Search

The plant Cissus tuberosa Moc is abundant in phenolics, has been documented to have neuroprotective properties. The study seeks to determine the neuroprotective effects of C. tuberosa ethanolic extract (CTE) against Parkinson's disease by evaluating its impact on motor dysfunction, cognitive deficits, neuroinflammation, and neurodegeneration in paraquat-induced Parkinson's disease models. The research hypothesizes that CTE can modulate key biomarkers involved in Parkinson's pathology, including α-synuclein, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), assessed through qRT-PCR, as well as interleukin-6 (IL-6) and TNF-α, evaluated through ELISA. Parkinson disease was induced by using paraquat intraperitoneally. The study was designed by considering various groups with their respective treatments, control group treated normally, disease control receiving paraquat (1 mg/kg, i.p.), standard treated grabbed with (levodopa+carbidopa), and three treatment groups received plant extract (150, 300, 600 mg/kg) respectively for 21 days study period. Both behavioral, and biochemical analysis were performed. HPLC analysis revealed the presence of several phenolic compounds. CTE significantly improved motor function and cognitive performance in rats, showing a dose-dependent reduction in paraquat-induced neurotoxicity (150 < 300 < 600 mg/kg, P<0.001). CTE significantly restored antioxidant enzyme levels (P<0.001), contributing to the alleviation of oxidative stress. Neurotransmitter levels were significantly improved in a dose-dependent manner (P<0.001), while acetylcholinesterase (AChE) levels were significantly reduced (P<0.001). CTE treatment showed significant restoration of brain tissue, reducing neuroinflammation and neurodegeneration, thereby preserving normal brain structure. ELISA testing demonstrated a significant (P<0.001) downregulation of IL-6 and TNF-α levels in CTE-treated groups. qRT-PCR results showed significant downregulation of α-synuclein, IL-1β, and TNF-α mRNA expression in CTE-treated groups compared to the diseased group, suggesting neuroprotective effects. The study concludes that CTE has potential therapeutic effects in alleviating Parkinson's disease symptoms, primarily through its antioxidant, anti-inflammatory, and neuroprotective properties., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saadullah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Mazus pumilus (MP) an Asian flowering plant, known for various reported pharmacological activities including antioxidant, anti-nociceptive, anti-inflammatory, anticancer, antibacterial, antifungal, and hepatoprotective effects. This study focused on further exploring Mazus pumilus' s methanol leaf extract (MPM) for bioactive principles and investigating its neuroprotective and cognition-enhancing potential in Alzheimer's disease models., Methods: For the phytochemical screening and identification, TLC, HPLC, and Fourier transform infrared (FTIR) were employed. In-vitro antioxidant potential was assayed by DPPH Free Radical Scavenging method, followed by in-vivo neuroprotective effect of MPM (100, 200, 300 mg/kg) using Wistar-albino rats, sodium azide for induction of AD and rivastigmine as standard. Over 21 days, we observed neurobehavioral changes and performed biochemical (GSH, CAT, SOD, and AchE activity) and histopathological evaluations., Results: Results revealed the presence of alkaloids, flavonoids, amino acids, terpenoids, glycosides, sterols, and saponins. HPLC analysis confirmed the presence of gallic acids, sinapic acid, and caffeic acid. DPPH confirmed the antioxidant effect of MPM, which served as a base for its potential neuroprotective activity. Biochemically, oxidative stress markers improved significantly post-treatment, with decreased GSH, SOD, CAT levels, and increased AchE activity, indicating a reversal of AD-induced changes. Behavioral assessments showed improvements in locomotion, memory, spatial learning, and cognition. Histologically, there was a dose-dependent reduction in neurodegenerative features like neurofibrillary tangles and amyloid beta plaques., Conclusions: Hence, this study concluded MPM is a promising candidate for prophylaxis and treatment of behavioral deficits and cognitive dysfunction in Alzheimer's disease., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Parkinson's disease (PD) is characterized by dopamine deficiency in the corpus striatum due to the degeneration of dopaminergic neurons in the substantia nigra. Symptoms include bradykinesia, resting tremors, unstable posture, muscular rigidity, and a shuffled gait. Thalictrum foetidum is traditionally used for neurodegenerative disorders. Objectives: This study aimed to explore the therapeutic potential of aqueous ethanolic extract of Thalictrum foetidum (AETF) against Parkinson-like symptoms and to investigate its underlying mechanism. Methodology: Thirty-six albino mice were randomly divided into 6 groups (n = 6): normal control, disease control, standard treatment (levodopa/carbidopa, 100/25 mg/kg), and 3 treatment groups (AETF at 200, 400, and 600 mg/kg). One hour before treatment, haloperidol (1 mg/kg, i. p .) was administered to induce Parkinson's disease in all groups except the normal control group. Results: Behavioral analysis showed significant improvement ( P < .001) in motor function, muscular coordination, and reduced muscular rigidity and tremors. AETF also reduced oxidative stress. Histological examination of the brain showed reduced Lewy bodies, neurofibrillary tangles, and plaque formation. Conclusion: AETF alleviated PD symptoms by reducing neurodegeneration, modulating oxidative stress, and inhibiting the expression of nuclear factor-κB (NF-κB) and associated inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

