Protective Effect Of Berberine Research Articles

Protective Effect of Berberine on Acute Gastric Ulcer by Promotion of Tricarboxylic Acid Cycle-Mediated Arachidonic Acid Metabolism.

Peptic ulcer is a high incidence gastrointestinal disease in China. Berberine (BBR) is a natural product isolated from the Chinese herb Coptis chinensis Franch that has protective effects in digestive diseases. We aimed to evaluate the ability of BBR to attenuate acute gastric ulcer induced by one-time administration of ethanol in the rat. Tissue pathological morphology, macroscopic score, ulcer healing rate, and serum levels of the inflammatory cytokines nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), and anti-inflammatory interleukin-10 (IL-10) were used to determine the efficacy of BBR and evaluated to identify the optimal dosage. Subsequently, transcriptome and metabolome sequencing were conducted in Control, Model, and optimal dosage groups to explore the pathogenesis of the disease and the mechanism of action of the drug. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), as well as those of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined by enzyme-linked immunosorbent assay to verify the results of transcriptomics and metabolomics analyses. BBR significantly improved the pathological morphology of gastric ulcers, increased the macroscopic score and healing rate, decreased serum levels of NO, IL-6, and PGE2, and increased serum levels of IL-10, thus effectively alleviating gastric ulcer severity. Transcriptome results showed that the therapeutic effect of BBR was mainly mediated by the arachidonic acid metabolism pathway at the gene level, which is closely associated with inflammation and increased levels of reactive oxygen species (ROS). The differentially accumulated metabolite prostaglandin E1, which is a negative regulator of ROS, was significantly up-regulated after BBR administration. The validation results indicated that BBR pretreatment increased SOD and GSH-Px enzyme activities, while reducing levels of the oxidative products MDA and MPO. This study demonstrated that BBR exerts a protective effect on acute gastric ulcer by promoting tricarboxylic acid cycle-mediated arachidonic acid metabolism.

Protective effects of berberine against β-amyloid-induced neurotoxicity in HT22 cells via the Nrf2/HO‐1 pathway

Neuronal apoptosis has been found to have a pivotal role in the course of Alzheimer’s disease (AD). Berberine (BBR), a potent antioxidant, occurs in plants such as Berberis, Phellodendron chinense, and Hydrastis canadensis. In this study, a neuronal apoptotic model was established in vitro using HT22 cells induced by Aβ25-35 to explore whether BBR contributes to protecting neurons against Aβ25-35-induced neurotoxicity, as well as its potential mechanisms. BBR was applied to HT22 cells for 1 h prior to exposing the cells to Aβ25-35 for 24 h. A CCK-8 assay was utilized to assess cell viability, and Annexin V − fluorescein isothiocyanate (FITC)/propidium iodide and Hoechst 33342 fluorescence staining were used to measure the rate of cell apoptosis. Existing scientific literature was also reviewed to further determine the effects of BBR on ROS production and mitochondrial function in HT22 cells. Furthermore, the expressions of proteins, including cytochrome C, cleaved caspase-3, p-p65, p65, and Nrf2/HO‐1 antioxidant axis were assessed by Western blotting. The data indicated that BBR markedly improved cell viability, inhibited apoptosis and intracellular ROS levels, improved mitochondrial membrane potentials, decreased the rate of p-p65/p65, cytochrome C, and cleaved caspase-3, and intensified the activity of Nrf2/HO‐1 antioxidants in HT22 cells. Overall, the findings indicated that BBR provides a certain level of neuroprotectiveness in HT22 cells exposed to Aβ25–35 via relieving oxidative stress, as well as by restraining the mitochondrial pathway of cellular apoptosis. In addition, the restraint of NF-κB activity and sensitization of the Nrf2/HO‐1 antioxidant axis, which together are intimately involved in the neuroprotection of BBR, may be possible mechanisms accounting for its effectiveness against Aβ25–35in vitro.

Modulatory effect of berberine on plasma lipoprotein (or lipid) profile: a review.

