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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).
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Polycystic Ovarian Syndrome (PCOS) is a metabolic, reproductive, and endocrine disorder affecting women of fertile age. This study aimed to formulate a phytochemicals-based standardized aqueous ethanolic extract of Rubia cordifolia (SERC) to explore its pharmacological potential in PCOS-induced female rats and elucidate its mechanism. HPLC analysis revealed the presence of phytochemicals such as chlorogenic acid, p-coumaric acid, gallic acid, and kaempferol. Thirty female adult rats were divided into two groups for induction of PCOS (5 female rats in the normal control group + 25 female rats in the disease-induced group). PCOS was induced by administering letrozole (1 mg/kg p.o.) for 6 weeks. After PCOS induction, animals of the disease-induced group were divided into five groups: one group used as disease control (PCOS) group, one group on metformin (20 mg/kg), and three groups on SERC (200, 400, and 600 mg/kg). Histopathological analysis showed that PCOS induction reduced corpus luteum and developing follicles and increased cystic follicles. In comparison, SERC treatment improved ovulation with more primary and developing follicles. SERC reduced the serum insulin, LH surge, and testosterone levels while improving the FSH, estrogen, and progesterone serum levels. SERC significantly improved the oxidation status of the liver and normalized the lipid profile and liver function markers. In conclusion, SERC treated PCOS, and the suggested mechanism might be the restoration of aromatase activity and background inflammatory status improvement in ovaries.
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Amorphous solid dispersion (ASD) has emerged to be an outstanding strategy among multiple options available for improving solubility and consequently biological activity. Interestingly several binary SD systems continue to exhibit insufficient solubility over time. Therefore, the goal of current research was to design ternary amorphous solid dispersions (ASDs) of hydrophobic model drug curcumin (CUR) to enhance the solubility and dissolution rate in turn, presenting enhanced anti-bacterial, antioxidant and anti-inflammatory activity. For this purpose several ternary solid dispersions (TSDs) consisting of Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) were prepared using solvent evaporation method. Both solubility and dissolution testing of prepared solid dispersion were performed to determine the increase in solubility and dissolution. Solid state investigation was carried out utilizing infrared spectroscopy, also known as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),Differential scanning calorimetry (DSC) and X-ray diffraction (XRD).Optimized formulations were also tested for their biological effectiveness including anti-bacterial, anti-oxidant and anti-inflammatory activity. Amid all Ternary formulations F3 entailing 20 % soluplus® remarkably improved the solubility (186 µg/ml ± 3.95) and consequently dissolution (91 % ± 3.89 %) of curcumin by 3100 and 9 fold respectively. These finding were also supported by FTIR, SEM, XRD and DSC. In-vitro antibacterial investigation of F3 also demonstrated significant improvement in antibacterial activity against both gram positive (Staphylococcus aureus, Bacillus cereus) and gram negative (Pseudomonas aeruginosa, Escherichia coli) bacteria. Among all the tested strains Staphylococcus aureus was found to be most susceptible with a zone of inhibition of 24 mm ± 2.87. Antioxidant activity of F3 was also notably enhanced (93 % ± 5.30) in contrast to CUR (69 % ± 4.79). In vitro anti-inflammatory assessment also exhibited that F3 markedly protected BSA (bovine serum albumin) from denaturation with percent BSA inhibition of 80 % ± 3.16 in comparison to CUR (49 % ± 2.91). Hence, F3 could be an effective solid dispersion system for the delivery of model hydrophobic drug curcumin.
