ABSTRACT
Liver diseases and their related complications endanger the health of millions of people worldwide. The prevention and treatment of liver diseases are still serious challenges both in China and globally. With the improvement of living standards, the prevalence of metabolic liver diseases, including non-alcoholic fatty liver disease and alcoholic liver disease, has increased at an alarming rate, resulting in more cases of end-stage liver disease. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently needed. Glycyrrhizin (GL), a triterpene glycoside from the roots of licorice plants, possesses a wide range of pharmacological and biological activities. Currently, GL preparations (GLPs) have certain advantages in the treatment of liver diseases, with good clinical effects and fewer adverse reactions, and have shown broad application prospects through multitargeting therapeutic mechanisms, including antisteatotic, anti-oxidative stress, anti-inflammatory, immunoregulatory, antifibrotic, anticancer, and drug interaction activities. This review summarizes the currently known biological activities of GLPs and their medical applications in the treatment of liver diseases, and highlights the potential of these preparations as promising therapeutic options and their alluring prospects for the treatment of liver diseases.
Subject(s)
Glycyrrhizic Acid , Liver Diseases , Humans , Glycyrrhizic Acid/pharmacology , Glycyrrhizic Acid/therapeutic use , Liver Diseases/drug therapy , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/pharmacology , Oxidative StressABSTRACT
BACKGROUND: (-)-Asarinin (Asarinin) is the primary component in the extract of the herb Asarum sieboldii Miq. It possesses various functions, including pain relief, anti-viral and anti-tuberculous bacilli effects, and inhibition of tumor growth. Gastric precancerous lesion (GPL) is a common but potentially carcinogenic chronic gastrointestinal disease, and its progression can lead to gastric dysfunction and cancer development. However, the protective effects of asarinin against GPL and the underlying mechanisms remain unexplored. METHODS: A premalignant cell model (methylnitronitrosoguanidine-induced malignant transformation of human gastric epithelial cell strain, MC cells) and a GPL animal model were established and then were treated with asarinin. The cytotoxic effect of asarinin was assessed using a CCK8 assay. Detection of intracellular reactive oxygen species (ROS) using DCFH-DA. Apoptosis in MC cells was evaluated using an annexin V-FITC/PI assay. We performed western blot analysis and immunohistochemistry (IHC) to analyze relevant markers, investigating the in vitro and in vivo therapeutic effects of asarinin on GPL and its intrinsic mechanisms. RESULTS: Our findings showed that asarinin inhibited MC cell proliferation, enhanced intracellular ROS levels, and induced cell apoptosis. Further investigations revealed that the pharmacological effects of asarinin on MC cells were blocked by the ROS scavenger N-acetylcysteine. IHC revealed a significant upregulation of phospho-signal transducer and activator of transcription 3 (p-STAT3) protein expression in human GPL tissues. In vitro, asarinin exerted its pro-apoptotic effects in MC cells by modulating the STAT3 signaling pathway. Agonists of STAT3 were able to abolish the effects of asarinin on MC cells. In vivo, asarinin induced ROS accumulation and inhibited the STAT3 pathway in gastric mucosa of mice, thereby halting and even reversing the development of GPL. CONCLUSION: Asarinin induces apoptosis and delays the progression of GPL by promoting mitochondrial ROS production, decreasing mitochondrial membrane potential (MMP), and inhibiting the STAT3 pathway.
