-like symptoms and memory dysfunction of PD mice induced by 6-OHDA. Then we studied the neuroprotective mechanism of schisandrol A by H.E., ELISA assay kits and Western blot. Results showed that schisandrol A may enhance the PI3K/AKT pathway, inhibit the IKK/IκBα/NF-κB pathway, reduce neuronal inflammation and oxidative stress, and enhance the survival of DA neurons in the brain of mice. These results indicate that schisandrol A is expected to be a potential drug for improving Parkinson's disease. • Schisandrol A could improve the motor symptoms of 6-OHDA-induced PD mice. • Schisandrol A could improve the nonmotor symptoms of 6-OHDA-induced PD mice. • Schisandrol A could enhance the PI3K/AKT pathway, inhibit the IKK/IκBα/NF-κB pathway. • Schisandrol A could reduce neuronal inflammation and oxidative stress, and enhance the survival of DA neurons. [ABSTRACT FROM AUTHOR]

Background: Schisandrol A, a lignan with anticancer effects, is one of the representative components that identifies Schisandra chinensis., Objective: A method for purifying schisandrol A from the stems of S. chinensis was established using an octadecylsilyl (ODS) column combined with preparative high-performance liquid chromatography (HPLC)., Materials and Methods: Crude extracts obtained from the stems of S. chinensis using 70% ethanol were separated on an AB-8 macroporous resin column and then eluted with a graded ethanol series. After 70% methanol was used in an ODS column separation, preparative HPLC was used for subsequent purification. The structure was identified by electrospray ionization-mass spectrometry, (1)H-nuclear magnetic resonance, and (13)C-nuclear magnetic resonance. HepG2 and Bel-7402 hepatocellular carcinoma cell lines were used for toxicological evaluation., Results: 21.4 mg of schisandrol A with a purity of 95.2% were collected. The cytotoxicity of the ODS-purified sample and schisandrol A were significantly stronger than that of a resin-purified sample., Conclusion: Schisandrol A was successfully extracted from the stems of S. chinensis and separated with an ODS column combined with preparative HPLC. The samples obtained during the purification process showed different levels of cytotoxicity on the HepG2 and Bel-7402 hepatocellular carcinoma cell lines.