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Sophora flavescens Ait.- Angelica sinensis (Oliv.) Diels drug pairing (SA) is a transformed drug pairing from Shengui pill, a traditional Chinese medicine prescription in the ninth volume of Traditional Chinese Medicine classic "Gu Jin Yi Jian", which is famous for clearing heat, moistening dryness, and promoting blood circulation. It is commonly used in the treatment of eczema, a skin condition that causes itching and inflammation. Despite its widespread use, there is still limited research on the mechanism of how SA treats eczema. This paper aims to fill this gap by conducting animal experiments to uncover the mechanism behind SA's therapeutic effects on eczema. Our findings provide a solid foundation for the clinical use of this TCM prescription. The basic purpose of this study is to clarify the therapeutic mechanism of Sophora flavescens-Angelica sinensis (SA) in the treatment and control of eczema. The chemical compositions of SA were analyzed using HPLC-Q-Orbitrap-MS. In vivo, a mouse model of eczema was created, and the serum levels of TNF-α and IL-1β were quantified using an enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining was performed to assess the pathological state of the mouse skin, and immunohistochemical technique (IHC) was employed to estimate the contents of TNF-α, TLR4, and NF-κB semi-quantitatively. The expression levels of TLR4, MyD88, and NF-κB mRNA were determined through real-time quantitative polymerase chain reaction (qRT-PCR). Western Blotting was utilized to identify the protein levels of TLR4, MyD88, and NF-κB in mouse skin tissue. SA identified 18 active chemicals, some of which were shown in vivo to inhibit the TLR4/MyD88/NF-κB signaling pathway while reducing serum levels of TNF-α and IL-1β, making them ideal agents for the treatment of eczema. SA's anti-inflammatory properties are attributed to its ability to reduce serum levels of TNF-α and IL-1β, likewise inhibit the TLR4/MyD88/NF-κB signaling pathway. [Display omitted] • Application of SG in the treatment of acute eczema. • Study on the mechanism of SG in the treatment of acute eczema for the first time. • The experiments were carried out in vivo. • The results showed that SG could reduce the expression of IL-1β and TNF-α. • The anti-inflammation effect of SG is mediated by TLR4/MyD88/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Licorice can nourish Pi (spleen) and thereby strengthening the digestive system according to the theory of traditional Chinese medicine. Licorice has been generally used in the compound prescription to treat intestinal inflammatory disease. Licochalcone A (Lico A) is one of the characteristic molecules from licorice. T-UCRs, which are transcribed from ultraconserved regions, are a new class of long noncoding RNAs related to the renewal of intestinal epithelial renewal. This study aimed to investigate the effect and the uc.173-related mechanism of Lico A on intestinal epithelial renewal. IE-6 and Caco-2 cells were used to evaluate the effect of Lico A on apoptosis, proliferation, and migration of IECs. The intestinal organoid was used to investigate ex vivo effect and mechanism of Lico A promoting intestinal organoid development. C57BL/6J mice (both normal and uc.173-deficient ones) were used to examine the in vivo effect of Lico A on the renewal of intestinal mucosa. The expression of three T-UCRs related to the intestinal mucosa renewal was altered in Lico A-treated IECs. Lico A promoted the proliferation and inhibited the apoptosis of IECs through uc.173/miR-195 pathway. The development of intestinal organoids and the renewal of intestinal mucosa of mice subjected to the 48-h FAST were all promoted by the treatment of Lico A. Moreover, the growth arrest of uc.173-deficient intestinal organoids and the atrophy of intestinal mucosa in uc.173-deficient mice could be rescued by the Lico A administration. Results in this paper suggest that targeting T-UCRs may be the novel therapeutic approach for the promotion of epithelial regeneration, and through stimulating the regeneration of intestinal mucosa, Lico A may become a new therapeutic agent for the maintenance of intestinal epithelial integrity. Licochalcone A promotes intestinal epithelial renewal through uc.173. [Display omitted] • Licochalcone A from licorice affects the expression of three T-UCRs related to the regeneration of intestinal mucosa. • Licochalcone A promotes the development of