Plant Alkaloid Research Articles

Synergy, Additive Effects, and Antagonism of Drugs with Plant Bioactive Compounds

Background/Objectives: The interaction of bioactive compounds derived from plants with drugs has become a significant area of investigation due to its potential to improve, reduce, or have no effect on therapeutic outcomes. Due to the dual effect of these interactions, elucidating the underlying mechanisms is essential for establishing a therapeutic strategy. This study emphasizes the significant findings, mechanisms, and clinical implications of drug–plant bioactive interactions. It calls for more studies to seek safe and effective incorporation into clinical practice. Methods: To identify relevant studies, we performed a systematic literature search based on various scientific databases from 11 August 2024 to 30 December 2024. The search will be based on relevant keywords such as synergy, antagonism, plant bioactive compounds, and drug interactions supplemented with secondary terms such as phytochemicals, herb-drug interactions, pharmacokinetics, and pharmacodynamics. Results: Plant bioactives, including polyphenols, flavonoids, alkaloids, and terpenoids, display valuable biological activities that can interact with medications in three principal ways: synergy, additive effects, and antagonism. Synergy occurs when the combined effects of plant chemicals and pharmaceuticals outweigh the sum of their separate effects, increasing therapeutic effectiveness or allowing dosage decrease to reduce adverse effects. Additive effects occur when the combined impact equals the total individual effects, resulting in better outcomes without increasing risk. Antagonism occurs when a plant ingredient reduces or counteracts the effects of a medicine, thereby jeopardizing treatment. In addition, specific interactions may have no discernible effect. The chemical makeup of bioactive chemicals, medication pharmacokinetics, and individual patient characteristics such as genetics and metabolism all impact the intricacy of these interactions. Conclusions: Pharmacokinetics and pharmacodynamics of drugs can be considerably modulated through their interactions with plant bioactive components, which may cause a significant decrease in efficacy or increase in toxicity of therapeutic agents. More studies are needed to clarify mechanisms of action, prove clinical relevance, and create guidelines for safe co-administration. This integrative approach can mitigate those risks and allow for therapeutic optimization by introducing pharmacogenomics and personalized medicine approaches.

Anti-inflammatory Alkaloids Targeting IL-1 against Respiratory Viral Infections: A Special Insight into Drug Development against SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the deadliest viruses among respiratory viruses which resulted in COVID-19 pandemic. The virus gets transmitted by the nasal route and moves down to the trachea, bronchi, and then to the lungs. Once replicated inside the alveolar cells, the SARS-CoV-2 makes the membrane of the alveolar sac porous, which causes the leaking of plasma from surrounding blood vessels into the alveolar sac leading to its buildup. This process results in the production of pro-inflammatory cytokines like interleukin-1β (IL-1β) and Tumor necrosis factor-α (TNF-α) by the helper T-cells at the site of the infection, causing difficulty in breathing. Plant-based alkaloids can be promising to treat viral infections. Plants have contributed to drug development against viruses like Herpes simplex virus (HSV), Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and viruses that cause respiratory diseases in humans. Plant alkaloids, either in the form of extract, infusion, or powder, have shown potential in treating viral diseases mainly by targeting the replication of viruses. Alkaloids like Tetrandrine, Oxymatrine, and Berberine have been shown to have a positive role in mediating pro-inflammatory cytokines like IL-1. These alkaloids thus inactivate the nuclear factor kappa-B (NF-kB) pathway, inhibiting the expression of its targeted genes, IL-1β and TNF-α. This inactivation of NF-kB results in reduced levels of IL-1 and TNF-α, and consequently reduced inflammation, decreasing the stress on the immune cells and increasing the ability of the patient to fight the infection. Despite vaccine development for SARS-CoV-2, the virus is continuously evolving into new varieties, posing a threat to humans and it is necessary to develop effective drug discovery programs. Natural products can pave the way in this regard. This review can contribute towards safer drug development against SARS-CoV-2, combating the threat of the ever-emerging variants of this virus.

Antifibrotic potential of reserpine (alkaloid) targeting Keap1/Nrf2; oxidative stress pathway in CCl4-induced liver fibrosis.