Berberine is a bioactive isoquinoline alkaloid compound extracted from various medicinal plants, such as Barberry. Berberine shows various pharmacological properties that are mainly attributed to its anti-inflammatory and antioxidant effects. A growing body of evidence has shown that berberine influences cholesterol metabolism, and consequently, may ameliorate dyslipidemias and atherosclerosis. Plasma high-density lipoprotein cholesterol (HDL-C) is known to have an independent negative association with incident cardiovascular disease (CVD). However, several outcomes trials and genetic studies have failed to meet expecting the beneficial effects of elevating plasma HDL-C concentrations. Hence, investigations are currently focused on enhancing the functionality of HDL particles, independent of their plasma concentrations. HDL particles show various qualities because of a heterogeneous composition. Consistent with complex metabolism and composition, various biological functions are found for HDL, such as anti-inflammatory, antioxidant, anti-apoptotic, and anti-thrombotic activities. Protective effects of berberine may impact the functionality of HDL; therefore, the present literature review was intended to determine whether berberine can amplify HDL function. It was concluded that berberine may regulate markers of HDL activity, such as apo-AI, cholesterol efflux, LCAT, PON1, and S1P activities and levels. Consequently, berberine may recuperate conditions with dysfunctional HDL and, therefore, have the potential to emerge as a therapeutic agent. However, further human trials of berberine are warranted to evaluate its impact on HDL function and cholesterol metabolism.

Effect of berberine on copper and zinc levels in chickens infected with Eimeria tenella

Berberine, a traditional Chinese medicine, was found to exhibit anticoccidial activity. However, its mechanism is unclear. Trace metals such as copper and zinc are extremely low (less than 0.01% of the total weight of the body) but play a vital role in organisms. In the present study, we investigated the effect of berberine on copper and zinc levels in chickens infected with Eimeria tenella. Firstly, our data confirmed that infected chickens with E. tenella exhibited classic impairment on the 8th day of post infection, such as weight loss and increased feed conversion. Further study showed that E. tenella infection decreased the contents of copper and zinc in the liver and serum of chickens. Berberine was similar to amprolium and significantly improved the pathogenic conditions. Berberine could restore copper and zinc imbalance caused by E. tenella in chickens to a large extent. Studies on the development of cecum lesions demonstrated that the protective effect of berberine on the intestinal cecum was similar to that of the Cu/Zn mixture. Additionally, the mRNA expression of several metal transport related genes of the chick small intestine, including zinc transporter 1, copper transporter 1 and divalent metal ion transporter 1, was elevated by the treatment with berberine. Taken together, we speculate that the anticoccidial activity of berberine may be related to the maintenance of certain metals (Cu/Zn) homeostasis by affecting mRNA expression of their transport genes. However, the mode of action of BBR on these vital metals in the chicks infected with E. tenella still needs to be further studied.

Protective effects of berberine as a natural antioxidant and anti-inflammatory agent against nephrotoxicity induced by cyclophosphamide in mice.

Cyclophosphamide is an alkylating agent with nephrotoxicity that constrains its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. Forty animal subjects were randomly separated into five categories of control (Group I), cyclophosphamide (200mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor-α (TNF-α) and interleukin 1 beta (IL-1β) levels as inflammatory mediators were assessed in kidney tissue. The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1β and increasing the level of GSH, CAT, SOD, and GPx activities. Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

Protective effect of berberine against tacrolimus-induced nephrotoxicity in LLC-PK1 cells

Protective effect of berberine against tacrolimus-induced nephrotoxicity in LLC-PK1 cells

The Potential of Medicinal Plants and Bioactive Compounds in the Fight Against COVID-19

The Potential of Medicinal Plants and Bioactive Compounds in the Fight Against COVID-19

Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway.