intestinal organoids and in vivo renewal of intestinal mucosa. • Licochalcone A reverses uc. 173-induced delay in intestinal epithelial renewal both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Duhuo Jisheng decoction is a traditional Chinese formula that has been widely used in clinical practice to treat osteoarthritis, which has the effects of removing invaded cold and dampness, relieving joint pain. However, it is difficult to determine the effective substances and mechanisms due to assorted herbs and components, and further research is needed. This study was designed to explore and verify the mechanism and targets of DHJSD in the treatment of OA via network analysis and experiments. In this study, the active ingredients of DHJSD were qualitatively analyzed by UPLC-QDA. Network analysis was used to identify common targets and pathways. Next, we explored the therapeutic mechanism of DHJSD through a rat model of knee osteoarthritis. HE staining was used to judge the establishment of the animal model. ELISA and Western blotting were used to verify the expression of key pathway proteins. In this study, seventeen chemical constituents in DHJSD were identified. According to the network analysis, we obtained the potential associated pathways of action. Then, molecular docking and SPR experiments showed that the sixteen identified components had high binding energies to IL-6. HE staining showed that the high-dose group of DHJSD had an obvious therapeutic effect on model rats. Compared with the model group, the levels of IL-1β, TNF-α, IL-6, MMP3, MMP13, ADAMTS4 and ADAMTS5 in serum and the expression of STAT3 and p-STAT3 protein in administration groups were significantly decreased. This result indicated that the IL-6/STAT3 signaling pathway was one of the important pathways regulated by DHJSD to improve OA. [Display omitted] • This paper first identified 17 compounds, found that DHJSD can treat OA by regulating IL-6/STAT3 pathway in vivo. [ABSTRACT FROM AUTHOR]

Ligusticum chuanxiong Hort. (Chuanxiong, LC), as an important traditional Chinese medicine (TCM), can not only be used as a monarch herb but also be used as a classic "Yin-Jing" (引经) medicine in compound prescriptions, e.g., Buyang Huanwu Decoction (BHD). Although LC has the effect of guiding components into the brain in BHD, there is still a lack of scientific evidence on this "Yin-Jing" effects. Herein, we used pharmacokinetics and tissue distributions to investigate "Yin-Jing" effects of LC. To simplify the study, four major constituents in BHD, i.e., Calycosin (CA), astragaloside IV (AI), paeoniflorin (PA), and amygdalin (AM) were combined to form a simple compound (abbreviated as CAPA here) to replace the original BHD in this paper. The Yin-Jing medical property of LC was confirmed by the compatibility of CAPA with LC or its different fractions (Fr. A ∼ Fr. F). To explore the "Yin-Jing" medical property of LC via pharmacokinetics and tissue distributions by ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS). The contents of CA, AI, PA, and AM were simultaneously determined by the established and validated UPLC-QQQ-MS method in different rat tissues and plasma after administration of CAPA with the combination of LC or Fr. A ∼ Fr. F. The pharmacokinetic parameters, e.g., T max , C max , AUC 0–t and MRT 0–t , were calculated to evaluate the efficiency of "Yin-Jing". The C max and AUC 0–t of CA, AI, PA, and AM were remarkably increased in rat brain tissues compared with those of the control group after compatibility of LC. This demonstrated that LC has the Yin-Jing effects on brain tissues. Additionally, Fr. B or Fr. C might be the material basis by specifically studying the distributions of CA, AI, PA, and AM in brain tissue based on mutual compatibility. The effects of Fr. B and Fr. C on distributions of these constituents in other tissues or plasma was also studied to verify the effects of Yin-Jing of LC. The results showed that the same upward trend is found in heart, liver and plasma, but the intensity is insignificant as that in brain tissue. Furthermore, the C max and AUC 0–t of some analytes in the rat spleen, lung, and kidney were significantly decreased compared with the control group (P < 0.05 or 0.01). LC has the function of Yin-Jing, especially guiding the components into the brain tissue. Moreover, Fr. B and Fr. C is suggested to be the pharmacodynamic material basis for the effect of Yin-Jing of LC. These finding explained that it was recommended to