Subject(s)
Dioxoles , Lignans , Precancerous Conditions , Humans , Mice , Animals , Reactive Oxygen Species/metabolism , Signal Transduction , Lignans/pharmacology , Cell Proliferation , Precancerous Conditions/chemically induced , Precancerous Conditions/drug therapy , Precancerous Conditions/pathology , Apoptosis , STAT3 Transcription Factor/metabolism , Cell Line, TumorABSTRACT
The SARS-CoV-2 virus, belonging to the Coronavirus genus, which poses a threat to human health worldwide. Current therapies focus on inhibiting viral replication or using anti-inflammatory/immunomodulatory compounds to enhance host immunity. This makes the active ingredients of traditional Chinese medicine compounds ideal therapies due to their proven safety and minimal toxicity. Previous research suggests that andrographolide and baicalin inhibit coronaviruses; however, their synergistic effects remain unclear. Here, we studied the antiviral mechanisms of their synergistic use in vitro and in vivo. We selected the SARS-CoV-2 pseudovirus for viral studies and found that synergistic andrographolide and baicalein significantly reduced angiotensin-converting enzyme 2 protein level and viral entry of SARS-CoV-2 into cells compared to singal compound individually and inhibited the major protease activity of SARS-CoV-2. This mechanism is essential to reduce the pathogenesis of SARS-CoV-2. In addition, their synergistic use in vivo also inhibited the elevation of pro-inflammatory cytokines, including IL-6 and TNF-α-the primary cytokines in the development of acute respiratory distress syndrome (the main cause of COVID-19 deaths). In conclusion, this study shows that synergistic andrographolide and baicalein treatment acts as potent inhibitors of coronavirus mechanisms in vitro and in vivo-and is more effective together than in isolation.
Subject(s)
Angiotensin-Converting Enzyme 2 , Diterpenes , Flavonoids , SARS-CoV-2 , Humans , Angiotensin-Converting Enzyme 2/metabolism , Down-Regulation , SARS-CoV-2/physiology , Cytokines/metabolism , Antiviral Agents/pharmacology , Antiviral Agents/metabolismABSTRACT
Drought is an important abiotic stress that constrains the quality and quantity of tea plants. The green leaf volatiles Z-3-hexenyl acetate (Z-3-HAC) have been reported to play an essential role in stress responses. However, the underlying mechanisms of drought tolerance in tea plants remain elusive. This study investigated the physiological, proteomic, and phosphoproteomic profiling of two tea plant varieties of Longjingchangye (LJCY) and Zhongcha 108 (ZC108) with contrasting drought tolerance characteristics under drought stress. Physiological data showed that spraying Z-3-HAC exhibited higher activities of superoxide dismutase (SOD) and catalase (CAT) in both LJCY and ZC108 but lower content of malondialdehyde (MDA) in LJCY under drought stress. The proteomic and phosphoproteomic analysis suggested that the drought tolerance mechanism of Z-3-HAC in LJCY and ZC108 was different. Proteomic analyses revealed that Z-3-HAC enhanced the drought tolerance of LJCY by fructose metabolism while enhancing the drought tolerance of ZC108 by promoting glucan biosynthesis and galactose metabolism. Furthermore, the differential abundance phosphoproteins (DAPPs) related to intracellular protein transmembrane transport and protein transmembrane transport were enriched in LJCY, and the regulation of response to osmotic stress and regulation of mRNA processing were enriched in ZC108. In addition, protein-phosphoprotein interactions (PPI) analyses suggested that energy metabolism and starch and sucrose metabolic processes might play critical roles in LJCY and ZC108, respectively. These results will help to understand the mechanisms by which Z-3-HAC enhances the drought resistance of tea plants at the protein level. SIGNIFICANT: Green leaf volatiles (GLVs) are important volatile organic compounds that play essential roles in plant defense against biotic and abiotic stresses. To understand the mechanisms of Z-3-HAC in improving the drought tolerance of tea plants, two contrasting drought tolerance varieties (LJCY and ZC108) were comparatively evaluated by proteomics and phosphoproteomics. This analysis evidenced changes in the abundance of proteins involved in energy metabolism and starch and sucrose metabolic processes in LJCY and ZC108, respectively. These proteins may elucidate new molecular aspects of the drought resistance mechanism of Z-3-HAC, providing a theoretical basis for drought resistance breeding of tea plants.
