المؤلفون: Sun, Yiran^1,2 (AUTHOR), He, Libo¹ (AUTHOR), Wang, Wang¹ (AUTHOR), Wang, Taoyu^1,2 (AUTHOR), Hua, Wan^1,2 (AUTHOR), Li, Tingting^1,2 (AUTHOR), Wang, Li^1,2 (AUTHOR), Gao, Tingyan^1,2 (AUTHOR), Chen, Fang^1,2 (AUTHOR), Tang, Lin^1,2 (AUTHOR) tanglin@scu.edu.cn

المصدر: Journal of Ethnopharmacology. Mar2021, Vol. 268, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *REACTIVE oxygen species, *EPITHELIAL cells, *INFLAMMATION, *LACTATE dehydrogenase, *MEDICINAL plants, *POLYPHENOLS, *PROTEINS, *WESTERN immunoblotting, *PLANT extracts, *CELL survival

مستخلص: Penthorum chinense Pursh is used for promoting diuresis and alleviating "heat"-associated disorders, which were considered to be related to diabetic in Traditional Chinese Medicine (TCM). Here, we aimed to evaluate the ability and underlying mechanism of the ethyl acetate fraction of Penthorum chinense Pursh stems (PSE) to inhibit vascular inflammation in high glucose (HG)-induced human umbilical vein endothelial cells (HUVEC cells). HUVEC cells were pre-treated with PSE following HG treatment. The cell viability, mitochondrial membrane potential (MMP), lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) generation were analyzed. Inflammatory, and antioxidant,-related proteins were analyzed using western blotting. Molecular docking and drug affinity targeting experiments (DARTS) were utilized to analyze and verify the binding of the Keap1 protein and polyphenols of PSE. HG can significantly increase the activity of lactic dehydrogenase (LDH), destroy the mitochondrial membrane potential (MMP), and promote the generation of reactive oxygen species (ROS), while PSE treatment reversed these changes. Mechanistically, PSE inhibited NF-κB and inflammatory cytokines activation induced by HG through activating the expression of Nrf2 and its downstream antioxidant proteins Heme oxygenase-1 (HO-1), NAD (P)H Quinone Dehydrogenase 1 (NQO1), Glutamate cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier (GCLM). Further study indicated that PSE activated Nrf2 antioxidant pathway mainly by the binding of primary polyphenols from PSE and the Keap1 protein. Taken together, the present data highlight the health benefits of polyphenols from Penthorum chinense Pursh. regarding diabetes, proving it to be an important source of health care products. Besides, binding of the Keap1 protein may be an effective strategy to activate Nrf2 antioxidant pathway and prevent diabetes. Image 1 • Polyphenols from Penthorum chinense Pursh. assuaged high glucose-induced endothelial cell damage through inhibiting ROS overproduction. • Polyphenols from Penthorum chinense Pursh. activated Nrf2-antioxidant signaling pathway in HUVEC cells. • Polyphenols from Penthorum chinense Pursh. suppressed high glucose-induced activation of NF-κB- inflammation signaling pathway in HUVEC cells. • Polyphenols from Penthorum chinense Pursh. entered to the Keap1 kelch domain and interacted with critical residues. [ABSTRACT FROM AUTHOR]

المؤلفون: Mbakazi, Y.¹ (AUTHOR), Kappo, A.P.¹ (AUTHOR), Soyingbe, O.S.² (AUTHOR), Nety, N.S.³ (AUTHOR), Makhafola, T.J.² (AUTHOR) jmakhafola@cut.ac.za, Chukwuma, C.I.² (AUTHOR), Dikhoba, M.P.² (AUTHOR), Mariri, N.G.² (AUTHOR), Mongalo, N.I.^1,4 (AUTHOR) Mongani@unisa.ac.za

المصدر: South African Journal of Botany. Nov2022, Vol. 150, p752-758. 7p.

