Emerging Therapeutic Potential of Cannabidiol (CBD) in Neurological Disorders: A Comprehensive Review.

Cannabidiol (CBD), derived from Cannabis sativa, has gained remarkable attention for its potential therapeutic applications. This thorough analysis explores the increasing significance of CBD in treating neurological conditions including epilepsy, multiple sclerosis, Parkinson's disease, and Alzheimer's disease, which present major healthcare concerns on a worldwide scale. Despite the lack of available therapies, CBD has been shown to possess a variety of pharmacological effects in preclinical and clinical studies, making it an intriguing competitor. This review brings together the most recent findings on the endocannabinoid and neurotransmitter systems, as well as anti-inflammatory pathways, that underlie CBD's modes of action. Synthesized efficacy and safety assessments for a range of neurological illnesses are included, covering human trials, in vitro studies, and animal models. The investigation includes how CBD could protect neurons, control neuroinflammation, fend off oxidative stress, and manage neuronal excitability. This study emphasizes existing clinical studies and future possibilities in CBD research, addressing research issues such as regulatory complications and contradicting results, and advocates for further investigation of therapeutic efficacy and ideal dose methodologies. By emphasizing CBD's potential to improve patient well-being, this investigation presents a revised viewpoint on its suitability as a therapeutic intervention for neurological illnesses.

Identification of genes governing resistance to PCN (Globodera rostochiensis) through transcriptome analysis in Solanum tuberosum.

Potato cyst nematodes (PCNs) are major pests worldwide that affect potato production. The molecular changes happening in the roots upon PCN infection are still unknown. Identification of transcripts and genes governing PCN resistance will help in the development of resistant varieties. Hence, differential gene expression of compatible (Kufri Jyoti) and incompatible (JEX/A-267) potato genotypes was studied before (0 DAI) and after (10 DAI) inoculation of Globodera rostochiensis J2s through RNA sequencing (RNA-Seq). Total sequencing reads generated ranged between 33 and 37 million per sample, with a read mapping of 48-84% to the potato reference genome. In the infected roots of the resistant genotype JEX/A-267, 516 genes were downregulated, and 566 were upregulated. In comparison, in the susceptible genotype Kufri Jyoti, 316 and 554 genes were downregulated and upregulated, respectively. Genes encoding cell wall proteins, zinc finger protein, WRKY transcription factors, MYB transcription factors, disease resistance proteins, and pathogenesis-related proteins were found to be majorly involved in the incompatible reaction after PCN infection in the resistant genotype, JEX/A-267. Furthermore, RNA-Seq results were validated through quantitative real-time PCR (qRT-PCR), and it was observed that ATP, FLAVO, CYTO, and GP genes were upregulated at 5 DAI, which was subsequently downregulated at 10 DAI. The genes encoding ATP, FLAVO, LBR, and GP were present in > 1.5 fold before infection in JEX-A/267 and upregulated 7.9- to 27.6-fold after 5 DAI; subsequently, most of these genes were downregulated to 0.9- to 2.8-fold, except LBR, which was again upregulated to 44.4-fold at 10 DAI.

A Comprehensive Review of the Pharmacological Importance of Dietary Flavonoids as Hepatoprotective Agents.

The liver is a crucial organ that is involved in various kinds of metabolic activity and a very stable accessory gland for the digestive system. Long-term or persistent inflammation and oxidative stress due to any reasons have a substantial impact on the beginning and continuation of chronic diseases such as hepatocellular carcinoma, liver cirrhosis, liver fibrosis, and other hepatic conditions. There are many sources which can help the liver to be healthy and enhance its metabolic potential of the liver. Since the diet is rich origin of bioactive along with antioxidant chemicals including flavonoids and polyphenols, it can control different stages of inflammation and hepatic diseases. Numerous food sources, notably vegetables, nuts, fruits, cereals, beverages, and herbal medicinal plants, are rich in bioactive chemicals called flavonoids and their derivatives like Flavones, Anthocyanins, Iso-flavonoid, Flavanones, Flavanols, and Flavan-3-ols. Most recently occurred research on flavonoids has demonstrated that they can regulate hepatoprotective properties. This is because they are essential parts of pharmaceutical and nutraceutical products due to their hepatoprotective, antioxidative, and immune-modulating characteristics. However, the characteristics of their hepatoprotective impact remain unclear. The purpose of this comprehensive review is to survey the flavonoid structure and enriched sources for their hepatoprotective and antioxidant effects concerning liver toxicity or injury.

