Comprehensive in vitro and in vivo evaluation of therapeutic potential of Bacopa-derived asiatic acid against a human oral pathogen Streptococcus mutans.

Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, this study aimed to demonstrate, for the first time, the antibacterial activity of phytocompound ASTA against S. mutans. The findings revealed that ASTA significantly inhibited the growth of S. mutans and the production of virulence factors such as acidurity, acidogenicity, and eDNA synthesis. Molecular docking analysis evaluated the potential activity of ASTA against S. mutans virulence genes, including VicR and GtfC. Furthermore, toxicity assessment of ASTA in human buccal epithelial cells was performed, and no morphological changes were observed. An in vivo analysis using Danio rerio (zebrafish) confirmed that the ASTA treatment significantly increased the survival rates of infected fish by hindering the intestinal colonization of S. mutans. Furthermore, the disease protection potential of ASTA against the pathognomonic symptom of S. mutans infection was proven by the histopathological examination of the gills, gut, and kidney. Overall, these findings suggest that ASTA may be a promising therapeutic and alternative drug for the treatment and prevention of oral infection imposed by S. mutans.

Modulatory potential of Bacopa monnieri against aflatoxin B1 induced biochemical, molecular and histological alterations in rats.

Oxidative injury is concerned with the pathogenesis of several liver injuries, including those from acute liver failure to cirrhosis. This study was designed to explore the antioxidant activity of Bacopa monnieri (BM) on Aflatoxin B1 (AFB1) induced oxidative damage in Wistar albino rats. Aflatoxin B1 treatment (200 µg/kg/day, p.o.) for 28 days induced oxidative injury by a significant alteration in serum liver function test marker enzymes (AST, ALT, ALP, LDH, albumin and bilirubin), inflammatory cytokines (IL-6, IL-10 and TNF-α), thiobarbituric acid reactive substances (TBARS) along with reduction of antioxidant enzymes (GSH, SOD, CAT), GSH cycle enzymes and drug-metabolizing enzymes (AH and AND). Treatment of rats with B. monnieri (20, 30 and 40 mg/kg for 5 days, p.o.) after 28 days of AFB1 intoxication significantly restored these parameters near control in a dose-dependent way. Histopathological examination disclosed extensive hepatic injuries, characterized by cellular necrosis, infiltration, congestion and sinusoidal dilatation in the AFB1-treated group. Treatment with B. monnieri significantly reduced these toxic effects resulting from AFB1. B. monnieriper se group (40 mg/kg) did not show any significant change and proved safe. The cytotoxic activity of B. monnieri was also evaluated on HepG2 cells and showed a good percentage of cytotoxic activity. This finding suggests that B. monnieri protects the liver against oxidative damage caused by AFB1, which aids in the evaluation of the traditional usage of this medicinal plant.

Investigating the Neuroprotective and Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

Investigating Bacopa monnieri L. Therapeutic Potential for the Treatment of Neurological Diseases.

The popular perennial creeping plant known as Bacopa monnieri (also known as Brahmi) is being utilized in the Indian Ayurvedic medicine practice. It has a variety of bioactive phytoconstituents that have been used therapeutically to treat a number of serious illnesses. Ancient Vedic scholars used this herb because of its pharmacological effects, particularly as a nerve booster and nootropic supporter. However, it is vital to comprehend the active phytochemical components of Bacopa monnieri extract (BME) and their molecular mechanisms in order to better grasp the effect of BME on neurological illnesses and diseases. Understanding its active phytochemical constituents and their molecular processes is essential. Numerous clinical investigations indicated that BME may have neuroprotective benefits, so it is worthwhile to re-evaluate this wellknown plant. Here, we focused on neurological problems as we examined the pharmacological and phytochemical characteristics of BME. For their effective usage in neuroprotection and cognition, many clinical concerns and the synergistic potential of Bacopa extract have been investigated. Alzheimer's disease is a neurological condition caused by the production of reactive oxygen species, which also causes amyloid-beta (Aß) and tau protein aggregation and increases neuro-inflammation and neurotoxicity. Our review offers a more indepth molecular understanding of the neuroprotective functions of BME, which can also be connected to its therapeutic management of neurological illnesses and cognitive-improving effects.

