The water extract of Amydrium sinense (Engl.) H. Li ameliorates Isoproterenol-induced cardiac hypertrophy through inhibiting the NF-κB signaling pathway.

OBJECTIVE: Pathologic cardiac hypertrophy (PCH) is a precursor to heart failure. Amydrium sinense (Engl.) H. Li (AS), a traditional Chinese medicinal plant, has been extensively utilized to treat chronic inflammatory diseases. However, the therapeutic effect of ASWE on PCH and its underlying mechanisms are still not fully understood. METHODS: A cardiac hypertrophy model was established by treating C57BL/6 J mice and neonatal rat cardiomyocytes (NRCMs) in vitro with isoprenaline (ISO) in this study. The antihypertrophic effects of AS water extract (ASWE) on cardiac function, histopathologic manifestations, cell surface area and expression levels of hypertrophic biomarkers were examined. Subsequently, the impact of ASWE on inflammatory factors, p65 nuclear translocation and NF-κB activation was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that oral administration of ASWE effectively improved ISO-induced cardiac hypertrophy in mice, as evidenced by histopathological manifestations and the expression levels of hypertrophic markers. Furthermore, the in vitro experiments demonstrated that ASWE treatment inhibited cardiac hypertrophy and suppressed inflammation response in ISO-treated NRCMs. Mechanically, our findings provided evidence that ASWE suppressed inflammation response by repressing p65 nuclear translocation and NF-κB activation. ASWE was found to possess the capability of inhibiting inflammation response and cardiac hypertrophy induced by ISO. CONCLUSION: To sum up, ASWE treatment was shown to attenuate ISO-induced cardiac hypertrophy by inhibiting cardiac inflammation via preventing the activation of the NF-kB signaling pathway. These findings provided scientific evidence for the development of ASWE as a novel therapeutic drug for PCH treatment.

Promising remedies for cardiovascular disease: Natural polyphenol ellagic acid and its metabolite urolithins.

BACKGROUND: Cardiovascular disease (CVD) is a significant worldwide factor contributing to human fatality and morbidity. With the increase of incidence rates, it is of concern that there is a lack of current therapeutic alternatives because of multiple side effects. Ellagic acid (EA), the natural polyphenol (C14H6O8), is abundant in pomegranates, berries, and nuts. EA and its intestinal microflora metabolite, urolithins, have recently attracted much attention as a potential novel "medicine" because of their wide pharmacological properties. PURPOSE: This study aimed to critically analyze available literature to summarize the beneficial effects of EA and urolithins, and highlights their druggability and therapeutic potential in various CVDs. METHODS: We systematically studied research and review articles between 1984 and 2022 available on various databases to obtain the data on EA and urolithins with no language restriction. Their cardiovascular protective activities, underlying mechanism, and druggability were highlighted and discussed comprehensively. RESULTS: We found that EA and urolithins may exert preventive and curative effects on CVD with negligible side effects and possibly regulate lipid metabolism imbalance, pro-inflammatory factor production, vascular smooth muscle cell proliferation, cardiomyocyte apoptosis, endothelial cell dysfunction, and Ca2+ intake and release. Potentially, this may lead to the prevention and amelioration of atherosclerosis, hypertension, myocardial infarction, cardiac fibrosis, cardiomyopathy, cardiac arrhythmias, and cardiotoxicities in vivo. Several molecules and signaling pathways are associated with their therapeutic actions, including phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, NF-κB, nuclear factor erythroid-2 related factor 2, sirtuin1, miRNA, and extracellular signal-regulated kinase 1/2. CONCLUSION: In vitro and in vivo studies shows that EA and urolithins could be used as valid candidates for early prevention and effective therapeutic strategies for various CVDs.

Curcumin-Loaded Platelet Membrane Bioinspired Chitosan-Modified Liposome for Effective Cancer Therapy.

