Multidrug-resistant pathogens are a significant clinical problem. Efflux pump inhibitors (EPIs) can restore the activities of existing antibiotics by interfering with drug efflux pumps located in bacterial cell membranes. Seaweeds are important sources of biologically active metabolites of natural origin; however, their potential as EPIs remains uninvestigated. Here, functional extracts from the brown seaweeds Laminaria japonica and Sargassum horneri and the red seaweeds Gracilaria sp. and Porphyra dentata were evaluated as potential EPIs against drug-resistant Escherichia coli. All these extracts were found to potentiate the activities of drugs in modulation tests, although not to the same extent. Synergistic effects of the extracts and the drug clarithromycin were observed from the onset of Time-kill assays, with no evidence of bacterial regrowth. Ethidium bromide accumulation studies revealed that the efflux decreased in the presence of each extract, as indicated by the presence of EPIs. Most identified EPIs that have been discovered to date have aromatic structures, and the seaweed extracts were found to contain various terpenes, terpenoids, phenolic compounds, indoles, pyrrole derivatives, alkaloids, and halogenated aromatic compounds. Our study highlights the potential of these compounds of the seaweeds as drug EPIs.

Wen-Jung Lu

Hsuan-Ju Lin

Pang-Hung Hsu

Margaret Lai

Jen-Yu Chiu

Hong-Ting Victor Lin

Brown and Red Seaweeds Serve as Potential Efflux Pump Inhibitors for Drug-Resistant Escherichia coli

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality. However, the therapies remain limited. Traditional Chinese medicine (TCM) has been used for treating kidney disease for thousands of years and is an effective alternative treatment for CKD patients in China and other Asian countries. In the present study, we aimed to investigate the effect and mechanism of Huangqi-Danshen decoction (HDD), a TCM herbal decoction, on treating CKD. CKD rat model was induced by adding 0.75&#x25; adenine to the diet for 4 weeks. HDD extract was administrated orally to CKD rats at the dose of 4.7 g/kg/d for consecutive 4 weeks in adenine-induced CKD rats. Kidney function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The pathological changes of kidney tissues were observed by periodic acid-Schiff (PAS) and Masson&#x2019;s trichrome staining. The proteins expression of renal fibrosis and mitochondrial dynamics were determined and quantified by Western blot analysis. CKD rats showed obvious decline in renal function as evidenced by increased levels of Scr and BUN, which were blunted by HDD treatment. HDD could also improve tubular atrophy and interstitial fibrosis of CKD rats. Moreover, HDD downregulated fibronectin, type IV collagen, and &#x3b1;-smooth muscle actin expression in CKD rats. Furthermore, mitochondrial dynamics was disturbed in CKD rats, which manifested as increased mitochondrial fission and decreased mitochondrial fusion. HDD treatment restored mitochondrial dynamics in CKD rats by repressing dynamin-related protein 1 and Mid 49/51 expression, promoting mitofusin 2 expression, and suppressing optic atrophy 1 proteolysis. In conclusion, HDD could significantly retard CKD progression through modulating mitochondrial dynamics.

Xinhui Liu

Shiying Huang

Fochang Wang

Lin Zheng

Jiandong Lu

Jianping Chen

Shunmin Li

Huangqi-Danshen Decoction Ameliorates Adenine-Induced Chronic Kidney Disease by Modulating Mitochondrial Dynamics

Green tea (Camellia sinensis) has many biological activities and may promote diabetic wound healing by regulation of circulating hypoxia responsive microRNAs (HRMs) which triggers the wound repairing process in diabetic and nondiabetic wounds. Thus, in this study, the potential effects of green tea extract (GTE) on the expression of miRNAs; miR-424, miR-199a, miR-210, miR-21, and fibrogenitic markers; hydroxyproline (HPX), fibronectin (FN), and nitric oxide (NO) were evaluated in wounds of diabetic and nondiabetic rats. The animals were topically treated with vaseline, 0.6&#x25; GTE, and 5&#x25;w/w povidone iodine (standard control). HPX, FN, and NO levels and microRNAs, miR-424, miR-210, miR-199a, and miR-21, were estimated in wound tissues using colorimetric, immunoassay, and molecular PCR analysis. In vitro analysis was performed to estimate active constituents and their antioxidant activities in methanolic green teat extract (GTE). Wounds treated with green tea, a dose of 0.6, healed significantly earlier than those treated with standard vehicle and vaseline treated diabetic wounds. Higher expressions of HRMs, miR-199a, and miR-21, and lower expression of HRMs, miR-424 and miR-210, were significantly reported in tissues following treatment with green tea extract compared to standard control vehicle. The tissues also contained more collagen expressed as measures of HPX, FN, and NO and more angiogenesis, compared to wounds treated with standard control vehicle. Diabetic and nondiabetic wounds treated with green tea (0.6&#x25;) for three weeks had lesser scar width and greater re-epithelialization in shorter periods when compared to standard control vehicle. Expression of HRMs, miR-199a, miR-21, and HRMs and miR-424 and miR-210 correlated positively with HPX, fibronectin, NO, better scar formation, and tensile strength and negatively with diabetes. In addition to antidiabetic and antioxidant activities of green tea components, GTE showed angiogenesis promoting activity in diabetic wound healing. In conclusion, Camellia sinensis extracts in a dose of 0.6&#x25; significantly promote more collagen and fibronectin deposition with higher expression of NO, promoting angiogenesis process via molecular controlling of circulating hypoxia responsive microRNAs: miR-424, miR-210, miR-199a, and miR-21 in diabetic and nondiabetic wounds. Our results support a functional role of circulating hypoxia responsive microRNAs: miR-424, miR-210, miR-199a, and miR-21 as potential therapeutic targets in angiogenesis and vascular remodeling in diabetic wound healing.

