Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications
Nitric oxide (NO) is a gaseous molecule that has a central role in signaling pathways involved in numerous physiological processes (e.g., vasodilation, neurotransmission, inflammation, apoptosis, and tumor growth). Due to its gaseous form, NO has a ...
Berberine: A comprehensive review on its isolation biosynthesis chemistry and pharmacology
The isoquinoline compounds from alkaloidal class have been excellent source of important phytoconstituents having wide range of pharmacological activities. Berberine is a protoberberine alkaloidal compound obtained from Berberis genus plants which belongs to family Barberidaceae. Due to its unique structural properties, berberine and its derivatives has been exploited extensively for its potential uses in various pharmacological targets such as cancer, inflammation, diabetes, gastrointestinal disorder, viral and microbial infections, neurological disorder like Alzheimer, anxiety, schizophrenia, depression, etc. This review illustrates the updated information on berberine with respect to its isolation, biosynthesis, chemical synthesis, structural modification and pharmacological activities. An extensive literature search were carried out in various search engine like PubMed, Google Scholars, Research Gate and SCOPUS by using keywords like Berberine, protoberberine alkaloids, isoquinoline derivatives, pharmacological effects, etc. Prephenic acid is the starting material for biosynthesis of berberine. Structural modifications lead to generation of various potential derivatives, which earn patents by researchers. Besides toxicities, the complications of low solubility and bioavailability should be eliminated. To improve its safety, efficacy and selectivity the berberine should be carefully derivatized.
Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases
Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Vascular diseases affecting vasculature in the heart, cerebrovascular disease, atherosclerosis, and diabetic complications have compromised quality of life for affected individuals and increase the burden on health care services. Berberine, a naturally occurring isoquinoline alkaloid form Rhizoma coptidis, is widely used in China as a folk medicine for its antibacterial and anti-inflammatory properties. Promisingly, an increasing number of studies have identified several cellular and molecular targets for berberine, indicating its potential as an alternative therapeutic strategy for vascular diseases, as well as providing novel evidence that supports the therapeutic potential of berberine to combat vascular diseases. The purpose of this review is to comprehensively and systematically describe the evidence for berberine as a therapeutic agent in vascular diseases, including its pharmacological effects, molecular mechanisms, and pharmacokinetics. According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity via the regulation of multiple signaling pathways, including AMP-activated protein kinase (AMPK), nuclear factor κB (NF-κB), mitogen-activated protein kinase silent information regulator 1 (SIRT-1), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), janus kinase 2 (JAK-2), Ca2+ channels, and endoplasmic reticulum stress. Moreover, we discuss the existing limitations of berberine in the treatment of vascular diseases, and give corresponding measures. In addition, we propose some research perspectives and challenges, and provide a solid evidence base from which further studies can excavate novel effective drugs from Chinese medicine monomers.
Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease
In recent years, the health of patients exposed to the consequences of the metabolic syndrome still requires the search for new solutions, and plant nutraceuticals are currently being intensively investigated. Berberine is a plant alkaloid possessing scientifically determined mechanisms of the prevention of the development of atherosclerosis, type 2 diabetes, and obesity, as well as cardiovascular complications and cancer. It positively contributes to elevated levels of fasting, postprandial blood glucose, and glycosylated hemoglobin, while decreasing insulin resistance. It stimulates glycolysis, improving insulin secretion, and inhibits gluconeogenesis and adipogenesis in the liver; by reducing insulin resistance, berberine also improves ovulation. The anti-obesity action of berberine has been also well-documented. Berberine acts as an anti-sclerotic, lowering the LDL and testosterone levels. The alkaloid exhibits an anti-inflammatory property by stalling the expression of cyclooxygenase 2 (COX-2) and prostaglandin E2. Berberine is neuroprotective and acts as an antidepressive. However, the outcomes in psychiatric patients are nonspecific, as it has been shown that berberine improves metabolic parameters in schizophrenic patients, acting as an adjuvant during antipsychotic treatment. Berberine acts as an anticancer option by inducing apoptosis, the cell cycle arrest, influencing MAPK (mitogen-activated protein kinase), and influencing transcription regulation. The inhibition of carcinogenesis is also combined with lipid metabolism.