مصطلحات موضوعية: *PHYTOCHEMICALS, *TIME-of-flight mass spectrometry, *ANTIBACTERIAL agents, *DICHLOROMETHANE, *PHTHALIC acid, *LACTATE dehydrogenase, *COLORECTAL cancer

مستخلص: • Methanol extract from Sarcophyte sanguinea bulb extract exhibited better antimicrobial activity compared to dichloromethane extract. • The extract further exhibited a potent antioxidant activity and notably higher quantities of 5-aminoimidazole-4-carboxamide-1-ád-ribofuranosyl 5′-monophosphate, phthalic acid and di(oct‑3-yl) ester. • Dichloromethane extract exhibited potent antioxidant activity in four different assays. Antibiotic resistance necessitates the need for continued search for new antimicrobial compounds. In this study, we report the antibacterial activity, cytotoxic, and antioxidant activity of Sarcophyte sanguinea subsp. piriei (Hutch.) B. The extracts were evaluated for antibacterial activity using the agar well diffusion, micro-dilution, minimum bactericidal concentrations (MBC) and lactate dehydrogenase (LDH) release assay. Furthermore, the cytotoxic effects of extracts were determined using MTT assay against Human Embryonic Kidney (HEK293), Human Breast Endocrine Cells (SKBR-3), Human Colorectal Carcinoma Cells (Caco-2) and Human Hepatocellular Carcinoma (HepG2) cells. The extracts were also assessed for antioxidant activity against 2,2-diphenyl-1-picryl hydrazyl (DPPH), 2–2′-Azino-di-[3-ethylbenzthiazoline sulfonate (ABTS), nitric oxide radicals and Fe2+ chelating assays. The methanol extract (MeOH) was subjected to GC-TOF-MS analysis. MeOH extract exhibited highest zone of inhibition (ZI) of 15.67 mm against Staphylococcus aureus. The extract further exhibited 67.0% inhibition against Escherichia coli in a lactate dehydrogenase (LDH) membrane damage assay. In the cytotoxicity assay, MeOH and DCM extracts had LC 50 value of 237 µg/ml and 221 µg/ml against SKBR-3 cell line respectively. Gas-chromatography time-of-flight mass spectrometry (GC/TOF-MS) analysis of methanol extract indicated the presence of 5-aminoimidazole-4-carboxamide-1-ád-ribofuranosyl 5′-monophosphate (36.827%), 3-O-methyl-d-glucose (36.827%) and phthalic acid, di(oct‑3-yl) ester (8.161%). Even though the investigated plant is suggested to have anticancer activities by traditional healers, the extracts had little inhibition on selected cancerous cell lines. Given the good antibacterial and antioxidant activity of the extracts, the plant may act as an immune booster and prevent infections in immunosuppressed cancer patients. Detected compounds may be influence the observed biological activity of the plant. [ABSTRACT FROM AUTHOR]

المؤلفون: Luo, Li¹ (AUTHOR), Lin, Jinxian¹ (AUTHOR), Chen, Sixin¹ (AUTHOR), Ni, Jiajie¹ (AUTHOR), Peng, Hongjie¹ (AUTHOR), Shen, Feihai^1,2 (AUTHOR) tobyshum12@163.com, Huang, Zhiying¹ (AUTHOR) hzhiying@mail.sysu.edu.cn

المصدر: Journal of Ethnopharmacology. Aug2024, Vol. 330, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *LIVER injuries, *LIVER disease prevention, *LYSOSOMES, *AUTOPHAGY, *ROSMARINIC acid, *CHOLECYSTOKININ, *ELECTRON microscopy, *CELLULAR signal transduction, *LACTATE dehydrogenase, *IMMUNODIAGNOSIS, *REVERSE transcriptase polymerase chain reaction, *PLANT extracts, *LIVER diseases, *JANUS kinases, *MICE, *GENE expression, *IMMUNOHISTOCHEMISTRY, *MESSENGER RNA, *LIVER cells, *MEDICINAL plants, *ANIMAL experimentation, *WESTERN immunoblotting, *OXIDOREDUCTASES, *GENE expression profiling, *ORGANIC compounds, *STAT proteins, *BIOLOGICAL assay, *STAINS & staining (Microscopy), *POLYPHENOLS, *CELL surface antigens