BackgroundBer, a Chinese herbal monomer has been reported to exhibit an array of pharmacological activities related to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). In the present study, we aimed to elucidate the effect of berberine (Ber) on a rat model of PCOS mediated via the PI3K/AKT signaling pathway.MethodsA PCOS animal model was induced with the administration of letrozole, and animals were then randomized into untreated or Ber and metformin hydrochloride treated groups. After administration, fasting blood glucose, HOMA‐IR, fasting insulin (FINS) values, and the serum hormone levels were measured in PCOS rats. The ovarian tissues were stained with hematoxylin and eosin and terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling (TUNEL) for pathological and apoptosis examination. Moreover, the effect of Ber on the proliferation and apoptosis of granulosa cells was detected by CCK‐8 assays and flow cytometry. The influence of Ber on granulosa cells was confirmed by blockade of the PI3K/AKT pathway. In addition, the modulatory effect of the blockade of the PI3K/AKT pathway on the expression of related proteins was demonstrated via western blotting.ResultsWe found that Ber was able to restore the serum hormone levels and improve IR in a PCOS rat model. The morphological lesions and apoptosis of the ovary were also restored by the Ber treatment. Blockade of the PI3K/AKT pathway attenuated the influences of Ber on the proliferation and apoptosis of granulosa cells.ConclusionThe beneficial effects of Ber on PCOS included alterations of the serum hormone levels, recovery of morphological lesions in the ovary, improvement of insulin resistance, and cell viability and inhibition of apoptosis, which were all mediated through the PI3K/AKT pathway.

Protective effect of berberine against LPS-induced endothelial cell injury via the JNK signaling pathway and autophagic mechanisms

ABSTRACT The role of autophagic mechanisms in the protective effect of berberine (BBR) on lipopolysaccharide (LPS)-induced injury in the endothelial cells human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) was investigated. Cell viability, proliferation, and apoptosis were detected by the CCK-8 assay, the EdU kit, and flow cytometry, respectively, and autophagy-related protein expression, the number of autophagic vacuoles, and LC3 double-fluorescence were examined using western blot analysis, transmission electron microscopy, and confocal microscopy, respectively. LPS resulted in a decrease in the cell viability and proliferation of HUVECs and HPMECs and an increase in the number of apoptotic cells, while BBR treatment resulted in an increase in cell viability and proliferation, as well as a decrease in cell apoptosis. Furthermore, BBR could inhibit LPS-induced autophagy, as demonstrated by its inhibitory effects on the LC3-II/LC3-I ratio and Beclin-1 levels and its promotive effect on p62 expression. Addition of the autophagy inducer rapamycin (RAPA) aggravated LPS-induced injury, while treatment with the autophagy blocker 3-methyladenine (3-MA) attenuated the injury. Further, the protective effect of BBR was inhibited by rapamycin. JNK inhibition by SP600125 inhibited LPS-induced autophagy, and BBR could not alter the LPS-induced autophagy in HUVECs and HPMECs that were pretreated with SP600125. The present data indicate that BBR attenuated LPS-induced cell apoptosis by blocking JNK-mediated autophagy in HUVECs and HPMECs. Therefore, the JNK-mediated autophagy pathway could be a potential target for the prevention and treatment of cardiovascular disease.

Protective effects of berberine against MPTP-induced dopaminergic neuron injury through promoting autophagy in mice

Berberine, an isoquinoline alkaloid isolated from Coptis chinensis, has been widely studied for its efficacy in the treatment of neurodegenerative diseases. However, the detailed mechanisms are unknown. In this study, the effects of berberine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease were investigated. We showed that treatment with berberine significantly ameliorates the degeneration of dopaminergic neurons in substantia nigra compacta (SNc) and improves motor impairment in MPTP-treated mice. Berberine also significantly decreased the level of α-synuclein and enhanced the microtubule-associated protein light chain 3 (LC3-II)-associated autophagy in the SN of MPTP-treated mice. Furthermore, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) was activated by berberine. Berberine's actions were abolished by pre-treatment with 3-methyladenine (an autophagy inhibitor) or compound c (an AMPK inhibitor) in the MPP+-treated SH-SY5Y cells. These results suggested that the protective effects of berberine on the toxicity of MPTP could be attributed to berberine-enhanced autophagy via the AMPK dependent pathway.