Subject(s)
Droughts , Proteomics , Proteomics/methods , Plant Breeding , Stress, Physiological , Plant Proteins/metabolism , Starch/metabolism , Sucrose , Tea , Gene Expression Regulation, PlantABSTRACT
The toxic pathogen theory, an important part of the theories of traditional Chinese medicine(TCM), began in the Qin and Han dynasties, formed in the Jin, Sui, Tang, and Song dynasties, developed rapidly in the Ming and Qing dynasties, and conti-nued to develop in contemporary times based on the achievements of its predecessors. The continuous exploration, practice, and inheri-tance of many medical practitioners over the generations have facilitated the enrichment of its connotation. The toxic pathogen is violent, fierce, dangerous, prolonged, rapid in transmission, easy to hurt the internal organs, hidden, and latent, with many changes, and it is closely related to the development of tumor diseases. TCM has a history of thousands of years in the prevention and treatment of tumor diseases. It is gradually realized that the etiology of tumor is mainly attributed to the deficiency of healthy Qi and excess of to-xic pathogen, and the struggle between healthy Qi and toxic pathogen runs through the whole course of tumor, with the deficiency of healthy Qi as the prerequisite and the invasion of toxic pathogen as the root of the occurrence. The toxic pathogen has a strong carcinogenic effect and is involved in the whole process of tumor development, which is closely related to the malignant behaviors of tumors, including proliferation, invasion, and metastasis. This study discussed the historical origin and modern interpretation of the toxic pathogen theory in the prevention and treatment of tumors, with aims of sorting out the theoretical system based on the toxic pathogen theory in the treatment of tumor diseases, and illustrating the importance of the toxic pathogen theory in the treatment of tumors in the context of modern research on pharmacological mechanisms and the development and marketing of relevant anti-tumor Chinese medicinal preparations.
Subject(s)
Medicine, Chinese Traditional , Cell Movement , ChinaABSTRACT
Highly photoluminescent N-doped carbon quantum dots (N-CDs) which the quantum yield reached 63% were prepared through hydrothermal treatment. The obtained N-CDs displayed a uniform distribution of particle size, superior stability in high-salt conditions, and excellent sensitivity. A green fluorescence probe based on N-CDs was constructed for ultrasensitive determination of myricetin in vine tea on account of the static quenching. The N-CDs presented excellent linear fluorescence response in the concentration range of 0.2-40 µM and 56-112 µM and with a low detection limit of 56 nM. Additionally, the practicability of the probe was verified in spiked vine tea sample, and the satisfactory recoveries of myricetin varied from 98.8% to 101.2%, with relative standard deviations in the range of 1.52%-3.48%. It is the first time to employ N-CDs without any material modification as a fluorescence sensor to detect myricetin, which is a promising approach to expand the path for myricetin screening.
Subject(s)
Quantum Dots , Carbon , Nitrogen , Fluorescent Dyes , Spectrometry, Fluorescence , TeaABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Gallic acid (GA) is a natural polyphenolic compound derived from Rhus chinensis Mill. with a variety of biological activities such as astringent sweat, cough, dysentery, hemostasis, and detoxification, and is widely used in China as a treatment for cough, bleeding, and gastrointestinal disorders. In recent years, the anticancer activity of GA has been demonstrated in a variety of cancers, affecting multiple cellular pathways associated with cancer onset, development and progression. AIM OF THE STUDY: To investigate the role and potential mechanism of GA on gastric precancerous lesions (GPL), the key turning point of gastritis to gastric cancer, with the aim of delaying, blocking or reversing the dynamic overall process of "inflammation-cancer transformation" and thus blocking GPL to prevent the development of gastric cancer. MATERIALS AND METHODS: In this study, we established N-Nitroso-N-methylurea (MNU)-induced GPL mice model and induced precancerous lesions of gastric cancer cells (MC), i.e. epithelial mesenchymal transition (EMT), in human gastric mucosal epithelial cells (GES-1) with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We used conventional pathology, immunohistochemistry, RNA sequencing, Western blot and other techniques to study the therapeutic effect of GA on GPL and its possiblemechanism in vitro and in vivo. RESULTS: The results showed that compared with normal GES-1 cells, MC cells had the characteristics of malignant cells such as abnormal proliferation, invasion and metastasis, accompanied by decreased expression of EMT-related protein E-cadherin and increased expression of N-cadherin and Vimentin. GA can inhibit the malignant behavior of MC cell proliferation and induce its G0/G1 phase arrest, which is achieved by downregulating the Wnt/ß-catenin signaling pathway and thereby inhibiting the EMT process. However, when we incubated with the Wnt pathway activator (Wnt agonist 1), the effect of GA was reversed. Furthermore, analysis of human gastric specimens showed that activation of the Wnt/ß-catenin pathway was significantly associated with GPL pathological changes. Meanwhile, GA reversed MNU-induced intestinal metaplasia and partial dysplasia in GPL mice. CONCLUSION: Taken together, these results indicate that GA prevents the occurrence and development of GPL by inhibiting the Wnt/ß-catenin signaling pathway and then inhibiting the EMT process, which may become potential candidates for the treatment of GPL.
