Abstract:
BACKGROUND:Zyflamend, a blend of herbal extracts, effectively inhibits tumor growth using preclinical models of castrate-resistant prostate cancer mediated in part by 5'-adenosine monophosphate-activated protein kinase (AMPK), a master energy sensor of the cell. Clinically, treatment with Zyflamend and/or metformin (activators of AMPK) had benefits in castrate-resistant prostate cancer patients who no longer responded to treatment. Two predominant upstream kinases are known to activate AMPK: liver kinase B1 (LKB1), a tumor suppressor, and calcium-calmodulin kinase kinase-2 (CaMKK2), a tumor promotor over-expressed in many cancers. The objective was to interrogate how Zyflamend activates AMPK by determining the roles of LKB1 and CaMKK2. METHODS:AMPK activation was determined in CWR22Rv1 cells treated with a variety of inhibitors of LKB1 and CaMKK2 in the presence and absence of Zyflamend, and in LKB1-null HeLa cells that constitutively express CaMKK2, following transfection with wild type LKB1 or catalytically-dead mutants. Upstream regulation by Zyflamend of LKB1 and CaMKK2 was investigated targeting protein kinase C-zeta (PKCζ) and death-associated protein kinase (DAPK), respectively. RESULTS:Zyflamend's activation of AMPK appears to be LKB1 dependent, while simultaneously inhibiting CaMKK2 activity. Zyflamend failed to rescue the activation of AMPK in the presence of pharmacological and molecular inhibitors of LKB1, an effect not observed in the presence of inhibitors of CaMKK2. Using LKB1-null and catalytically-dead LKB1-transfected HeLa cells that constitutively express CaMKK2, ionomycin (activator of CaMKK2) increased phosphorylation of AMPK, but Zyflamend only had an effect in cells transfected with wild type LKB1. Zyflamend appears to inhibit CaMKK2 by DAPK-mediated phosphorylation of CaMKK2 at Ser511, an effect prevented by a DAPK inhibitor. Alternatively, Zyflamend mediates LKB1 activation via increased phosphorylation of PKCζ, where it induced translocation of PKCζ and LKB1 to their respective active compartments in HeLa cells following treatment. Altering the catalytic activity of LKB1 did not alter this translocation. DISCUSSION:Zyflamend's activation of AMPK is mediated by LKB1, possibly via PKCζ, but independent of CaMKK2 by a mechanism that appears to involve DAPK. CONCLUSIONS:Therefore, this is the first evidence that natural products simultaneously and antithetically regulate upstream kinases, known to be involved in cancer, via the activation of AMPK.
journal_name
BMC Complement Altern Medjournal_title
BMC complementary and alternative medicineauthors
MacDonald AF,Bettaieb A,Donohoe DR,Alani DS,Han A,Zhao Y,Whelan Jdoi
10.1186/s12906-018-2255-0subject
Has Abstractpub_date
2018-06-18 00:00:00pages
188issue
1issn
1472-6882pii
10.1186/s12906-018-2255-0journal_volume
18pub_type
杂志文章abstract:BACKGROUND:Verbascum thapsus is used in tribal medicine as an antispasmodic, anti-tubercular agent and wormicide. In this study, we investigated the antispasmodic and anthelmintic activities of crude aqueous methanolic extract of the plant. METHODS:V. thapsus extracts were tested against roundworms (Ascaridia galli) a...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-12-29
更新日期:2012-03-30 00:00:00
abstract:BACKGROUND:Euphorbia hirta linn., is a species of Euphorbiaceae family. They are known as asthma plant, barokhervi. The plant E. hirta is famous for its medicinal importance among the tribal population. It is a common practice to use the whole to heal wounds. Several pharmacological properties including antiseptic, ant...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-017-1930-x
更新日期:2017-08-24 00:00:00
abstract:BACKGROUND:Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. One of the plants with great medicinal potentials is Diospyros kaki which is mainly cultivated in Asian countries including Korea, Japan, and China. Astringent D. kaki is a wild sp...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-019-2659-5
更新日期:2019-09-23 00:00:00
abstract:BACKGROUND:In contrast to the guidelines of World Health Organization (WHO) and United States-Centers for Disease Control and prevention (US-CDC), the Chinese national guidelines recommend the use of steroids, intravenous immunoglobulin (IVIG), or traditional Chinese herbs (TCHs) in hand-foot-mouth disease (HFMD) manag...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-018-2259-9
更新日期:2018-06-20 00:00:00
abstract:BACKGROUND:Saliva is fundamental to our oral health and our well-being. Many factors can impair saliva secretion, such as adverse effects of prescribed medication, auto-immune diseases (for example Sjögren's syndrome) and radiotherapy for head and neck cancers. Several studies have suggested a positive effect of acupun...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章,评审
doi:10.1186/s12906-018-2124-x
更新日期:2018-02-13 00:00:00
