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Biomedicine & Pharmacotherapy =... Jan 2024Depression, a global neuropsychiatric disorder, brings a serious burden to patients and society as its incidence continues to rise. Berberine is one of the main...
BACKGROUND
Depression, a global neuropsychiatric disorder, brings a serious burden to patients and society as its incidence continues to rise. Berberine is one of the main compounds of a variety of Chinese herbal medicines and has been shown to have multiple pharmacological effects. However, whether berberine can exert antidepressant effects in vivo and in vitro and its related mechanisms remain to be explored.
METHODS
The chronic restraint stress (CRS) method and corticosterone (CORT) were applied to simulate depression-like behavior in vivo and neuronal apoptosis in vitro, respectively. The antidepressant effects of berberine were evaluated by behavioral tests and changes in the content of monoamine neurotransmitters. Inflammatory cytokines were detected and immunofluorescence staining was used to observe the expression levels of apoptosis-related proteins. RT-qPCR and Western blot were used to examine the mRNA and protein expression (or phosphorylation) levels of biomarkers of the PI3K/AKT/CREB/BDNF signaling pathways.
RESULTS
Behavioral tests and levels of neurotransmitters proved that berberine could effectively ameliorate depression-like symptoms in CRS mice. Meanwhile, the results of ELISA and immunofluorescence staining showed that berberine could alleviate inflammatory status and reduce cell apoptosis in vivo and in vitro. Moreover, the changes of the PI3K/AKT/CREB/BDNF signaling pathway induced by CRS or CORT in mouse hippocampus or HT-22 cells were significantly reversed by berberine.
CONCLUSION
Our current study suggested that berberine could exert antidepressant effects in vitro and in vivo, which may be associated with the PI3K/AKT/CREB/BDNF signaling pathway.
Topics: Humans; Mice; Animals; Proto-Oncogene Proteins c-akt; Berberine; Brain-Derived Neurotrophic Factor; Phosphatidylinositol 3-Kinases; Antidepressive Agents; Signal Transduction; Depression; Corticosterone; Neurotransmitter Agents; Hippocampus
PubMed: 38113631
DOI: 10.1016/j.biopha.2023.116012 -
Biomedicine & Pharmacotherapy =... Jul 2023Berberine (BBR), a major alkaloid in Coptis chinensis, and (-)-epigallocatechin-3-gallate (EGCG), a major catechin in green tea, are two common phytochemicals with...
Berberine (BBR), a major alkaloid in Coptis chinensis, and (-)-epigallocatechin-3-gallate (EGCG), a major catechin in green tea, are two common phytochemicals with numerous health benefits, including antibacterial efficacy. However, the limited bioavailability restricts their application. Advancement in the co-assembly technology to form nanocomposite nanoparticles precisely controls the morphology, electrical charge, and functionalities of the nanomaterials. Here, we have reported a simple one-step method for preparing a novel nanocomposite BBR-EGCG nanoparticles (BBR-EGCG NPs). These BBR-EGCG NPs exhibit improved biocompatibility and greater antibacterial effects both in vitro and in vivo relative to free-BBR and first-line antibiotics (i.e., benzylpenicillin potassium and ciprofloxacin). Furthermore, we demonstrated a synergistic bactericidal effect for BBR when combined with EGCG. We also evaluated the antibacterial activity of BBR and the possible synergism with EGCG in MRSA-infected wounds. A potential mechanism for synergism between S. aureus and MRSA was also explored through ATP determination, the interaction between nanoparticles and bacteria, and, then, transcription analysis. Furthermore, our experiments on S. aureus and MRSA confirmed the biofilm-scavenging effect of BBR-EGCG NPs. More importantly, toxicity analysis revealed that the BBR-EGCG NPs had no toxic effects on the major organs of mice. Finally, we proposed a green method for the fabrication of BBR-EGCG combinations, which may provide an alternative approach to treating infections with MRSA without using antibiotics.