Berberine suppresses bone loss and inflammation in ligature-induced periodontitis through promotion of the G protein-coupled estrogen receptor-mediated inactivation of the p38MAPK/NF-κB pathway

ObjectiveThis study aimed to explore the protective actions of berberine on inflammation, and alveolar bone loss in ligature-induced periodontitis, as well as its mechanism of action MethodsMicro-computed tomography was conducted to analyze the alveolar bone loss, and hematoxylin and eosin staining was carried out to observe the histopathological changes and inflammation status. Furthermore, enzyme linked immunosorbent assay (ELISA) was conducted to evaluate the levels of TNF-α, IL-1β, and IL-10, as well as western blots to determine the levels of GPR30 and the activity of the p38MAPK/NF-κB pathway. ResultsBerberine distinctly suppressed alveolar bone loss and inflammation in rats exposed to ligature-induced periodontitis. As well as this, berberine significantly decreased the levels of phosphorylated p38MAPK and phosphorylated NF-κB 65 through upregulating the GRP30 protein levels, this protective effects of berberine were reversed by injection of G15, along with the upregulated activity of the p38MAPK/NF-κB pathway in rats with periodontitis. ConclusionsBerberine had a clear inhibitory effect on alveolar bone loss and inflammation in rats exposed to ligature-induced periodontitis, and its putative mechanism of action was attributed to the downregulation of the activity of the P38MAPK/NF-κB pathway, mediated by the G Protein-coupled estrogen receptor.

Macrovascular Protecting Effects of Berberine through Anti-inflammation and Intervention of BKCa in Type 2 Diabetes Mellitus Rats.

The aim of this study was to examine the effect of berberine on diabetes mellitus in vivo and in vitro, and elucidate the underlying mechanisms. Rat models of type 2 diabetes mellitus (T2DM) were established and were treated with berberine. Pathological changes in the thoracic aorta, and inflammatory factor and adiponectin levels were investigated. Vascular smooth muscle cells (VSMCs) of the thoracic aorta were cultured and treated with berberine. Cellular proliferation, migration, and inflammatory factor levels were investigated. Responses of vascular rings to phenylephrine (PE) and sodium nitroprusside (SNP) after berberine intervention and the changes of relaxation responses to SNP after adding Iberiotoxin (IbTX) were investigated. Berberine ameliorated the pathological status of the thoracic aorta in the T2DM rats. Berberine significantly inhibited the C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and increased the adiponectin level compared with the model group. Compared with the model group, berberine inhibited the proliferation and migration of VSMCs in vitro, and reduced tumor growth factor-β1 (TGF-β1), IL-6, and TNF-α levels. Furthermore, the contraction of thoracic aorta to PE was reduced, while the relaxation response of thoracic aorta to SNP was increased, after the berberine intervention in the T2DM rats. The relaxation response of thoracic aorta to SNP in the model and berberine groups decreased after the IbTX treatment. Protective effects of berberine against macrovascular complications induced by diabetes mellitus may be attributed to inhibiting of the inflammation and intervening of the calcium- activated potassium (BKCa).

Berberine protects against diabetic kidney disease via promoting PGC-1α-regulated mitochondrial energy homeostasis.

