Unveiling the Psychedelic Journey: An Appraisal of Psilocybin as a Profound Antidepressant Therapy.

Depression, a global health concern with significant implications for suicide rates, remains challenging to treat effectively with conventional pharmacological options. The existing pharmaceutical interventions for these illnesses need daily dosing, are accompanied by various adverse effects, and may exhibit limited efficacy in certain cases. However, hope emerges from an unlikely source-Psilocybin, a natural hallucinogen found in certain mushrooms. Recently, this enigmatic compound has garnered attention for its potential therapeutic benefits in addressing various mental health issues, including depression. Psilocybin alters mood, cognition, and perception by acting on a particular subtype of serotonin receptors in the brain. It's feasible that these shifts in consciousness will promote healing development, offering a novel approach to depression management. This comprehensive review explores psilocybin, derived from specific mushrooms, and its implications in the treatment of depression. The study examines new perspectives and therapeutic possibilities surrounding psilocybin, addressing existing gaps in academic literature. It delves into its biosynthesis, unique mechanisms of action, therapeutic applications, and anti-depressive effects. By uncovering the potential of this mind-altering substance, the review aims to advance psychiatric care, offering hope to those globally affected by depression.

Burgeoning therapeutic strategies to curb the contemporary surging viral infections.

Significant efforts and initiatives were already made in the health care systems, however in the last few years; our world is facing emergences of viral infections which potentially leading to considerable challenges in terms of higher morbidity, mortality, increased and considerable financial loads on the affected populations. Over ten major epidemics or pandemics have been recorded in the twenty-first century, the ongoing coronavirus pandemic being one of them. Viruses being distinct obligate pathogens largely dependent on living beings are considered as one of the prominent causes of death globally. Although effective vaccines and antivirals have led to the eradication of imperative viral pathogens, the emergences of new viral infections as well as novel drug-resistant strains have necessitated the implementation of ingenious and efficient therapeutic approaches to treat viral outbreaks in the future. Nature being a constant source of tremendous therapeutical resources has inspired us to develop multi-target antiviral drugs, overcoming the challenges and limitations faced by pharmaceutical industry. Recent breakthroughs in the understanding of the cellular and molecular mechanisms of viral reproduction have laid the groundwork for potential treatment approaches including antiviral gene therapy relying on the application of precisely engineered nucleic acids for disabling pathogen replication. The development of RNA interference and advancements in genome manipulating tools have proven to be especially significant in this regard. In this review, we discussed mode of actions and pathophysiological events associated with the viral infections; followed by distributions, and advancement made towards the detection strategies for timely diagnosis. In the later section, current approaches to cope up the viral pathogens and their key limitations have also been elaborated. Lastly, we also explored some novel and potential targets to treat such infections, where attentions were made on next generation gene editing technologies.

Phytotherapeutic Approach in the Management of Cisplatin Induced Vomiting; Neurochemical Considerations in Pigeon Vomit Model.

