Schisandrae Chinensis Fructus Research Articles

Efficacy and Mechanism of Schisandra chinensis Fructus Water Extract in Alzheimer's Disease: Insights from Network Pharmacology and Validation in an Amyloid-β Infused Animal Model.

Schisandra chinensis Fructus (SCF) is a traditional medicinal herb containing lignans that improves glucose metabolism by mitigating insulin resistance. We aimed to investigate the therapeutic potential and action mechanism of SCF for Alzheimer's disease (AD) using a network pharmacology analysis, followed by experimental validation in an AD rat model. The biological activities of SCF's bioactive compounds were assessed through a network pharmacology analysis. An AD rat model was generated by infusing amyloid-β peptide (Aβ) (25-35) into the hippocampus to induce Aβ accumulation. The AD rats were fed either 0.5% dextrin (AD-Con) or 0.5% SCF (AD-SCF group) in a high-fat diet for seven weeks. The rats in the normal/control group received an Aβ (35-25) infusion (no Aβ deposition) and were fed a control diet (Normal-C). Aβ deposition, memory function, inflammation, and glucose/lipid metabolism were evaluated. The network analysis revealed significant intersections between AD-related targets and bioactive SCF compounds, like gomisin A, schisandrin, and longikaurin A. Key AD genes prostaglandin-endoperoxide synthase-2 (PTGS2, cyclooxygenase-2) and acetylcholinesterase (AChE) were linked to SCF compounds. In the rats with AD induced by bilaterally infusing amyloid-β (25-35) into the hippocampus, the 0.5% SCF intake mitigated hippocampal amyloid-β deposition, neuroinflammation, memory deficits, and dysregulated glucose and lipid metabolism versus the AD controls. SCF reduced hippocampal AChE activity, inflammatory cytokine expression related to PTGS2, and malondialdehyde contents and preserved neuronal cell survival-related factors such as brain-derived neurotrophic factor and ciliary neurotrophic factor similar to normal rats. The neuroprotective effects validated the network analysis findings. SCF could be a potential AD therapeutic agent by activating the parasympathetic nervous system to reduce hippocampal oxidative stress and inflammation, warranting further clinical investigations of its efficacy.

Alpha Hydroxyl Acids from Mume Fructus and Schisandrae Chinensis Fructus Prevent Obesity by Inhibiting Intestinal Lipase in Diet-Induced Obese Mice.

Restriction of lipid uptake and absorption from the diet is regarded as an efficient strategy for the management of obesity, while lipase inhibition could successfully block the digestion of dietary lipids. Mume Fructus (MF) and Schisandrae Chinensis Fructus (SCF) were used as fruits, the biological effect of which on obesity desired more attention. Herein, the extracts of MF and SCF displayed significant efficacy in managing obesity in mice fed with a high-fat diet, via the inhibition of hydrolase activity of lipase in the digestive tract. Using the bioactivity guidance strategy, citric acid and malic acid were identified as the major lipase inhibitors from MF and SCF, respectively, which could prevent body weight gain, along with adipose tissue formation, and alleviate hyperlipidemia and hepatic steatosis in obese mice. Above all, MF and SCF could be used for the management of obesity via the lipase inhibition by citric acid and malic acid, displaying potential applications in healthy foods, nutritional supplements, and pharmaceutical materials.

Effective strategy for distinguishing raw and vinegar Schisandrae Chinensis Fructus based on electronic eye and electronic tongue combined with chemometrics.

