Effect of green Fe2O3 nanoparticles in controlling Fusarium fruit rot disease of loquat in Pakistan.

The subtropical fruit known as the loquat is prized for both its flavour and its health benefits. The perishable nature of loquat makes it vulnerable to several biotic and abiotic stressors. During the previous growing season (March-April 2021), loquat in Islamabad showed signs of fruit rot. Loquat fruits bearing fruit rot symptoms were collected, and the pathogen that was causing the disease isolated and identified using its morphology, microscopic visualisation, and rRNA sequence. The pathogen that was isolated was identified as Fusarium oxysporum. Green synthesized metallic iron oxide nanoparticles (Fe2O3 NPs) were employed to treat fruit rot disease. Iron oxide nanoparticles were synthesized using a leaf extract of the Calotropis procera. Characterization of NPs was performed by different modern techniques. Fourier transform infrared spectroscopy (FTIR) determined the existence of stabilizing and reducing compounds like phenol, carbonyl compounds, and nitro compounds, on the surface of Fe2O3 NPs. X-ray diffraction (XRD) explained the crystalline nature and average size (~49 nm) of Fe2O3 NPs. Energy dispersive X-ray (EDX) exhibited Fe and O peaks, and scanning electron microscopy (SEM) confirmed the smaller size and spherical shape of Fe2O3 NPs. Following both in vitro and in vivo approaches, the antifungal potential of Fe2O3 NPs was determined, at different concentrations. The results of both in vitro and in vivo analyses depicted that the maximum fungal growth inhibition was observed at concentration of 1.0 mg/mL of Fe2O3 NPs. Successful mycelial growth inhibition and significantly reduced disease incidence suggest the future application of Fe2O3 NPs as bio fungicides to control fruit rot disease of loquat.

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.

Curative potential of Populus ciliata Wall ex. Royle extract against adjuvant-induced arthritis and peripheral neuropathy in Wistar rats.

Populus ciliata (PCCR) is traditionally used to treat muscular swelling, inflammation, pain, and fever. The current study was designed to validate the potential of aqueous ethanolic extract of the plant against inflammation, peripheral neuropathy, and pain in arthritic rats. The PCCR was chemically characterized by gas chromatography-mass spectroscopy and high-performance liquid chromatography. In vitro antioxidant, and in vitro anti-inflammatory assays were carried out on PCCR. For anti-arthritic potential, Wistar rats' rear paws were injected with 0.1 ml Complete Freund's Adjuvant using methotrexate (3 mg/kg/week) as standard control. PCCR at 100, 200, and 400 mg/kg was given orally to arthritic rats for 21 days. The PCCR exhibited significant inhibition of bovine serum albumin denaturation (IC-50: 202.1 µg/ml), egg albumin denaturation (IC-50:553.5 mg/ml) and RBC membrane stabilization (IC-50: 122.5 µg/ml) and antioxidant (IC-50 = 49.43 µg/ml) activities. The PCCR notably decreased the paw diameter and increased body weight of treated arthritic animals as equated to diseased control. The treatment notably (p < 0.05-0.0001) decreased malondialdehyde, and increased superoxide dismutase, reduced glutathione, and catalase in the liver and sciatic nerve homogenate in compared to diseased rats. The PCCR treatment remarkably (p < 0.05-0.0001) regulated the levels of nor-adrenaline and serotonin in sciatic nerve in contrast to diseased rats. Treatment with PCCR improved the motor activity, pain, ligament degeneration, and synovial hyperplasia in arthritic rats. Moreover, PCCR significantly (p < 0.01-0.0001) decreased the IL-6 and TNF-α. It is evident from the current study that PCCR had ameliorated polyarthritis and peripheral neuropathy through reduction of inflammatory markers, and improvement of oxidative stress might be due to presence of phenolic acids, flavonoids, phytosterols, and other fatty acids.

Evaluation of Antidiabetic Activity of Oxadiazole Derivative in Rats.