Background and PurposeDisordered lipid metabolism and disturbed mitochondrial bioenergetics play pivotal roles in the initiation and development of diabetic kidney disease (DKD). Berberine is a plant alkaloid, used in Chinese herbal medicine. It has multiple therapeutic actions on diabetes mellitus and its complications, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity, and alleviation of oxidative damage. Here, we investigated the reno‐protective effects of berberine.Experimental ApproachWe used samples from DKD patients and experiments with models of DKD (db/db mice) and cultured podocytes, to characterize energy metabolism profiles using metabolomics. Molecular targets and mechanisms involved in the regulation of mitochondrial function and bioenergetics by berberine were investigated, along with its effects on metabolic alterations in DKD mice.Key ResultsMetabolomic analysis suggested altered mitochondrial fuel usage and generalized mitochondrial dysfunction in patients with DKD. In db/db mice, berberine treatment reversed the disordered metabolism, podocyte damage and glomerulosclerosis. Lipid accumulation, excessive generation of mitochondrial ROS, mitochondrial dysfunction, and deficient fatty acid oxidation in DKD mouse models and in cultured podocytes were suppressed by berberine. These protective effects of berberine were accompanied by activation of the peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) signalling pathway, which promoted mitochondrial energy homeostasis and fatty acid oxidation in podocytes.Conclusion and ImplicationsPGC‐1α‐mediated mitochondrial bioenergetics could play a key role in lipid disorder‐induced podocyte damage and development of DKD in mice. Restoration of PGC‐1α activity and the energy homeostasis by berberine might be a potential therapeutic strategy against DKD.

Protective effect of Berberine on reproductive function and spermatogenesis in diabetic rats via inhibition of ROS/JAK2/NFκB pathway.

Diabetes mellitus (DM) induces impairment of male reproductive system and is considered as a key factor that could partially provide an explanation for male infertility. Thus, understanding the mechanism underlying DM-induced infertility will aid in the identification of novel therapeutic stratagems. To delineate the role of ROS/JAK2/NFκB pathway in DM-induced low reproductive function and impaired spermatogenesis. Additionally, to investigate the protective effect of monomeric Berberine (BB) that inhibits ROS/JAK2/NFκB pathway, in the pathogenesis of DM-induced infertility. 12-week-old male Sprague-Dawley rats were divided into four groups: control group, DM group, control plus BB group, and DM plus BB group. Streptozotocin was used to induce DM. After treating the rats with BB for 4weeks, fertility tests were conducted to investigate the reproductive function, and testis weight along with sperm motility was assessed through microscope. Oxidative stress was evaluated by DHE staining. TUNEL staining was utilized to detect the state of apoptosis. Cell experiments were carried out to define the role of BB in vitro. Immunohistochemistry, immunofluorescence, and Western blotting were employed to measure the protein expression. Our results indicate that the reproductive function of DM rats was low, accompanied by decreased testis weight and sperm motility in addition to the impairment of the seminiferous tubules. However, there was a significant improvement in the reproductive function parameters in the BB-treated DM rats. Subsequently, our data revealed that DM rats produce an increased level of ROS in the testis, which activates JAK2 further activating the NFκB pathway, leading to increased apoptosis and impaired cells in the testicles. However, BB could attenuate the ROS production and abrogate activation of JAK2/NFκB pathway, thus inhibiting the apoptosis in the testicular cells of DM rats. ROS/JAK2/NFκB pathway is involved in the DM-induced low reproductive function and impaired spermatogenesis. BB can play a protective role in preserving the reproductive function and spermatogenesis in DM by inhibiting ROS/JAK2/NFκB pathway.

Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer's disease.

Berberine (a protoberberine isoquinoline alkaloid) has shown promising pharmacological activities, including analgesic, anti-inflammatory, anticancer, antidiabetic, anti-hyperlipidemic, cardioprotective, memory enhancement, antidepressant, antioxidant, anti-nociceptive, antimicrobial, anti- HIV and cholesterol-lowering effects. It is used in the treatment of the neurodegenerative disorder. It has strong evidence to serve as a potent phytoconstituent in the treatment of various neurodegenerative disorders such as AD. It limits the extracellular amyloid plaques and intracellular neurofibrillary tangles. It has also lipid-glucose lowering ability, hence can be used as a protective agent in atherosclerosis and AD. However, more detailed investigations along with safety assessment of berberine are warranted to clarify its role in limiting various risk factors and AD-related pathologies. This review highlights the pharmacological basis to control oxidative stress, neuroinflammation and protective effect of berberine in AD, which will benefit to the biological scientists in understanding and exploring the new vistas of berberine in combating Alzheimer's disease.