Schisandrae Chinensis Fructus (SCF), a traditional Chinese medicine, has been used in treating virtual injury and strain since ancient times. The Chinese Pharmacopoeia reveals that SCF includes raw (RSCF) and vinegar-processed (VSCF) decoction pieces. This study developed an effective method combining the electronic eye (e-eye), electronic tongue (e-tongue), and chemometrics to discriminate RSCF and VSCF from the perspective of chemical composition, color, and taste. First, RSCF were collected and processed into VSCF, and their color parameters, e-tongue sensory properties, high-performance liquid chromatography (HPLC) and ultra-HPLC (UPLC) characteristic fingerprints, and nominal ingredients were determined. Multivariate statistical analyses, including principal component, linear discriminant, similarity, and partial least squares discriminant analyses, were conducted. HPLC and UPLC fingerprints were established, demonstrating a > 0.900 similarity. The content determination indicated increased schisantherin A, schisantherin B, and schisandrin A contents in VSCF. The e-eye data demonstrated a > 1.5 total color difference before and after processing ΔE*ab, indicating the significantly changed sample color and appearance before and after processing. The e-tongue technology was used to quantitatively characterize the taste of RSCF and VSCF. The t-test revealed significantly reduced sourness, aftertaste-bitter, and aftertaste-astringent values of SCF after vinegar processing. Principal component and partial least squares discriminant analyses indicated that e-eye and e-tongue realize the rapid RSCF and VSCF identification. The proposed comprehensive strategy of electronic eye and electronic tongue combined with chemometrics demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be developed into a novel and accurate method for discriminating RSCF and VSCF.

Effects of Schisandrae Chinensis Fructus Lignans on Alertness of Rats With Sleep Deprived by Treadmill Exercise

Objective To investigate the effects of Schisandrae Chinensis Fructus lignans on the alertness of the rats with sleep deprived by treadmill exercise and the underlying neurobiological mechanism. Methods According to the random number table method,SD male rats were assigned into control,sleep deprivation,low-,medium-,and high-dose Schisandrae Chinensis Fructus lignans,and atomoxetine hydrochloride groups,with 8 rats in each group.The rats in other groups except the control group were subjected to sleep deprivation by treadmill exercise for 3 d.During the deprivation period,each administration group was administrated with the corresponding drug by gavage,and a 5-9 hole tester was used to test the alertness performance of rats in each group. Furthermore,other SD male rats were selected and randomized into control,sleep deprivation,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride groups,with 10 rats in each group.The rats were modeled with the sleep deprivation method the same as that above and administrated with corresponding agents.ELISA was employed to measure the serum level of orexin A in each group of rats.The protein levels of c-Fos,orexin receptor 1,and orexin receptor 2 in the prefrontal cortex of rats in each group were observed by immunofluorescence and Western blotting. Results Compared with the control group,sleep deprivation reduced the choice accuracy (P<0.001) and increased the omission responses,omission percent,and mean correct response latency (P=0.002,P=0.003,P=0.020).Compared with the sleep deprivation group,medium- and high-dose Schisandrae Chinensis Fructus lignans and atomoxetine hydrochloride improved the alertness of rats,as demonstrated by the increased choice accuracy (P=0.001,P=0.006,P<0.001) and reduced omission responses (P=0.001,P=0.001,P<0.001),omission percent (P=0.001,P=0.002,P<0.001),and mean correct response latency (P=0.018,P=0.003,P=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum (P<0.001),up-regulated expression of c-Fos (P<0.001),and down-regulated expression of orexin receptor 1 (P=0.037) in the prefrontal cortex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride lowered the orexin A level in the serum (P=0.005,P=0.029),down-regulated the expression of c-Fos (P=0.028,P=0.036),and up-regulated the expression of orexin receptor 1 (P=0.043,P=0.013) in the prefrontal cortex. Conclusion Schisandrae Chinensis Fructus lignans may antagonize the alertness decrease caused by sleep deprivation by regulating the secretion of orexin and the expression of orexin receptor 1 in the prefrontal cortex.

Determination of fifteen illegal colorants in traditional Chinese medicines by two hydrophobic DES-based microextraction methods coupled with an HPLC-DAD

