Effect of Curcumin and Coenzyme Q10 Alone and in Combination on Learning and Memory in an Animal Model of Alzheimer's Disease.

The most frequent neurodegenerative illness among senior people and the main cause of dementia is Alzheimer's disease. The present dementia medications available only help with the symptoms of cognitive deficits and have several negative effects. The current study's goal is to assess the effects of curcumin and coenzyme Q10, two herbal medicines, both separately and in combination, on learning and memory before comparing them to the industry standard drug. A total of 42 adult healthy Wistar rats were used in our study. In this experiment, rats were given daily doses of 2.5 mg/kg of body weight of scopolamine hydrobromide for 7 days to induce Alzheimer's disease. On the eighth day, behavioural testing was conducted. Following testing, scopolamine and the test medications were given daily for the following 21 days. On days 29 and 30, behavioural testing was conducted once more, and then animals were slaughtered. Brain homogenate was produced for the estimation of molecular and biochemical markers. Curcumin has demonstrated a dose-response relationship, with a higher dose (200 mg/kg b.w. p.o.) being more effective than a lower dose (100 mg/kg b.w. p.o.). Similar to the greater dose of curcumin, coenzyme Q10 (200 mg/kg b.w. p.o.) has also been found to improve memory and learning. Higher doses of curcumin and coenzyme Q10 had more pronounced and meaningful effects. Acetylcholinesterase and TNF levels increased in scopolamine-induced memory impairment, but these effects were restored by the test medications, and improved by the combined therapy. These outcomes are comparable to those of the common medication memantine. As a result, we may infer from our results that curcumin at higher doses and its combination with coenzyme Q10 (200 mg/kg b.w. p.o.) have a significant impact on cognitive impairment in animal models of Alzheimer's disease and can be utilised alone or as an add-on therapy for the condition.

Increased Serum Levels of Matrix-metalloproteinase-9, Cyclo-oxygenase-2 and Prostaglandin E-2 in Patients with Chronic Obstructive Pulmonary Disease (COPD).

Chronic obstructive pulmonary disease (COPD), a heterogeneous lung disorder that is characterized by airflow obstruction and the third leading cause of death, globally. COPD is influenced by environmental and genetic factors. Here, we measured the serum level of matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE-2) and reveal the correlation between their levels in COPD subjects. In this study, we included a total of 79 COPD and 79 healthy controls. We assessed demographic profile, risk factors, respiratory symptoms, clinical history, COPD Assessment Test (CAT) score and spirometry. Further, we determined the serum levels of MMP-9, COX-2 and PGE-2 by enzyme-linked immunosorbent assay (ELISA). The correlation between their serum levels was also determined. Among the studied population age, gender, body mass index and socioeconomic status were comparable. Serum levels of MMP-9, COX-2 and PGE-2 were significantly increased in the COPD group than in healthy controls (P < 0.0001). Moreover, MMP-9, COX-2 and PGE-2 levels were increased with the GOLD grades and CAT score (> 10). Serum levels of MMP-9, COX-2 and PGE-2 was enhanced in patients with larger clinical history (> 20 years) than those with lower clinical history (< 10 years). Serum levels of MMP-9 and COX-2; MMP-9 and PGE-2; COX-2 and PGE-2 showed a positive correlation (P < 0.0001) with the COPD group. Our data demonstrate that serum levels of MMP-9, COX-2 and PGE-2 were correlated with the GOLD grade, CAT score and clinical history of the COPD group, pointing that they can be used as a indicators to understand the disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-021-00973-2.

The Relationship Between Clinical Phenotypes and Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stages/Groups in Patients With Chronic Obstructive Pulmonary Disease.

