DOCSLIB.ORG

Compounds of Traditional Chinese Medicine and Neuropathic Pain

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Compounds of Traditional Chinese Medicine and Neuropathic Pain Available online at www.sciencedirect.com Chinese Journal of Natural Medicines 2020, 18(1): 28–35 doi: 10.1016/S1875-5364(20)30002-9 Compounds of traditional Chinese medicine and neuropathic pain LI Shun-Hua2Δ, LI Lin1,3Δ, YANG Ru-Nan1,3, LIANG Shang-Dong1,3, * 1 Neuropharmacology Laboratory of Physiology Department, Medical School of Nanchang University, Nanchang 330006, China; 2 Undergraduate Student of Class 155 of Nanchang University Queen Marry University of London Joint Programme, Nanchang 330006, China; 3 Jiangxi Provincial Key Laboratory of Autonomic Nervous Function and Disease, Nanchang 330006, China Available online 20 Jan., 2020 [ABSTRACT] Neuropathic pain (NP) has become a serious global health issue and a huge clinical challenge without available effect- ive treatment. P2 receptors family is involved in pain transmission and represents a promising target for pharmacological intervention. Traditional Chinese medicine (TCM) contains multiple components which are effective in targeting different pathological mechanisms involved in NP. Different from traditional analgesics, which target a single pathway, TCMs take the advantage of multiple compon- ents and multiple targets, and can significantly improve the efficacy of treatment and contribute to the prediction of the risks of NP. Compounds of TCM acting at nucleotide P2 receptors in neurons and glial cells could be considered as a potential research direction for moderating neuropathic pain. This review summarized the recently published data and highlighted several TCMs that relieved NP by acting at P2 receptors. [KEY WORDS] Traditional Chinese medicine; Diabetic neuropathic pain; HIV-gp120-associated neuropathic pain; Chronic constric- tion injury; Nucleotide receptors [CLC Number] R284, R965 [Document code] A [Article ID] 2095-6975(2020)01-0028-08 Introduction For all types of drugs, 20% to 40% of patients either experi- ence a less than 30% pain relief or have intolerable side ef- Neuropathic pain (NP) is defined as pain caused by a le- fects [5-7]. Therefore, developing novel compounds for the ef- sion or disease of the somatosensory system, belongs to fective management of NP with little influence on other nor- chronic pain. The typical symptoms of NP include spontan- mal physiological functions is necessary. eous pain, allodynia (pain response to normally innocuous Nucleotides of purinergic signaling were proposed as ex- stimuli), hyperpathia (abnormal pins-and-needles or electric- tracellular signaling molecules in 1972 [8]. Purinergic recep- shock-like sensations), and hyperalgesia (aggravated pain evoked by non-noxious stimuli) [1-3]. NP has become a seri- tors include P1 receptors and P2 receptors, which bind to ad- ous global health issue, with estimated prevalence rates ran- enosine-5′-triphosphate (ATP) and its analogues [adenosine- [9] ging from 1% to 8.9% of the total population [4]. Its long dur- 5′-diphosphate (ADP) and adenosine] respectively . Purino- ation reduces the quality of patients’ life and places a heavy ceptors are widely distributed in both the peripheral and burden on society. Although various drugs, including antide- central nervous systems (CNS), being present in neurons and [9-10] pressants, anti-epileptics, opioids, and topical anesthetics, are glia . To date, seven homomeric (P2X1, P2X2, P2X3, used for clinical treatment of NP, their side effects are marked, P2X4, P2X5, P2X6, and P2X7), and six heteromeric P2X re- and their therapeutic effects are generally limited [5-6]. Com- ceptors (P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6, and [10] plete freedom from NP often cannot be achieved by drugs. P2X4/6) have been identified . P2Y receptors consist of P2Y1-12. Purinergic signaling was proposed and hypothes- ized for the initiator and modulator of pain [11]. Since then, [Received on] 27-Jul.