Subject(s)
Precancerous Conditions , Stomach Neoplasms , Humans , Mice , Animals , Wnt Signaling Pathway , Epithelial-Mesenchymal Transition , Stomach Neoplasms/genetics , Gallic Acid/pharmacology , Gallic Acid/therapeutic use , Cough , Cell Movement , beta Catenin/metabolism , Cell Proliferation , Precancerous Conditions/chemically induced , Precancerous Conditions/drug therapy , Methylnitronitrosoguanidine , Cadherins/metabolism , Cell Line, TumorABSTRACT
In China, traditional Chinese medicine (TCM) has been widely used for coronavirus infectious disease 2019 (COVID-19) prevention, treatment, and recovery and has played a part in the battle against the disease. A variety of TCM treatments have been recommended for different stages of COVID-19. But, to the best of our knowledge, a comprehensive database for storing and organizing anti-COVID TCM treatments is still lacking. Herein, we developed TCM2COVID, a manually curated resource of anti-COVID TCM formulas, natural products (NPs), and herbs. The current version of TCM2COVID (1) documents over 280 TCM formulas (including over 300 herbs) with detailed clinical evidence and therapeutic mechanism information; (2) records over 80 NPs with detailed potential therapeutic mechanisms; and (3) launches a useful web server for querying, analyzing and visualizing documented formulas similar to those supplied by the user (formula similarity analysis). In summary, TCM2COVD provides a user-friendly and practical platform for documenting, querying, and browsing anti-COVID TCM treatments, and will help in the development and elucidation of the mechanisms of action of new anti-COVID TCM therapies to support the fight against the COVID-19 epidemic. TCM2COVID is freely available at http://zhangy-lab.cn/tcm2covid/.
ABSTRACT
Cancer stem cells (CSCs) lead to the occurrence and progression of cancer due to their strong tumorigenic, self-renewal, and multidirectional differentiation abilities. Existing cancer treatment methods cannot effectively kill or inhibit CSCs but instead enrich them and produce stronger proliferation, invasion, and metastasis capabilities, resulting in cancer recurrence and treatment resistance, which has become a difficult problem in clinical treatment. Therefore, targeting CSCs may be the most promising approach for comprehensive cancer therapy in the future. A variety of natural products (NP) have significant antitumor effects and have been identified to target and inhibit CSCs. However, pharmacokinetic defects and off-target effects have greatly hindered their clinical translation. NP-based nanoformulations (NPNs) have tremendous potential to overcome the disadvantages of NP against CSCs through site-specific delivery and by improving their pharmacokinetic parameters. In this review, we summarize the recent progress of NPNs targeting CSCs in cancer therapy, looking forward to transforming preclinical research results into clinical applications and bringing new prospects for cancer treatment.