Hadeel A. Al-Rawaf

Sami A. Gabr

Ahmad H. Alghadir

Circulating Hypoxia Responsive microRNAs (HRMs) and Wound Healing Potentials of Green Tea in Diabetic and Nondiabetic Rat Models

The present study examined the effects of tetrandrine suppressing proliferation, targeting LC3, p62, and Beclin-1 autophagy genes by inhibiting PI3K/AKT/mTOR signaling in Triple-negative breast cancer (TNBC) MDA-MB-231 cell. Cell viability and apoptosis were evaluated by MTT and Annexin-V/PI double staining. Cytotoxicity was determined with LDH assay. Western Blot and Immunofluorescence were used to measure the protein levels of p62/SQSTM1, Beclin1, LC3-II/LC3-I, and PTEN/PI3K/AKT/mTOR signaling. Results showed that tetrandrine inhibited the MDA-MB-231 cell proliferation and induced the apoptosis. Tetrandrine at doses of 12.8, 16.1, and 25.7μmol/L showed significant cytotoxicity on MDA-MB-231 cells (p&lt;0.01). Tetrandrine induced MDA-MB-231 cell autophagy by decreasing p62/SQSTM1 expression, improving the expression of Beclin1 and LC3-II/LC3-I (p&lt;0.01), inhibiting the PI3K/AKT /mTOR pathway by downregulating the expression of p-AKT <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04979992pt" id="M1" height="11.6412pt" version="1.1" viewBox="-0.0498162 -11.5914 24.8853 11.6412" width="24.8853pt"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><path id="g58-113" d="M327 325C324 350 312 408 304 433C283 442 256 451 213 451C120 451 59 391 59 320C59 243 125 210 188 181C237 158 266 136 266 93C266 52 231 24 195 24C134 24 93 81 74 148L42 143C42 106 51 37 59 23C78 8 125 -12 177 -12C257 -12 345 35 345 127C345 198 292 234 216 264C171 283 131 305 131 348C131 387 156 416 195 416C243 416 277 378 297 317L327 325Z"/></g><g transform="matrix(.0091,0,0,-0.0091,3.495,-5.741)"><path id="g58-99" d="M384 109C349 76 310 59 268 59C197 59 123 113 120 245C240 248 367 259 384 262C403 266 407 275 407 296C407 376 338 451 254 451H253C201 451 148 425 105 378C65 334 39 272 39 203C39 88 112 -12 235 -12C266 -12 339 5 402 84L384 109ZM230 411C285 411 319 365 319 313C319 298 313 293 294 293C236 291 180 290 125 290C141 370 185 411 230 411Z"/></g><g transform="matrix(.0091,0,0,-0.0091,7.444,-5.741)"><path id="g58-112" d="M185 344V453C137 433 92 421 41 413V386C100 378 104 375 104 310V106C104 41 97 35 33 30V0H268V30C190 35 185 41 185 107V283C206 340 240 371 267 371C282 371 296 364 310 351C316 344 325 343 336 348C357 357 369 378 369 399C369 424 345 451 310 451C262 451 219 397 187 344H185Z"/></g><g transform="matrix(.0091,0,0,-0.0091,10.902,-5.741)"><path id="g50-53" d="M462 177V227H365V632H320C217 496 116 350 21 208V177H284V109C284 43 280 38 190 31V0H451V31C369 38 365 43 365 108V177H462ZM284 227H88C155 336 218 430 282 519H284V227Z"/></g><g transform="matrix(.0091,0,0,-0.0091,15.334,-5.741)"><path id="g50-56" d="M453 623H65C60 580 56 530 46 472H80C103 538 110 548 175 548H389C310 380 195 168 90 0L98 -12L175 -2C273 206 366 408 462 610L453 623Z"/></g><g transform="matrix(.0091,0,0,-0.0091,19.767,-5.741)"><path id="g50-52" d="M290 377C321 398 342 415 358 430C378 450 389 473 389 502C389 578 329 635 238 635H237C184 635 137 610 109 578L64 515L88 493C112 529 154 573 208 573S303 542 303 482C303 409 233 370 141 341L149 308C165 313 190 319 215 319C272 319 341 283 341 193C342 98 292 43 222 43C163 43 122 72 96 94C88 101 79 100 70 94C61 87 47 73 46 60C44 47 48 37 62 23C76 10 118 -12 165 -12C238 -12 430 62 430 223C430 297 379 359 290 375V377Z"/></g></svg>/AKT, p-PI3K/PI3K p110α, and p-mTOR <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04979992pt" id="M2" height="11.6412pt" version="1.1" viewBox="-0.0498162 -11.5914 29.3336 11.6412" width="29.3336pt"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><use xlink:href="#g58-113"/></g><g transform="matrix(.0091,0,0,-0.0091,3.495,-5.741)"><use xlink:href="#g58-99"/></g><g transform="matrix(.0091,0,0,-0.0091,7.444,-5.741)"><use xlink:href="#g58-112"/></g><g transform="matrix(.0091,0,0,-0.0091,10.902,-5.741)"><path id="g50-51" d="M414 144C384 79 371 75 317 75H135L276 221C367 316 408 376 408 465C408 570 327 635 237 635C179 635 131 609 100 575L42 494L67 471C94 510 138 565 205 565C277 565 321 517 321 435C321 348 258 270 195 195C146 137 88 81 33 26V0H411C423 44 433 88 446 135L414 144Z"/></g><g transform="matrix(.0091,0,0,-0.0091,15.334,-5.741)"><use xlink:href="#g50-53"/></g><g transform="matrix(.0091,0,0,-0.0091,19.766,-5.741)"><use xlink:href="#g50-53"/></g><g transform="matrix(.0091,0,0,-0.0091,24.198,-5.741)"><path id="g50-57" d="M253 635C142 635 71 555 71 471C71 401 113 353 178 316C144 294 106 267 91 252C70 231 46 202 46 157C46 51 132 -12 241 -12C328 -12 442 52 442 168C442 257 379 305 311 343C354 373 380 398 388 407C406 428 417 458 417 487C417 568 348 635 253 635ZM240 600C288 600 340 563 340 481C340 423 313 387 279 360C207 394 148 427 148 499C148 549 182 600 240 600ZM252 23C188 23 129 73 129 163C129 217 162 266 211 298C289 260 360 217 360 144C360 69 312 23 252 23Z"/></g></svg>/mTOR and upregulating PTEN expression. These findings revealed that tetrandrine could suppress proliferation and induce autophagy in MDA-MB-231 cell by inhibiting the PI3K/AKT/mTOR pathway and might be a promising anti-triple-negative breast cancer drug.

