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Nutrients Aug 2022: Berberine is a natural alkaloid with hypoglycemic properties. However, its therapeutic use is limited by a very low oral bioavailability. Here we developed a new oral...
: Berberine is a natural alkaloid with hypoglycemic properties. However, its therapeutic use is limited by a very low oral bioavailability. Here we developed a new oral formulation of berberine based on Sucrosomial technology and tested its effect on insulin resistance. : Sucrosomial berberine was first tested in vitro in the hepatoma cell line Huh7 to assess its effect on proteins involved in glucose homeostasis and insulin resistance. The pharmacokinetics and efficacy on insulin resistance were then studied in C57BL/6 mice fed with standard (SD) and high-fat diet (HFD) for 16 weeks and treated daily during the last 8 weeks with oral gavage of Sucrosomial berberine or berberine. : Sucrosomial berberine did not affect Huh7 cell viability at concentrations up to 40 µM. Incubation of Huh7 with 20 µM of Sucrosomial and control berberine induced glucokinase (GK) and the phosphorylation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), both known targets for the control of insulin resistance. In vivo, we observed an 8-fold higher plasma concentration after 3 weeks of oral administration of 50 mg/kg/day of Sucrosomial formulation compared to berberine. HFD, compared to SD, induced insulin resistance in mice as determined by oral glucose tolerance test (OGTT). The treatment with a 6.25 mg/kg/daily dose of Sucrosomial berberine significantly reduced the area under the curve (AUC) of OGTT (73,103 ± 8645 vs. 58,830 ± 5597 mg/dL × min), while control berberine produced the same effects at 50 mg/Kg/day (51518 ± 1984 mg/dL × min). Under these conditions, the two formulations resulted in similar berberine plasma concentration in mice. Nevertheless, a different tissue distribution of metabolites was observed with a significant accumulation of reduced, demethylated and glucuronide berberine in the brain after the oral administration of the Sucrosomial form. Glucuronide berberine plasma concentration was higher with Sucrosomial berberine compared to normal berberine. Finally, we observed similar increases of AMPK phosphorylation in the liver in response to the treatment with Sucrosomial berberine and berberine. : The Sucrosomial formulation is an innovative and effective technology to improve berberine gastrointestinal (GI) absorption with proven in vitro and in vivo activity on insulin resistance.
Topics: AMP-Activated Protein Kinases; Animals; Berberine; Glucuronides; Insulin; Insulin Resistance; Mice; Mice, Inbred C57BL
PubMed: 36079851
DOI: 10.3390/nu14173595 -
Molecules (Basel, Switzerland) Jun 2023Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial... (Review)
Review
Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin-the active principle of the thistle-was traditionally used for lipid metabolism disorders and to sustain liver function. This review describes the major defects of insulin signaling leading to IR and the main properties of the three mentioned natural substances, their molecular targets and synergistic action mechanisms. The actions of berberine, quercetin and silymarin are partially superimposable as remedies against reactive oxygen intermediates generated by a high-lipid diet and by NADPH oxidase, which is triggered by phagocyte activation. Furthermore, these compounds inhibit the secretion of a battery of pro-inflammatory cytokines, modulate intestinal microbiota and are especially able to control the various disorders of the insulin receptor and post-receptor signaling systems. Although most of the evidence on the effects of berberine, quercetin and silymarin in modulating insulin resistance and preventing cardiovascular disease derive from experimental studies on animals, the amount of pre-clinical knowledge strongly suggests the need to investigate the therapeutic potential of these substances in human pathology.
Topics: Animals; Humans; Silymarin; Quercetin; Insulin Resistance; Berberine; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Silybum marianum
PubMed: 37298967
DOI: 10.3390/molecules28114491 -
Pharmacological Research Mar 2021The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal...
The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.