The oxadiazole ring has long been used for the treatment of several diseases. This study aimed to analyze the antihyperglycemic and antioxidant roles of the 1,3,4-oxadiazole derivative with its toxicity. Diabetes was induced through intraperitoneal administration of alloxan monohydrate at 150 mg/kg in rats. Glimepiride and acarbose were used as standards. Rats were divided into groups of normal control, disease control, standard, and diabetic rats (treated with 5, 10, and 15 mg/kg of 1,3,4-oxadiazole derivative). After 14 days of oral administration of 1,3,4-oxadiazole derivatives (5, 10, and 15 mg/kg) to the diabetic group, the blood glucose level, body weight, glycated hemoglobin (HbA1c), insulin level, antioxidant effect, and histopathology of the pancreas were performed. The toxicity was measured by estimating liver enzyme, renal function, lipid profile, antioxidative effect, and liver and kidney histopathological study. The blood glucose and body weight were measured before and after treatment. Alloxan significantly increased blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine. In contrast, body weight, insulin level, and antioxidant factors were reduced compared to the normal control group. Treatment with oxadiazole derivatives showed a significant reduction in blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine as compared to the disease control group. The 1,3,4-oxadiazole derivative significantly improved body weight, insulin level, and antioxidant factors compared to the disease control group. In conclusion, the oxadiazole derivative showed potential antidiabetic activity and indicated its potential as a therapeutic.

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.

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.

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.

Antidiabetic Potential and Antioxidant Activity of Olea europaea subsp. Cuspidata (Indian Olive) Seed Extracts.

The aim of the present study was to evaluate the antioxidant and antidiabetic potential of Indian olive seed extracts. Plant seeds were sequentially extracted with n-hexane, chloroform, methanol, and water. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging and alpha-amylase inhibitory activities of extracts were carried out. Olea europaea methanolic extract (MEOE) and aqueous extract (AEOE) were orally administered to normoglycemic and alloxan-treated diabetic rats so as to determine their hypoglycemic effect. High-performance liquid chromatography (HPLC) analysis showed gallic acid, ferulic acid, quercetin, and vanillic acid in MEOE. It was found that the methanolic and aqueous extracts exhibited the maximum DPPH and alpha-amylase inhibition activities, respectively. MEOE and AEOE exerted a significant decline in the fasting blood sugar in diabetic animals (p < 0.05); however, they did not cause hypoglycemia in nondiabetic animals. Treatment with MEOE and AEOE reduced the aggravated liver and kidney function biomarkers. Aggravated levels of oxidative stress biomarkers including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and malondialdehyde (MDA) were restored by treatment with MEOE. Moreover, MEOE improved the count of islets of Langerhans in the pancreas, fatty changes, and enlarged sinusoidal spaces in the liver and necrosis of the glomerulus and tubular cells of the kidney in diabetic rats. This study showed that the African olive seed extract effectively managed experimental diabetes and restored the normal functions and histology of the liver and kidney in diabetic rats through the reduction of oxidative stress.

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism.

Background: Ethnopharmacological relevance: Brugmansia, a genus of the Solanaceae family, has historically been utilized in many different parts of the world as an anti-inflammatory for treating skin infections, wounds, and bodily aches and pains. The current study aimed to investigate the potential benefits of a methanolic extract of Brugmansia aurea in the management of diabetes and underlying complications in alloxanized-induced diabetic rats. Materials and methods: Animals were divided into nine groups (n = 6). Four groups received different standard oral hypoglycemic agents; three groups received 100, 200, and 400 mg/kg of B. aurea leaf extract for six consecutive weeks, and the remaining two were normal and disease control groups. All groups received alloxan (150 mg/kg) except for the normal control. Only those animals whose glucose levels were raised to 200 mg/dl were selected for the study. After a 6-week dosage period, various biochemical parameters, as well as HbA1c, antioxidant profile, oral glucose tolerance test (OGTT), insulin sensitivity, histopathology, and insulin resistance, were measured and compared with the untreated diabetic group. Results: Brugmansia aurea leaf extract at a dose of 400 mg/kg showed potent antidiabetic activity by reducing blood glucose levels (p < 0.001) after 6 weeks of treatment. OGTT data showed that B. aurea exhibited significant (p < 0.001) glucose tolerance by significantly reducing blood glucose levels in just 2 h post-treatment. Other tests showed that plant extract significantly increased (p < 0.001) insulin sensitivity and decreased (p < 0.001) insulin resistance. The biochemical profile showed reduced triglyceride and cholesterol, while the antioxidant profile showed restoration of antioxidant enzymes in the pancreas, kidney, and liver tissues of treated rats. Conclusion: The present study indicated that crude extracts of B. aurea increase insulin sensitivity and reduce hyperlipidemia in diabetic rats, which rationalizes the traditional medicinal use of this plant as an antidiabetic agent.