Chaetomium globosum KPC3: An Antagonistic Fungus Against the Potato Cyst Nematode, Globodera rostochiensis.

The potato cyst nematode (Globodera rostochiensis) is one of the most economically important pests of potato (Solanum tuberosum L.), causing significant economic losses worldwide. The identification of biocontrol agents for the sustainable management of G. rostochiensis is crucial. In this study, a potential biocontrol agent, Chaetomium globosum KPC3, was identified based on sequence analysis of the DNA internal transcribed spacer (ITS) region, the translation elongation factor 1-alpha (TEF1-α) gene, and the second largest subunit of the RNA polymerase II (RPB2) gene. The pathogenicity test of C. globosum KPC3 against cysts and second-stage juveniles (J2s) revealed that fungus mycelium fully parasitized the cyst after 72 h of incubation. The fungus was also capable of parasitizing the eggs inside the cysts. The culture filtrate of C. globosum KPC3 caused 98.75% mortality in J2s of G. rostochiensis after 72 h of incubation. The pot experiments showed that the combined application of C. globosum KPC3 as a tuber treatment at a rate of 1 lit kg-1 of tubers and a soil application at a rate of 500 ml kg-1 of farm yard manure (FYM) resulted in significantly lesser reproduction of G. rostochiensis compared to the rest of the treatments. Altogether, C. globosum KPC3 has the potential to be used as a biocontrol agent against G. rostochiensis and can be successfully implemented in integrated pest management programs.

Antidepressive-Like Effect of Aegle marmelos Leaf Extract in Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviour in Rats.

Background: Depression is a psychiatric disorder leading to anhedonia and lack of interest and motivation. Depressive symptoms are triggered by stressful life events, and patients with major depression are at significantly increased risk of attempting suicide. The crucial concern in depression treatment with antidepressant medications is that few weeks are required to show the therapeutic effect along with moderate side effects. The use of herbal medications is a new strategy for the treatment of depression which is often based on medicinal plants.Aegle marmelos (L.) Corr. (family: Rutaceae) is reported to have several actions on the central nervous system producing beneficial effects in anxiety, Alzheimer's disease, Parkinson's disease, epilepsy, and convulsion. Thus, the current investigation designed to assess the antidepressant activity of the standardized hydroethanolic extract of Aegle marmelos (EAM) leaves in male rats exposed to the chronic unpredictable mild stress (CUMS) paradigm. Methods: Rats were divided in 5 groups. The control group was not subjected to experimental CUMS paradigm, while 4 other groups were subjected to CUMS paradigm to induce depression-like behaviour from day 1 to day 28. Following the CUMS paradigm, 4 groups were divided as CUMS disease control, CUMS+EAM (150 mg/kg, p.o.), CUMS+EAM (300 mg/kg, p.o.), and CUMS+imipramine (15 mg/kg, p.o.), and treatment was given for seven consecutive days to the respective groups (day 29 to day 35). Behavioural parameters such as open field test, forced swim test, sucrose feeding test, and tail suspension test on day 1, day 28, and day 35 were measured, and biochemical parameters such as plasma corticosterone level, serotonergic system (5-HT, 5-HIAA, and 5-HT/5-HIAA), mitochondrial function, and proinflammatory mediators (TNF-α, IL-1ß, and IL-6) were estimated in hippocampus (HIP) and prefrontal cortex (PFC) regions of the brain on day 35, after the behavioural observations. On the other hand, phytochemical profile of Aegle marmelos was done. Results: On day 35, EAM (300 mg/kg) significantly reduced the immobility time during the tail suspension test from 208.66 ± 4.72 s to 108.83 ± 4.81 s and forced swim test from 200.16 ± 4.12 s to 148.5 ± 4.58 s. It also enhanced the behavioural parameters in the open field test such as ambulation from 26.5 ± 2.14 to 56.5 ± 1.80, rearing from 8.33 ± 0.71 to 19 ± 0.57, time spent in centre from 9.16 ± 0.9 to 17.16 ± 0.79 s, total distance travelled from 2.36 ± 0.12 to 4.68 ± 0.10 m, and anhedonia in the sucrose feeding test from 109.33 ± 1.08 to 135.83 ± 3.91 mL. The stimulation of the HPA axis resulting elevated corticosterone level caused by CUMS was reduced by EAM (300 mg/kg) from 80.12 ± 2.020 to 48.25 ± 2.407 µg/dL. Furthermore, EAM (300 mg/kg) increase CUMS-induced changes in serotonin (5-HT) level in HIP and PFC from 3.132 ± 0.09586 to 4.518 ± 0.1812 and 4.308 ± 0.1593 to 5.262 ± 0.1014 ng/mg protein, respectively. EAM (300 mg/kg) significantly attenuated the CUMS-induced changes in proinflammatory cytokine production and mitochondrial function in HIP and PFC. One group used to determine the acute toxicity as per OECD-23 standard protocol which resulted that 300 mg/kg EAM has no significant acute toxicity. Total phenolic content and total flavonoid content of standardized hydroalcoholic extract of AM was found 95.024 ± 2.431 and 36.820 ± 3.41, respectively, and additional identification tests showed the presence of alkaloids, tannins, saponins, cardiac glycosides, flavonoids, and terpenoids. Conclusion: On the basis of findings, EAM can be inferred as a potential antidepressant-like effect of this plan in preclinical research.

