Biochemical Estimations Research Articles

Formulation and optimization of xanthohumol loaded solid dispersion for effective treatment of Parkinson's disease in rats: In vitro and in vivo assessment

Xanthohumol (XH) is a prenylated flavonoid that possesses neuroprotective effects by increasing the levels of dopamine (DA), reducing oxidative stress, and neuroinflammation against Parkinson's disease (PD). However, the neuroprotective efficacy of XH in managing PD is limited by its low solubility, poor bioavailability, and less blood-brain barrier (BBB) permeability leading to decreased therapeutic activity. To overcome these limitations, XH-loaded solid dispersion (SD) has been formulated using the Central Composite Design (CCD) approach. The optimized formulation was evaluated by determining the angle of repose, drug loading, percentage drug release, PXRD, DSC, FTIR, and SEM. The results of PXRD, DSC, and SEM demonstrated the formation of SD. The XH-SD showed a 6.45-fold enhancement in dissolution rate, a 12.7-fold increase in Cmax, and 26.11-fold increase in XH's area under curve (AUC) as compared to the naïve XH. In the pharmacokinetic studies, XH-SD showed a 42.20 folds increase in relative bioavailability(0-∞) compared to naïve XH. To assess pharmacodynamic effects, PD was induced using rotenone. The motor and non-motor functions were evaluated by assessing various behavioral parameters such as catalepsy, spontaneous locomotor activity and muscle coordination test. The formulation exhibited dose-dependent effects, with both low and high doses of XH-SD resulting in significant enhancements (P < 0.001) in motor functions in rats induced with PD. Furthermore, biochemical estimations showed that XH-SD at both doses increased the levels of dopamine (DA), and reduced oxidative stress and neuroinflammation.

Modulation of tyrosine receptor imposed by Estrogen in Memory and Cognition in Female Rats.

The present study aimed to investigate the potential role of estrogen in modulating the pathogenesis of dementia-type-AD phenotype, possibly by tyrosine kinase. Female Wistar rats were ovariectomized (OVX) and were treated with Diethylstilbesterol (DES), an estrogen analogue (20μg/kg/day, i.m.), and Imatinib, a tyrosine kinase inhibitor (30mg/kg/day, orally), for two months. Animals underwent surgical ovariectomy exhibited significant memory deficits in spatial memory assessment as mean dwell time, short-term memory as spontaneous alteration, and novel object recognition after a chronic period of 4 weeks. OVX animals administered with DES produced significant restoration of memory dysfunction in comparison to OVX, as exhibited by Morris water maze (p=0.0003), Y maze (p<0.0001), and NORT. Imatinib prior to DES treatment in OVX animals showed significant decline in memory functions, which confirms the potential involvement of tyrosine receptor kinase activity in improved memory functions offered by estrogen. Levels of estradiol were significantly (p<0.0001) lower in the OVX group compared to normal which was significantly (p<0.0001) restored in the OVX+E group. Biochemical estimations of TBARS, glutathione, and acetylcholinesterase levels in the brain showed a significant increase in oxidative stress among the OVX group. However, a significant restoration of oxidative changes with TBARS (p=0.0496), glutathione (p<0.0001), and acetylcholinesterase activity (p=0.0201) of OVX animals receiving DES was observed in comparison to animals receiving imatinib followed by DES. These implications in the brain signify that estrogen and tyrosine kinase play an important role in the pathogenesis of dementia. In conclusion, estrogen offers neurochemical mediation for cognition and memory possibly via modulation of tyrosine kinase signaling in female subjects.

Engineering Budesonide Microparticles for Enhancing Pulmonary Targeting: Validation through In Vivo Investigations