Cancer is a serious threat to human health, and chemotherapy for cancer is limited by severe side effects. Curcumin (CUR) is a commonly used natural product for antitumor treatment without safety concerns. However, low bioavailability and poor tumor accumulation are great obstacles for its clinical application. Our previous research has demonstrated that platelet membrane-camouflaged nanoparticles can efficiently ameliorate the in vivo kinetic characteristics and enhance the tumor affinity of payloads. Nevertheless, the antitumor efficiency of this formulation still needs to be thoroughly investigated, and its drug release behavior is limited. Herein, CUR-loaded platelet membrane bioinspired chitosan-modified liposome (PCLP-CUR) was constructed to improve CUR release. PCLP-CUR was shown to have long retention time, improved bioavailability, strong tumor targeting capacity and effective cellular uptake. The incorporation of chitosan enabled PCLP-CUR to release cargoes quickly under mild acidic tumor conditions, leading to more complete drug release and favoring subsequent treatment. Both in vitro and in vivo investigations showed that PCLP-CUR could significantly enhance the anticancer efficacy of CUR with minimal side effects through biomimetic membrane and chitosan modification. In summary, this developed delivery system can provide a promising strategy for tumor-targeting therapy and phytochemical delivery.

Comparative Analysis of the Metabolites and Biological Activity of Cultivated and Wild Lignosus rhinocerotis.

In this paper, Lignosus rhinocerotis (Cooke) Ryvarden (L. rhinocerotis) cultivated in rice medium (LRR) and in sawdust medium (LRS) was harvested. Then, in terms of the LRR, LRS, and wild L. rhinocerotis (LRW), the total flavonoid contents, total polyphenol contents, total polysaccharide contents, and metabolites were detected; antioxidants of their aqueous extracts and anti-inflammatory of their polysaccharides were performed. In addition, the possible mechanism of the polysaccharides of L. rhinocerotis inhibiting lung damage was elucidated. The results showed that 32 compounds were characterized in L. rhinocerotis, including flavonoids, terpenoids, lignans, and steroids and there were 20 compounds in cultivated and wild L. rhinocerotis; LRR has the highest total polyphenol and flavonoid contents, as well as ABTS and DPPH scavenging capacity. The total polysaccharide contents and the FRAP scavenging capacity of wild L. rhinocerotis were higher than those of cultivated L. rhinocerotis. The inhibition of polysaccharides of LRW (PLRW) on LPS-induced MRC-5 damage was stronger than that of the polysaccharides from cultivated L. rhinocerotis. The PLRW may alleviate lung damage by inhibiting the NLRP3 pathway and thereby suppressing the inflammatory response. In summary, both cultivated and wild L. rhinocerotis are abundant in bioactive components and have antioxidant and anti-inflammatory activities.

Hirsutine, a novel megakaryopoiesis inducer, promotes thrombopoiesis via MEK/ERK/FOG1/TAL1 signaling.