Evaluating the effects of Bacopa monnieri on cognitive performance and sleep quality of patients with mild cognitive impairment: A triple-blinded, randomized, placebo-controlled trial.

INTRODUCTION: Mild cognitive impairment is the middle level of natural cognitive impairment during primary steps of dementia. There are a few studies about improving the cognitive performance and sleep quality in patients with a limited dementia. So, this study was conducted to evaluate the effects of Bacopa monnieri on cognitive performance and sleep quality of patients with mild cognitive impairment. MATERIALS AND METHODS: In this study, 62 patients with mild cognitive impairment were categorized into two groups of control and intervention. The intervention group received one pill of 160 mg Bacopa monnieri extract in 2 months, and the control group received a pill containing starch powder. The cognitive impairment and sleep quality was assessed using a questionnaire containing demographic information, Montreal Cognitive Assessment, and the Pittsburg Sleep Quality Index in three time-points of before the study, one months after the intervention and 2 months after the intervention (the end of study). RESULTS: The results showed no statistically significant difference between two groups in all three time-points in overall cognitive performance score and its 6 parameters (P > 0.05). While in the field of attention at the end of the first month (P = 0.033) and the end of the second month (P = 0.004), it was significant difference between the study groups. Also, in the field of verbal fluency at the end of the second month, this difference was significant (P = 0.003). The cognitive performance overall score showed no significant difference between two groups in first (P = 0.939) and second time-points (P = 0.661), although it was significant at third time-point (P = 0.029). There was no statistically significant difference between two groups in all time-points for sleep quality overall score (P > 0.05). CONCLUSION: The results showed that Bacopa monnieri can improve the cognitive performance overall score and some of its parameters, but it had no effect on sleep quality.

Exploring the excellence of commercial Brahmi products from Thai online markets: Unraveling phytochemical contents, antioxidant properties and DNA damage protection.

Brahmi (Bacopa monnieri (L.) Wettst.) is extensively used as a nutritional supplement in various commercial products as the plant contains abundant phytochemicals and has antioxidant properties. This study assessed the phytochemical contents, antioxidant properties, and DNA damage protection among seven Brahmi products sold through Thai online markets. Results showed that the P6 sample exhibited 3.5-7.5 fold higher bacoside contents than values observed in the other six product samples. The P6 sample also demonstrated the highest TTC, TFC, and TPC compared to the other brands. For antioxidant activity, the samples (P1-P7) displayed high capacity to scavenge DPPH free radicals with slightly significant differences ranging from 78.37 ± 0.25 to 87.21 ± 0.05 at p-value ≤0.01. The P6 sample showed strong protection against H2O2-induced oxidation of DNA strand breakage, indicating highly potent phytochemical compounds with effective free radical scavenging activity, and the ability to prevent DNA damage. The P6 sample showed promise as a valuable ingredient for the development of functional food products. However, further in vivo animal and clinical studies are required to explore the neuroprotective enhancement effects of Brahmi extracts.

Analyzing the Antihyperglycemic Effect of Cissus quadrangularis and Bacopa monnieri on 3T3-L1 Cell Lines.

Background Cissus quadrangularis is a perennial shrub of the grape family. Other names for it include devil's backbone, veld grape, and pirandai (Tamil). Bacopa monnieri, a perennial plant, is native to wetlands in eastern and southern India. The 3T3-L1 cell line, which was created from 3T3 cells, was used in the scientific study. The current study's purpose is to evaluate the antihyperglycemic benefits of B. monnieri and C. quadrangularis, which will be added to the current arsenal of efficient herbal hypoglycemic medications. Aim To analyze and compare the anti-hyperglycaemic effects of the two plant extracts, C. quadrangularis and B. monnieri using a 3T3-L1 cell line. Materials and methods C. quadrangularis seeds were gathered, and extraction was conducted. The B. monnieri plant was harvested, and a rotary evaporator was used to extract the flower. Adipocyte cells were obtained from NCCS, Pune. A CO2 incubator was used to incubate the cells. The MTT assay and gene expression analysis were done on the cell line samples. Results The antihyperglycemic effects of C. quadrangularis IRS mRNA levels of 0.7 and AKT mRNA levels of 0.7 are compared to B. monnieri IRS1 mRNA levels of 0.6 and AKT mRNA levels of 0.6 to build better diabetic treatments. The antihyperglycemic benefits of C. quadrangularis levels of IRS mRNA and AKT mRNA are compared to the influence of B. monnieri IRS1 mRNA and AKT mRNA on the development of better diabetic drugs. Conclusion Comparing the effects of C. quadrangularis and B. monnieri on the 3T3 cell line by gene expression of IRS mRNA and AKT mRNA suggests that the particular AKT downregulation shows that insulin suppresses gluconeogenesis and C. quadrangularis inhibits hyperglycemia in 3T3-L1 cells, while research on in vitro rats suggests that B. monnieri may minimize the signs and symptoms of diabetes via enhancing IRS1/AKT signaling.