AbstractThe study aimed to develop and evaluate budesonide inhalation micro‐suspension to target inflammation in the lower trachea and bronchi. Initially, the slurry phase is prepared by dispersing the drug (0.25 and 0.5 mg ml−1) in the Water for Injection with polysorbate 80. The slurry is mixed with the aqueous phase comprising other excipients. The mixture is further subjected to the treatment with homogenizer. The prepared formulations are subjected to various physio‐chemical analysis like description, density, pH, osmolality, viscosity, shelf life, impurities, assay, particle size, etc. Andersen cascade impactor is used to estimate the aerodynamic performance. In vivo analysis is initiated with the induction of Asthma in Sprague Dawley rats by ovalbumin challenge intranasally and the treatment is given with the aid of a nebulizer. Lastly, the biochemical estimations are carried out in blood and bronchoalveolar lavage fluid (BALF). The lungs are also subjected to morphological and histological evaluations. The physio‐chemical and analytical examination indicated a stable formulation that is compliant with the standard guidelines. The D90 value of the test formulation is ≤4.5 µm. Cascade impactor evaluation estimated almost, 2–10% higher amount of budesonide reaching the target region as compared to the marketed product. Test formulation attenuated the manifestation of ovalbumin‐induced asthma through suppression of inflammatory cell count in blood and BALF, and modulation of Lactate dehydrogenase and Alkaline Phosphatase levels which is further confirmed by histopathological analysis. The formulated budesonide micro‐suspension demonstrated stability, safety, and efficient delivery to the target site.

Exploring the Potential Antidiabetic Effects of Alkannin (A Naphthoquinone Compound): In Vivo and In Silico Studies

Background It is estimated that the plant has been utilized in India’s traditional medical system for close to 2,500 years. Alkanin is a key active component in Boraginaceae medicinal plant roots. Many scientists are interested in this tiny molecule due to its biological potential. Purpose To examine the hypoglycemic effects of alkannin (a naphthoquinone pigment). Methods Initially, we determined the dosage of alkannin by conducting an acute oral toxicity study per Organisation for Economic Co-operation and Development guidelines. Subsequently, streptozocin was used to induce diabetes in mice, and we chose several parameters such as body weight, food and water intake, blood glucose level, and biochemical estimation for the in vivo evaluation. The enhanced pharmacokinetic features of alkannin, such as its better cytochromes P450 metabolism profiles and higher intestinal absorption as compared to glimepiride, were validated by in silico investigations utilizing Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) and AutoDock Vina. Results In particular, blood glucose levels and body weight in the alkannin-treated group drastically decreased to 138 ± 1.45 mg/dL and 27.9±0.54 g, respectively, as compared with the diabetic-treated group. Moreover, alkaline phosphatase levels dropped to 57.26 ± 3.05 U/L in the alkannin group, suggesting enhanced liver and kidney functions. Creatinine levels also decreased from 1.44 ± 0.10 mg/dL to 0.92 ± 0.09 mg/dL, and serum glutamic oxaloacetic transaminase/aspartate aminotransferase levels decreased from 64.16 ± 3.14 U/L to 47.85 ± 2.01 U/L. Additionally, diabetic controls maintained cholesterol levels between 102.1 ± 11.46 mg/dL and 93.53 ± 2.61 mg/dL. With a considerable binding score of –9.2 kcal/mol for alkannin, molecular docking demonstrated a high degree of binding efficiency and robust interaction with biological targets. The docking results revealed that alkannin exhibits drug-like properties. In addition, it satisfies the lead likeness requirement and has a lower synthetic accessibility score compared to glimepiride. Conclusion The results revealed the promising characteristics and positive outcomes of alkannin, underscoring its potential as a viable candidate for further investigation and prospective advancement as a treatment drug for diabetes.

Antiinflammatory and Antioxidant Mediated Nephroprotection of Melatonin and Rosuvastatin in Carboplatin Induced Nephrotoxicity: An Experimental Study