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In this study, we synthesized PVA-g-poly(AMPS) nanogels with the aim of enhancing the solubility and dissolution of ticagrelor (TGR). Ticagrelor, a noncompetitive, reversible P2Y12 receptor antagonist, is prescribed to treat acute coronary syndrome. Ticagrelor has restricted oral bioavailability (≈36%) because of its poor solubility and permeability. The free radical polymerization methodology was employed to synthesize nanogels with varied concentrations of poly(vinyl alcohol) (polymer), 2-acrylamido-2-methylpropanesulfonic acid (monomer), and N,N-methylene bis(acrylamide) (crosslinker). The prepared nanogels were analyzed by swelling studies, % drug entrapment efficiency (DEE), solubility studies, in vitro drug release studies, zeta sizer, Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The optimized formulation (PA5) revealed a particle size of 45.86 nm, with a polydispersity index (PDI) of 0.41 and a %DEE of 85.1%. FTIR spectroscopy, XRD, and SEM confirmed the formation of crosslinked nanogels with amorphous and porous structures, and TGA/DSC proved their thermal stability. In vitro dissolution studies showed 99.91% drug release, and the ticagrelor solubility from the synthesized formulations was significantly improved up to 8.2-fold. All formulations followed the Korsmeyer-Peppas model with the Fickian diffusion as the release mechanism. The toxicity studies carried out on rats and the MTT assay on the Caco-2 cell line validated the biocompatibility of the nanogel formulations. The outcomes of the current study led to the conclusion that the PVA-g-poly(AMPS) nanogels synthesized by us could be used as dedicated pharmaceutical delivery systems to achieve enhanced solubility and dissolution of ticagrelor.
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[This corrects the article DOI: 10.1021/acsomega.3c09667.].
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Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05-0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01-0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05-0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.
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Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza. High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer.
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Background: Cigarette smoke (CS) is one of the primary causes of acute lung injury (ALI) via provoking pulmonary inflammation and oxidative stress. Despite substantial studies, no effective treatment for ALI is presently available. Purpose: New prospective treatment options for ALI are required. Thus, this project was designed to investigate the in vivo and in vitro protective effects of 70 % methanolic-aqueous crude extract of whole plant of Cichorium intybus (Ci.Mce) against CS-induced ALI. Study design: /methods: Initially, male Swiss albino mice were subjected to whole-body CS exposure for 10 continuous days to prepare CS-induced ALI models. Normal saline (10 mL/kg), Ci.Mce (100, 200, 300 mg/kg), and Dexamethasone (1 mg/kg) were orally administered to respective animal groups 1 h prior to CS-exposure. 24 hrs after the last CS-exposure, BALF and lungs were harvested to study the key characteristics of ALI. Next, HPLC analysis was done to explore the phytoconstituents. Results: Ci.Mce exhibited significant reductions in lung macrophage and neutrophil infiltration, lung weight coefficient, and albumin exudation. Additionally, it effectively ameliorated lung histopathological alterations and hypoxemia. Notably, Ci.Mce exerted inhibitory effects on the excessive generation of IL-6, IL-1ß, and KC in both CS-induced ALI murine models and CSE-stimulated RAW 264.7 macrophages. Noteworthy benefits included the attenuation of oxidative stress induced by CS, evidenced by decreased levels of MDA, TOS, and MPO, alongside enhanced TAC production. Furthermore, Ci.Mce demonstrated a marked reduction in CS-induced NF-κB expression, both in vivo and in vitro. Conclusion: Consequently, Cichorium intybus could be a therapeutic option for CS-induced ALI due to its ability to suppress inflammatory reactions, mitigate oxidative stress, and quell NF-κB p65 activation.
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Polycystic ovarian syndrome (PCOS) is a complex metabolic and endocrine disorder which affects women of reproductive age. It is a condition in which ovaries produce an excessive amount of androgen (the male sex hormone). Saraca asoca (Roxb.) Willd. is a plant of the Fabaceae family. This plant has been traditionally used as a uterine tonic in leucorrhea and dysmenorrhea due to its various pharmacological activities. In this study, the ethanolic extract of S. asoca (EESA) was evaluated for its potential to be used for the management of PCOS. HPLC analysis revealed the presence of various phytoconstituents: kaempferol, rutin, (-)-epicatechin, salicylic acid, and gallic acid. For PCOS induction, 30 adult female rats were randomly divided into two groups: the control group (n = 5) and the PCOS group (n = 25). Letrozole (1 mg/kg/day) was administered per orally (p.o.) for a period of 7 weeks for the induction of disease. Weekly body weight measurements and daily vaginal cytology examinations were performed for disease confirmation. After disease induction, the PCOS group was further divided into five groups (n = 5), that is, disease control, metformin, and EESA (200, 400, and 600 mg/kg) groups, respectively, and given treatment doses for next 5 weeks. After the treatment period, all animals were weighed and euthanized humanly. Blood samples were collected for hormonal assays, lipid profiles, and liver function tests. For histological assessment of ovarian cysts, ovaries were dissected. Livers were preserved to evaluate EESA's antioxidant properties. Histopathology analysis revealed that EESA reduced body weight and the number of cystic follicles. Furthermore, it also lowered the elevated levels of serum testosterone, luteinizing hormone, insulin, and malonaldehyde in PCOS rats while increasing the levels of follicle-stimulating hormone, estradiol, progesterone, prolactin, and other antioxidant enzymes such as superoxide dismutase, glutathione, and catalase. It can be concluded that EESA exhibited beneficial effects in normalizing the perturbed hormonal profile and improved the ovary status by decreasing the cystic follicle and improving the ovulation status in a dose-dependent manner.