Anticancer activity of Bacopa monnieri through apoptosis induction and mitophagy-dependent NLRP3 inflammasome inhibition in oral squamous cell carcinoma.

BACKGROUND: Bacopa monnieri (BM) is traditionally used in human diseases for its antioxidant, anti-inflammatory and neuroprotective effects. However, its anticancer potential has been poorly understood. AIM: The aim of this study was to explore the detailed anticancer mechanism of BM against oral cancer and to identify the bioactive BM fraction for possible cancer therapeutics. RESULTS: We performed bioactivity-guided fractionation and identified that the aqueous fraction of the ethanolic extract of BM (BM-AF) had a potent anticancer potential in both in vitro and in vivo oral cancer models. BM-AF inhibited cell viability, colony formation, cell migration and induced apoptotic cell death in Cal33 and FaDu cells. BM-AF at low doses promoted mitophagy and BM-AF mediated mitophagy was PARKIN dependent. In addition, BM-AF inhibited arecoline induced reactive oxygen species production in Cal33 cells. Moreover, BM-AF supressed arecoline-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation through mitophagy in Cal33 cells. The in vivo antitumor effect of BM-AF was further validated in C57BL/6J mice through a 4-nitroquinolin-1-oxide and arecoline-induced oral cancer model. The tumor incidence was significantly reduced in the BM-AF treated group. Further, data obtained from western blot and immunohistochemistry analysis showed increased expression of apoptotic markers and decreased expression of inflammasome markers in the tongue tissue obtained from BM-AF treated mice in comparison with the non-treated tumor bearing mice. CONCLUSION: In conclusion, BM-AF exhibited potent anticancer activity through apoptosis induction and mitophagy-dependent inhibition of NLRP3 inflammasome activation in both in vitro and in vivo oral cancer models. Moreover, we have investigated apoptosis and mitophagy-inducing compounds from this plant extract having anticancer activity against oral cancer cells.

Amelioration of Amyloid-ß Induced Alzheimer's Disease by Bacopa monnieri through Modulation of Mitochondrial Dysfunction and GSK-3ß/Wnt/ß-Catenin Signaling.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent dementia, affecting a large number of populations. Despite being under scrutiny for decades, an effective therapeutic option is still not available. METHODS AND RESULTS: This study explores the therapeutic role of a nootropic herb Bacopa monnieri (BM) in AD-like pathological conditions produced by injecting preformed amyloid-ß42 (Aß42 ) fibril bilaterally into hippocampus of Wistar rats, and ethanolic extract of BM is orally administered for 4 weeks. Assessment of behavioral changes reveals that BM treatment ameliorates Aß42 -induced cognitive impairment and compromised explorative behavior. Supplementation of BM also reduces oxidative stress biomarkers, proinflammatory cytokines, and cholinesterase activity in the AD rats. Additionally, BM treatment restores Bcl-2-associated X protein (Bax)/ B-cell lymphoma 2 (Bcl-2) imbalance, increases neurotrophic factors expression, and prevents neurodegeneration validated by quantifying Nissl-positive hippocampal neurons. Interestingly, BM administration eliminates amyloid plaques in the hippocampal region and normalizes the Aß42 -induced increase in phospho-tau and total tau expression. Mechanistic investigations reveal that BM interacts with glycogen synthase kinase (GSK-3ß) and restores Wnt/ß-catenin signaling. CONCLUSION: BM has been used in diet as a nootropic herb for several centuries. This study highlights the anti-Alzheimer activity of BM from the behavioral to the molecular level by modulating mitochondrial dysfunction, and GSK-3ß mediates the Wnt/ß-catenin signaling pathway.