Background: Platinum compounds like cisplatin, carboplatin used as anticancer drugs are known to cause nephrotoxicity. There is a need of drugs to prevent the drug induced nephrotoxicity. This experimental study was done to assess the nephroprotective role of rosuvastatin in carboplatin induced nephrotoxicity models and to compare it with melatonin. Methodology: A total of 36 albino rats were randomly divided into 6 groups (n=6). Group I was control group. In Groups II to VI nephrotoxicity was induced by intraperitoneal administration of a single dose of Carboplatin 128mg/kg on day 5. In Group II, no drug was administered. In group III and IV melatonin 5mg/kg and 10mg/kg was administered orally once a day for 10 days. In group V and VI, rosuvastatin 10mg/kg and 20mg/kg was administered orally once a day for 10 days. Blood was collected on day 0 for the baseline values and at an interval of 7 and 11 days for biochemical and antioxidant estimation. Kidneys were dissected at the end of study, weighed and renal tissue was subjected to histopathological analysis. Results: There was a significant decrease in urea, creatinine and uric acid in all the treatment groups. Also a significant decrease (p&lt;0.05) was seen in MDA levels in treatment groups as compared to the negative control. A non-significant decrease was observed in IL-18 levels in the treatment groups. Also, histopathology of kidney tissues showed that in treatment groups, there were less changes in interstitium and vessels. Conclusion: Melatonin and rosuvastatin has shown a nephroprotective effect in carboplatin induced nephrotoxicity in terms of improved renal function tests, reduced IL-18 showing anti-inflammatory action, antioxidant action by decreasing MDA and increasing GSH and by histopathological studies of kidney tissue

Efficient physics-informed transfer learning to quantify biochemical traits of winter wheat from UAV multispectral imagery

Accurate and efficient estimation of biochemical traits, including leaf index area (LAI), leaf chlorophyll content (LCC) and canopy chlorophyll content (CCC), is crucial for crop growth monitoring in agricultural management. Recent advancements in unmanned aerial vehicle (UAV) multispectral remote sensing have enabled fast and cost-effective measurements of these traits. However, traditional statistical regression models trained on specific datasets lack scalability and transferability across practical field conditions without retraining. This study proposed an efficient physics-informed transfer learning model (PITL) for winter wheat biochemical traits estimation from UAV multispectral data. The PITL integrates the strengths of physical radiative transfer simulations and deep neural network architectures through transfer learning to improve the estimation of biochemical traits from UAV multispectral data. The PITL was tested with convolutional neural network (CNN), deep neural network (DNN), and long short-term memory (LSTM) architectures. Results indicated that PITLDNN had better accuracy than PITLCNN and PITLLSTM models in predicting LAI (R2=0.94, RMSE = 0.32 m2/m2), LCC (R2=0.81, RMSE = 5.20 μg/cm2) and CCC (R2=0.928, RMSE = 0.2 g/m2). Moreover, PITLDNN demonstrated higher capability in computational efficiency, making it suitable for processing large volumes of UAV multispectral data in crop growth monitoring applications. Furthermore, PITL's integration of radiative transfer knowledge with labeled field data yielded higher predictive accuracy compared to physically-based inversion model, pure data-driven deep neural network approaches, and hybrid models. This study highlighted the performance of PITLDNN in accurately and efficiently quantifing biochemical traits from UAV multispectral data, thereby providing timely and accurate information for guiding crop growth monitoring applications.

Effect of Niosomal Encapsulation of Quercetin and Silymarin and their Combination on Dimethylnitrosoamine-induced and Phenobarbital promoted Hepatocellular Carcinoma in Rat Model.

Hepatocellular carcinoma is a particularly dangerous and severe kind of liver cancer. Many anticancer drugs fail to complete the treatment of hepatocellular carcinoma without any side effects. There should be appropriate and without side effective treatments for hepatocellular carcinoma. The objective of the current study was to evaluate how quercetin and silymarin in a niosomal formulation affected hepatocyte carcinoma caused by diethylnitrosamine. Five groups were created from the thirty male rats. Normal control (untreated group), tumor group (administered dimethylnitrosoamine 200 mg/kg), treatment group I (administered 50 mg/kg of niosomal encapsulated quercetin), treatment group II (administered 50 mg/kg of niosomal encapsulated silymarin), and treatment group III (administered 50 mg/kg of niosomal encapsulated quercetin + silymarin). Then, biochemical estimation, serum analysis, and histopathological examination were carried out. Treatment group III, treated with niosomal encapsulation of a combination of quercetin + silymarin 50 mg/kg, demonstrated the significant restoration of alpha-fetoprotein and carcinoembryonic antigen and also antioxidants like superoxide dismutase and nitric oxide. The histopathological examination showed improved liver architecture in this group compared to other treatment groups. Our findings revealed that a potent anticancer effect was observed in treatment group III as niosomal formulation increased the bioavailability of the drug within the body. In order to completely understand the underlying processes and evaluate the therapeutic effectiveness of these chemicals in the therapy of hepatocellular carcinoma, further investigation and clinical trials are required.