Pharmacological Potential of the Standardized Methanolic Extract of Prunus armeniaca L. in the Haloperidol-Induced Parkinsonism Rat Model.

Parkinson's disease (PD) is a complex, age-related neurodegenerative disease that causes neuronal loss and dysfunction over time. An imbalance of redox potential of oxidative stress in the cell causes neurodegenerative diseases and dysfunction of neurons. Plants are a rich source of bioactive substances that attenuate oxidative stress in a variety of neurological disorders. The aim of the present study was to evaluate the Prunus armeniaca L. methanolic extract (PAME) for anti-Parkinson activity in rats. PD was induced with haloperidol (1 mg/kg, IP). The PAME was administered orally at 100, 300, and 800 mg/kg dose levels for 21 days. Behavioral studies (catalepsy test, hang test, open-field test, narrow beam walk, and hole-board test), oxidative stress biomarkers (SOD, CAT, GSH, and MDA) levels, neurotransmitters (dopamine, serotonin, and noradrenaline) levels, and acetylcholinesterase activity were quantified in the brain homogenate. Liver function tests (LFTs), renal function tests (RFTs), complete blood count (CBC), and lipid profiles were measured in the blood/serum samples to note the side effects of PAME at the selected doses. Histopathological analysis was performed on the brain (anti-PD study), liver, heart, and kidney (to check the toxicity of PAME on these vital organs). Motor functions were improved in the behavioral studies. Dopamine, serotonin, and noradrenaline levels were significantly increased (P < 0.001), whereas the level of acetylcholinesterase was decreased significantly (P < 0.001). The levels of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were increased, while malondialdehyde (MDA) and nitrite levels were decreased in the PAME-treated groups significantly compared with the disease control group, hence reducing oxidative stress. The incidence of toxicity was determined by biochemical analysis of LFT and RFT biomarkers testing. The histopathological analysis indicated that neurofibrillary tangles and plaques decreased in a dose-dependent manner in the PAME-treated groups. Based on the data, it is concluded that PAME possessed good anti-Parkinson activity, rationalizing the plant's traditional use as a neuroprotective agent.

Pterostilbene improves CFA-induced arthritis and peripheral neuropathy through modulation of oxidative stress, inflammatory cytokines and neurotransmitters in Wistar rats.

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.

Berberis aristata DC Extract Counteracts the High Fat Diet-Induced Reproductive Toxicity in Female Wistar Rats via Modulating Oxidative Stress and Resistance to Leptin and Insulin.

BACKGROUND: The plant Berberis aristata is traditionally used and scientifically validated for treating obesity and hyperlipidemia. It is also traditionally used to treat gynecological abnormalities. Therefore, the present study was designed to evaluate the therapeutic potential of Berberis aristata for obesity-related reproductive changes and chemically characterize it. METHODS: High-fat diet was given to 36 female rats for six weeks to induce obesity and infertility. These obese rats were treated with 10 mg/kg orlistat or the plant extract at 125-500 mg/kg for 45 days. RESULTS: The GC-MS analysis of the plant extract included fructose, thymic acid and other hydrocarbons. The plant extract revealed a remarkable free radical scavenging activity. The treated animals exhibited a decrease in total cholesterol and triglycerides (p<0.001), insulin and leptin levels (p<0.05), visceral fat, and body weight while increasing the estradiol level at 500 mg/kg dose of the plant extract as compared with untreated animals as demonstrated from the histology of the ovary. Oxidative stress biomarkers such as superoxide dismutase, nitric oxide, malondialdehyde and reduced glutathione were significantly (p<0.01-0.001) ameliorated in treated rats. CONCLUSION: B. aristata exhibited substantial potential against obesity-inducedreproductive damage in female rats by reducing oxidative stress and resistance to leptin and insulin.