abstract:BACKGROUND:Soshiho-tang (SST, Xiao-chai-hu-tang in Chinese and Sho-saiko-to in Japanese), an oriental herbal formula, is used for treatment of chronic liver diseases. Although many researchers have studied the pharmacological properties of SST, information about its safety and toxicity is limited. Therefore, we evaluat...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-12-266
更新日期:2012-12-27 00:00:00
abstract:BACKGROUND:Six Chinese herb formulas, namely, the Weijing decoction (WJ), the Maxingshigan decoction (MXSG), the Yuebijiabanxia decoction (YBBX), the Qingqihuatan decoction (QQHT), the Dingchuan decoction (DC) and the Sangbaipi decoction (SBP), are commonly used, along with routine pharmacotherapy, to manage the acute ...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章,meta分析
doi:10.1186/s12906-019-2633-2
更新日期:2019-08-22 00:00:00
abstract:BACKGROUND:Much research has been done in Northeast Asia to show the efficacy of traditional medicine. While MEDLINE contains many biomedical articles including those on traditional medicine, it does not categorize those articles by specific research area. The aim of this study was to provide a method that searches for...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-017-1596-4
更新日期:2017-01-28 00:00:00
abstract:BACKGROUND:Breast cancer is the most common type of malignancy in women worldwide. Euphorbia humifusa Willd (EuH) is a plant that is widely used as a traditional medicine. However, no systemic studies on the anti-cancer effects of EuH have been reported. The aim of this study is to evaluate the anti-metastatic effect o...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-016-1404-6
更新日期:2016-10-24 00:00:00
abstract:BACKGROUND:Osteosarcoma is the most common bone tumor and is associated with a poor prognosis. Conventional therapies, surgery and chemotherapy, are still the standard but soon reach their limits. New therapeutic approaches are therefore needed. Conventional aqueous mistletoe extracts from the European mistletoe (Viscu...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-016-1545-7
更新日期:2017-01-07 00:00:00
abstract:BACKGROUND:Nuna Kadugu (NK), a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK ...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-12-190
更新日期:2012-10-22 00:00:00
abstract:BACKGROUND:Hyaluronidases have been found as the target enzymes in the development of osteoarthritis (OA) disease. While there is still no curative treatment for this disease, recent studies on the treatment of OA were focused on the effectiveness of natural products which are expected to improve the symptoms with mini...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-13-213
更新日期:2013-08-23 00:00:00
abstract:BACKGROUND:Colorectal cancer remains one of the leading causes of cancer death worldwide. Traditional Chinese Medicine (TCM) has played a positive role in colorectal cancer treatment. There is a great need to establish effective herbal formula for colorectal cancer treatment. Based on TCM principles and clinical practi...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-13-128
更新日期:2013-06-08 00:00:00
abstract:BACKGROUND:Uncaria sinensis (US) has long been used in traditional Korean medicine to relieve various nervous-related symptoms and cardiovascular disease. We recently showed the neuroprotective and cerebrovascular protective effects of US on cerebral ischemia; however, its effects on the blood-brain barrier (BBB) are p...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-015-0678-4
更新日期:2015-05-27 00:00:00
abstract:BACKGROUND:The National Institutes of Health reported in 2007 that approximately 38% of United States adults have used at least one type of Complementary and Alternative Medicine (CAM). There are no studies available that assess general CAM use in US pregnant women.The objectives of our study were to determine the prev...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-14-85
更新日期:2014-03-04 00:00:00
abstract:BACKGROUND:In ayurvedic traditional medicine Gentiana kurroo Royle (family; Gentianaceae) is used to treat several metabolic diseases. This plant is rich in various compounds belonging to flavonoids and glycosides. Till now little work has been carried out on immunomodulatory and anti-inflammatory potential of this pla...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-017-1593-7
更新日期:2017-01-28 00:00:00
abstract:BACKGROUND:Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years. This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients. METHODS:A four-center, open-label randomize...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/1472-6882-12-197
更新日期:2012-10-29 00:00:00
abstract:BACKGROUND:To overcome the escalating problems associated with infectious diseases and drug resistance, discovery of new antimicrobials is crucial. The present study aimed to carry out in vitro antimicrobial analysis of 15 medicinal plant species selected according to their traditional medicinal uses in Gurage and Silt...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-015-0822-1