Subject(s)
Biological Products , Neoplasms , Biological Products/pharmacology , Biological Products/therapeutic use , Cell Differentiation , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Neoplastic Stem Cells/pathologyABSTRACT
BACKGROUND AND ETHNOPHARMACOLOGICAL RELEVANCE: Semen aesculi (SA), a traditional Chinese herb, has been used in the treatment of gastrointestinal disease for thousands of years. The escin was the main components of SA. A growing number of research showed that escin has a wide range of pharmacological activities in intestinal barrier dysfunction. AIM OF THE STUDY: Inflammatory bowel diseases (IBD) are an idiopathic disease of the intestinal tract with the hallmark features of mucosal inflammation and loss of barrier function. The theory of traditional Chinese medicine (TCM) suggests that SA plays a potential role in protecting the gastrointestinal diseases. The present study aimed to explore the effects of SA on the intestinal barrier under existing inflammatory conditions and elucidate underlying mechanisms. MATERIALS AND METHODS: The bioactive components of SA and their predicted biological targets were combined to develop a compound target pathway network. It is used to predict the bioactive components, molecular targets, and molecular pathways of SA in improving IBD. The ingredients of SA were extracted by decoction either in water and ethanol and separated into four fractions (AE, EE, PEE and PCE). The effects of extractions were evaluated in the lipopolysaccharide (LPS)-induced RAW264.7 macrophages cell model, LPS-induced intestinal barrier injury model and imodium-induced constipation model. The high-performance liquid chromatography (HPLC) analysis was performed to identify the bioactive components. RESULTS: The compound-target pathway network was identified with 10 bioactive compounds, 166 IBD-related targets, and 52 IBD-related pathways. In LPS-induced RAW264.7 cells, PEE and PCE significantly decreased nitric oxide (NO) production and TNF-α level. In mice, PEE and PCE administration improved intestinal barrier damage, increased intestinal motility, reduced levels of TNF-α and diamine oxidase (DAO). Furthermore, PEE and PCE administration not only decreased expression of p-Akt, p-IκBα, nuclear p-p65, and TNF-α level, but also increased expression of the zonula occludin-1 (ZO-1) in LPS-induced intestinal barrier injury model. The escin content of AE, EE, PEE and PCE gradually increased with an increase of the bioactivity. CONCLUSIONS: Escin was the main bioactive components of SA. The effects of SA on IBD were mediated by repairing the intestinal barrier and promoting intestinal motility. The mechanism of action of SA is related to inhibiting the Akt/NF-κB signaling pathway in intestinal tissue, at least, in part. Our results provide a scientific basis for further exploring the mechanisms involved in the beneficial effects of SA in IBD.
Subject(s)
Inflammatory Bowel Diseases , Lipopolysaccharides , Animals , Escin , Inflammatory Bowel Diseases/drug therapy , Lipopolysaccharides/pharmacology , Mice , NF-kappa B/metabolism , Network Pharmacology , Proto-Oncogene Proteins c-akt , Semen , Tumor Necrosis Factor-alphaABSTRACT
The mechanisms of colostrum-mediated virus transmission are difficult to elucidate because of the absence of experimental animal models and the difficulties in tissue sample collection from mothers in the peripartum period. Porcine epidemic diarrhea virus (PEDV) is a reemerging enteropathogenic coronavirus that has catastrophic impacts on the global pig industry. PEDV primarily infects neonatal piglets by multiple routes, especially 1- to 2-day-old neonatal piglets. Here, our epidemiological investigation and animal challenge experiments revealed that PEDV could be vertically transmitted from sows to neonatal piglets via colostrum, and CD3+ T cells in the colostrum play an important role in this process. The results showed that PEDV colonizing the intestinal epithelial cells (IECs) of orally immunized infected sows could be transferred to CD3+ T cells located just beneath the IECs. Next, PEDV-carrying CD3+ T cells, with the expression of integrin α4ß7 and CCR10, migrate from the intestine to the mammary gland through blood circulation. Arriving in the mammary gland, PEDV-carrying CD3+ T cells could be transported across mammary epithelial cells (MECs) into the lumen (colostrum), as illustrated by an autotransfusion assay and an MECs/T coculture system. The PEDV-carrying CD3+ T cells in colostrum could be interspersed between IECs of neonatal piglets, causing intestinal infection via cell-to-cell contact. Our study demonstrates for the first time that colostrum-derived CD3+ T cells comprise a potential route for the vertical transmission of PEDV. IMPORTANCE The colostrum represents an important infection route for many viruses. Here, we demonstrate the vertical transmission of porcine epidemic diarrhea virus (PEDV) from sows to neonatal piglets via colostrum. PEDV colonizing the intestinal epithelial cells could transfer the virus to CD3+ T cells located in the sow intestine. The PEDV-carrying CD3+ T cells in the sow intestine, with the expression of integrin α4ß7 and CCR10, arrive at the mammary gland through blood circulation and are transported across mammary epithelial cells into the lumen, finally leading to intestinal infection via cell-to-cell contact in neonatal piglets. Our study not only demonstrates an alternative route of PEDV infection but also provides an animal model of vertical transmission of human infectious disease.