Attenuating effect of Prosopis cineraria against paraquat-induced toxicity in prepubertal mice, Mus musculus.

Several herbicides, especially paraquat, are persistent organic pollutants which cause damage to humans and animals through reactive oxygen and nitrogen species. Prosopis cineraria (L.) Druce exhibits antioxidant activity and can effectively manage tremors. Therefore, the present research assessed the preventive effect of Prosopis cineraria (L.) Druce ethanolic extract (PCDE) against paraquat-induced toxicity in prepubertal mice. The plant extract was chemically characterized by a high-performance liquid chromatography-diode array detector (HPLC-DAD). The PCDE was orally administered to prepubertal mice for continuous 21 days, 2 h before paraquat exposure (2 mg/kg for consecutive 3 days per week for 3 weeks). The changes in behavior, motor coordination, memory, muscle movement, anxiety, and neurotransmitter levels in the brain were assessed. Histopathology and estimation of oxidative stress parameters in the brain, liver, kidney, and heart tissues were also carried out. HPLC-DAD analysis showed a high amount of quercetin, kaempferol, and ellagic acid derivatives in the plant extract. The PCDE showed improved muscle coordination, muscle movement and memory, and reduced anxiety in prepubertal mice. Moreover, levels of dopamine and noradrenaline were increased in the brain. It successfully ameliorated the oxidative stress in different organs by increasing the level of glutathione and superoxide dismutase and by reducing malondialdehyde. The histopathological assessment showed the plant extract effectively mitigated paraquat-induced pathological lesions in the neurons, neuroglia, hepatocytes, and kidney tissues. It is concluded from the present study that the treatment with PCDE had prevented the paraquat-induced toxicity in the brain, liver, kidney, and heart through the reduction of oxidative stress possibly due to the presence of phenolic compounds and flavonoids.

Anti-Parkinson's evaluation of Brassica juncea leaf extract and underlying mechanism of its phytochemicals.

Background: Parkinson's disease (PD) is associated with progressive neuronal damage and dysfunction. Oxidative stress helps to regulate neurodegenerative and neuronal dysfunction. Natural compounds could attenuate oxidative stress in a variety of neurological disorders. B. juncea is a rich source of antioxidants. The present study aimed to evaluate the therapeutic potential of B. juncea leaves for the treatment of PD by applying behavioral, in vivo and in silico studies. For in vivo studies rats were divided into six groups (n = 6). Group-I served as normal control (vehicle control). Group-II was disease control (haloperidol 1 mg/kg). Group-III was kept as a standard group (L-Dopa 100 mg/kg + carbidopa 25 mg/kg). Groups (IV-VI) were the treatment groups, receiving extract at 200-, 400- and 600 mg/kg doses respectively, for 21 days orally. Results: In vivo study results showed that the extract was found to improve muscles strength, motor coordination, and balance in PD. These behavioral outcomes were consistent with the recovery of endogenous antioxidant defence in biochemical analysis which was further corroborated with histopathological ameliorations. Dopamine levels increased and monoamine oxidase B (MAO-B) levels decreased dose-dependently in the brain during the study. Herein, we performed molecular docking analysis of the proposed extracted phytochemicals has explained that four putative phytochemicals (sinapic acid, rutin, ferulic acid, and caffeic acid) have presented very good results in terms of protein-ligand binding interactions as well as absorption, distribution, metabolism, excretion & toxicity (ADMET) profile estimations. Conclusion: The undertaken study concluded the anti-Parkinson activity of B. juncea and further suggests developments on its isolated compounds in PD therapeutics.

