One novel enzymatic-extractable polysaccharide (ES1) from fruiting bodies of Laetiporus sulphureus was obtained by isolation and purification using a DEAE Seplife FF chromatographic column and a Sephacryl S-400HR column. The hepatoprotective ability of ES1 against chronic alcoholic liver disease (ALD) and its underlying mechanism were explored. The results indicated that ES1 could alleviate liver damage in ALD mice by activating sequestosome-1/nuclear factor E2-related factor 2 (P62/Nrf2) pathway to increase antioxidant enzyme activities against oxidative stress, regulating adenosine monophosphate-activated protein kinase (AMPK) pathway to promote fatty acid oxidation and inhibit cholesterol synthesis against lipid metabolism disorders, and improving gut microbiota (increasing the relative abundances of Ligilactobacillus and Akkermansia, and reducing the relative abundances of Enterococcus, Romboutsia, Allobaculum, Coriobacteriaceae_UCG-002, Dubosiella and Faecalibaculum) against intestinal barrier dysfunction. Meantime, structural analysis showed that ES1 with molecular weight of 25.79 kDa was composed of α-D-Manp-(1→, →2,6)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →3)-α-L-Fucp-(1→, and α-D-Glcp-(1→, and its structure was also inferred. Therefore, these data support the application of ES1 as a potential functional food or drug for treating ALD.

The present study aimed to isolate compounds from Caragana jubata (Pall.) Poir. and evaluate their in vitro neuroprotective effects. The compounds were isolated by various column chromatographic techniques and semipreparative HPLC. The structures of the new compounds were elucidated using HR‒ESI‒MS, UV, IR, 1D and 2D NMR, and single X-ray diffraction data analysis. Furthermore, their absolute configurations were determined through ECD spectroscopic data analysis. An oxygen‒glucose deprivation/reperfusion (OGD/R)-induced PC12 cell model and LPS-induced NO release from a BV2 cell model were established to evaluate their in vitro neuroprotective effects. Four undescribed compounds (1‒4), comprising one rare rearranged isoflavanone derivative with a 6/6/6/6 four-ring system, one isoflavanone, and two isoflavones, together with 21 known compounds, were isolated from C. jubata. The steric configurations of compound 5 were determined for the first time. Compounds 1‒5, 7‒9, 11‒12, 14‒15, and 17‒21 showed protective effects against OGD/R-induced PC12 cells in a range of 3.125 to 25 µM. (‒)-Caraflavonoid B (2b) displayed the most prominent protective activity. In addition, compound 2b had antineuroinflammatory activity. Results of network pharmacology indicate compound 2b may exert anti-ischemic stroke (anti-IS) effect by modulating multiple targets and pathways.

Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used to predict potential targets related to the anti-IS effect of ISL. The binding ability of ISL to potential core targets was further analyzed by molecular docking and molecular dynamics (MD) simulations. By establishing an oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cell model, the anti-IS mechanisms of ISL were investigated via RT-qPCR and Western Blot (WB). As a result, network pharmacology analysis revealed that APP, ESR1, MAO-A, PTGS2, and EGFR may be potential core targets of ISL for anti-IS treatment. Molecular docking and molecular dynamics simulation results revealed that ISL can stably bind to the five potential core targets and form stable complex systems with them. The results of the cell experiments revealed a significant anti-IS effect of ISL. Additionally, mRNA and protein expression levels of APP, MAO-A and PTGS2 or ESR1 in the ISL treatment group were significantly lower or higher than those in the OGD/R group In conclusion, ISL may improve IS by regulating the protein expression levels of APP, ESR1, MAO-A, and PTGS2.

