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Aim: The aim of this study was to monitor prescription patterns, clinical outcomes, and adverse drug reactions (ADR) among patients of various interstitial lung diseases (ILDs). Materials and Methods: This prospective study was conducted in the Department of Pharmacology and Therapeutics in collaboration with the Department of Respiratory Medicine, King George's Medical University, Lucknow, for a period of 12 months (October 2020-September 2021). A total of 77 patients were enrolled after satisfying the inclusion and exclusion criteria. The prescriptions were collected, and necessary details were noted on the case report form. After completion of the study, the data were analyzed for prescription patterns, clinical outcomes, and quality of life with the help of a validated questionnaire-King's Brief ILD (KBILD) questionnaire. At the same time, ADRs, if any, were assessed using Hartwig's Severity Assessment Scale and Naranjo Causality Assessment Scale. Results: The most common ILD was acute/chronic hypersensitivity pneumonitis (HP). Average number of drugs per encounter was 4.45. Crepitations were the most common clinical signs. Clubbing and rhonchi were reported maximum in idiopathic pulmonary fibrosis. It was found that psychological, breathlessness and activities, chest symptoms, and total KBILD reduced significantly after 3 months as compared to baseline with a statistically significant difference as P < 0.01. ADRs were found in 23.38% (18) of the subjects. Maximum ADR reported was gastritis (9.09%), followed by hepatitis (3.90%). Conclusion: The high proportion of patients clinically diagnosed with HP in our study highlights the importance of a detailed environmental exposure history in the diagnostic evaluation of patients with ILD to avoid inaccurate diagnoses. ADR-related hospital admissions are a significant problem in the health-care system.
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BACKGROUND AND OBJECTIVE: Tobacco smoking is an established risk factor for chronic obstructive pulmonary disease (COPD). Current evidence suggests that non-tobacco-related risk factors vary geographically and are less understood than smoking. This study aims to compare the risk factors, symptoms, and clinical features of smoking (S-COPD) and non-smoking (NS-COPD) in a COPD population. MATERIALS AND METHODS: In this retrospective cross-sectional study, 489 COPD patients were screened. Data on socio-demographics, smoking and medical history, other risk factors, symptoms, and clinical characteristics including COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) Dyspnea Scale were examined. RESULTS: Of the total selected 416 COPD patients, 35.34% were NS-COPD while 64.66% were S-COPD. S-COPD was predominant in males, whereas NS-COPD was predominant in females (P < 0.0001). In NS-COPD, biomass fuel exposure was a major risk factor (P < 0.0001), and 61% of subjects had a biomass fuel exposure index of >60. In bivariate and multivariate analyses, no risk factors were correlated with forced expiratory volume in 1 second (FEV1)% predicted, while among clinical features, duration of illness (P = 0.001) was correlated with lower values of FEV1 in the multivariate table of S-COPD. In the multivariate analysis, biomass fuel exposure (P = 0.039) and CAT score (P < 0.0001) were correlated with FEV1(%) in NS-COPD. CONCLUSION: Biomass fuel exposure is a substantial risk factor for NS-COPD and was correlated with FEV1(%) predicted. In addition, the CAT score correlated with disease severity in patients with NS-COPD. The development of COPD in non-smokers is being recognized as a separate phenotype and it should be managed according to risk factors.
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Antibody-drug conjugates (ADCs) are an important class of cancer therapies. They are complex molecules, comprising an antibody, a cytotoxic payload, and a linker. ADCs intend to confer high specificity by targeting a unique antigen expressed predominately on the surface of the tumor cells than on the normal cells and by releasing the potent cytotoxic drug inside the tumor causing cytotoxic cell death. Despite high specificity to tumor antigens, many ADCs are associated with off-target and on-target off-tumor toxicities, often leading to safety concerns before achieving the desirable clinical efficacy. Therefore, it is crucial to improve the therapeutic index (TI) of ADCs to enable the full potential of this important therapeutic modality.The review summarizes current approaches to improve the translation of safety, pharmacokinetics, and TI of ADCs. Common safety findings of ADCs resulting from off-target and on-target toxicities and nonclinical approaches to de-risk ADC safety will be discussed; multiple approaches of using preclinical and clinical dose and exposure data to calculate TI to guide clinical dosing will be elaborated; different approaches to improve TI of ADCs, including selecting the right target, right payload-linker and patients, optimizing physicochemical properties, and using fractionation dosing, will also be discussed.
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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.
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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.
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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.
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Trophoblast cell-surface antigen 2 (Trop 2) is a transmembrane glycoprotein that is highly expressed in various cancer types with relatively low or no baseline expression in most normal tissues. Its overexpression is associated with tumor growth and poor prognosis; Trop 2 is, therefore, an ideal therapeutic target for epithelial cancers. Several Trop 2 targeted therapeutics have recently been developed for the treatment of cancers, such as anti-Trop 2 antibodies and antibody-drug conjugates (ADCs), as well as Trop 2-specific cell therapy. In particular, the safety and clinical benefit of Trop 2-based ADCs have been demonstrated in clinical trials across multiple tumor types, including those with limited treatment options, such as triple-negative breast cancer, platinum-resistant urothelial cancer, and heavily pretreated non-small cell lung cancer. In this review, we elaborate on recent advances in Trop 2 targeted modalities and provide an overview of novel insights for future developments in this field.