The death rate due to liver cancer approaches 2 million annually, the majority is attributed to fibrosis. Currently, there is no efficient, safe, non-toxic, and anti-fibrotic drug available, suggesting room for better drug discovery. The current study aims to evaluate the anti-fibrotic role of reserpine, an alkaloid plant compound against CCl4-induced liver fibrosis. In-silico docking analysis showed the interaction of reserpine with keap1 protein with the binding energy -9.0kcal/mol. In-vitro, biochemical analysis, anti-oxidative indexes, and inflammatory cytokines analysis were performed in HepG2 cells. The non-toxic nature of the compound (<100μg/ml) was evaluated through MTT assay in HepG2 and Vero cell lines. The antifibrotic potential of the reserpine compound (dose of 0.5mg/kg) was assessed in CCl4-administered C57BL/6J mice models. Hematoxylin & Eosin and Masson staining were performed to study the morphological changes of liver tissues. Immune histochemistry (IHC) analysis was performed to evaluate the effect of reserpine on the liver fibrosis marker. The biochemical assay indicated a significant decrease in ALT, AST, and MDA levels and increased catalase enzyme post-6-week reserpine treatment in mice models. Gene expression analysis revealed that the reserpine targets oxidative stress Keap1/Nrf2 pathway and down-regulated Keap1 expression by 5-fold and up-regulated Nrf2 and Nqo1 expression by 6 and 4.5-fold respectively showing its antioxidant response. It suppressed the expression of Cyp2e1 by 2.2-fold, illustrating the compound's ability to block lipid peroxidation. Histological and immunostaining exhibited improved hepatocyte morphology and reduced collagen deposition in liver tissues due to reserpine. Reserpine treatment lowered the fibrotic markers α-SMA and Col-1 by 1.3 and 1.5 folds respectively as compared to the control group and increased the expression of miR-200a and miR-29b by 15.5 and 8.2 folds (p<0.05) while decreased miR-128-1-5p expression by 5-fold. A comprehensive In-silico, In-vitro, and In-vivo analysis revealed that reserpine has a strong anti-fibrotic effect against the CCl4-induced liver fibrosis in C57BL/6J mice model by targeting the Keap1/Nrf2 pathway.

Seed bacterization with siderophore-producing bacteria: a strategy to enhance growth and alkaloid content in Catharanthus roseus.

Catharanthus roseus is a medicinal plant widely known for producing monoterpenoid indole alkaloids (MIAs), including therapeutic compounds such as vinblastine and vincristine, which are crucial for cancer treatment. However, the naturally low concentration of these alkaloids in plant tissues poses a significant challenge for large-scale production. This study explores the application of siderophore-producing bacteria for seed bacterization of Catharanthus roseus to enhance the production of MIAs, including vindoline, catharanthine, and vinblastine. Utilizing High-Performance Liquid Chromatography (HPLC), we observed a significant increase in the concentration of these alkaloids in bacterized plants compared to controls. FTIR spectra of treated plants showed strong correlations with standard alkaloid mixtures, confirming higher alkaloid accumulation. Our findings demonstrate that bacterial siderophores play a vital role in optimizing iron uptake, which is crucial for secondary metabolite biosynthesis. This research highlights the potential of using microbial biotechnology to improve the yield of valuable pharmaceutical compounds in medicinal plants. Enhancing the biosynthetic pathways of MIAs offers a sustainable and efficient strategy for boosting the production of key therapeutic alkaloids in Catharanthus roseus, paving the way for advanced biotechnological applications in plant-based drug production.

Antibiotic Resistance of Staphylococcus aureus Strains-Searching for New Antimicrobial Agents-Review.

Inappropriate and excessive use of antibiotics is responsible for the rapid development of antimicrobial resistance, which is associated with increased patient morbidity and mortality. There is an urgent need to explore new antibiotics or alternative antimicrobial agents. S. aureus a commensal microorganism but is also responsible for numerous infections. In addition to innate resistance to β-lactam antibiotics, S. aureus strains resistant to methicillin (MRSA) often show resistance to other classes of antibiotics (multidrug resistance). The advancement of phage therapy against MRSA infections offers a promising alternative in the context of increasing antibiotic resistance. Therapeutic phages are easier to obtain and cheaper to produce than antibiotics. However, there is still a lack of standards to ensure the safe use of phages, including purification, dosage, means of administration, and the quantity of phages used. Some bacteria have developed defense mechanisms against phages. The use of phage cocktails or the combination of antibiotics and phages is preferred. For personalized therapy, it is essential to set up large collections to enable phage selection. In the future, the fight against MRSA strains using phages should be based on a multidisciplinary approach, including molecular biology and medicine. Other therapies in the fight against MRSA strains include the use of endolysin antimicrobial peptides (including defensins and cathelicidins). Researchers' activities also focus on the potential use of plant extracts, honey, propolis, alkaloids, and essential oils. To date, no vaccine has been approved against S. aureus strains.