The aim of the present study was to screen for the key hepatoprotective constituents of Odontites vulgaris Moench. As a result, the D30 elution fraction, separated by D101 macroporous adsorption resin column chromatography, had the most prominent protective effect on carbon tetrachloride-damaged HepG2 cells, the most significant 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging ability, and the highest total phenol and total flavonoid contents, indicating that the D30 elution fraction may be the active fraction for liver protection. Ultra-performance liquid chromatography analyses revealed that ipolamiide, 8-epiloganin, and acteoside were the main components. Results of the bioactivity evaluation demonstrated that acteoside had hepatoprotective activity, with a half-maximal effective concentration value of 35.32 ± 5.33 µM. Results of network pharmacology and molecular docking showed that acteoside had an affinity binding energy of -6.53 and -5.59 kcal/mol to matrix metalloproteinase-12 (MMP-12) and HSP90AA1, respectively, indicating good binding between acteoside and MMP-12 and HSP90AA1. All the findings in the present study reveal that acteoside may be the key hepatoprotective constituent of O vulgaris, which deserves further study.

Pholidota cantonensis Rolfe is an edible medicinal plant in the genus Pholidota of the family Orchidaceae. This plant is used to prepare medicated food in China and has been reported to possess anti-α-glucosidase activity. To date, little is known about the active substances responsible for the observed anti-α-glucosidase activity. In the present study, we aimed to screen and characterize the α-glucosidase inhibitory fraction of P. cantonensis using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC–Q–TOF–MS/MS) analysis and molecular docking. As a result, the 50

Searching for new anti-ischemic stroke (anti-IS) drugs has always been a hot topic in the pharmaceutical industry. Natural products are an important source of discovering anti-IS drugs. The aim of the present study is to extract, rapidly prepare and explore the neuroprotective effect of texasin, a main active constituent from Caragana jubata (Pall.) Poir., which is a kind of Tibetan medicine with a clear anti-IS effect. The results showed that 95% ethanol was the optimal extraction solvent. A three-step rapid preparation method for texasin was successfully established, with a purity of 99.2%. Texasin at the concentration of 25-100 mu M had no effect on the viability of normal cultured PC12 cells; 12.5 and 25 mu M texasin could enhance the viability of PC12 cells damaged by oxygen and glucose deprivation/reoxygenation (OGD/R), and their effects are comparable to the positive drug edaravone at the concentration of 50 mu M. Compared with the normal group, the expression of Bcl-2 protein in OGD/R-injured PC12 cells was downregulated (p < 0.01), and that of PERK, eIF2 alpha, ATF4, CHOP, Bax and Cleaved caspase-3 proteins were upregulated (p < 0.01, p < 0.001). Compared with the OGD/R group, 25 mu M texasin could upregulate the expression of Bcl-2 protein (p < 0.01), and downregulate that of PERK, eIF2 alpha, ATF4, CHOP, Bax and Cleaved caspase-3 proteins (p < 0.01, p < 0.001). The 7-OH and 1-O of texasin formed H-bonds with residues Cys891 of the hinge beta-strand of PERK, which is crucial for kinase inhibitors. The above results suggest that the method established in the present study achieved rapid preparation of high-purity texasin. Texasin might inhibit neuronal apoptosis via the regulation of endoplasmic reticulum stress PERK/eIF2 alpha/ATF4/CHOP signalling pathway to exert a protective effect on OGD/R-injured PC12 cells. Aiding by molecular docking, texasin was assumed to be a potential PERK inhibitor.

The Poaceae family, the fifth largest family of angiosperms, has always been an important source of cereal crops, medicinal crops, and industrial crops. However, comprehensive studies on the biological activity and chemical composition of many species are lacking. In the present study, we tested the total flavonoid and total phenol contents and antioxidant, alpha-glycosidase, alpha-amylase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE)-inhibitory activities of five Poaceae plants ( Echinochloa crus-galli, Miscanthus floridulus, Sporobolus fertilis, Bromus japonicus, and Eleusine indica). As a result, the 95 % ethanol (EtOH) extract of M. floridulus (EMF) was found to possess strongest abovementioned activities among the extracts of the five different species. The IC50 value of the DPPH radical scavenging activity was 23.18 + 0.36 mu g/mL, and those of the anti-AChE, anti-BChE and anti-alpha-glycosidase activities were 49.92 + 1.44, 100.37 + 2.48, and 50.01 + 2.15 mu g/mL, respectively. Forty-four compounds were identified from the EMF through liquid chromatography-hybrid ion trap-time of flight mass spectrometry (LC-IT-TOF-MS) analysis, and the majority of these compounds were flavonoids and organic acids. In general, the obtained results highlight the medicinal value of the five members of the Poaceae family. More importantly, M. floridulus has potential for the development of multitarget anti-Alzheimer's disease (AD) and antidiabetic agents in the pharmaceutical industry.