-2019 [Research funding] This work was supported by the National Natur- many subsequent research studies have expanded this al Science Foundation of China (Nos. 81570735, 8181101216, concept. P2X and P2Y receptors are involved in the modula- 31560276, 81970749, and 81870574). tion of pain transmission. After nerve injury, ATP is released [*Corresponding author] Tel/Fax: 86-791-86360552, E-mail: liangsd @hotmail.com from the nerve endings of primary sensory neurons. Extracel- ∆These authors contributed equally to this work. lular ATP triggers the activation of different P2 receptors, These authors have no conflict of interest to declare. which induce the production and release of bioactive factors – 28 – LI Shun-Hua, et al. / Chin J Nat Med, 2020, 18(1): 28–35 including cytokines and neurotrophic factors, which in turn convulsants (e.g., gabapentin, pregabalin, and topical lido- lead to the hyperexcitability of sensory neurons and, con- caine). Opioid analgesics and tramadol are recommended as sequently, NP developed [10-11]. second-line therapies. However, they are sometimes used as Ligand-gated ion channel P2X receptor has seven sub- first-choice drugs [25]. But those therapies only offer marginal types, among which the P2X3, P2X4, and P2X7 subtypes are relief because of either a lack of efficacy or the risk of unac- most related to pain transmission [11-12]. It has been reported ceptable side effects (e.g., sedation, dizziness, edema, and that P2X antagonists were successful in relieving NP [13-14]. ataxia) [23]. Patients with NP continue to have moderately P2X3 receptor antagonists (A-317491, RO3 and RO4) have severe pain on average, despite taking prescribed medica- exhibited their potent ability to relieve NP [15-17]. An effective tions for their condition [26]. Furthermore, the development of P2X4 receptor antagonist named paroxetine has been sugges- tolerance, and the risks of addiction and abuse, significantly ted to successfully relieve NP [18]. P2X7 receptor antagonists limit the clinical application of NP pharmacotherapy. No (A-740003, KN-62 and KN-04) produced antinociceptive ef- treatment option has been shown to reverse NP. Therefore, fects in NP [19]. Among the G protein coupled P2Y receptor the discovery of novel therapeutic alternatives with superior family, only the P2Y12 receptor subtype is clearly known to effectiveness and minimal adverse effects would be beneficial. be involved in NP onset. Several genetic deletions of P2Y12 Currently, more attention has been focused on herbal for- receptors produce analgesic effect [20-22]. These observations mulations in the field of drug discovery, especially on medi- indicate that drugs selectively targeting specific P2 receptors cinal plants and herbal extracts from traditional Chinese can exert their analgesic activity at the site of receptor, thus medicine (TCM) (Fig. 1), which are increasingly used world- limiting the occurrence of unwanted side effects [9-11]. wide. TCM has unique advantages in the clinical prevention The advantage of traditional Chinese medicine in NP and treatment of NP because of its fewer complications and treatment side effects compared with synthetic drugs. Moreover, the NP, a kind of chronic pain, is the focus of many research multiple components and targets of TCM avoid the shortcom- studies due to the high incidence, complex pathogenesis, and ings of clinical drugs targeting a single pathway [27]. Several lack of efficient treatments. Trauma (surgery, amputation), studies have indicated that natural products could be a good metabolic disorders (diabetes, uremia), infection (herpes source of the new specific molecules needed for the treat- zoster, HIV), poisoning (chemotherapy), vascular disease (ar- ment of pain-related diseases through the regulation of P2 re- teritis nodosa), and malnutrition are considered to be incent- ceptors [28-29]. For example, the TCM compound Emodin acts ives for the initiation of NP [23]. NP is an area of largely un- at tumor cells to inhibit their migratory ability via P2X7 met therapeutic need due to its complex underlying patho- blockade [30]. Recently, the antagonistic effect of bioflavon- physiology and heterogeneous etiology [5, 7]. The presently oids from the methanolic extract fractions of Rheedia logifo- available treatment for NP contains non-pharmacological ap- lia on the P2X7 receptor has been found to promote analges- proaches, such as electroacupuncture [24], and drugs. On the ic action on inflammatory pain [31]. In addition, it has been re- basis of randomized clinical trials, medications are recom- ported that bioactive molecules contained in analgesic prepa- mended as first-line treatments for NP include certain antide- rations from TCM (e.g., tetramethylpyrazine, sodium ferulate, pressants [e.g., tricyclic antidepressants (TCAs), serotonin and puerarin) can inhibit P2X3-mediated pain transmission in norepinephrine reuptake inhibitors (SNRIs)] and certain anti- primary afferent neurons [28]. Thus, TCM may be an alterna- CH OH H 3 OH OH O OH OH O O H3C HO O HO O H H O OH H3C OH CH 3 OH O OH O O Emodin Resveratrol Artemisinin Quercetin O O HO O HO OH HO N O O H OO O CH3 O OH CH3 O HO O H HO Curcumin Andrographolide Osthole Sinomenine Fig. 1 Chemical structures of different TCMs – 29 – LI Shun-Hua, et al. / Chin J Nat Med, 2020, 18(1): 28–35 tive option to relieve and manage NP by acting at P2 receptors. odeficiency virus (HIV), and herpes infections, the resultant Classical drug research focuses mainly on a single active NP is often modifiable with prevention strategies. Therefore, compound. Systemic administration can reduce local drug after precise prediction of the disease risk, TCM can provide concentration
