Effect of Clotrimazole Suppositories on Distribution of Pathogens in Vaginal Secretions and Oxidative Stress in Patients with Vaginitis.

Objective: To evaluate the impact of clotrimazole suppositories on the distribution of vaginal pathogens and oxidative stress in patients with vaginitis. Methods: A total of 120 patients with vaginitis were recruited from our hospital between January 2021 and December 2022 and were divided into an observation group and a control group using a random envelope method. The control group received treatment with miconazole tablets alone, while the observation group received combined treatment with miconazole tablets and clotrimazole suppositories. Vaginal secretions were collected from the subjects for pathogenic microbial testing. The clinical efficacy of the patients was evaluated, and indicators related to vaginal microecology and microbial imbalance were examined. Serum levels of IL-8, CRP, TNF-α, IL-6, PCT, P, LH, FSH, SOD, MDA, NO, and ET-1 were measured in the subjects. Results: Among patients with vaginitis, bacteria, fungi, and gram-negative cocci accounted for a relatively high proportion, with bacterial infections accounting for more than 30% and fungal and gram-negative cocci infections both exceeding 10%. Pathogenic infections such as Chlamydia and Trichomonas were less than 10%. The observation group showed significantly higher clinical efficacy compared to the control group, with a statistically significant difference (P < .05). Following treatment, the observation group exhibited significantly lower scores for itching, vaginal discharge, and burning sensation compared to the control group, with a statistically significant difference (P < .05). After treatment, the observation group had significantly lower bacterial density and Nugent score, higher cleanliness, positive lactobacilli rate, and pH value compared to the control group, and the difference was statistically significant (P < .05). After treatment, the observation group demonstrated significantly lower blood levels of IL-8, CRP, TNF-α, IL-6, and PCT compared to the control group, with a statistical significance of P < .05. Similarly, the levels of P, LH, and FSH hormones in the observation group were significantly lower than those in the control group, also with a statistical significance of P < .05. In contrast, the levels of SOD and NO in the observation group were significantly higher, while the levels of MDA and ET-1 were significantly lower compared to the control group, with a statistical significance of P < .05. Conclusion: Clotrimazole suppositories have been shown to significantly enhance therapeutic outcomes for patients with vaginitis by alleviating inflammation, rebalancing vaginal microecology, regulating hormone secretion, and mitigating oxidative stress.

Cevanine-type alkaloids from the bulbs of Fritillaria unibracteata var. wabuensis and their antifibrotic activities in vitro.

Steroidal alkaloids are the main bioactive components of the bulbs of Fritillaria, which have been used as traditional Chinese medicine, known as "Beimu", for the treatment of cough for thousands of years in China. Cough and dyspnea are the most common symptoms observed in patients with pulmonary fibrosis. However, the antifibrotic activity of steroidal alkaloids has not been reported yet. In this study, two previously unreported cevanine-type steroidal alkaloids (1 and 2), four previously undescribed cevanine-type alkaloid glycosides (3-6), and 19 known steroidal alkaloids (7-25) were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. The structures of these compounds were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, as well as DP4+ NMR calculations. The biological evaluation showed that compounds 2, 7-10, 14, 15, and 17 downregulated fibrotic markers induced by transforming growth factor-ß (TGF-ß) in MRC-5 cells. Moreover, compounds 14 and 17 dose dependently inhibited TGF-ß-induced epithelial-mesenchymal transition in A549 cells, alleviated TGF-ß-induced migration and proliferation of fibroblasts, and decreased the expression of fibrotic markers, fibronectin, and N-cadherin in TGF-ß-induced MRC-5 cells. The research showed the potential of cevanine-type alkaloids as a class of natural antifibrotic agents.

Establishing an integrated, four-dimensional quality assessment system for traditional Chinese medicine: A case study of Shuanghuanglian oral liquid.