مستخلص: Rosmarinic acid (RA), a natural polyphenol abundant in numerous herbal remedies, has been attracting growing interest owing to its exceptional ability to protect the liver. Toosendanin (TSN), a prominent bioactive compound derived from Melia toosendan Siebold & Zucc., boasts diverse pharmacological properties. Nevertheless, TSN possesses remarkable hepatotoxicity. Intriguingly, the potential of RA to counteract TSN-induced liver damage and its probable mechanisms remain unexplored. This study is aimed at exploring whether RA can alleviate TSN-induced liver injury and the potential mechanisms involved autophagy. CCK-8 and LDH leakage rate assay were used to evaluate cytotoxicity. Balb/c mice were intraperitoneally administered TSN (20 mg/kg) for 24 h after pretreatment with RA (0, 40, 80 mg/kg) by gavage for 5 days. The autophagic proteins P62 and LC3B expressions were detected using western blot and immunohistochemistry. RFP-GFP-LC3B and transmission electron microscopy were applied to observe the accumulation levels of autophagosomes and autolysosomes. LysoTracker Red and DQ-BSA staining were used to evaluate the lysosomal acidity and degradation ability respectively. Western blot, immunohistochemistry and immunofluorescence staining were employed to measure the expressions of JAK2/STAT3/CTSC pathway proteins. Dual-luciferase reporter gene was used to measure the transcriptional activity of CTSC and RT-PCR was used to detect its mRNA level. H&E staining and serum biochemical assay were employed to determine the degree of damage to the liver. TSN-induced damage to hepatocytes and livers was significantly alleviated by RA. RA markedly diminished the autophagic flux blockade and lysosomal dysfunction caused by TSN. Mechanically, RA alleviated TSN-induced down-regulation of CTSC by activating JAK2/STAT3 signaling pathway. RA could protect against TSN-induced liver injury by activating the JAK2/STAT3/CTSC pathway-mediated autophagy and lysosomal function. [Display omitted] • TSN suppressed JAK2/STAT3/CTSC pathway-mediated autophagy. • RA alleviated TSN-induced hepatotoxicity by activating JAK2/STAT3/CTSC pathway. • STAT3 participated in the transcriptional activation of CTSC. [ABSTRACT FROM AUTHOR]

المؤلفون: Saber, Mona M.¹ (AUTHOR) mona.magdy@pharma.cu.edu.eg, Radi, Mai Hussin^1,2 (AUTHOR), El-Shiekh, Riham A.^1,3 (AUTHOR) riham.adel@pharma.cu.edu.eg, Abdel-Sattar, Essam^1,3 (AUTHOR) essam.abdelsattar@pharma.cu.edu.eg, El-Halawany, Ali M.³ (AUTHOR) ali.elhalawany@pharma.cu.edu.eg

المصدر: Journal of Ethnopharmacology. Mar2024, Vol. 321, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *CANCER chemotherapy, *CARDIOTOXICITY, *MEDICINAL plants, *HIGH performance liquid chromatography, *VENTRICULAR ejection fraction, *COMBINATION drug therapy, *MYOCARDIUM, *HEART cells, *CARDIOMYOPATHIES, *DOXORUBICIN, *ANIMAL experimentation, *METHANOL, *CALIBRATION, *HEART, *CREATINE kinase, *DIETARY supplements, *HYDROCARBONS, *COMPARATIVE studies, *CELL survival, *ISOENZYMES, *DESCRIPTIVE statistics, *HISTOLOGICAL techniques, *LACTATE dehydrogenase, *DOSE-effect relationship in pharmacology, *PLANT extracts, *CELL lines, *STATISTICAL correlation, *CARDIOTONIC agents, *MICE, *THIN layer chromatography, *PHARMACODYNAMICS