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-1β. 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-1β, 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saadullah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Metabolic disorders pose significant global health challenges, necessitating innovative therapeutic approaches. This study focused on the multifaceted therapeutic potential of berberine-enriched extract (BEE) in mitigating metabolic impairment induced by streptozotocin (STZ) in a rat model and compared the effects of BEE with berberine (BBR) and metformin (MET) to comprehensively evaluate their impact on various biochemical parameters. Our investigation reveals that BEE surpasses the effects of BBR and MET in ameliorating metabolic impairment, making it a promising candidate for managing metabolic disorders. For this, 30 male Wistar rats were divided into five groups ( n = 6): control (CN), STZ, STZ + MET, STZ + BBR, and STZ + BEE. The treatment duration was extended over 4 weeks, during which various biochemical parameters were monitored, including fasting blood glucose (FBG), lipid profiles, inflammation, liver and kidney function biomarkers, and gene expressions of various metabolizing enzymes. The induction of metabolic impairment by STZ was evident through an elevated FBG level and disrupted lipid profiles. The enriched extract effectively regulated glucose homeostasis, as evidenced by the restoration of FBG levels, superior to both BBR and MET. Furthermore, BEE demonstrated potent effects on insulin sensitivity, upregulating the key genes involved in carbohydrate metabolism: GCK, IGF-1, and GLUT2. This highlights its potential in enhancing glucose utilization and insulin responsiveness. Dyslipidemia, a common occurrence in metabolic disorders, was effectively managed by BEE. The extract exhibited superior efficacy in regulating lipid profiles. Additionally, BEE exhibited significant anti-inflammatory properties, surpassing the effects of BBR and MET in lowering the levels of inflammatory biomarkers (IL-6 and TNF-α), thereby ameliorating insulin resistance and systemic inflammation. The extract's superior hepatoprotective and nephroprotective effects, indicated by the restoration of liver and kidney function biomarkers, further highlight its potential in maintaining organ health. Moreover, BEE demonstrated potent antioxidant properties, reducing oxidative stress and lipid peroxidation in liver tissue homogenates. Histopathological examination of the pancreas underscored the protective effects of BEE, preserving and recovering pancreatic β-cells damaged by STZ. This collective evidence positions BEE as a promising therapeutic candidate for managing metabolic disorders and offers potential benefits beyond current treatments. In conclusion, our findings emphasize the remarkable therapeutic efficacy of BEE and provide a foundation for further research into its mechanisms, long-term safety, and clinical translation., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H 2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid ® 244FP and poloxamer ® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