Bacopa monnieri: A promising herbal approach for neurodegenerative disease treatment supported by in silico and in vitro research.

Neurodegenerative disorders, caused by progressive neuron loss, are a global health issue. Among the various factors implicated in their pathogenesis, dysregulation of acetylcholinesterase activity has been recognized as a key contributor. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, important for neural transmission. Evaluating phyto-compounds from Bacopa monnieri Linn. through in vitro and in silico analysis may expand their role as alternative therapeutic agents by modulating the function of acetylcholinesterase and complementing existing treatments. To accomplish this objective, chemical structures of phyto-compounds were retrieved from PubChem database and subjected to in silico and in vitro approaches. Virtual screening was performed through molecular docking and molecular dynamic simulation resulting in four top hit compounds including quercetin, apigenin, wogonin, and bacopaside X (novel lead compound for acetylcholinesterase inhibitor) with least binding score. Further, dose dependent acetylcholinesterase inhibition biochemical assay depicted that bacopaside X, apigenin, quercetin, and wogonin exhibited strong potential against acetylcholinesterase with IC50 values of 12.78 µM, 13.83 µM, 12.73 µM and 15.48 µM respectively, in comparison with the donepezil (IC50: 0.0204 µM). The in silico and in vitro research suggests that B. monnieri phyto-compounds have the potential to modulate molecular targets associated with neurodegenerative diseases and have a role in neuroprotection.

Protection by Nano-Encapsulated Bacoside A and Bacopaside I in Seizure Alleviation and Improvement in Sleep- In Vitro and In Vivo Evidences.

Therapeutic options to contain seizures, a transitional stage of many neuropathologies, are limited due to the blood-brain barrier (BBB). Herbal nanoparticle formulations can be employed to enhance seizure prognosis. Bacoside A (BM3) and bacopaside I (BM4) were isolated from Bacopa monnieri and synthesized as nanoparticles (BM3NP and BM4NP, respectively) for an effective delivery system to alleviate seizures and associated conditions. After physicochemical characterization, cell viability was assessed on mouse neuronal stem cells (mNSC) and neuroblastoma cells (N2a). Thereafter, anti-seizure effects, mitochondrial membrane potential (MMP), apoptosis, immunostaining and epileptic marker mRNA expression were determined in vitro. The seizure-induced changes in the cortical electroencephalogram (EEG), electromyography (EMG), Non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep were monitored in vivo in a kainic acid (KA)-induced rat seizure model. The sizes of BM3NPs and BM4NPs were 165.5 nm and 689.6 nm, respectively. They were biocompatible and also aided in neuroplasticity in mNSC. BM3NPs and BM4NPs depicted more than 50% cell viability in N2a cells, with IC50 values of 1609 and 2962 µg/mL, respectively. Similarly, these nanoparticles reduced the cytotoxicity of N2a cells upon KA treatment. Nanoparticles decreased the expression of epileptic markers like fractalkine, HMGB1, FOXO3a and pro-inflammatory cytokines (P < 0.05). They protected neurons from apoptosis and restored MMP. After administration of BM3NPs and BM4NPs, KA-treated rats attained a significant reduction in the epileptic spikes, sleep latency and an increase in NREM sleep duration. Results indicate the potential of BM3NPs and BM4NPs in neutralizing the KA-induced excitotoxic seizures in neurons.

Phenyl glycosides from Bacopa monnieri with their antioxidant and anti-inflammatory activities.

Bacopa monnieri (L.) Wettst (Plantaginaceae), is traditionally used in many countries as neural tonic and memory enhancer, or to relieve acute pain and inflammation. This study described the isolation and identification of one new, bacomoside D3 (1), and seven known phenyl glycosides (2 - 8). The structures of isolates were established by analysis of their spectroscopic data or hydrolysis followed by HPLC analysis together with a comparison to those reported in the literature. These compounds were evaluated for antioxidant and anti-inflammatory activities. Among them, compounds 4 and 5 exhibited strong DPPH radical scavenging activity with IC50 values of 9.77 ± 0.08 and 3.50 ± 0.04 µM, respectively. Compounds 2 and 5 significantly inhibited TNF-α production in LPS-stimulated RAW264.7 cells with IC50 values of 40.60 ± 3.05 and 38.19 ± 1.75 µM, respectively. Furthermore, the active compounds could be efficient inhibitors of oxidants by interfering with the DPPH activity in silico study.