Load more

Recommended publications
  • Editorial Modulation of Oxidative Stress: Pharmaceutical and Pharmacological Aspects 2018
    Hindawi Oxidative Medicine and Cellular Longevity Volume 2019, Article ID 6380473, 3 pages https://doi.org/10.1155/2019/6380473 Editorial Modulation of Oxidative Stress: Pharmaceutical and Pharmacological Aspects 2018 Robert E. Smith ,1 Tomris Ozben ,2 and Luciano Saso 3 1Park University, 8700 River Park Drive, Parkville, MO 64152, USA 2Department of Biochemistry, Akdeniz University Medical Faculty Campus, Dumlupinar Street, 07070 Antalya, Turkey 3Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy Correspondence should be addressed to Robert E. Smith; [email protected] Received 5 June 2019; Accepted 9 June 2019; Published 3 July 2019 Copyright © 2019 Robert E. Smith et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chronic, low-grade, smoldering inflammation (also called in vitro tests for total antioxidant capacity emerged. They parainflammation) can lead to cardiovascular and neurode- were based on measuring the destruction of oxidized test generative diseases, as well as many types of cancer [1]. It compounds by reacting directly with the antioxidants in can be caused by obesity, metabolic syndrome, and even foods [1, 2]. periodontal disease. One of the articles in this special issue However, as scientists and physicians learned more about tells how adding antioxidants to dental materials can help to human nutrition, they realized that the caloric restriction prevent oxidative stress in gingival fluid (“Influence of Dental that worked for other organisms did not work for humans Restorations on Oxidative Stress in Gingival Crevicular [1, 2].
    [Show full text]
  • Anthocyanins and Intestinal Barrier Function: a Review
    Journal of International Society for Food Bioactives Nutraceuticals and Functional Foods Review J. Food Bioact. 2019;5:18–30 Anthocyanins and intestinal barrier function: a review Jonathan C. Valdez and Bradley W. Bolling* Department of Food Science, University of Wisconsin-Madison, 1605 Linden Dr., Madison, WI 53706, USA *Corresponding author: Bradley W Bolling, 1605 Linden Dr. Madison, WI 53706, USA. Tel: 608-890-0212; E-mail: [email protected] DOI: 10.31665/JFB.2019.5175 Received: December 15, 2018; Revised received & accepted: December 31, 2018 Citation: Valdez, J.C, and Bolling, B.W (2019). Anthocyanins and intestinal barrier function: a review. J. Food Bioact. 5: 18–30. Abstract Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation.- Ber ries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and prevent- ing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocya- nins and their known microbial catabolites modulate intestinal barrier function. Keywords: Colitis; Barrier function; Anthocyanin; Metabolism; Inflammatory Bowel Diseases.
    [Show full text]
  • Long-Term Sodium Ferulate Supplementation Scavenges Oxygen Radicals and Reverses Liver Damage Induced by Iron Overloading
    molecules Article Long-Term Sodium Ferulate Supplementation Scavenges Oxygen Radicals and Reverses Liver Damage Induced by Iron Overloading Yang Qiao 1,†, Huan He 2,†, Zeyu Zhang 2, Zhangping Liao 2, Dong Yin 3, Dan Liu 2,*, Bo Yi 4,* and Ming He 1,* 1 Jiangxi Provincial Institute of Hypertension, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China; [email protected] 2 Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang 330006, China; [email protected] (H.H.); [email protected] (Z.Z.); [email protected] (Z.L.) 3 Jiangxi Provincial Key Laboratory of Molecular Medicine at the Second Affiliated Hospital, Nanchang University, Nanchang 330006, China; [email protected] 4 Second Abdominal Surgery Department, Jiangxi Province Tumor Hospital, Nanchang 330029, China * Correspondence: [email protected] (D.L.); [email protected] (B.Y.); [email protected] (M.H.); Tel.: +86-185-0791-5527 (D.L.); +86-135-1700-7527 (B.Y.); +86-791-8636-2231 (M.H.) † These authors contributed equally to this work. Academic Editor: Derek J. McPhee Received: 12 August 2016; Accepted: 8 September 2016; Published: 16 September 2016 Abstract: Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU). We determined the protective role of SF against liver injury by examining liver-to-body ratio (%), transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection.