Synergistic Amelioration of Letrozole-induced Polycystic Ovary Syndrome in Rats: A Therapeutic Approach with Apple Cider Vinegar and Metformin Combination.

The present study was conducted to evaluate the combination effect of apple cider vinegar (ACV) and metformin against letrozole-induced polycystic ovary syndrome (PCOS).Female Wistar rats were administered letrozole (1mg/kg/day, p.o) for 21 days, except for the control group of animals. On the 22nd day, PCOS-induced animals were segregated into 4 groups and administered with CMC, ACV, metformin, and a combination of ACV and metformin, respectively. The treatments were continued for 15 days, and on the 36th day, all the animals were sacrificed for biochemical (blood glucose, lipid profile), hormonal (sex hormones and adiponectin), and pro-inflammatory mediator estimations in blood samples. The ovarian tissue samples were used for oxidative stress parameters and histological alterations.The PCOS control animals showed a significant alteration in the estrous cycle. The administration of letrozole resulted in the alteration of hormonal balance and elevation of body weights, glycemic state, lipid profile, pro-inflammatory mediators in serum, and oxidative stress in ovarian samples. Individual treatment groups and combination treatment groups reversed the letrozole-induced alterations in PCOS animals, and more promising results were observed with combination therapy than with individual treatment groups. Further, the therapeutic potential of the combination treatment group was also confirmed by the histological observations in the ovarian samples.The study showed that the combination of ACV and metformin significantly alleviated letrozole-induced PCOS complications in rats. This might have been achieved by mitigating the hormonal imbalance, pro-inflammatory, hyperglycemic, and hyperlipidemic states in serum, and oxidative stress in the ovary samples.

Enzyme Response in Thermotolerant Silkworm Breeds under Beauveria bassiana Infection

A study on enzyme activity in thermotolerant bivoltine silkworm breeds under Beauveria bassiana disease was conducted at the Department of Sericulture, UAS, GKVK, Bengaluru during 2021-23. Thermotolerant bivoltine breeds viz., B1, B4 and B8, were resistant to muscardine and CSR4, a muscardine susceptible breeds were used in this study. A batch of silkworms of all the breeds were inoculated with 6.86 × 104 spores / ml of B. bassiana @ 0.5 ml per silkworm immediately after 4th moult and another batch were reared under normal condition. The haemolymph was collected from these breeds at 48, 96 and 144 hours post inoculation (hpi) with B. bassiana spores in both inoculated and control batches. Biochemical estimation of amylase, protease and trehalase enzyme activities in the haemolymph. The amylase activity increased from 48 hpi to 144 hpi in all the breeds under both control and muscardine inoculation, but being lesser under inoculation. The protease activity was found higher in B1 breed from 48 hpi to 144 hpi under both control and inoculated conditions. Trehalase activity was enhanced at all time intervals under control conditions in B1, B4 and B8 breeds and CSR4 breed shows decreased at 144 hpi under both control and inoculation conditions. Thus increased enzyme activity in B1 and B4 breeds could be associated with their better performance for survival and economic parameters under inoculated condition. The correlational studies revealed that haemolymph amylase, protease and trehalase were found to be positively corelated with cocoon weight (g) and negatively correlated with larval mortality (%). Thus, the study revealed that silkworm breeds like B1, B4 and B8 as productive breeds and hence may be used for future breeding programmes for evolution of new robust silkworm breeds.

Potential of Selected Underutilized Leafy Vegetables Against CCL4 Induced Oxidative Stress on Wistar Rats

