Ethnopharmacology

Protective effect of Shaoyao Decoction against colorectal cancer via the Keap1–Nrf2–ARE signaling pathway Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Xiaoyan Wang, Shakir M. Saud, Xiwen Zhang, Weidong Li, Baojin Hua Abstract Ethnopharmacological relevance Ulcerative colitis is one of the three high risk factors for colorectal cancer. Studies have found that about 20% of cancers are caused by repeated chronic inflammatory stimuli over a long period of time. Ulcer-related colorectal cancer is one of the main causes of death in patients with ulcerative colitis. At present, surgery is the first choice for the treatment of colorectal cancer, combined with radiotherapy and chemotherapy, which have serious side effects. However, reportedly, a compound prescription of Chinese traditional medicine Shaoyao Decoction (SYD) commonly used to treat damp-heat dysentery has anti-colorectal cancer effect. Thus this study described the effect of SYD to AOM/DSS-induced colon cancer model. Aim of the study In this study, modern biomedical approaches were employed for investigating the protective/preventive effects of SYD in mice with azoxymethane (AOM)/DSS-induced CRC. Materials and methods The mice pretreated with AOM/DSS were randomly allocated to SYDL, SYDM, SYDH group and SASP (sulfasalazine) group. Mice without AOM/DSS treatment were randomly divided into PBS control group and SYD control group. Results It was found that SYD inhibited the production of inflammatory cytokines, TNF-α, IL-1β, superoxide dismutase (SOD), and malonaldehyde (MDA), and increased the antioxidant indices, as measured by the mRNA expression of GR, TR, HO-1, γ-GCSc, γ-GCSm, NQO-1, UGT1A1, and UGT1A10 in AOM-treated mice. Particularly, the expressions rates of NF-κB and Ki-67 in the SYD-treated experimental groups were significantly lower than those in the model group, indicating that the proliferative ability of the CRC tissues was weaker in the SYD-treated experimental groups. Moreover, the positive levels of Nrf2 in the SYD-treated experimental groups were slightly higher than those in the model group, suggesting that SYD exhibited antioxidant activity. Conclusions To sum up, our results suggest that SYD inhibits the development of acute/chronic colitis and prevents colitis-associated CRC by suppressing inflammation and preventing oxidative stress-induced cellular damage. Graphical abstract

Danhong Huayu Koufuye prevents venous thrombosis through antiinflammation via Sirtuin 1/NF-κB signaling pathway Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Han Liu, Peng Li, Juan Lin, Wenpei Chen, Haibiao Guo, Jianyun Lin, Jin Liu, Ziqi Lu, Xiaolan Yao, Yang Chen, Baoqin Lin Abstract Ethnopharmacological relevance Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiongrhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (Citrus aurantium L.). DHK prevents deep vein thrombosis (DVT) through antiinflammation. However, the antiinflammatory mechanism of DHK is still unknown. Objective The aim of this study was to evaluate whether DHK prevented venous thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway. Methods Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4 mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25 mg/kg/d, p.o.), resveratrol (50 mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. Blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK. Results DHK remarkably prevented DVT. DHK had no effects on blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527. Conclusion DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway. Graphical abstract

Preparation, structural identification and intervention on immunodeficiency mice of enzymatic peptides from Mauremys mutica and Cuora trifasciata Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Yan-bo Lv, Qing Zhou, Yang Fan, Jiu-liang Zhang Abstract Ethnopharmacology relevancy Mauremys mutica (Asian yellow pond turtle, YPT) and Cuora trifasciata (Chinese three-striped box turtle, TBT) are traditional Chinese medicine. They possess many biological characteristics, such as immune enhancement, anti-inflammatory, anti-cancer effects. They have long been used as folk anti-cancer drugs in central and southern China. However, there was no studies to compare the immune enhancement effect of YPT and TBT, nor to identify the structures of YPT peptides and TBT peptides. Aims of the study: The aim of this study was to evaluate the protective efficacy of YPT and TBT on immunodeficient mice and to compare the primary structures of YPT peptides and TBT peptides. Materials and methods The protein extracts were extracted using boiling water, and peptides were obtained by hydrolyzing protein extract with alkaline protease. Cyclophosphamide (CTX) was used to induce immunodeficiency in mice. The immune enhancement effect was evaluated by measuring body weight gain curve, thymus index, spleen index, serum SOD activity and GSH-Px activity. Primary structure of peptides identified by HPLC-ESI-MS/MS. Results The protein extracts and peptides of the YPT and TBT had certain recovery effects on immunodeficient mice. YPT peptides has the best effect on the recovery of damaged immune organs in mice. In the identification of the primary structure of the polypeptide, YPT and TBT have some similar peptide segments, but there are also many differences. This may be the reason why they have the same function and different effects, which lays the foundation for the follow-up mechanism researches. Conclusions Two kinds of healthy turtle protein extracts and peptides had certain recovery effects on immune injury in mice. YPT peptides possessed the best effect on the recovery of immunodeficiency. Graphical abstract