add LC into some prescriptions for treating cardiovascular and cerebrovascular diseases caused by Qi deficiency and blood stasis. This has laid a certain foundation for the research on the Yin-Jing efficacy of LC to better clarify the theory of TCM and guide the clinical application of Yin-Jing drugs. [Display omitted] • To explore the Yin-Jing property of LC by pharmacokinetics and tissue distribution. • A UPLC-MS method was established for the determination of analytes in rat tissues and plasma. • LC has the Yin-Jing function, particularly guiding components into the brain. • Fr. B or Fr. C maybe the material basis of LC for its Yin-Jing efficacy. [ABSTRACT FROM AUTHOR]

The roots of Achyranthes bidentata Blume are one of the regularly used herbal drugs in Chinese medicine, and has been applied for strengthening the muscle and bone for a long time. However, its effect on muscle remains unclear. This paper aims to explore the anti-muscle atrophy effect of A. bidentata , and to clarify the possible signaling pathways involved. The saponin extract of the roots of A. bidentata (ABSE) was prepared and analyzed, and its activity on myoblast differentiation was assayed with C2C12 cell culture. ABSE was then orally administered at dosage of 35, 70 and 140 mg/kg/day to disuse-induced muscle atrophy mice. The studies on mice body weight and muscle quality were conducted, and Western blot was used for exploring the possible signaling pathways involved in the muscle protective action aided with transcriptome analysis. The total saponin content of ABSE was 59.1%. ABSE promoted the C2C12 cells differentiation to myotube in C2C12 differentiation assay. Further study with disuse-induced muscle atrophy mice model demonstrated that ABSE significantly increased muscle fiber diameter as well as the proportion of slow muscle fibers. Possible mechanism study aided with transcriptome analysis revealed that ABSE alleviated muscle atrophy at least through activation of PI3K/Akt pathway in vivo & vitro. The saponin extract of the root of A. bidentata (ABSE) has a protective effect on muscle atrophy, and showed a considerable potential in prevention and treatment of muscle atrophy. [Display omitted] • The saponin extract of A. bidentata (ABSE) was prepared and analyzed. • ABSE promoted the differentiation of C2C12 cells to myotubes. • ABSE displayed a protective effect on muscle atrophy in vivo. • ABSE activated PI3K/Akt pathway in vivo & in vitro. • ABSE increased protein levels of Myogenin and MyoD. [ABSTRACT FROM AUTHOR]

Different Physalis plants have been widely employed in traditional medicine for management of diabetes mellitus. Previous studies with respect to the in vivo antidiabetic activity of Physalis plants illustrated that they improved glucose and lipid metabolism in streptozotocin (STZ) -induced diabetic rats yet the mechanism of action of bioactive constituents of the different organs of Physalis plants on diabetes remains obscure. Our objective is to study the effects of the different organs of ground cherry (P. pruinosa) on diabetes in rat models and elucidate their mechanism of actions through serum pharmacochemistry combined to network pharmacology analyses and in-vivo testing. Characterization of the constituents in the drug-dosed serum samples relative to the blank serum after treatment with different extracts was performed by UPLC -MS/MS technique. The absorbed metabolites where then subjected to network pharmacology analysis to construct an interaction network linking "compound-target-pathway". In vivo verification was implemented to determine a hypothesized mechanism of action on a STZ and high fat diet induced type II diabetes mellitus (T2DM) model based on functional and enrichment analyses of the Kyoto Encyclopedia of Genes and Genome and Gene Ontology. Identification of a total of 73 compounds (22 prototypes and 51 metabolites) derived from P. pruinosa extracts was achieved through comparison of the serum samples collected from diabetic control group and extracts treated groups. The identified compounds were found to belong to different classes according to their structural type including withanolides, physalins and flavonoids. The absorbed compounds in the analyzed serum samples were considered as the potential bioactive components. The component-target network was found to have 23 nodes with 17 target genes including MAPK8, CYP1A1 and CYP1B1. Quercetin and withaferin A were found to possess the highest combined score