Background Chronic obstructive pulmonary disease (COPD) cannot be properly characterised by a single metric, forced expiratory volume in the first second (FEV1), due to its complexity and heterogeneity. The GOLD 2017 report contained the ABCD evaluation method to measure airflow limitation, symptoms, and/or exacerbation risk. Objective The purpose of this study was to explore the relationship between clinical characteristics and GOLD groups or stages in patients with COPD. Methods This cross-sectional observational study was conducted at the department of respiratory medicine, King George's Medical University, Lucknow, Uttar Pradesh, India, between 2019 and 2022. Here, stable COPD patients' demographics, clinical characteristics, and the number of exacerbations were compared between the groups following the GOLD 2022 report. An unpaired t-test with Welch's correction, chi-square test, Fisher's exact test, one-way ANOVA, and Kruskal-Wallis test were used for statistical significance. Results In this study, 349 stable COPD patients (256 males and 93 females) were selected. The GOLD 2017 categorization placed 78 (22.4%) patients in group A, 158 (45.3%) in B, 44 (12.6%) in C, and 69 (19.8%) in D. Further, we used GOLD 2017 to classify COPD patients into 16 subgroups (1A-4D). FEV1 (% predicted) decreased across groups A to D (p<0.0001). Groups C and D had a longer duration of illness, higher COPD assessment test (CAT) score, higher Modified Medical Research Council (mMRC) dyspnea scale, longer exacerbation history, and more COPD hospitalizations in the previous year than groups A and B. More symptomatic patients (B and D) exhibited lower FEV1 (% predicted) and more severe airflow limitation than less symptomatic patients (A and C) (p=0.0002). Symptomatic individuals exhibited higher CAT and mMRC dyspnea scores (p<0.0001). Groups C and D comprised older patients and those with longer disease duration, higher mMRC dyspnea scale and CAT, lower FEV1, and more severe airflow limitation (A and B). Conclusion The present study demonstrates the distribution of COPD patients' clinical phenotypes in an Indian population. We conclude that the combined COPD assessment according to the GOLD 2022 guideline provides a better understanding of COPD.

Correction: Shoaib et al. Neuroprotective Effects of Dried Tubers of Aconitum napellus. Plants 2020, 9, 356.

We are sorry to report that some images in Figure 1 reported in our recently published paper [...].

Neuroprotective Effects of Dried Tubers of Aconitum napellus.

The present study was designed to explore the neuroprotective properties of Aconitum napellus (Ranunculaceae). The plant detoxification was done using either water, or cow or goat milk as per the Ayurvedic shodhana method. The evaluation of the neuroprotective role of A. napellus was performed on diabetic neuropathy induced by streptozotocin in Sprague Dawley (SD) rats. Body mass, blood sugar level, oral glucose tolerance test, hyperalgesia, cold allodynia, motor co-ordination test, and locomotor activity, oxidative biomarkers (TBARS, reduced glutathione, catalase and superoxide dismutase) and sciatic nerve histomorphology were assessed. The in vitro studies were done on human neuroblastoma cell line SHSY-5Y and used an MTT assay to assess the antiproliferative activity of different extracts. Results suggest that the goat milk treated chloroform extract has less percentage of aconitine. After administration of the detoxified chloroform extract to the diabetic animals, there was a significant improvement in the myelination and degenerative changes of the nerve fibers along with behavioral changes (p < 0.05 as compared with diabetic control group). The findings of the in vitro research show an effective neuroprotective role of A. napellus. This suggests that A. napellus should be further investigated for its effect in diabetic pathology.

QSAR modeling and docking analysis of D2 receptor with known olanzapine derivatives.

Dopamine (D2) receptors are known drug targets for various antipsychotics used in Schizophrenia. Therefore, it is of interest to analyze the binding features of D2 receptors with known olanzapine derivatives for further consideration using molecular docking and QSAR analysis. A 2D QSAR model was built using energy-based descriptors generated by docking as independent variable and known Ki value of Olanzapine derivatives with D2 Receptor as dependent variable. QSAR model provided coefficient of determination of r2 of 0.7 in multiple linear regression analysis. The predictive performance of QSAR model was assessed using different cross-validation procedures. Thus, data shows that a ligand-receptor binding interaction for D2 Receptor using a QSAR model is promising approach to design novel and potent inhibitors of D2 Receptor.

Evaluation of Noxious Consequence of Bark Extract of Onosma echioides Linn Root: Hematology, Biochemistry, and Histopathological Findings.