Keywords: berberine, metabolic syndrome, cancer, cancer prevention, obesity, type 2 diabetes mellitus, ischemic heart disease, stroke, myocardial infarction, atherosclerosis, polycystic ovary syndrome, clinical trials
Berberine is an isoquinoline alkaloid, which has demonstrated significant therapeutic potential in the treatment of various diseases, including tumors, acute and chronic infections, autoimmune disorders, and diabetes. Studies have demonstrated that berberine exhibits polypharmacological effects, including antibacterial, anti-inflammatory, antioxidant, and hypoglycemic activities. To further elucidate the multifaceted pharmacological mechanisms of berberine, we reviewed 7 targets of berberine identified through co-crystal structure analysis, including filamentous temperature-sensitive protein Z (FtsZ), QacR, BmrR, phospholipase A2 (PLA2), RamR, NIMA-related kinase 7 (NEK7), and mesenchymal-epithelial transition (MET). Through target fishing, molecular docking, and surface plasmon resonance (SPR) analyses, combined with cellular and molecular experiments, we further identified 6 targets of berberine. These findings provide a comprehensive summary of berberine’s direct molecular targets, offering a theoretical foundation for further exploration of its diverse pharmacological activities.
Berberine and health outcomes: an overview of systematic reviews - BMC Complementary Medicine and Therapies
Background Berberine is an isoquinoline alkaloid isolated from Chinese herb coptis chinensis and other berberis plants which can be used to treat a wide range of chronic diseases. However, the current research evidence on the therapeutic effects of berberine has not been summarized. We aimed to synthesize the current evidence on the systematic review (SRs) of berberine for the treatment of diverse conditions. Methods A comprehensive search of the Cochrane Library, PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP, and SinoMed was performed from the database inception to April 11, 2024. SRs on berberine were included and evaluated. The methodological quality and the reporting quality of each SR were assessed using the AMSTAR-2 tool and PRISMA checklist, respectively. The quality of evidence was appraised based on the GRADE. Results Fifty-four SRs were included and analyzed. Overall, associations were found between berberine and 70 health outcomes concerned with 9 diseases. Berberine has improved most outcomes of these diseases: 78% (25/32) cardiovascular disease outcomes, 92.59% (25/27) type 2 diabetes mellitus outcomes, 94.74% (18/19) gastrointestinal disorders outcomes, 72.22% (13/18) polycystic ovary syndrome (PCOS) outcomes, 86.67% (13/15) non-alcoholic fatty liver disease (NAFLD) outcomes, 92.31% (12/13) schizophrenia outcomes, 90.91% (10/11) metabolic syndrome outcomes, 57.14% (4/7) obesity outcomes, and 100.00% (6/6) dyslipidemia outcomes. There was a high overlap of primary studies (CCA 15%) in the SRs of PCOS, NAFLD, obesity, and schizophrenia. Only one SR was rated as high quality while eight SRs were rated as low quality and forty-five SRs as very low quality according to AMSTAR-2. Regarding the reporting quality, Item 14, 15, 21, and 22 were poorly reported for the included SRs in terms of PRSMA assessment. For GRADE, eight outcomes were rated as high quality evidence, twenty-two outcomes were rated as moderate quality, and 110 outcomes were rated as low quality. Conclusion Current evidence suggests that berberine has beneficial effects on a range of health outcomes for people with chronic diseases. Specifically, berberine significantly improves type 2 diabetes, gastrointestinal disorders, schizophrenia, metabolic syndrome, and dyslipidemia outcomes. However, caution is needed considering the shortcomings in the quality of the relevant system reviews included.
Berberine in Non-Alcoholic Fatty Liver Disease—A Review
The incidence of Non-Alcoholic Fatty Liver Disease (NAFLD) has been rapidly increasing during the last decade. It is a relevant health problem that affects 25% of the general population. NAFLD involves an extensive array of clinical conditions. So ...
The recombinant shingles vaccine is associated with lower risk of dementia
A natural experiment including more than 200,000 people who received a shingles vaccine reveals that, within 6 years of vaccination, the recombinant vaccine is associated with lower risk of dementia than is the live vaccine.
Die 10 Symptome v. Alzheimer | Deutschland | Alzheimer's Association
Gedächtnisverlust, der das tägliche Leben beeinträchtigt, kann ein Symptom von Alzheimer sein. Erfahren Sie mehr über die 10 Warnzeichen von Alzheimer und was Sie unternehmen können, wenn sie diese Warnzeichen bemerken.
Ventilation strategies and indoor air quality in Swedish primary school classrooms
The present study aimed at investigating the effects of ventilation strategies on indoor air quality (IAQ) in schools. Measurements of thermal environ…
The nasal microbiome modulates risk for SARS-CoV-2 infection
These results suggest that natural variation in the nasal microbiome significantly
impacts ACE2/TMPRSS2 expression in the nasal cavity and the near-term risk of SARS-CoV-2
infection in adults. Modifying the nasal microbiome could potentially reduce COVID-19
risk.