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This study investigated pH-responsive Terbinafine HCL (TBH)-loaded nanogels as a new approach to treating superficial fungal infections. Acrylic acid (AA) is a synthetic monomer that was crosslinked with a natural polymer (gelatin) using a free radical polymerization technique to fabricate gelatin-g-poly-(acrylic acid) nanogels. Ammonium persulphate (APS) and N, N'-methylene bisacrylamide (MBA) were used as the initiator and crosslinker, respectively. Developed gelatin-g-poly-(acrylic acid) nanogels were evaluated for the swelling study (pH 1.2, 5, 7.4), DEE, particle size, FTIR, thermal stability (TGA, DSC), XRD, SEM, DEE, and in vitro drug release study to obtain optimized nanogels. Optimized nanogels were incorporated into 1% HPMC gel and then evaluated in comparison with Lamisil cream 1% for TBH stratum corneum retention, skin irritation, and in vitro and in vivo antifungal activity studies. Optimized nanogels (AAG 7) demonstrated a 255 nm particle size, 82.37% DEE, pH-dependent swelling, 92.15% of drug release (pH) 7.4 within 12 h, and a larger zone of inhibition compared to Lamisil cream. HPMC-loaded nanogels significantly improved the TBH skin retention percentage, as revealed by an ex vivo skin retention study, indicating the usefulness of nanogels for topical use. In vivo studies conducted on animal models infected with a fungal infection have further confirmed the effectiveness of nanogels compared with the Lamisil cream. Hence, Gelatin-g-poly-(acrylic acid) nanogels carrying poorly soluble TBH can be a promising approach for treating superficial fungal infections.
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The most common female endocrinopathy, polycystic ovarian syndrome (PCOS), generally affects women of childbearing age. Hippophae rhamnoides L. has been traditionally used to improve menstrual cyclicity. Gas chromatography by flame ionization detection analysis showed that it contained various phytoconstituents such as omega-3 fatty acid, phytosterols, palmitic acid, oleic acid, and linoleic acid. H. rhamnoides L. (HR) nano-emulsion was also formulated. HR and its encapsulated nano-emulsion (HRNE) were evaluated for the treatment of PCOS. Thirty-five healthy female adult albino rats were acquired and divided into seven groups (n = 5). Letrozole (1 mg/kg) was used for 5 weeks to induce the disease. To confirm disease (PCOS) induction, the animals were weighed weekly and their vaginal smears were analyzed daily under a microscope. After PCOS induction, animals were treated with metformin, HR, and HRNE with two different doses (0.5/kg and 1 g/kg, p.o.) for 5 weeks. At the end of the treatment, animals were euthanized, and blood was collected for hormonal assessment, lipid profiling, and liver functioning test assessment. Both the ovaries were preserved for histopathology and liver for the purpose of assessment of antioxidant potential. The results revealed that HR and HRNE at both doses improved the hormonal imbalance; follicle-stimulating hormone, estrogen, and progesterone levels are increased, while luteinizing hormone surge and testosterone level are controlled. Insulin sensitivity is improved. Ovarian histopathology showed that normal ovarian echotexture is restored with corpus luteum and mature and developing follicles. HR and HRNE also improved the lipid profile and decreased lipid peroxidation (MDA) with improved antioxidant markers (SOD, CAT, and GSH). Results were statistically analyzed by one-way analysis of variance and were considered significant only if p < 0.05. In conclusion, it can be postulated that H. rhamnoides L. proved effective in the management of PCOS and its nano-emulsion effects were statistically more significant, which might be due to better bioavailability.
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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.