The dyeing and adulteration of traditional Chinese medicines (TCMs) are continuously updated. Valuable analytical methods for the daily inspection of illegal colorant additives in TCMs and the preparations are in demand. Two deep eutectic solvent (DES)-based vortex-assisted liquid-liquid microextraction (VA-LLME) and ultrasonic-assisted solid-liquid microextraction (UA-SLME) were developed for the sample pretreatment of ten water-soluble colorants and five water-insoluble colorants, respectively, followed by an HPLC-DAD detection. Fifteen colorants were analyzed at four detection wavelengths within 40 min of gradient elution. The optimal DES of VA-LLME and UA-SLME were screened from 23 homemade DESs. The factors affecting the extraction efficiency of VA-LLME and UA-SLME were optimized systematically. Under the optimal conditions, ten water-soluble colorants analyzed by DES-based VA-LLME-HPLC-DAD showed good linearity (R ≥ 0.9995) within the optimal linear range. The LODs and LOQs were 0.2–1.0 μg g−1 and 0. 5–5.0 μg g−1, respectively. The recoveries of spiked samples were 80.2%–104.7 %, with RSDs ≤ 4.39 %. Five water-insoluble colorants of Sudan I‒IV and Sudan 7B analyzed by DES-based UA-SLME-HPLC-DAD showed good linearity (R ≥ 0.9995) within the optimal linear range. The LODs and LOQs were 0.8–8.0 μg g−1 and 4.0–40.0 μg g−1, respectively. The recoveries of spiked samples were 94.2%–103.1 %, with RSDs ≤ 4.81 %. The proposed DES-based VA-LLME-HPLC-DAD was successfully applied to analyze six water-soluble yellow colorants in Cuscutae Semen, salted Cuscutae Semen, and four water-soluble red colorants in Schisandrae Chinensis Fructus. The proposed DES-based UA-SLME-HPLC-DAD was successfully applied to analyze five water-insoluble red colorants in Dieda pills. The study provides analytical method options for routine tests of water-soluble, water-insoluble, or both water-soluble/-insoluble illegal colorant additives in herbal medical materials and preparations by the relevant proposed DES-based sample pretreatment method or a combination of the two proposed DES-based methods.

A versatile economic strategy by HPLC–CAD for quantification of structurally diverse markers in quality control of Shengmai Formula from raw materials to preparations

BackgroundShengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PurposeWe aimed to establish a versatile analysis strategy using HPLC–CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. MethodBy optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. ResultsIn total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. ConclusionThe established versatile analysis strategy based on HPLC–CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.

The combination of Schisandrin C and Luteolin synergistically attenuates hepatitis B virus infection via repressing HBV replication and promoting cGAS-STING pathway activation in macrophages.

HBV infection can result in severe liver diseases and is one of the primary causes of liver cell carcinoma-related mortality. Liuwei Wuling tablet (LWWL) is a traditional Chinese medicine formula, with a protecting liver and decreasing enzyme activity, usually used to treat chronic hepatitis B with NAs in clinic. However, its main active ingredients and mechanism of action have not been fully investigated. Hence, we aimed to screen the active ingredient and effective ingredient combinations from Liuwei Wuling tablet to explore the anti-herpatitis B virus activity and mechanism. Analysis and screening of effective antiviral components in LWWL by network pharmacology, luteolin (Lut) may be a compound with significant antiviral activity. The mechanism of antiviral action of Lut was also found by real-time PCR detection and western blotting. Meanwhile, we established a co-culture model to investigate the antiviral mechanism of Schisandrin C (SC), one of the main active components of Schisandra chinensis fructus (the sovereign drug of LWWL). Next, HBV-infected mice were established by tail vein injection of pAAV-HBV1.2 plasmid and administered continuously for 20days. And their antiviral capacity was evaluated by checking serum levels of HBsAg, HBeAg, levels of HBV DNA, and liver levels of HBcAg. In this study, we conducted network pharmacology analysis on LWWL, and through in vitro experimental validation and data analysis, we found that luteolin (Lut) possessed obviously anti-HBV activity, inhibiting HBV replication by downregulating hepatocyte nuclear factor 4α (HNF4α) via the ERK pathway. Additionally, we established a co-culture system and proved that SC promoted activation of cGAS-STINIG pathway and IFN-β production in THP-1 cells to inhibit HBV replication in HepG2.2.15 cells. Moreover, we found the combination of SC and Lut shows a greater effect in inhibiting HBV compared to SC or Lut alone in HBV-infected mice. Taken together, our study suggests that combination of SC and Lut may be potential candidate drug for the prevention and treatment of chronic hepatitis B.

