ABSTRACT
Macleaya cordata is a Chinese herbal medicine containing a variety of highly cardiotoxic alkaloids, and might result in cardiac failure. Venous-arterial Extracorporeal membrane oxygenation (VA-ECMO) could be used as a therapeutic option in patients poisoned by Macleaya cordata complicating refractory cardiogenic shock or cardiac arrest. A 60-year-old man suffered from severe arrhythmia, cardiogenic shock and cardiac arrest after consuming Macleaya cordata. The patient received VA-ECMO support in the emergency department at 5 hours after hospitalization, and was weaned from VA-ECMO on day 4, and was discharged with complete clinical improvement on Day 12. VA-ECMO is an effective method in treating cardiogenic shock or cardiac arrest induced by severe poisoning from Chinese herbal medicine. Timely and appropriate interventions with venoarterial extracorporeal membrane oxygenation devices could improve clinical outcomes in these patients.
Subject(s)
Drugs, Chinese Herbal , Extracorporeal Membrane Oxygenation , Heart Arrest , Poisons , Humans , Male , Middle Aged , Drugs, Chinese Herbal/poisoning , Heart Arrest/etiology , Retrospective Studies , Shock, Cardiogenic/therapy , Shock, Cardiogenic/etiologyABSTRACT
As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney disease (CKD). In vivo experiments, 40 female SD (8-week-old) rats were randomized into four groups, namely, control group (negative control), POF model group, JPYS treatment group, and triptorelin treatment group (positive control). JPYS group was treated with JPYS decoction (oral, 11 g/kg) for 60 days, and the triptorelin group was treated with triptorelin (injection, 1.5 mg/kg) for 10 days before the administration of cyclophosphamide (CTX) (50 mg/kg body weight) to establish POF model. We examined apoptosis, mitochondrial function, and target gene (ASK1/JNK pathway and mitochondrial fusion/fission) expression. In vitro experiments, the KGN human granulosa cell line was used. Cells were pretreated with CTX (20, 40, and 60 µg/mL) for 24 h, followed by JPYS-containing serum (2, 4, and 8 %) for 24 h. Thereafter, these cells were employed to assess apoptosis, mitochondrial function, and target gene levels of protein and mRNA. In vivo, JPYS alleviated injury and suppressed apoptosis in POF rats. In addition, JPYS improved ovarian function. JPYS inhibit apoptosis of granulosa cells through improving mitochondrial function by activating ASK1/JNK pathway. In vitro, JPYS inhibited KGN cell apoptosis through inhibited ASK1/JNK pathway and improved mitochondrial function. The effects of GS-49977 were similar to those of JPYS. During POF, mitochondrial dysfunction occurs in the ovary and leads to granulosa cell apoptosis. JPYS decoction improves mitochondrial function and alleviates apoptosis through ASK1/JNK pathway.