Subject(s)
Colostrum , Coronavirus Infections , Infectious Disease Transmission, Vertical , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Animals, Newborn , Colostrum/virology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Female , Infectious Disease Transmission, Vertical/veterinary , Porcine epidemic diarrhea virus/physiology , Swine , Swine Diseases/transmission , Swine Diseases/virology , T-Lymphocytes/virologyABSTRACT
Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne, a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the therapeutic effects of DCL on dextran sulfate sodium (DSS)-induced colitis with a focus on identifying the molecular mechanisms involved in DCL-mediated anti-inflammatory activity in macrophages. First, oral administration of DCL (5-15 mg/kg) not only ameliorated symptoms of colitis and colonic barrier injury, but also inhibited the expression of proinflammatory cytokines and myeloperoxidase in colon tissues in DSS-challenged mice. Furthermore, DCL also exhibited significant anti-inflammatory activity in LPS/IFNγ-stimulated RAW264.7 macrophages. Importantly, DCL significantly suppressed the phosphorylation and degradation of IκBα and subsequent NF-κB nuclear translocation, and enhanced the nuclear accumulation of Nrf2 in LPS/IFNγ-treated RAW264.7 cells. Mechanistically, DCL could directly interact with IKKα/ß and Keap1, thereby leading to the inhibition of NF-κB signalling and the activation of Nrf2 pathway. Furthermore, DCL-mediated actions were abolished by dithiothreitol, suggesting a thiol-mediated covalent linkage between DCL and IKKα/ß or Keap1. These findings demonstrated that DCL ameliorates colitis by targeting NF-κB and Nrf2 signalling, suggesting that DCL may be a promising candidate in the clinical treatment of colitis.
ABSTRACT
Red phosphorus (RP) has a suitable energy band structure and excellent photocatalytic properties. However, there are some problems, such as low quantum efficiency and serious photogenerated electron-hole recombination. The S-scheme heterostructure shows great potential in facilitating the separation and transfer of photogenerated carriers and obtaining strong photo-redox ability. Herein, hydrothermally treated red phosphorus (HRP) was combined with Bi2O2CO3 to construct Bi2O2CO3/HRP S-scheme heterojunction composite. The Bi2O2CO3 content was optimized, and the 5 %Bi2O2CO3/HRP composite obtained at 5 %Bi2O2CO3 mass fraction exhibited the strongest photoreduction ability. The Cr(VI) photoreduction and photolytic hydrogen production rates were as high as 0.22 min-1 and 157.2 µmol â¢h-1, which were 7.3 and 3.0 times higher than those of HRP, respectively. The promoted photocatalytic activity could be attributed to the formation of S-scheme heterojunctions, which accelerated the separation and transfer of useful photogenerated electron-hole pairs, while enhancing the recombination of relatively useless photogenerated electron-hole pairs, thereby resulting in the highest photocurrent density (17.3 µA/cm2) of the 5 %Bi2O2CO3/HRP composite, which was 1.6 and 4.3 times higher than pure Bi2O2CO3 (10.5 µA/cm2) and pure HRP (4.0 µA/cm2), respectively. This work would provide an advanced approach to enhance the photocatalytic activity of RP.
Subject(s)
Light , Phosphorus , Catalysis , ChromiumABSTRACT
Exosomes (EXs), a type of extracellular vesicles, are secreted from virtually all types of cells. EXs serve as cell-to-cell communicators by conveying proteins and nucleic acids with regulatory functions. Increasing evidence shows that EXs are implicated in the pathogenesis of central nervous system (CNS) diseases. Moreover, EXs have recently been highlighted as a new promising therapeutic strategy for in vivo delivery of nucleotides and drugs. Studies have revealed that infusion of EXs elicits beneficial effects on the CNS injury animal models. As compared to cell-based therapy, EXs-based therapy for CNS diseases has unique advantages, opening a new path for neurological medicine. In this review, we summarized the current state of knowledge of EXs, the roles and applications of EXs as a viable pathological biomarker, and EX-based therapy for CNS diseases.