Zhumian Granules improves PCPA-induced insomnia by regulating the expression level of neurotransmitters and reducing neuronal apoptosis

Ethnopharmacological relevanceSleep problems, according to Traditional Chinese medicine (TCM) philosophy, are attributed to the imbalance between yin and yang. Zhumian Granules, also known as Sleep-aid Granules or ZG, are a traditional Chinese herbal remedy specifically designed to alleviate insomnia. This formula consists of many components, including Wu Wei Zi (Schisandrae Chinensis Fructus), Suan Zao Ren (Ziziphi Spinosae Semen), and other medicinal plants. According to the pharmacology of Traditional Chinese Medicine (TCM), Wu Wei Zi and Suan Zao Ren have the ability to relax the mind and promote sleep. When taken together, they may balance the opposing forces of yin and yang. Therefore, ZG may potentially be used as a therapeutic treatment for insomnia. Aim of the studyThis research was specifically developed to establish a strong empirical basis for the subsequent advancement and utilization of ZG in the management of insomnia. This research aimed to gather empirical data to support the effectiveness of ZG, thereby providing useful insights into its potential therapeutic advantages for persons with insomnia. Materials and methodsThis study utilized Zhumian Granules (ZG), a traditional Chinese herbal decoction, to examine its sedative and hypnotic effects on mice with PCPA-induced insomnia. The effects were assessed using the pentobarbital-induced sleep test (PIST), Morris water maze test (MWM), and autonomic activity test. The levels of neurotransmitters in each group of mice were evaluated using UPLC-QQQ-MS. The impact of ZG on the quantity and structure of hippocampal neurons was seen in brain tissue slices using immunofluorescence labeling. ResultsZG was shown to possess active sedative properties, effectively lowering the distance of movement and lengthening the duration of sleep. ZG mitigated the sleeplessness effects of PCPA by elevating the levels of 5-hydroxytryptamine (5-HT), 4-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid (5-HIAA), while reducing the levels of dopamine (DA) and norepinephrine (NE), as well as decreasing neuronal death. ConclusionsThis research confirmed the sedative and hypnotic properties of ZG and elucidated its probable mechanism involving neurotransmitters.

A novel traditional Chinese medicine combination for radiation

ObjectiveTo formulate an efficacious radioprotective combination of Chinese medicines with minimal toxicity. MethodsAqueous and alcoholic extracts from 38 traditional Chinese herbs were prepared. To produce drug-containing sera, rats received six doses of each extract via oral gavage at 12-h intervals. Subsequently, human lung epithelial BEAS-2B cells were cultured in these drug-containing sera. The cell viability was assessed after different doses of irradiation to identify the radioprotective effects of Chinese herbal extracts. The efficacy of a selected Chinese herbal extract combination was further confirmed through cell viability analysis via in vitro colony formation and survival rate assessments in C57BL/6 mice post-irradiation. ResultsExtracts from Angelicae Sinensis Radix (ASR; two extracts), Citri Reticulatae Pericarpium (CRP), Platycladi Cacumen (PC), Schisandrae chinensis Fructus (SF), Scutellariae Radix (SR), and Glycyrrhizae Radix et Rhizome (GRR) demonstrated radioprotective effects. The combination of the seven Chinese herbal extracts notably increased the survival and viability of the BEAS-2B cells exposed to varying doses of X-rays. Moreover, the group of mice receiving Chinese medicine combination and irradiation exhibited prolonged survival after exposure to 6.5 ​Gy X-rays with a median survival of （14 ​± ​2）d compared to （11 ​± ​2）d in the irradiated group without the herbal treatment. Additionally, the Chinese medicine combination group displayed a significantly higher 28 ​d survival rate (30%) compared to the irradiation-only group (16.6%, P ​< ​0.05). ConclusionThe novel combination of Chinese herbal extracts from ASR, CRP, PC, SF, SR, and GRR has the potential for radiation protection applications.

Neuroprotective effects of polysaccharide of Schisandrae Chinensis Fructus in aging mice

This study aimed to investigate the effects of Schisandra Chinensis Fructus polysaccharide (SCP) on learning and memory, hippocampal antioxidant activity and Keap1/Nrf2 signal transduction pathway in an aging mouse model. The step-down test was used to observe learning and memory. Biochemical analysis was used to detect Superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Nrf2, HO-1, and Keap1 gene expression in the hippocampus were measured by quantitative real-time polymerase chain reaction (qRT-PCR). SCP can improve the learning and memory ability (P&lt;0.05), increase hippocampal SOD activity, decrease MDA levels, up-regulate Nrf2 and HO-1 gene expressions, down-regulate Keap1 gene expression (P&lt;0.05). Our findings suggest that SCP can improve brain damage in D-galactose-induced aging mice, improve antioxidant enzyme activity, reduce lipid peroxidation, and has obvious anti-aging effects. Its anti-aging activity may be related to activating the Keap1/Nrf2 signal transduction pathway in the hippocampus.