Topics: Animals; Anxiety; Berberine; Equol; Fecal Microbiota Transplantation; Female; Gastrointestinal Microbiome; Ovariectomy; Rats; Rats, Sprague-Dawley
PubMed: 33493658
DOI: 10.1016/j.phrs.2021.105439 -
Nutrients Sep 2022Maintaining healthy body weight is an important component of any effective diabetes management plan. However, glycemic management using insulin generally leads to weight...
Maintaining healthy body weight is an important component of any effective diabetes management plan. However, glycemic management using insulin generally leads to weight gain. In addition, weight loss medications prescribed for diabetes management are often associated with adverse side effects, which limit their long-term usage. Alternatively, nutrition intervention provides a safe, readily accessible, and inexpensive option for diabetes management. This study describes a composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin for glycemic and weight management. Functional complementarity between berberine, cinnamaldehyde, and curcumin provides an effective means to improve insulin sensitivity without increasing adiposity. In primary human omental preadipocytes, cinnamaldehyde and curcumin additively enhance insulin-stimulated activation of Akt2 and glucose uptake, whereas berberine inhibits de novo fatty acid biosynthesis and fat cell differentiation. In a diet-induced obesity murine model, a dietary supplement with berberine, cinnamaldehyde, and curcumin prevents weight gain, improves glucose tolerance, and reduces HbA1c, blood lipids, visceral adiposity, and liver steatosis. Collectively, the composition of phytonutrients comprising berberine, cinnamaldehyde, and curcumin protects against obesity and pre-diabetic conditions in a diet-induced obesity murine model. Safety and efficacy assessment of nutrition intervention using combined berberine, cinnamaldehyde, and curcumin for glycemic and weight management in future clinical trials are warranted.
Topics: Acrolein; Animals; Berberine; Blood Glucose; Curcumin; Diabetes Mellitus; Disease Models, Animal; Fatty Acids; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lipids; Mice; Obesity; Phytochemicals; Weight Gain
PubMed: 36145160
DOI: 10.3390/nu14183784 -
IUBMB Life Oct 2020Cancer, even currently, is one of the main reasons for mortality and morbidity, worldwide. In recent years, a great deal of effort has been made to find efficient... (Review)
Review
Cancer, even currently, is one of the main reasons for mortality and morbidity, worldwide. In recent years, a great deal of effort has been made to find efficient therapeutic strategies for cancer, however, particularly with regards to side effects and the possibility of complete remission. Berberine (BBR) is a nature-driven phytochemical component originated from different plant groups such as Berberis vulgaris, Berberis aquifolium, and Berberis aristata. BBR is a well-known nutraceutical because of its wide range of pharmacological activities including anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide. In addition, it exhibits inhibitory effects on multiple types of cancers. In this review, we have elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Autophagy; Berberine; Berberis; Cell Cycle Checkpoints; Humans; Neoplasms; Plants, Medicinal
PubMed: 32735398
DOI: 10.1002/iub.2350 -
In Vivo (Athens, Greece) 2023High-fat diets induce shifts in the gut microbial community structure in patients or animals with non-alcoholic steatohepatitis (NASH). The objective of this study was...
BACKGROUND/AIM
High-fat diets induce shifts in the gut microbial community structure in patients or animals with non-alcoholic steatohepatitis (NASH). The objective of this study was to investigate the influence of metformin (MET) and berberine (BER) on the intestinal microbiota of rats with NASH.
MATERIALS AND METHODS
Forty specific pathogen-free male Sprague-Dawley rats were randomized into 4 groups. Model rats were fed high-fat diets to create NASH models. MET or BER rats were administrated MET or BER, respectively, at the onset of induction of NASH. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides were examined. Plasma endotoxin levels were measured using the turbidimetric endotoxin assay. The incidence of bacterial translocation describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs. Hematoxylin and eosin and oil red O staining were used for histopathological analysis. High throughput 16S rRNA sequencing was carried out for analyzing the composition of intestinal microbiota.