Onosma echioides is a perennial herb widely used for the treatment of various ailments such as sciatica, gout, and rheumatism. This study focused on toxicological assessment of bark extract of O. echioides root. In subacute toxicity study, 20 Sprague Dawley rats (140 ± 10 g body weight) were randomly grouped into two groups of 10 rats each (5 male and 5 female). Effect of the n-hexane extract of O. echioides (100 mg/kg body weight/day) was studied for a period of 28 days using control and treated groups. Effects of the extract on body weight, food consumption, water intake, serum glucose, and hematology, biochemistry, and histopathology were evaluated. The histopathology was carried out to evaluate the degenerative changes in liver, heart, and kidney. Result of acute toxicity study showed dose-dependent increase in mortality. LD50 was found to be 1,000 mg/kg body weight. The subacute toxicity data showed that the treated group did not show any change in behavior and urinalysis whereas an increase in body weight was observed in the male treated group. A significant but nontoxic effect was observed on food and water consumption. Significant increases in RBC (female treated group; **p < .01), neutrophil (both male and female treated group; **p < .01), MCV (female treated group, **p < .01), MCH (both male and female treated groups; **p < .01), and MCHC (both male and female treated groups; *p < .05) levels were observed; a significant changes were observed in total bilirubin (*p < .05), BUN (**p < .01), potassium (*p < .05), and ALT (**p < .01) levels. The relative organ weights of vital organs at this dose did not show any significant change. In conclusion, the toxicity data showed that the bark extract of O. echioides root does not possess any adverse effect at a fixed dose, which provides a support for its further safety study and biocompatibility application.

Beneficial effects of n-hexane bark extract of Onosma echioides L. on diabetic peripheral neuropathy.

Onosma echioides Linn (Boraginaceae) is the most frequently used curative herb widely used for kidney obstruction, sciatic pain, and gout. The present study was designed to investigate the therapeutic effects of n-hexane bark extract of O. echioides (OE) L. root in vivo against Streptozotocin-induced diabetic neuropathy in SD rats. For in vivo activity, the experiment was categorized into five different groups (n = 5). Group-I was considered as nondiabetic/normal control (NC) treated with 0.5% carboxymethyl cellulose (CMC), Group II as diabetic control, Group-III, IV, and V served as diabetic treated with OE 50, OE 100, and pregabalin at a dose of 50, 100, and 10 mg/kg body weight, orally, respectively. Body weight, blood glucose, oral glucose tolerance test, behavioral studies (motor coordination test, thermal hyperalgesia, cold allodynia, locomotor activity, oxidative biomarkers (thio barbituric acid reactive substances [TBARS], superoxide dismutase [SOD], glutathione [GSH], and catalase), and histopathology of the sciatic nerve were performed. Treatment with OE showed a dose-dependent increase in neuroprotective activity by improving the myelination and decreasing the axonal swelling of nerve fibers. The verdicts of behavioral activities showed a remarkable effect on animals after the treatment of extract and standard drug pregabalin. In conclusion, our findings supported the traditional application of OE and explored its importance in the management of diabetic neuropathy. Additional clinical experiments may provide novel therapeutic drugs for diabetes and its complications.

Cure of human diabetic neuropathy by HPLC validated bark extract of Onosma echioides L. root.

HPLC validated hexane bark extract of Onosma echioides L. root (OE) was evaluated for cure of human diabetic neuropathy in human neuroblastoma cell line. HPLC analysis was performed. Human neuroblastoma cells were grouped into control, normal glucose, high glucose (HG) and HG plus different concentrations of OE extract (10, 25 and 50 µg/mL). MTT, DCFH-DA staining and nuclear condensation assays were performed on neuroblastoma cells to evaluate antiproliferative activity, ROS activity level and apoptotic effect of OE. HPLC analysis revealed the existence of maximum yield of shikonin in n-hexane extract of OE. Exposure with different concentrations of OE effectively decreased ROS level and apoptosis of cells and as a result improved the viability of cells in a dose dependent manner in response to HG-induced oxidative stress. Thus, OE possesses the property to cure human diabetic neuropathy and further can be clinically tested for its use in diabetic neuropathy.

