Retraction of "Toxicological Screening of 4-Phenyl-3,4-dihydrobenzo[h]quinolin-2(1H)-one: A New Potential Candidate for Alzheimer's Treatment".

[This retracts the article DOI: 10.1021/acsomega.1c00654.].

A remarkable study to unveil the relationship between fluorescence life time decay(ns) and nonlinear optical parameters of series of porphyrin and polyoxometalates hybrids.

Relationship between excited state dynamics and nonlinear optical (NLO) parameters is very unique. Herein, three different polyoxometalates (POMs) namely WD-POM (Wells-Dawson POM) based porphyrin hybrids WDPOM3PyP, Trans-2WDPOM2PyP, and 3WDPOMPyP (having one, two, and three WD-POM respectively), and their porphyrin precursors with (Trishydroxyl amino methane) namely Tris3PyP, Trans-2Tris2PyP, and 3TrisPyP respectively have been used for the study. Fluorescence decay and Z-scan studies by using nanosecond (ns) time span conveys the corresponding lifespan for each excited state, along with the NLO analysis respectively. The calculated lifetime data were found in the range of 3WDPOMPyP (τ1 = 5.65 ns), Trans-2WDPOM2PyP (τ1 = 2.21 ns), and WDPOM3PyP (τ1 = 1.96 ns). Third order NLO measurements represented that WDPOM3PyP showed better NLO response (χ3 = 2.26 × 10-10esu and ß = 1.54 × 10-5 esu) as compared to Trans-2WDPOM2PyP (χ3 = 1.73 × 10-10 esu and ß = 1.53 × 10-5 esu), and 3WDPOMPyP (χ3 = 1.55 × 10-10 esu and ß = 0.65 × 10-5 esu) obtained at wavelength of 532 nm. Electrochemical studies have shown that the minor energy differences between the singlet and triplet excited states are responsible for intercrossing system (ISC) that helps in the transfer of electrons from porphyrin moiety to WD-POM. By absorbing a photon, the excited species were produced causing an initial charge transfer. This charge transfer state undergoes an electron transfer decaying to the lowest triplet state, and singlet state causing an increase in NLO. The obtained results indicated potential uses in photonic and all-optical switching devices.

Biochemical properties and biological potential of Syzygium heyneanum with antiparkinson's activity in paraquat induced rodent model.

Syzygium heyneanum is a valuable source of flavonoids and phenols, known for their antioxidant and neuroprotective properties. This research aimed to explore the potential of Syzygium heyneanum ethanol extract (SHE) in countering Parkinson's disease. The presence of phenols and flavonoids results in SHE displaying an IC50 value of 42.13 when assessed in the DPPH scavenging assay. Rats' vital organs (lungs, heart, spleen, liver, and kidney) histopathology reveals little or almost no harmful effect. The study hypothesized that SHE possesses antioxidants that could mitigate Parkinson's symptoms by influencing α-synuclein, acetylcholinesterase (AChE), TNF-α, and IL-1ß. Both in silico and in vivo investigations were conducted. The Parkinson's rat model was established using paraquat (1 mg/kg, i.p.), with rats divided into control, disease control, standard, and SHE-treated groups (150, 300, and 600 mg/kg) for 21 days. According to the ELISA statistics, the SHE treated group had lowers levels of IL-6 and TNF-α than the disease control group, which is a sign of neuroprotection. Behavioral and biochemical assessments were performed, alongside mRNA expression analyses using RT-PCR to assess SHE's impact on α-synuclein, AChE, TNF-α, and interleukins in brain homogenates. Behavioral observations demonstrated dose-dependent improvements in rats treated with SHE (600 > 300 > 150 mg/kg). Antioxidant enzyme levels (catalase, superoxide dismutase, glutathione) were significantly restored, particularly at a high dose, with notable reduction in malondialdehyde. The high dose of SHE notably lowered acetylcholinesterase levels. qRT-PCR results indicated reduced mRNA expression of IL-1ß, α-synuclein, TNF-α, and AChE in SHE-treated groups compared to disease controls, suggesting neuroprotection. In conclusion, this study highlights Syzygium heyneanum potential to alleviate Parkinson's disease symptoms through its antioxidant and modulatory effects on relevant biomarkers.