Berberine protects steatotic donor undergoing liver transplantation via inhibiting endoplasmic reticulum stress-mediated reticulophagy.

Steatotic livers are more susceptible to ischemia/reperfusion injury, and increase the risk of primary graft non-function after liver transplantation. The protective effects of berberine have been described in various liver pathological models. However, it is unknown if berberine exerts its beneficial action in steatotic donors undergoing liver transplantation. In the present study, male Wistar rats were fed with high-fat diet (HFD) for 12 weeks to induce moderate steatotic liver. Then orthotropic liver transplantation was constructed. Berberine (200 mg/kg/d) was given intragastrically one week before liver transplantation. Thapsigargin (TG) (0.2 mg/kg) was administrated intravenously 24 h before liver transplantation. Liver function, oxidative stress, and inflammatory cytokine were detected by biochemical or histopathological analysis. The morphology of autophagosomes and endoplasmic reticulum (ER) was observed by transmission electron microscopy. The expression of CHOP, BIP, the phosphorylation of PERK, LC3-II/I, Beclin-1, and p62 were determined by Western blot assay. The co-localization of endoplasmic reticulum marker (KDEL) and autophagic protein (LC3B) was analyzed by immunofluorescence microscopy. The level of reticulophagy hallmark (FAM134B) was determined by immunohistochemistry. Compared with HFD + LT group, berberine ameliorated hepatocellular damage, decreased the oxidative stress level and inflammatory cytokine release. Simultaneously, berberine inhibited the expression of both endoplasmic reticulum stress parameters and autophagy-related proteins. Additionally, the co-localization of endoplasmic reticulum marker and LC3B was also reduced in HFD + BBR + LT group. berberine down-regulated the level of FAM134B. TG reversed the beneficial effects of berberine. Our study revealed that berberine exerts protective effects on steatotic livers undergoing transplantation by inhibiting endoplasmic reticulum stress-mediated reticulophagy. Impact statement Berberine is isolated from traditional Chinese medicine plants and has dramatically therapeutic potential against inflammation, diarrhea, and diabetes. But the benefits of BBR on steatotic grafts after liver transplantation remain poorly understood. Our findings might help explain the mechanism of berberine in protecting steatotic livers undergoing transplantation and give advantageous insights that berberine has potential as a suitable candidate for preventing hepatic injury after steatotic liver transplantation by inhibiting ER stress-mediated reticulophagy.

Protective effects of berberine against exhaustion exercise induced myocardial injury in rats