2,7,2'-Trihydroxy-3,4,4'7'-tetramethoxy-1,1'-biphenanthrene (1), a previously undescribed biphenanthrene, and five known phenanthrenes, i.e. 2,5-dihydroxy-4-methoxy-9,10-dihydroxyphenanthrene (2), 2,4dihydroxy-7-methoxy-9,10-dihydroxyphenanthrene (3),7-hydroxy-2-methoxy-phenanthrene1,4-dione (4), 7-hydroxy-2-methoxy-9,10-dihydro-phenan threne-1,4-dione (5), and 4,4',7,7'-tetrahydroxy-2,2'-dimethoxy-9,9',10, 10'-tetrahydro-1,1'-biphenanthrene (6) were isolated from the whole plant (stems, leaves, roots and fruits) of Liparis nervosa (Thunb.) Lindl., which is a medicinal plant of the genus Liparis in the Orchidaceae family. The structures of isolates were identified using spectroscopic methods, including NMR and mass spectrometry. Additionally, the cytotoxic potency of all the isolates against human lung cancer A549 cell line was evaluated by an MTT assay. All the isolated compounds showed cytotoxic activities with IC50 values in the range of 10.20 +/- 0.81 to 42.41 +/- 2.34 mu M. The obtained data highlight the importance of L. nervosa as a source of natural lead compounds for cancer therapy. [GRAPHICS] .

Objective: The objective of this study was to decipher chemical interactions between Danshen and Danggui using liquid chromatography-mass spectrometry (LC-MS) and explore the mechanisms of Danshen-Danggui against stroke using network pharmacology and molecular docking. Materials and Methods: First, the chemical compounds of Danshen-Danggui were profiled using ultra-high-performance liquid chromatography (HPLC)-quadrupole time-of-flight MS. Accurately characterized compounds in various proportions of Danshen-Danggui were quantified using HPLC combined with triple quadrupole electrospray tandem MS. Network pharmacology was used to uncover the essential mechanisms of action of Danshen-Danggui against stroke. Discovery Studio Software was used for the molecular docking verification of key active chemicals and stroke-related targets. Results: A total of 53 compounds were characterized, and 22 accurately identified constituents (10 phenolic acids, 8 phthalides, and 4 tanshinones) were quantified in 15 proportions of Danshen-Danggui. The quantification results showed that Danggui significantly increased the dissolution of most phenolic acids (compounds from Danshen), whereas Danshen promoted the dissolution of most phthalides (compounds from Danggui). Overall, the combination of Danshen and Danggui at a 1:1 ratio resulted in the maximum total dissolution rate. Further network pharmacology and molecular docking results indicated that Danshen-Danggui exerted anti-stroke effects mainly by regulating inflammation-related (tumor necrosis factor, hypoxia-inducible factor, and toll-like receptor) signaling pathways, which ranked among the top three pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Conclusion: The chemical compounds in Danshen-Danggui could interact with each other to increase the dissolution of the most active compounds, which could provide a solid basis for uncovering the compatibility mechanisms of Danshen-Danggui and Danshen-Danggui-based formulae.

