Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro.

OBJECTIVE: To explore the synergic mechanism of ginsenoside Rg1 (Rg1) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs. METHODS: The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+], potassium ions [K+] and calcium ions [Ca2+] levels, and Nav1.5, Kv4.2, and RyR2 genes expressions in each group were examined. RESULTS: For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ via regulating Nav1.5, RyR2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs. CONCLUSION: Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+].

Traditional Chinese Medicine as a complementary therapy in combat with COVID-19-A review of evidence-based research and clinical practice.

AIM: To examine the literature on Traditional Chinese Medicine (TCM) used in the treatment, prevention and supportive care in patients with COVID-19. DESIGN: A narrative review was performed. DATA SOURCES: A systematic and comprehensive search was conducted on both Chinese and English electronic databases: China National Knowledge Infrastructure, Wanfang Data, CINAHL, Embase, Cochrane, PubMed, PsycINFO. Articles published from 1 December 2019 -1 April 2020 were included in this review. REVIEW METHODS: Studies reporting on the treatment and prevention of COVID-19 using TCM regardless of study designs were included. In addition, grey literatures, including media reports on Chinese government websites or official media websites and treatment guidelines were searched for TCM treatment and prevention on COVID-19. RESULTS: Limited research has been published on the use of TCM for COVID-19. We qualitatively described and synthesized the published research and current clinical practice on the use of TCM for COVID-19, and focused on the following areas: TCM treatment used in SARS, MERS, H1N1; TCM treatment plan for COVID-19; TCM in Prevention and Treatment at Early Stage of COVID-19; TCM emotional therapy; and personalized TCM treatment plan. CONCLUSION: The combination of western medicine and TCM in treatment, and treatment based on the local condition, isolation, personal protective measures are of great significance for the prevention and treatment of COVID-19. Relevant laboratory research and clinical evaluation should be continued to collect scientific evidences on the efficacy of TCM. IMPACT: TCM has been used in the treatment and prevention of COVID-19 in China, and the clinical evidences indicated that TCM regulates immunity and exerts anti-viral effect simultaneously. This review provides practical recommendation for the policymakers in the selection process of the treatment and preventive measures for the global pandemic of COVID-19.

Anti-Osteoporotic Activity of an Edible Traditional Chinese Medicine Cistanche deserticola on Bone Metabolism of Ovariectomized Rats Through RANKL/RANK/TRAF6-Mediated Signaling Pathways.

Given the limitations of existing therapeutic agents for treatment of postmenopausal osteoporosis, there still remains a need for more options with both efficacy and less adverse effects. Cistanche deserticola Y. C. Ma is known as a popular tonic herb traditionally used to treatment deficiency of kidney energy including muscle weakness in minority area of Asian counties. Based on the theory of "kidney dominate bone," an ovariectomized (OVX) rat model of postmenopausal osteoporosis was used to evaluate the therapeutic effect of C. deserticola extract (CDE) on bone loss. Forty eight female Sprague-Dawley rats, aged about 12 weeks, were randomly assigned into six groups including sham group orally administrated with 0.5% carboxymethyl cellulose sodium (CMC-Na) (sham), positive group treated with 1 mg/kg of estradiol valerate (EV), low, moderate, and high dosage groups orally administrated with 200, 400, and 800 mg/kg/day of CDE, respectively. After 3 months of continuous intervention, CDE exhibited significant anti-osteoporotic activity evidenced by the enhanced total bone mineral density, ameliorated bone microarchitecture; increased alkaline phosphatase activity; decreased deoxypyridinoline, cathepsin K, tartrate-resistant acid phosphatase, and malondialdehyde levels; whereas the body, uterus, and vagina weights in OVX rats were not influenced by CDE intervention. In addition, a seemed contradictory phenomenon on levels of calcium and phosphorus between OVX and sham rats were observed and elucidated. Mechanistically, CDE significantly down-regulated the levels of TRAF6, RANKL, RANK, NF-κB, IKKß, NFAT2, and up-regulated the phosphatidylinositol 3-kinase (PI3K), AKT, osteoprotegerin, and c-Fos expressions, which implied CDE could suppress RANKL/RANK-induced activation of downstream NF-κB and PI3K/AKT pathways, and ultimately, preventing activity of the key osteoclastogenic proteins NFAT2 and c-Fos. All of the data suggested CDE possessed potential anti-osteoporotic activity and this effect was, at least in part, involved in modulation of RANKL/RANK/TRAF6-mediated NF-κB and PI3K/AKT signaling as well as c-Fos and NFAT2 levels. Therefore, CDE may represent a useful promising remedy candidate for treatment of postmenopausal osteoporosis.

Homocysteine: A modifiable culprit of cognitive impairment for us to conquer?