Objective: To investigate the effect and possible mechanism of berberine (Ber) on myocardial injury induced by exhaustion exercise (Ee). Methods: Forty healthy male SPF Sprague-Dawley rats were randomly divided into 5 groups using the random unit group design method: control group, Ee group and Ee plus Ber group (low: 50 mg·kg(-1)·d(-1), medium: 100 mg·kg(-1)·d(-1) and high dose: 150 mg·kg(-1)·d(-1), n=8 each). Ber (1.5 ml) or equal volume saline was given per gavage for 14 days. Rats assigned to Ee groups underwent Ee swimming once daily and rats in control group remain sedentary. After 14 days, echocardiographic measurements were performed and left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular diastolic diameter (LVIDd) and left ventricular systolic diameter (LVIDs) were obtained. The morphological structure of heart was detected by HE and Masson staining. Serum superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Cardiomyocytes apoptosis was detected by TUNEL method. The protein expression of myocardial hypertrophy marker protein B-type natriuretic peptide (BNP) and apoptotic marker protein (Bcl-2, Bax) in rat myocardial tissue was detected by Western blot. Results: (1) Both LVFS and LVEF were significantly lower, and LVIDs and LVIDd were significantly larger in Ee group than those in control group (all P<0.01). The LVFS and LVEF in medium dose of Ber and high-dose Ber groups were significantly higher, and the LVIDs and LVIDd were significantly smaller than those in Ee group (all P<0.01). (2) The results of HE staining showed that the myocardial cells in control group were closely arranged, regular, normal in morphology, clear in structure, and uniform in staining. The myocardial cells of rats in Ee group were disarranged, cell staining was uneven, and vacuoles appeared in the cytoplasm. The disorder of myocardial cell arrangement and unequal staining in the medium dose of Ber were attenuated than in Ee group. The Masson staining results showed that the myocardial cells in control group were closely arranged, regular, normal in shape, clear in structure, and rarely blue-stained (fibrosis). Myocardial cells in rats in Ee group showed obvious fibrosis. The myocardial cell fibrosis in rats with medium dose of Ber was significantly reduced than exercise group. (3) MDA content in myocardial tissue of rats in Ee group was significantly higher than that of control group, and MDA content in myocardial tissue of rats in medium dose of Ber group was significantly lower than in Ee group (P<0.01). The SOD activity of myocardial tissue in rats was significantly lower than that of control group, while that of rats with medium dose of Ber was significantly higher than that of rats in Ee group (P<0.01). (4) TUNEL staining results showed that only a small amount of apoptosis myocardial cells were seen in control group, and a large number of apoptosis myocardial cells were seen in rats in Ee group. However, the number of apoptotic cardiomyocytes in medium dose of Ber was significantly lower than that in Ee group. The AI of rat cardiomyocytes was significantly higher than that of control group (P<0.01), and the AI of rat cardiomyocytes in median dose of Ber group was significantly lower than in Ee group (P<0.01). (5) BNP and Bax protein expression in the myocardial tissues of rats in Ee group were significantly higher than in control group (P<0.01). BNP and Bax protein expression in the myocardial tissues in median dose of Ber group were significantly lower than that of Ee group (P<0.01). The myocardial protein expression level of Bax was significantly higher, and the myocardial protein level of Bcl-2 was significantly lower in Ee group than in control group (both P<0.01), treatment with median dose of Ber could partly reverse above changes (both P<0.01). Conclusion: Ber can attenuate exhaustion exercise induced myocardial injury and remodeling in rats, and the beneficial effects of Ber might possibly be mediated by reducing free radical release and cardiomyocytes apoptosis.

The protective effects of Berberine and Hesperidin on inflammatory factor-stimulating cardiac fibroblasts.

The previous work has shown that Berberine and Hesperidin have beneficial effects on cardiovascular diseases. However, the underlying mechanisms remain unknown. This study aimed to investigate the effect of Berberine and Hesperidin on inflammatory cytokine secretion, proliferation, differentiation, and collagen synthesis of cardiac fibroblasts stimulated by the transforming growth factor-β1 (TGF-β1), and the potential of these drugs to regulate the Notch1 signaling pathway. Neonatal rat primary cardiac fibroblasts were stimulated with 5 ng/mL TGF-β1 as model (TGF) group. In the Berberine (TGF+B) group cells were given TGF-β1, along with 1.25/2.5/5/10 mg/L Berberine, while the Hesperidin (TGF+H) group was treated with TGF-β1 and 12.5/25/50/100 µmmol/L Hesperidin. Cellular proliferation, differentiation, and collagen synthesis were evaluated. The role of the Notch1 signaling pathway in the protective effects of Berberine and Hesperidin was analyzed by using γ-secretase inhibitor (DAPT) to block the Notch1 pathway. 5/10 mg/L Berberine intervention could noticeably decrease both TGF-β1 and IL-1β levels, 25/50/100 µmol/L Hesperidin could reduce IL-1β secretion from TGF-β1 stimulated cardiac fibroblasts. Both Berberine and Hesperidin decreased the expression of α-SMA and cell viability in a concentration-dependent manner; however, the apoptosis of cardiac fibroblasts was not influenced. 10 mg/L Berberine or at least 50 µmol/L Hesperidin could noticeably decrease MMP-1 expression, and at least 5 mg/L Berberine or 100 µmol/L Hesperidin could markedly reduce MMP-9 expression. Using DAPT to block Notch1 signaling could reverse the protective effects of Berberine and Hesperidin. Berberine and Hesperidin can reduce the secretion of inflammatory cytokines, differentiation, and proliferation, and increase the collagen synthesis of cardiac fibroblasts stimulated by TGF-β1 via the Notch1 signaling pathway.