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Doença de Parkinson , Camundongos , Animais , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Haloperidol/toxicidade , Haloperidol/uso terapêutico , Dopamina/metabolismo , Encéfalo/metabolismoRESUMO
Acute myeloid leukemia (AML) is a highly heterogeneous subtype of hematological malignancies with a wide spectrum of cytogenetic and molecular abnormalities, which makes it difficult to manage and cure. Along with the deeper understanding of the molecular mechanisms underlying AML pathogenesis, a large cohort of novel targeted therapeutic approaches has emerged, which considerably expands the medical options and changes the therapeutic landscape of AML. Despite that, resistant and refractory cases caused by genomic mutations or bypass signalling activation remain a great challenge. Therefore, discovery of novel treatment targets, optimization of combination strategies, and development of efficient therapeutics are urgently required. This review provides a detailed and comprehensive discussion on the advantages and limitations of targeted therapies as a single agent or in combination with others. Furthermore, the innovative therapeutic approaches including hyperthermia, monoclonal antibody-based therapy, and CAR-T cell therapy are also introduced, which may provide safe and viable options for the treatment of patients with AML.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Imunoterapia , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing involves initiation of inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Despite the availability of multiple preparations for management of burn wound, there is dire need for efficacious alternative agents. Current approaches for burn wound management include pharmaceutical agents and antibiotics. However, high cost of synthetic drugs and accelerated resistance to antibiotics is challenging for both developed and developing nations. Among alternative options, medicinal plants have been a biocompatible, safe and affordable source of preventive/curative approaches. Due to cultural acceptance and patient compliance, there has been a focus on the use of botanical drugs and phytochemicals for burn wound healing. Keeping in consideration of medicinal herbs and phytochemicals as suitable therapeutic/adjuvant agents for burn wound management, this review highlights therapeutic potential of 35 medicinal herbs and 10 phytochemicals. Among these, Elaeis guineensis, Ephedra ciliate and Terminalia avicennioides showed better burn wound healing potential with varied mechanisms such as modulation of TNF-alpha, inflammatory cytokines, nitric oxide, eicosanoids, ROS and leukocyte response. Phytochemicals (oleanolic acid, ursolic acid, kirenol) also showed promising role in burn wound management though various pathways involving such as down regulation of TNF-alpha, IL-6 and inflammatory mediators including plasma proteases and arachidonic acid metabolites. This review provides a pavement for therapeutic/adjuvant use of potential botanical drugs and novel druggable phyto-compounds to target skin burn injury with diverse mechanisms, affordability and safety profile.
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Plantas Medicinais , Humanos , Fator de Necrose Tumoral alfa , Cicatrização , Inflamação , Compostos Fitoquímicos/farmacologiaRESUMO
Background: Polycystic ovarian syndrome (PCOS) is an endocrine metabolic disorder of women. Purpose: This study aimed to explore the potential of aqueous extract of Garcinia cambogia Desr. (AEGC) in PCOS. Methodology: The HPLC was used to determine the phytoconstituents present in Garcinia cambogia. Thirty adult female albino rats were divided into 6 groups: Normal control (NC) disease Control (PCOS; letrozole 1 mg/kg), plant extract (AEGC 100, 300, 500 mg/kg) and standard (metformin; 20 mg/kg). Disease was confirmed by vaginal smear cytology. After 10 weeks, animals were euthanized, ovaries dissected for histopathology, blood collected for hormonal and biochemical analysis. Results: HPLC analysis showed the presence of phenolic contents; chlorogenic acid, gallic acid, coumaric acid while flavonoid contents were quercetin, kaempferol, and rutin. After treatment, there was dose dependent reduction of weight, ovarian cysts, improvement of follicle growth. DPPH radical scavenging percentage was 67.89%. Hormonal analysis showed a significant improvement (P < .05) in follicle stimulating hormone (FSH), estrogen, and progesterone while a reduction in testosterone, luteinizing hormone (LH) and insulin level. Antioxidant enzymatic markers were significantly (P < .05) increased. Lipid profile and LFTs were also improved. Conclusions: The study validated the potential of Garcinia cambogia in the management of PCOS.