Subject(s)
Drugs, Chinese Herbal , Primary Ovarian Insufficiency , Rats , Female , Humans , Animals , Primary Ovarian Insufficiency/metabolism , Triptorelin Pamoate/metabolism , Triptorelin Pamoate/pharmacology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Apoptosis , Granulosa Cells/metabolism , Mitochondria/metabolismABSTRACT
BACKGROUND: Sacha inchi (Plukenetia volubilis L.) tea has been used as an adjuvant treatment for diabetes in Pu'er, in the Yunnan province of China. The effects of sacha inchi tea on diabetes and the underlying mechanisms remain unknown. This study was conducted to investigate the influence of a water extract of sacha inchi (P. volubilis L.) leaves (PWE) on hypoglycemic activity and gut microbiota composition in mice with streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM). During the 6 weeks of the study, T1DM mice were administered PWE intragastrically at 400 mg kg-1 body weight (BW) per day. RESULTS: Treatment with PWE reduced excessive loss of BW and excessive intake of food. It significantly decreased blood glucose levels and improved oral glucose tolerance. The treatment caused protective histopathological transformations in sections of the pancreas, leading to decreased insulin resistance and improved insulin sensitivity. Treatment with PWE also significantly ameliorated disorders of the gut microbiota structure and increased the richness and diversity of intestinal microbial species in T1DM mice. At the genus level, the populations of several crucial bacteria, such as Akkermansia, Parabacteroides, and Muribaculum increased in the PWE treatment group but the abundance of Ruminiclostridium and Oscillibacter decreased. CONCLUSIONS: Treatment with PWE can ameliorate hyperglycemic symptoms in STZ-induced T1DM mice, and the anti-diabetic effect of PWE was related to the amelioration of gut microbial structural disorder and the enrichment of functional bacteria. © 2022 Society of Chemical Industry.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 1 , Euphorbiaceae , Gastrointestinal Microbiome , Animals , China , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 1/drug therapy , Euphorbiaceae/chemistry , Mice , Plant Extracts , Plant Oils/chemistry , Streptozocin , TeaABSTRACT
Depressed people are prone to sleep disturbance, which may in return perpetuate the depression. Both depression and sleep disturbance influence proinflammatory cytokines interleukin (IL) 6 and 1ß. Thus interventions for depression should consider the effect on sleep disturbance, and vice versa. Integrative Body-Mind-Spirit (IBMS) and Qigong interventions have been applied in a wide range of health and mental health conditions, including depression and sleep disturbance. This study aimed to evaluate the effect of these two mind-body therapies for persons with both depressive symptoms and sleep disturbance. A three-arm randomized controlled trial was conducted among 281 participants, who were randomly assigned to either IBMS, Qigong or wait list control group. Participants in IBMS and Qigong groups received eight weekly sessions of intervention. Outcome measures were plasma concentrations of IL-6 and IL-1ß, and a questionnaire containing Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, Somatic Symptom Inventory, Perceived Stress Scale and Body-Mind-Spirit Holistic Well-being Scale. Outcomes were assessed at baseline (T0), immediate post-intervention (T1) and at three-months post-intervention (T2). Besides intervention efficacy analysis, path analysis was performed to explore the relations among perceived stress, depression, sleep disturbance, and IL-6 and IL-1ß values. The study found both IBMS and Qigong reduced depression, sleep disturbance, painful and painless somatic symptoms, IL-6 and IL-1ß levels, and increased holistic well-being. The effect sizes of IBMS and Qigong, mostly in the medium magnitude range, were approximatively equivalent. Path analysis models revealed a predictive role of perceived stress in depression and sleep disturbance, a bidirectional relationship between depression and sleep disturbance, and significant influence of depression and sleep disturbance on IL-6 and IL-1ß. Compared with control, the findings support the efficacy of IBMS and Qigong interventions in relieving depression and sleep disturbance, and in reducing IL-6 and IL-1ß levels.