Integrated pathological cell fishing and network pharmacology approach to investigate main active components of Er-Xian decotion for treating osteoporosis Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Nani Wang, Pingcui Xu, Xuping Wang, Weixuan Yao, Zhongming Yu, Renjie Wu, Xiaowen Huang, Yuyang Si, Dan Shou Abstract Ethnopharmacological relevance Oxidative damage to osteoblasts was a key factor in the development of osteoporosis. Er-Xian Decotion (EXD) is widely used in China for the treatment of osteoporosis, which has a variety of antioxidant active ingredients. EXD may be an important source of protection against oxidative damage in osteoblasts, but the anti-osteoporotic active components of EXD is currently unclear. Aim of the study This work established an effective and reliable drug screening method to find main active ingredients in EXD (M-EXD) that can protect osteoblasts against oxidative stress and achieve anti-osteoporosis effects. Materials and methods H2O2-induced osteoblast cell fishing with UHPLC-QTOF/MS was firstly used to discover the potential active components from EXD. Afterword, the EXD compound-osteoporosis target network was constructed using network pharmacology, thus potentially anti-osteoporosis ingredients were founded, and their combination were defined as the M-EXD. Finally, pharmacology effects of M-EXD was evaluated by ovariectomized rats, prednisolone induced-zebrafish and H2O2-induced osteoblasts. Results 40 candidate active ingredients in EXD were initially screened out via pathological cell fishing. According to network pharmacology result, M-EXD consisted of 13 ingredients since they had a close relationship with 65 osteoporosis-related targets. Pharmacological evaluation showed that M-EXD significantly ameliorated oxidative stress in H2O2-induced osteoblast model, evidently reversed the activity of ALP, ROS, GSH-px, NO and MDA compared with the model group. M-EXD showed better anti-oxidative activities than individual ingredients, presenting obvious synergetic effects. In osteoporosis rat and zebrafish models, M-EXD also demonstrated good anti-osteoporotic properties by mitigating the osteoporosis bone loss and increasing serum bone morphogenetic protein 2, and reversing osteocalcin expression in bone tissue. It significantly ameliorated oxidative stress in the in-vivo models. Moreover, M-EXD and EXD showed similar anti-osteoporotic and anti-oxidative properties, while the rest components of EXD had no satisfactory anti-osteoporotic efficacy. Conclusions Our work successfully identified the main active components in EXD, which could represent the efficacy of EXD on treating osteoporosis, and meanwhile, it also provided an effective strategy to investigate active ingredients from natural medicines, which might be helpful for drug development and application. Graphical abstract

Ethnopharmacology in the Upper Guadiana River area (Castile-La Mancha, Spain) Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Diego Rivera, Alonso Verde, José Fajardo, Concepción Obón, Vicente Consuegra, José García-Botía, Segundo Ríos, Francisco Alcaraz, Arturo Valdés, Alejandro del Moral, Emilio Laguna Abstract Ethnopharmacological relevance Determining traditional remedies for human pathologies is relevant, when compared with the standard materia medica of the pharmacopoeias and dietary supplement databases, because we can assess the species and uses that have been previously studied and target understudied species for further pharmacological investigation. Background The aim of this study was to systematically record and analyze medicinal uses of natural resources (Plantae, Animalia, Fungi and minerals), mostly local, in the territories adjoining the upper Guadiana River and its tributaries. We were particularly interested in recording resources and pathologies linked to wetland areas, especially in the National Parks Las Tablas de Daimiel and Cabañeros. Wetlands are interesting because they present a double face in relation with human health: Wetlands furnish hydration, safe water, nutrition, and medicinal resources; are places from which people derive their livelihood. However wetlands are also sites of exposure to pollution or toxicants, and infectious diseases; and sites of physical hazards. We wanted to identify procedures for preparation of medicinal formulae and routes of administration. We also intended to detect whether a geographical pattern exists or not in our records in relation to the use of local resources. Methods We used semi-structured interviews with one-to-one informants or groups, from 1998 to 2018. Raw data were introduced in a Firebird database and analyzed. To identify ingredients and pathologies we consulted local floras and epidemiological literature. Finally, we compared documented pathologies, remedies and ingredients in the historical context of medicinal uses of natural resources in Castile-La Mancha and especially in Ciudad Real. Results 126 pathologies and 220 species furnishing ingredients have been recorded from the interviews. In total, 188 are plants and 20 animals. The most commonly used species include Malva sylvestris, Phlomis lychnitis, Genista tridentata and Thymus mastichina. Most records refer to flowers, or fruits, of locally available plant species, classified as Mediterranean, European or widespread that belong to the Lamiaceae, Compositae or Leguminosae. Ingredients which are collected in open shrublands, known as "garrigue", and dry grasslands furnish a relevant proportion of records while the imported ingredients remain marginal. The contribution of wetlands, riverine habitats and irrigated fields and gardens as a source of medicinal resources is 36% of the records. It is relatively high considering its limited presence in terms of total extension within the study area. The most frequently reported diseases are respiratory, gastrointestinal, dermatological and infectious or parasitic. Conclusions Along the Guadiana River in the Ciudad Real province exists a wide and deep knowledge of traditional remedies for the treatment of common pathologies, based fundamentally on the use of local flora, fauna and mineral resources. The uses and ingredients documented are useful for further pharmacological investigation to improve health care for a wide range of pathologies. Graphical abstract