مستخلص: Euphorbia plants have long been used as traditional medicine in China, Europe, America, Turkey, India, Africa, Iran, and Pakistan because of its high medicinal value and health advantages especially as a remedy for several types of cancer. Doxorubicin (DOX) is one of the most frequently prescribed drugs in cancer chemotherapy, with dose-limiting cardiotoxicity. The development of medicinal approaches to attenuate drug's toxicity represents an area of great concern in cancer research. Because research on this topic is still disputed and limited, we aim to investigate the potential of supplementation with Euphorbia grantii Oliv. on DOX-induced cardiomyopathy in Ehrlich carcinoma bearing mice. The high-performance thin layer chromatography (HPTLC) analysis of total methanolic extract (TE), and its bioactive dichloromethane fraction (DCMF) was applied for the determination of friedelin. Male BALB/c mice were used to keep the Ehrlich ascites tumor cells. The experiment was performed for a 2-weeks period. A good linearity relationship was found to be with correlation coefficient (r2) value of 0.9924 for the isolated friedelin. Limit of detection (LOD) and limit of quantitation (LOQ) was found to be 0.00179, and 0.000537 ng/band respectively for friedelin. The amount of friedelin in the TE and DCMF were determined by using calibration curve of standard as 106.32 ± 5.69 μg, and 159.2 ± 4.24 μg friedelin/mg extract, respectively. DOX-induced cardiomyopathy by decreasing the ejection fraction (EF) compared to the Ehrlich and negative control groups. It resulted in a decrease in the EF by 30 and 39% compared to the other groups. High and low doses of the TE and DCMF did not result in significantly different ejection fractions compared to the Ehrlich group. Co-administration of DCMF with DOX ameliorated the alteration in the serum CKMB and LDH levels. As revealed from histopathological study, DOX impairs viability of cardiac myocytes and DCMF could effectively and extensively counteract this action of DOX and potentially protect the heart from severe toxicity of DOX. Finally, our results indicated that Euphorbia grantii Oliv. would be the best option to reduce DOX adverse effects. [Display omitted] • The cardioprotective effects of E. grantii against DOX-induced cardiotoxicity was authenticated. • This action was achieved through amelioration of CKMB, and LDH levels after Ehrlich injection and DOX treatment. • Diterpenoids and triterpenoids are responsible for their biological activities. • HPTLC analysis was applied for the standardization of the extract and bioactive fraction using the isolated; friedelin. [ABSTRACT FROM AUTHOR]

المؤلفون: El-Sawy, Samer A.¹ (AUTHOR), Amin, Yahia A.^1,2 (AUTHOR) yahiaamin2030@gmail.com, El-Naggar, Sabry A.³ (AUTHOR), Abdelsadik, Ahmed^4,5 (AUTHOR)

المصدر: Journal of Ethnopharmacology. Sep2023, Vol. 313, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *OBESITY complications, *HYPOGONADISM, *TESTIS, *HUMAN reproduction, *BIOMARKERS, *MEDICINAL plants, *FOLLICLE-stimulating hormone, *ANIMAL experimentation, *TESTOSTERONE, *SUPEROXIDE dismutase, *CREATINE kinase, *ANTIOXIDANTS, *APOPTOSIS, *SPERM motility, *RATS, *MALONDIALDEHYDE, *CATALASE, *ISOENZYMES, *OXIDATIVE stress, *LEAVES, *LUTEINIZING hormone, *LACTATE dehydrogenase, *PLANT extracts, *ORLISTAT, *CASPASES, *DIETARY fats, *PHARMACODYNAMICS