Consuming More of Daily Caloric Intake at Dinner Predisposes to Obesity. A 6-Year Population-Based Prospective Cohort Study
Background/Objectives It has been hypothesized that assuming most of the caloric intake later in the day leads to metabolic disadvantages, but few studies are available on this topic. Aim of our study was to prospectively examine whether eating more of the daily caloric intake at dinner leads to an increased risk of obesity, hyperglycemia, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Subjects/Methods 1245 non-obese, non-diabetic middle-aged adults from a population-based cohort underwent a 3-day food record questionnaire at enrollment. Anthropometric values, blood pressure, blood metabolic variables, and estimated liver fat were measured at baseline and at 6-year follow-up. Design Prospective cohort study. Results Subjects were divided according to tertiles of percent daily caloric intake at dinner. A significant increase in the incidence rate of obesity (from 4.7 to 11.4%), metabolic syndrome (from 11.1 to 16.1%), and estimated NAFLD (from 16.5 to 23.8%) was observed from the lower to higher tertile. In a multiple logistic regression model adjusted for multiple covariates, subjects in the highest tertile showed an increased risk of developing obesity (OR = 2.33; 95% CI 1.17–4.65; p = 0.02), metabolic syndrome (OR = 1.52; 95% CI 1.01–2.30; p = 0.04), and NAFLD (OR = 1.56; 95% CI 1.10–2.22; p = 0.01). Conclusions Consuming more of the daily energy intake at dinner is associated with an increased risk of obesity, metabolic syndrome, and NAFLD.
⏰ Your body’s metabolism follows a circadian rhythm—eating late throws it off.
In a 6-year study, those who ate most of their calories at dinner had:
⚠️ 2x higher risk of obesity
🩺 1.5x higher risk of metabolic syndrome
🍔 1.6x higher risk of fatty liver disease
🧵 1/9
N-acetyl cysteine (NAC), as a nutritional supplement, is a greatly applied antioxidant in vivo and in vitro. NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis. It acts directly as a scavenger of free radicals, ...
Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day
Non-rapid eye movement sleep (NREMS) is accompanied by a decrease in cerebral metabolism, which reduces the consumption of glucose as a fuel source and decreases the overall accumulation of oxidative stress in neural and peripheral tissues. Enabling ...
Luteolin Ameliorates Non-alcoholic Fatty Liver Disease via Regulation of Hepatic Lipid Uptake, Autophagy, and Apoptosis in WD/CCl4-induced Mice - Jingjing Hu, Dongyue Pang, Ning Tian, Rongyin Qin, 2024
Background and Purpose Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insul...
Spermidine is essential for fasting-mediated autophagy and longevity
Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.
High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study - PMC
(1) Background: Spermidine is a biogenic polyamine that plays a crucial role in mammalian metabolism. As spermidine levels decline with age, spermidine supplementation is suggested to prevent or delay age-related diseases. However, valid ...
NHS England » NHS highlights dementia symptoms to look out for over Christmas as numbers diagnosed soar
As family and friends gather for the festive period, the NHS is highlighting the signs and symptoms of dementia to look out for in loved ones. Common early symptoms of dementia that may appear some time before an official medical diagnosis include: emotional changes such as irritability forgetfulness struggling to follow a conversation or find […]
Enhancement of Learning and Memory by Elevating Brain Magnesium
Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using…
Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial
Sleep problems challenge overall wellbeing. Magnesium has been implicated to benefit sleep, although the clinical evidences varied based on the magnesium source used. Magnesium L-threonate (MgT) is a promising intervention due to its brain bioavailability and effects on cognition, memory and mood. We investigated MgT supplementation on sleep quality and daily function.
Patients/methods: Eighty 35-55-year-olds with self-assessed sleep problems participated in a randomized, double-blind, placebo-controlled, parallel-arm study, taking 1 g/day of MgT or placebo for 21 days. Sleep and daily behaviors were measured subjectively using standardized questionnaires including the Insomnia Severity Index, Leeds Sleep Evaluation Questionnaire, and Restorative Sleep Questionnaire, and objectively using an Oura ring. The Profile of Mood States questionnaire and a daily diary were used to evaluate mood, energy and productivity, and record any safety concerns.
Results: The MgT group maintained good sleep quality and daytime functioning, while placebo declined. From objective Oura ring measurements, MgT significantly (p 0.05) improved vs placebo deep sleep score, REM sleep score, light sleep time, and activity and readiness parameters activity score, activity daily movement score, readiness score, readiness activity balance, and readiness sleep balance. From subjective questionnaires, MgT significantly (p 0.05) improved vs placebo behavior upon awakening, energy and daytime productivity, grouchiness, mood and mental alertness. MgT was safe and well tolerated.