Subject(s)
Interleukin-6 , Sleep Wake Disorders , Cytokines , Depression/psychology , Depression/therapy , Humans , Sleep , Sleep Wake Disorders/therapyABSTRACT
PURPOSE: This study aimed to assess the efficacy of traditional Chinese medicine (TCM) in septic patients treated with ulinastatin. METHODS: PubMed, EmBase, and the Cochrane library were searched up to January 2021 to identify randomized controlled trials. The weight mean difference (WMD) and relative risk (RR) with 95% confidence intervals were used with the random-effects model. RESULTS: Twenty-three randomized controlled trials with 1903 septic patients were included. TCM significantly reduced the APACHE II score (WMD: -5.18; Pâ<â.001), interleukin-6 (WMD: -63.00; Pâ<â.001), tumor necrosis factor-α (WMD: -8.86; Pâ<â.001), c-reactive protein (WMD: -9.47; Pâ<â.001), mechanical ventilation duration (WMD: -3.98; Pâ<â.001), intensive care unit stay (WMD: -4.18; Pâ<â.001), procalcitonin (WMD: -0.53; Pâ<â.001), lipopolysaccharide (WMD: -9.69; Pâ<â.001), B-type natriuretic peptide (WMD: -159.87; Pâ<â.001), creatine kinase isoenzyme MB (WMD: -45.67; Pâ<â.001), cardiac troponin I (WMD: -0.66; Pâ<â.001), and all-cause mortality risk (RR: 0.55; Pâ<â.001). CONCLUSIONS: TCM lowers inflammation levels and reduces the risk of all-cause mortality for septic patients.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Glycoproteins/therapeutic use , Sepsis/drug therapy , Trypsin Inhibitors/therapeutic use , Drugs, Chinese Herbal/administration & dosage , Glycoproteins/administration & dosage , Humans , Randomized Controlled Trials as Topic , Treatment Outcome , Trypsin Inhibitors/administration & dosageABSTRACT
OBJECTIVE: To investigate the antibacterial activity of patchouli alcohol (PA) against 127 bacteria strains, including the common bacteria and drug-resistant bacteria strains both in the in vitro and in vivo tests. METHODS: For the in vitro trial, the antibacterial property of PA against 107 Gram-positive and 20 Gram-negative bacteria strains was screened by agar double dilution method. For the in vivo trial, specific pathogen free Kunming strain of both male and female white mice, were used to test the protective ability of PA after being injected with the median lethal dose of the tested strains. RESULTS: PA possessed antibacterial activity against all the tested 127 strains. In the in vitro test, PA could inhibit both Gram-negative bacteria (25-768µg/mL) and Gram-positive bacteria (1.5-200µg/mL). Particularly, PA was active against some drug-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA). PA also exhibited in vivo anti-MRSA activity in mice via intraperitoneal injection. PA could protect mice entirely infected with MRSA at 100 and 200 mg/kg, while 80% mice injected with MRSA could be protected at a low dose of 50µg/mL. CONCLUSION: PA might be a potential antibacterial drug from natural sources and might be worthy to explore its mechanism and application in further study.
Subject(s)
Pogostemon , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Methicillin-Resistant Staphylococcus aureus , Mice , Microbial Sensitivity Tests , SesquiterpenesABSTRACT
BACKGROUND: New therapeutic drugs are urgently needed against visceral leishmaniasis because current drugs, such as pentavalent antimonials and miltefosine, produce severe side effects and development of resistance. Whether cyclosporine A (CsA) and its derivatives can be used as therapeutic drugs for visceral leishmaniasis has been controversial for many years. METHODS: In this study, we evaluated the efficacy of CsA and its derivative, dihydrocyclosporin A (DHCsA-d), against promastigotes and intracellular amastigotes of Leishmania donovani. Sodium stibogluconate (SSG) was used as a positive control. RESULTS: Our results showed that DHCsA-d was able to inhibit the proliferation of L. donovani promastigotes (IC50: 21.24 µM and 12.14 µM at 24 h and 48 h, respectively) and intracellular amastigotes (IC50: 5.23 µM and 4.84 µM at 24 and 48 h, respectively) in vitro, but CsA treatment increased the number of amastigotes in host cells. Both DHCsA-d and CsA caused several alterations in the morphology and ultrastructure of L. donovani, especially in the mitochondria. However, DHCsA-d showed high cytotoxicity towards cells of the mouse macrophage cell line RAW264.7, with CC50 values of 7.98 µM (24 h) and 6.65 µM (48 h). Moreover, DHCsA-d could increase IL-12, TNF-α and IFN-γ production and decrease the levels of IL-10, IL-4, NO and H2O2 in infected macrophages. On the contrary, CsA decreased IL-12, TNF-α, and IFN-γ production and increased the levels of IL-10, IL-4, NO and H2O2 in infected macrophages. The expression of L. donovani cyclophilin A (LdCyPA) in promastigotes and intracellular amastigotes and the expression of cyclophilin A (CyPA) in RAW 264.7 cells were found to be significantly downregulated in the CsA-treated group compared to those in the untreated group. However, no significant changes in LdCyPA and CyPA levels were found after DHCsA-d or SSG treatment. CONCLUSIONS: Our findings initially resolved the dispute regarding the efficacy of CsA and DHCsA-d for visceral leishmaniasis treatment. CsA showed no significant inhibitory effect on intracellular amastigotes. DHCsA-d significantly inhibited promastigotes and intracellular amastigotes, but it was highly cytotoxic. Therefore, CsA and DHCsA-d are not recommended as antileishmanial drugs.