NMDA receptor modulation by Esculetin: Investigating behavioral, biochemical and neurochemical effects in schizophrenic mice model.

Schizophrenia, a global mental health disorder affecting approximately 1 % of the population, is characterized by neurotransmitter dysregulation, particularly dopamine, serotonin, and glutamate. Current antipsychotic therapies, despite their efficacy, are accompanied by adverse effects, which has motivated researchers to investigate more secure substitutes. This study examines the potential antipsychotic effects of esculetin, a natural coumarin derivative recognized for its wide-ranging pharmacological activities (anti-inflammatory, antioxidant, anti-pathogenic, anticancer, and neuroprotective), in animal model of schizophrenia induced by ketamine. In order to induce disease, acute and chronic ketamine administration was performed on Swiss albino mice, supplemented with esculetin (as the test substance) and clozapine (as the reference standard). Behavioral studies and biochemical assays were performed to evaluate positive, negative, and cognitive symptoms of schizophrenia, as well as antioxidant and oxidant levels in various brain regions. Esculetin demonstrated significant improvements in behavioral symptoms, attenuated oxidative stress and neuroinflammation, and modulated neurotransmitter levels. Afterwards, ELISA was performed to evaluate levels of schizophrenia biomarkers AChE, BDNF. Moreover, proinflammatory cytokines (IL-6 and TNF-α) and NF-κB were also determined. Histopathological parameters of under study brain parts i.e., hippocampus, cortex and striata were also assessed. Esculetin and clozapine significantly (***p < 0.0001) altered ketamine induced behavioral symptoms and attenuated ketamine induced oxidative stress and neuroinflammation. Additionally, esculetin significantly (***p < 0.0001) altered neurotransmitter (dopamine, serotonin, glutamate) levels. ELISA analysis depicts ketamine reduced BDNF levels in hippocampus, cortex and striata while esculetin significantly (***p < 0.0001) increased BDNF levels in under study three parts of brain. Histopathological changes were seen in test groups. The findings of this study indicate that esculetin may have therapeutic potential in the treatment of schizophrenia induced by ketamine. As a result, esculetin may have the potential to be utilized as a treatment for schizophrenia.

Sensing potential of C6N8 for ammonia (NH3) and nitrogen triflouride (NF3): A DFT study.

The detection of toxic gases (NH3 and NF3) in regulating and monitoring air quality in the atmosphere has drawn a lot of attention. Herein, we explored a novel material (C6N8) for the detection of the important but toxic gases (NH3 and NF3). We investigated the interactions of the NH3 and NF3 with C6N8 through DFT at B3LYP, ωB97XD, and non-DFT M06-2X. Counterpoise interaction energy values (Eint. cp.) of NH3@C6N8 and NF3@C6N8 are -0.45 eV and -3.51 eV (for B3LYP), -0.42 eV and 2.11 eV (for ωB97XD) and -0.44 eV and -3.41eV (for M06-2X), respectively. Complexes having the most stable configurations were then subjected to further analyses including frontier molecular orbitals, H-L gap, and conductivity of complexes. An increase in the H-L gap in complexes (NH3@C6N8 and NF3@C6N8) is observed. The conductivity of NH3@C6N8 and NF3@C6N8 decreases as compared to C6N8. A considerable change in dipole moment was seen in C6N8 before and after complex formation. This is because of the shifting of charge between C6N8 and gases (NH3 and NF3). CHELPG and NBO charge analysis were used to evaluate the amount of charge transfer between C6N8 and gases. These analyses demonstrate that NH3 and NF3 withdraw electron density from C6N8. It was found that NH3 tends to be physically adsorbed on C6N8 while NF3 adsorbs chemically on C6N8. NCI and QTAIM analyses were performed to investigate the kind of interactions between the surface (C6N8) and gases (NH3 and NF3). Furthermore, the recovery time of NH3@C6N8 and NF3@C6N8 shows that C6N8 can be a better choice for sensing NH3 and NF3 gases.

Current Updates on the Role of MicroRNA in the Diagnosis and Treatment of Neurodegenerative Diseases.