Integrating pharmacophore mapping, virtual screening, density functional theory, molecular simulation towards the discovery of novel apolipoprotein (apoE ε4) inhibitors.

AIM: An integrated protocol of virtual screening involving molecular docking, pharmacophore probing, and simulations was established to identify small novel molecules targeting crucial residues involved in the variant apoE ε4 to mimic its behavior as apoE2 thereby eliminating the amyloid plaque accumulation and facilitating its clearance. MATERIALS AND METHODS: An excellent ligand-based and structure-based approach was made to identify common pharmacophoric features involving structure-based docking with respect to apoE ε4 leading to the development of apoE ε4 inhibitors possessing new scaffolds. An effort was made to design multiple-substituted triazine derivatives series bearing a novel scaffold. A structure-based pharmacophore mapping was developed to explore the binding sites of apoE ε4 which was taken into consideration. Subsequently, virtual screening, ADMET, DFT searches were at work to narrow down the proposed hits to be forwarded as a potential drug likes candidates. Further, the binding patterns of the best-proposed hits were studied and were forwarded for molecular dynamic simulations of 10 ns for its structural optimization. RESULTS: Selectivity profile for the most promising candidates was studied, revealing significantly C13 and C15 to be the most potent compounds. The proposed hits can be forwarded for further study against apoE ε4 involved in neurological disorder Alzheimer's.

Development of a recombinase polymerase based isothermal amplification combined with lateral flow assay (HLB-RPA-LFA) for rapid detection of "Candidatus Liberibacter asiaticus".

Huanglongbing (HLB) or citrus greening is highly destructive disease that is affecting the citrus industry worldwide and it has killed millions of citrus plants globally. HLB is caused by the phloem limited, Gram negative, non-culturable, alpha-proteobacterium, 'Candidatus Liberibacter asiaticus'. Currently, polymerase chain reaction (PCR) and real time PCR have been the gold standard techniques used for detection of 'Ca. L. asiaticus'. These diagnostic methods are expensive, require well equipped laboratories, not user-friendly and not suitable for on-site detection of the pathogen. In this study, a sensitive, reliable, quick and low cost recombinase polymerase based isothermal amplification combined with lateral flow assay (HLB-RPA-LFA) technique has been developed as a diagnostic tool for detection of 'Ca. L. asiaticus'. The assay was standardized by designing the specific primer pair and probe based on the conserved 16S rRNA gene of 'Ca. L. asiaticus'. The assay was optimized for temperature and reaction time by using purified DNA and crude plant extracts and the best HLB-RPA-LFA was achieved at the isothermal temperature of 38°C for 20 to 30 min. The efficacy and sensitivity of the assay was carried out by using field grown, HLB-infected, HLB-doubtful and healthy citrus cultivars including mandarin, sweet orange cv. mosambi, and acid lime. The HLB-RPA-LFA did not show cross-reactivity with other citrus pathogens and is simple, cost-effective, rapid, user-friendly and sensitive. Thus, the HLB-RPA-LFA method has great potential to provide an improved diagnostic tool for detection of 'Ca. L. asiaticus' for the farmers, nurserymen, disease surveyors, mobile plant pathology laboratories, bud-wood certification and quarantine programs.

Core/shell nanoassembly of amphiphilic naproxen-polyethylene glycol: synthesis, characterisation and evaluation as drug delivery system.