Maternal stress-induced changes in adolescent and adult offspring: Neurobehavioural improvement and telomere maintenance.

Maternal stress (MS) during gestation is known to increase the risk for the development of behavioural and physiological disorders and advances cellular aging. In this study, we investigated whether the supplementation of standardized Bacopa monnieri extract (CDRI-08/BME) or l-Carnosine (L-C) to the mother exposed to social stress during gestation modify the effect on their offspring's neurobehaviour, antioxidant defence gene expression, telomere length, and telomere biology. To test this, timed pregnant rats were subjected to social stress during the gestational day (GD) 16-18. A subset of stressed pregnant rats received either BME [80 mg/kg in 0.5% gum acacia (per-orally; p.o)] or L-C [1 mg/kg (p.o)] every day from GD-10 to until their pup's attained postnatal day (PND)-23. We observed that MS induced anxiety-like behaviour, altered inter-limb coordination, antioxidant defence genes [Superoxide dismutase (SOD1,2), Catalase (CAT), Glutathione peroxidase-3 (GPX3)], telomerase reverse transcriptase (TERT), shelterin complex subunits (TRF1, RAP1B, POT1) protein level and shorten telomere length. Notably, supplementation of BME/L-C dampens the MS, thus the effect on neurobehaviour, antioxidant defence gene expression, and telomere biology is minimized in their offspring. Together, our results suggest that supplementation of BME/L-C during gestation dampens the MS and reduced oxidative stress-mediated changes in telomere shortening/biology and associated neurobehaviour in offspring born following MS.

Comprehensive analysis using DNA metabarcoding, SCAR marker based PCR assay, and HPLC unveils the adulteration in Brahmi herbal products.

BACKGROUND: Brahmi is one of the important nootropic botanicals, widely sold in the market, with the name "Brahmi'' being used to describe both Bacopa monnieri and Centella asiatica species. The Brahmi herbal products market is expanding; hence, economically motivated adulteration is highly prevalent. METHODS AND RESULTS: This study aimed to develop DNA-based methods, including SCAR marker-based PCR and metabarcoding, to authenticate Brahmi herbal products and compare these methods with HPLC. These methods have been validated using mock controls (in-house blended formulations). All targeted plant species in mock controls were detected successfully with all three methods, whereas, in market samples, only 22.2%, 55.6%, and 50.0% were found positive for Brahmi by PCR assay, DNA metabarcoding, and HPLC, respectively. Metabarcoding can detect the presence of non-labeled plants together with targeted species, which is an advantage over PCR assay or HPLC. CONCLUSION: SCAR marker-based PCR is a rapid and cost-effective method for detecting the presence of B. monnieri and C. asiatica. However, in this study, the success rate of PCR amplification was relatively low because the primers targeted either RAPD or ITS-based SCAR markers. HPLC assay, although an alternative, was unable to detect the presence of other botanicals, just like the SCAR marker-based PCR assay. On the other hand, metabarcoding can be utilized to identify the target plants, even in very small quantities, while also providing simulated identification of other botanicals. This study successfully addressed the need for quality control of Brahmi herbal products and provided the first-time report of DNA metabarcoding for such products.

Exploring the ameliorative potential of Bacopa monnieri in acetic acid induced ulcerative colitis in mice.

The aim of the present study was to evaluate the role of Bacopa monnieri in acetic-acid-induced ulcerative colitis in mice. Acetic acid (3%v/v, in 0.9% saline) was infused intrarectally to induce ulceration in mice. Administration of acetic acid resulted in severe inflammation of the colon along with an increase in the myeloperoxidase (MPO) activity assessed on 7th day. Treatment with Bacopa monnieri extract (20 mg/kg and 40 mg/kg, p.o) and saponin-rich fraction (5 mg/kg and 10 mg/kg; p.o) for 7 days i.e. 2 days before and 5 days after acetic acid infusion, significantly attenuated the colonic inflammation in a dose-dependent manner. Furthermore, it also reduced the MPO levels and the disease activity score as compared to the control group. It may be concluded that Bacopa monnieri has the potential for ameliorating acetic-acid-induced colitis and its saponin-rich fraction may be responsible for this effect.