The quality of traditional Chinese medicine (TCM) is the premise to ensure its safety and effectiveness in clinical application. In this study, a complete quality control system for four-dimensional fingerprinting of TCM was innovatively constructed based on multiple detection techniques, and the quality of Shuanghuanglian oral liquid (SHL) was evaluated. Electrochemical fingerprinting (ECFP) as an emerging method without pretreatment provides rich and quantifiable information for SHL samples. The first quantitative ECFP of SHL was developed by the B-Z oscillation system. Eight characteristic parameters were analyzed and a good linear relationship was found between the oscillation lifetime and sample volume, by which the calculated values of the added sample volume (VL) showed different fluctuations between samples. What is more, high-performance liquid chromatography five-wavelength fusion fingerprint (HPLC-FWFP), GC fingerprint (GC-FP), and UV quantum fingerprint (UV-QFP) was established. Meanwhile, the purity of the peaks of the HPLC-FWFP was verified by the dual-wavelength absorption coefficient ratio spectrum (DWAR). Equal weighted ratio quantitative fingerprinting method (EWRQFM) was successfully proposed to extract all potential features for the overall quality assessment of the samples. Finally, a comprehensive evaluation strategy was proposed, namely the variation coefficient weighting algorithm (VCWA). The results of qualitative and quantitative evaluation of HPLC-FWFP, GC-FP, electrochemical quantum fingerprints (EC-QFP), and UV-QFP were integrated by this method. The established evaluation system is also a suitable strategy to control the quality of other TCM preparations.

Professor FU Wen-bin's experience in treating "five delays and five weaknesses" in children with yang-oriented approach. / 符文彬教授从阳论治小儿"五迟五软"经验概要.

Professor FU Wen-bin, based on the concept of the "yang-oriented approach", identifies "yang deficiency with excess yin" as the underlying pathological mechanism of "five delays and five weaknesses" in children. He recommends a treatment model that included acupuncture, moxibustion, and rehabilitation, integrating various therapeutic methods of acupuncture, refined moxibustion, and auricular point sticking. Specific acupoints along the conception vessel, governor vessel, and bladder meridian, as well as related acupoints with tonifying effects on spleen and kidney, are selected to achieve the therapeutic goal of "promoting yang and nourishing yang simultaneously".

The Effect of Continuing Nursing Intervention on Peritoneal Dialysis Patients and the Occurrence of Peritonitis: A Meta-Analysis.

Background: Chronic kidney disease, affecting millions globally, has emerged as a significant health concern alongside tumors, diabetes, and cardiovascular diseases. Peritoneal dialysis is a widely used therapeutic intervention, but its effectiveness can be compromised by complications such as peritonitis. Methods: We conducted a comprehensive search across eight international databases to obtain controlled trials evaluating the impact of continuous nursing on peritonitis occurrence in peritoneal dialysis patients. Following stringent quality assessment, data analysis was performed using RevMan 5.3 software. Results: Our meta-analysis included 15 controlled trials. Of these, 13 reported peritonitis rates in both intervention and control groups. Continuous nursing was associated with a significant reduction in peritonitis incidence (OR: 0.32; 95% CI: 0.23,0.44) and complications (SMD: 3.21; 95% CI: 1.17,5.25; P = .01), as well as a decrease in serum creatinine levels (SMD: -130.06; 95% CI: -195.46,-64). Conclusion: The findings of this study support the possibility that ongoing nursing is beneficial for the complications and creatinine for peritoneal dialysis patients.

Hyperelatolides A-D, Antineuroinflammatory Constituents with Unusual Carbon Skeletons from Hypericum elatoides.

Four new δ- and γ-lactone derivatives, hyperelatolides A-D (1-4, respectively), were discovered from the aerial portions of Hypericum elatoides R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the ß- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 µM, respectively. Moreover, the mechanistic study revealed that lactone 1 significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.

Thorough evaluation of the Chinese medicine preparations and intermediates using high performance liquid chromatography fingerprints and ultraviolet quantum fingerprints along with antioxidant activity: Shuanghuanglian oral solution as an example.

The growing global popularity of traditional Chinese medicine (TCM) has generated a growing interest in the quality control of TCM products. Shuanghuanglian Oral Liquid (SHL) is a commonly used TCM formula for treating respiratory tract infections. In this study, we present a thorough evaluation method for the quality of SHL and its intermediates. We assessed the quality through multi-wavelength fusion high-performance liquid chromatogram (HPLC) fingerprints of 40 batches of SHL samples and 15 batches of intermediates. Meanwhile, we introduced a new method called multi-markers assay by monolinear method (MAML) to quantify ten components in SHL, and revealed quality transmitting of ten components from intermediates to formulations. This information allowed us to establish a quality control system for intermediates, ensuring their quality consistency. Furthermore, we proposed UV quantum fingerprinting as an orthogonal complement to the quality evaluation by HPLC fingerprint. The relationship between fingerprinting and antioxidant capacity was also established. Overall, this study presented a novel and integrated approach for the quality evaluation of TCM products, providing valuable information for ensuring the safety and efficacy of TCM products for consumers.

