Xiebai San alleviates acute lung injury by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating multiple metabolisms.

BACKGROUND: Acute lung injury (ALI) often leads to serious respiratory diseases with high incidence rates and mortality. For centuries, Xiebai San (XBS) has been a classical traditional Chinese medicine (TCM) about respiratory illness such as pneumonia in children. However, the related mechanism of XBS against ALI remains indistinct. PURPOSE: To reveal specific targets of XBS in lipopolysaccharide (LPS)-induced ALI mice using integrated pharmacology. STUDY DESIGN: The integrated method was to expound mechanism and targets of XBS inhibited ALI. METHODS: The primary components in XBS were identified by ultra high performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS). The potential drug targets were established using network pharmacology. The anti-ALI effect of XBS was evaluated in mice. Additionally, therapeutic targets were screened by integrating metabolome and transcriptome and verified in lung tissue. RESULTS: In total, 163 chemical components were identified in XBS, and a network of "3 drugs-18 components-86 targets" for XBS against ALI was constructed. In ALI mice, XBS alleviated lung inflammation by decreasing permeation and expression of neutrophils, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in bronchoalveolar lavage fluid (BALF), serum, and lung tissue. Next, the transcriptome of lung tissue was analyzed and enriched, indicating the importance of mitogen-activated protein kinase (MAPK), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and others, which was consistent with network pharmacology prediction. Also, western blotting and immunohistochemistry results showed that XBS was against ALI mainly by inhibiting extracellular signal regulated kinase (ERK) and signal transducer and activator of transcription 3 (Stat3) phosphorylation. In addition, the metabolome of lung tissue revealed that XBS mainly regulated pathways involved in arachidonic acid, glycerophospholipid, and tryptophan metabolisms. The expression levels of leukotriene, phosphatidylcholine, kynurenine, and others were also verified. CONCLUSION: XBS alleviated inflammation of ALI by inhibiting the phosphorylation of the ERK/Stat3 pathway and regulating arachidonic acid, glycerophospholipid, and tryptophan metabolisms. This study will guide clinical precision medicine and promote modernization of XBS.

Ginkgolides with anti-PAF activity from Ginkgo biloba L.

Four undescribed ginkgolides, including two rare sesquiterpene ginkgolides (compounds 1 and 2) and two diterpenoid ginkgolides (compounds 3 and 4), were isolated from Ginkgo biloba L. The structures of these four ginkgolides were identified based on extensive spectroscopic analysis, DP4+ probability analysis and X-ray diffraction. Compounds 1 and 2 exhibited excellent antiplatelet aggregation activities with IC50 values of 1.20 ± 0.25 and 4.11 ± 0.34 µM, respectively.

[Improvement of high-quality evaluation criteria of Chinese patent medicines based on whole process control].

Chinese patent medicines(CPMs) are unique therapeutic drugs in China. Establishing and improving the evaluation criteria is an important measure to promote the high-quality development of CPMs. Based on the "evaluation criteria of high-grade CPMs with quality as the core index" established by our group in 2018, the "high-quality evaluation criteria for CPMs based on whole process control" was proposed in the present study in 2022. The scope of application and basic principles of the new criteria were clarified. A quality evaluation scoring table was established in the new criteria, including five parts: raw material selection, production process, quality control, efficacy evaluation, and brand building. The technical evaluation indexes involved have increased from 20% in the original criteria to 70% in the new criteria, and efficacy evaluation has been added in the new criteria. The subjective evaluation indicators account for a large proportion in the original criteria, which is prone to bias. The improved criteria overcome this shortcoming. It is expected that the new criteria as a basis can play a better role in the selection of high-quality products of CPMs, guide enterprises and institutions to participate actively in the evaluation and research of high-quality CPMs, and promote the high-quality development of CPMs.

Corylin ameliorates chronic ulcerative colitis via regulating the gut-brain axis and promoting 5-hydroxytryptophan production in the colon.