更新日期:2015-08-18 00:00:00
abstract:BACKGROUND:Pingchuan Formula (PCF) is a traditional Chinese recipe. PCF improves chronic airway inflammation by correcting the imbalance of T-helper cell ratio. The purpose of this study was to investigate the effect of PCF on pathological changes in the lungs of asthmatic mice in terms of Treg/Th17 balance. METHODS:A...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-015-0755-8
更新日期:2015-07-16 00:00:00
abstract:BACKGROUND:During recent years the market for homeopathic education media has increasingly diversified with old (books, seminars) and new media (video-seminars, pc-programs, homeo-wiki and internet-courses). However, little is known about homeopaths' preferences in using educational media and their requirements of this...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-12-95
更新日期:2012-07-13 00:00:00
abstract:BACKGROUND:Idiopathic infertility is a significant number of causes of male infertility. Empirical treatments are used for idiopathic male infertility, and antioxidant supplementation is a kind of management of oxidative stress related infertility. We investigated the antioxidant effects of the modified Ojayeonjonghwan...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-14-367
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:Cnidii Rhizoma is the dried root stem of Cnidium officinale Makino. Cnidii Rhizoma (CR) has been used to treat menstrual irregularity, menstrual pain, and menopause in Korea. However, the effects and mechanisms of CR on RANKL-induced osteoclastogenesis pathway remain to be elucidated. In this study, we inves...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-019-2611-8
更新日期:2019-08-09 00:00:00
abstract:BACKGROUND:Neurotoxin-Nna (NT), an analgesic peptide separated from the venom of Naja naja atra, has reported to have an exceptional specificity to block transmission of the nerve impulse by binding to the α- subunit of the nicotinic acetylcholine receptor in the membrane. However, little information is available on th...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/1472-6882-13-86
更新日期:2013-04-15 00:00:00
abstract:BACKGROUND:Moxibustion (a type of Chinese medicine which involves burning a herb close to the skin) has been used to correct a breech presentation. Evidence of effectiveness and safety from systematic reviews is encouraging although significant heterogeneity has been found among trials. We assessed the feasibility of c...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1472-6882-11-81
更新日期:2011-09-26 00:00:00
abstract:BACKGROUND:Anoectochilus formosanus has been used as a Chinese folk medicine and is known as the "King of medicine" in Chinese society due to its versatile pharmacological effects such as anti-hypertension, anti-diabetes, anti-heart disease, anti-lung and liver diseases, anti-nephritis and anti-Rheumatoid arthritis. Ki...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-016-1054-8
更新日期:2016-02-25 00:00:00
abstract:BACKGROUND:Flavonoids and other polyphenols play a protective role in liver diseases and possess a high antioxidant capacity. OBJECTIVE:To compare and evaluate the antioxidant and hepatotoprotective activities of 4 deserts plants, Fagonia indica Burm. f., Calotropis procera R.Br., Zygophylum hamiense Schweinf. and Sal...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-015-0919-6
更新日期:2015-11-09 00:00:00
abstract:BACKGROUND:To evaluate and compare effects of an integrative treatment (IT), therapeutic acupuncture (TA), and conventional treatment (CT) in alleviating symptoms of anxiety and depression in psychologically distressed primary care patients. METHODS:An open, pragmatic randomized controlled trial comparing the three tr...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1472-6882-13-308
更新日期:2013-11-07 00:00:00
abstract:BACKGROUND:Suo Quan Wan (SQW) is a Chinese traditional prescription that has been used in clinical treatment of lower urinary tract symptoms for centuries. However, scientific basis of SQW efficacy and mechanism is still needed. This study investigated the effect of SQW on bladder function and transient receptor potent...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-015-0898-7
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Rhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double-blind, placebo-controlled crossover study to investigate its efficacy in acute mount...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1472-6882-13-298
更新日期:2013-10-31 00:00:00
abstract:BACKGROUND:Herbal materials should be stored at optimal conditions in order to retain their nutritional quality. Proper storage has a significant impact on the quality of the herbs and spices. METHODS:The effects of storage temperature (5 and 15 °C) and time (4 and 8 months) on the phytochemical constituents associate...
journal_title:BMC complementary and alternative medicine
pub_type: 杂志文章
doi:10.1186/s12906-016-1352-1
更新日期:2016-09-29 00:00:00