BACKGROUND: Thrombocytopenia (TP) remains a challenge in clinical hematology. TP may have serious consequences, such as recurrent skin and mucosal bleeding and increased risk of intracranial and internal organ hemorrhage. However, effective and safe therapeutic drugs for the long-term management of TP are still lacking. PURPOSE: This study aimed to identify more effective active compounds for TP therapy. METHODS: Liquid chromatography-mass spectrometry-nuclear magnetic resonance analysis was used to confirm the medicinal species and chemical structure of Hirsutine (HS). The proliferation of HS was examined by Cell Counting Kit (CCK-8) assay on cells lines. The effect of HS on megakaryocyte differentiation was analyzed by evaluating the expression of CD41, CD42b, and DNA ploidy via flow cytometry (FCM). The morphology of megakaryocytes and intermediate cells was observed using an optical microscope. K562 cells were then stained with Giemsa and benzidine. qRT-PCR was used to examine the mRNA expression of GATA-1, GATA-2, FOG-1, TAL-1, RUNX-1, NF-E2, and KLF-1 in K562 cells. Protein levels of the transcription factors were analyzed by western blotting. An MEK inhibitor was used to verify the relationship between the MEK/ERK signaling pathway and CD41/CD42b (FCM), FOG-1, and TAL-1. The Kunming thrombocytopenia mouse model was established by X-ray irradiation (4 Gy) and used to test HS activity and related hematopoietic organ index in vivo. Finally, computer simulations of molecular docking were used to predict the binding energies between HS-MEK and HS-ERK. RESULTS: We preliminarily identified HS by screening a plant-sourced compound library for natural compounds with megakaryocytic differentiation and maturation (MKD/MKM)-promoting activity. We found that HS not only enhanced MKD/MKM of K562 and Meg01 cells, but also suppressed the decline of peripheral platelet levels in X-ray-induced myelosuppressive mice. In addition, HS promoted MKD via activation of MEK-ERK-FOG1/TAL1 signaling, which may be the key molecular mechanism of HS action in TP treatment. Molecular docking simulations further verified that HS targets the signaling protein MEK with high-affinity. CONCLUSION: In this study, we report for the first time that hirsutine boosts MKD/MKM through the MEK/ERK/FOG1/TAL1 signaling pathway and thus represents a promising treatment option for TP.

Yao medicine Amydrium hainanense suppresses hepatic fibrosis by repressing hepatic stellate cell activation via STAT3 signaling.

Ethnopharmacological relevance: Hepatic fibrosis (HF) occurs in response to chronic liver injury and may easily develop into irreversible liver cirrhosis or even liver cancer. Amydrium hainanense water extract (AHWE) is a water-soluble component extracted from the Yao medicine Amydrium hainanense (H.Li, Y.Shiao & S.L.Tseng) H.Li, which is commonly used for treating inflammatory diseases in folk. Previous evidence suggested that AHWE significantly inhibited hepatic stellate cell activation. However, little is known regarding the therapeutic effect of AHWE in HF and its underlying action mechanism. Objective: Investigation of the therapeutic effect of AHWE in HF and its underlying mechanism. Methods: The therapeutic effect of AHWE was tested in vivo using an HF mouse model via an intraperitoneal injection of carbon tetrachloride (CCl4). Histological evaluation of liver injury and fibrosis were tested by H&E staining and Masson's trichrome staining. Serum levels of ALT, AST, collagen type I (Col I), and hydroxyproline (HYP) were measured. The mRNA expression of liver fibrotic and inflammatory genes were tested, and the protein levels of alpha smooth muscle actin (α-SMA) and signal transducers and activators of transcription 3 (STAT3) were analyzed. The in vitro experiments were conducted using HSC-T6 and RAW264.7 cell lines. Results: Treatment with AHWE significantly reversed histopathological liver damage and liver function abnormalities in CCl4 mouse model. Also, the serum levels of ALT, AST, Col I, and HYP in CCl4-induced HF mice were improved in AHWE treatment. Further, AHWE showed a remarkable inhibitory effect on the expression of fibrosis markers (Acta2, Col1a1, and Col3a1) and inflammatory factors (Stat3, Tnfa, Il6, and Il1b) induced by CCl4. The results of in vitro experiments were consistent with those obtained in vivo. In addition, it is shown that STAT3 signaling was involved in the anti-fibrotic effects of AHWE as evidenced by STAT3 overexpression. Conclusion: The present study proposed a novel ethnomedicine for HF and suggested the underlying role of STAT3 signaling pathway regulation in this anti-fibrotic effect of the proposed medicine. These findings would serve as solid scientific evidence in support of the development of AHWE as a novel alternative or complementary therapy for HF prevention and treatment.

A Comprehensive Review of Genus Sanguisorba: Traditional Uses, Chemical Constituents and Medical Applications.