Topics: Mice; Animals; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Catechin; Berberine; Anti-Bacterial Agents; Staphylococcal Infections; Nanocomposites
PubMed: 37196539
DOI: 10.1016/j.biopha.2023.114856 -
Molecules (Basel, Switzerland) Jun 2022Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is... (Review)
Review
Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer's disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.
Topics: Alkaloids; Anti-Inflammatory Agents; Berberine; Diabetes Mellitus, Type 2; Female; Humans; Nanotechnology; Pharmaceutical Preparations
PubMed: 35744831
DOI: 10.3390/molecules27123705 -
Computational and Mathematical Methods... 2022Berberine exhibits polytrophic medicinal roles in various diseases and is safe and effective. However, its role and the underlying mechanism in the replication of herpes...
Berberine exhibits polytrophic medicinal roles in various diseases and is safe and effective. However, its role and the underlying mechanism in the replication of herpes simplex virus 1 (HSV-1) remain unreported. This research aimed to determine the functional mechanisms of berberine on HSV-1 infection. We determined the CC50 (405.11 ± 15.67 M) and IC50 (45.6 ± 6.84 M) of berberine on HEK293T cells infected with HSV-1. Berberine inhibited the transcription and translation of HSV-1 activity-related genes (gD, ICP-4, ICP-5, and ICP-8) in HSV-1-infected HEK293T cells dose-dependently. Berberine also inhibited the phosphorylation of MAPK proteins (JNK and p38) and inflammatory responses induced by HSV-1 infection in HEK293T cells dose-dependently. In conclusion, berberine attenuates HSV-1 replication through its activity, infective ability, and inflammatory response. Our research indicated that berberine may be a candidate drug for HSV-1 infection.
Topics: Humans; Herpesvirus 1, Human; Berberine; HEK293 Cells; Virus Replication; Antiviral Agents
PubMed: 36276998
DOI: 10.1155/2022/7137401 -
Journal of Ovarian Research Jan 2021Ovarian cancer is the first leading cause of death in gynecological cancers. The continuous survival and metastasis of cancer cells are the main causes of death and poor...
Ovarian cancer is the first leading cause of death in gynecological cancers. The continuous survival and metastasis of cancer cells are the main causes of death and poor prognosis in patients with ovarian cancer. Berberine is an effective component extracted from the rhizomes of coptis chinensis and phellodendron chinensis. In our study, we aim to explore the molecular mechanism underlying the regulation of proliferation, migration and invasion by berberine in ovarian cancer cells. CCK8 assay was used for detection of proliferative capacity of SKOV3 and 3AO cells. Wound healing assay was used to estimate cell migration and transwell assay was used to assess cell invasion. The mRNA expression of miR-145 and MMP16 were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The protein level of MMP16 was detected by western blot analysis. In addition, luciferase reporter assays were used to demonstrate MMP16 was a target of miR-145. The results demonstrated berberine inhibited proliferation, migration and invasion, promoted miR-145 expression, and decreased MMP16 expression in SKOV3 and 3AO cells. MMP16 was a target of miR-145. Moreover, downregulation of MMP16 contributed to the inhibition of proliferation, migration and invasion by berberine. Together, our results revealed that berberine inhibited proliferation, migration and invasion through miR-145/MMP16 in SKOV3 and 3AO cells, highlighting the potentiality of berberine to be used as a therapeutic agent for ovarian cancer.