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-1β, 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., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The simultaneous coexistence of complicated metabolic conditions like obesity and diabetes within an individual is known as diabesity. Obesity is the key factor for many chronic diseases, including insulin resistance and type 2 diabetes (T2D). Metabolic stress due to nutrient overload releases different inflammatory mediators. Secreted frizzled-related protein 4 (SFRP4) is also an inflammatory mediator that impairs insulin secretion. SFRP4 acts as an early biomarker for diabesity expressed with interleukin-1 beta (IL-1β) in the adipose tissues that hinder the exocytosis of insulin-secreting granules from the pancreatic β-cells and is a potential target for preserving β-cell dysfunction and the diabesity treatment. The current study aimed to screen potential bioactive compounds targeting and inhibiting the diabesity-linked SFRP4 protein through an in silico approach. The three-dimensional (3D) structure of human SFRP4 was predicted through comparative modeling techniques and evaluated by various online bioinformatics tools. The molecular docking and MD simulation investigations were carried out against phytochemicals with anti-diabetic and anti-obesity properties to shortlist the best SFRP4 inhibitor. Hesperetin, Curcumin, Isorhamnetin, Embelin, Epicatechin, and Methyl Eugenol interacted strongly with SFRP4 by displaying zero RMSD and binding affinities of -6.5, -6.4, -6.3, -5.3, -6.3 and -5.8 kcal/mol respectively. Additionally, the root mean square fluctuation and root mean square deviation graphs from the MD simulation results demonstrated that hesperetin has good variations throughout the simulation period as compared to others. This dynamic stability and control behavior of hesperetin, when it interacts with SFRP4, shows that it has the potential to modulate the function and activity of the protein. Therefore, hesperetin is identified as an effective and top drug candidate through this analysis for preserving beta-cell function and treating diabesity by targeting SFRP4. The findings of this study could be useful in the design and development of diabesity drugs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rehman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The aim of this study was to investigate the disruptions of metabolic pathways induced by bisphenol A (BPA) and explore the potential therapeutic intervention provided by resveratrol (RSV) in mitigating these disruptions through the modulation of biochemical pathways. Wistar albino rats were divided into three groups: group 1 served as the control, group 2 received 70 mg/Kg of BPA, and group 3 received 70 mg/kg of BPA along with 100 mg/Kg of RSV. After the treatment period, various biomarkers and gene expressions were measured to assess the effects of BPA and the potential protective effects of RSV. The results revealed that BPA exposure significantly increased the serum levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines such as TNF-α and IL-6. Concurrently, BPA exposure led to a reduction in the levels of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as GLUT4 and HDL cholesterol. However, the administration of RSV along with BPA significantly ameliorated these alterations in the biomarker levels induced through BPA exposure. RSV treatment effectively reduced the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines, while increasing the levels of antioxidant enzymes, GLUT4, and HDL cholesterol. Furthermore, BPA exposure suppressed the mRNA expression of glucokinase (GCK), insulin-like growth factor 1 (IGF-1), and glucose transporter 2 (GLUT2) and up-regulated the mRNA expression of uncoupling protein 2 (UCP2), which are all critical biomarkers involved in glucose metabolism and insulin regulation. In contrast, RSV treatment effectively restored the altered mRNA expressions of these biomarkers, indicating its potential to modulate transcriptional pathways and restore normal metabolic function. In conclusion, the findings of this study strongly suggest that RSV holds promise as a therapeutic intervention for BPA-induced metabolic disorders. By mitigating the disruptions in various metabolic pathways and modulating gene expressions related to glucose metabolism and insulin regulation, RSV shows potential in restoring normal metabolic function and counteracting the adverse effects induced by BPA exposure. However, further research is necessary to fully understand the underlying mechanisms and optimize the dosage and duration of RSV treatment for maximum therapeutic benefits.