BACKGROUND: Cognitive impairment, including mild cognitive impairment and its progressive deterioration to dementia, results in great hazards to the patient and the surrounding society. While some of the risk factors are unmodifiable, such as age, lower educational attainment, and genetic factors, another proposed one-homocysteine, an amino acid produced in the methylation cycle of protein metabolism is modifiable by cheap and easily accessible B-vitamins treatments in medical practice. OBJECTIVE AND METHODS: To investigate the relationship between homocysteine and cognitive impairment, elucidate the underlying pathophysiological mechanisms and exploit any potential therapeutic values of homocysteine-lowering treatments in prevention and/or treatment in cognitive decline, we searched on the PUBMED databases surrounding around the physiological homocysteine metabolism, detrimental effects of abnormal homocysteine concentrations on the brain, and review observational and interventional experiments to date estimating the relationship between homocysteine and cognitive impairment with relatively powerful evidence. RESULTS: Intrinsic and environmental factors help maintain the normal homocysteine concentrations, and pathological homocysteine concentrations exert adverse effects mediated by cellular and vascular pathways. Although many observational studies have suggested a causal link between hyperhomocysteinemia and cognitive impairment, the majority of randomized controlled trials failed to observe marked benefits on cognition by homocysteine-lowering treatments using B-vitamins, partly arising from some design limitations including: not identifying individuals at earlier stages of cognitive impairment who are most likely to benefit, overlooking any latent safety hazards of multiple vitamin supplementation, lack of sensitive and domain-specific cognitive tests, and interference of other underappreciated factors. CONCLUSION: More studies are required to better explain the related pathophysiological mechanisms, improve experimental methods, and investigate the preventive or/and therapeutic effects of homocysteine-lowering strategies on cognitive impairment.

Cynomorium songaricum prevents bone resorption in ovariectomized rats through RANKL/RANK/TRAF6 mediated suppression of PI3K/AKT and NF-κB pathways.

AIM: Cynomorium songaricum Rupr., an edible and important Traditional Chinese medicine has long been used in folk for treatment of kidney deficiency, was chosen to estimate the antiosteoporotic activity and underlying molecular mechanism on rats induced by ovariectomy (OVX). MAIN METHODS: 9 of 45 rats were underwent bilateral laparotomy without removing the ovaries as sham group, remains were underwent bilateral ovariectomy and equally randomized into four groups: with vehicle (0.5% CMC-Na) as model group, estradiol valerate (1 mg/kg body weight/day) as positive control, with 100 and 300 mg/kg body weight/day of ethanol extracts of C. songaricum extract (CSE) as low and high dosage groups, respectively. KEY FINDINGS: After 12 weeks of continues orally intervention, the decreases of bone mineral density, bone mineral content, tissue mineral content, as well as the increases of bone trabecular separation and bone resorption markers were significantly reversed by CSE in the OVX rats, and in particular, a contradictory phenomenon on calcium and phosphorus contents was observed and elucidated. Mechanistically, the expressions of tumor-necrosis factor receptor-associated factor 6 (TRAF 6), nuclear factor kappa B (RANK) and its ligand (RANKL), as well as the nuclear factor kappa B (NF-κB), phosphoinositide 3­kinase (PI3K) and protein kinase B (AKT) levels were significantly down-regulated by CSE intervention, whereas the osteoprotegerin (OPG) was significantly up-regulated by CSE as compared to the control. SIGNIFICANCE: Concisely, C. songaricum exhibited potential therapeutic effect on bone metabolism of ovariectomized rats, and this effect was possibly exerted by RANKL/RANK/TRAF6 mediated down-regulation of NF-κB and PI3K/AKT pathways.

Echinacoside, an Inestimable Natural Product in Treatment of Neurological and other Disorders.

Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of Parkinson's and Alzheimer's diseases, some important issues arose. These included the identification of active metabolites as having poor bioavailability in prototype form, the definite molecular signal pathways or targets of ECH with the above effects, and limited reliable clinical trials. Thus, it remains unresolved as to whether scientific research can reasonably make use of this natural compound. A systematic summary and knowledge of future prospects are necessary to facilitate further studies for this natural product. The present review generalizes and analyzes the current knowledge on ECH, including its broad distribution, different preparation technologies, poor pharmacokinetics and kinds of therapeutic uses, and the future perspectives of its potential application.

Syringin prevents bone loss in ovariectomized mice via TRAF6 mediated inhibition of NF-κB and stimulation of PI3K/AKT.

BACKGROUND: Syringin, also called eleutheroside B, is a main bioactive phenolic glycoside in Acanthopanax senticosus (Rupr. et Maxim.) Harms. Based on the "kidney dominates bone" theory of TCM, A. senticosus can strengthen bone and Syringin may be one of the responsibilities. PURPOSE: The objectives of this study were to estimate the osteoporotic activity of Syringin and reveal the possible molecular mechanisms in vivo. METHODS: Sixty female ICR mice were randomly assigned into sham operated group (SHAM, treated with vehicle) and five ovariectomized subgroups (n = 10 each), treated with vehicle as OVX group, estradiol valerate (EV, 1 mg/kg/day) as positive group, and Syringin (10, 20 and 40 mg/kg/day) as low, moderate and high dosage groups. The therapeutic effect of Syringin against osteoporosis was systematically analyzed by determining the bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and serum biochemical parameters, and the molecular mechanism was also evaluated. RESULTS: After three months of orally administrated intervention, Syringin (10, 20 and 40 mg/kg/day) significantly improved the BMD, bone maximum load and trabecular bone microarchitecture in ovariectomized mice, evidenced by the increased bone mineral content, tissue mineral content, tissue mineral density, trabecular thickness and trabecular number, as well as the decreased trabecular separation in OVX mice. Meanwhile, the activities of tartrate-resistant acid phosphatase, deoxypyridinoline and cathepsin K in OVX mice were also inhibited by Syringin, while the increased body weight and decreased uterus weight seemed not influenced by Syringin administration. Concerning the underlying molecular mechanisms, Syringin significantly downregulated the expression of tumor-necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) and receptor activator of nuclear factor kappa B ligand (RANKL) proteins levels, upregulated the expression of osteoprotegerin (OPG), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) levels, suggesting that Syringin prevented bone lost by TRAF6-mediated inhibition of NF-κB and stimulation of PI3K/AKT, and subsequently increasing the OPG/RANKL ratio and inhibiting the osteoclastogenesis, finally promoting bone formation. CONCLUSIONS: All of the data implied Syringin possessed the potent anti-osteoporosis activity on ovariectomized mice, and the underlying molecular mechanism may be related to the NF-κB and PI3K/AKT signaling pathways.