Topics: Berberine; Cell Line, Tumor; Female; Humans; Matrix Metalloproteinase 16; MicroRNAs; Neoplasm Metastasis; Ovarian Neoplasms; Transfection
PubMed: 33407764
DOI: 10.1186/s13048-020-00752-2 -
Ginekologia Polska 2024Polycystic ovary syndrome (PCOS) is a widely prevalent condition that affects approximately 5-10% of women of reproductive age. Although first described in the 18th... (Review)
Review
Polycystic ovary syndrome (PCOS) is a widely prevalent condition that affects approximately 5-10% of women of reproductive age. Although first described in the 18th century, a detailed account of the disease was not provided until Stein and Leventhal's 1935 report. Due to the varied symptomatology of PCOS, treatment must be tailored and often involves using multiple drugs for optimal pharmacotherapy. Berberine, an alkaloid with a longstanding history of use, has gained popularity as a potential treatment option for PCOS. Previous studies have demonstrated that berberine can improve hormonal imbalances by reducing testosterone and FAI, increasing SHBG, and mitigating the clinical symptoms of androgen excess, including hirsutism and acne. Moreover, berberine enhances the therapeutic effects of other drugs commonly used in PCOS, such as metformin and oral contraceptive pills. It is generally well-tolerated with a favourable safety profile. However, further research is warranted to establish conclusive evidence regarding berberine's mechanistic underpinnings, therapeutic potential, and long-term safety as a PCOS treatment modality.
Topics: Humans; Polycystic Ovary Syndrome; Berberine; Female; Metformin; Testosterone; Hypoglycemic Agents
PubMed: 38108460
DOI: 10.5603/gpl.95138 -
Molecules (Basel, Switzerland) Sep 2022Cancer is the most commonly diagnosed type of disease and a major cause of death worldwide. Despite advancement in various treatment modules, there has been little... (Review)
Review
Cancer is the most commonly diagnosed type of disease and a major cause of death worldwide. Despite advancement in various treatment modules, there has been little improvement in survival rates and side effects associated with this disease. Medicinal plants or their bioactive compounds have been extensively studied for their anticancer potential. Novel drugs based on natural products are urgently needed to manage cancer through attenuation of different cell signaling pathways. In this regard, berberine is a bioactive alkaloid that is found in variety of plants, and an inverse association has been revealed between its consumption and cancer. Berberine exhibits an anticancer role through scavenging free radicals, induction of apoptosis, cell cycle arrest, inhibition of angiogenesis, inflammation, PI3K/AKT/mammalian target of rapamycin (mTOR), Wnt/β-catenin, and the MAPK/ERK signaling pathway. In addition, synergistic effects of berberine with anticancer drugs or natural compounds have been proven in several cancers. This review outlines the anticancer effects and mechanisms of action of berberine in different cancers through modulation of various cell signaling pathways. Moreover, the recent developments in the drug delivery systems and synergistic effect of berberine are explained.
Topics: Antineoplastic Agents; Apoptosis; Berberine; Biological Products; Cell Line, Tumor; Cell Proliferation; Humans; Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; beta Catenin
PubMed: 36144625
DOI: 10.3390/molecules27185889 -
Inflammopharmacology Dec 2022Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to... (Review)
Review
Coronavirus disease 2019 (Covid-19) is a global diastrophic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Covid-19 leads to inflammatory, immunological, and oxidative changes, by which SARS-CoV-2 leads to endothelial dysfunction (ED), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and multi-organ failure (MOF). Despite evidence illustrating that some drugs and vaccines effectively manage and prevent Covid-19, complementary herbal medicines are urgently needed to control this pandemic disease. One of the most used herbal medicines is berberine (BBR), which has anti-inflammatory, antioxidant, antiviral, and immune-regulatory effects; thus, BBR may be a prospective candidate against SARS-CoV-2 infection. This review found that BBR has anti-SARS-CoV-2 effects with mitigation of associated inflammatory changes. BBR also reduces the risk of ALI/ARDS in Covid-19 patients by inhibiting the release of pro-inflammatory cytokines and inflammatory signaling pathways. In conclusion, BBR has potent anti-inflammatory, antioxidant, and antiviral effects. Therefore, it can be utilized as a possible anti-SARS-CoV-2 agent. BBR inhibits the proliferation of SARS-CoV-2 and attenuates the associated inflammatory disorders linked by the activation of inflammatory signaling pathways. Indeed, BBR can alleviate ALI/ARDS in patients with severe Covid-19. In this sense, clinical trials and prospective studies are suggested to illustrate the potential role of BBR in treating Covid-19.