RESULTS
High-fat diets caused NASH after 16-week induction. Administration of MET and BER ameliorated NASH by attenuating hepatic steatosis and inflammation and decreasing the plasma levels of endotoxin. MET and BER restored the composition of the intestinal microbiota disrupted by NASH. Both MET and BER altered the abundance of Atopobiaceae, Brevibacterium, Christensenellaceae, Coriobacteriales, Papillibacter, Pygmaiobacter, and Rikenellaceae RC9 in rats with NASH. The screened intestinal microbiota may be responsible for the improvement in fat accumulation and glucose metabolism.
CONCLUSION
MET and BER demonstrated beneficial effects on the intestinal microbiota, which was disturbed in NASH. This finding may explain the functional mechanism of MET and BER in NASH.
Topics: Humans; Rats; Male; Animals; Non-alcoholic Fatty Liver Disease; Berberine; Gastrointestinal Microbiome; Metformin; RNA, Ribosomal, 16S; Rats, Sprague-Dawley; Diet, High-Fat; Endotoxins; Liver; Disease Models, Animal
PubMed: 37652508
DOI: 10.21873/invivo.13308 -
Frontiers in Endocrinology 2022Berberine is a natural active ingredient extracted from the rhizome of , which interacts with multiple intracellular targets and exhibits a wide range of pharmacological... (Review)
Review
Berberine is a natural active ingredient extracted from the rhizome of , which interacts with multiple intracellular targets and exhibits a wide range of pharmacological activities. Previous studies have preliminarily confirmed that the regulation of mitochondrial activity is related to various pharmacological actions of berberine, such as regulating blood sugar and lipid and inhibiting tumor progression. However, the mechanism of berberine's regulation of mitochondrial activity remains to be further studied. This paper summarizes the molecular mechanism of the mitochondrial quality control system and briefly reviews the targets of berberine in regulating mitochondrial activity. It is proposed that berberine mainly regulates glycolipid metabolism by regulating mitochondrial respiratory chain function, promotes tumor cell apoptosis by regulating mitochondrial apoptosis pathway, and protects cardiac function by promoting mitophagy to alleviate mitochondrial dysfunction. It reveals the mechanism of berberine's pharmacological effects from the perspective of mitochondria and provides a scientific basis for the application of berberine in the clinical treatment of diseases.
Topics: Berberine; Drugs, Chinese Herbal; Mitochondria; Mitophagy; Rhizome
PubMed: 36034426
DOI: 10.3389/fendo.2022.982145 -
European Journal of Drug Metabolism and... Jan 2022Huanglian-Houpo decoction (HH), which is recorded in the famous traditional Chinese medicine monograph "Puji Fang," contains two individual herbs, Huanglian (Rhizoma...
BACKGROUND AND OBJECTIVES
Huanglian-Houpo decoction (HH), which is recorded in the famous traditional Chinese medicine monograph "Puji Fang," contains two individual herbs, Huanglian (Rhizoma coptidis) and Houpo (Magnoliae officinalis cortex). It was regularly used to treat seasonal epidemic colds and influenzas in ancient China. Our laboratory discovered that HH has a significant anti-H1N1 influenza virus effect. However, no pharmacokinetic and pharmacodynamic data concerning the anti-H1N1 influenza virus activity of HH are available to date. In the current study, the concentration-time profiles of two major components of HH, berberine and magnolol, in rat plasma were investigated.
METHODS
An integrate pharmacokinetic approach was developed for evaluating the holistic pharmacokinetic characteristics of berberine and magnolol from HH. Additionally, the inhibition rate and levels of IFN-β in MDCK cells infected by influenza virus were analyzed. Data were calculated using 3p97 with pharmacokinetic analysis.
RESULTS
The estimated pharmacokinetic parameters were maximum plasma concentration (C) 0.9086 μg/ml, area under the concentration-time curve (AUC) 347.74 μg·min/ml, and time to reach C (T) 64.69 min for berberine and C = 0.9843 μg/ml, AUC= 450.64 μg·min/ml, T = 56.86 min for magnolol, respectively. Furthermore, integrated pharmacokinetic and pharmacodynamic analysis showed that the highest plasma concentration, inhibition rate and interferon-β (IFN-β) secretion of HH first increased and then weakened over time, reaching their peaks at 60 min. The plasma concentration of HH is directly related to the anti-influenza virus effect.