in the C-T network. Integrated serum pharmacochemistry and network pharmacology analyses revealed the enrichment of leaves extract with the active constituents, which can be utilized in T2DM treatment. In the top KEGG pathways, lipid and atherosclerosis metabolic pathways in addition to T2DM pathways were found to be highly prioritized. The diabetic rats, which received leaves extract exhibited a substantial increment in GLUT2, INSR, IRS-1 , PI 3 K-p85 and AKT-ser473 proteins by 105%, 142%, 109%, 81% and 73%, respectively relative to the untreated diabetic group. The immunoblotting performed for MAPK and ERK1/2 part of the inflammatory pathway studied in STZ induced diabetic rats revealed that leaves, calyces and stems extracts resulted in a substantial diminish in p38-MAPK, ERK 1/2 , NF-κB, and TNF-α. Histopathological examination revealed that the hepatic histoarchitecture was substantially improved in the leaves, stems, and clayces-treated rats in comparison with untreated diabetic rats. Further, pancreatic injuries, which induced by STZ were dramatically altered by the treatment with P. pruinosa leaves, calyces and stems extracts. β-cells in diabetic rats received leaves extract disclosed moderate insulin immunostaining with a notable increase in the mean insulin area%. The study in hand offers a comprehensive study to clarify the bioactive metabolites of the different organs of P. pruinosa. The basic pharmacological effects and underlying mechanism of actions in the management of STZ and high fat diet induced T2DM were specifically covered in this paper. [Display omitted] • Mechanism of action of bioactive constituents of Physalis on diabetes type 2 suggested. • Absorbed metabolites subjected to network pharmacology to construct interaction network. • 17 target genes including MAPK8, CYP1A1 and CYP1B1 were top hits. • Diabetic rats receiving leaves extract showed increase in GLUT2, PI 3 K-p85 and AKT-ser473 proteins. • Stems extracts resulted in a significant diminish in p38-MAPK, ERK 1/2 , NF-κB, and TNF-α. [ABSTRACT FROM AUTHOR]

Marsdenia tenacissima (Roxb.) Moon, (M. tenacissima) a traditional herbal medicine, has been used for thousands of years. It is noted in Dian Nan Ben Cao that M. tenacissima is bitter in flavor and cold in property, and extracts possess diverse pharmacological effects, including immunomodulation and anti-tumor activities. The anti-tumor effects of M. tenacissima extracts (MTE) have been repeatedly confirmed, and this medicine has also been extensively applied in cancer treatment or prognostic adjuvant therapy, with significant curative effect. This study aims to comprehensively analyze the anti-tumor mechanism of M. tenacissima starting from the key features of traditional Chinese medicine and by studying the main active components individually to identify anti-tumor targets in the context of hepatocellular carcinoma. Molecular network profiling and multi-omic joint analyses were conducted using an H22 mouse model of hepatocellular carcinoma to determine the main active ingredients in MTE and the underlying anti-tumor mechanisms. Tenacissosides I, H, and G (TI,TH and TG) were found to be the likely active ingredients of MTE in the treatment of hepatocellular carcinoma. These compounds were shown to promote apoptosis, inhibit angiogenesis and improve immune function through targeting P53, JAK-1 and HIF1α, respectively. For the first time, based on the theory that multiple components and multiple targets synergistically exert the beneficial effects of a traditional Chinese medicine, this paper comprehensively analyzes the mechanisms of action of M. tenacissima and provides a novel strategy for the subsequent development of anti-tumor therapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Our recently published paper demonstrated that ethyl acetate fractions obtained from Cymbopogon citratus (DC.) Stapf (C. citratus) leaves, which are consumed as infusion in folk medicine due to their therapeutic properties, are rich in polyphenols and exhibit promising antioxidant activity by acting through different mechanisms in vitro. However, studies regarding the toxicity of these fractions are necessary to investigate their safe use in future biomedical applications. This study aimed to investigate the toxicity of ethyl acetate (obtained in acidic and basic conditions and after the essential oil removal from the leaves) and chloroform fractions, essential oil, and its pure constituents, citral and