Topics: Humans; SARS-CoV-2; Berberine; Antioxidants; Prospective Studies; Respiratory Distress Syndrome; Antiviral Agents; Anti-Inflammatory Agents; COVID-19 Drug Treatment
PubMed: 36183284
DOI: 10.1007/s10787-022-01080-1 -
Molecules (Basel, Switzerland) Mar 2020Berberine is multifunctional natural product with potential to treat diverse pathological conditions. Its broad-spectrum anticancer effect through direct effect on... (Review)
Review
Berberine is multifunctional natural product with potential to treat diverse pathological conditions. Its broad-spectrum anticancer effect through direct effect on cancer cell growth and metastasis have been established both in vitro and in vivo. The cellular targets that account to the anticancer effect of berberine are incredibly large and range from kinases (protein kinase B (Akt), mitogen activated protein kinases (MAPKs), cell cycle checkpoint kinases, etc.) and transcription factors to genes and protein regulators of cell survival, motility and death. The direct effect of berberine in cancer cells is however relatively weak and occur at moderate concentration range (10-100 µM) in most cancer cells. The poor pharmacokinetics profile resulting from poor absorption, efflux by permeability-glycoprotein (P-gc) and extensive metabolism in intestinal and hepatic cells are other dimensions of berberine's limitation as anticancer agent. This communication addresses the research efforts during the last two decades that were devoted to enhancing the anticancer potential of berberine. Strategies highlighted include using berberine in combination with other chemotherapeutic agents either to reduce toxic side effects or enhance their anticancer effects; the various novel formulation approaches which by order of magnitude improved the pharmacokinetics of berberine; and semisynthetic approaches that enhanced potency by up to 100-fold.
Topics: Antineoplastic Agents; Apoptosis; Berberine; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Drug Compounding; Drug Discovery; Humans; Molecular Structure
PubMed: 32245062
DOI: 10.3390/molecules25061426 -
Immunity, Inflammation and Disease Jan 2023Among the most frequent demyelinating autoimmune disorders of the central nervous system (CNS) is multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is...
INTRODUCTION
Among the most frequent demyelinating autoimmune disorders of the central nervous system (CNS) is multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is used as an animal model of multiple sclerosis. Berberine is an alkaloid found in some medicinal plants with anti-inflammatory effects.
METHODS
C57BL/6 female mice were used and divided into three groups: (1) The control group received PBS, (2) the low-dose treatment group received 10 mg/kg of berberine, and (3) The high-dose treatment group received 30 mg/kg of berberine. Myelin Oligodendrocyte Glycoprotein and complete Freund's adjuvant were subcutaneously administered to induce EAE. Mice were given intraperitoneal injections of pertussis toxin on the day of immunization and 2 days later. Histological studies showed low lymphocyte infiltration and demyelination of CNS in the treated groups.
RESULTS
The clinical scores of the treatment group with low-dose berberine (T1: 2 ± 0.13) and high-dose berberine (T2: 1.5 ± 0.14) were significantly (p < .001) lower than the control group (CTRL: 4.5 ± 0.13). Treatment groups decreased pro-inflammatory cytokines (IFN-γ, TNF-α, interleukin [IL]-17) (p < .001) as well as increased anti-inflammatory cytokine expression (IL-4, IL-10, IL-27, IL-33, IL-35, TGF-β) (p < .01) when compared to the CTRL group. Treatment groups with berberine reduced expression of the Th1 and Th17 cytokines and transcription factors (p < .001) and increased expression of transcription factors and Th2 and Treg cytokines (p < .01) in contrast to CTRL group.
CONCLUSION
Berberine appears to have a protective effect on disease development and alleviating disease status in EAE, which appears to be due to the cell expansion and function of Treg and Th2 cells in addition to berberine's anti-inflammatory properties.
Topics: Animals; Mice; Anti-Inflammatory Agents; Berberine; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Mice, Inbred C57BL; Multiple Sclerosis; Neuroinflammatory Diseases; T-Lymphocytes, Regulatory; Th2 Cells; Transcription Factors
PubMed: 36705421
DOI: 10.1002/iid3.766