Subject(s)
Antiprotozoal Agents/pharmacology , Cyclosporine/pharmacology , Cyclosporins/pharmacology , Leishmania donovani/drug effects , Leishmaniasis, Visceral/parasitology , Animals , Drug Evaluation, Preclinical , Humans , Interferon-gamma/immunology , Interleukin-10/immunology , Interleukin-2/immunology , Leishmania donovani/growth & development , Leishmania donovani/physiology , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/immunology , Macrophages/immunology , Macrophages/parasitology , Mice , RAW 264.7 CellsABSTRACT
BACKGROUND: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction. METHODS/DESIGN: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine. DISCUSSION: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.
Subject(s)
Alopecia/drug therapy , Antineoplastic Agents/adverse effects , Breast Neoplasms/pathology , Drugs, Chinese Herbal/administration & dosage , Glycine max/chemistry , Adolescent , Adult , Aged , Alopecia/chemically induced , Anthracyclines/adverse effects , Breast Neoplasms/drug therapy , Double-Blind Method , Female , Glycyrrhiza/chemistry , Humans , Middle Aged , Multicenter Studies as Topic , Quality of Life , Randomized Controlled Trials as Topic , Taxoids/adverse effects , Treatment Outcome , Young AdultABSTRACT
Licorice is a medicinal herb widely used to treat inflammation-related diseases in China. Isoliquiritigenin (ISL) is an important constituent of licorice and possesses multiple bioactivities. In this study, we examined the selective anti-AML (acute myeloid leukemia) property of ISL via targeting FMS-like tyrosine kinase-3 (FLT3), a certified valid target for treating AML. In vitro, ISL potently inhibited FLT3 kinase, with an IC50 value of 115.1 ± 4.2 nM, and selectively inhibited the proliferation of FLT3-internal tandem duplication (FLT3-ITD) or FLT3-ITD/F691L mutant AML cells. Moreover, it showed very weak activity toward other tested cell lines or kinases. Western blot immunoassay revealed that ISL significantly inhibited the activation of FLT3/Erk1/2/signal transducer and activator of transcription 5 (STAT5) signal in AML cells. Meanwhile, a molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 flank tumor growth and prolonged survival in the bone marrow transplant model via decreasing the expression of Ki67 and inducing apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor. ISL could also be a potential natural bioactive compound for treating AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licorice might possess potential therapeutic effects for treating AML, providing a new strategy for anti-AML.
Subject(s)
Chalcones/administration & dosage , Enzyme Inhibitors/administration & dosage , Glycyrrhiza , Leukemia, Myeloid, Acute/drug therapy , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , Administration, Oral , Animals , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Female , Humans , Leukemia, Myeloid, Acute/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Molecular Docking Simulation/methods , Treatment Outcome , Xenograft Model Antitumor Assays/methods , fms-Like Tyrosine Kinase 3/metabolismABSTRACT
INTRODUCTION: The Chinese medicine formulation, tumour-shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect. OBJECTIVE: To develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin-3-O-neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction. METHODS: An ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile-water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre-treatment. RESULTS: The linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra-day and inter-day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively. CONCLUSION: The bioactive compounds of TSD samples were successfully quantified via UPLC-MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction.