Diversified cassane family diterpenoids from the leaves of Caesalpinia minax exerting anti-neuroinflammatory activity through suppressing MAPK and NF-κB pathways in BV-2 microglia.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.

Phytoecdysteroids from Dianthus superbus L.: Structures and anti-neuroinflammatory evaluation.

Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.

Exploring the anti-metastatic effects of Astragalus mongholicus Bunge-Curcuma aromatica Salisb. on colorectal cancer: A network-based metabolomics and pharmacology approach.

BACKGROUND: Colorectal cancer (CRC) is a common malignancy that can significantly diminish patients' quality of life. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (AC) is an ancient Chinese medicinal combination used for the treatment of CRC. However, the core ingredients and targets involved in regulating lipid and amino acid metabolism in CRC remain unknown. We aimed to explore the key components and pharmacological mechanisms of AC in the treatment of CRC through a comprehensive analysis of network metabolomics, network pharmacology, molecular docking, and biological methods. METHODS: Ultra-performance liquid chromatography/mass spectrometry (MS) was used for quality control. Gas chromatography/MS and liquid chromatography/MS were used to detect metabolites in the feces and serum of CRC mice. A network pharmacology approach and molecular docking were used to explore the potential genes involved in the CRC-target-component network. The effect of AC on tumor immunity was investigated using flow cytometry and polymerase chain reaction. RESULTS: AC, high-dose AC, and 5-fluorouracil treatment reduced liver metastasis and tumor mass. Compared with the CRC group, 2 amino acid metabolites and 14 lipid metabolites (LPC, PC, PE) were upregulated and 15 amino acid metabolites and 9 lipid metabolites (TG, PE, PG, 12-HETE) were downregulated. Subsequently, through network analysis, four components and six hub genes were identified for molecular docking. AC can bind to ALDH1B1, ALDH2, CAT, GOT2, NOS3, and ASS1 through beta-Elemene, canavanine, betaine, and chrysanthemaxanthin. AC promoted the responses of M1 macrophages and down-regulated the responses of M2 macrophages, Treg cells, and the gene expression of related factors. CONCLUSION: Our research showed that AC effectively inhibited the growth and metastasis of tumors and regulated metabolism and immunity in a CRC mouse model. Thus, AC may be an effective alternative treatment option for CRC.

Discovery of diversified cassane diterpenoids as potent antibacterial agents from Caesaplinia pulcherrima and their mechanisms.

BACKGROUND: Natural products play a significant role in the development of novel bactericide candidates. Caesalpinia pulcherrima, a traditional medicine, had anti-inflammatory, antimicrobial, and antifeedant activities, therefore the previous bioassay results of C. pulcherrima implied that its main active ingredients may have potential to be used as botanical bactericides. RESULTS: Bio-guided isolation of C. pulcherrima was conducted to obtain 11 novel cassane diterpenoids (capulchemins A-K) and 10 known sesquiterpenes. Their structures were established by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. Capulchemins A-F possess a rare aromatic C ring, while capulchemin K with a 15,16-degradative carbon skeleton represents a rare group of cassane diterpenes. Capulchemin A exhibited remarkable antibacterial activity against four phytopathogenic bacteria, particularly against Pseudomonas syringae pv. actinidae and Bacillus cereus, with minimal inhibitory concentration values of 3.13 µM. Meanwhile, capulchemin A showed significant control effect on kiwifruit canker in vivo. Further investigation of its mechanism of antibacterial activity revealed that compound 1 was closely related to destroy cell membrane to cause cell death. Additionally, some of those cassane diterpenoids showed potential antifeedant against Mythimna separate walker and Plutella xylostella. Consequently, capulchemin A could have the potential to be used as a template for the development for new eco-friendly NP-based bactericides. CONCLUSION: These data contribute to a better understanding of the antibacterial activity of cassane diterpenes. Cassane diterpenes have been discovered to be leading to broad application prospects in the development as novel botanical bactericides. © 2023 Society of Chemical Industry.

Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense.

Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.

Genomic and Metabolomic Analyses of the Medicinal Fungus Inonotus hispidus for Its Metabolite's Biosynthesis and Medicinal Application.

Inonotus hispidus mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for indigestion, cancer, diabetes, and gastric illnesses. Although I. hispidus is recognized as a rare edible medicinal macrofungi, its genomic sequence and biosynthesis potential of secondary metabolites have not been investigated. In this study, using Illumina NovaSeq combined with the PacBio platform, we sequenced and de novo assembled the whole genome of NPCB_001, a wild I. hispidus isolate from the Aksu area of Xinjiang Province, China. Comparative genomic and phylogenomic analyses reveal interspecific differences and evolutionary traits in the genus Inonotus. Bioinformatics analysis identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Additionally, molecular networks of metabolites exhibit differences in chemical composition and content between fruiting bodies and mycelium, as well as association clusters of related compounds. The deciphering of the genome of I. hispidus will deepen the understanding of the biosynthesis of bioactive components, open the path for future biosynthesis research, and promote the application of Inonotus in the fields of drug research and functional food manufacturing.

Chromosome-Level Genome Sequences, Comparative Genomic Analyses, and Secondary-Metabolite Biosynthesis Evaluation of the Medicinal Edible Mushroom Laetiporus sulphureus.

Laetiporus sulphureus mushroom is a complementary and alternative medicine that has anticancer, antioxidation, and analgesic effects and immunomodulatory activity; it is used as a treatment for cough and rheumatism and is a functional food that can improve physical fitness. Even though L. sulphureus has garnered considerable biotechnological and pharmacological interest due to its excellent cellulose-degrading ability and diverse biological activities, its biosynthetic potential regarding polysaccharides and secondary metabolites has not been thoroughly examined. In this study, we sequenced and assembled the whole genome of a wild L. sulphureus isolate, NWAFU-1, from the Qinling Mountains in China. Comparative genomes analysis revealed genomic differences between subspecies, and phylogenomic analysis revealed evolutionary divergence as well as genome expansion and contraction of individual Polyporaceae family species. Bioinformatics investigation identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary-metabolite biosynthesis, which included multiple terpenoids, nonribosomal peptides, and polyketides. The locations of biosynthetic core genes were mapped and displayed on chromosomes and contigs. Totals of 143 proteins from 126 coding genes were identified and divided into 14 cytochrome P450 families. Furthermore, the biosynthetic network of tetracyclic triterpenoid active components was postulated by genome mining of related genes combined with the molecular network of metabolites. The genome analysis of L. sulphureus in this study improves the understanding of the biosynthesis of active compounds, which will lay a theoretical foundation for subsequent research on active-compound biosynthesis and promote the application of Laetiporus in the field of drug research and functional-food creation. IMPORTANCE L. sulphureus is a parasitic basidiomycete fungus that causes brown rot. The fruiting bodies of L. sulphureus are used as ancient medicines in China and Europe to cure cancer, analgesia, cough, and rheumatism and are considered a functional food that regulates the body and improves health. L. sulphureus was inferred to be a tetrapolar system based on a high-quality genome, which will aid molecular breeding and artificial farming. Screening polysaccharide synthesis candidate genes and comparing carbohydrate-associated genes in brown-rot basidiomycetes help understand their growth. Identifying core genes for secondary-metabolite biosynthesis, gene cluster family analysis, and comparative cluster analysis will guide heterologous-biosynthesis investigations of these genes and help elucidate the biosynthetic pathways for L. sulphureus bioactive natural components. The biosynthesis network of tetracyclic triterpenes was mapped using metabolite profiling and genome scanning. This work explores the biosynthetic capacity of L. sulphureus-derived natural products and lays the foundation for biosynthetic studies of them.

Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19.