BACKGROUND: MicroRNAs (miRNA) are small noncoding RNAs that play a significant role in the regulation of gene expression. The literature has explored the key involvement of miRNAs in the diagnosis, prognosis, and treatment of various neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The miRNA regulates various signalling pathways; its dysregulation is involved in the pathogenesis of NDD. OBJECTIVE: The present review is focused on the involvement of miRNAs in the pathogenesis of NDD and their role in the treatment or management of NDD. The literature provides comprehensive and cutting-edge knowledge for students studying neurology, researchers, clinical psychologists, practitioners, pathologists, and drug development agencies to comprehend the role of miRNAs in the NDD's pathogenesis, regulation of various genes/signalling pathways, such as α-synuclein, P53, amyloid-ß, high mobility group protein (HMGB1), and IL-1ß, NMDA receptor signalling, cholinergic signalling, etc. Methods: The issues associated with using anti-miRNA therapy are also summarized in this review. The data for this literature were extracted and summarized using various search engines, such as Google Scholar, Pubmed, Scopus, and NCBI using different terms, such as NDD, PD, AD, HD, nanoformulations of mRNA, and role of miRNA in diagnosis and treatment. RESULTS: The miRNAs control various biological actions, such as neuronal differentiation, synaptic plasticity, cytoprotection, neuroinflammation, oxidative stress, apoptosis and chaperone-mediated autophagy, and neurite growth in the central nervous system and diagnosis. Various miRNAs are involved in the regulation of protein aggregation in PD and modulating ß-secretase activity in AD. In HD, mutation in the huntingtin (Htt) protein interferes with Ago1 and Ago2, thus affecting the miRNA biogenesis. Currently, many anti-sense technologies are in the research phase for either inhibiting or promoting the activity of miRNA. CONCLUSION: This review provides new therapeutic approaches and novel biomarkers for the diagnosis and prognosis of NDDs by using miRNA.

The entrancing role of dietary polyphenols against the most frequent aging-associated diseases.

Aging, a fundamental physiological process influenced by innumerable biological and genetic pathways, is an important driving factor for several aging-associated disorders like diabetes mellitus, osteoporosis, cancer, and neurodegenerative diseases including Alzheimer's and Parkinson's diseases. In the modern era, the several mechanisms associated with aging have been deeply studied. Treatment and therapeutics for age-related diseases have also made considerable advances; however, for the effective and long-lasting treatment, nutritional therapy particularly including dietary polyphenols from the natural origin are endorsed. These dietary polyphenols (e.g., apigenin, baicalin, curcumin, epigallocatechin gallate, kaempferol, quercetin, resveratrol, and theaflavin), and many other phytochemicals target certain molecular, genetic mechanisms. The most common pathways of age-associated diseases are mitogen-activated protein kinase, reactive oxygen species production, nuclear factor kappa light chain enhancer of activated B cells signaling pathways, metal chelation, c-Jun N-terminal kinase, and inflammation. Polyphenols slow down the course of aging and help in combatting age-linked disorders. This exemplified in the form of clinical trials on specific dietary polyphenols in various aging-associated diseases. With this context in mind, this review reveals the new insights to slow down the aging process, and consequently reduce some classic diseases associated with age such as aforementioned, and targeting age-associated diseases by the activities of dietary polyphenols of natural origin.

Curcuminoids-enriched extract and its cyclodextrin inclusion complexes ameliorates arthritis in complete Freund's adjuvant-induced arthritic mice via modulation of inflammatory biomarkers and suppression of oxidative stress markers.

Curcuma longa extract and its marker curcuminoids have potential use in inflammatory conditions. However, curcuminoids solubility and bioavailability are major hindrances to their bioactivity. The current study investigated green extraction-based curcuminoids-enriched extract (CRE) prepared from C. longa and its cyclodextrin inclusion complexes, i.e., binary inclusion complexes (BC) and ternary inclusion complexes (TC), in complete Freund's adjuvant (CFA)-induced mice for their comparative anti-arthritic efficacy. CRE, BC, and TC (2.5 and 5 mg/kg) with the standard drug diclofenac sodium (13.5 mg/kg) were orally administered to mice for 4 weeks. Variations in body weight, hematological and biochemical parameters, along with gene expression analysis of arthritis biomarkers, were studied in animals. The histopathological analysis and radiographic examination of joints were also performed. CRE, BC and TC treatment significantly restored the arthritic index, histopathology and body weight changes. The concentration of C-reactive protein, rheumatoid factor and other liver function parameters were significantly recovered by curcuminoids formulations. The pro-inflammatory cytokines (NF-κB, COX-2, IL-6, IL-1ß, and TNF-α) gene expression was considerably (p < 0.001) downregulated, while on the other side, the anti-inflammatory genes IL-4 and IL-10 were upregulated by the use of CRE and its complexes. The concentration of antioxidant enzymes was considerably (P < 0.001) recovered by CRE, BC and TC with marked decrease in lipid peroxidation, erosion of bone, inflammation of joints and pannus formation in comparison to arthritic control animals. Therefore, it is concluded that green CRE and its cyclodextrin formulations with enhanced solubility could be considered as an applicable therapeutic choice to treat chronic polyarthritis.