Conclusions: This showed MgT improved sleep quality, especially deep/REM sleep stages, improved mood, energy, alertness, and daily activity and productivity. These are consistent with how MgT works in neuron cells and animal models, suggesting broader positive impacts on overall brain health.
Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α
Clinical studies have shown that about two-thirds of patients with chronic pain suffer from short-term memory (STM) deficits and an effective drug for treatment of the neurological disorder is lacking at present.
Objective: We tested whether chronic oral application of magnesium L-threonate (MgT), which has been shown to improve memory in normal and aging animals by elevating Mg2+ in the brain, could prevent or restore the STM deficits induced by spared nerve injury (SNI), an animal model of chronic neuropathic pain. The mechanisms underlying the effect of MgT on STM deficits were also investigated.
Study design: The experiments were conducted in a random and double-blind fashion in adult male rats. MgT was administrated via drinking water at a dose of 609 mg/kg/d for 2 weeks, starting either one week before SNI (preventative group) or one week after SNI (therapeutic group), and water without the drug served as control.
Methods: STM was accessed with a novel object recognition test (NORT), followed by recording of long-term potentiation (LTP) in the hippocampus in vivo and the measurement of the expression of tumor necrosis factor-α (TNF-α) with Western Blot or Immunohistochemistrical staining, a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor (NMDAR) currents were recorded with patch clamp in CA1 neurons in acute and cultured hippocampal slices.
Result: We found that chronic oral application of MgT was able to prevent and restore the deficits of STM and of LTP at CA3-CA1 synapses in the hippocampus induced by SNI. Furthermore, both preventative and therapeutic chronic oral application of MgT blocked the up-regulation of TNF-α in the hippocampus, which has been previously shown to be critical for memory deficits. SNI reduced NMDAR current and the effect was dramatically attenuated by elevating extracellular Mg2+ concentration ([Mg2+]○). In cultured hippocampal slices, chronic application of recombinant rat TNF-α (rrTNF-α) for 3 days reduced NMDAR current in a concentration-dependent manner and the effect was again blocked by elevating [Mg2+]○.
Limitations: We showed that oral application of MgT inhibited the over-expression of TNF-α and rescued the dysfunction of the NMDAR, but the causal relationship between them remains elusive.
Conclusions: Our data suggested that oral application of MgT was able to prevent and restore the STM deficits in an animal model of chronic neuropathic pain by reversing the dysfunction of the NMDAR, and normalization of TNF-α expression may play a role in the effect. Oral application of MgT may be a simple and potent means for handling this form of memory deficit.
Magnesium-L-threonate improves sleep quality and daytime functioning in adults with self-reported sleep problems: A randomized controlled trial
Sleep problems challenge overall wellbeing. Magnesium has been implicated to benefit sleep, although the clinical evidences varied based on the magnesium source used. Magnesium L-threonate (MgT) is a promising intervention due to its brain bioavailability and effects on cognition, memory and mood. We investigated MgT supplementation on sleep quality and daily function.
Patients/methods
Eighty 35–55-year-olds with self-assessed sleep problems participated in a randomized, double-blind, placebo-controlled, parallel-arm study, taking 1 g/day of MgT or placebo for 21 days. Sleep and daily behaviors were measured subjectively using standardized questionnaires including the Insomnia Severity Index, Leeds Sleep Evaluation Questionnaire, and Restorative Sleep Questionnaire, and objectively using an Oura ring. The Profile of Mood States questionnaire and a daily diary were used to evaluate mood, energy and productivity, and record any safety concerns.
Results
The MgT group maintained good sleep quality and daytime functioning, while placebo declined. From objective Oura ring measurements, MgT significantly (p 0.05) improved vs placebo deep sleep score, REM sleep score, light sleep time, and activity and readiness parameters activity score, activity daily movement score, readiness score, readiness activity balance, and readiness sleep balance. From subjective questionnaires, MgT significantly (p 0.05) improved vs placebo behavior upon awakening, energy and daytime productivity, grouchiness, mood and mental alertness. MgT was safe and well tolerated.
Conclusions
This showed MgT improved sleep quality, especially deep/REM sleep stages, improved mood, energy, alertness, and daily activity and productivity. These are consistent with how MgT works in neuron cells and animal models, suggesting broader positive impacts on overall brain health.
Estradiol Patches Safe, Effective in Prostate Cancer
Investigators report that estradiol works as well as luteinizing hormone–releasing hormone agonists for testosterone suppression and have a much better side-effect profile.
Diet Changes Show Promise in Early Prostate Cancer
A high omega-3, low omega-6 diet with fish oil led to a significant reduction in a biomarker for prostate cancer progression in men with prostate cancer on active surveillance.