Scutellariae radix ("Huang-Qin" in Chinese) is a well-known traditional herbal medicine and popular dietary supplement in the world, extensively used in prescriptions of TCMs as adjuvant treatments for coronavirus pneumonia 2019 (COVID-19) patients in China. According to the differences in its appearance, Scutellariae radix can be classified into two kinds: ZiQin (1∼3 year-old Scutellariae baicalensis with hard roots) and KuQin (more than 3 year-old S. baicalensis with withered pithy roots). In accordance with the clinical theory of TCM, KuQin is superior to ZiQin in cooling down the heat in the lung. However, the potential active ingredients and underlying mechanisms of Scutellariae radix for the treatment of COVID-19 remain largely unexplored. It is still not clear whether there is a difference in the curative effect of ZiQin and KuQin for the treatment of COVID-19. In this research, network pharmacology, LC-MS based plant metabolomics, and in vitro bioassays were integrated to explore both the potential active components and mechanism of Scutellariae radix for the treatment of COVID-19. As the results, network pharmacology combined with molecular docking analysis indicated that Scutellariae radix primarily regulates the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin, and blocks SARS-CoV-2 spike binding to human ACE2 receptors. In vitro bioassays showed that baicalein and scutellarein exhibited more potent anti-inflammatory and anti-infectious effects than baicalin, the component with the highest content in Scutellariae radix. Moreover, baicalein inhibited SARS-CoV-2's entry into Vero E6 cells with an IC50 value of 142.50 µM in a plaque formation assay. Taken together, baicalein was considered to be the most crucial active component of Scutellariae radix for the treatment of COVID-19 by integrative analysis. In addition, our bioassay study revealed that KuQin outperforms ZiQin in the treatment of COVID-19. Meanwhile, plant metabolomics revealed that baicalein was the compound with the most significant increase in KuQin compared to ZiQin, implying the primary reason for the superiority of KuQin over ZiQin in the treatment of COVID-19.

Schisantherin D from Schisandra chinensis (Turcz.) Baill. exhibits anti-liver fibrosis capacity via modulating ETBR involved signaling, an in vitro and in vivo study.

Excess levels of chemical hepatotoxicants (alcohol, aflatoxin B1), oxidative drugs (acetaminophen) and some cytokines (ET-1, TGF-ß1) can induce chronic or acute liver injury. After these, the severe hepatic disease, especially the liver fibrosis (LF) occurs without taking measures, which brings threat to human health. The dibenzocyclooctadiene lignans of S. chinensis (SCDLs) were found to act as the hepatoprotective components via blocking endothelin B receptor (ETBR). While study on its anti-LF mechanisms especially for its refined compound of schisantherin D (SC-D) is still a lack. So this study aims to investigate the anti-fibrosis effect of SC-D with in vitro and in vivo assays. Bioinformatics analysis revealed the close relations of ETBR to Smad2, Smad3, Nrf2, etc. in LF-related signaling pathways (such as TGF-ß/Smad and Nrf2/ARE). Histopathological staining on livers showed the recovery trend in SC-D treated LF mice. SC-D also modulated expressions of ETBR and fibrosis or anti-oxidative related proteins (such as TIMP1, p-Smad2/3, Nrf2, Smad7, etc.) in LF mice livers. Serum levels of TNF-α, COLI, ALT, AST and LDH in SC-D treated mice were also downregulated compared with LF mice, and upregulated expression of GSH. In vitro studies, SC-D also modulated expressions of LF-related proteins to the normal tendency in LX-2 cell, while weakened its anti- LX-2 proliferation effect by transfections of si-Smad7 or si-Nrf2. Accordingly the anti-LF approach of SC-D showed relations with modulating ETBR linked fibrosis and anti-oxidative related signaling. Also, Smad7 and Nrf2 might be the key factors for SC-D mediated anti-LF effect.

Further sesquiterpenoids from Pittosporum qinlingense and their anti-inflammatory activity.

Four new sesquiterpenoid glycoside esters, Pitqinlingoside N-Q (1-4), together with eleven known metabolites (5-15), were isolated from 95% EtOH extract of the twigs, fruits and leaves of P. qinlingense. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including IR, UV, HRMS, NMR and electronic circular dichroism spectra. Unusal glycoside esters are characterized by the presence of polyacylated ß-D-fucopyranosyl and ß-d-glucopyranosyl units. Pitqinlingoside N (1), O (2), P (3), boscialin (5) and arvoside C (6) showed significant nitric oxide production inhibition in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values ranging from 1.58 to 28.74 µM. Structure-activity relationships of the isolated compounds are discussed.