Carica papaya seed extract slows human sperm Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): V. Ghaffarilaleh, D. Fisher, R. Henkel Abstract Ethnopharmacological relevance Traditional healers use Carica papaya seeds as a remedy for diseases and as a contraceptive for men and abortion in women. Material and methods Semen samples from 35 healthy men were allowed to liquefy and subsequently incubated for 60 min in Human Tubular Fluid medium containing 1% bovine serum albumin with aqueous C. papaya seed extract at concentrations of zero, 0.025, 0.25, 2.5, 25, 250 and 2500 μg/ml. Afterwards, sperm were washed and used for assessment of capacitation and acrosome reaction, DNA fragmentation, vitality, motility, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP). Results The extract showed no effects on straight-line velocity, linearity, straightness, beat-cross frequency and the percentage of capacitated, acrosome-reacted sperm. In contrast, vitality, total motility, progressive motility, curvilinear velocity, average-path velocity and the percentages of hyper-activated, ROS-positive and MMP-intact sperm decreased significantly (P < 0.05), while the percentage of DNA-fragmented sperm increased (P < 0.05). Conclusions Our data show that aqueous C. papaya seed extract significantly and negatively affects sperm motility parameters crucial for fertility; and thus, poses as a likely candidate for male contraception. Graphical abstract

Mass spectrometry-based urinary metabolomics for the investigation on the mechanism of action of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves against ischemic stroke in rats Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Rongjin Wang, Liqiang Shi, Shu Liu, Zhiqiang Liu, Fengrui Song, Zhiheng Sun, Zhongying Liu Abstract Ethnopharmacological relevance As a traditional Chinese medicine, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. leaves (ESL) can treat ischemic, neurasthenia, and hypertension diseases. However, only few studies have been conducted on the mechanism of action of ESL for ischemic disease treatment. Aim of the study This study aimed to discover the potential biomarkers in the rats caused by ischemic stroke and build a gene–enzyme–biomarker network to explore the mechanism of ESL treatment on ischemic stroke further. Materials and methods The urinary metabolomics strategy was developed by combining UPLC-Q-TOF/MS with multivariate data analysis. The gene-enzyme-biomarker network was built by Cytoscape 3.6.0 on the basis of the potential biomarkers filtered out via urinary metabolomic analysis. Then, the potential target enzymes of ESL in the treatment of ischemic stroke were selected for further validation analysis via the ELISA kits. Results A total of 42 biomarkers associated with ischemic stroke have been identified, among which 38 species can be adjusted by ESL, including 5′-methylthioadenosine, prostaglandin A2, l-methionine, aldosterone, 11b-hydroxyprogesterone, prostaglandin E3, dehydroepiandrosterone, taurine, 5-methoxyindoleacetate, and p-cresol glucuronide. These biomarkers were involved in several metabolic pathways, including taurine and hypotaurine, arachidonic acid, cysteine and methionine, steroid hormone biosynthesis, tryptophan, and tyrosine metabolism pathways. The gene–enzyme–biomarker network was built, and three predicted target proteins, including cyclooxygenase-2 (COX-2), monoamine oxidase (MAO), and nitric oxide synthase (NOS), were selected as the potential target enzymes for ESL in ischemic stroke treatment. Conclusions All results showed that ESL can play a therapeutic role in treating ischemic stroke through different pathways. This study will provide an overall view of the mechanism underlying the action of ESL against ischemic stroke. Graphical abstract