Nutritional immunology might become even more important in prevention of disease. Underutilized leafy vegetables are the richest source of many bioactive compounds especially phenolic compounds with excellent antioxidant properties. Increased consumption of diets containing leafy vegetables may give positive results to human health. The underutilized leafy vegetables which includes Indian pennywort, Sessile joyweed, Red amaranth, Red spinach, Asiatic day flower, Indian sorrel, Roselle leaves are quantified for its phenols, flavonoids and vitamins contents by HPLC-LC MS method. The phenols, flavonoids and vitamins ranged from 0.186 – 12014 µg/g, 0.018 – 785.25 µg/g and 0.361 – 18466.56 ng/g in the underutilized leafy vegetables. Based on the bioactive compounds present, herbal preparations are developed and evaluated for hepatoprotective property against CCL4 induced intoxication in wistar rat model. Biochemical estimation in blood serum (AST/SGOT, ALT/SGPT, ALP, Total bilirubin) and antioxidant enzyme estimation in liver homogenate (SOD, GOD, LPO) showed positive results to reduce hepatotoxicity in CCL4 intoxicated wistar rat model. This exploration can helps in addressing importance of bioactive components present in underutilized leafy vegetables in combating various degenerative diseases and also proved the nutraceutical potential of leafy vegetables. Further which can be used for development of functional foods with the present pre-clinical data.

Farnesyl pyrophosphate synthase inhibitors with antiosteoporosis efficacy in ovariectomized rats: A mixed binding approach beyond bisphosphonates

The primary focus of bisphosphonate medications is on targeting human farnesyl pyrophosphate synthase (hFPPS), an essential regulator of mammalian isoprenoids. Yet, these drugs encounter limitations due to their restricted "druglike" properties and their effectiveness primarily in treating skeletal disorders. In this study, we synthesized novel non-bisphosphonate compounds, using 4,4'-(ethane-1,2-diylbis(oxy))bis(3-methoxybenzaldehyde) (1) as a starting compound, with the aim of targeting hFPPS through a mixed binding approach. Among the various compounds tested, compounds 4a and 4b exhibited significant inhibition of hFPPS activity, with IC50 values of 1.108 and 1.24 μM, respectively. Docking studies further revealed that both compounds bound within the allylic binding site and near the isopentenyl diphosphate (IPP) site within the hFPPS pocket. Molecular dynamic simulations were performed on the best docking pose of the most potent compound 4a to confirm the formation of a stable complex with hFPPS. In an in vivo study conducted on ovariectomized rats, various biochemical markers including osteocalcin, estradiol, osteoprotegerin, bone mineral content, and density were negatively impacted, while levels of bone specific alkaline phosphatase, receptor activator of nuclear factor kappa-Β ligand, serum/urinary calcium, and phosphate increased. Notably, compound 4a exhibited antiresorptive properties similar to zoledronate, effectively restoring most of the perturbed biochemical estimations. These findings suggest the potential of compound 4a, a non-bisphosphonate compound, as alternative therapeutic agents for combating osteoporosis.

Sexual dimorphism in neurobehavioural phenotype and gut microbial composition upon long-term exposure to structural analogues of bisphenol-A

Bisphenol S (BPS) and Bisphenol F (BPF), the analogues of the legacy endocrine disrupting chemical, Bisphenol A (BPA) are ubiquitous in the environment and present in various consumer goods, and potentially neurotoxic. Here, we studied sex-specific responses of bisphenols on behavioural phenotypes, including their association with pro-inflammatory biomarkers and altered neurotransmitters levels, and the key gut microbial abundances. Neurobehavioural changes, using standard test battery, biochemical and molecular estimations for inflammatory cytokines, neurotransmitters, and oxido-nitrosative stress markers, gene expression analysis using qRT-PCR, H&E based histological investigations, gut permeability assays and Oxford Nanopore-based 16S-rRNA metagenomics sequencing for the gut microbial abundance estimations were performed. Bisphenol(s) exposure induces anxiety and depression-like behaviours, particularly in the male mice, with heightened pro-inflammatory cytokines levels and systemic endotoxemia, altered monoamine neurotransmitters levels/turnovers and hippocampal neuronal degeneration and inflammatory responses in the brain. They also increased gut permeability and altered microbial diversity, particularly in males. Present study provides evidence for sex-specific discrepancies in neurobehavioural phenotypes and gut microbiota, which necessitate a nuanced understanding of sex-dependent responses to bisphenols. The study contributes to ongoing discussions on the multifaceted implications of bisphenols exposure and underscores the need for tailored regulatory measures to mitigate potential health risks associated with them.