The bitter truth: how insects cope with toxic plant alkaloids.

Plants are unique organisms that have developed ingenious strategies to cope with environmental challenges, such as herbivorous insects. One of these strategies is the synthesis of a vast array of chemical compounds, known as specialized metabolites, that serve many ecological functions. Among the most fascinating and diverse groups of specialized metabolites are the alkaloids, which are characterized by the presence of a nitrogen atom within a heterocyclic ring. While some have medicinal and recreational applications, others are highly unpalatable and/or toxic. The effects of alkaloids on both humans and insects can be very diverse, affecting their physiology and behavior. Insects that feed on alkaloid-containing plants have evolved various mechanisms to cope with the consequences of these toxins. These include sequestration, where insects store alkaloids in specialized tissues or organs, enzymatic detoxification through enzymes such as cytochrome P450 monooxygenases and glutathione S-transferases, and behavioral adaptations such as selective feeding. In this review, we explore the relationships between plant alkaloids and the evolutionary adaptations that enable insects to exploit alkaloid-rich plants as food sources and ecological niches minimizing the harmful effects of these natural compounds. We aim to provide a comprehensive and updated overview of this fascinating and complex ecological interaction.

Hematological Changes Provoked by Natural Alkaloids

Background and aims: Plant alkaloids are naturally occurring nitrogen-containing chemicals with a wide range of therapeutic applications. They have been reported to cure a considerable number of illnesses, including cancer, diabetes, malaria, and heart dysfunction. This study sought to evaluate the impact of several plant alkaloids on hematological parameters in animals. Methods: The results of different plant extracts containing alkaloids in laboratory animals on hematological indices such as red blood cell (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct), white blood cell count, platelet count, and others using normal laboratory methods were gathered from scientific papers and databases using keywords such as plant alkaloids, alkaloid toxicity, hematological parameters, hematological changes, blood, and animals. Results: Plant alkaloids identified through the search had different impacts on hematological indices. Some alkaloids raised RBC count, Hb concentration, and Hct, while others lowered these values. Platelet count was generally observed to increase, but there were exceptions. Certain alkaloids found in some plants have no substantial influence on hematological parameters. Conclusion: Plant alkaloids can cause various changes in hematological parameters in animals. These alterations might be useful or deleterious depending on the alkaloid and its concentration. Understanding these effects is essential for the safe and effective use of plant-based therapies.

Advancements in MRSA treatment: the role of berberine in enhancing antibiotic therapy

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a significant public health problem. This study investigated the antimicrobial properties and mechanisms of berberine (BBR), a plant alkaloid, against MRSA, evaluating its potential to enhance antibiotic therapy.ResultsBerberine only demonstrated variable but significant inhibitory effects on 50 clinical MRSA strains. When combined with antibiotics, synergistic effects were observed only with amikacin in 6 of the 50 MRSA strains. BBR disrupted MRSA cell wall integrity, leading to leakage of cellular contents. Network pharmacology analysis revealed that BBR targets multiple pathways essential for bacterial survival.ConclusionThe study confirmed the potent antimicrobial activity of berberine against MRSA and its capability to act synergistically with traditional antibiotics. Berberine’s impact on cell wall integrity and bacterial survival pathways highlights its potential as an adjunct therapy in MRSA treatment.

A Validated Trigonelline-Based Method for the Standardization and Quality Control of Trigonella foenum-graecum L.