Genus Sanguisorba (family: Rosaceae) comprises nearly 148 species, distributed widely across the temperate and subtropical regions of the Northern Hemisphere. Sanguisorba officinalis L. (S. officinalis) has been used as a hemostatic and scald treating medicine in China for a long time. Numerous studies have demonstrated that plant extracts or monomers from S. officinalis exhibit several pharmacological effects, such as anti-cancer, anti-virus, anti-inflammation, anti-bacteria, neuroprotective and hepatoprotective effects. The other species of genus Sanguisorba are also being studied by researchers worldwide. Sanguisorba minor Scop. (S. minor), as an edible wild plant, is a common ingredient of the Mediterranean diet, and its young shoots and leaves are often mixed with traditional vegetables and consumed as salad. Reports on genus Sanguisorba available in the current literature were collected from Google Scholar, Web of Science, Springer, and PubMed. The Plant List (http://www.theplantlist.org./tpl1.1/search?q=Sanguisorba), International Plant Name Index (https://www.ipni.org/?q=Sanguisorba) and Kew Botanical Garden (http://powo.science.kew.org/) were used for obtaining the scientific names and information on the subspecies and cultivars. In recent years, several in vivo and in vitro experiments have been conducted to reveal the active components and effective monomers of S. officinalis and S. minor. To date, more than 270 compounds have been isolated and identified so far from the species belonging to genus Sanguisorba. Numerous reports on the chemical constituents, pharmacologic effects, and toxicity of genus Sanguisorba are available in the literature. This review provides a comprehensive understanding of the current traditional applications of plants, which are supported by a large number of scientific experiments. Owing to these promising properties, this species is used in the treatment of various diseases, including influenza virus infection, inflammation, Alzheimer's disease, type 2 diabetes and leukopenia caused by bone marrow suppression. Moreover, the rich contents and biological effects of S. officinalis and S. minor facilitate these applications in dietary supplements and cosmetics. Therefore, the purpose of this review is to summarize the recent advances in the traditional uses, chemical constituents, pharmacological effects and clinical applications of genus Sanguisorba. The present comprehensive review may provide new insights for the future research on genus Sanguisorba.

Essential Oil-Rich Chinese Formula Luofushan-Baicao Oil Inhibits the Infection of Influenza A Virus through the Regulation of NF-κB P65 and IRF3 Activation.

BACKGROUND: Luofushan-Baicao Oil (LBO) is an essential oil-rich traditional Chinese medicine (TCM) formula that is commonly used to treat cold, cough, headache, sore throat, swelling, and pain. However, the anti-influenza activities of LBO and the underlying mechanism remain to be investigated. METHODS: The in vitro anti-influenza activity of LBO was tested with methyl thiazolyl tetrazolium (MTT) and plaque assays. The effects of LBO on the expressions of viral nucleoprotein and cytokines were evaluated. In the polyinosinic-polycytidylic acid- (Poly I: C-) induced inflammation model, the influences of LBO on the expression of cytokines and the activation of NF-κB P65 (P65) and interferon regulatory factor 3 (IRF3) were tested. After influenza A virus (IVA) infection, mice were administered with LBO for 5 days. The lung index, histopathologic change, the expression of viral protein, P65, and IRF3 in the lung tissue were measured. The levels of proinflammatory cytokines in serum were examined. RESULTS: In vitro, LBO could significantly inhibit the infection of IVA, decrease the formation of plaques, and reduce the expression of viral nucleoprotein and cytokines. LBO could also effectively downregulate the expression of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interferon-ß and the activation of P65 and IRF3 in Poly I:C-treated cells. In the IVA-infected mice model, inhalation of LBO with atomizer could decrease the lung index, alleviate the pathological injury in the lung tissue, and reduce the serum levels of IL-1ß and IL-6. LBO could significantly downregulate the expression of viral protein (nucleoprotein, PB2, and matrix 2 ion channel) and the phosphorylation of P65 and IRF3 in the lungs of mice. CONCLUSION: The therapeutic effects of LBO on treating influenza might result from the regulation of the immune response of IVA infection. LBO can be developed as an alternative therapeutic agent for influenza prevention.