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The acute promyelocytic leukemia (APL) driver ZBTB16/RARα is generated by the t(11;17) (q23;q21) chromosomal translocation, which is resistant to combined treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) or conventional chemotherapy, resulting in extremely low survival rates. In the current study, we investigated the effects of hyperthermia on the oncogenic fusion ZBTB16/RARα protein to explore a potential therapeutic approach for this variant APL. We showed that Z/R fusion protein expressed in HeLa cells was resistant to ATO, ATRA, and conventional chemotherapeutic agents. However, mild hyperthermia (42 °C) rapidly destabilized the ZBTB16/RARα fusion protein expressed in HeLa, 293T, and OCI-AML3 cells, followed by robust ubiquitination and proteasomal degradation. In contrast, hyperthermia did not affect the normal (i.e., unfused) ZBTB16 and RARα proteins, suggesting a specific thermal sensitivity of the ZBTB16/RARα fusion protein. Importantly, we found that the destabilization of ZBTB16/RARα was the initial step for oncogenic fusion protein degradation by hyperthermia, which could be blocked by deletion of nuclear receptor corepressor (NCoR) binding sites or knockdown of NCoRs. Furthermore, SIAH2 was identified as the E3 ligase participating in hyperthermia-induced ubiquitination of ZBTB16/RARα. In short, these results demonstrate that hyperthermia could effectively destabilize and subsequently degrade the ZBTB16/RARα fusion protein in an NCoR-dependent manner, suggesting a thermal-based therapeutic strategy that may improve the outcome in refractory ZBTB16/RARα-driven APL patients in the clinic.
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Hipertermia Induzida , Leucemia Promielocítica Aguda , Humanos , Antineoplásicos/farmacologia , Trióxido de Arsênio/uso terapêutico , Células HeLa , Leucemia Promielocítica Aguda/terapia , Leucemia Promielocítica Aguda/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas de Fusão Oncogênica/uso terapêutico , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Tretinoína/farmacologia , Tretinoína/uso terapêuticoRESUMO
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.
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Convolvulus , Ratos , Animais , Ratos Wistar , Metanol , Pomadas , Quercetina , Antioxidantes/farmacologia , Glicogênio Sintase Quinase 3 beta , Simulação de Acoplamento Molecular , Cicatrização , Emolientes , Extratos Vegetais/farmacologia , GentamicinasRESUMO
Aim: Liver regulates metabolism of biomolecules and injury of liver causes distortion of metabolic functions. This injury may be oxidative or inflammatory induced by numerous factors including alcohol, pathogens and xenobiotics. This scientific study was planned to investigate the anti-inflammatory and anti-oxidant potential of p-coumaric acid (p-CA) on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN) induced liver injury. Methods: DPPH analysis, reducing power assay and HPLC analysis were performed during in-vitro studies of p-CA. Similarly, in-vivo experiments were performed using Wistar Albino rats. Normal control and intoxicated group received (5mL/kg normal saline p.o), standard treatment groups received ascorbic acid (100mg/kg p.o) and silymarin (25mg/kg p.o), while p-CA treatment groups received (100mg/kg p.o) for 28-days. After completion of 28-days, LPS/D-GalN injection (300 mg D-GalN/kg and 10 µg LPS/kg i.p.) was given at 6th, 12th and 24-hours to all groups except normal control group. Animals were sacrificed; serum and liver samples were harvested and subjected to biochemical and histological examinations, respectively. Results: The results revealed that p-CA possess strong antioxidant activity. Increased levels of leukocyte infiltration (TLC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), lipid panel (eg TG, TC, LDL-C, VLDL-C), whereas decreased HDL-C levels noticed in LPS/D-GalN groups as compared to normal control groups. Pro-Inflammatory markers (eg TNF-α, IL-6, IL-1ß) and lipid peroxidation marker, eg malondialdehyde (MDA) increased while superoxide dismutase (SOD) and reduced glutathione (GSH) levels were decreased significantly in groups treated with LPS/D-GalN. ANOVA with Bonferroni post hoc analysis was used for statistical analysis of. H&E staining was done to assess architectural abnormalities among liver cells. Conclusion: In conclusion, p-CA could ameliorate LPS/D-GalN induced hepatic injury via regulation of immune responses, liver function enzymes, lipid profile, oxidative stress and pro-inflammatory markers.
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Doença Hepática Induzida por Substâncias e Drogas , Silimarina , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Aspartato Aminotransferases/metabolismo , Bilirrubina , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , LDL-Colesterol , Ácidos Cumáricos , Galactosamina/farmacologia , Glutationa/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Fígado , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Solução Salina/farmacologia , Silimarina/farmacologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
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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.