Subject(s)
Berberine Alkaloids/chemistry , Cevanes/chemistry , Drugs, Chinese Herbal/chemistry , Leiomyoma/drug therapy , Phytochemicals/chemistry , Berberine Alkaloids/isolation & purification , Cevanes/isolation & purification , Chromatography, High Pressure Liquid , Humans , Limit of Detection , Phytochemicals/isolation & purification , Tandem Mass SpectrometryABSTRACT
Toxoplasma gondii is one of the most widespread obligatory parasitic protozoa and infects nearly all warm-blooded animals, leading to toxoplasmosis. The therapeutic drugs currently administered, like the combination of pyrimethamine and sulfadiazine, show high rates of toxic side effects, and drug resistance is encountered in some cases. Resveratrol is a natural plant extract with multiple functions, such as antibacterial, anticancer, and antiparasite activities. In this study, we evaluated the inhibitory effects of resveratrol on tachyzoites of the Toxoplasma gondii RH strain extracellularly and intracellularly. We demonstrate that resveratrol possesses direct antitoxoplasma activity by reducing the population of extracellularly grown tachyzoites, probably by disturbing the redox homeostasis of the parasites. Moreover, resveratrol was also able to release the burden of cellular stress, promote apoptosis, and maintain the autophagic status of macrophages, which turned out to be regulated by intracellular parasites, thereby functioning indirectly in eliminating T. gondii In conclusion, resveratrol has both direct and indirect antitoxoplasma effects against RH tachyzoites and may possess the potential to be further evaluated and employed for toxoplasmosis treatment.
Subject(s)
Antiparasitic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Resveratrol/pharmacology , Toxoplasma/drug effects , Toxoplasmosis/drug therapy , Animals , Apoptosis/drug effects , Cell Line , Host-Parasite Interactions/drug effects , Humans , Macrophages/immunology , Mice , Plant Extracts/pharmacology , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose (D-gal)-elicited senescent mice brain, its effects on liver and kidney injury have not yet been explored. In this work, mice were subjected to hypodermic injection with D-gal (200 mg/kg) and orally gavaged with AS (20, 40, or 80 mg/kg) once a day for 8 successive weeks. Results revealed that AS significantly improved liver and kidney function as assessed by organ index and functional parameters. In addition, AS pretreatment effectively ameliorated the histological deterioration. AS attenuated the MDA level and markedly enhanced the activities and gene expressions of antioxidative enzymes, namely Cu, Zn-SOD, CAT, and GPx. Furthermore, AS markedly inhibited the D-gal-mediated increment of expressions of inflammatory cytokines iNOS, COX-2, IκBα, p-IκBα, and p65 and promoted the IκBα expression level in both hepatic and renal tissues. In sum, AS pretreatment could effectively guard the liver and kidney of mice from D-gal-induced injury, and the underlying mechanism was deemed to be intimately related to attenuating oxidative response and inflammatory stress.
Subject(s)
Angelica sinensis/chemistry , Chemical and Drug Induced Liver Injury/drug therapy , Drugs, Chinese Herbal/administration & dosage , Galactose/adverse effects , Inflammation/drug therapy , Kidney Diseases/drug therapy , Oxidative Stress/drug effects , Animals , Chemical and Drug Induced Liver Injury/metabolism , Chromatography, Supercritical Fluid , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Humans , Inflammation/genetics , Inflammation/metabolism , Kidney/drug effects , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Liver/drug effects , Male , Malondialdehyde/metabolism , MiceABSTRACT
Hao Jia Xu Re Qing Granules (HJ), is an effective clinically used antipyretic based on traditional Chinese medicine. Although its antipyretic therapeutic effectiveness is obvious, its therapeutic mechanism has not been comprehensively explored yet. In this research, we first identified potential biomarkers which may be relevant for the antipyretic effect of HJ based on urine metabolomics using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A rat model of fever was established using the yeast-induced febrile response. Total-ion-current metabolic profiles of different groups were acquired and the data were processed by multivariate statistical analysis-partial least-squares discriminant analysis. As envisioned, the results revealed changes of urine metabolites related to the antipyretic effect. Fourteen potential biomarkers were selected from the urine samples based on the results of Student's t-test, "shrinkage t", variable importance in projection and partial least-squares discriminant analysis. N-Acetylleucine, kynurenic acid, indole-3-ethanol, nicotinuric acid, pantothenic acid and tryptophan were the most significant biomarkers found in the urine samples, and may be crucially related to the antipyretic effect of HJ. Consequently, we propose the hypothesis that the significant antipyretic effect the HJ may be related to the inhibition of tryptophan metabolism. This research thus provides strong theoretical support and further direction to explain the antipyretic mechanism of HJ, laying the foundation for future studies.