Investigating MARK4 inhibitory potential of Bacopaside II: Targeting Alzheimer's disease.

Microtubule affinity regulating kinase 4 (MARK4) is known to hyperphosphorylate tau protein, which subsequently causes Alzheimer's disease (AD). MARK4 is a well-validated drug target for AD; thus, we employed its structural features to discover potential inhibitors. On the other hand, complementary and alternative medicines (CAMs) have been used for the treatment of numerous diseases with little side effects. In this regard, Bacopa monnieri extracts have been extensively used to treat neurological disorders because of their neuroprotective roles. The plant extract is used as a memory enhancer and a brain tonic. Bacopaside II is a major component of Bacopa monnieri; thus, we studied its inhibitory effects and binding affinity towards the MARK4. Bacopaside II show a considerable binding affinity for MARK4 (K = 107 M-1) and inhibited kinase activity with an IC50 value of 5.4 µM. To get atomistic insights into the binding mechanism, we performed Molecular dynamics (MD) simulation studies for 100 ns. Bacopaside II binds strongly to the active site pocket residues of MARK4 and a number of hydrogen bonds remain stable throughout the MD trajectory. Our findings provide the basis for the therapeutic implication of Bacopaside and its derivatives in MARK4-related neurodegenerative diseases, especially AD and neuroinflammation.

Advanced network pharmacology study reveals multi-pathway and multi-gene regulatory molecular mechanism of Bacopa monnieri in liver cancer based on data mining, molecular modeling, and microarray data analysis.

Liver cancer is a malignant tumor that grows on the surface or inside the liver. The leading cause is a viral infection with hepatitis B or C virus. Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer. A list of studies evidences the therapeutic efficacy of Bacopa monnieri against liver cancer, but the precise molecular mechanism is yet to be discovered. This study combines data mining, network pharmacology, and molecular docking analysis to potentially revolutionize liver cancer treatment by identifying effective phytochemicals. Initially, the information on active constituents of B. monnieri and target genes of both liver cancer and B. monnieri were retrieved from literature as well as from publicly available databases. Based on the matching results between B. monnieri potential targets and liver cancer targets, the protein-protein interaction (PPI) network was constructed using the STRING database and imported into Cytoscape for screening of hub genes based on their degree of connectivity. Later, the interactions network between compounds and overlapping genes was constructed using Cytoscape software to analyze the network pharmacological prospective effects of B. monnieri on liver cancer. Gene Ontology (GO) and KEGG pathway analysis of hub genes revealed that these genes are involved in the cancer-related pathway. Lastly, the expression level of core targets was analyzed using microarray data (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790). Further, the GEPIA server and PyRx software were used for survival and molecular docking analysis, respectively. In summary, we proposed that quercetin, luteolin, apigenin, catechin, epicatechin, stigmasterol, beta-sitosterol, celastrol, and betulic acid inhibit tumor growth by affecting tumor protein 53 (TP53), interleukin 6 (IL6), RAC-alpha serine/threonine protein kinases 1 (AKT1), caspase-3 (CASP3), tumor necrosis factor (TNF), jun proto-oncogene (JUN), heat shot protein 90 AA1 (HSP90AA1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), and SRC proto-oncogene (SRC). Through, microarray data analysis, the expression level of JUN and IL6 were found to be upregulated while the expression level of HSP90AA1 was found to be downregulated. Kaplan-Meier survival analysis indicated that HSP90AA1 and JUN are promising candidate genes that can serve as diagnostic and prognostic biomarkers for liver cancer. Moreover, the molecular docking and molecular dynamic simulation of 60ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between the compound and binding pockets of HSP90AA1 and JUN. Despite that, in vivo and in vitro studies are mandatory to unveil pharmacokinetics and biosafety profiles to completely track the candidature status of B. monnieri in liver cancer.