geraniol. The toxicity of C. citratus samples was evaluated by using Artemia salina (A. salina) and human blood cells (leukocytes and erythrocytes). The A. salina lethality assay demonstrated that C. citratus fractions were moderately toxic with LC 50 values ranging from 146.12 to 433.15 μg mL−1, whereas the essential oil and isolated compounds were highly toxic with LC 50 lower than 100 μg mL−1. Leukocyte viability decreased after incubation in the presence of the fractions obtained after the essential oil removal from the plant leaves, as well as in the presence of essential oil, citral and geraniol. The same samples increased the osmotic fragility of erythrocytes, and field emission gun scanning electron microscopy (FESEM) analysis revealed significant changes in cell morphology. Interestingly, our results suggest that the previous removal of essential oil from plant leaves facilitated the extraction of cytotoxic compounds from C. citratus. It was demonstrated that C. citratus ethyl acetate and chloroform fractions, essential oil, as well citral and geraniol were considered toxic to A. salina , cytotoxic to human blood cells and showed to induce alterations in the erythrocyte membrane at higher concentrations. These fractions will be further investigated to identify the phytochemicals involved in the observed cytotoxic effects and explored using in vivo models. [Display omitted] • Cymbopogon citratus samples and isolated compounds were toxic for Artemia salina. • Citral, geraniol and essential oil increased osmotic fragility in human erythrocytes. • FESEM analysis showed that some samples changed erythrocytes morphology. • The removal of essential oil from leaves enhanced the extraction of cytotoxic compounds. [ABSTRACT FROM AUTHOR]

Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. We use TGF-β1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway. [Display omitted] • This paper provides in-vitro and in-vivo experimental data of XFBD to protect against pulmonary fibrosis. • XFBD could alleviate macrophages infiltration and fibroblast activation in pulmonary fibrosis. • The possible pharmacodynamic mechanism of XFBD is targeting the IL6/STAT3 signaling axis. [ABSTRACT FROM AUTHOR]

Premna microphylla turcz is traditionally used as a folk remedy. Its roots, stems and leaves can be invoked as medicines, which have the functions of detoxification, swelling and hemostasis. It belongs to the Premna in the Verbenaceae and is mainly distributed in the mountains of southeastern China. However, there are few reports of in-depth studies on the anti-inflammatory effects of polysaccharide, which was the main component in Premna microphylla turcz. The flies were fed with standard corn flour-yeast medium to cause inflammation by sodium lauryl sulfate (SDS). The treatment group contained Premna microphylla turcz polysaccharide (pPMTLs) extract. The survival rate was obtained by feeding a vial containing five layers of filter paper, which was infiltrated with the 5% sucrose solution contaminated with SDS or SDS polysaccharide. The microvilli and nucleus of the midgut epithelial cells of different treatments were observed by transmission electron microscope, and the expression of inflammation-related genes was detected by real-time quantitative PCR (qRT-PCR). Finally, 16S rDNA analysis was conducted on the differences in the composition of the intestinal microbes of Drosophil a. In the current study, we showed that pPMTLs significantly prolonged the life span of SDS-inflamed flies from 5 days to 6 days. And pPMTLs reduced the rupture of microvilli in the midgut and restored the nuclear structure. In addition, pPMTLs significantly improved expression level of immune-related genes in Inflammation Drosophila especially the defensin (4.32 ± 0.75 vs 9.97 ± 0.52 SDS-polysaccharide group: SDS group, p < 0.001). The analysis of intestinal microbiota showed that pPMTLs decreased the relative abundance of Raoultella while Wolbachia increased (p < 0.05). Collectively, our results revealed the potential application of pPMTLs in enhancing inflammation defense, which would be enormous significance for the inflammation-related disorders treatment. • PMTLs polysaccharides showed excellent immunomodulatory activity in vivo. • Intestinal immunity was significantly enhanced by PMTLs polysaccharides. • Polysaccharides effectively reduced harmful intestinal bacteria. • Polysaccharides could significantly improve the expression of AMPs. [ABSTRACT FROM AUTHOR]