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Curcumin (Cur) entrapped poly(vinyl alcohol) (PVA)/gelatin composite films were prepared by cross-linking with tannic acid (TA) as bioactive dressings for rapid wound closure. Films were evaluated for mechanical strength, swelling index, water vapor transmission rate (WVTR), film solubility, and in-vitro drug release studies. SEM revealed uniform and smooth surfaces of blank (PG9) and Cur-loaded composite films (PGC4). PGC4 exhibited excellent mechanical strength (tensile strength (TS) and Young's modulus (YM) were 32.83 and 0.55 MPa, respectively), swelling ability (600-800% at pH 5.4, 7.4, and 9), WVTR (2003 ± 26), and film solubility (27.06 ± 2.0). Sustained release (81%) of the encapsulated payload was also observed for 72 h. The antioxidant activity determined by DPPH free radical scavenging showed that the PGC4 possessed strong % inhibition. The PGC4 formulation displayed higher antibacterial potential against S. aureus (14.55 mm zone of inhibition) and E. coli (13.00 mm zone of inhibition) compared to blank and positive control by the agar well diffusion method. An in-vivo wound healing study was carried out on rats using a full-thickness excisional wound model. Wounds treated with PGC4 showed very rapid healing about 93% in just 10 days post wounding as compared to 82.75% by Cur cream and 80.90% by PG9. Furthermore, histopathological studies showed ordered collagen deposition and angiogenesis along with fibroblast formation. PGC4 also exerted a strong anti-inflammatory effect by downregulating the expression of pro-inflammatory cytokines (TNF-α and IL-6 were lowered by 76% and 68% as compared to the untreated group, respectively). Therefore, Cur-loaded composite films can be an ideal delivery system for effective wound healing., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

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-1β, TNF-α, IL-1α and β 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current study was designed to formulate ternary solid dispersions (TSDs) of dexibuprofen (Dex) by solvent evaporation to augment the solubility and dissolution profile, in turn providing gastric protection and effective anti-inflammatory activity. Initially, nine formulations (S1 to S9) of binary solid dispersions (BSDs) were developed. Formulation S1 comprising a 1:1 weight ratio of Dex and Syloid 244FP ® was chosen as the optimum BSD formulation due to its better solubility profile. Afterward, 20 TSD formulations were developed using the optimum BSD. The formulation containing Syloid 244FP ® with 40% Gelucire 48/16 ® (S18) and Poloxamer 188 ® (S23) successfully enhanced the solubility by 28.23 and 38.02 times, respectively, in pH 6.8, while dissolution was increased by 1.99- and 2.01-fold during the first 5 min as compared to pure drug. The in vivo gastroprotective study in rats suggested that the average gastric lesion index was in the order of pure Dex (8.33 ± 2.02) > S1 (7 ± 1.32) > S18 (2.17 ± 1.61) > S23 (1.83 ± 1.04) > control (0). The in vivo anti-inflammatory study in rats revealed that the percentage inhibition of swelling was in the order of S23 (71.47 ± 2.16) > S18 (64.8 ± 3.79) > S1 (54.14 ± 6.78) > pure drug (18.43 ± 2.21) > control (1.18 ± 0.64) after 6 h. ELISA results further confirmed the anti-inflammatory potential of the developed formulation, where low levels of IL-6 and TNF alpha were reported for animals treated with S23. Therefore, S23 could be considered an effective formulation that not only enhanced the solubility and bioavailability but also reduced the gastric irritation of Dex.