Neuroprotective potential of Malva neglecta is mediated via down-regulation of cholinesterase and modulation of oxidative stress markers.

Alzheimer's disease affects daily routine due to loss of memory and decline in cognition. In vitro data showed acetylcholine esterase inhibition activity of Malva neglecta but no in vivo evidence is available. The current study aims to investigate the anti-Alzheimer's activity of Malva neglecta methanolic extract in the AlCl3-induced Alzheimer disease rats' model. Thirty Wistar rats were divided into six groups and respective doses were given orally for 21 days. Behavioural observations were recorded and biochemical analysis was performed on brain homogenate. Improvement in memory and cognition was noted in treated rats as compared to disease control. A dose-dependent decrease (0.530 ± 0.009 at 200 mg/kg, 0.212 ± 0.007 at 400 mg/kg, 0.173 ± 0.005 at 600 mg/kg) in AChE activity was noted in the treatment groups with reference to disease control value (1.572 ± 0.013). This decrease in AChE activity is linked with an increase in acetylcholine in the brain which plays a key role in retaining memory. Oxidative stress biomarkers; GSH (66.77 ± 0.01 at 600 mg/kg), SOD (26.60 ± 0.10 at 600 mg/kg), CAT (21.46 ± 0.01 at 600 mg/kg) levels were increased with a decrease in MDA (103.33 ±0.49 at 600 mg/kg) level in a dose-dependently manner in the treatment groups as compared to disease control respective values. It is concluded that Malva neglecta could ameliorate Alzheimer's symptoms possibly by decreasing AChE activity and oxidative stress.

Screening of Synthetic Isoxazolone Derivative Role in Alzheimer's Disease: Computational and Pharmacological Approach.

Alzheimer's disease (AD) is age-dependent neurological disorder with progressive loss of cognition and memory. This multifactorial disease is characterized by intracellular neurofibrillary tangles, beta amyloid plaques, neuroinflammation, and increased oxidative stress. The increased cellular manifestations of these markers play a critical role in neurodegeneration and pathogenesis of AD. Therefore, reducing neurodegeneration by decreasing one or more of these markers may provide a potential therapeutic roadmap for the treatment of AD. AD causes a devastating loss of cognition with no conclusive and effective treatment. Many synthetic compound containing isoxazolone nucleus have been reported as neuroprotective agents. The aim of this study was to explore the anti-Alzheimer's potential of a newly synthesized 3,4,5-trimethoxy isoxazolone derivative (TMI) that attenuated the beta amyloid (Aß1-42) and tau protein levels in streptozotocin (STZ) induced Alzheimer's disease mouse model. Molecular analysis revealed increased beta amyloid (Aß1-42) protein levels, increased tau protein levels, increased cellular oxidative stress and reduced antioxidant enzymes in STZ exposed mice brains. Furthermore, ELISA and PCR were used to validate the expression of Aß1-42. Pre-treatment with TMI significantly improved the memory and cognitive behavior along with ameliorated levels of Aß1-42 proteins. TMI treated mice further showed marked increase in GSH, CAT, SOD levels while decreased levels of acetylcholinesterase inhibitors (AChEI's) and MDA intermediate. The multidimensional nature of isoxazolone derivatives and its versatile affinity towards various targets highpoint its multistep targeting nature. These results indicated the neuroprotective potential of TMI which may be considered for the treatment of neurodegenerative disease specifically in AD.

Anti-urolithiatic activity of Salvia hispanica L. seeds in ethylene glycol induced urolithiasis rat's model.