Bioactivities of serotonin transporter mediate antidepressant effects of Acorus tatarinowii Schott Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Feng-Hong Zhang, Zhi-Mei Wang, Yan-Ting Liu, Ji-Sheng Huang, Shuang Liang, Hong-Hua Wu, Yan-Tong Xu Abstract Ethnopharmacological relevance Acrorus tatarinowii Schott has been widely used in the treatments of neuropsychiatric and digestive disorders in clinical practices of traditional Chinese medicine for thousands of years. Both clinical and preclinical studies demonstrated antidepressant effects of A. tatarinowii. However, the possible action mechanisms of antidepressant effects of A. tatarinowii remain unraveled. Aim of the study: The present study aimed to investigate the roles of serotonin transporter (SERT) in antidepressant effects of A. tatarinowii. Materials and methods Antidepressant effects of water extract of A. tatarinowii were evaluated by forced swimming test (FST), tail suspension test (TST) and locomotor activity test. The water extract was analyzed by ultra high performance liquid chromatography (UPLC) method. Two major fractions of A. tatarinowii, petroleum ether extract and water extract after petroleum ether processed, were prepared and analyzed by UPLC method. Further, volatile oil extracted by ether extraction, solid phase micro-extraction (SPME) and hydro-distillation were compared and analyzed by gas chromatography-mass spectrometer (GC-MS) method. Finally, major constituents of water extract of A. tatarinowii were isolated by preparative high performance liquid chromatography (HPLC) and identified by extensive spectroscopic analyses. Effects of all of the above mentioned samples on SERT activity were tested by a high content assay (HCA). Results Results of FST, TST and locomotor activity confirmed that water extract of A. tatarinowii significantly decreased mice immobility time but did not change mice locomotor activity. UPLC analysis results revealed that the water extract contained trace amount of β-asarone (0.0004206%) and α-asarone (0.0001918%). HCA results demonstrated that the water extract significantly enhanced SERT activity at 100 μg/mL. Further, GC-MS and UPLC analyses revealed that petroleum ether extract contained high content of β-asarone (45.63%) and α-asarone (12.50%). GC-MS analysis results demonstrated that the volatile oil extracted by ether extraction, SPME and hydro-distillation contained similar major components. HCA results verified that the petroleum ether extract significantly enhanced SERT activity at 1.56 μg/mL. Moreover, UPLC analysis of water extract after petroleum ether processed did not show any characteristic peaks. HCA results demonstrated that this extract significantly inhibited SERT activity at 50–100 μg/mL. Finally, phytochemistry investigation on the water extract of A. tatarinowii afforded seven constituents including veratric acid (9), anisic acid (7), 3,4,5-trimethoxybenzoic acid (3), trans-isoferulic acid (2), 2,4,5-trimethoxybenzoic acid (11), 4-hydroxybenzoic acid (6) and syringic acid (13). Their structures were established on the basis of nuclear magnetic resonance (NMR) and mass spectrometer (MS) data and comparative UPLC analyses. HCA results demonstrated the major components of the water extract of A. tatarinowii demonstrated SERT enhancement/inhibition activities. Conclusions This study first systematically demonstrated the roles of SERT activity in antidepressant effects of A. tatarinowii, including water extract, major fractions and main constituents. These results revealed that A. tatarinowii could regulate SERT activities in bidirectional ways. Graphical abstract Serotonin transporters play important roles in antidepressant effects of Acorus tatarinowii.