Formulation and Characterization of Silibinin Entrapped Nano-Liquid Crystals for Activity against Aβ1-42 Neurotoxicity in In-Vivo Model.

Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aβ1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aβ1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5nm, -21mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) techniquewere employed to understand monomer inhibition effect of SIL-NLCs on Aβ1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aβ1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aβ1-42 aggregate, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aβ1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.

Trichoderma produces methyl jasmonate-rich metabolites in the presence of Fusarium, showing biostimulant activity and wilt resistance in tomatoes

Bioactive secondary metabolites from fungi, including Trichoderma, are an excellent source of plant biostimulants. Although production of novel biostimulants from known microbes is critical, challenging them may produce novel bioactive compounds. With this hypothesis, the study used live Fusarium chlamydosporum (FOL7) culture as the inducer during T. harzianum (IF63) growth in broth. Plate assays and gas chromatography-mass spectrometry (GC-MS) analysis were used to characterise the metabolites. Microscopy, pot experiments and, biochemical estimations of the defence-related enzymes in tomato plants established the biostimulant activity of the induced Trichoderma metabolites. Fungal crude metabolites (FCM) obtained from IF63+FOL7 extracts (TF.ex) showed increased antimicrobial activity. TF.ex at 50 μg mL−1, inhibited the FOL7 growth by 68.33% compared to the Trichoderma alone extract. Scanning electron microscopy (SEM) revealed morphological disruption of FOL7 mycelia by TF.ex. GC-MS analysis of the extracts revealed the presence of approximately 64 compounds, of which at least 13 were detected explicitly in TF.ex. Methyl (3-oxo-2-pentylcyclopentyl) acetate (Methyl dihydrojasmonate), a lipid functionally related to jasmonic acid, was the major metabolite (∼21%) present in TF.ex. Tomato seed dressing with TF.ex promoted plant growth and induced systemic resistance against FOL7 compared to alone Trichoderma and Fusarium extracts. The TF.ex treatment increased the superoxide dismutase (33%) and catalase activity by 2.5-fold in tomato plants. The study concludes that fungal secondary metabolites may be modulated by providing appropriate challenges to produce effective metabolite-based biostimulants for agricultural applications.

Gas Chromatography-Mass Spectrometry (GC-MS) Analysis of Scaphium Affine Seed Extract and Assessment of Its Anti-hemorrhoidal Efficacy.

Seeds of plant Scaphium affine are traditionally used by the healers of "India" for the treatment of piles. The primary objective of the study was to assess the anti-hemorrhoidal potential of the ethanolic seed extract of Scaphium affine. After the soxhlet extraction method, the seed extract from Scaphium affine was first submitted to phytochemical standardization and then GC-MS analysis. Rats were given Croton oil and Jatropha oil to develop hemorrhoids, and Scaphium affine seed extract (ESA) was administered orally for 5 days and 3 days, respectively, at doses of 1000 and 500 mg/kg. The Rectoanal coefficient (RAC) was calculated as an inflammatory marker. The hemorrhoidal tissues were also subjected to cytokine profiling, biochemical estimation and histopathology. ESA demonstrated the presence of flavonoids, saponins, phytosterols, phenols, and tannins. GCMS analysis elucidated the presence of hexadecanoic acid 2 hydroxy -1,3 propane diyl ester,9 Octadecanoic acid ethyl ester, Cyclohexane 1,4 di methyl cis, Farnesol isomer,1, E-11, Z-13 octa decatriene, Stigmasterol, N-(5 ethyl -1,3,4-thiadiazol-yl) benzamide, N, N Dinitro 1,3,5,7 tetraza bicyclo 93,3,1) as major phytoconstituents. The results depicted more potent anti-hemorrhoidal activity of ESA at 1000 mg/kg, p.o., which was evident through a decrease in RAC. A significant decline in the levels of IL-1β, IL-6, and TNF-α expression was observed, along with the restoration of altered antioxidants and enzymes. Histopathological analysis confirmed the tissue recovery as it revealed minimal inflammation and decreased dilated blood vessels in treated animals. Based on the results it can be concluded that seeds of Scaphium affine showed significant anti-hemorrhoid agents which may be attributed to their anti-inflammatory and anti-oxidant potential due to the presence of certain phytoconstituents in it. The study also supports the traditional use of seeds of Scaphium affine for the first time in the treatment of hemorrhoids.