Plumula Nelumbinis: A review of traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety.

ETHNOPHARMACOLOGICAL RELEVANCE: Plumula Nelumbinis, the green embryo of the mature seeds of Nelumbo nucifera Gaertn, has a medical history of over 400 years. It is widely used for clearing the heart and heat, calming the mind, and promoting astringent essence and hemostasis in traditional Chinese medicine. Moreover, it usually dual use as food and medicine. This review aimed to evaluate the therapeutic potential of Plumula Nelumbinis by summarizing its botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety. METHODS: This review summarized published studies on Plumula Nelumbinis in the Chinese Pharmacopoeia and literature databases including PubMed, Web of Science, Baidu Scholar, Wiley and China Knowledge Resource Integrated Database (CNKI), and limits the different research articles in botany, traditional uses, phytochemistry, pharmacology, pharmacokinetics and safety about Plumula Nelumbinis. RESULTS: Plumula Nelumbinis is used to treat hypertension, arrhythmia, severe aplastic anemia, insomnia, encephalopathy and gynecological disease in traditional Chinese medicine and clinical studies. More than 130 chemicals have been isolated and identified from Plumula Nelumbinis, including alkaloids, flavonoids, polysaccharides and volatile oil. In addition, pharmacological effects, such as protective effects against cardiovascular diseases, neurological diseases, lung and kidney injury, anti-inflammatory and anticancer activities, were also evaluated by in vitro and in vivo studies. Moreover, the potential signaling pathways regulated by Plumula Nelumbinis in cardiovascular and neurological diseases and perspectives on Plumula Nelumbinis research were discussed. CONCLUSION: Plumula Nelumbinis, a commonly used Chinese medicine, has a variety of traditional and modern therapeutic uses. Some traditional uses, especially the treatment of cardiovascular and neurological diseases, have been verified by pharmacological investigation. However, the pharmacological molecular mechanisms, pharmacokinetics and toxicology of Plumula Nelumbinis are still incomplete. In the future, a series of systematic studies on active compounds identification, pharmacological mechanism clarification, quality and safety evaluation are necessary.

Preparation of P-g-C3N4-WS2 nanocomposite and its application in photoelectrochemical detection of 5-formylcytosine.

DNA formylation (5-formylcytosine, 5fC) is a major epigenetic modification involved in alterations in the DNA double helix structure and protein identification. Due to the low amount in all mammalian tissues and cells, it is necessary to develop a rapid, sensitive and efficient method for detecting 5fC for further understanding the biological functions of 5fC. Thus, a novel PEC biosensor was constructed using P-g-C3N4-WS2 nanocomposite as photoactive material. Firstly, AuNPs/P-g-C3N4-WS2/ITO electrode was prepared as substrate electrode. Secondly, the probe DNA and complementary DNA (containing 5fC base) was modified to the electrode surface based on the formation of Au-S bonds between AuNPs and thiol group on the probe DNA and hybridization, respectively. Finally, the amino functionalized MnO2 nanoflowers were further modified to the electrode surface by covalent interaction between the aldehyde group on the 5fC and the amino group on MnO2 nanoflowers. The sensitive and specific detection of 5fC can be achieved by oxidizing ascorbic acid with MnO2 nanoflowers and quenching the photoactivity of P-g-C3N4-WS2 nanocomposite. The sensor has a detection range of 0.01-200 nM and a detection limit of 3.8 pM. Moreover, this sensor has excellent detection specificity, stability and reproducibility.

The identification of highly similar crude oils by infrared spectroscopy combined with pattern recognition method.

Based on attenuated total reflectance mid-infrared spectroscopy and moving window correlation coefficient method, a efficient analytical tool is presented for rapid identification of crude oil type. Spectra between highly similar crude oils can be easily distinguished by the spectral searching method. Compared with NIR, IR method can distinguish highly similar mixed crude oils given in the study. Parameters of the moving window correlation coefficient method are studied in the paper.