A bioactivity-guided separation strategy was used to identify novel antistroke compounds from Gymnadenia conopsea (L.) R. Br., a medicinal plant. As a result, 4 undescribed compounds (1–2, 13, and 17) and 13 known compounds, including 1 new natural product (3), were isolated from G. conopsea. The structures of these compounds were elucidated through comprehensive spectroscopic techniques, such as 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and quantum chemical calculations. An oxygen–glucose deprivation/reoxygenation (OGD/R)-injured rat pheochromocytoma (PC12) cell model was used to evaluate the antistroke effects of the isolates. Compounds 1–2, 10–11, 13–15, and 17 provided varying degrees of protection against OGD/R injury in the PC12 cells at concentrations of 12.5, 25, and 50 µM. Among the tested compounds, compound 17 demonstrated the most potent neuroprotective effect, which was equivalent to that of the positive control drug (edaravone). Then, transcriptomic and bioinformatics analyses were conducted to reveal the regulatory effect of compound 17 on gene expression. In addition, quantitative real-time PCR (qPCR) was performed to verify the results of the transcriptomic and bioinformatics analyses. These results suggest that the in vitro antistroke effect of compound 17 may be associated with the regulation of the Col27a1 gene. Thus, compound 17 is a promising candidate for the development of novel antistroke drugs derived from natural products, and this topic should be further studied.

Edgeworthia gardneri (Wall.) Meisn., a member of the genus Edgeworthia in the family Thymelaeaceae, has long been applied as an edible and medicinal plant in China. E. gardneria has a hypoglycemic effect and is used to prepare daily drinks for the prevention and treatment of diabetes. However, the hypoglycemic substances involved remain unknown. The present study aimed to screen the α-glucosidase-inhibitors of E. gardneri and analyze its chemical profile using a ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) method. As a result, the ethyl acetate fraction (EAF) had significant α-glucosidase-inhibitory and antioxidant activities but did not show an α-amylase-inhibitory activity. A total of 67 compounds were identified in the EAF by UPLC-Q-TOF-MS/MS analysis; among them, 48 compounds were first discovered in the genus Edgeworthia. Additionally, five flavonoids, namely, isoorintin, secoisolaricirinol, tiliroside, chrysin, and kaempferol, had α-glucosidase-inhibitory activities. Rutin had a α-amylase-inhibitory activity. Daphnoretin, a kind of coumarin, has α-glucosidase and α-amylase-inhibitory activities. These findings enrich the chemical library of E. gardneria. EAF has a selective α-glucosidase-inhibitory activity, and flavonoids and coumarins may be the active components of EAF. E. gardneria has important value for developing multiple-target hypoglycemic drugs.