Background Fenugreek, or Trigonella foenum-graecum L, is an edible and medicinal plant of the Fabaceae family. Fenugreek seeds are rich in proteins, lipids, and essential nutrients, and they also contain various phytochemicals, including flavonoids, steroidal saponins, coumarin, and alkaloids such as trigonelline. Trigonelline (TG) is a bioactive plant alkaloid initially extracted from fenugreek seeds. A substantial portion of fenugreek’s health benefits may rely on the presence of TG. This study addresses the critical need for a fast, green, and economical method that overcomes inefficiencies, high solvent usage, and sensitivity limitations in the quantification of TG. Methods Fenugreek seeds from various origins were extracted using three green solvents: acetone (ACt), ethanol (EtOH), and water (H2O). The UPLC-MS/MS method was developed and validated using a green mobile phase of H2O: EtOH, and an r2-value of 0.999 in the linearity range of 0.1-500 ppb was adopted. The method was validated with an accuracy of 98.6% for trace analysis of TG using a small amount (10 mg) of fenugreek samples from five different origins. Results The average extract yield was 5.36 mg/100 mg with a standard deviation (SD) of 6.3, with the highest extract yield observed in H2O. The ESI (+ve) of the UPLC-MS/MS resulted in the fragmentation pattern (m/z) 138→94.10→92.05→78.20. The TG quantification revealed an average TG concentration of 181.4 ppb (SD = 176.4), with the highest amount of TG in H2O extract (mean = 392.7, SD = 132.4 ppb), followed by EtOH (mean = 91.9, SD = 83.3 ppb) and ACt (mean = 59.5, SD = 30.9 ppb). The TG amount observed in the validation step substantiated the efficiency and reproducibility of the developed method. Conclusions The method may be used as an effective tool for a green, rapid, economical, and eco-friendly extraction and quantification of TG in diverse matrices of pharmaceutical, cosmeceutical, herbal, and food products.

Combination of Probe Electrospray Ionization Mass Spectrometry and Mass Spectrometry Imaging to Analyze Plant Alkaloids in Narcissus tazetta

Plant alkaloids are used in a variety of medicines, such as anti-cancer drugs and analgesics. Among these plant alkaloids, galanthamine is an Amaryllidaceae type alkaloid with acetylcholinesterase inhibition activity used in the treatment of neurological diseases such as Alzheimer's disease. Although the chemical synthesis of galanthamine has been successfully achieved, Narcissus tazetta is the main source of its production. Research shows that the galanthamine content varies not only with the type of daffodil but also with the stage of development and the part of the plant. Pharmaceutical companies seek plant species with higher galanthamine content to increase pharmaceutical availability. In this study, we were able to rapidly confirm the presence of alkaloids, such as galanthamine, lycorine, and tazettine in the N. tazetta sample using the probe electrospray ionization coupled with quadrupole time-of-flight type mass spectrometry. After confirmation of the components, we then visualized the distribution of the alkaloids by mass spectrometry imaging using the atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometer. In our method, we can provide qualitative data and visualized data immediately.

A Validated Trigonelline-Based Method for the Standardization and Quality Control of Trigonella foenum-graecum L.

Background Fenugreek, or Trigonella foenum-graecum L, is an edible and medicinal plant of the Fabaceae family. Fenugreek seeds are rich in proteins, lipids, and essential nutrients, and they also contain various phytochemicals, including flavonoids, steroidal saponins, coumarin, and alkaloids such as trigonelline. Trigonelline (TG) is a bioactive plant alkaloid initially extracted from fenugreek seeds. A substantial portion of fenugreek’s health benefits may rely on the presence of TG. This study addresses the critical need for a fast, green, and economical method that overcomes inefficiencies, high solvent usage, and sensitivity limitations in the quantification of TG. Methods Fenugreek seeds from various origins were extracted using three green solvents: acetone (ACt), ethanol (EtOH), and water (H2O). The UPLC-MS/MS method was developed and validated using a green mobile phase of H2O: EtOH, and an r2-value of 0.999 in the linearity range of 0.1-500 ppb was adopted. The method was validated with an accuracy of 98.6% for trace analysis of TG using a small amount (10 mg) of fenugreek samples from five different origins. Results The average extract yield was 5.36 mg/100 mg with a standard deviation (SD) of 6.3, with the highest extract yield observed in H2O. The ESI (+ve) of the UPLC-MS/MS resulted in the fragmentation pattern (m/z) 138→94.10→92.05→78.20. The TG quantification revealed an average TG concentration of 181.4 ppb (SD = 176.4), with the highest amount of TG in H2O extract (mean = 392.7, SD = 132.4 ppb), followed by EtOH (mean = 91.9, SD = 83.3 ppb) and ACt (mean = 59.5, SD = 30.9 ppb). The TG amount observed in the validation step substantiated the efficiency and reproducibility of the developed method. Conclusions The method may be used as an effective tool for a green, rapid, economical, and eco-friendly extraction and quantification of TG in diverse matrices of pharmaceutical, cosmeceutical, herbal, and food products.