Huangjia Ruangan Granule Inhibits Inflammation in a Rat Model with Liver Fibrosis by Regulating TNF/MAPK and NF-κB Signaling Pathways.

The Huangjia Ruangan granule (HJRG) is a clinically effective Kampo formula, which has a significant effect on liver fibrosis and early liver cirrhosis. However, the mechanism underlying HJRG in treating liver fibrosis remains unclear. In this study, carbon tetrachloride (CCl4) was used to induce liver fibrosis in rats to clarify the effect of HJRG on liver fibrosis and its mechanism. Using network pharmacology, the potential mechanism of HJRG was initially explored, and a variety of analyses were performed to verify this mechanism. In the liver fibrosis model, treatment with HJRG can maintain the liver morphology, lower the levels of AST and ALT in the serum, and ameliorate pathological damage. Histopathological examinations revealed that the liver structure was significantly improved and fibrotic changes were alleviated. It can effectively inhibit collagen deposition and the expression of α-SMA, reduce the levels of the rat serum (HA, LN, PC III, and Col IV), and inhibit the expression of desmin, vimentin, and HYP content in the liver. Analyzing the results of network pharmacology, the oxidative stress, inflammation, and the related pathways (primarily the TNF signaling pathway) were identified as the potential mechanism of HJRG against liver fibrosis. Experiments confirmed that HJRG can significantly increase the content of superoxide dismutase and glutathione and reduce the levels of malondialdehyde and myeloperoxidase in the rat liver; in addition, HJRG significantly inhibited the content of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and reduced the expression of inflammatory regulators (Cox2 and iNOS). Meanwhile, treatment with HJRG inhibited the phosphorylation of NF-κB P65, IκBα, ERK, JNK, and MAPK P38. Moreover, HJRG treatment reversed the increased expression of TNFR1. The Huangjia Ruangan granule can effectively inhibit liver fibrosis through antioxidation, suppressing liver inflammation by regulating the TNF/MAPK and NF-κB signaling pathways, thereby preventing the effect of liver fibrosis.

Highly oxygenated chemical constitutes and rearranged derivatives with neurotrophic activity from Ganoderma cochlear.

ETHNOPHARMACOLOGICAL RELEVANCE: The morphological characteristics of Ganoderma cochlear (Blume & T. Nees) Bres were identical to G. sinsense J.D. Zhao, L.W. Hsu & X.Q. Zhang, however, with the fungus stipe lying in the back of the pileus. Fruiting bodies and spores of G. cochear have been traditionally used for smoothing, sleeping improvement, memory impairment, anti-aging, and prolonging life. Alzheimer's disease (AD) is a chromic progressive neurodegenerative disorder associated with loss of memory and cognition. Hallmarks of AD include aging, amyloid-ß plaques, neurofibrillary tangles, neuron loss, neuronal degeneration, network disruption, cognitive dysfunction, inflammation and oxidation stress. In this study, norlanostanoids from G. cochear are identified as potential neurotrophic chemists related to the memory impairment usage to slow down pathogenetic process and restore neural circuits for AD. AIM OF STUDY: Chemical and biological investigations in this study uncovered the potential constituents related to the traditional usage of G. cochlear. MATERIALS AND METHODS: The extract of the mushrooms was purified using various column chromatography techniques and high-performance liquid chromatography (HPLC). The structures of the isolates were elucidated by combination of spectral, and single crystal X-ray diffraction analysis. The neurotrophic activity was evaluated by the differentiation state of PC12 cells, and the dose-dependent and time-dependant expression of growth-associated protein (GAP-43) was analyzed by western blotting. RESULTS: Ganorbifates J-T (1-11), eleven previously undescribed triterpenoids together with five known trinorlanostanoids (12-16) were isolated from the fruiting bodies of G. Cochlear. Among them, ganorbifates N-O (5-6) had a demethylation at C-28 compared to the classic skeleton of 3,4-seco-25,26,27-trinorlanostanoids to form a new group of 3,4-seco-25,26,27,28-tetranorlanostanoids. Based on this, a novel skeleton of ganorbifate M (4) was further established by the arrangement of C-29 from C-4 to C-7. A plausible biosynthetic pathway of compounds 4-6 was proposed. Eight of the sixteen isolates showed neurotrophic activity with the concentration of 10 µM. Furthermore, compound 15 exhibited a dose-dependent neurogenic activity, and also strengthened the expression of the growth-associated protein (GAP-43) in NGF-induced PC-12 cells, whereas 11 showed an inhibitory effect at higher concentration. CONCLUSION: These results demonstrated that 3,4-seco-norlanostanoids had reliable potential in promoting the outgrowth of PC-12 cells and could be used in the prevention and treatment of Alzheimer's disease, which is consist with the beneficial effects of G. Cochlear.