Cisplatin induced vomiting involves multiple mechanisms in its genesis and a single antiemetic agent do not cover both the phases (acute & delayed) of vomiting in clinics; necessitating the use of antiemetics in combination. Cannabis sativa and other selected plants have ethnopharmacological significance in relieving emesis. The aim of the present study was to investigate the intrinsic antiemetic profile of Cannabis sativa (CS), Bacopa monniera (BM, family Scrophulariaceae), and Zingiber officinale (ZO, family Zingiberaceae) in combinations against vomiting induced by highly emetogenic anticancer drug-cisplatin in pigeons. We have analysed the neurotransmitters which trigger the vomiting response centrally and peripherally. Electrochemical detector (ECD) was used for the quantification of neurotransmitters and their respective metabolites by high performance liquid chromatography in the brain stem (BS) and area postrema (AP) while peripherally in the small intestine. Cisplatin (7 mg/kg i.v.) induced reliable vomiting throughout the observation period (24 hrs). CS-HexFr (10 mg) + BM-MetFr (10 mg)-Combination 1, BM-ButFr (5 mg) + ZO-ActFr (25 mg)-Combination 2, ZO-ActFr (25 mg) + CS-HexFr (10 mg)-Combination 3, and CS-HexFr (10 mg) + BM-ButFr (5 mg)-Combination 4; provided ~30% (30 ± 1.1), 70% (12 ± 0.4; P < 0.01), 60% (19 ± 0.2; P < 0.05) and 90% (05 ± 0.1; P < 0.001) protection, respectively, against cisplatin induced vomiting as compared to cisplatin control. Standard MCP (30 mg) provided ~50% (23 ± 0.3) protection (P > 0.05). CS Hexane fraction (10 mg/kg), BM methanolic (10 mg/kg) and bacoside rich n-butanol fraction (5 mg/kg) and ZO acetone fraction (25 mg/kg) alone provided ~62%, 36%, 71%, and 44% protection, respectively, as compared to cisplatin control. The most effective and synergistic combination 4 was found to reduce 5HT and 5HIAA (P < 0.05-0.001) in all the brain areas area postrema (AP)+brain stem (BS) and intestine at the 3rd hour of cisplatin administration. In continuation, at the 18th of cisplatin administration reduction in dopamine (P < 0.001) in the AP and 5HT in the brain stem and intestine (P < 0.001) was observed. The said combination did not change the neurotransmitters basal levels and their respective metabolites any significantly. In conclusion, all the tested combinations offered protection against cisplatin induced vomiting to variable degrees, where combination 4 provided enhanced attenuation by antiserotonergic mechanism at the 3rd hour while a blended antidopaminergic and antiserotonergic mechanism at the 18th hour after cisplatin administration.

Identification of phytochemical inhibitors of SARS-CoV-2 protease 3CLpro from selected medicinal plants as per molecular docking, bond energies and amino acid binding energies.

Recent worldwide outbreak of SARS-COV-2 pandemic has increased the thirst to discover and introduce antiviral drugs to combat it. The bioactive compounds from plant sources, especially terpenoid have protease inhibition activities so these may be much effective for the control of viral epidemics and may reduce the burden on health care system worldwide. Present study aims the use of terpenoid from selected plant source through bioinformatics tools for the inhibition of SARS-COV-2. This study is based on descriptive analysis. The Protein Data Bank and PubChem database were used for the analysis of SARS-COV-2 protease and plant source terpenoids. Molecular docking by using molegro virtual docker (MVD) software was carried out. The findings of study are based on the inhibitory actions of different plant sourced terpenoid against SARS-COV-2. As per the available resources and complementary analysis these phytochemicals have capacity to inhibit 3CLpro protease. The study reports that (3,3-dimethylally) isoflavone (Glycine max), licoleafol (Glycyrrhiza uralensis), myricitrin (Myrica cerifera), thymoquinone (Nigella sativa), bilobalide, ginkgolide A (Ginkgo biloba), Salvinorin A (Salvia divinorum), citral (Backhousia citriodora) and prephenazine (drug) showed high activity against SARS-COV-2 protease 3CLpro. The drug like and ADMET properties revealed that these compounds can safely be used as drugs. Cross structural analysis by using bioinformatics study concludes that these plant source terpenoid compounds can be effectively used as antiprotease drugs for SARS-COV-2 in future.

Phytochemical Analysis, α-Glucosidase and Amylase Inhibitory, and Molecular Docking Studies on Persicaria hydropiper L. Leaves Essential Oils.