Serum metabolomics study of anti‐aging mechanisms of different processed Schisandra chinensis fructus products

AbstractThis study aimed to investigate the anti‐aging mechanism of raw and various processed Schisandrae chinensis fructus (SF) products by examining differences in serum metabolites in D‐galactose (D‐gal)‐induced aging rats. The study provides a metabolomic basis for SF as a tonic. The ultra‐high‐performance liquid chromatography‐Q‐time of flight‐tandem mass spectrometry technique was employed for serum metabolomic analysis of the anti‐aging effects of differently processed SF products. Multivariate statistical analysis, MetaboAnalyst, and Human Metabolome Database were utilized for pattern recognition and identification of characteristic metabolites. Enzyme‐linked immunosorbent assay results revealed significant differences between the aging model group and the blank group (p &lt; 0.01). Treatment with various processed SF products significantly improved related indicators in aging rats (p &lt; 0.05, p &lt; 0.01). Arginine and seven other metabolites exhibited direct effects on aging. Wine‐processed Schisandrae (WS) treatment adjusted these biomarkers in aging rats to normal levels. WS significantly delayed D‐gal‐induced aging in rats by modulating endogenous biomarkers in relevant metabolic pathways, providing a scientific basis for its enhanced suitability as a tonic from a metabolomic perspective.

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

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

Rapid identification of chemical constituents in Hugan tablets by ultra-performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry.

Hugan tablet is a Chinese medicine preparation. It is composed of Bupleuri Radix, Artemisiae Scopariae Herba, Isatidis Radix, Schisandrae Chinensis Fructus, Suis Fellis Pulvis, and Vigna radiata L. It has the effects of dispersing stagnated liver qi, strengthening the spleen and eliminating food to be used for the treatment of chronic hepatitis and early cirrhosis. However, the chemical composition of Hugan tablet is complex and not fully understood, which hampers the research in pharmacology. In this study, a reliable method for the rapid analysis and identification of the chemical components in Hugan tablet by their characteristic fragments and neutral losses using ultra-performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry was developed. A total of 144 chemical components were tentatively identified, including 57 organic acids, 19 flavonoids, 23 alkaloids, 18 lignans, 7 saponins, and 20 others. These components may be the active ingredients of Hugan tablet. The established method can systematically and rapidly analyze the chemical components in Hugan tablet, which provides a basis for the pharmacodynamic substance study and is meaningful for the quality control of Hugan tablet.

Schisandrol A, a bioactive constituent from Schisandrae Chinensis Fructus, alleviates drug-induced liver injury by autophagy activation via exosomes

ObjectiveTo 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. MethodChemical 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. ResultWe 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. ConclusionSchisandrol A alleviated the symptoms of DILI in mice by inhibiting oxidative stress and inflammation, whereas, it alleviated DILI by activating autophagy in the exosomes.

A traditional prescription comprising Astragali Radix and Schisandra chinensis Fructus induces apoptosis and protective autophagy in hepatocellular carcinoma cells