Lignans from Eucommia ulmoides Oliver leaves exhibit neuroprotective effects via activation of the PI3K/Akt/GSK-3ß/Nrf2 signaling pathways in H2O2-treated PC-12 cells.

BACKGROUND: Neuronal apoptosis and oxidative stress have the most crucial influence on neurodegenerative diseases, including Parkinson's disease. Rat adrenal pheochromocytoma cells (PC-12) induced by H2O2 are one of the primary in vitro models of Parkinson's disease (PD) . Previous studies have found that E ulmoides leaf extract exerts good neuroprotective activity and has the potential to treat neurodegenerative diseases. However, the molecular pathways involved in the neuroprotective effects of its primary leaf component, lignans, have not yet been well elucidated yet. PURPOSE: This study aimed to evaluate the neuroprotective effects of lignans in E. ulmoides leaves and to explore the underlying mechanism. METHODS: Cell viability was measured using the CCK-8 assay. Apoptosis was assessed by calcein/PI staining. The release levels of ROS and LDH were assessed using a commercial assay kit. The enzyme activities of SOD and GPx were measured using kits. The establishment of the compound-target-pathway-disease network was performed using a database and computer software. Antioxidant proteins (HO-1, NQO-1, and Cat) and related regulatory proteins (Nrf2, GSK-3ß, p-GSK 3ß (Ser 9), Akt, p-Akt (Tyr326), PI3K) were detected by western blotting. Apoptosis in the zebrafish head was assessed using acridine orange (AO) staining. RESULTS: In the present study, 12 lignans were isolated and characterized from E. ulmoides leaves, including a new compound, (-)-7­epi-pinoresinol mr1 (1). Compounds 1-12 exerted neuroprotective effects in H2O2-treated PC-12 cells by increasing cell viability, improving the enzyme activity of SOD and GPx, and reducing levels of ROS and LDH. Compared to the positive control group (25 µM hesperetin), cell viability in response to 25 µM compound 1 (78.0 ± 0.8%) was highest, but its relative percent LDH release (20.1 ± 2.5%) was the lowest; 25 µM compound 4 resulted in the lowest ROS release levels (101.7 ± 2.6%) and highest SOD enzyme activity (35.9 ± 4.2 U/mg), and the GPx enzyme activity of 25 µM compound 1 was strongest (197.6 ± 0.6 U/mg). Next, the potential targets (PI3K, GSK-3ß) of the test compounds' antioxidant activity were identified using pharmacological network analysis. Using DAVID software for pharmacological network analysis, potential targets (PI3K, GSK-3ß, and SOD2) of 12 lignans were identified. Based on the initial screening results, biological experiments confirmed that diepoxylignans 1, 2, and 4 exerted significant neuroprotection by regulating the PI3K/AKT/GSK-3ß/Nrf2 signaling pathways, increasing protein expression of HO-1, NQO-1, and CAT, and enhancing the antioxidant enzyme activity of SOD and GPx. CONCLUSION: Our experiments first propose that the diepoxylignans from E. ulmoides leaves exert neuroprotective effects via activation of the PI3K/Akt/GSK-3ß/Nrf2 signaling pathway. These findings further indicate that lignans could be the primary components of E. ulmoides Oliver as agents for the prevention and treatment of neurodegenerative diseases. Collectively, Eucommia ulmoides leaves with important research value may be a potential candidate for traditional Chinese medicine for treating oxidative stress-related neurodegenerative diseases.