Omega-3 fatty acid attenuates oxidative stress in cerebral cortex, cerebellum, and hippocampus tissue and improves neurobehavioral activity in chronic lead-induced neurotoxicity.

Objectives: In view of the increasing risk of lead on human health, the present study has been carried out to investigate the neuroprotective effect of omega-3 fatty acid on chronic lead-induced neurotoxicity and behavioral impairment in rats. Methods: Different neurobehavioral parameters, biochemical assays, and histopathological analyses in brain regions of rats were conducted. Results: Rats exposed to different doses of lead (lead acetate 2.5, 5.0, 7.5 mg/kg body weight p.o. for 90 days) caused a significant decrease in body weight, brain weight, and behavioral changes as compared to controls. Abnormal histopathological and increased levels of lead in blood and brain regions increased the levels of ROS, LPO, PCC and decreased the levels of GSH with concomitant reduction in SOD, CAT, and GPx activities in the brain region of rats treated with different doses of lead as compared to controls. Co-treatment of lead with omega-3 fatty acid (500 mg/kg body weight p.o. for 90 days) decreased the levels of ROS, LPO, PCC, and increased the level of GSH, also increased SOD, CAT, and GPx activity and showed improvements in behavioral as well as histopathological changes as compared to lead-treated groups. Discussion: Our results proved that omega-3 fatty acid improved behavioral deficits, altered histopathological and oxidative stress in lead-intoxicated rats. Among three different doses, 2.5 mg/kg b.wt. of lead along with omega-3 fatty acid was the most preventive dose for the neurotoxicity. This work reveals the potential of omega-fatty acid as a protective drug for lead neurotoxicity.

Chemoprotective effect of nanocurcumin on 5-fluorouracil-induced-toxicity toward oral cancer treatment.

INTRODUCTION: Cancer of oral cavity is the uncontrolled expansion of damaged cell within the mouth cavity. 5-fluorouracil (5-FU) chemotherapy was focused to kill the cancer cell, but it would affect the surrounding normal cells during oral cancer treatment. This study included the evaluation of chemoprotective effects of curcumin (CU), as an herbal remedy, on 5-FU-induced-cytotoxicity toward oral cancer treatment, loaded within a nanocarrier system. CU was combined with 5-FU chemotherapy as a combinational drug-delivery system to evaluate synergistic effects. MATERIALS AND METHODS: Nanoformulation of CU (nano-CU) and nanoformulation of 5-FU (nano-FU) were prepared by employing homogenization with high-energy sonication. The characterizations of prepared nanoformulations were evaluated on the basis of particle size, zeta potential, and polydispersity index (PDI) values. The chemopreventive effect of nano-CU on 5-FU induced-toxicity and synergistic efficacy were optimized through different in-vitro assays. RESULTS: The average particle size of nano-CU and nano-FU were up to 200 nm, negatively-charged, and shown up to 4th-day control release of the drug within the acceptable concentration. IC50 value for growth inhibition was calculated as 47.89 and 26.19 µg/ml, respectively, for nano-CU and nano-FU. OCC was pretreated with nano-CU and shown the protective effect by reducing 5-FU induced-cytotoxicity by preventing normal cells through reduced viability. The DPPH-indicated fluorescence-tagged cells had quantified for antioxidant effect as it reduces intracellular reactive oxygen species level in OCC. Along with alteration in cell protein expression, Blc2, and Bax, shows enhanced apoptosis rate in OCC. CONCLUSION: Nano-CU provides chemoprotective nature towards 5-FU induced-toxicity, along with synergistic effects in oral cancer treatment.

Hypolipidaemic Effects of Gymnema sylvestre on High Fat Diet Induced Dyslipidaemia in Wistar Rats.