Alkaloids of dendrobium nobile lindl. Altered hepatic lipid homeostasis via regulation of bile acids Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): Si Huang, Qing Wu, Hao Liu, Hua Ling, Yuqi He, Changhong Wang, Zhengtao Wang, Yanliu Lu, Yuanfu Lu Abstract Ethnopharmacological relevance Accumulation of hepatic lipid promotes systemic metabolic dysfunction and results in fatty liver. Our previous studies have shown that the alkaloids of Dendrobium nobile Lindl. (DNLA) could regulate the lipid metabolism gene expression in livers of mice. However, the protective effects on hepatic lipid homeostasis and the underlying mechanisms are still unclear. Materials and methods The C57BL/6 male mice were randomly divided into four groups, including control group, model group, DNLA treatment group, and simvastatin positive control group. Mice in the control group and the other three groups were fed with control diet and high fat diet during the full course of this study, respectively. Hepatic lipid accumulation was induced by HFD in mice after 18 weeks of feeding. DNLA (15 mg/kg) and simvastatin (20 mg/kg) were administrated intragastrically in the DNLA treatment group and simvastatin positive control group for another 18 weeks, respectively. HE staining and Oil-Red-O staining of liver tissues were observed. TC and TG levels in liver were assayed. The amount of major bile acids in mice livers were quantified by UPLC-MS. Expression levels of genes were tested by the real-time PCR. Results The results of HE staining and Oil-Red-O staining showed that DNLA could improve hepatic lipid homeostasis. DNLA significantly decreased liver TC and TG levels in the DNLA group. Moreover, the UPLC-MS analysis showed that DNLA did not only influence the hepatic bile acid quantity but did raise the hydrophilicity. Compared with the model group, DNLA decreased the hepatic levels of several free bile acids, including LCA, DCA, CA, and CDCA, and increased most important taurine-conjugated bile acids levels in liver, including TMCAs, TCDCA, TUDCA, and THDCA. In addition, DNLA also decreased the CA/CDCA ratio. The gene expression levels of Cyp27a1, Cyp3a11, Fxr, and Shp were up-regulated in DNLA treatment group. Conclusion DNLA may improve the hepatic abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the taurine-conjugated bile acids which are highly hydrophilic and contribute to the excretion of cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption. Graphical abstract

Dalspinin isolated from Spermacoce hispida (Linn.) protects H9c2 cardiomyocytes from hypoxic injury by modulating oxidative stress and apoptosis Publication date: 15 September 2019 Source: Journal of Ethnopharmacology, Volume 241 Author(s): R. Lakshmi Sundaram, Hannah R. Vasanthi Abstract Ethnopharmacological relevance Spermacoce hispida (S.hispida), a potential medicinal plant has been traditionally used as an antibacterial, antieczemic, antihypertensive, antidiabetic and antihyperlipidemic agent. Although, this plant has been claimed to protect against oxidative injury and inflammatory conditions in recent studies, its cardioprotective effect and the active constituents responsible for its bioactivity is sparsely studied. Hence this work is undertaken to study the active biomolecule responsible for modulating the cardiomyocytes on hypoxic injury relevant to its ethanopharmacology. Aim of the study The current study is to isolate and characterize a bioactive molecule from S.hispida, which exhibits protection against hypoxic injury in an in vitro hypoxic model of cultured H9c2 cardiomyocytes. Materials and methods The methanolic extract of S.hispida plant was fractionated with various solvents sequentially. The ethyl acetate fraction that was concentrated and chromatographed over silica gel column eluted 18 fractions, which yielded 5 compounds, which were characterized using spectral data. The isolated new compound was further tested for its protective effect against hypoxic injury, wherein cobalt chloride (CoCl2) was used to induce hypoxia in H9c2 cardiomyoblasts. To evaluate the protective effect of the isolated compound, the markers of oxidative stress, apoptosis, and cell death were checked by endogenous levels of antioxidants, [malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH)], lactate dehydrogenase (LDH) activity and immunoblot (HIF-α, Bcl2, Bax, procaspase and cleaved caspase-3). Results Among the five compounds isolated and characterized from S. hispida methanolic extract, β-sitosterol, ursolic acid, quercetin and rutin were known phytochemicals, while the new isoflavone was identified as dalspinin-7-0-β-D-galactopyranoside (DBG). Among the isolated compounds, the antioxidant potential of DBG confirmed by DPPH free radical scavenging and ORAC assays was superior. CoCl2-induced hypoxic condition significantly decreased cell viability, SOD activity, GSH concentration and increased the level of MDA and LDH activity. Western blot studies revealed an upregulation of HIF-1α, Bax and caspase and down regulation of Bcl-2 expression. The oxidative abnormalities were ameliorated by DBG pretreatment, as deduced by the reduced CoCl2-induced cytotoxicity, MDA concentration, LDH activity and the expression of HIF-1α, Bax and caspase and the enhanced levels of SOD, GSH and Bcl2 expression in a dose-dependent manner. Conclusion DBG protects H9c2 cells from CoCl2-induced hypoxic damage by mitigating oxidative stress and preserving cell viability. The overall findings highlight the protective action of DBG, a potential source of antioxidant of natural origin against hypoxic injury and may help in mitigating the progress of oxidative stress in cardiac cell death. Graphical abstract

Alexandros Sfakianakis
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