    [Show full text]
  • Role of Flavonoids and Nitrates in Cardiovascular Health
    Role of flavonoids and nitrates in cardiovascular health Article Accepted Version Lovegrove, J. A., Stainer, A. and Hobbs, D. A. (2017) Role of flavonoids and nitrates in cardiovascular health. Proceedings of the Nutrition Society, 76 (2). pp. 83-65. ISSN 0029-6651 doi: https://doi.org/10.1017/S0029665116002871 Available at http://centaur.reading.ac.uk/69126/ It is advisable to refer to the publisher’s version if you intend to cite from the work. See Guidance on citing . To link to this article DOI: http://dx.doi.org/10.1017/S0029665116002871 Publisher: Cambridge University Press All outputs in CentAUR are protected by Intellectual Property Rights law, including copyright law. Copyright and IPR is retained by the creators or other copyright holders. Terms and conditions for use of this material are defined in the End User Agreement . www.reading.ac.uk/centaur CentAUR Central Archive at the University of Reading Reading’s research outputs online 1 ROLE OF FLAVONOIDS AND NITRATES IN CARDIOVASCULAR HEALTH Julie A Lovegrove1,2*, Alex Stainer2 and Ditte A Hobbs1,2 1Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, and 2Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Whiteknights, Reading, RG6 6AP, UK. *Corresponding author: Professor Julie A Lovegrove, email: [email protected], fax: +44 (0) 118 931 0080 Running title: Flavonoids, nitrates and CVD Key words: platelet function; blood pressure; dietary nitrate; flavonoids; vascular function; Abbreviations: CVD, cardiovascular
    [Show full text]
  • Hydrogen Sulfide Exhibits Cardioprotective Effects by Decreasing Endoplasmic Reticulum Stress in a Diabetic Cardiomyopathy Rat Model
    MOLECULAR MEDICINE REPORTS 14: 865-873, 2016 Hydrogen sulfide exhibits cardioprotective effects by decreasing endoplasmic reticulum stress in a diabetic cardiomyopathy rat model FANG LI*, JIAN LUO*, ZHIXIONG WU, TING XIAO, OU ZENG, LIN LI, YAN LI and JUN YANG Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China Received March 13, 2015; Accepted March 7, 2016 DOI: 10.3892/mmr.2016.5289 Abstract. Endoplasmic reticulum (ER) stress is critical in Introduction the occurrence and development of diabetic cardiomyopathy (DC). Hydrogen sulfide (H2S) has been found to be the third In diabetic patients, a wide range of structural reconfigura- gaseous signaling molecule with anti-ER stress effects. tion has been observed, such as cardiomyocyte hypertrophy, Previous studies have shown that H2S acts as a potent inhibitor ventricular dilation, prominent interstitial fibrosis (1,2), of fibrosis in the heart of diabetic rats. This study aimed to diastolic and systolic dysfunction, and left ventricular demonstrate whether H2S exhibits protective effects on the hypertrophy (3,4). This disease process is termed diabetic myocardium of streptozotocin (STZ)-induced diabetic rats cardiomyopathy (DC), which is a heart muscle-specific by suppressing ER stress. In this study, diabetic models were disease without other vascular pathology (5,6). Investigation established by intraperitoneal (i.p.) injection of 40 mg/kg revealed that patients with diabetes mellitus (DM) were more STZ. The STZ-treated mice were divided into three groups, likely to suffer from coronary artery disease, hypertension and subsequently treated with normal saline, 30 µmol/kg and mortality following myocardial infarction (7,8), while or 100 µmol/kg NaHS, i.p., respectively, for 8 weeks.