Feed-induced hypersalivation in horses from Austria, Germany and Switzerland.

While previous reports come mostly from the southern Americas, several outbreaks of hypersalivation in horses were observed in Middle Europe from 2016 to 2018. To describe feed-induced hypersalivation in European horses. Analysis of feedstuffs. Veterinarians and horse or stable owners were encouraged to submit feedstuffs from case outbreaks of hypersalivation in which, infectious diseases or other systemic causes of the syndrome were ruled out and intoxication was suspected. Feedstuff analysis was performed, including gross examination, microscopic analysis of fine particles, and for hay and forage mycological culturing and mycotoxin testing. Eleven case outbreaks were investigated. Typical clinical findings in the horses were either foamy saliva around the mouth or serous salivation with puddles forming on the ground. Some horses also showed lesions of the gingival mucosa and/or the tongue. Foamy hypersalivation, sometimes combined with lesions of tongue and/or gingiva, was associated with finding of ergot sclerotia and ergot alkaloids in hay or pasture plants (ergocornin and ergocorninin having the highest concentrations). Serous hypersalivation with massive loss of fluid was associated with the fungus Rhizoctonia spp. As indicated by the detection of traces of swainsonine, mycotoxin production on the forage was seen as likely cause. The cessation of clinical signs took days to weeks after diet change, probably depending on the duration, type and amount of toxin intake. Small number of case outbreaks, records of clinical findings and horses' management were incomplete and were reported by horse owners. Hypersalivation due to mycotoxins in the feed has become an emerging problem for horses in middle Europe.

Abstract 4138546: From Nature’s Remedy to Cardiac Emergency: A Case of Takotsubo Cardiomyopathy Induced by High-Dose Berberine Supplementation

Introduction: Takotsubo cardiomyopathy (TCM) is a reversible cardiac condition often precipitated by emotional or physical stress. Certain medications have also been implicated. While prognosis is generally favorable, associated QTc prolongation and ventricular arrhythmias can be life threatening, necessitating identification of potential triggers. This report highlights TCM in a patient using high-dose berberine, a plant alkaloid known for its hypoglycemic properties. Case description: A 69-year-old female with a history of type 2 diabetes mellitus, and hyperlipidemia presented after a syncopal event. It was preceded by sudden onset of dizziness, nausea, and vomiting. She had been using berberine for a year to lower her blood sugar and had recently switched to a higher dose of a more potent formulation. Vitals were unremarkable. Initial evaluation revealed a prolonged QTc interval of 659 ms (Figure 1A) and elevated troponin-I levels. She was treated with intravenous magnesium, which improved her QTc to 540 ms and revealed new T-wave inversions in the precordial leads. Echocardiogram showed an ejection fraction (EF) of 35%, with LV apical akinesia and hypercontractile basal segments. Cardiac catheterization ruled out significant coronary artery disease, leading to a diagnosis of TCM. Berberine was discontinued, and guideline-directed medical therapy was initiated. Given the presentation with syncope and high suspicion of aborted sudden cardiac death (SCD), she was discharged with a wearable cardioverter-defibrillator (WCD) as a precaution due to the risk of ventricular arrhythmias during recovery. At her 8-week follow-up, QTc and EF had normalized (Figure 1B), prompting WCD removal. Conclusion: The pathophysiology of berberine-induced cardiomyopathy remains uncertain and requires further research. This case underscores the importance of recognizing the potential cardiotoxic effects of berberine, particularly when used in high doses. A thorough medication and supplement history is crucial in patients presenting with unexplained cardiac symptoms. The reversible nature of TCM, when promptly recognized and treated, highlights the need for comprehensive follow-up to ensure recovery of cardiac function.

A Validated Trigonelline-Based Method for the Standardization and Quality Control of Trigonella foenum-graecum L.