Subject(s)
Antipyretics/pharmacokinetics , Biomarkers/urine , Drugs, Chinese Herbal/pharmacokinetics , Metabolome/drug effects , Metabolomics/methods , Animals , Antipyretics/pharmacology , Biomarkers/metabolism , Chromatography, High Pressure Liquid , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Female , Fever/metabolism , Male , Rats , Rats, Sprague-Dawley , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Ziziphus jujuba (Mill.), known as Jujuba Fructus (JF) or jujube, is a well-known Traditional Chinese Medicine (TCM) for blood nourishment and sedation effect. Apart from prescribing as single herb alone, JF is very often being included in multi-herbal decoctions to prolong, enhance and harmonize pharmaceutical effects of decoctions while at the same time reducing toxicity. Here, we aimed to compare the protective and differentiating activities of three chemically standardized jujube-containing decoctions, including Guizhi Tang (GZT), Neibu Dangguijianzhong Tang (NDT) and ZaoTang (ZOT) in cultured PC12 cells. MATERIALS AND METHODS: The protein expressions of neurofilaments, including NF68, NF160 and NF200, under the herbal treatment were revealed by western blot. The determination of neurite outgrowth in cultured PC12 cells upon the treatment of herbal extracts was performed by light microscope equipped with a phase-contrast condenser and SPOT imaging software. The protective effect against tBHP-induced cytotoxicity under the herbal treatment was measured by MTT assay. A luciferase reporter construct carrying four repeats of anti-oxidant response element (ARE) and a downstream luciferase reporter gene luc2P was transfected into PC12 cells to study the transcriptional activation of ARE. The mRNA expression of antioxidant enzymes under the herbal treatment was analyzed by quantitative real-time PCR. RESULTS: These jujube-containing decoctions processed similar neuro-protective and brain beneficial properties. The herbal treatment induced the protein expression of neurofilaments. Neurite outgrowth was observed under the herbal treatment. In parallel, the pre-treatment of herbal extracts protected PC 12 cells against oxidative stress-induced apoptosis in a dose-dependent manner. Moreover, the herbal treatments triggered the mRNA expressions of relevant anti-oxidation genes, i.e. glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modulatory subunit (GCLM), glutathione S-transferase (GST) and NAD(P)H quinone oxidoreductase (NQO1) via the activation of anti-oxidant response element (ARE). CONCLUSION: The results therefore demonstrated neuro-protective and differentiating properties of the three closely related decoctions, and which subsequently illustrated the enhancement function of jujube within a multi-herbal decoction.