Yubo Guo

Xiaohua Pei

Tetrandrine-Induced Autophagy in MDA-MB-231 Triple-Negative Breast Cancer Cell through the Inhibition of PI3K/AKT/mTOR Signaling

Shuang-Huang-Lian (SHL), an herbal formula of traditional Chinese medicine, is clinically used for bronchial asthma treatment. Our previous study found that SHL prevented basophil activation to suppress Th2 immunity and stabilized mast cells through activating its mitochondrial calcium uniporter. Sporadic clinical reports that SHL was used for the treatment of bronchial asthma can be found. Thus, in this study, we systematically investigated the effects of SHL on asthmatic responses using a shrimp protein (SP)- induced mouse model. SHL significantly inhibited airway inspiratory and expiratory resistance, and histological studies suggested it reduced thickness of airway smooth muscle and infiltration of inflammation cells. It also could alleviate eosinophilic airway inflammation (EAI), including reducing the number of eosinophils and decreasing eotaxin and eosinophil peroxidase levels in the bronchoalveolar lavage fluid (BALF). Further studies indicated that SHL suppressed SP-elevated mouse mast cell protease-1 and IgE levels, prevented Th2 differentiation in mediastinal lymph nodes, and lowered Th2 cytokine (e.g., IL-4, IL-5, and IL-13) production in BALF. In conclusion, SHL attenuates airway hyperresponsiveness and EAI mainly via the inhibition of mast cell activation and Th2 immunity, which may help to elucidate the underlying mechanism of SHL on asthma treatment and support its clinical use.