OBJECTIVE: Medicinal plants and essentials oils are well known for diverse biological activities including antidiabetic potential. This study was designed to isolate essential oils from the leaves of Persicaria hydropiper L. (P. hydropiper), perform its phytochemical analysis, and explore its in vitro antidiabetic effects. MATERIALS AND METHODS: P. hydropiper leaves essential oils (Ph.Los) were extracted using a hydrodistillation apparatus and were subjected to phytochemical analysis using the gas chromatography mass spectrometry (GC-MS) technique. Ph.Lo was tested against two vital enzymes including α-glucosidase and α-amylase which are important targets in type-2 diabetes. The identified compounds were tested using in silico approaches for their binding affinities against the enzyme targets using MOE-Dock software. RESULTS: GC-MS analysis revealed the presence of 141 compounds among which dihydro-alpha-ionone, cis-geranylacetone, α-bulnesene, nerolidol, ß-caryophyllene epoxide, and decahydronaphthalene were the most abundant compounds. Ph.Lo exhibited considerable inhibitory potential against α-glucosidase enzyme with 70% inhibition at 1000 µg mL-1 which was the highest tested concentration. The inhibitory activity of positive control acarbose was 77.30 ± 0.61% at the same tested concentration. Ph.Lo and acarbose exhibited IC50 of 170 and 18 µg mL-1 correspondingly. Furthermore, dose-dependent inhibitions were observed for Ph.Lo against α-amylase enzyme with an IC50 of 890 µg mL-1. The top-ranked docking conformation was observed for ß-caryophyllene epoxide with a docking score of -8.3182 against α-glucosidase, and it has established seven hydrogen bonds and one H-pi interaction at the active site residues (Phe 177, Glu 276, Arg 312, Asp 349, Gln 350, Asp 408, and Arg 439). Majority of the identified compounds fit well in the binding pocket of Tyr 62, Asp 197, Glu 233, Asp 300, His 305, and Ala 307 active residues of α-amylase. ß-Caryophyllene epoxide was found to be the most active inhibitor with a docking score of -8.3050 and formed five hydrogen bonds at the active site residues of α-amylase. Asp 197, Glu 233, and Asp 300 active residues were observed to be making polar interactions with the ligand. CONCLUSIONS: The current study revealed that Ph.Lo is rich in bioactive metabolites which might contribute to its enzyme inhibitory potential. Inhibition of these enzymes is the key target in reducing postprandial hyperglycemia. However, further detailed in vivo studies are required for their biological and therapeutic activities.

Selenium-enriched probiotics improve hepatic protection by regulating pro-inflammatory cytokines and antioxidant capacity in broilers under heat stress conditions.

OBJECTIVE: High ambient temperature in poultry is a challenging and fatal stress among environmental factors. It affects the production quality, damages the liver, and increases mortality in broilers. The present study is focused to explore appropriate utilization of Selenium (Se) as a feed additive in broiler chickens against high temperature. MATERIALS AND METHODS: Day-old male broiler chickens (Ross 308) (n = 200) were grouped according to the supplements used in their basal diets such as: corn-soybean basal diet as control (Con), a basal diet containing sodium selenite, basal diet with probiotics, and a basal diet containing selenium-enriched probiotics (SP). At the end of the experimental period of 42 days, the liver was isolated and was used to determine the antioxidant capacity through a spectrophotometer. Inflammatory and anti-inflammatory cytokines production in the liver was measured through a real-time polymerase chain reaction. RESULTS: Hepatic analyses revealed the decreased level of malondialdehyde, whereas glutathione, glutathione peroxidase (GSH-Px), and superoxide dismutase levels were increased in the SP group. Furthermore, supplementation of SP significantly up-regulated the mRNA expression of glutathione peroxidase 1 (GPx1), GPx4, IL6, and IL10 and down-regulated the expression of pro-inflammatory cytokines. CONCLUSION: It is thus concluded that SP as a potential nutritive supplement may facilitate hepatic protection by suppressing hepatic oxidation, inflammation, and necrosis during the high ambient temperature of summer.

Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.

BACKGROUND: Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. METHODS: Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. RESULTS: Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. CONCLUSION: The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation of its antiemetic effect.

Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of Polygonatum verticillatum.

BACKGROUND: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders. METHODS: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules. RESULTS: In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102 ± 0.19 µg/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and ß-sitosterol. CONCLUSIONS: These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation.