Pharmacological and toxicological evaluation of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxoide against haloperidol induced Parkinson like symptoms in animal model: In-vitro and in-vivo studies.

In Parkinson's disease (PD), degradation of dopaminergic neurons in substantia nigra causes striatal deficiency of dopamine, which results in tremors, bradykinesia with instability in posture, rigidity and shuffled gait. Prevalence of PD increases with age as from 65 to 85 years. In an attempt to devise targeted safe therapy, nanoparticles of methyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (MBD) (MBDN), were prepared and their acute toxicity and safety was evaluated. Thirty-six healthy albino mice were randomly divided into six groups (n = 6): normal control, diseased control, standard (levodopa/carbidopa (100/25 mg/kg) and the remaining three groups were administered 1.25, 2.5 and 5 mg/kg MBDN during 21 days study. Except control, all mice, were injected haloperidol (1 mg/ kg i.p.) 1-h prior to treatment to induce PD. Acute toxicity test showed, no effect of MBDN on lipid profile, brain, renal and liver function and histoarchitecture of kidney, liver and heart, except decreased (p < 0.05) platelet count. Behavioral studies showed significant improvement (p < 0.001) in motor function and reduction of oxidation status in a MBDN in a dose dependent manner. Thus, the study findings revealed significance of MBDN as a selective MAO-B inhibitor for the improvement of Parkinson's symptoms in animal model.

Ginsenosides in cancer: Targeting cell cycle arrest and apoptosis.

Despite the existence of extensive clinical research and novel therapeutic treatments, cancer remains undefeated and the significant cause of death worldwide. Cancer is a disease in which growth of cells goes out of control, being also able to invade other parts of the body. Cellular division is strictly controlled by multiple checkpoints like G1/S and G2/M which, when dysregulated, lead to uncontrollable cell division. The current remedies which are being utilized to combat cancer are monoclonal antibodies, chemotherapy, cryoablation, and bone marrow transplant etc. and these have also been greatly disheartening because of their serious adverse effects like hypotension, neuropathy, necrosis, leukemia relapse and many more. Bioactive compounds derived from natural products have marked the history of the development of novel drug therapies against cancer among which ginsenosides have no peer as they target several signaling pathways, which when abnormally regulated, lead to cancer. Substantial research has reported that ginsenosides like Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2 etc. can prevent and treat cancer by targeting different pathways and molecules by induction of autophagy, neutralizing ROS, induction of cancerous cell death by controlling the p53 pathway, modulation of miRNAs by decreasing Smad2 expression, regulating Bcl-2 expression by normalizing the NF-Kb pathway, inhibition of inflammatory pathways by decreasing the production of cytokines like IL-8, causing cell cycle arrest by restricting cyclin E1 and CDC2, and induction of apoptosis during malignancy by decreasing ß-catenin levels etc. In this review, we have analyzed the anti-cancer therapeutic potential of various ginsenoside compounds in order to consider their possible use in new strategies in the fight against cancer.

Administration of α-lipoic acid and silymarin attenuates aggression by modulating endocrine, oxidative stress and inflammatory pathways in mice.

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice.

Dose Dependent Effects of Aqueous Extract of Garcinia cambogia Desr. Against Letrozole Induced Polycystic Ovarian Syndrome in Female Adult Rats With Possible Mechanisms Exploration.