    [Show full text]
  • GPCR/G Protein
    Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com GPCR/G Protein G Protein Coupled Receptors (GPCRs) perceive many extracellular signals and transduce them to heterotrimeric G proteins, which further transduce these signals intracellular to appropriate downstream effectors and thereby play an important role in various signaling pathways. G proteins are specialized proteins with the ability to bind the nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP). In unstimulated cells, the state of G alpha is defined by its interaction with GDP, G beta-gamma, and a GPCR. Upon receptor stimulation by a ligand, G alpha dissociates from the receptor and G beta-gamma, and GTP is exchanged for the bound GDP, which leads to G alpha activation. G alpha then goes on to activate other molecules in the cell. These effects include activating the MAPK and PI3K pathways, as well as inhibition of the Na+/H+ exchanger in the plasma membrane, and the lowering of intracellular Ca2+ levels. Most human GPCRs can be grouped into five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and Secretin, forming the GRAFS classification system. A series of studies showed that aberrant GPCR Signaling including those for GPCR-PCa, PSGR2, CaSR, GPR30, and GPR39 are associated with tumorigenesis or metastasis, thus interfering with these receptors and their downstream targets might provide an opportunity for the development of new strategies for cancer diagnosis, prevention and treatment. At present, modulators of GPCRs form a key area for the pharmaceutical industry, representing approximately 27% of all FDA-approved drugs. References: [1] Moreira IS. Biochim Biophys Acta. 2014 Jan;1840(1):16-33.
    [Show full text]
  • Terminalia Fagifolia Mart. & Zucc. Elicits Vasorelaxation of Rat Thoracic
    © 2019. Published by The Company of Biologists Ltd | Biology Open (2019) 8, bio035238. doi:10.1242/bio.035238 RESEARCH ARTICLE Terminalia fagifolia Mart. & Zucc. elicits vasorelaxation of rat thoracic aorta through nitric oxide and K+ channels dependent mechanism Emanuella F. de Carvalho1, AndréF. Nunes1,Náiguel C. B. Silva1, Joaõ Paulo da Silva Gomes2, Renato P. de Sousa2, Valdelânia G. Silva1, Paulo H. M. Nunes1,3, Rosimeire F. Santos1, Mariana H. Chaves2, Aldeidia P. Oliveira1,3 and Rita C. M. Oliveira1,3,* ABSTRACT KEY WORDS: Terminalia fagifolia, Vasorelaxation, Potassium channels, Nitric oxide Terminalia fagifolia Mart. & Zucc. (Combretaceae) is a plant commonly found in the regions of the Brazilian cerrado, popularly used for the treatment of gastrointestinal disorders. There are no INTRODUCTION reports in the literature on the use of T. fagifolia for the treatment of the Terminalia fagifolia Mart. & Zucc is part of the Combretaceae cardiovascular system conditions. Nevertheless, plants of the same family, which is composed of by around 600 species distributed in genus, such as Terminalia arjuna (Roxb.) Wight & Arn and Terminalia 18 genera. Terminalia is composed of by around 200 species. It is a superba Engler & Diels, present cardioprotective, hypotensive and species found in the Brazilian cerrado, popularly-known as capitão- vasodilatating effects. In light of this, the aim of the study was to do-mato, mirindiba and pau-de-bicho (Almeida et al., 1998; Ayres investigate the effect of the ethanolic extract (Tf-EE) and of its et al., 2009). aqueous (Tf-AQF), hexanic (Tf-HEXF) and hydroethanolic (Tf-HAF) Several plants of the Combretaceae botanical family present partition fractions obtained from the stem bark of T.
    [Show full text]
  • Cardioprotective Effect of Sodium Ferulate in Diabetic Rats Xiaohong Xu1#, Haijuan Xiao2#, Jiangpei Zhao3, Tongfeng Zhao2 
    Int. J. Med. Sci. 2012, 9 291 Ivyspring International Publisher International Journal of Medical Sciences 2012; 9(4):291-300. doi: 10.7150/ijms.4298 Research Paper Cardioprotective Effect of Sodium Ferulate in Diabetic Rats Xiaohong Xu1#, Haijuan Xiao2#, Jiangpei Zhao3, Tongfeng Zhao2 1. Department of Endocrinology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, PR China. 2. Department of Geriatrics, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, PR China. 3. Department of Geriatrics, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310000, PR China. # Xiaohong Xu and Haijuan Xiao contributed equally to this work. Corresponding author: Tongfeng Zhao, Ph.D., Department of Geriatrics, the Second Affiliated Hospital, School of Medi- cine, Zhejiang University, Hangzhou 310000, PR China. Tel: +86 571 887784720; Fax: +86 571 87022660; E-mail: [email protected] © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/ licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2012.02.28; Accepted: 2012.05.29; Published: 2012.06.05 Abstract Reactive oxygen species (ROS) play important roles in the occurrence and development in diabetic cardiomyopathy (DC). Ferulic acid is one of the ubiquitous compounds in diet. So- dium ferulate (SF) is its sodium salt. SF has potent free radical scavenging activity and can effectively scavenge ROS. The study investigated the effect of SF on cardioprotection in di- abetic rats. The diabetic rats induced by streptozotocin (STZ) were treated with SF (110mg/kg) by gavage per day for 12 weeks.