Berberine-rich extract (BRE) prepared from Berberis lycium root bark using green extraction approach and its marker compound berberine has a broad spectrum of clinical applications. Berberine's potential pharmacological effects include anticancer, antidiarrheal, antidiabetic, antimicrobial and anti-inflammatory activities. In current work, BRE and berberine were evaluated for their therapeutic prospects in inflammation models. The comparative effect of BRE and berberine against inflammation was determined through in vitro chemiluminescence technique. The in vivo anti-inflammatory evaluation of BRE and berberine (25, 75, and 125 mg/kg) compared to diclofenac (10 mg/kg) was performed in carrageenan and formaldehyde-induced inflammation in Wistar rats. Histopathological and biochemical studies were conducted to find the comparative anti-inflammatory potential of BRE and berberine on pathological hallmarks induced by formaldehyde. Moreover, the modulatory effects on inflammatory biomarkers were also investigated through qPCR. ELISA (enzyme-linked immunoassay test assay) was performed to investigate the expression of pathological protein biomarkers like TNF-α and IL-6 and levels of antioxidant enzymes were estimated in liver homogenates. Both BRE and berberine markedly (p < .001) reduced paw diameter and inflammation in carrageenan and formaldehyde-induced inflammation. The levels of antioxidant enzymes were recovered (p < .001) by BRE and berberine treatments, and compared to the formaldehyde-treated inflammation model. Both BRE and berberine remarkably downregulated the mRNA and protein expression of inflammatory biomarkers. BRE similar to berberine mitigated the level of antioxidant enzymes in liver homogenate. The undertaken study suggests that BRE, a natural, green, and therapeutically bioequivalent to berberine could be used as an economical phytomedicine in the treatment of inflammatory disorders. PRACTICAL APPLICATIONS: Anti-inflammatory drugs like NSAIDS are associated with serious adverse effects like gastrointestinal ulcer, worsening of preexisting cardiovascular disorders, and renal failure. Therefore, there is a constant demand to develop novel, inexpensive therapeutic strategies to treat the inflammatory disorder with the least harmful effects. Pure phytochemicals with anti-inflammatory potential are costly and hard to isolate, therefore green microwave-assisted extraction technique is developed to get the rich bioequivalent extract. Berberis lycium a medicinal plant with berberine as a major bioactive constituent, has wide acceptance in traditionally used medicine and as food. Pharmacological studies revealed its hepatoprotective, anticancer, antidiabetic, and antihypertensive activities. BRE was prepared by green microwave-assisted extraction and enrichment by resin column to get a higher yield of berberine. The comparative anti-inflammatory effect of BRE and berberine was determined by in vitro and in vivo studies. Results obtained from this experimental work contribute beneficial guidance that reinforces the use of the BRE to treat inflammatory disorders., (© 2022 Wiley Periodicals LLC.)

Objective: The aim of the study was to assess the knowledge, attitudes and practices of students regarding the use of antibiotics in Punjab, Pakistan. Participants: 525 medical and non-medical students from Punjab in Pakistan. Methods: The t-test and ANOVA were used to compare the average response of respondents. Chi-square test was used to measure the association of different elements. Results: The mean age was 20.78 ± 2.10%. About 14% of the students agreed about the appropriateness of antibiotics for viral infections, and 15% of students said they stopped taking the drugs when symptoms subsided. 65.7% of students took antibiotics only when prescribed by a doctor and 54% bought antibiotics without prescription. Statistically significant results were found among the students who had heard about the antibiotic resistance ( p  < 0.05). Conclusion: This study will help assess the adequacy of current educational campaigns, maximize rationalization of antibiotic use, and minimize gaps in knowledge and attitudes.

Polycystic ovarian syndrome (PCOS) is an heterogenous, endocrine, metabolic, and multidisciplinary disorder of reproductive-aged females that aggravates insulin resistance, hyperandrogenism, obesity, menstrual irregularities, and infertility. Bitter melon is consumed as vegetable in various parts of the world. The purpose of this study was to provide the rationale for the folkloric uses of bitter melon (Momordica charantia L.) in reproductive abnormalities. HPLC analysis of standardized aqueous methanolic extract of bitter melon revealed the presence of various phytochemicals such as quercetin, gallic acid, benzoic acid, chlorogenic acid, syringic acid, p -coumaric acid, ferulic acid, and cinnamic acid. Twenty-five Swiss albino adult female rats (120-130 g) were acquired and divided into two groups (5 + 20). Letrozole (1 mg/kg p.o .) was used for four weeks to induce PCOS in twenty rats. Disease induction was confirmed by vaginal smear cytology analysis under the microscope. Animals were further divided into four groups, with one group as PCOS group, and the remaining three are treated with standardized extract of bitter melon (500 mg/kg p.o. ), bitter melon plus metformin (500 mg/kg p.o. ), and metformin alone for the period of next four weeks. After four weeks, the rats were euthanized at diestrus stage. Ovaries of the experimental animals were removed and fixed in 10% buffered formalin, and blood samples were obtained from direct cardiac puncture and stored. Ovaries histopathological analysis showed cystic follicles (9-10) in PCOS group, while, in all the treatment groups, we found developing and mature follicles. Similarly, hormone analysis showed significant ( p < 0.001) reduction of LH surge, insulin, and testosterone levels and improvement in FSH levels. Lipid profile and antioxidant enzymes status were also significantly ( p < 0.001) improved. In conclusion, the study validates the bitter melon potential as an insulin sensitizer and ovulation enhancer and authenticates its potential in PCOS management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Liaqat Hussain et al.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Uzma Saleem et al.)