مستخلص: Artemisia annua L., known as "sweet wormwood," is widely used in Egyptian folk medicine. Egyptians implement the aerial parts in the treatment of respiratory, digestive and sexual dysfunctions. However, the mechanism by which Artemisia annua improves testicular function is still being discovered. This study aimed to evaluate the modulatory effects of the crude leaf extract of Artemisia annua (AAE) on a high-fat diet induced testicular dysfunction in rats and compare it with the antilipolytic drug Orlistat. Forty adult rats were randomly classified and assigned to four groups. The first group typically consumed a balanced diet and served as a negative control (GP1). A high-fat diet-induced obesity was applied to the other three groups for 12 weeks. A positive control remained on HFD for another 8 weeks, which is GP2. Other groups were administered for 8 consecutive weeks either with Orlistat (50 mg/kg body weight) or AAE (100 mg/kg body weight), which have been defined as GP3 and GP4, respectively. Testosterone (TST), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in the sera of all groups. In addition, the oxidant/antioxidant biomarkers such as protein carbonyl, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) activities, lactate dehydrogenase (LDH) and creatine kinase isoenzyme-B (CK-MB) were determined. An immunohistochemical stain with the apoptotic marker caspase-3 and the proliferating cell nuclear antigen (PCNA) were also investigated. In the testes of the obese group, the results showed hormonal imbalance, an increase in oxidative stress biomarkers and apoptosis. In the group treated with orlistat (GP3), noticeably more perturbations were noted. The obese rats that had been treated with AAE (GP4) showed a significantly reduced level of oxidative stress, hormonal balance restoration and reduced apoptosis. The crude leaf extract of A. annua is a potential herbal therapeutic for the treatment of obesity-related testicular dysfunction and the restoration of hormonal imbalance in obese rats. [Display omitted] • A high-fat diet induces obesity, oxidative stress and sperm deformities, altering testis physiology. • A high-fat diet alters testicular hormonal balance and the maintenance of sperm quality. • Orlistat treatment in obese rats revealed substantial testicular damage and aggravated the effects of a high-fat diet. • Artemisia Annua Extract (AAE) counteracts high-fat diet deleterious effect on testicular functions. • AAE ameliorates high-fat diet-induced spermatogenesis malformations and hormonal secretion. • AAE can be used to recover the hormonal balance and improve sperm quality in men with obese fertility disorders. [ABSTRACT FROM AUTHOR]

المؤلفون: Li, Meichen¹ (AUTHOR), Fan, Yanhua¹ (AUTHOR), Zhong, Ting¹ (AUTHOR), Yi, Ping¹ (AUTHOR), Fan, Chengcheng¹ (AUTHOR), Wang, Andong¹ (AUTHOR), Liu, Jianyu¹ (AUTHOR) burningice@126.com, Xu, Yongnan¹ (AUTHOR) ynxu@syphu.edu.cn

المصدر: Fitoterapia. Apr2019, Vol. 134, p81-87. 7p.

مصطلحات موضوعية: *PROTEIN metabolism, *APOPTOSIS, *CELL culture, *CELL lines, *CELLULAR signal transduction, *CHROMATOGRAPHIC analysis, *FLAVONOIDS, *HIGH performance liquid chromatography, *HYDROGEN peroxide, *LACTATE dehydrogenase, *MEDICINAL plants, *NEURODEGENERATION, *NUCLEAR magnetic resonance spectroscopy, *RESEARCH funding, *STAINS & staining (Microscopy), *THIN layer chromatography, *WESTERN immunoblotting, *PLANT extracts, *OXIDATIVE stress, *CELL survival

مستخلص: In this study, a new flavonolignan vernicilignan A was isolated from Toxicodendron vernicifluum. The neuroprotective effects of this compound against H 2 O 2 induced cell injury in SH-SY5Y cells were evaluated by MTT assay and LDH release assay. Vernicilignan A dose-dependently attenuated the cell injury and LDH release induced by H 2 O 2 in SH-SY5Y cells. Further study indicated that vernicilignan A reduced cell apoptosis caused by H 2 O 2 treatment via regulation of some apoptotic related proteins including Bax, Bcl-2, caspase 3 and caspase 9. Also, vernicilignan A increase the cell viability of H 2 O 2 treated cells via the activation of Akt and GSK3β. Base on the findings, vernicilignan A exhibited neuroprotective effects through the activation of PI3K/Akt signaling and inhibition of mitochondria apoptosis pathway. Vernicilignan A might be a promising therapeutic agent for oxidative stress induced neurodegenerative diseases. Unlabelled Image [ABSTRACT FROM AUTHOR]

المؤلفون: Wang, Jing¹, Luo, Weizao^1,2, Li, Bing¹, Lv, Junping³, Ke, Xiuhui¹, Ge, Dongyu¹, Dong, Ruijuan¹, Wang, Chunguo⁴, Han, Yue¹, Zhang, Cong¹, Yu, Haichuan⁵, Liao, Yan¹ liaoyanaa@sohu.com

المصدر: Journal of Ethnopharmacology. Dec2018, Vol. 227, p237-245. 9p.