    [Show full text]
  • Ginsenoside-Rd Induces Cholesterol Efflux from Macrophage-Derived Foam Cells Conjunction with Cardiovascular, Pharmacological and Biochemical Evaluations
    npg Section 6: Cardiovascular Pharmacology 56 10.1038/aps.2013.113 model of brain stem death that employed microinjection of the organophosphate S6.1 insecticide mevinphos bilaterally into RVLM of Sprague-Dawley rats was used, in Ginsenoside-Rd induces cholesterol efflux from macrophage-derived foam cells conjunction with cardiovascular, pharmacological and biochemical evaluations. Da-yan CAO, Ya LIU*, Xiao-hui LI*. Institute of Materia Medica and Department of Results: A significant increase in TrkB protein, phosphorylation of TrkB at Tyr516 Pharmaceutics, College of Pharmacy, Third Military Medical University, Chongqing (pTrkBY516), Shc at Tyr317 (pShcY317) or extracellular signal-regulated kinase (ERK) 400038, China at Thr202/Tyr204, or Ras activity in RVLM occurred preferentially during the pro- Aim: Ginsenoside-Rd, a purified component from panax notoginseng saponins, life phase of experimental brain stem death. Microinjection bilaterally into RVLM has been described to reduce atherosclerotic lesion formation, yet the mechanism of a specific TrkB inhibitor, K252a, antagonized those increases. Pretreatment with is not fully understood. This study is designed to investigate the potential role of anti-pShcY317 antiserum, Src homology 3 binding peptide (Grb2/SOS inhibitor), Ginsenoside-Rd in modulating cholesterol deposition and to explore its underlying farnesylthioacetic acid (Ras inhibitor), manumycin A (Ras inhibitor) or GW5074 mechanisms in macrophages. Methods: The murine macrophage-derived foam (Raf-1 inhibitor) blunted the preferential augmentation of Ras activity or ERK cells induced by 25 μg/mL oxidized low-density lipoprotein (oxLDL) in RAW264.7 phosphorylation in RVLM and blocked the upregulated nitric oxide synthase I cells for 48 h. Ginsenoside-Rd 10, 20 μmol/L was added during oxLDL incubation (NOS I)/protein kinase G (PKG) signaling, the pro-life cascade that sustains central respectively.
    [Show full text]
  • Beetroot, a Remarkable Vegetable: Its Nitrate and Phytochemical
    antioxidants Review Beetroot, A Remarkable Vegetable: Its Nitrate and Phytochemical Contents Can be Adjusted in Novel Formulations to Benefit Health and Support Cardiovascular Disease Therapies Diego dos S. Baião, Davi V. T. da Silva and Vania M. F. Paschoalin * Instituto de Química, Universidade Federal do Rio de Janeiro, Avenida Athos da Silveira Ramos 149, Rio de Janeiro 21941-909, Brazil; [email protected] (D.d.S.B.); [email protected] (D.V.T.d.S.) * Correspondence: [email protected]; Tel.: +55-21-3938-7362; Fax: +55-21-3938-7266 Received: 4 September 2020; Accepted: 2 October 2020; Published: 8 October 2020 Abstract: The cardioprotective effects of dietary nitrate from beetroot in healthy and hypertensive individuals are undeniable and irrefutable. Nitrate and nitrate-derived nitrite are precursors for nitric oxide synthesis exhibiting an effect on cardiomyocytes and myocardial ischemia/reperfusion, improving endothelial function, reducing arterial stiffness and stimulating smooth muscle relaxation, decreasing systolic and diastolic blood pressures. Beetroot phytochemicals like betanin, saponins, polyphenols, and organic acids can resist simulated gastrointestinal digestion, raising the hypothesis that the cardioprotective effects of beetroots result from the combination of nitrate/nitrite and bioactive compounds that limit the generation of reactive oxygen species and modulate gene expression. Nitrate and phytochemical concentrations can be adjusted in beet formulations to fulfill requirements for acute or long-term supplementations, enhancing patient adherence to beet intervention. Based on in vitro, in vivo, and clinical trials, beet nitrate and its bioactive phytochemicals are promising as a novel supportive therapy to ameliorate cardiovascular diseases. Keywords: beetroot-food interventions; nitric oxide; betanin; polyphenols; antioxidant activity; clinical trials 1.