The occurrence of fungal infections has increased over the past two decades. It is observed that superficial fungal infections are treated by conventional dosage forms, which are incapable of treating deep infections due to the barrier activity possessed by the stratum corneum of the skin. This is why the need for a topical preparation with advanced penetration techniques has arisen. This research aimed to encapsulate fluconazole (FLZ) in a novasome in order to improve the topical delivery. The novasomes were prepared using the ethanol injection technique and characterized for percent entrapment efficiency (EE), particle size (PS), zeta potential (ZP), drug release, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and antifungal activity. The FN7 formulation with 94.45% EE, 110 nm PS and -24 ZP proved to be the best formulation. The FN7 formulation showed a 96% release of FLZ in 8 h. FTIR showed the compatibility of FLZ with excipients and DSC studies confirmed the thermal stability of FLZ in the developed formulation. The FN7 formulation showed superior inhibition of the growth of Candida albicans compared to the FLZ suspension using a resazurin reduction assay, suggesting high efficacy in inhibiting fungal growth.

Traditionally, Sarcococca saligna has been used for the treatment of arthritis and many other inflammatory disorders. The current study was planned to give scientific evidence to this traditional use of S. saligna. Phytochemical profiling of SSME was carried out by using electrospray ionization mass spectrometry (ESI-MS/MS). Complete Freund's adjuvant (CFA), 150 μL was injected in the subplantar region of the left hind paw to induce arthritis in rats. Aqueous methanolic extract of S. saligna (SSME) was administered orally at 250, 500, or 1000 mg/kg dose from the 7th day to the 28th day of the study to explore its anti-arthritic potential. Histopathological and radiographic assessment of joints and enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) analyses were performed. Determination of oxidative stress biomarkers in the serum was also carried out. ESI-MS/MS identified ten such phytoconstituents which have reported strong anti-inflammatory and anti-arthritic activity. The SSME extract considerably reduced paw inflammation and arthritic index, subdued cachexia, and significantly improved biochemical and hematological changes. Oxidative stress decreased in SSME administered rats dose-dependently. Histopathological and radiographic evaluations also showed the anti-arthritic activity of SSME, which was associated with the downregulation of tumor necrosis factor (TNF)-α, nuclear factor (NF)-kB, COX-2, interleukin (IL)-6, and IL-1β and upregulation of I-kB, IL-4, and IL-10, in contrast to disease group rats. The outcomes of the study proposed that S. saligna have anti-arthritic potential, supporting its traditional use for rheumatoid arthritis treatment., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: the primary function of the kidney is to eliminate metabolic waste products and xenobiotics from the circulation. During this process, the kidney may become vulnerable to toxicity., Objective: it was aimed to investigate the impact of thymoquinone (TQ) in mercuric chloride (HgCl 2 )-induced nephrotoxicity through estimation of various proteins involved in natural defense mechanisms., Material and Methods: HgCl 2 (0.4 mg/kg) was administered to all groups ( n = 5) except for the normal control. Three treatment groups received TQ (5, 10, and 15 mg/kg) 60 min before HgCl 2 administration. The protective effect of TQ was evaluated from renal and liver function biomarkers, urine examination, glomerulus filtration rate (GFR), histopathological features, oxidative stress biomarkers, Hsp-70, apoptosis biomarkers, and gene expression., Results: TQ significantly attenuated hazardous effects of HgCl 2 on renal and hepatic tissues. Urine albumin and glucose were considerably low in the treated groups in comparison with the HgCl 2 group. TQ treatment also enhanced % GFR in rats. TQ-enhanced superoxide dismutase, catalase, and glutathione levels by enhancing the expression level of nuclear factor erythroid 2-related factor 2 (Nrf2). TQ increased Hsp-70 and Bcl-2 levels and reduced caspase-3 activity. TQ also protected cells against HgCl 2 -induced cell death and decreased % DNA fragmentation. TQ increased the expression of protective proteins metallothionein I and II and reduced the expression of kidney injury molecule-1 (Kim-1)., Conclusion: TQ showed protective effects against HgCl 2 -induced nephrotoxicity through modifications of various constitutive and inducible protein and enzyme levels in renal tissues., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