Simultaneous determination of seven phenylethanoid glycosides in Cistanches Herba by a single marker using a new calculation of relative correction factor.

Current quantitative analysis of multi-components by a single marker is usually performed by using liquid chromatography methods coupled with ultraviolet or mass spectrometry detection to afford the relative correction factors between reference standard and other components. However, low durability of the relative correction factors caused by different chromatographic system leading this approach lacking a high accuracy. In the present study, a simple but effective method was established by employing the absorption coefficient (E1 cm 1%) to calculate the relative correction factors instead of peak area or height. The absorption coefficient, a fundamental constant of physics, has been widely used for qualitative and quantitative analysis in Pharmacopoeia all over the world. According to the absorbance coefficient ratio between echinacoside and other compounds, the content of seven phenylethanoid glycosides in Cistanche deserticola and Cistanches tubulosa were determined simultaneously. The low standard method difference on quantitative measurement of seven compounds in Cistanches Herba between our method and the external standard method proved the consistency of the two methods. Using an ultra high performance liquid system, these seven bioactive phenylethanoid glycosides were baseline separated in 8 min. All the data suggested that the method was accurate and reliable for the determination of multi-components when authentic standard substances were unavailable.

Perceptions and experiences of patients living with implantable cardioverter defibrillators: a systematic review and meta-synthesis.

BACKGROUND: Sudden cardiac deaths have become a growing major public health concern that affects the world. Despite the various etiologies, life-threatening cardiac arrhythmias attribute the main cause of sudden cardiac deaths. Therefore in certain groups of high-risk patients, the Implantable Cardioverter Defibrillator (ICD) has been recommended as either a secondary or primary prophylactic method of prevention. OBJECTIVE: To summarise the perceptions of ICD recipients and provide an overview of their experiences with regards to the quality of life, coping strategies, and learning needs. METHODS: A systematic search was conducted using CINAHL, MEDLINE, PsycINFO, Scopus, Cochrane Library, and Web of Science. Primary research articles published from January 2005 to January 2016 that met the inclusion criteria were selected and assessed for methodological quality. RESULTS: Thirty-nine articles consisting of 16 qualitative studies, 22 quantitative studies, and 1 mixed methods study were included for the meta-synthesis. Findings extracted from these studies were grouped into eight subthemes with 'living the ICD experience: a constant process of redefining oneself' emerging as an over-arching theme. CONCLUSION: This review provides insight into the perspectives and experiences of ICD recipients. Current evidence highlights the need for healthcare professionals to improve future care standards and develop a patient-centric holistic program that meets the specific needs of ICD recipients. Moreover, future studies are required to address the research gaps identified and also explore the perceptions of patients living with ICD in the Asian context.

Magnetoencephalography assessment of evoked magnetic fields and cognitive function in subcortical ischemic vascular dementia patients.

OBJECTIVE: To investigate the relationship between cognitive impairment and somatosensory evoked magnetic field and auditory evoked magnetic field changes in elderly male patients with subcortical ischemic vascular dementia (SIVD). METHODS: Magnetoencephalography (MEG) was used to record evoked magnetic field changes from 4 SIVD patients (76-88 years), 3 patients with vascular cognitive impairment with no dementia (VCI-ND; 74-87 years), and 6 healthy volunteers (72-85 years). Latency peaks, equivalent current dipole (ECD) strength, and bilateral ECD position were recorded. The MEG data were superimposed on magnetic resonance imaging to produce magnetic source imaging. RESULTS: Compared to controls, SIVD patients showed increased M20 latency and ECD strength. There were no significant differences in M20 inter-hemispheric positions across diagnostic categories. At M100, SIVD patients showed delayed auditory evoked magnetic field latency compared to controls. However, ECD strength and 3-dimensional inter-hemispheric differences were similar across the groups at the M100 measurement. CONCLUSIONS: Changes in somatosensory and auditory evoked magnetic field changes correlated with cognitive impairment in SIVD patients. Magnetic field latency measures may provide an objective and sensitive index for early dementia detection and monitoring of cognitive function.