Background Fenugreek, or Trigonella foenum-graecum L, is an edible and medicinal plant of the Fabaceae family. Fenugreek seeds contain a variety of phytochemicals, including proteins, lipids, amino acids, vitamins, flavonoids, steroidal saponins, coumarin, and alkaloids. Trigonelline TG is a bioactive plant alkaloid initially extracted from fenugreek seeds. A substantial portion of fenugreek’s health benefits may rely on the presence of TG. This study addresses the research gap for a fast, green, and economical method for quantifying trigonelline (TG) in fenugreek. Methods Fenugreek seeds from various origins were extracted using three green solvents: acetone (ACt), ethanol (EtOH), and water (H2O). The UPLCMSMS method was developed and validated using a green mobile phase of H2O: EtOH, and an r2-value of 0.999 in the linearity range of 0.1-500 ppb was adopted. The method was validated with an accuracy of 98.6% for trace analysis of TG using a small amount (10 mg) of fenugreek samples from five different origins. Results The average extract yield (±SD) was 5.36±6.3, with the highest extract yield observed in H2O. The ESI (+ve) of the UPLCMSMS resulted in the fragmentation pattern (m/z) 138→94.10→92.05→78.20. The TG quantification revealed an average TG concentration of 181.4, with the highest amount of TG in H2O extract (392.7±132.4 ppb), followed by EtOH (91.9±83.3 ppb) and ACt (59.5±30.9 ppb). The TG amount observed in the validation step substantiated the efficiency and reproducibility of the developed method. Conclusions The method may be used as an effective tool for a green, rapid, economical, and eco-friendly extraction and quantification of TG in diverse matrices of pharmaceutical, cosmeceutical, herbal, and food products.

Homoharringtonine in the treatment of acute myeloid leukemia: A review.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by the accumulation of immature myeloid precursor cells. Over half of AML patients fail to achieve long-term disease-free survival under existing therapy, and the overall prognosis is poor, necessitating the urgent development of novel therapeutic approaches. The plant alkaloid homoharringtonine (HHT), which has anticancer properties, was first identified more than 40 years ago. It works in a novel method of action that prevents the early elongation phase of protein synthesis. HHT has been widely utilized in the treatment of AML, with strong therapeutic effects, few toxic side effects, and the ability to enhance AML patients' prognoses. In AML, HHT can induce cell apoptosis through multiple pathways, exerting synergistic antitumor effects, according to clinical and pharmacological research. About its modes of action, some findings have been made recently. This paper reviews the development of research on the mechanisms of HHT in treating AML to offer insights for further research and clinical therapy.

Endophytic bacteria in Camellia reticulata pedicels: isolation, screening and analysis of antagonistic activity against nectar yeasts.

Camellia reticulata, an ancient plant species endemic to Yunnan Province, China, remains underexplored in terms of its endophytic bacterial communities. The plant tissue pedicel serves as the connection between the flower and the stem, not only delivers nutrients but also transmits metabolic substances from endophytic bacteria to the nectar during long-term microbial colonization and probably improves the antagonistic activity of nectar against yeast. Hence, 138 isolates of endophytic bacteria have been isolated in this study from the pedicels of 12- and 60-year-old C. reticulata. Comparative analysis revealed significantly higher density of endophytic bacteria in older trees. Among these isolates, 29 exhibited inhibitory effects against nectar yeasts. Most of the isolates displayed positive results for Gram staining, catalase reaction, gelatin liquefaction, and motility. Additionally, the isolates demonstrated the ability to utilize diverse substrates, such as glucose, nitrate, and starch. Based on 16S rRNA molecular biology analysis, these isolates were identified to be 11 different species of 6 genera, with the majority belonging to Bacillus genus. Notably, C1 isolate, identified as Bacillus spizizenii, exhibited strongest antagonistic effect against three yeasts, i.e., Metschnikowia reukaufii, Cryptococcus laurentii, and Rhodotorula glutinis, with minimum inhibitory concentration values below 250 μg/mL. Major metabolites of B. spizizenii were aminoglycosides, beta-lactams, and quinolones, which possess antimicrobial activities. Furthermore, KEGG enrichment pathways primarily included the synthesis of plant secondary metabolites, phenylpropanoids, amino acids, alkaloids, flavonoids, neomycin, kanamycin, and gentamicin. Therefore, antagonistic activity of B. spizizenii against yeasts could be attributed to these antibiotics. The findings highlight the diverse endophytic bacteria associated with C. reticulata, indicating their potential as a valuable resource of bioactive metabolites. Additionally, this study provides new insights into the role of endophytic bacteria of pedicels in enhancing nectar resistance against yeasts.

Comparison of genotoxic impurities in extracted nicotine vs. synthetic nicotine.