Berberine Attenuated Oxidative Stress Induced by Sodium Nitrite in Rat Liver

Background: Berberine is a well-known alkaloid derived from Berberis species. Objectives: The present study aimed to investigate the hepatoprotective properties of berberine and elucidate its probable mechanisms against sodium nitrite toxicity. Methods: Forty animals were randomly classified into five equal groups to be treated for 60 days, including group 1: Control, group 2: Berberine-treated (100 mg/kg), group 3: Sodium nitrite-treated (80 mg/kg), group 4: Sodium nitrite together with 50 mg/kg of berberine, and group 5: Sodium nitrite together with 100 mg/kg of berberine. The protective effects of berberine against sodium nitrite induced-liver damage were investigated using parameters related to oxidative stress, inflammation, fibrosis, and apoptosis in the hepatocytes. Results: Treatment of rats with sodium nitrite considerably increased alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, malondialdehyde (MDA) content, tumor necrosis factor (TNF)-α expression, caspase-3 activity, and transforming growth factor (TGF)-β1 concentration (P < 0.05) and significantly declined the levels of reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), and glutathione peroxidase (GPx) (P < 0.05). The treatment of intoxicated rats with 100 mg/kg of berberine significantly reversed these changes and reached the values approximately to the normal level. However, berberine 50 mg/kg failed to normalize the disturbances. Conclusions: This study demonstrated that berberine could decrease sodium nitrite-induced liver injury in a dose-dependent manner probably due to its antioxidant, anti-inflammatory, anti-apoptotic, and antifibrotic capacities.

Protective effect of berberine on aconite‑induced myocardial injury and the associated mechanisms.

Aconitum plants, which have analgesic, diuretic and anti-inflammatory effects, have been widely used to treat various types of disease. However, the apparent toxicity of Aconitum-derived agents, particularly in the cardiovascular system, has largely limited their clinical use. Thus, the present study investigated whether berberine (Ber), an isoquinoline alkaloid, may reduce myocardial injury induced by aconitine (AC) in rats and the underlying mechanisms. Rats (n=40) were randomly divided into four groups: Control, Chuan-wu and Chuan-wu + Ber (8 and 16 mg/kg doses). Electrocardiograms (ECG) of the rats were recorded and serum biomarkers of cardiac function [lactate dehydrogenase (LDH), creatine kinase (CK) and CK-MB] were assayed. Histopathological changes were assessed using myocardial tissue sectioning and hematoxylin and eosin staining. Additionally, the effects of Ber on AC-induced arrhythmias in rats were observed. The changes in ECG following AC perfusion were observed, and the types and onset time of arrhythmias were analyzed. Furthermore, the effects of Ber and AC on papillary muscle action potentials were observed. The results suggested that Ber ameliorated myocardial injury induced by Chuan-wu, which was indicated by reduced arrhythmias and decreased LDH, CK and CK-MB levels in serum. Furthermore, histological damage, including dilation of small veins and congestion, was also markedly attenuated by Ber. In addition, the occurrence of arrhythmias was significantly delayed, and the dosage of AC required to induce arrhythmias was also increased by Ber pretreatment. Additionally, AC-induced changes in action potential amplitude, duration of 30% repolarization and duration of 90% repolarization in the papillary muscle were attenuated by Ber. All of these results indicate that Ber had a preventive effect on acute myocardial injury induced by Chuan-wu and arrhythmias caused by AC, which may be associated with the inhibition of delayed depolarization and triggered activity caused by AC. Thus, combination treatment of Ber with Aconitum plants may be a novel strategy to prevent AC-induced myocardial injury in clinical practice.