Background: Polycystic ovarian syndrome (PCOS) is an endocrine metabolic disorder of women. Purpose: This study aimed to explore the potential of aqueous extract of Garcinia cambogia Desr. (AEGC) in PCOS. Methodology: The HPLC was used to determine the phytoconstituents present in Garcinia cambogia. Thirty adult female albino rats were divided into 6 groups: Normal control (NC) disease Control (PCOS; letrozole 1 mg/kg), plant extract (AEGC 100, 300, 500 mg/kg) and standard (metformin; 20 mg/kg). Disease was confirmed by vaginal smear cytology. After 10 weeks, animals were euthanized, ovaries dissected for histopathology, blood collected for hormonal and biochemical analysis. Results: HPLC analysis showed the presence of phenolic contents; chlorogenic acid, gallic acid, coumaric acid while flavonoid contents were quercetin, kaempferol, and rutin. After treatment, there was dose dependent reduction of weight, ovarian cysts, improvement of follicle growth. DPPH radical scavenging percentage was 67.89%. Hormonal analysis showed a significant improvement (P < .05) in follicle stimulating hormone (FSH), estrogen, and progesterone while a reduction in testosterone, luteinizing hormone (LH) and insulin level. Antioxidant enzymatic markers were significantly (P < .05) increased. Lipid profile and LFTs were also improved. Conclusions: The study validated the potential of Garcinia cambogia in the management of PCOS.

Toxicity profiling of Burgmansia aurea Lagerh. Leaves using acute and sub-acute toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Toxicity studies in appropriate animal models are an integral and very important component of pre-clinical studies in drug development. Brugmansia aurea lagerh. is used for both medicinal and non-medical purposes, including treating skin infections, different types of physical discomfort, inflammation, cough, hallucinations, and evil protection. AIM OF THE STUDY: This study was designed to detect any hazardous effects of B. aurea on animals and find out its LD50. MATERIALS & METHODS: An acute toxicity study was performed to find out the LD50 value and sub-acute toxicity study was performed to find out the toxicity on repeated dose administration till 28 days. Both studies were performed according to the organization of economic cooperation and development (OECD) 425 and 407 respectively. For the acute oral toxicity study, animals were divided into two groups, group I normal control (NC) and group II received a 2000mg/kg dose of B.aurea leaves extract. In the sub-acute toxicity study, male and female animals were divided into eight groups, I-IV for males and V-VIII for females received control, 100, 200 & 400mg/kg B. aurea leaves extract respectively. Hematological and biochemical markers were estimated at the end of each study. RESULTS: Results revealed that no mortality and morbidity were observed in acute oral as well as sub-acute toxicity studies. Oxidative stress markers were increased significantly in all organs of the treatment groups in both studies. Animals significantly decreased their food and water intake in an acute oral toxicity study. A slight difference in renal function tests was observed in the acute oral toxicity study when compared with the normal control group. No significant change in histopathology was observed in both studies on selected organs. CONCLUSION: This study concluded that B. aurea can be safely used for pharmacological purposes.

The wound healing potential of Hedychium spicatum Sm. and Zinnia peruviana (L.) ethanolic extracts against excision wound model in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants used for wound healing, are key to unlock the doors for combating the resistance of pathogens by provision of new source of compounds. AIM OF THE STUDY: This study is aimed to evaluate and compare the wound healing properties of ethanolic extract of Hedychium spicatum Sm. rhizome and of Zinnia peruviana's leaves and roots. MATERIALS & METHODS: Albino rats were divided into 10 groups (n = 6), control, positive control, negative control, untreated, Hedychium spicatum Sm. (125 mg/kg), Hedychium spicatum Sm (250 mg/kg), Zinnia peruviana (L.)(Leaves) (125 mg/kg), Zinnia peruviana (L.) (Leaves) (250 mg/kg), Zinnia peruviana (L.)(Roots) (125 mg/kg), Zinnia peruviana (L.)(Roots) (250 mg/kg) respectively. Excision wound of 1.5 cm wound was inflicted on the dorsal side of each rat except control group. 5% CMC gel, fusidic acid and extract gels were applied topically once daily on the wound area which was measured at intervals of 3 days until epithelization and complete wound closure. Different biochemical markers were analyzed in both blood and skin to validate the wound healing potential of these plants. RESULTS: Topical application of an ethanolic extract of Hedychium spicatum Sm. (250 mg/kg) had significant (p ˂ 0.001) rate of wound healing and reduced epithelization period. Marked amelioration of hydroxyproline content, remarkable results on histopathological changes, reduction in oxidative stress was observed with Hedychium spicatum Sm. ethanolic extract at dose level of 250 mg/kg in comparison with untreated group. CONCLUSION: This study concluded that the Hedychium spicatum Sm. rhizome ethanolic extract gel is effective in wound repair and may possess potential for the development of dermatologic preparation for topical diseases.