Small molecule-based amphiphiles self-assemble into nanostructures (micelles) in aqueous medium which are currently being explored as novel drug delivery systems. Here, naproxen-polyethylene glycol (N-PEG), a small molecule-derived amphiphile, has been synthesised, characterised and evaluated as hydrophobic drug carrier. 1H, 13C Nuclear magnetic resonance (NMR), mass spectrometry (MS) and Fourier-transform infrared spectroscopy (FTIR) confirmed the formation of N-PEG and dynamic light scattering (DLS) revealed the formation of nano-sized structures of ∼228 nm. Transmission electron microscope (TEM) analysis showed aggregation behaviour of the structures with average size of ∼230 nm. Biodegradability aspect of the micellar-structured N-PEG was demonstrated by lipase-mediated degradation studies using DLS and TEM. High encapsulation efficiency followed by release in a sustained manner of a well-known anticancer drug, doxorubicin, demonstrated the feasibility of the new drug delivery system. These results advocate the promising potential of N-PEG micelles as efficient drug delivery system for specific delivery to cancerous cells in vitro and in vivo.

Effect of combined herbal feed additives on methane, total gas production and rumen fermentation.

The present study was to evaluate effect of herbal feed additives on methane and total gas production during the rumen fermentation for environment and animal health concern. Different parts of the five medicinal plants were selected such as leaf and small stems of Ocimum sanctum (Tulsi), roots of Curcuma longa (Haldi), fruits of Emblica officinalis (Amla), leaves of Azadirachta indica (Neem) and leaves and small stem of Clerodendrum phlomidis (Arni) for our study. Addition of different herbal additive combinations did not influence IVDMD and total gas production however methane production (mg/g of substrate DM) was significantly (P<0.05) reduced in Amla: Neem and Neem: Arni combinations. Total nitrogen significantly (P<0.01) increased in the combinations of Tulsi: Haldi and Amla: Neem. TCA-ppt-N is significantly (P<0.01) increased in Tulsi: Haldi, Haldi: Amla, Amla: Neem and Neem: Arni however NH3-N (mg/dl) significantly decreased in all treatments. We conclude that the screening of plant combinations, Amla: Neem and Neem: Arni have potential to decrease methane production and our herbal feed supplements have no side-effects on the ruminant in small amount.

Treatment of infectious disease: beyond antibiotics.

Several antibiotics have been discovered following the discovery of penicillin. These antibiotics had been helpful in treatment of infectious diseases considered dread for centuries. The advent of multiple drug resistance in microbes has posed new challenge to researchers. The scientists are now evaluating alternatives for combating infectious diseases. This review focuses on major alternatives to antibiotics on which preliminary work had been carried out. These promising anti-microbial include: phages, bacteriocins, killing factors, antibacterial activities of non-antibiotic drugs and quorum quenching.

Purification and physicochemical characterization of a serine protease with fibrinolytic activity from latex of a medicinal herb Euphorbia hirta.

A 34 kDa serine protease, designated as hirtin, with fibrinolytic activity was purified to homogeneity from the latex of Euphorbia hirta by the combination of ion exchange and gel filtration chromatography. The N-terminal sequence of hirtin was found to be YAVYIGLILETAA/NNE. Hirtin exhibited esterase and amidase activities along with azocaseinolytic, gelatinolytic, fibrinogenolytic and fibrinolytic activities. It preferentially hydrolyzed Aα and α-chains, followed by Bß and ß, and γ and γ-γ chains of fibrinogen and fibrin clot respectively. The optimum pH and temperature for enzyme activity was found to be pH 7.2 and 50 °C respectively. Enzymatic activity of hirtin was significantly inhibited by PMSF and AEBSF. It showed higher specificity for synthetic substrate p-tos-GPRNA for thrombin. The CD spectra of hirtin showed a high content of ß-sheets as compared to α-helix. The results indicate that hirtin is a thrombin-like serine protease and may have potential industrial and therapeutic applications.

Identification and characterization of integron mediated antibiotic resistance in pentachlorophenol degrading bacterium isolated from the chemostat.