مصطلحات موضوعية: *LIVER analysis, *ENZYME analysis, *PROTEIN metabolism, *POLYSACCHARIDES, *STATISTICAL significance, *GLUTATHIONE, *IN vivo studies, *MEDICINAL plants, *CYTOCHROME P-450, *NUCLEAR factor E2 related factor, *ANIMAL experimentation, *SUPEROXIDE dismutase, *HEPATOTOXICOLOGY, *MALONDIALDEHYDE, *GENE expression, *HISTOLOGICAL techniques, *LACTATE dehydrogenase, *PLANT extracts, *ALTERNATIVE medicine, *MICE, *ALANINE aminotransferase, *ASPARTATE aminotransferase

مستخلص: Abstract Ethnopharmacological relevance The Sagittaria sagittifolia L. polysaccharide (SSP) is a purified form of a homogeneous polysaccharide isolated from the root tubers of S. sagittifolia , which has been used as a protectant against hepatotoxicity induced by coadministration of isoniazid and rifampicin. However, the protective effect of SSP against isoniazid- and rifampicin-induced liver injury has never been studied. Aim of the study In this study, the hepatoprotective effect of SSP and its underlying mechanism were investigated in mice with isoniazid- and rifampicin-induced liver injury. Materials and methods Liver injury was induced in mice by intragastric administration of isoniazid and rifampicin, and the mice were divided into the following six groups: standard control (administration of saline by gavage), model (intragastric administration of isoniazid and rifampicin at 100 mg/kg/day each), positive control (100 mg/kg/day silymarin by gavage 4 h after isoniazid and rifampicin administration), and SSP-treated (200, 400, or 800 mg/kg/day SSP by gavage after isoniazid and rifampicin administration). Subsequently, blood and liver samples were collected from all the animals and were assessed. Results SSP significantly alleviated the liver injury, as evidenced by decreased activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in the serum and a decreased level of malondialdehyde in the liver, as well as by an increased level of glutathione and increased activities of superoxide dismutase and catalase in the liver. SSP also effectively reduced the pathological tissue damage. The gene and protein expression of cytochrome P450 (CYP) 2E1 and CYP3A4 was inhibited by SSP. The gene and protein expression of nuclear factor erythroid 2-related factor 2 (NRF2), glutamate-cysteine ligase, and heme oxygenase-1 were induced by SSP, whereas that of Kelch-like ECH-associated protein 1 was inhibited. Conclusions SSP exerts a protective effect against isoniazid- and rifampicin-induced liver injury in mice. The underlying mechanisms may involve activation of NRF2 and its target antioxidant enzymes and inhibition of the expression of CYPs. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

المؤلفون: Lai, Zelin¹ (AUTHOR), Li, Cong¹ (AUTHOR), Ma, Huihan² (AUTHOR), Hua, Shiting¹ (AUTHOR), Liu, Zhizheng¹ (AUTHOR), Huang, Sixian¹ (AUTHOR), Liu, Kunlin¹ (AUTHOR), Li, Jinghuan¹ (AUTHOR), Feng, Zhiming¹ (AUTHOR), Cai, Yingqian¹ (AUTHOR), Zou, Yuxi¹ (AUTHOR), Tang, Yanping¹ (AUTHOR), Jiang, Xiaodan¹ (AUTHOR) jiangxd@smu.edu.cn

المصدر: Journal of Ethnopharmacology. May2023, Vol. 308, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *CYTOKINES, *MEDICINAL plants, *NEURONS, *SEQUENCE analysis, *AUTOPHAGY, *ANIMAL experimentation, *WESTERN immunoblotting, *GLYCOSIDES, *SIGNAL peptides, *APOPTOSIS, *NEUROINFLAMMATION, *GENE expression, *LACTATE dehydrogenase, *GENE expression profiling, *ENZYME-linked immunosorbent assay, *FLUORESCENT antibody technique, *BRAIN injuries, *ACUTE diseases, *MICE, *CASPASES