Ethnopharmacological relevance: Salvia miltiorrhiza Bunge (Danshen) and Ligusticum chuanxiong Hort. (Chuanxiong) is the core herb pair in traditional Chinese medicines (TCMs) formulae for treating ischemic stroke. However, the synergistic effect of Danshen-Chuanxiong against anti-ischemic stroke and its compatibility mechanism remains unclear.Aim of the study: This study aimed to uncover the compatibility mechanism of Danshen-Chuanxiong against ischemic stroke through chemical profiling, pharmacodynamics evaluation, network pharmacology and experimental validation. Materials and methods: Ultra-high performance liquid chromatography (UHPLC) combined with quadrupole timeof-flight tandem mass spectrometry (QTOF-MS) and UHPLC connected with tandem triple quadrupole mass spectrometry (QQQ-MS) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of Danshen-Chuanxiong against ischemic stroke were comprehensively evaluated by the middle cerebral artery occlusion reperfusion (MCAO/R) mice model, zebrafish ischemic stroke model and glutamic acid-induced PC12 cells injury model. Afterwards, network pharmacology and molecular docking were applied to dissect the significant active compounds and potential mechanisms. Finally, the key target proteins were experimentally validated by Western blot. Results: 83 compounds were characterized in Danshen-Chuanxiong by UHPLC-QTOF-MS analysis, and 4 compounds were tentatively identified for the first time. The quantification results (24 accurately identified compounds) in 13 proportions of Danshen-Chuanxiong revealed that Danshen significantly increased the dissolution of most phthalides (from Chuanxiong), while Chuanxiong facilitated the dissolution of most phenolic acids (from Danshen) in solution. The anti-ischemic stroke effects of Danshen-Chuanxiong were significantly better than Danshen or Chuanxiong in attenuating infarct size, reducing brain edema and neurological scores in MCAO/R mice. Also, compared with single herbs, this herb pair exerted better effects of suppressing the incidence of cerebral thrombosis in zebrafish, and increasing the cell viability of glutamic acid-induced PC12 cells. In network pharmacology, 7 effective compounds (rosmarinic acid, chlorogenic acid, salvianolic acid B, (Z)-ligustilide, ferulic acid, caffeic acid, tanshinone IIA) and 5 hub targets (AKT, TNF- & alpha;, IL-1 & beta;, CASP3 and BCL2) as well as 4 key pathways were predicted. Western blot results showed that Danshen-Chuanxiong exert therapeutic effects mainly through decreasing the protein expressions of TNF-& alpha;, IL-1I3 and Cleaved-CASP3, elevating the levels of pAKT and BCL2.Conclusions: This work provided an integration strategy for uncovering the synergistic effects and compatibility mechanism of Danshen-Chuanxiong herb pair for treating ischemic stroke, and laid foundation for the further development and utilization of this herb pair.

Introduction: The whole grass Parnassia palustris L. has long been used as Mongolian medicine in China. However, few data are available on its phytochemical profile and bioactivity. This study aims to investigate several sec-ondary metabolite profiles and bioactivities of P. palustris extract and its fractions. Methods: A spectrophotometric method was used to measure the total phenol, total phenolic acid, total flavonoid, and total terpenoid contents of the extract and different extraction sites. 2,2-Diphenyl-1-picrylhydrazyl(DPPH)/ 2,2 '-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) assays were performed to evaluate in vitro anti-oxidant activities. alpha-Glycosidase/alpha-amylase/acetylcholinesterase (AChE)/butyrylcholinesterase (BChE)-inhibi-tory activities were determined using spectrophotometric methods. A Cell Counting Kit-8 (CCK-8) assay was carried out to test tumor cytotoxicity. Results: The n-butanol fraction (NBF) had the highest total phenol/flavonoid/phenolic acid contents, and the petroleum ether fraction (PEF) had the highest total terpenoid content. The IC50 values of DPPH and ABTS radicals scavenged by the 95% ethanol crude extract of the whole grasses of P. palustris (EEP), ethyl acetate fraction (EAF), NBF, and aqueous fraction (AF) were in the range of 15.33 +/- 1.24 to 87.33 +/- 3.86 mu g/mL and 75.33 +/- 2.87 to 815.67 +/- 7.76 mu g/mL, respectively. The NBF showed the best scavenging effects, while the PEF did not show activities in either assay. EEP, PEF, EAF, and AF did not show inhibitory activities against AChE, except for NBF (IC50 = 484.00 +/- 9.93 mu g/mL). The IC50 values of EEP, NBF, and AF in the BChE-inhibitory assay were in the range of 220.24 +/- 8.56 to 413.93 +/- 2.03 mu g/mL, with NBF exhibiting the best BChE-inhibitory activity. Additionally, neither PEF nor EAF showed inhibitory effects against BChE. None of the test samples were found to have inhibitory activities against alpha-glucosidase and alpha-amylase. EEP, PEF, EAF, and NBF exhibited cytotoxicity against the HepG2 cell line, with IC50 values in the range of 92.93 +/- 7.61 to 377.93 +/- 13.43 mu g/mL. EAF showed the best tumor cytotoxicity, while AF had no cytotoxicity. In general, NBF was found to have potent in vitro antioxidant activity and dual AChE/BChE inhibitory activity for the first time. The EAF exhibited potent tumor cytotoxic activity against the HepG2 cell line. The results of Pearson's correlation analysis showed that flavonoids and phenols may be responsible for the BChE-inhibitory activity of P. palustris. Furthermore, phenols may contribute to its antioxidant activity. Conclusion: NBF has the potential for the development of new antioxidants and anti-Alzheimer's disease (AD) drugs. The present report will be helpful for better understanding and applying this traditional medicinal plant in the future.