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., (© 2021 The Author(s). Published by BRI.)

Cucurbita pepo is used as a vegetable in Pakistan and its seeds are also rich in tocopherol. Data showed the pivotal role of tocopherol in the treatment of Parkinson's disease (PD). The current study was designed to probe into the antiparkinson activity of methanolic extract of C. pepo (MECP) seeds in the haloperidol-induced Parkinson rat model. Behavioral studies showed improvement in motor functions. The increase in catalase, superoxide dismutase, glutathione levels whereas the decreases in the malondialdehyde and nitrite levels were noted in a dose-dependent manner. Acetylcholine-esterase (AchE) activity was increased. Molecular docking results revealed significant binding interaction of selected phytoconstituents within an active site of target protein AchE (PDB ID: 4EY7). Furthermore, α-synuclein was up regulated with down regulation of TNF-α and IL-1β in the qRT-PCR study. Subsequently, ADMET results on the basis of structure to activity predictions in terms of pharmacokinetics and toxicity estimations show that selected phytochemicals exhibited moderately acceptable properties. These properties add knowledge towards the structural features which could improve the bioavailability of selected phytochemicals before moving towards the initial phase of the drug development. Our integrated drug discovery scheme concluded that C. pepo seeds could ameliorate symptoms of PD and may prove a lead remedy for the treatment of PD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Obesity has become a genuine global pandemic due to lifestyle and environmental modifications, and is associated with chronic lethal comorbidities. Various environmental factors such as lack of physical activity due to modernization and higher intake of energy-rich diets are primary obesogenic factors in pathogenesis of obesity. Genome-wide association study has identified the crucial role of FTO (fat mass and obesity) in human obesity. A bunch of SNPs in the first intron of FTO has been identified and subsequently correlated to body mass index and body composition. Findings of in silico, in vitro, and in vivo studies have manifested the robust role of FTO in regulation of energy expenditure and food consumption. Numerous studies have highlighted the mechanistic pathways behind the concomitant functions of FTO in adipogenesis and body size. Current investigation has also revealed the link of FTO neighbouring genes i.e., RPGRIP1L, IRX3 and IRX5 and epigenetic factors with obesity phenotypes. The motive behind this review is to cite the consequences of FTO on obesity vulnerability., (© 2021 John Wiley & Sons Australia, Ltd.)

Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead to neuronal cell death. Alzheimer's disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset and gradually worsens. Neuropathology, AD is characterized by the presence of neuroinflammation, mitochondrial dysfunction, increased oxidative stress, decreased antioxidant defense as well as increased acetylcholinesterase activity. Moreover, enhanced expression of amyloid precursor proteins leads to neural apoptosis, which has a vital role in the degeneration of neurons. The inability of commercial therapeutics to treat a single feature of AD pathology leads to the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid; latest studies revealed that ellagic acid can initiate numerous cell signaling transmissions and decrease the progression of neurodegeneration. The neuroprotective effects of ellagic acid to protect the neurons against neurodegenerative events are due to its antioxidant effect, iron chelating, and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mechanism of action of ellagic acid against AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tribulus terrestris (T.T.) is a rich source of flavonoids and saponins, which have been reported to have neuroprotective and antioxidant potential. The current study was planned to investigate the anti-Parkinson's activity of T. terrestris methanol extract (TTME). It was hypothesized that TTME possessed antioxidant potential and can ameliorate Parkinson's disease (PD) via modulation of α-synuclein, acetylcholinesterase (AChE), TNF-α, and IL-1β. To test this hypothesis, in silico and in vivo studies were performed. The PD model in rats was prepared by giving haloperidol, 1 mg/kg, i.p. Rats were divided into six groups: control, disease control, standard, and treatment groups receiving TTME orally at 100, 300, and 1000 mg/kg dose levels for 21 days. Behavioral observations and biochemical analyses were done. The TTME modulatory effect on mRNA expression of α-synuclein, AChE, TNF-α, and interleukins in the brain homogenate was estimated by RT-PCR. Compounds detected in HPLC analysis disrupted the catalytic triad of AChE in in silico studies. Behavioral observations showed significant ( p < 0.05) improvement in a reversal of catatonia, muscular strength, locomotor functions, stride length, and exploration in a dose-dependent manner (1000 >300 >100 mg/kg) of PD rats. Endogenous antioxidant enzyme levels CAT, SOD, GSH, and GPx were significantly restored at a high dose ( p < 0.05) with a notable ( p < 0.05) decrease in the MDA level in TTME-treated groups. TTME at a high dose significantly ( p < 0.05) decreased the level of acetylcholinesterase. RT-PCR results are showing down-regulation in the mRNA expression levels of IL-1β, α -synuclein, TNF-α, and AChE in TTME-treated groups compared to the disease control group, indicating neuroprotection. It is concluded that TTME has potential to ameliorate the symptoms of Parkinson's disease., Competing Interests: The authors declare no competing financial interest.

Tribulus terrestris (T.T) is enriched with steroidal saponins and flavonoids which have neuroprotective effect. The study was aimed to explore the potential of T.T methanol extract (T.T ME) for anti-Alzheirmer activity along with its safety evaluation. Plant was characterized by physicochemical, phytochemical and GCMS analyses whereas acute oral toxicity (OECD 425) was performed for safety evaluation. AlCl 3 induced Alzheimer's disease rat model was used for anti-Alzheirmer activity. T.T ME was given orally at 100, 300 and 1000 mg/kg doses for 21 days and behavioral parameters were observed on 22nd study day. Physicochemical parameters were in permissible limits. GCMS analysis showed eight different compounds and benzene dicarboxylic acid showed maximum % peak area (64.19). No mortality was noted in acute toxicity study. Behavioral studies showed highly significant (p<0.001) improvement in T.T ME treated groups. Antioxidant enzymes and acetylcholinesterase levels were significantly (p<0.05) improved on treatment with T.T ME. Histopathological analysis indicated that neurofibrillary tangles were significantly improved in T.T ME treated groups. Biochemical and behavioral results suggested that T.T contained lead compounds which are effective in the treatment of Alzheimer disease.

The evolution of antibiotic resistance in bacteria has increased research in the development of alternative therapies to conventional drugs. In this study, isolated phages were characterized and antibacterial activity was determined by standard agar disc diffusion method. The phages showed maximum propagation at 37°C to 40°C and highest viability at pH 7. Sugars influenced the bacteriophage viability. Sodium chloride decreased the phage propagation. Calcium chloride and magnesium chloride increased the phage propagation up to a certain limit. SDS-PAGE analysis confirmed the presence of protein cover and showed the various bands ranging from 10 to 200 kDa. Nucleic acid analysis confirmed the presence of RNA with a size of approximately 20 kb. Transmission electron microscopy indicated that the phages belong to Siphoviridae, Leviviridae, and Podoviridae families.