CONCLUSION
The results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN-β secretion.
Topics: Animals; Antiviral Agents; Area Under Curve; Berberine; Biphenyl Compounds; China; Drugs, Chinese Herbal; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Lignans; Male; Models, Animal; Phytotherapy; Rats; Rats, Inbred Strains
PubMed: 34635990
DOI: 10.1007/s13318-021-00724-x -
BioMed Research International 2019Berberine (BBR) is an isoquinoline alkaloid isolated from various types of plants, including those from the Berberidaceae, Ranunculaceae, and Papaveraceae families. It... (Review)
Review
Berberine (BBR) is an isoquinoline alkaloid isolated from various types of plants, including those from the Berberidaceae, Ranunculaceae, and Papaveraceae families. It has long been used in traditional Chinese medicine for treating diarrhea and gastrointestinal disorders. The medicinal properties of BBR include antimicrobial, anti-inflammatory, antioxidative, lipid-regulatory, and antidiabetic actions. Importantly, the efficacy of BBR against cancers has been assessed in several experimental studies and clinical trials. Gastrointestinal (GI) cancers are a group of the most prevalent cancers worldwide that are associated with high morbidity and mortality, and their associated mortality has been increasing over the years. Thus, GI cancers have become a burden to the patients and health care systems. This review summarizes the cellular and molecular mechanisms underlying the therapeutic effects of BBR and explores its potential preventive and therapeutic applications against GI cancers.
Topics: Anti-Inflammatory Agents; Berberine; Gastrointestinal Neoplasms; Humans; Medicine, Chinese Traditional
PubMed: 31950049
DOI: 10.1155/2019/6831520 -
Journal of Cellular and Molecular... Nov 2023Heterotopic ossification (HO) is a pathological process that often occurs in soft tissues following severe trauma. There is no effective therapy for HO. The BMP...
Heterotopic ossification (HO) is a pathological process that often occurs in soft tissues following severe trauma. There is no effective therapy for HO. The BMP signalling pathway plays an essential role in the pathogenesis of HO. Our previous study showed that AMPK negatively regulates the BMP signalling pathway and osteogenic differentiation. The present study aims to study the effect of two AMPK activators berberine and aspirin on osteogenic differentiation and HO induced by traumatic injury. The effects of two AMPK activators, berberine and aspirin, on BMP signalling and osteogenic differentiation were measured by western blot, ALP and Alizarin red S staining in C3H10T1/2 cells. A mouse model with Achilles tenotomy was employed to assess the effects of berberine and aspirin on HO using μCT and histological analysis. First, our study showed that berberine and aspirin inhibited phosphorylation of Smad1/5 induced by BMP6 and the inhibition was attributed to the down-regulation of ALK2 expression. Second, the combination of berberine and aspirin yielded more potent effects on BMP signalling. Third, we further found that there was an additive effect of berberine and aspirin combination on osteogenic differentiation. Finally, we found that berberine and aspirin blocked trauma-induced ectopic bone formation in mice, which may be through suppression of phosphorylation of Smad1/5 in injured tissues. Collectively, these findings indicate that berberine and aspirin inhibit osteogenic differentiation in C3H10T1/2 cells and traumatic HO in mice, possibly through the down-regulation of the BMP signalling pathway. Our study sheds a light on prevention and treatment of traumatic HO using AMPK pharmacological activators berberine and aspirin.
Topics: Mice; Animals; Berberine; Osteogenesis; AMP-Activated Protein Kinases; Aspirin; Cell Differentiation; Ossification, Heterotopic
PubMed: 37605888
DOI: 10.1111/jcmm.17919