This study aimed to separate the anti-acetylcholinesterase (anti-AChE) compounds from Odontites vulgaris Moench, a member of the Orobanchaceae famly, using a bioactivity-guided isolation strategy. Active fractions were selected according to the results of AChE-inhibitory activities. Then, various chromatographic packings were performed to separate the compounds from the active fractions, followed by identifying their structures using 1D NMR and HR–ESI–MS analyses. In addition, the isolated compounds were tested for their AChE-inhibitory activities. As a result, the bioactivity-guided isolation of O. vulgaris resulted in the acquisition of twenty-three compounds. Aloe emodin ( 10) had a significant AChE-inhibitory activity (IC 50 = 13.48 ± 1.35 µM). The IC 50 values of eight compounds ( 4 , 5 , 7 , 9 , 15 , 19 , 21 and 23 ) were in the range of 40.24 ± 5.73 to 69.26 ± 3.56 µM, indicating their moderate AChE-inhibitory activities. Compounds 3 , 11 , 13 , 14 , 17 and 18 showed weak AChE-inhibitory activities, for their IC 50 values ranged from 82.47 ± 2.12 to 147.98 ± 4.93 µM. The majority of the isolated compounds had AChE-inhibitory activities, indicating O. vulgaris is a source of natural anti-AChE inhibitors. Compounds 1 – 3 , 5 , 7 – 10 , 12 , 15 and 16–21 were first reported from the genus and the plant. These findings enriched the results of the phytochemical study of Odontites and O. vulgaris . The IC 50 values of the positive control galantamine was 0.59 ± 0.03 µM. AChE-inhibitory activities of the tested compounds were much weaker than galantamine. Further seperation to the active subfractions need to be carried out to search for more minor compounds with higher AChE-inhibitory activities. Additionally, whether the isolated compounds have other anti-Alzheimer’s disease activities need further investigations to unveil.

ETHNOPHARMACOLOGICAL RELEVANCE:Caragana jubata, belonging to the Leguminosae family, is a shrubby medicinal plant distributed in high-altitude areas of China. The red heartwood of C. jubata is the original source of 'zuomuxing', a Tibetan medicine that promotes blood circulation and removes blood stasis to treat different diseases associated with the blood. AIM OF THE STUDY:To date, research on the chemical constituents of C. jubata remains very limited. The anti-ischemic stroke (anti-IS) effects of this plant have not been studied. The aim of the present study was to analyze the chemical profile of C. jubata, establish various anti-IS models to comprehensively evaluate the anti-IS effects of C. jubata, and explore the mechanism of action. MATERIALS AND METHODS:Ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was chosen to analyze the chemical profile. A middle cerebral artery occlusion reperfusion (MCAO/R) model, zebrafish cerebral thrombosis model, and oxygen-glucose deprivation/reperfusion (OGD/R) model in PC12/BV2 cells were used to thoroughly evaluate the anti-IS effects of C. jubata. Additionally, western blotting and immunofluorescence staining were used to detect the mechanism of action. RESULTS:Fifty-three compounds were identified from a 95% ethanol extract of C. jubata (ECJ) by UPLC-QTOF-MS analysis. 17 and 7 compounds were identified from C. jubata and the genus Caragana for the first time. ECJ was found to attenuate infarct size and reduce brain edema and neurological scores in MCAO/R rats. ECJ notably reduced the zebrafish cerebral thrombosis incidence in a dose-dependent manner compared with that in the model group. Surprisingly, compared to the positive control drug aspirin, 50 μg/ml ECJ exhibited a better therapeutic effect than aspirin at 30 μg/ml. Additionally, ECJ significantly increased the viability of PC12/BV2 cells injured by OGD/R. Moreover, ECJ inhibited the protein expression of M1 markers (TNF-α, iNOS, and IL-1β) and increased that of M2 markers (Arg-1 and CD206) in OGD/R-injured BV2 cells. ECJ significantly decreased the immunofluorescence intensity of CD16 and increased that of CD206. CONCLUSIONS:The results from UPLC-QTOF-MS analysis showed that ECJ was rich in flavonoids. The results from pharmacological experiments verified the anti-IS effects of C. jubata in vivo and in vitro for the first time. In addition, ECJ could regulate the polarization of microglia. The present study highlights the medicinal value of C. jubata, thus providing a theoretical basis for the further development of new drugs from C. jubata to treat IS.