Antioxidant, Anti-Inflammatory and Anti-Obesity Potential of Extracts Containing Phenols, Chlorophyll and Carotenoids from Mexican Wild Populations of Bacopa monnieri (L.) Wettst.

Some of the species of the genus Bacopa have been used in Pharmacopoeia worldwide. However, in Mexico, Bacopa monnieri has neither been extensively cultivated nor studied, nor has their use in traditional medicine been reported. The aim of this work was to assess the taxonomic verification of the four wild populations of B. monnieri, the chemical content of their pigments and phenols and to provide an analysis of their potential bioactivity. B. monnieri wild populations from Mexico were validated using molecular markers. Chromatographic profiling using HPLC-PDA revealed 21 compounds comprising 12 chlorophylls and nine carotenoids; of the latter, the major ones were lutein (0.921 ± 0.031 µg/mg of dry extract) and ß-carotene (0.095 ± 0.003 µg/mg of dry extract). The total phenolic content, determined using the Folin-Ciocalteu assay, ranged from 54.8 ± 5.8 to 70.3 ± 2.2 µg of gallic acid equivalents (GAE)/mg. Plant extracts scavenged from the free radical DPPH in IC50 ranged from 130.6 ± 3.0 to 249.9 ± 12.1 µg dry extract/mL. In terms of the anti-inflammatory potential, the most effective extract was from a soil-based plant from Jalisco (BS), reduced from nitric oxide in a RAW 264.7 culture medium, with an IC50 value of 134 µg of dry extract/mL. The BS extract showed a significant neutral lipid-reducing activity in the zebrafish model, ranging from 3.13 µg/mL p < 0.05 to 100 µg/mL p < 0.0001. Overall, the extracts analyzed here for the first time seem promising for future use because of their antioxidant, anti-inflammatory and anti-obesity potential.

Importance of high-quality evidence regarding the use of Bacopa monnieri in dementia.

Background: Bacopa monnieri (BM), a commonly used herb, has shown neuroprotective effects in animal and in vitro studies; but human studies on patients with Alzheimer's Disease (AD) have been inconclusive. Further high-quality trials are required to conclusively state the utility of BM in AD and other neurodegenerative dementias. Methods: In the present study, we did a narrative review of the current challenges in designing clinical trials of BM in dementia and their evidence-based recommendations. Results: Many facets of the BM trials need improvement, especially effect size and sample size estimation. Current assessment and outcomes measures need a more holistic approach and newer scales for diagnosing and monitoring prodromal AD. The stringent guidelines in CONSORT and STROBE are often considered difficult to implement for clinical trials in ayurvedic medications like BM. However, adherence to these guidelines will undoubtedly improve the quality of evidence and go a long way in assessing whether BM is efficacious in treating AD/prodromal AD patients and other neurodegenerative dementias. Conclusion: Future studies on BM should implement more randomized controlled trials (RCTs) with an appropriate sample size of accurately diagnosed AD/prodromal AD patients, administering a recommended dosage of BM and for a pre-specified time calculated to achieve adequate power for the study. Researchers should also develop and validate more sensitive cognitive scales, especially for prodromal AD. BM should be evaluated in accordance with the same rigorous standards as conventional drugs to generate the best quality evidence.

Use of an exotic host plant reduces viral burden in a native insect herbivore.

Incorporation of exotic plants into the diets of native herbivores is a common phenomenon, influencing interactions with natural enemies and providing insight into the tritrophic costs and benefits of dietary expansion. We evaluated how use of an exotic plant, Plantago lanceolata, impacted immune performance, development and susceptibility to pathogen infection in the neotropical herbivore Anartia jatrophae (Lepidoptera: Nymphalidae). Caterpillars were reared on P. lanceolata or a native plant, Bacopa monnieri, and experimentally infected with a pathogenic virus, Junonia coenia densovirus. We found that virus-challenged herbivores exhibited higher survival rates and lower viral burdens when reared on P. lanceolata compared to B. monnieri, though immune performance and development time were largely similar on the two plants. These findings reveal that use of an exotic plant can impact the vulnerability of a native herbivore to pathogen infection, suggesting diet-mediated protection against disease as a potential mechanism facilitating the incorporation of novel resources.