مستخلص: Hydroxysafflor yellow A (HSYA) is the principal bioactive compound isolated from the plant Carthamus tinctorius L. and has been reported to exert neuroprotective effects against various neurological diseases, including traumatic brain injury (TBI). However, the specific molecular and cellular mechanisms underlying HSYA-mediated neuroprotection against TBI are unclear. This study explored the effects of HSYA on autophagy and the NLRP3 inflammasome in mice with TBI and the related mechanisms. Mice were subjected to TBI and treated with or without HSYA. Neurological severity scoring, LDH assays and apoptosis detection were first performed to assess the effects of HSYA in mice with TBI. RNA-seq was then conducted to explore the mechanisms that contributed to HSYA-mediated neuroprotection. ELISA, western blotting, and immunofluorescence were performed to further investigate the mechanisms of neuroinflammation and autophagy. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was applied to determine the connection between autophagy and the NLRP3 inflammasome. HSYA significantly decreased the neurological severity score, serum LDH levels and apoptosis in mice with TBI. A total of 921 differentially expressed genes were identified in the cortices of HSYA-treated mice with TBI and were significantly enriched in the inflammatory response and autophagy. Furthermore, HSYA treatment markedly reduced inflammatory cytokine levels and astrocyte activation. Importantly, HSYA suppressed neuronal NLRP3 inflammasome activation, as indicated by decreased levels of NLRP3, ASC and cleaved caspase-1 and a reduced NLRP3+ neuron number. It increased autophagy and ameliorated autophagic flux dysfunction, as evidenced by increased LC3 II/LC3 I levels and decreased P62 levels. The effects of HSYA on the NLRP3 inflammasome were abolished by 3-MA. Mechanistically, HSYA may enhance autophagy through AMPK/mTOR signalling. HSYA enhanced neuronal autophagy by triggering the AMPK/mTOR signalling pathway, leading to inhibition of the NLRP3 inflammasome to improve neurological recovery after TBI. [Display omitted] • HSYA inhibits neuronal NLRP3 inflammasome activation after TBI. • HSYA augments neuronal autophagy and ameliorates autophagic flux dysfunction. • HSYA induces autophagy to suppress NLRP3 inflammasome. • HSYA may trigger AMPK/mTOR signalling to enhance autophagy. [ABSTRACT FROM AUTHOR]

المؤلفون: Gan, Yanxiong^1,2 ganyanxiong@139.com, Zheng, Shichao³ zsc305@hotmail.com, Zhao, Jiaqi^1,2 513142926@qq.com, Zhang, Chen^1,2 zhangchen_baiji@163.com, Gao, Tianhui^1,2 gaotianhui1349@163.com, Liao, Wan^1,2 liaowan2011@126.com, Fu, Qiang⁴ Peter028@126.com, Fu, Chaomei^1,2 chaomeifu@126.com

المصدر: Journal of Ethnopharmacology. Jul2018, Vol. 221, p10-19. 10p.

مصطلحات موضوعية: *ALGORITHMS, *ASPARTATE aminotransferase, *CELLULAR signal transduction, *HEPATITIS, *HIGH performance liquid chromatography, *INFLAMMATORY mediators, *INFORMATION retrieval, *LACTATE dehydrogenase, *LIVER, *MEDICINAL plants, *METABOLISM, *TRANSFORMING growth factors-beta, *DNA-binding proteins, *PHYTOCHEMICALS, *ALANINE aminotransferase, *ONTOLOGIES (Information retrieval), *DISEASE progression, *CURCUMIN, *PHARMACODYNAMICS