Background: Previous studies have found that neuroinflammation is closely associated with microglial polarization. Due to the various side effects of current drugs used to treat neuroinflammation, it is important to explore alternative drugs with anti-inflammatory activity for neuroinflammation. We investigated the effect of SCH 644343 on neuroinflammation induced by OGD/R and explored the mechanism in vitro.Method: The CCK-8 assay was used to assess cell viability after SCH 644343 treatment in the model of OGD/R in vitro. Molecular docking technology was used to evaluate binding to the IL-4 and SREBP-1 proteins. WB, immunofluorescence and qRT‒PCR were used to assess the expression of M1 microglia-associated and M2 microglia-associated proteins in microglia and explore the mechanism of action of SCH 644343 on the IL-4/SREBP-1 pathway.Results: SCH 644343 (SCH) exerted a significant effect against OGD/R in BV2 and PC12 cells in vitro by inhibiting M1 microglial polarization and promoting M2 microglial polarization. SCH was shown to have strong binding affinity for the IL-4 and SREBP-1 proteins. Furthermore, suppression of IL-4 and SREBP-1 protein expression by pretreatment with the IL-4 inhibitor and SREBP-1 inhibitor 25-hc attenuated the effect of SCH in vitro.Conclusion: SREBP-1 protein expression was increased after neuroinflammation, and SCH was shown to protect neuronal cells by regulating microglial polarization via the IL-4/SREBP-1 pathway.

Ischemic stroke (IS), a kind of acute cerebrovascular disease, is one of the most common diseases, and it endangers the lives and health of elderly individuals. Inflammation is a key factor leading to stroke, making it a potential therapeutic target. Previous studies have found that neuroinflammation is closely associated with microglial polarization. Due to the various side effects of current drugs used to treat neuroinflammation, it is important to explore alternative drugs with anti-inflammatory activity for neuroinflammation treatment. In the present study, we investigated the effect of SCH 644343 (SCH), a natural compound, on neuroinflammation induced by IS and explored the mechanism. We found that SCH meliorated the phenotypes of IS in vivo, which was correlated with the increased percentage of infiltrated M2 macrophages in brain after stroke. SCH exerted a significant effect against oxygen-glucose deprivation/reoxygenation (OGD/R) in BV2 cells in vitro by inhibiting M1 microglial polarization and promoting M2 microglial polarization. Furthermore, suppression of SREBP-1 expression by pretreatment with the SREBP-1 inhibitor 25-HC attenuated the effect of SCH on IS in vitro. Taken together, SCH exerts anti-IS effect by promoting microglial polarization via the IL-4/SREBP-1 signaling pathway.