Subject(s)
Antioxidants/pharmacology , Drugs, Chinese Herbal/pharmacology , Neurogenesis/drug effects , Neurons/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Ziziphus/chemistry , Animals , Antioxidant Response Elements , Antioxidants/isolation & purification , Apoptosis/drug effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/isolation & purification , Gene Expression Regulation, Enzymologic , Neurofilament Proteins/metabolism , Neuronal Outgrowth/drug effects , Neurons/enzymology , PC12 Cells , Phytotherapy , Plant Extracts/isolation & purification , Plants, Medicinal , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Transfection , tert-Butylhydroperoxide/toxicityABSTRACT
Five isoliquiritigenin analogues, including a new methylene-bridged bischalcone (1), were isolated from Spatholobus suberectus. Cytotoxicity screening of these isolates and several synthetic derivatives indicated that the introduction, removal, position modification, or glycosylation of hydroxy groups in isoliquiritigenin did not improve the resultant cytotoxicity against the MCF-7 and MDA-MB-231 human breast cancer cell lines. In addition, cyclization of OH-2' chalcones or reduction of the α,ß-unsaturated carbonyl double bond decreased such cytotoxicity substantially. However, methylation of hydroxy groups resulted in a marked increase in such cytotoxic activity. Among these active isoliquiritigenin analogues, 3',4',5',4â³-tetramethoxychalcone (3h) was obtained as a compound with promising cytotoxic activity.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Chalcones/isolation & purification , Chalcones/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Fabaceae/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Breast Neoplasms/drug therapy , Cell Proliferation/drug effects , Chalcones/chemistry , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Female , Humans , Molecular StructureABSTRACT
Cordyceps sinensis is an endoparasitic fungus widely used as a tonic and medicinal food in the practice of traditional Chinese medicine (TCM). In historical usage, Cordyceps specifically is referring to the species of C. sinensis. However, a number of closely related species are named themselves as Cordyceps, and they are sold commonly as C. sinensis. The substitutes and adulterants of C. sinensis are often introduced either intentionally or accidentally in the herbal market, which seriously affects the therapeutic effects or even leads to life-threatening poisoning. Here, we aim to identify Cordyceps by DNA sequencing technology. Two different DNA-based approaches were compared. The internal transcribed spacer (ITS) sequences and the random amplified polymorphic DNA (RAPD)-sequence characterized amplified region (SCAR) were developed here to authenticate different species of Cordyceps. Both approaches generally enabled discrimination of C. sinensis from others. The application of the two methods, supporting each other, increases the security of identification. For better reproducibility and faster analysis, the SCAR markers derived from the RAPD results provide a new method for quick authentication of Cordyceps.
Subject(s)
Cordyceps/genetics , DNA, Fungal/genetics , DNA, Ribosomal Spacer/genetics , Base Sequence , Genetic Markers , Molecular Sequence Data , Molecular Typing , Mycological Typing Techniques , Random Amplified Polymorphic DNA Technique , Sequence Analysis, DNAABSTRACT
Dioscin (DIS), one of the most abundant bioactive steroidal saponins in Dioscorea sp., is used as a complementary medicine to treat coronary disease and angina pectoris in China. Although the pharmacological activities and pharmacokinetics of DIS have been well demonstrated, information regarding the final metabolic fates is very limited. This study investigated the in vivo metabolic profiles of DIS after oral administration by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method. The structures of the metabolites were identified and tentatively characterized by means of comparing the molecular mass, retention time and fragmentation pattern of the analytes with those of the parent compound. A total of eight metabolites, including seven phase I and one phase II metabolites, were detected and tentatively identified for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. In addition, a possible metabolic pathway on the biotransformation of DIS in vivo was proposed. This study provides valuable and new information on the metabolism of DIS, which will be helpful for further understanding its mechanism of action.
Subject(s)
Chromatography, High Pressure Liquid/methods , Dioscorea/chemistry , Diosgenin/analogs & derivatives , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Mass Spectrometry/methods , Animals , Diosgenin/chemistry , Diosgenin/metabolism , Male , Molecular Structure , Rats , Rats, Sprague-DawleyABSTRACT
Angelica Sinensis Radix (roots of Angelica sinensis; ASR) is a popular herbal supplement in China for promoting blood circulation. Today, sulfur-fumigation is commonly used to treat ASR as a means of pest control; however, the studies of sulfur-fumigation on the safety and efficacy of ASR are very limited. Here, we elucidated the destructive roles of sulfur-fumigation on ASR by chemical and biological assessments. After sulfur-fumigation, the chemicals in ASR were significantly lost. The biological activities of anti-platelet aggregation, induction of NO production and estrogenic properties were compared between the water extracts of non-fumigated and sulfur-fumigated ASR. In all cases, the sulfur-fumigation significantly reduced the biological properties of ASR. In addition, application of water extract deriving from sulfur-fumigated ASR showed toxicity to cultured MCF-7 cells. In order to ensure the safety and to achieve the best therapeutic effect, it is recommended that sulfur-fumigation is an unacceptable approach for processing herbal materials.