Antipyretic and anticonvulsant activity of Polygonatum verticillatum: comparison of rhizomes and aerial parts.

The current study was undertaken to explore the antipyretic and anticonvulsant profile of the Polygonatum verticillatum in established pharmacological paradigms. The crude methanol extract of rhizomes (PR) and aerial parts (PA) of the plant were tested in Brewer's-yeast-induced pyrexia and pentylenetetrazole-induced convulsion test. PR and PA both evoked prominent antipyretic activity (p < 0.01) in a dose-dependent manner during all assessment times at the dose of 50, 100, and 200 mg/kg intraperitoneally. The protection elicited by PR (82.20%) at 200 mg/kg was comparable with aspirin (88.48%) as a standard drug at 100 mg/kg. However, PA was less potent, and maximum protection was 64% at 200 mg/kg. Both PR and PA were devoid of any anticonvulsant activity. Our results demonstrated prominent evidence of antipyretic activity of P. verticillatum that is consistent with the folk uses of the plant. In addition from a biodiversity point of view, PA of the plant can also be used as an alternate of PR.

Bronchodilator activity of aerial parts of Polygonatum verticillatum augmented by anti-inflammatory activity: attenuation of Ca²âº channels and lipoxygenase.

Polygonatum verticillatum is commonly used for the treatment of asthma and inflammation. The current study was aimed to scrutinize the pharmacological profile of methanolic extract of the aerial parts (PA). Isolated tracheal preparations were used for the evaluation of bronchodilatory activity, whilst the in vivo carrageenan-induced paw oedema test and an in vitro lipoxygenase (LOX) inhibitory assay were used for the assessment of the anti-inflammatory profile of PA. When tested against carbachol and K⁺ (80 mM)-induced contractions, PA caused complete inhibition of isolated rabbit tracheal preparations in a dose-dependent mode, similar to verapamil. While elucidating possible mechanism, PA shifted the Ca²âº concentration-response curves to the right, analogous to that produced by verapamil, confirming a Ca²âº channel blocker-like activity. PA provoked profound reduction in paw oedema with a maximum protection of 60.87% at 200 mg/kg i.p. in a dose-dependent manner which was augmented by its prominent LOX inhibitory activity (IC50 : 125 µg/mL). These findings authenticated its therapeutic potential in the treatment of asthmatic and inflammatory conditions.

Role of different additives and metallic micro minerals on the enhanced citric acid production by Aspergillus niger MNNG-115 using different carbohydrate materials.

The present investigation deals with the promotry effect of different additives and metallic micro minerals on citric acid production by Aspergillus niger MNNG-115 using different carbohydrate materials. For this, sugar cane bagasse was fortified with sucrose salt medium. Ethanol and coconut oil at 3.0% (v/w) level increased citric acid productivity. Fluoroacetate at a concentration of 1.0 mg/ml bagasse enhanced the yield of citric acid significantly. However, the addition of ethanol and fluoroacetate after 6 h of growth gave the maximum conversion of available sugar to citric acid. In another study, influence of some metallic micro-minerals viz. copper sulphate, molybdenum sulphate, zinc sulphate and cobalt sulphate on microbial synthesis of citric acid using molasses medium was also carried out. It was found that copper sulphate and molybdenum sulphate remarkably enhanced the production of citric acid while zinc sulphate was not so effective. However, cobalt sulphate was the least effective for microbial biosynthesis of citric acid under the same experimental conditions. In case of CuSO(4), the strain of Aspergillus niger MNNG-115 showed enhanced citric productivity with experimental (9.80%) over the control (7.54%). In addition, the specific productivity of the culture at 30 ppm CuSO(4) (Q(p) = 0.012a g/g cells/h) was several folds higher than other all other concentrations. All kinetic parameters including yield coefficients and volumetric rates revealed the hyper productivity of citric acid by CuSO(4) using blackstrap molasses as the basal carbon source.