INTRODUCTION: Hyperlipidaemia is a well known risk factor for cardiovascular diseases. Lifestyle modification can be the initial step to reduce cholesterol levels. There are various drugs which are used to control dyslipidaemia. Treatment of lipid abnormalities is a lifelong battle. Moreover, the safety and effectiveness of long term lipid lowering treatment are questionable. Gymnema Sylvestre (GS) is a well known herb with various medicinal properties. AIM: To explore the hypolipidaemic activity of GS leaves extract. MATERIALS AND METHODS: Adult healthy female wistar rats, 30 in number, divided into five groups, weighing 150- 200 g were used. Dyslipidaemia was induced in rats by feeding them on high fat diet for four weeks. For the next four weeks GS extract was used as test drug while Atorvastatin was used as standard drug. Blood sample was collected for estimation of lipid profile on day 0, week 4 and week 8. Data was recorded as mean±SEM (Standard error of mean). Paired t-test and one way Analysis of Variance (ANOVA) followed by Dunnett's post hoc test was used for comparison. A p-value <0.05 was considered statistically significant. SPSS Statistics 20 (IBM software) was used for the analysis. RESULTS: Feeding rats with high fat diet for four weeks led to obesity and dyslipidaemia in rats. GS at both the doses (100mg/kg and 200mg/kg) significantly improved the lipid profile. Total Cholesterol (TC), Triglycerides (TG), Very Low Density Lipoprotein (VLDL) and Low Density Lipoprotein (LDL) values reduced significantly while that of High Density Lipoprotein (HDL) increased significantly. GS 200 mg/kg was found more effective than GS 100 mg/kg. GS improved the value of lipid profile significantly but the effect was found inferior to Atorvastatin. CONCLUSION: From the present study it can be concluded that GS possess an effective hypolipidaemic effect. Hence it can be included as an add on therapy in dyslipidaemia after further confirmatory studies.

New 4'-substituted benzoyl-ß-D glycoside from the fruit pulp of Terminalia belerica with antiplatelet and antioxidant potency.

BACKGROUND: The fruit Terminalia belerica is a rich source of vitamins, acids, and nutraceuticals which have free radical scavenging activity. Thus, the ethanolic extract of fruit and its isolated compound (Tb-01) were intended to estimate antiplatelet and antioxidant activities. METHODS: The ethanolic extract was submitted to Si-gel CC and the compound was isolated. The compound Tb-01 was characterized as benzoyl-ß-D-(4'→10″ geranilanoxy)-pyranosides on the basis of spectral data [ultra violet (UV), infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and Mass Spectroscopy] and chemical analyses. The ethanolic extract and Tb-01 at different concentrations were in vitro screened for antiplatelet and antioxidant activity. The antiplatelet activity was carried out by using platelet rich plasma prepared by centrifugation of rabbit whole blood (containing 0.9% sodium citrate as anticoagulant) and antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl, reducing power, and nitric oxide anion scavenging activity models. RESULTS: The compound Tb-01 was an amorphous brownish powder, yield 0.64% (w/w), melting point 105-110 °C, Retardation factor/Retention Value (R f value) at 0.42 in methanol:chloroform (20:80) solvent system, UV absorption maxima at 243 nm, and molecular peak [M + H]+ at 394.15 m/z. It was observed that the ethanolic extract and Tb-01 at different concentrations showed significant antiplatelet and antioxidant activity. The antioxidant activity, like scavenging of 1,1-diphenyl-2-picrylhydrazyl radicals, nitric oxide radical, and reductive power were found to be concentration-dependent and increased when increasing amounts of sample were used. CONCLUSION: Mass spectra and 1H NMR confirmed the isolated compound structure which was supported by 13C NMR and IR spectra. Tb-01could be promising for future applications in the treatment of blood clots, pulmonary embolism, and other related diseases.

Attenuation of lead neurotoxicity by supplementation of polyunsaturated fatty acid in Wistar rats.