A bacterial consortium was developed by continuous enrichment of microbial population isolated from sediment core of pulp and paper mill effluent in mineral salts medium (MSM) supplemented with pentachlorophenol (PCP) as sole source of carbon and energy in the chemostat. The consortia contained three bacterial strains. They were identified as Escherichia coli, Pseudomonas aeruginosa and Acinetobacter sp. by 16S rRNA gene sequence analysis. Acinetobacter sp. readily degraded PCP through the formation of tetrachloro-p-hydroquinone (TecH), 2-chloro-1,4-benzenediol and products of ortho ring cleavage detected by gas chromatograph/mass spectrometer (GC-MS). Out of the three acclimated PCP degrading bacterial strains only one strain, Acinetobacter sp. showed the presence of integron gene cassette as a marker of its stability and antibiotic resistance. The strain possessed a 4.17 kb amplicon with 22 ORF's. The plasmid isolated from the Acinetobacter sp. was subjected to shotgun cloning through restriction digestion by BamHI, HindIII and SalI, ligated to pUC19 vector and transformed into E. coli XLBlue1alpha, and finally selected on MSM containing PCP as sole source of carbon and energy with ampicillin as antibiotic marker. DNA sequence analysis of recombinant clones indicated homology with integron gene cassette and multiple antibiotic resistance genes.

Enrichment, isolation and characterization of pentachlorophenol degrading bacterium Acinetobacter sp. ISTPCP-3 from effluent discharge site.

Three pentachlorophenol (PCP) degrading bacterial strains were isolated from sediment core of pulp and paper mill effluent discharge site. The strains were continuously enriched in mineral salts medium supplemented with PCP as sole source of carbon and energy. One of the acclimated strains with relatively high PCP degradation capability was selected and characterized in this study. Based on morphology, biochemical tests, 16S rDNA sequence analysis and phylogenetic characteristics, the strains showed greatest similarity with Acinetobacter spp. The strain was identified as Acinetobacter sp. ISTPCP-3. The physiological characteristics and optimum growth conditions of the bacterial strain were investigated. The results of optimum growth temperature revealed that it was a mesophile. The optimum growth temperature for the strain was 30 degrees C. The preferential initial pH for the strain was ranging at 6.5-7.5, the optimum pH was 7. The bacterium was able to tolerate and degrade PCP up to a concentration of 200 mg/l. Increase in PCP concentration had a negative effect on biodegradation rate and PCP concentration above 250 mg/l was inhibitory to its growth. Acinetobacter sp. ISTPCP-3 was able to utilize PCP through an oxidative route with ortho ring-cleavage with the formation of 2,3,5,6-tetrachlorohydroquinone and 2-chloro-1,4-benzenediol, identified using gas chromatograph-mass spectrometric (GC-MS) analysis. The degradation pathway followed by isolated bacterium is different from previously characterized pathway.

Characterization of pentachlorophenol degrading bacterial consortium from chemostat.

A microbial consortium was developed by continuous enrichment of bacterial population isolated from sediment core of pulp and paper mill effluent in mineral salts medium (MSM) supplemented with pentachlorophenol (PCP) as sole source of carbon and energy in the chemostat. The enriched consortium contained three bacterial strains identified as Escherichia coli (PCP1), Pseudomonas aeruginosa (PCP2) and Acinetobacter sp. (PCP3) by morphological and biochemical tests, further confirmation was done using 16S rDNA sequence analysis. The potency of bacterial isolates in degradation of PCP was monitored in terms of growth and utilization of PCP as substrate with spectrophotometer and gas chromatograph-mass spectrometer (GC-MS) analysis. The strains were tested for their utilization of various organic compounds. The strain PCP3, showed higher potency to utilize PCP as sole source of carbon and energy than PCP1 and PCP2. The bacterial strain were able to utilize PCP through an oxidative and reductive route as indicated with the formation of tetrachloro-p-hydroquinone (TeCH), 2-chloro-1,4-benzenediol and 2,3,4,6-tetrachlorophenol, respectively.

Induction of in vitro flowering in Capsicum frutescens under the influence of silver nitrate and cobalt chloride and pollen transformation

The influence of silver nitrate (AgNO3) and cobalt chloride (CoCl2) on shoot multiplication and in vitro flowering in Capsicum frutescens Mill. was investigated. Exogenous administration of AgNO3 and CoCl2 at a concentration of 30 micronM resulted in the maximum tissue response in terms of shoot length and number of shoots after 45 days culturing on MS medium. Both silver nitrate (40 micronM) and cobalt chloride (30 micronM) influenced in vitro flowering after 25 and 45 days respectively. This is the first report on in vitro flowering in C. frutescens. The study also demonstrated successful transformation of pollen obtained from the in vitro flowers. Since capsicum is highly recalcitrant to in vitro plant regeneration, the results of the study may be highly useful in transformation of capsicum using germ free in vitro flowers.