Lycopene alleviates BCG-induced depressive phenotypes in mice by disrupting 5-HT3 receptor – IDO1 interplay in the brain

The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents in the brain. Since molecular docking analysis revealed lycopene as a potent 5-HT3 receptor antagonist and IDO1 inhibitor, we hypothesized that lycopene might disrupt the interplay between the 5-HT3 receptor and IDO1 to mitigate depression. In mice, the depression-like phenotypes were induced by inoculating Bacillus Calmette-Guerin (BCG). Lycopene (intraperitoneal; i.p.) was administered alone or in combination with 5-HT3 receptor antagonist ondansetron (i.p.) or IDO1 inhibitor minocycline (i.p.), and the behavioral screening was performed by the sucrose preference test, open field test, tail suspension test, and splash test which are based on the different principles. Further, the brains were subjected to the biochemical analysis of serotonin and its precursor tryptophan by the HPLC. The results showed depression-like behavior in BCG-inoculated mice, which was reversed by lycopene administration. Moreover, prior treatment with ondansetron or minocycline potentiated the antidepressant action of lycopene. Minocycline pretreatment also enhanced the antidepressant effect of ondansetron indicating the regulation of IDO1 activity by 5-HT3 receptor-triggered signaling. Biochemical analysis of brain samples revealed a drastic reduction in the levels of tryptophan and serotonin in depressed animals, which were restored following treatment with lycopene and its combination with ondansetron or minocycline. Taken together, the data from molecular docking, behavioral experiments, and biochemical estimation suggest that lycopene might block the 5-HT3 receptor and consequently inhibit the activity of IDO1 to ameliorate BCG-induced depression in mice.

Studies of the Carbohydrates Content in Tissues of Hamster (Mesocricetus Auratus) Infected with Hookworm (Ancylostoma Ceylanicum)

Hookworm infections are the helminthic infection that affects tropical and subtropical areas. Several laboratory animals have been infected with hookworms. Due to parasitic infection, the structure and function of tissues undergo severe derangements and metabolic disorders. In the present study, a hamster, Mesocricetus auratus was infected with a hookworm, Ancylostoma ceylanicum. Investigation of the Carbohydrate content of A.ceylanicum in M. auratus was studied in control and infected ones. Understanding the level of pathogenicity caused by an A. ceylanicum infection can be aided by examining the total amount of carbohydrates present in the tissues of the host, M. auratus. A biochemical estimation of the total carbohydrate content was made. The brain and spleen were found to have higher carbohydrate contents. There was decreased carbohydrate activity in the kidney, liver, gut, and muscle. The present study depicted the alterations in the total carbohydrate content in various tissues of the host, M. auratus due to the infection of A. ceylanicum. The result of the data obtained in the various tissues due to infection was found to be statistically significant. It was further plotted graphically plotted and interpreted. The research work done in the present study helped to understand the biochemical changes taking place in the host, Mesocricetus auratus due to hookworm, Ancylostoma ceylanicum infection.

Synergistic Effects of Cinnamomum verum and Stingless Bee Honey on Isoproterenol-induced Cardiac Hypertrophic Murine Model

Abstract Objectives: This study aimed to validate the synergistic effects of Cinnamomum verum (C. verum) barks and stingless bee honey (SBH) against cardiac hypertrophy (CH). Materials and Methods: Isoproterenol (ISO-group II-30 mg/kg)-induced cardiac hypertrophic Wistar rats were used in this study. Hypertrophic rats were treated using the reference drug losartan (LOS Group III: 50 mg/kg) and aqueous extracts of C. verum barks and SBH (ACH Group IV: 250 mg/kg and 250 mg/kg). CH was characterized by electrocardiography, hypertrophic indices, and biochemical estimations such as total glucose, protein, albumin, lipid profiles, cardiac marker enzymes, and histopathological studies. Results: Rats received ISO had increased levels of glucose, protein, cholesterol, triglycerides, very low-density lipoprotein, and low-density lipoprotein, coupled with decreased levels of albumin and high-density lipoprotein. These levels were restored to near normal when treated with ACH extracts of the standard drugs. Contrary to the ISO-induced myocardial damaged hearts, ACH extracts had a profound effect compared to LOS, which was also reflected in histopathological studies. Conclusion: These data explicitly reveal that the ACH have a synergistic cardioprotective (antihypertrophic) effect.