مستخلص: Ethnopharmacological relevance Curcuma phaeocaulis Val. ( CP ), as the vital medicines for blood-breaking and disorder-eliminating, has been widely used for hepatitis with good curative effects. Owing to the complexity of traditional Chinese medicine, the pharmacological mechanism of CP remains unclear. To solve this problem, a protein network module-based approach was proposed in this study. Materials and methods Firstly, the content of active components of CP was detected based on HPLC-DAD. Then the liver protection of CP on Con A-induced hepatitis was validated via the analysis of serum levels of ALT, AST and LDH and histological findings. Next, the targets of CP components obtained from TCMD database were predicted by STITCH and ChEMBL retrieval. In addition, the protein interaction network (PIN) of CP was constructed by Cytoscape based on protein-protein interaction of targets obtained from STRING database. Following the topological analysis of CP PIN, it showed to exhibit the properties of scale-free, small world, and modularity matched with the property of complex biological networks. Finally, the functional modules were identified by gene ontology enrichment analysis based on Molecular Complex Detection algorithm. Results The functional modules indicated that the mechanism of CP acting on the hepatitis is significantly associated with NF-κB and TGF-β signaling pathway. More interestingly, curcumin, demethoxycurcumin and bisdemethoxycurcumin were the main active components of CP acting on the hepatitis, which were demonstrated to be associated with the inflammatory process that occurs during the progression of hepatitis. Conclusion The protein network module-based approach is an efficient way to investigate the pharmacological mechanisms of CP . [ABSTRACT FROM AUTHOR]

المؤلفون: Choucry, Mouchira A.¹ mouchira.choucry@pharma.cu.edu.eg, Khalil, Mohammed N.A.¹ mohamed.nabil@pharma.cu.edu.eg, El Awdan, Sally A.² sallyelawdan@ymail.com

المصدر: Journal of Ethnopharmacology. Mar2018, Vol. 214, p47-57. 11p.

مصطلحات موضوعية: *ISCHEMIA prevention, *INFLAMMATION prevention, *REPERFUSION injury, *THERAPEUTICS, *ENZYME metabolism, *ALTERNATIVE medicine, *ANIMAL experimentation, *APOPTOSIS, *BARK, *CREATININE, *FLAVONOIDS, *GLUTATHIONE, *HISTOLOGICAL techniques, *INTERLEUKINS, *KIDNEYS, *LACTATE dehydrogenase, *LEAVES, *LIQUID chromatography, *MASS spectrometry, *MEDICINAL plants, *AYURVEDIC medicine, *RATS, *PLANT stems, *TUMOR necrosis factors, *DNA-binding proteins, *PLANT extracts, *OXIDATIVE stress, *BLOOD urea nitrogen, *IN vivo studies

مستخلص: Ethnopharmacological relevance Crateva nurvala stem bark is commonly used in Ayruveda in treatment of many renal injuries, e.g., urinary lithiasis, diuretic and nephroprotective. However, its protective effect against renal ischaemia/reperfusion, the major cause of acute kidney injury, has never been studied. Moreover, no comprehensive chemical profiling of its extracts was recorded. Aim of the study Assessment of the protective effect of the plant extracts against renal ischaemia/reperfusion and elucidation of the possible mechanism of action. Then, to determine its bioactive constituents using modern UPLC-HRMS technique. Material and methods Unilateral ischaemia was induced by clamping the left renal artery for 1 h then reperfusion for 24 h. Rats were divided in 4 groups: i) sham-operated group, ii) ischaemia/reperfusion, I/R group, iii) I/R protected by previous administration of Crateva leaves extract, CLE group and iv) I/R protected by previous administration of Crateva bark extract, CBE group. At the end of reperfusion, blood samples were analyzed for renal function biomarkers. Kidneys were examined histopathologically and their homogenates were used in determining the intracellular levels of oxidative stress, inflammatory, and apoptosis markers. Results Leaves and bark extracts attenuated the deleterious effects of I/R apparent in reducing LDH, creatinine and blood urea nitrogen levels. The extracts reduced the oxidative stress by replenishing the glutathione levels and Nrf2 factor levels. Moreover, extracts decreased levels of pro-inflammatory TNF-α, NF-κβ and IL-6; which ultimately resulted in reducing the pro-apoptotic caspase-3. Bark and leave extracts have quite similar chemical profile where 42 compounds of various chemical classes were identified. Flavonoids are the major class of the bioactive phytochemicals Conclusion C. nurvala extracts had effectively ameliorated the deleterious effects of renal I/R by mainly counteracting oxidative stress and presumably inflammation. Consequently, it can be used as a complementary treatment with other agents. In this aspect, leaves stand as a sustainable alternative to bark. The presented chemical profiling can be used in future standardization and quality control of the drug. [ABSTRACT FROM AUTHOR]