Pharmacological screening of silibinin for antischizophrenic activity along with its acute toxicity evaluation in experimental animals.

Silibinin (SIL), a flavolignan extracted from the medicinal plant "silybum marianum (milk thistle)", has traditionally been used to treat liver disease. This phytochemical has displayed neuroprotective properties, its activity against schizophrenia is not elucidated. The present study was designed to evaluate the antipsychotic potential of silibinin and probe its toxic potential. The acute oral toxicity study was assessed as per OECD 425 guidelines. Animals were divided into two groups of female rats (n = 6): one group served as the normal control and the other group received a 2,000 mg/kg dose of SIL. We also evaluated the antipsychotic potential of SIL. To this end, animals were divided into six groups (n = 10) of mice for both the preventive and curative protocols. Group I (CMC 1 mL/kg) served as the normal control and received CMC 1 mL/kg; group II was the diseased group treated with ketamine (10 mg/kg) i.p; group III was the standard group treated with clozapine 1 mg/kg; groups IV, V, and VI served as the treatment groups, receiving SIL 50, 100, and 200 mg/kg, respectively, orally for both protocols. Improvement in positive symptoms of the disease was evaluated by stereotypy and hyperlocomotion, while negative symptoms (behavioral despair) were determined by a forced swim test and a tail suspension test in the mice models. The results suggested that the LD50 of SIL was greater than 2,000 mg/kg. Moreover, SIL prevented and reversed ketamine-induced increase in stereotypy (p < 0.001) and behavioral despair in the forced swim and tail suspension tests (p < 0.001). Taken together, the findings suggest that silibinin is a safe drug with low toxicity which demonstrates significant antipsychotic activity against the positive and negative symptoms of schizophrenia.

The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson's disease animal model.

Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.

Sarcococca saligna ameliorated D-galactose induced neurodegeneration through repression of neurodegenerative and oxidative stress biomarkers.

Sarcococca saligna is a valuable source of bioactive secondary metabolites exhibiting antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities. The study was intended to explore the therapeutic pursuits of S. saligna in amelioration of cognitive and motor dysfunctions induced by D-galactose and linked mechanistic pathways. Alzheimer's disease model was prepared by administration of D-galactose subcutaneous injection100 mg/kg and it was treated with rivastigmine (100 mg/kg, orally) and plant extract for 42 days. Cognitive and motor functions were evaluated by behavioral tasks and oxidative stress biomarkers. Level of acetylcholinesterase, reduced level of glutathione, protein and nitrite level, and brain neurotransmitters were analyzed in brain homogenate. The level of apoptosis regulator Bcl-2, Caspases 3 and heat shock protein HSP-70 in brain homogenates were analyzed by ELISA and colorimetric method, respectively. AChE, IL-1ß, TNF-α, IL-1α and ß secretase expressions were analyzed by RT-PCR. S. saligna dose dependently suppressed the neurodegenerative effects of D-galactose induced behavioral and biochemical impairments through modulation of antioxidant enzymes and acetylcholinesterase inhibition. S. saligna markedly (P < 0.05) ameliorated the level of brain neurotransmitters, Bcl-2, HSP-70 and Caspases-3 level. S. saligna at 500-1000 mg/kg considerably recovered the mRNA expression of neurodegenerative and neuro-inflammatory biomarkers, also evident from histopathological analysis. These findings suggest that S. saligna could be applicable in cure of Alzheimer's disease.

Antidepressant activity of phytochemicals of Mangifera indica seeds assisted by integrated computational analysis.

Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. The depression model was prepared by exposing mice to various stressors from 9:00 am to 2:00 pm during 42 days study period. MIS extract and fluoxetine were given daily for 30 min before exposing animals to stressors. ADP was evaluated by various behavioural tests and biochemical analysis. Results showed increased physical activity in mice under behavioural tests, plasma nitrite and malondialdehyde (MDA) levels and monoamine oxidase A (MAO-A) activity decreased dose-dependently in MIS treated mice and superoxide dismutases (SOD) levels increased in treated groups as compared to disease control. With the peculiar behaviour and significant interactions of the functional residues of target proteins with selected ligands along with the best absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, it is concluded that catechin could be the best MAO-A inhibitor at a binding energy of -8.85 kcal/mol, and two hydrogen bonds were generated with Cys406 (A) and Gly443 (A) residues of the active binding site of MAO-A enzyme. While catechin at -6.86 kcal/mol generated three hydrogen bonds with Ala263 (A) and Gly434 (A) residues of the active site of monoamine oxidase B (MAO-B) enzyme and stabilized the best conformation. Therefore, it is highly recommended to test the selected lead-like compound catechin in the laboratory with biological system analysis to confirm its activity as MAO-A and MAO-B inhibitors so it can be declared as one of the novel therapeutic options with anti-depressant activity. Our findings concluded that M. indica seeds could be a significant and alternative anti-depressant therapy.

Inhibition of Oxidative Stress and the NF-κB Pathway by a Vitamin E Derivative: Pharmacological Approach against Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder. In this study, PD was induced via (ip) injection of haloperidol (1 mg/kg/day). Animals were divided into seven groups (n = 70). Group I received the vehicle carboxymethylcellulose (CMC; 0.5%), group II was treated with designated 1 mg/kg haloperidol, and group III received the standard drug Sinemet (100 mg/kg), while groups IV-VII received a tocopherol derivative (Toco-D) at dose levels of 5, 10, 20, and 40 mg/kg, respectively, via the oral route. All groups received haloperidol for 23 consecutive days after their treatments except the control group. The improvement in locomotor activity and motor coordination was evaluated by using behavioral tests. Oxidative stress markers, neurotransmitters, and monoamine oxidase B (MAO-B) as well as NF-κB levels in the whole brain were measured. mRNA expression analysis of α-synuclein was carried out using the PCR technique. Toco-D at 20 mg/kg showed the maximum improvement in locomotor activity. The levels of antioxidant enzymes and neurotransmitters were also increased by the treatment with Toco-D. Inflammatory cytokine levels and mRNA expression of α-synuclein were decreased by Toco-D in treated animals. This study concluded that Toco-D might be effective in the improvement of locomotor activity and motor coordination in haloperidol-induced PD.

Wound Healing Potential and In Silico Appraisal of Convolvulus arvensis L. Methanolic Extract.

Convolvulus arvensis L. is rich in phenolic compounds and traditionally used to treat wounds, skin ulcer, and inflammation. The current study is aimed at scientifically potentiating its traditional wound healing use. The methanolic extract of C. arvensis stem (CaME) was analyzed for HPLC and GC-MS analyses. The binding modes of active compounds were investigated against protein targets glycogen synthase kinase-3ß (GSK-3ß), transforming growth factor-beta (TGF-ß), c-myc, and ß-catenin by molecular docking followed by molecular dynamic simulations which revealed some conserved mode of binding as reported in crystal structures. The antioxidant potential of CaME was evaluated by in vitro methods such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, and ferric reducing power assays. Ointment formulations of 10 and 20% CaME were applied topically and evaluated for wound healing potency against the excisional wound on the skin of Wistar rats. Gentamycin (0.1%) served as standard therapy. The healing process was observed for 20 days in the form of wound size and epithelialization followed by histopathological evaluation of the wound area. Chemical characterization showed the presence of 7-hexadecenoic acid, 2-hexadecylicosan-1-ol, quercetin, gallic acid, ferulic acid, and other compounds. The plant extract exhibited significant in vitro antioxidant activity. The animals treated with 10% ointment showed moderate healing, whereas the treatment with 20% CaME revealed healing potential comparable to the standard 0.1% gentamycin as coevidenced from histopathological evaluation of skin. The study corroborates promising potential of C. arvensis on the healing of wounds, which possibly will be attributed to its antioxidant activity, fatty acids, quercetin, and gallic and caffeic acids, and binding potential of its phytoconstituents (phenolic acids) with wound healing targets.