Cardioprotective Potentials of Anacardium occidentale Nuts Methanolic Extract in Diabetes-Induced Cardiac Dysfunction in Rats

Background: The unwanted adverse toxicity displayed by synthetic antidiabetic medicine leads to the search for effective natural medicine to combat diabetes complications. This study investigated the cardioprotective of Anacardium occidentale nuts methanolic in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Materials and methods: Forty male adult Wistar were used and fed with HFD for 6 weeks before diabetes induction. The rats were grouped into 5 groups, 8 rats/group. Group I: normal control; Group II: diabetic control; Group III &amp; IV: diabetic rats + 100 mg/kgb.wt &amp; 200 mg/kgb.wt Anacardium occidentale nuts methanolic extract; Group V: diabetic rats + 200 mg/kgb.wt metformin. The rats were sacrificed on the experiment’s last day, blood samples were collected and the hearts were isolated for biochemical parameters estimation. Results: Food intake, water intake, plasmas insulin, Fasting Blood Glucose (FBG), glycosylated hemoglobin (HbA1c), cardiac enzymes, lipid profile, inflammatory cytokines, malondialdehyde, fibrotic marker, caspase-3 in cardiac of diabetic rats were elevated (p &lt; 0.05) significantly. Body weight, cardiac antioxidant, and anti-apoptotic marker levels diminished (p &lt; 0.05) significantly in diabetic rats. 100 mg/kgb.wt &amp; 200 mg/kgb.wt of Anacardium occidentale nuts methanolic extract administration significantly suppressed the plasma insulin, FBG, HbA1c, cardiac lipid profile, cardiac enzymes biomarker, cardiac inflammatory cytokines, cardiac malondialdehyde, cardiac fibrotic marker, cardiac caspase-3, food intake &amp; water intake and increased the body weight, cardiac antioxidant &amp; cardiac anti-apoptotic marker in the diabetic rats. Conclusion: Anacardium occidentale nuts attenuate cardiac injury in diabetes. It could be a natural medicine to manage diabetes-cardiovascular complications.

Anxiety-, and depression-like behavior following short-term finasteride administration is associated with impaired synaptic plasticity and cognitive behavior in male rats

Finasteride, a 5α-Reductase inhibitor, is used to treat male pattern baldness and benign prostatic hyperplasia. Several clinical studies show that chronic finasteride treatment induces persistent depression, suicidal thoughts and cognitive impairment and these symptoms are persistent even after its withdrawal. Previous results from our lab showed that repeated administration of finasteride for six days induces depression-like behavior. However, whether short-term finasteride administration induces anxiety-like behavior and memory impairment and alters synaptic plasticity are not known, which formed the basis of this study. Finasteride was administered to 2–2.5 months old male Wistar rats for six days and subjected to behavioral evaluation, biochemical estimation and synaptic plasticity assessment. Anxiety-like behavior was evaluated in the elevated plus maze (EPM), open field test (OFT), light/dark test (LDT), and novelty suppressed feeding test (NSFT), and learning and memory using novel object recognition test (NORT) and novel object location test (NOLT) and depression-like behavior in the sucrose preference test (SPT). Synaptic plasticity in the hippocampal Schaffer collateral-CA1 was evaluated using slice field potential recordings. Plasma corticosterone levels were estimated using ELISA. Finasteride administration induced anxiety-like behavior in the EPM, OFT, LDT and NSFT, and depression-like behavior in the SPT. Further, finasteride induced hippocampal dependent spatial learning and memory impairment in the NOLT. In addition, finasteride decreased basal synaptic plasticity and long-term potentiation (LTP) in the hippocampus. A trend of increased plasma corticosterone levels was observed following repeated finasteride administration. These results indicate the potential role of corticosterone and synaptic plasticity in finasteride-induced effects and further studies will pave way for the development of novel neurosteroid-based therapeutics in neuropsychiatric diseases.