Urolithiasis is a disorder of kidneys in which stones formation occur due to the excessive deposition of minerals in the urinary tract. It affects 12% of the population worldwide. Salvia hispanica seeds are rich source of quercetin which has preventive role in renal stone formation. The study objective was to explore scientifically the anti-urolithiatic effect of Salvia hispanica seed's methanol extract using in vitro and in vivo urolithiasis models. For in-vitro study nucleation, growth and aggregation assays were performed. In vivo study was performed on rats and they were divided into six groups (n=6). Group-I was given vehicle only. Group-II was disease control, treated with 0.75% EG in drinking water which triggered urolithiasis. Groups-III received cystone (750 mg/kg, orally). Groups IV-VI were treated with extract at 100, 300 and 700 mg/kg doses orally once daily. Groups III-VI additionally received 0.75% EG in drinking water. In vitro study revealed concentration dependent increase in percentage inhibition of crystal's nucleation, growth and aggregation. In vivo study revealed anti-urolithiatic activity by lowering oxalate, calcium, phosphate, sodium and potassium levels in the urine and the serum uric acid, blood urea nitrogen, total proteins and total albumin. Salvia hispanica seeds are good alterative of allopathic anti-urolithiatic drugs to treat urolithiasis.

Pharmacological and toxicological evaluation of two anti-asthmatic polyherbal formulations.

The study aim was to evaluate the toxic potential of two polyherbal formulation i.e. " PH 1 & PH 2" and scientific validation of their anti-asthmatic use. Acute oral toxicity study as per OECD 425 TG was conducted. For validation of anti-asthmatic claim, in vivo assay named Ovalbumin (OVA)-induced murine method in Wistar rats was used. Eosinophils and IgE antibody were quantified post-administration of low and high doses of the formulations. No mortality was observed in acute toxicity study. Elevated levels of alkaline phosphatase and damaged liver structure indicating the hepatotoxicity were more pronounced in PH 2 treated rats. Congestion in kidney tissue and increased urea level were evident of the nephrotoxic nature of PH 2 in animals. Treatment with selected polyherbal products decreased the MDA level while increasing the SOD and GSH levels in lung tissue homogenates. The maximum decrease in IgE load (3.18 ± 0.08 IU/mL) was found in rats treated with 12 mg/kg dose of PH 1 followed by 100 mg/kg dose of PH 2 (3.44 ± 0.06 IU/mL). It was concluded that both polyherbal formulations had anti-asthmatic activities, however, PH 1 exhibited the liver and kidney toxicity and should be cautiously used.

Green synthesized selenium doped zinc oxide nano-antibiotic: synthesis, characterization and evaluation of antimicrobial, nanotoxicity and teratogenicity potential.

A facile, green synthesis of selenium doped zinc oxide nano-antibiotic (Se-ZnO-NAB) using the Curcuma longa extract is reported to combat the increased emergence of methicillin-resistant Staphylococcus aureus (MRSA). The developed Se-ZnO-NAB were characterized for their physicochemical parameters and extensively evaluated for their toxicological potential in an animal model. The prepared Se-ZnO-NABs were characterized via Fourier transformed infrared spectroscopy to get functional insight into their surface chemistry, scanning electron microscopy revealing the polyhedral morphology with a size range of 36 ± 16 nm, having -28.9 ± 6.42 mV zeta potential, and inductively coupled plasma optical emission spectrometry confirming the amount of Se and Zn to be 14.43 and 71.70 mg L-1 respectively. Moreover, the antibacterial activity against MRSA showed significantly low minimum inhibitory concentration at 6.2 µg mL-1 when compared against antibiotics. Also, total protein content and reactive oxygen species production in MRSA, under the stressed environment of Se-ZnO-NAB, significantly (p < 0.05) decreased compared to the negative control. Moreover, the results of acute oral toxicity in rats showed moderate variations in blood biochemistry and histopathology of vital organs. The teratogenicity and fetal evaluations also revealed some signs of toxicity along with changes in biochemical parameters. The overall outcomes suggest that Se-ZnO-NAB can be of significant importance for combating multi-drug resistance but must be used with extreme caution, particularly in pregnancy, as moderate toxicity was observed at a toxic dose of 2000 mg kg-1.