BACKGROUND: Chronic ulcerative colitis (UC) is a lifelong disease, patients with chronic UC have a high prevalence of common mental disorders. The increasing interest in the role of gut-brain axis is seen in inflammatory bowel diseases. PURPOSE: Corylin is a representative flavonoid compound isolated from the Psoraleae Fructus. This study aimed to identify the effects and mechanism of corylin on the inflammation interactions and 5-HT synthesis between the gut and brain in chronic UC. METHODS: Dextran sulfate sodium (DSS) induced chronic UC mouse model was established to assess the therapeutic effect of corylin on chronic UC symptoms. The expression of inflammatory cytokines was detected in the colon and brain. The expression of tight junction (TJ) proteins of intestinal mucosal barrier and blood-brain barrier (BBB) and the ionized calcium-binding adaptor molecule 1 (Iba1) in the hippocampus were determined by western blotting and immunofluorescence staining. In addition, several tryptophan (Trp) metabolites and related neurotransmitters in faeces, colon, serum, and brain were detected by UPLC-MS/MS. The interaction between corylin and 5-hydroxytryptophan decarboxylase (5-HTPDC) was performed by molecular docking and surface plasmon resonance (SPR). Finally, the changes of gut microbiota composition were analyzed by 16S rRNA sequencing. RESULTS: Corylin significantly alleviated colitis symptoms and inhibited inflammatory response in the colon and brain of DSS-induced chronic UC mice. The TJ proteins of intestinal mucosal barrier and BBB were improved and the expression of Iba1 in the hippocampus was normalized after corylin treatment. In addition, corylin treatment increased the expression of neurotransmitters in the brain, especially 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP), but the expression of 5-HT in the colon was inhibited. Further study firstly proved that corylin could bind to the 5-HTDPC, and then inhibit the expression of 5-HTDPC and VB6, resulting in the 5-HT reduction and 5-HTP accumulation in the colon. Moreover, the intake of corylin transformed the diversity and composition of intestinal microbiota, Bacteroides, Escherichia-Shigella, and Turicibacter were decreased but Dubosiella, Enterorhabdus, and Candidatus_Stoquefichus were increased. CONCLUSION: Corylin administration ameliorated DSS-induced colitis and inhibited intestinal inflammation and neuroinflammation via regulating the inflammation interactions across gut-brain axis and increasing 5-HTP generation in the colon.

Flavonoids dimers from the fruits of Psoralea corylifolia and their cytotoxicity against MCF-7 cells.

Nine new flavonoids dimers, psocorylins R-Z (1-9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3-9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.

Dynamic process and mechanism of crude oil release from silty intertidal sediment under different influencing factors.

Under tidal scouring, residual petroleum in the intertidal sediment after oil spills could release again, causing secondary pollution in the marine ecosystem. The current study aimed to investigate the dynamic process and principles of crude oil release from silty intertidal sediment under different influencing factors and screened for the key factors. In this paper, the fitting equations and correlation between the release amount and various factors were explored through the single-factor and orthogonal experiments. Then, the key influencing factors were selected for multi-factor fitting of the release amount. The results showed that the oil release amount rose with the increase in oil concentration, oscillation frequency, and release time, but decreased with an increase in salinity. As the pH decreased, the oil release amount increased. The relationship between release amount and concentration/oscillation frequency can be equipped by the polynomial equation, and the average R2 was 0.95 and 0.84, respectively. The release amount can be fitted by the Lagergren pseudo-second-order kinetic equation with time, with the average R2 0.89. The pH was negatively correlated with the release amount in the fresh contaminated sediment but positively correlated with the weathered one. The correlation between each factor and oil release amount was ranked (from large to small) as oil concentration, oscillation frequency, salinity, time, and pH. At last, a polynomial equation can be fitted between the key influencing factors (oil concentration and oscillation frequency) and the release amount. The results can provide a theoretical basis for predicting the secondary pollution owing to the oil re-release from intertidal sediment.

[Biotransformation of psoralenoside and isopsoralenoside in Psoraleae Fructus incubated with human intestinal bacteria flora in vitro].

Absorption is crucial to the resultant efficacy of oral drugs where the intestinal bacteria flora functions as one of the first-pass effects.The present study investigated the biotransformation of psoralenoside and isopsoralenoside in Chinese medicine Psoraleae Fructus(the dried fruit of Psoralea corylifolia) with the internationally recognized human intestinal bacteria flora model in vitro.Pso-ralenoside and isopsoralenoside were anaerobically incubated with human intestinal bacteria flora at 37 ℃, respectively, and biotransformation products were analyzed and identified using high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS) and comparison with reference standards.The main biotransformation products of psoralenoside were psoralen and a small amount of 6,7-furano-hydrocoumaric acid, and the main biotransformation products of isopsoralenoside were isopsoralen and a small amount of 5,6-furano-hydrocoumaric acid.

Constituents promoting osteogenesis from the fruits of Psoralea corylifolia and their structure-activity relationship study.

The mature fruit of Psoralea corylifolia L. is a common traditional Chinese medicine used to tonify the kidney and yang, and as well as to treat osteoporosis. Systematic phytochemical investigations have established the most comprehensive constituent library to date, covering over 180 compounds. In this study, 109 chemical constituents containing 37 undescribed compounds were reported and incorrect structures of four known coumarins were corrected. The structures of these undescribed compounds were elucidated using spectroscopic methods, single-crystal X-ray diffraction, Rh2(OCOCF3)4 and Mo2(OAc)4-induced circular dichroism spectra. To identify potentially active compounds and investigate their structure-activity relationship (SAR), 89 constituents in the library were evaluated for their osteogenic differentiation and mineralisation activities in MC3T3-E1 cells. We found that coumarins, isoflavones, flavonones, and meroterpenoids were the material basis for Psoralea corylifolia-based treatment of osteoporosis, with some compounds exhibiting excellent activities. These compounds function via the estrogen receptor (ER) pathway and were natural phytoestrogen. Further SAR analysis showed that compounds with an intact isopentenyl replacement possessed superior activities, which was explained by their improved affinity with the ER.