Yuan Gao

Qiaoling Fei

Ruijuan Qi

Rui Hou

Yixin Han

Runlan Cai

Guibo Sun

Yun Qi

Shuang-Huang-Lian Attenuates Airway Hyperresponsiveness and Inflammation in a Shrimp Protein-Induced Murine Asthma Model

Piper carpunya Ruiz &#x26; Pav. (Piperaceae) is a perennial aromatic shrub of Amazonian area of Ecuador and Peru, belonging to the ethnomedicine of these countries. The traditional preparations of the crude drug (fresh leaves used topically as is, and dried leaves in infusions or decoctions) are known for anti-inflammatory, antiulcer, antidiarrheal, antiparasitic effects, and wound healing properties. In light of this traditional evidence, chemical composition (GC-MS) and biological activity, i.e., antioxidant, antifungal (yeast) capacities, and genotoxicity, of Amazonian P. carpunya leaf essential oil (EO) have been investigated in order to valorize some of the putative ethnomedical effects. The EO was obtained through steam distillation of fresh leaves (yield: 7.6 g/kg [0.76&#x25;]; refractive index at 20&#xb0;C: 1.49; density: 0.928 g/mL). Chemical characterization performed through GC-MS evidenced the presence of 21 compounds (96.2&#x25; of the total). The most abundant constituents were piperitone (26.2&#x25;), limonene (9.5&#x25;), elemicin (7.2&#x25;), and &#x3b2;-phellandrene (5.6&#x25;). In vitro DPPH antioxidant assay showed a weak radical scavenging ability (IC50) if compared to positive control. Low bioactivity of the EO was also demonstrated against yeast, but it showed an interesting synergistic activity (FIC index of EO+fluconazole) against Candida sp. strains. Ames test evidenced the safety of the EO concerning genotoxicity.

Jos&#xe9; L. Ballesteros

Massimo Tacchini

Antonella Spagnoletti

Alessandro Grandini

Guglielmo Paganetto

Luca Maria Neri

Arianna Marengo

Letizia Angiolella

Alessandra Guerrini

Gianni Sacchetti

Rediscovering Medicinal Amazonian Aromatic Plants: Piper carpunya (Piperaceae) Essential Oil as Paradigmatic Study

Objective. Panax ginseng is used widely for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of P. ginseng. We aimed to investigate the protective effect of ginsenoside Re on isoproterenol-induced myocardial fibrosis and heart failure in rats. Methods. A model of myocardial fibrosis and heart failure was established by once-daily subcutaneous injection of isoproterenol (5 mg/kg/day) to rats for 7 days. Simultaneously, rats were orally administrated ginsenoside Re (5 or 20 mg/kg) or vehicle daily for 4 weeks. Results. Isoproterenol enhanced the heart weight, myocardial fibrosis, and hydroxyproline content in rat hearts. Ginsenoside Re inhibited (at least in part) the isoproterenol-induced increase in heart weight, myocardial fibrosis, and hydroxyproline content. Compared with the isoproterenol group, treatment with ginsenoside Re ameliorated changes in left ventricular systolic pressure, left ventricular end diastolic pressure, and the positive and negative maximal values of the first derivative of left ventricular pressure. Ginsenoside Re administration also resulted in decreased expression of transforming growth factor (TGF)-&#x3b2;1 in serum and decreased expression of Smad3 and collagen I in heart tissue. Conclusion. Ginsenoside Re can improve isoproterenol-induced myocardial fibrosis and heart failure by regulation of the TGF-&#x3b2;1/Smad3 pathway.

Quan-wei Wang

Xiao-feng Yu

Hua-li Xu

Xue-zhong Zhao

Da-yuan Sui

Ginsenoside Re Improves Isoproterenol-Induced Myocardial Fibrosis and Heart Failure in Rats

About this journal

Evidence-Based Complementary and Alternative Medicine seeks to apply scientific rigor to the study of complementary and alternative medicine, emphasizing on health outcome, while documenting biological mechanisms of action.

Journal profile

Meet the editorial board

Chief Editor,&nbsp;Jian-Li Gao works as research professorship at the Zhejiang Chinese Medical University, China. Her research focuses on hypertension and oncology, as well as evidence-based use of Traditional Chinese Medicine in reducing the side effects of conventional cancer treatments.&nbsp;

Editor spotlight

Submit your proposal

Do you think there is an emerging area of research that really needs to be highlighted? Or an existing research area that has been overlooked or would benefit from deeper investigation? Raise the profile of a research area by leading a Special Issue.

Special Issues

Author guidelines

Editorial board

Databases and indexing

Evidence-Based Complementary and Alternative Medicine - Table of contents 2019

Evidence-Based Complementary and Alternative Medicine | Hindawi

title

Evidence-Based Complementary and Alternative Medicine seeks to apply scientific rigor to the study of complementary and alternative medicine, emphasizing on health outcome, while documenting biological mechanisms of action.

description

Evidence-Based Complementary and Alternative Medicine

https://images.hindawi.com/journals/ecam/ecam.banner.jpg

twitter:card

twitter:description

twitter:site

twitter:title

twitter:url

twitter:image