Subject(s)
Alzheimer Disease/therapy , Biological Therapy , Dementia, Vascular/therapy , Exosomes , Parkinson Disease/therapy , Stroke/therapy , Animals , HumansABSTRACT
The tubers and roots of Aconitum (Ranunculaceae) are widely used as heart medicine or analgesic agents for the treatment of coronary heart disease, chronic heart failure, rheumatoid arthritis and neuropathic pain since ancient times. As a type of natural products mainly extracted from Aconitum plants, Aconitum alkaloids have complex chemical structures and exert remarkable biological activity, which are mainly responsible for significant effects of Aconitum plants. The present review is to summarize the progress of the pharmacological, toxicological, and pharmacokinetic studies of Aconitum alkaloids, so as to provide evidence for better clinical application. Research data concerning pharmacological, toxicological and pharmacokinetic studies of Aconitum alkaloids were collected from different scientific databases (PubMed, CNKI, Google Scholar, Baidu Scholar, and Web of Science) using the phrase Aconitum alkaloids, as well as generic synonyms. Aconitum alkaloids are both bioactive compounds and toxic ingredients in Aconitum plants. They produce a wide range of pharmacological activities, including protecting the cardiovascular system, nervous system, and immune system and anti-cancer effects. Notably, Aconitum alkaloids also exert strong cardiac toxicity, neurotoxicity and liver toxicity, which are supported by clinical studies. Finally, pharmacokinetic studies indicated that cytochrome P450 proteins (CYPs) and efflux transporters (ETs) are closely related to the low bioavailability of Aconitum alkaloids and play an important role in their metabolism and detoxification in vivo.
Subject(s)
Aconitum , Alkaloids , Aconitum/chemistry , Alkaloids/pharmacology , Alkaloids/toxicity , Biological Availability , Phytochemicals/pharmacology , Phytochemicals/toxicity , Plant Roots/chemistryABSTRACT
Potato common scab is an important soilborne disease worldwide that can significantly reduce the quality and economic values of potato. The disease is caused by multiple species of Streptomyces, which are not well controlled due to lack of effective strategies. Streptomyces galilaeus has been recently identified as a dominant species causing potato common scab in Inner Mongolia, China. This study was focused on screening and characterizing antagonists for biological control against pathogenic S. galilaeus. Bacterial strain PBSH9 was isolated from a potato tuber. PBSH9 was identified as a Streptomyces sp. on the basis of morphological, physiological, and biochemical characteristics, as well as DNA sequence analysis. PBSH9 inhibited S. galilaeus with a diameter of inhibitory zone of 19.8 mm on agar plates. The extracellular filtrate of PBSH9 also inhibited S. galilaeus growth with a diameter of inhibition zone of 10.0 mm. Furthermore, PBSH9 promoted potato sprouting and emergence. Disease control was up to 81.88% in greenhouse trials, and from 47.64 to 73.97% in 3-year field trials. Among the tested inoculation methods, seed treatment was more effective than soil drenching for PBSH9 application. PBSH9 not only effectively controlled potato common scab but also increased potato growth. Thus, it can be a potential candidate for biocontrol agent.
Subject(s)
Solanum tuberosum , Streptomyces , China , Plant DiseasesABSTRACT
Manipulating light transmission by shading is the most effective method of improving the nutritional value and sensory qualities of tea. In this study, the metabolic profiling of two tea cultivars ("Yulv" and "Maotouzhong") in response to different shading periods during the summer season was performed using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS) and gas chromatography-mass spectrometry (GC-MS). The metabolic pathway analyses showed that the glycolytic pathway and the tricarboxylic acid cycle (TCA cycle) in the leaves and shoots of "Maotouzhong" were significantly inhibited by long-term shading. The nitrogen metabolism in the leaves of the two cultivars was promoted by short-term shading, while it was inhibited by long-term shading. However, the nitrogen metabolism in the shoots of the two cultivars was always inhibited by shading, whether for short or long-term periods. In addition, the intensity of the flavonoid metabolism in both tea cultivars could be reduced by shading. These results revealed that shading could regulate the carbon and nitrogen metabolism and short-term shading could improve the tea quality to some extent.