New bakuchiol dimers from Psoraleae Fructus and their inhibitory activities on nitric oxide production.

BACKGROUND: Dried fruits of Psoralea corylifolia L. (Psoraleae Fructus) is one of the most popular traditional Chinese medicine with treatment for nephritis, spermatorrhea, pollakiuria, asthma, and various inflammatory diseases. Bakuchiol is main meroterpenoid with bioactive diversity from Psoraleae Fructus. This study was designed to seek structural diverse bakuchiol derivants with anti-inflammatory activities from this plant. METHODS: Various column chromatography methods were used for isolation experiment. Structures and configurations of these compounds were determined by spectroscopic methods and single-crystal X-ray diffraction. Their inhibition on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were evaluated by the Griess reaction. RESULTS: Twelve unpresented bakuchiol dimmers, bisbakuchiols M-U (1-9) and bisbakuchiol ethers A-C (10-12), along with five known compounds (13-17), were isolated from the fruits of Psoralea corylifolia L. Compounds 1-3, 10-12, 16 and 17 exhibited inhibitory activities against LPS-induced NO production in RAW264.7 macrophages, and the inhibition of compound 1 (half maximal inhibitory concentration (IC50) value = 11.47 ± 1.57 µM) was equal to that of L-N(6)-(1-iminoethyl)-lysine (IC50 = 10.29 ± 1.10 µM) as a positive control. CONCLUSIONS: Some compounds exhibited inhibitory activities against NO production, and the study of structure-activity relationship suggested that uncyclized compounds with oxygen substitution at C-12/12' showed strong inhibitory activities, and carbonyl units contributed to enhanced activities.

The benzofuran glycosides from the fruits of Psoralea corylifolia L.

Six new glucosides of benzofuran (1-6), together with three known glucosides of benzofuran (8, 9, 14), nine flavonoids (12, 13, 15, 18, 19, 20, 21, 22 and 24), three coumarins (16, 17, 23) and four other-typic compounds (7, 10, 11 and 25) were isolated from the fruits of Psoralia corylifolia L. Their structures were elucidated by extensive spectroscopic methods. The biosynthesis pathway of benzofuran system was discussed. Besides, all isolated compounds and additional ring-opening derivatives of psoralen/isopsoralen (P-1, P-2, IP-1 and IP-2) were assayed for inhibition of nitric oxide (NO) production on lipopolysaccharides-induced RAW 264.7 macrophage cells. The results of the assay showed that the glycosides showed weaker or no effects, while most isolated non-glycoside compounds showed moderate or high activities. And the structure-activity relationships of non-glycoside compounds were discussed.

Poly-pharmacokinetic strategy represented the synergy effects of bioactive compounds in a traditional Chinese medicine formula, Si Shen Wan and its separated recipes to normal and colitis rats.

Si Shen Wan is a classic traditional Chinese medicine formula, which has been used to treat chronic colitis for thousands of years. Many research and experience show that Si Shen Wan was developed by the combination of two sets of "Herb Pairs," Er Shen Wan and Fructus Schisandrae Chinensis Powder. This research aimed to revealing the effective substances, guide the clinical treatment, and represent the synergy effects from the view of pharmacokinetics. An ultra high performance liquid chromatography with tandem mass spectrometry method was established and validated for simultaneous quantification of 26 main bioactive compounds in normal and colitis rat plasma after oral administration of Si Shen Wan and its "Herb Pairs" extract. The method validation results illustrated that the experimental method was reliable and reproducible for quantitative determination of the biological samples. The pharmacokinetic behaviors in different groups were compared and discussed comprehensively, which indicated that the treatment of Si Shen Wan has a superiority in synthetic action of the "Herb Pairs" for the higher peak concentrations and bioavailability of some mainly components. Furthermore, the synergy effect was still existing backed up again for the longer eliminate time and a better bioavailability in colitis groups. The pharmacokinetics research of multiple components in Si Shen Wan and its "Herb Pairs" supplied a significant basis for better understanding the metabolic mechanism of these formulas in both normal and pathological state.

Multi-Target Anti-Alzheimer Activities of Four Prenylated Compounds from Psoralea Fructus.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is mediated by multiple signaling pathways. In recent years, the components of Psoralea Fructus (PF) have demonstrated some anti-Alzheimer effects both in vitro and in vivo. To further reveal the active compounds of PF and their mechanisms regulating key targets of AD, in this study, we identified four prenylated compounds from the 70% ethanolic aqueous extract of PF, namely bavachin, bavachinin, bavachalcone, and isobavachalcone. Multi-target bioactivity analysis showed that these compounds could differentially inhibit neuroinflammation, oxidative damage, and key AD-related protein targets, such as amyloid ß-peptide 42, ß-secretase, glycogen synthase kinase 3ß, and acetylcholinesterase. These compounds may generate beneficial effects in AD prevention and treatment.