Ethnopharmacological relevanceHepatocellular carcinoma (HCC) poses a growing challenge to global health efforts. The 5-year survival rate of HCC patients is still dismal. A traditional prescription Qi-Wei-Wan (QWW) comprising Astragali Radix and Schisandra chinensis Fructus has traditionally been used for HCC treatment according to traditional Chinese medicine theory, but the pharmacological basis is not clear. Aim of the studyThis study aims to investigate the anti-HCC effects of an ethanolic extract of QWW (hereafter, QWWE) and the mechanism of action. Materials and methodsAn UPLC-Q-TOF-MS/MS method was developed to control the quality of QWWE. Two human HCC cell lines (HCCLM3 and HepG2) and a HCCLM3 xenograft mouse model were employed to investigate the anti-HCC effects of QWWE. The anti-proliferative effect of QWWE in vitro was determined by MTT, colony formation and EdU staining assays. Apoptosis and protein levels were examined by flow cytometry and Western blotting, respectively. Nuclear presence of signal transducer and activator of transcription 3 (STAT3) was examined by immunostaining. Transient transfection of pEGFP-LC3 and STAT3C plasmids was performed to assess autophagy and determine the involvement of STAT3 signaling in QWWE’s anti-HCC effects, respectively. ResultsWe found that QWWE inhibited the proliferation of and triggered apoptosis in HCC cells. Mechanistically, QWWE inhibited the activation of SRC and STAT3 at Tyr416 and Tyr705, respectively; inhibited the nuclear translocation of STAT3; lowered Bcl-2 protein levels, while increased Bax protein levels in HCC cells. Over-activating STAT3 attenuated the cytotoxic and apoptotic effects of QWWE in HCC cells. Moreover, QWWE induced autophagy in HCC cells by inhibiting mTOR signaling. Blocking autophagy with autophagy inhibitors (3-methyladenine and chloroquine) enhanced the cytotoxicity, apoptotic effect and the inhibitory effect on STAT3 activation of QWWE. Intragastric administration of QWWE at 10 mg/kg and 20 mg/kg potently repressed tumor growth and inhibited STAT3 and mTOR signaling in tumor tissues, but did not significantly affect mouse body weight. ConclusionQWWE exhibited potent anti-HCC effects. Inhibiting the STAT3 signaling pathway is involved in QWWE-mediated apoptosis, while blocking mTOR signaling contributes to QWWE-mediated autophagy induction. Blockade of autophagy enhanced the anti-HCC effects of QWWE, indicating that the combination of an autophagy inhibitor and QWWE might be a promising therapeutic strategy for HCC management. Our findings provide pharmacological justifications for the traditional use of QWW in treating HCC.

Screening of Q-markers for the wine-steamed Schisandra chinensis decoction pieces in improving allergic asthma

BackgroundTraditional Chinese medicine (TCM) posits that Chinese medicinal materials can only be clinically used after being processed and prepared into decoction pieces. Schisandra Chinensis Fructus (derived from the dried and mature fruits of Schisandra chinensis (Turcz.) Baill.) has been used as a traditional antiasthmatic, kidney strengthening, and hepatoprotective agent for 2000 years. The results of previous research show that decoction pieces of wine-steamed Schisandra chinensis (WSC) are more effective than raw decoction pieces of Schisandra chinensis (RSC) for treating cough and asthma. Steaming with wine was demonstrated to promote the dissolution of ingredients. However, the relationship between the changes in the components of the decoction pieces of WSC and the therapeutic effect remains unclear.MethodsThe efficacies of decoctions of RSC and WSC were compared using allergic asthma rats. The potential bioactive components in the serum of the WSC treatment group and the changes in the chemical composition of the RSC decoction pieces before and after wine steaming were determined by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC H-CLASS XEVO TQD) to speculate quality markers (Q-markers) related to the efficacy of WSC, which were subsequently verified based on a zebrafish inflammation model.ResultsSteaming RSC decoction pieces with wine was found to promote improvement of allergic asthma. Reverse tracing of 22 components detected in the serum of the high dose group of WSC (WSC-H) resulted in 12 ingredients being finally designated as potential effective components. Among these ingredients, 5 components, Schisandrin, Schisandrol B, Schisandrin A, Schisandrin B, and Gomisin D, had higher dissolution rates than RSC after steaming with wine. Validation by an inflammatory zebrafish model showed that these 5 ingredients had a dose-dependent effect and were therefore Q-markers for WSC in the treatment of allergic asthma.ConclusionIn this study, changes in the components of decoction pieces of RSC and WSC and Q-markers related to WSC efficacy were identified, providing valuable information for expanding the application of WSC and establishing a specific quality standard for WSC.

Anxiolytic-like effect of Suanzaoren–Wuweizi herb-pair and evidence for the involvement of the monoaminergic system in mice based on network pharmacology

BackgroundSuanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice.MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the “drug-active ingredient-disease-target-pathway” was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice.ResultsThe results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment.ConclusionsThe anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.