Nicotine is a chiral alkaloid; nitrogen-containing organic compound that occurs naturally. (S)-nicotine is extracted from Tobacco plants and used as the key addictive ingredient in many smoking products. Synthetic nicotine has gained the interest of many smoking product manufacturers over the last few decades due to the ease and low cost of manufacturing. Another claimed advantage of synthetic nicotine is the absence of genotoxic impurities that form during the extraction process of nicotine. These impurities are other plant alkaloids, phenolic compounds, and heavy metals. Additionally, the U. S. FDA has implemented new regulations on the quality control of synthetic nicotine. However, only a very few research articles have been published on assessing the complete impurity profile of synthetic nicotine. Therefore, the need to know the composition difference between tobacco-extracted nicotine vs. synthetic nicotine is highly necessary. In this research study, the impurity profile of thirteen different lots of synthetic nicotine was compared with fourteen lots of nicotine extracted from plants using in-house analytical methods. First, the samples were tested for other alkaloids and phenols by reversed-phase High-Performance Liquid Chromatography (HPLC). Second, the chiral purity was analyzed by normal phase HPLC. Third, lead and arsenic content were tested by atomic absorption and fluorescence spectrometry. Fourth, nicotine-specific nitrosamines were tested by LC-MS. The reversed phase HPLC data suggested similar quantities of total impurities in both synthetic and tobacco-extracted nicotine (0.1%). However, synthetic nicotine lacks some impurities such as cotinine, nornicotine, and nicotine-N-oxide. Additionally, the synthetic nicotine lots used in this study have high enantiomeric purity similar to the tobacco-extracted nicotine.

Berberine and palmatine, acting as allosteric potential ligands of α7 nAChR, synergistically regulate inflammation and phagocytosis of microglial cells.

Berberine and palmatine are isoquinoline quaternary alkaloids derived from Chinese medicinal herbs. These alkaloids have shown promising synergy in inhibiting acetylcholinesterase (AChE), indicating their potential in treating Alzheimer's disease (AD). Besides, the anti-inflammatory effects of berberine and palmatine have been widely reported, although the underlying mechanism remains unclear. Here, we found that berberine and palmatine could induce calcium ion (Ca2+) influx via activating α7 nicotinic acetylcholine receptor (α7 nAChR) in cultured microglial cells, possibly serving as its allosteric potential ligands. Furthermore, we examined the synergistic anti-inflammatory effects of berberine and palmatine in the LPS-induced microglia, that significantly suppressed the production of TNF-α and iNOS. Notably, this suppression was reversed by co-treatment with a selective antagonist of α7 nAChR. Moreover, the alkaloid-induced microglial phagocytosis was shown to be mediated by the induction of Ca2+ influx through α7 nAChR and subsequent CaMKII-Rac1-dependent pathway. Additionally, the combination of berberine and palmatine, at low concentration, protected against the LPS-induced endoplasmic reticulum stress and mitochondrial dysfunction in microglia. These findings indicate the potential of berberine and palmatine, either individually or in combination, in contributing to anti-AD drug development, which provide valuable insights into the mechanisms by which natural products, such as plant alkaloids, exert their anti-AD effects.

Nanocarrier-Assisted Delivery of Berberine Promotes Diabetic Alveolar Bone Regeneration by Scavenging ROS and Improving Mitochondrial Dysfunction.

Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects. Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis. Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats. Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.

Cancer Pathways Targeted by Berberine: Role of microRNAs.

Cancer is a complex and heterogeneous malignant disease. Due to its multifactorial nature, including progressive changes in genetic, epigenetic, transcript, and protein levels, conventional therapeutics fail to save cancer patients. Evidence indicates that dysregulation of microRNA (miRNA) expression plays a crucial role in tumorigenesis, metastasis, cell proliferation, differentiation, metabolism, and signaling pathways. Moreover, miRNAs can be used as diagnostic and prognostic markers and therapeutic targets in cancer. Berberine, a naturally occurring plant alkaloid, has a wide spectrum of biological activities in different types of cancers. Inhibition of cell proliferation, metastasis, migration, invasion, and angiogenesis, as well as induction of cell cycle arrest and apoptosis in cancer cells, is reported by berberine. Recent studies suggested that berberine regulates many oncogenic and tumor suppressor miRNAs implicated in different phases of cancer. This review discussed how berberine inhibits cancer growth and propagation and regulates miRNAs in cancer cells. And how berberine-mediated miRNA regulation changes the landscape of transcripts and proteins that promote or suppress cancer progression. Overall, the underlying molecular pathways altered by berberine and miRNA influencing the tumor pathophysiology will enhance our understanding to combat the malignancy.