Subject(s)
Camellia sinensis/metabolism , Camellia sinensis/radiation effects , Carbon/metabolism , Nitrogen/metabolism , Plant Leaves/chemistry , Camellia sinensis/chemistry , Chromatography, Liquid , Crop Production , Flavonoids/chemistry , Flavonoids/metabolism , Gas Chromatography-Mass Spectrometry , Light , Metabolomics , Plant Leaves/metabolism , Plant Leaves/radiation effects , Tandem Mass SpectrometryABSTRACT
Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor-α level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and ß-oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase 1α in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-α, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.
Subject(s)
Adipose Tissue, White/drug effects , Diet/adverse effects , Iridoids/chemistry , Lipid Mobilization/drug effects , Obesity/drug therapy , Animals , Disease Models, Animal , Male , RatsABSTRACT
Female Wistar rats were treated with orally administered soy isoflavones at concentrations of 0, 25, 50, or 100mg/kg body weight from weaning until sexual maturity (3 mo.), and ovarian steroidogenesis was evaluated. After soy isoflavones were administered, a significant (P<0.05) decrease (44%) in the serum estrodial levels of the high-dose (HD) group were observed. Cultured granulosa cells from the middle- (MD) and HD groups showed significantly (P<0.05) reduced (31%, 45%, respectively) in vitro estradiol secretion, and those from the HD group showed significantly (P<0.05) reduced progesterone (25%) secretion. Compared with the control group, the mRNA expression of the steroidogenic acute regulatory protein (Star), cytochromeP450 cholesterol side chain cleavage (Cyp11a1 and Cyp19a1), and hydroxysteroid dehydrogenase 3b (Hsd3b) genes also decreased. Real-time quantitative PCR and Western blotting revealed a significant (P<0.05) decrease in key transcription factor steroidogenic factor-1 (SF-1) expression in the HD group. The detection of DNA methylation using bisulfitesequencing PCR (BSP) suggested a significantly (P<0.05) increased total methylation rate in the proximal SF-1 promoter in the HD group. Further studies showed that treatment with soy isoflavones can significantly (P<0.05) increase the mRNA expression of DNA methyltransferase (DNMT) 1 and DNMT3a. This study proved that soy isoflavone administration from weaning until sexual maturity could inhibit ovarian steroidogenesis, suggesting that SF-1 might play an important role in this effect. In addition, DNA methylation might play a role in the downregulation of SF-1 gene expression induced by soy isoflavones.
Subject(s)
DNA Methylation/drug effects , Isoflavones/pharmacology , Steroidogenic Factor 1/metabolism , Weaning , Animals , Aromatase/genetics , Aromatase/metabolism , Cholesterol Side-Chain Cleavage Enzyme/genetics , Cholesterol Side-Chain Cleavage Enzyme/metabolism , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA Methyltransferase 3A , Dose-Response Relationship, Drug , Down-Regulation , Estradiol/blood , Female , Ovary/drug effects , Ovary/metabolism , Phosphoproteins/genetics , Phosphoproteins/metabolism , Promoter Regions, Genetic , Rats , Rats, Wistar , Glycine max/chemistry , Steroidogenic Factor 1/genetics , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
BACKGROUND: The tea plant, Camellia sinensis (L.) O. Kuntz, is a perennial woody plant widely cultivated for the production of a popular non-alcoholic beverage. To rapidly identify and evaluate two different color tea varieties (yellowish and purplish), the main phenotypic traits and quality components were tested in the present study. The metabolic profiles of tea shoots and leaves were also analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: The yellowish variation had a higher active level with respect to metabolism of catechins, and the contents of luteolin and kaempferol 3-α-d-glucoside were much higher compared to in the other variations. However, the purplish variation had a low content of theanine and a high content of caffeine. The contents of quercetin and kaempferol 3-α-d-galactoside were highest in purplish leaves. Moreover, the yellowish variation had the highest total quality scores for green teas and black teas, whereas the purplish variation had the highest scores for oolong teas. CONCLUSION: Both the yellowish variation and the purplish variation represent excellent breeding materials and are worthy of breeding as new tea cultivars. The yellowish variation is more suitable for making high-grade green teas or black teas, whereas the purplish variation is suitable for producing fine quality oolong teas. © 2016 Society of Chemical Industry.