Elsholtzia rugulosa Hemsl., a species of the Labiatae family, has a long history of use as a honey plant, herbal tea, and folk medicine in China. However, little is known about its composition and biological activities. The present study aimed to investigate the total phenol and flavonoid contents, phytochemical composition, and multiple biological activities of this plant. The total flavonoid content of the ethyl acetate fraction (EAF) was higher than those of the petroleum ether fraction (PEF), n-butanol fraction (NBF), and water fraction (WF). The EAF also had much stronger antioxidant, cytotoxic, hepatoprotective, and acetylcholinesterase (AChE) and α-glucosidase inhibitory activities than the PEF, NBF, and WF. More importantly, the IC50 values of the EAF and NBF against α-glucosidase were much lower than that of the positive control acarbose, indicating their potent α-glucosidase inhibitory activities. The isolation of the EAF led to the acquisition of 9 compounds, four of which (β-daucosterol, methyl rosmarinate, betulinic acid, and oleanolic acid) possessed significant α-glucosidase inhibitory activities. Maltol 6'-O-(5-O-p-coumaroyl)-β-D-apiofuranosyl-β-D-glucopyranoside and rosmarinic acid were the major phenolic compounds in the EAF according to the HPLC-DAD analysis. All these findings indicate that the EAF, NBF, and some isolated compounds have the potential to be developed as antidiabetic drugs. Moreover, the dual inhibition of AChE and butyrylcholinesterase (BChE) of certain fractions indicates their potential in the development of anti-Alzheimer's disease drugs. The present study provides a new understanding of the phytochemistry and bioactivity of E. rugulosa.

Eleven phenylpropanoids were isolated from the whole grass of Liparis nervosa, an orchidaceous medicinal plant. Their structures were elucidated as (+)-Syringaresinol (1), (-)-Syringaresinol-4-O-β-D-glucopyranoside (2), Sinapaldehyde (3), Coniferyl aldehyde (4), Syringin (5), Sinapaldehye-4-O-β-D-glucoside (6), 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (7), C-Veratroylglycol (8), 7S, 7′S, 8R, 8′R-icariol A2 (9), Erigeside 2 (10), and Methylsyringin (11) by comparing the spectroscopic data and physicochemical constants from the isolated compounds with the data reported in the literature. Compounds 1 and 9 were found to have potent in vitro antioxidant activities in the DPPH and ABTS assays, and their IC50 values were lower than those of vitamin C. More importantly, compound 9 had a strong α-glucosidase inhibitory activity with an IC50 value of 43.76 ± 2.03 µM, which was much lower than that of acarbose (IC50 = 273.12 ± 11.84 µM), indicating that compound 9 has the potential for the development of hypoglycemic drugs. In conclusion, the present study suggests that phenylpropanoids may be the additional representative type of active constituents in L. nervosa, which provides a new line of evidence to understand this medicinal plant.

A bioassay-guided approach was employed to identify the active compounds from the whole herb of Spiranthes sinensis (Pers.) Ames, an orchidaceous medicinal plant. As a result, fourteen compounds were obtained from the active fractions. The structures of the isolates were identified as methyl 4-[2-(butoxymethyl)-5-formyl-pyrrol-1-yl] butyrate (1), 5,3′-dihydroxy-3,7,4′-trimethoxyflavone (2), populnin (3), scutellarein (4), quercetin (5), kaempferol (6), stigmasterol-3-O-β-D-glucopyranoside (7), β-daucosterol (8), trans-p-hydroxy cinnamic acid (9), 4-hydroxybenzoic acid methyl ester (10), 3-(4-tolyloxy)-propanoic acid (11), 2-benzothiazolol (12), ethyl ferulate (13) and kumatakenin (14) by comparing the spectroscopic data from the isolated compounds with the data reported in the literature. Compound 1 was a new natural compound. Compounds 2, 4–6 and 9–14 were first reported from the genus Spiranthes. Compound 7 was isolated from S. sinensis for the first time. In addition, compounds 5, 6, 11 and 13 were found to have potent anti-acetylcholinesterase (anti-AChE) activities with IC50 values ranging from 8.63 ± 0.37 to 19.97 ± 1.05 μg/mL, which indicates that S. sinensis has the potential in the development of new anti-Alzheimer’s disease (anti-AD) drugs.