    [Show full text]
  • Lessons Learned
    Prevention and Reversal of Chronic Disease Copyright © 2019 RN Kostoff PREVENTION AND REVERSAL OF CHRONIC DISEASE: LESSONS LEARNED By Ronald N. Kostoff, Ph.D., School of Public Policy, Georgia Institute of Technology 13500 Tallyrand Way, Gainesville, VA, 20155 [email protected] KEYWORDS Chronic disease prevention; chronic disease reversal; chronic kidney disease; Alzheimer’s Disease; peripheral neuropathy; peripheral arterial disease; contributing factors; treatments; biomarkers; literature-based discovery; text mining ABSTRACT For a decade, our research group has been developing protocols to prevent and reverse chronic diseases. The present monograph outlines the lessons we have learned from both conducting the studies and identifying common patterns in the results. The main product of our studies is a five-step treatment protocol to reverse any chronic disease, based on the following systemic medical principle: at the present time, removal of cause is a necessary, but not necessarily sufficient, condition for restorative treatment to be effective. Implementation of the five-step treatment protocol is as follows: FIVE-STEP TREATMENT PROTOCOL TO REVERSE ANY CHRONIC DISEASE Step 1: Obtain a detailed medical and habit/exposure history from the patient. Step 2: Administer written and clinical performance and behavioral tests to assess the severity of symptoms and performance measures. Step 3: Administer laboratory tests (blood, urine, imaging, etc) Step 4: Eliminate ongoing contributing factors to the chronic disease Step 5: Implement treatments for the chronic disease This individually-tailored chronic disease treatment protocol can be implemented with the data available in the biomedical literature now. It is general and applicable to any chronic disease that has an associated substantial research literature (with the possible exceptions of individuals with strong genetic predispositions to the disease in question or who have suffered irreversible damage from the disease).
    [Show full text]
  • Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins
    molecules Review Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins Vladimir I. Muronetz 1,2,*, Kseniya Barinova 1, Sofia Kudryavtseva 2, Maria Medvedeva 2, Aleksandra Melnikova 1,2, Irina Sevostyanova 1, Pavel Semenyuk 1 , Yulia Stroylova 1,3 and Matej Sova 4 1 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; [email protected] (K.B.); [email protected] (A.M.); [email protected] (I.S.); [email protected] (P.S.); [email protected] (Y.S.) 2 Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia; sofi[email protected] (S.K.); [email protected] (M.M.) 3 Institute of Molecular Medicine, Sechenov First Moscow State Medical University Trubetskaya St. 8, Bldg. 2, 119991 Moscow, Russia 4 Faculty of Pharmacy, University of Ljubljana, Aškerˇceva7, 1000 Ljubljana, Slovenia; matej.sova@ffa.uni-lj.si * Correspondence: [email protected]; Tel.: +7-495-939-1456 Academic Editor: Ludovic Jean Received: 22 September 2020; Accepted: 9 October 2020; Published: 12 October 2020 Abstract: This review presents the main properties of hydroxycinnamic acid (HCA) derivatives and their potential application as agents for the prevention and treatment of neurodegenerative diseases. It is partially focused on the successful use of these compounds as inhibitors of amyloidogenic transformation of proteins. Firstly, the prerequisites for the emergence of interest in HCA derivatives, including natural compounds, are described. A separate section is devoted to synthesis and properties of HCA derivatives. Then, the results of molecular modeling of HCA derivatives with prion protein as well as with α-synuclein fibrils are summarized, followed by detailed analysis of the experiments on the effect of natural and synthetic HCA derivatives, as well as structurally similar phenylacetic and benzoic acid derivatives, on the pathological transformation of prion protein and α-synuclein.
    [Show full text]