BACKGROUND: Among various types of polyunsaturated fatty acid (PUFA), omega-3 fatty acids play a crucial role in development and function of the brain. This study was undertaken to investigate the possible neuroprotective efficacy of omega-3 fatty acid on lead-induced neurotoxicity in rats. MATERIAL AND METHODS: The experiment was carried out on 32 male Wistar rats divided into four groups. The first group (control) was treated with distilled water and second group with lead acetate at the doses of 3 mg/kg b.wt. (body weight)/oral, whereas third and fourth groups were simultaneously treated with lead acetate (3 mg/kg b.wt.) plus omega-3 fatty acid (300 mg/kg b.wt./oral) and lead acetate (3 mg/kg b.wt.) plus vitamin E (100 mg/kg b.wt./oral), respectively, for a period of 90 days. Their biochemical and histopathological investigations have been carried out. RESULTS: The level of lead was markedly elevated in brain (4.71-fold) and blood (5.65-fold), also increased levels of ROS, GSH, LPO with concomitant reduction in the activities of delta-ALAD, CAT, SOD, and GPx. In addition, lead-induced brain damage was indicated by histopathological changes. Omega-3 fatty acid resulted in marked improvement in most of the biochemical parameters as well as histopathological changes in rats. The results obtained were compared with vitamin E as the standard antioxidant agents. DISCUSSION: Omega-3 fatty acid significantly (P < 0.05) decreased the effect of lead-induced brain damage as well as biochemical changes similar to that of standard drug, vitamin E. So, our result suggested that omega-3 fatty acid may play a protective role in lead-induced neurotoxicity and associated human health risk.

Clinical evaluation of analgesic activity of guduchi (tinospora cordifolia) using animal model.

INTRODUCTION: Pain is a very well-known signal of ill health and analgesics are the drugs that are used to relieve pain. The main problem with these drugs remains that of side effects. Safer alternatives are natural herbs. Guduchi (Tinospora cordifolia) is one such plant with analgesic potential but few studies are there. OBJECTIVE: To evaluate the analgesic activity of commercially available extract of Guduchi (T. cordifolia). MATERIALS AND METHODS: For this purpose commercially available extract of Guduchi (T. cordifolia) by Himalaya Drug Company, Bangalore was used. Albino rats were divided randomly in three groups of six rats each. Group 1 (control) received distilled water orally, group 2 (test) received T. cordifolia extract in dose of 300 mg/kg orally and group 3(standard) received Pentazocine in dose 10mg/kg intraperitoneally. Analgesic activity was evaluated using hot plate and abdominal writhing method. All the observations were analysed statistically using student's t-test. OBSERVATION AND RESULTS: T. cordifolia extract significantly (p<0.05) increased the response time and decreased the number of writhes in hot plate method and abdominal writhing method respectively, on comparison with the control group. CONCLUSIONS: The above findings suggest that this commercially available extract of Guduchi (T. cordifolia) possess analgesic activity. This analgesic activity probably involves peripheral as well as central mechanisms as the extract showed analgesic activity in both hot plate and abdominal writhing method.

Molecular Docking studies of D2 Dopamine receptor with Risperidone derivatives.

In this work, 3D model of D2 dopamine receptor was determined by comparative homology modeling program MODELLER. The computed model's energy was minimized and validated using PROCHECK and Errat tool to obtain a stable model structure and was submitted in Protein Model Database (PMDB-ID: PM0079251). Stable model was used for molecular docking against Risperidone and their 15 derivatives using AutoDock 4.2, which resulted in energy-based descriptors such as Binding Energy, Ligand Efficiency, Inhib Constant, Intermol energy, vdW + Hbond + desolv Energy, Electrostatic Energy, Total Internal Energy and Torsional Energy. After that, we have built quantitative structure activity relationship (QSAR) model, which was trained and tested on Risperidone and their 15 derivatives having activity value pKi in µM. For QSAR modeling, Multiple Linear Regression model was engendered using energy-based descriptors yielding correlation coefficient r2 of 0.513. To assess the predictive performance of QSAR models, different cross-validation procedures were adopted. Our results suggests that ligand-receptor binding interactions for D2 employing QSAR modeling seems to be a promising approach for prediction of pKi value of novel antagonists against D2 receptor.