Subject(s)
Angelica sinensis/chemistry , Drugs, Chinese Herbal/chemistry , Fumigation , Sulfur/chemistry , Animals , Drugs, Chinese Herbal/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , MCF-7 Cells , Nitric Oxide/metabolism , Plant Extracts/chemistry , Plant Roots/chemistry , Platelet Aggregation/drug effects , RabbitsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Tang (DBT), a Chinese herbal decoction commonly used in treating women׳s ailments, contains two herbs: Angelica Sinensis Radix (ASR) and Astragali Radix (AR). Traditionally, ASR had to be pre-treated with yellow wine before the herbal preparation, which reduced the amount of volatile oil in water extract of ASR and DBT, and meanwhile the volatile oil-reduced DBT processed better bioactivities in cell cultures. The present study aimed to investigate the effect of volatile oil from ASR (Angelica oil) on the solubility of AR-derived ingredients and the biological properties of DBT. MATERIALS AND METHODS: To standardize Angelica oil, four marker chemicals in ASR were determined by GC-QQQ-MS/MS. Subsequently, fifteen gram of AR was boiled with different amounts of Angelica oil. The amounts of astragaloside IV, calycosin, formononetin, total polysaccharides, total saponins and total flavonoids, all derived from AR, were extracted and determined by HPLC-UV/ELSD. To reveal the effect of Angelica oil on DBT functions, several cell assays related to the traditional functions of DBT were selected, including anti-platelet aggregation, induction of NO production, hematopoetic, estrogenic and osteogenic properties. RESULTS: The inclusion of Angelica oil in AR during preparation significantly decreased the amount of AR-derived astragaloside IV, calycosin, formononetin, total saponins and total flavonoids in the final water extract. In parallel, an inclusion of Angelica oil caused a decrease of DBT׳s estrogenic and hematopoetic activities in cultured cells. Moreover, the Angelica oil decreased DBT-induced cell proliferation of cultured MG-63 and endothelial cells. CONCLUSIONS: The results indicated that Angelica oil was a negative regulator for DBT chemically and biologically, which supported the traditional practice of preparing DBT by using the wine-treated ASR.
Subject(s)
Angelica sinensis/chemistry , Angelica/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Astragalus Plant/chemistry , Drugs, Chinese Herbal/pharmacology , Oils, Volatile/pharmacology , Antineoplastic Agents, Phytogenic/analysis , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/chemistry , HEK293 Cells , Humans , MCF-7 Cells , Medicine, Chinese Traditional , Molecular Structure , Oils, Volatile/analysis , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Chemical change during boiling of herbal mixture is a puzzle. By using Danggui Buxue Tang (DBT), a herbal decoction that contains Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), we developed a model in analyzing the hydrolysis of flavonoid glycosides during the boiling of herbal mixture in water. A proper preparation of DBT is of great benefit to the complete extraction of bioactive ingredients. Boiling of DBT in water increased the solubility of AR-derived astragaloside IV, calycosin, formononetin, calycosin-7-O- ß -D-glucoside, and ononin in a time- and temperature-dependent manner: the amounts of these chemicals reached a peak at 2 h. The glycosidic resides of AR, calycosin-7-O- ß -D-glucoside, and ononin could be hydrolyzed during the moderate boiling process to form calycosin and formononetin, respectively. The hydrolysis efficiency was strongly affected by pH, temperature, and amount of herbs. Interestingly, the preheated herbs were not able to show this hydrolytic activity. The current results supported the rationality of ancient preparation of DBT in boiling water by moderate heat.