Moisture content measurement model of whole package of Chinese medicinal materials based on microwave transmission technology

In view of the relatively low representativeness of manual sampling inspection, and long time-consuming in oven detection of moisture content, which delayed the subsequent production period, this paper proposed a scheme for rapid moisture quantitative detection for Chinese medicinal materials by microwave transmission technology, and took 8 different types of Chinese medicinal mate-rials as examples to analyze the feasibility and reliability of the scheme for the detection results of moisture content of the whole package of Chinese medicine. In the experiment, the least square method was used to establish the measurement model of microwave absorption rate-moisture content for each kind of medicinal material. The results showed that the microwave transmission measurement of moisture content achieved high-precision measurement of the moisture content of Schisandrae Chinensis Fructus, Ziziphi Spinosae Semen, Poria, Pheretima, Lilii Bulbus, Scutellariae Radix, and Galli Gigerii Endothelium Corneum. The measurement model of Ziziphi Spinosae Semen had the highest accuracy, and the R~2 and root mean square error of the validation set were 0.951 5 and 0.15%, respectively. At the same time, this study found that the microwave absorption intensity of animal medicines including Pheretima and Galli Gigerii Endothelium Corneum was much weaker than that of plant medicines such as Schisandrae Chinensis Fructus, but there was also a good linear relationship between microwave absorption and moisture content, which proved the universality of this method. However, this method was not suitable for Phellodendri Chinensis Cortex because its package contained iron wire. For the whole package of medicinal materials with uniform density and no metal inside, the microwave transmission technology for moisture content measurement can be used to detect the moisture content, which is an effective alternative method to detect the moisture content of medicinal materials.

Combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus ameliorates aluminum-induced Alzheimer's disease via reducing BACE1 expression

Being the most common form of dementia, Alzheimer's disease (AD) has a series of modifiable risk factors, including metal ions represented by aluminium. Aluminium (Al) exhibits its neurotoxic effects, especially mainly by affecting amyloid-β protein (Aβ) aggregation and Tau hyperphosphorylation. As reported in our previous study, the combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus (AS) had a neuroprotective effect. This study aimed to evaluate the anti-AD effect of AS and the mechanism by which AS reduces the neurotoxic effect of Al. Firstly, we used aluminium-maltol (Al(mal)3) to construct a mouse model of AD and performed oral administration of AS, followed by behavioral experiments, and we collected the mouse brain for immunohistochemistry analysis. In vivo results showed that AS significantly improved Al-induced cognitive decline in mice, and reduced the levels of Aβ1–42 and P-Tau in the brain, which further proved the anti-AD effect of AS. Then, in order to explore the mechanism by which AS reduced Aβ1–42, Al-induced PC12 cells were used for the in vitro experiments. Compared with other ratios, the ratio of Alpinia Oxyphylla Fructus: Schisandra Chinensis Fructus (AO:SC) = 1:2 could better improve the cell viability and reduce the Aβ1–42 level. According to western blot and quantitative real-time polymerase chain reaction (qPCR) results, AS ameliorated the pathological process by downregulating the expression of β-secretase (BACE1), rather than by reducing the expression of amyloid precursor protein (APP) or Tau. These results suggest that AS ameliorated Al-induced AD by affecting the expression of BACE1 and reducing the level of Aβ1–42, thereby exerting a neuroprotective effect. Combined with previous studies, this study shows that AS has potential for further research and development in AD treatment.

Network Pharmacology Analysis of Bioactive Components and Mechanisms of Action of Qi Wei Wan Formula for Treating Non-Small Cell Lung Carcinoma

Astragali Radix (AR) and Schisandrae chinensis Fructus (SCF) have been used individually and in traditional Chinese medicine (TCM) formulas for treating non-small cell lung carcinoma (NSCLC). Qi Wei Wan (QWW), a 2-herb TCM formula composed of AR and SCF, is used to treat blood deficiency, fatigue, and metabolic abnormalities. We speculate that QWW may be more effective in treating NSCLC than AR or SCF alone. We identified 28 bioactive compounds in QWW and 322 targets of these compounds from databases. Network pharmacology analysis was used to identify 248 putative NSCLC-related gene targets of the bioactive compounds in QWW. Common target genes were analyzed to build protein–protein interaction networks. Implicated biological functions and pathways (p53, PI3K-Akt, etc) were identified by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. Molecular docking of core target proteins with the key active compounds was also performed. This study identified the potential gene targets and mechanisms involved in the anti-NSCLC effects of QWW.