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Moléculas de Adhesión Celular/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/fisiología , Moléculas de Adhesión Celular/química , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/fisiología , Humanos , Inmunoconjugados/uso terapéutico , Inmunoterapia AdoptivaRESUMEN
We are sorry to report that some images in Figure 1 reported in our recently published paper [...].
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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.
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India has got rich cultural inheritage in the forms of Ayurveda texts which are a rich and ample source of herbs, shrubs, trees and affluent in medicinally active phytoconstituents. Aconitum napellus is used for the cure of many ailments including rheumatoid arthritis, sciatica and gout. The present work attempts to evaluate the physicochemical and preliminary phytochemical studies on the tubers of Aconitum napellus along with its antidiabetic activity. The herbal standardization was carried out on the basis of organoleptic properties, physical characteristics and physicochemical properties. The body weight of ACON-I (1.25 mg/kg) and ACON-II (2.5 mg/kg) was recorded as 190.40 and 209.40 g, respectively, compared with 163.00 g in diabetic rats at day 28. The body weight of ACON-I and ACON-II was significantly increased compared with diabetic rats (p < 0.01). However, the body weight of ACON-I and ACON-II was decreased significantly (p < 0.01) compared with normal group (222.60 g). The blood glucose levels of diabetic rats and ACON-I group were recorded as 277.800 and 152.400 mg/dl, respectively, compared with 83.600 mg/dl in normal rats (p < 0.01). However, the HbA1c levels of diabetic rats and ACON-I group were recorded as 11.306 and 6.936% Hb, respectively, compared with 4.539% Hb in normal rats. The glucose and HbA1c levels of diabetic and ACON-I groups were significant compared with normal group (p < 0.01). The results of antidiabetic activity showed that the plant can be used as a potent source for the treatment of diabetes and its complications. The results of this work provided the referential information for the identification and standardization of Aconitum napellus along with its role as a hypoglycemic agent.
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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.
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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.
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Boraginaceae/toxicidad , Corteza de la Planta , Extractos Vegetales/farmacología , Alanina Transaminasa/sangre , Animales , Bilirrubina/sangre , Boraginaceae/química , Eritrocitos , Femenino , Corazón , Hematología , Riñón , Dosificación Letal Mediana , Hígado , Masculino , Neutrófilos , Corteza de la Planta/química , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Potasio/sangre , Ratas Sprague-Dawley , Factores SexualesRESUMEN
BACKGROUND AND PURPOSE: Inhibition of the T- and B-cell interaction through the CD40/CD40 ligand (L) axis is a favourable approach for inflammatory disease treatment. Clinical studies of anti-CD40L molecules in autoimmune diseases have met challenges because of thromboembolic events and adverse haemostasis. VIB4920 (formerly MEDI4920) is a novel CD40L antagonist and Tn3 fusion protein designed to prevent adverse haemostasis and immunopharmacology. We evaluated the pharmacokinetics, activity and toxicity of VIB4920 in monkeys. EXPERIMENTAL APPROACH: Cynomolgus monkeys received i.v. or s.c. 5-300 mg·kg-1 VIB4920 or vehicle, once weekly for 1 month (Studies 1 and 2) or 28 weeks (Study 3). VIB4920 exposure and bioavailability were determined using pharmacokinetic analyses, and immune cell population changes via flow cytometry. Pharmacological activity was evaluated by measuring the animals' capacity to elicit an immune response to keyhole limpet haemocyanin (KLH) and tetanus toxoid (TT). KEY RESULTS: VIB4920 demonstrated linear pharmacokinetics at multiple doses. Lymphocyte, monocyte, cytotoxic T-cell and NK cell counts were not significantly different between treatment groups. B-cell counts reduced dose-dependently and the T-cell dependent antibody response to KLH was suppressed by VIB4920 dose-dependently. The recall response to TT was similar across treatment groups. No thromboembolic events or symptoms of immune system dysfunctionality were observed. CONCLUSIONS AND IMPLICATIONS: VIB4920 demonstrated an acceptable safety profile in monkeys. VIB4920 showed favourable pharmacokinetics, dose-dependent inhibition of a neoantigen-specific immune response and no adverse effects on immune function following long-term use. Our data support the use of VIB4920 in clinical trials.
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Enfermedades Autoinmunes , Ligando de CD40 , Animales , Linfocitos B , Macaca fascicularisRESUMEN
Introduction Tuberculosis (TB) remains an important cause of morbidity and mortality worldwide. There are more than 20 drugs available for TB treatment. Hepatotoxicity is the most serious adverse drug reaction of anti-TB drugs. Various pathogenesis and genetic factors are associated with antituberculosis drug-induced hepatotoxicity (ATDIH). Antituberculosis drugs (ATDs) are mostly metabolized by N-acetyltransferase 2 (NAT2). Therefore, in this study, we aim to evaluate the role of the NAT2 genotype in ATDIH in the eastern Uttar Pradesh population. Methods A total of 100 TB patients who had been treated with anti-TB drugs were enrolled in this studied. In this group, 70 TB patients did not develop drug-induced hepatotoxicity (tolerant control group) and 30 TB patients developed ATDIH (ATDIH group). The genetic polymorphisms of the NAT2 genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype and allele frequencies were evaluated by the t-test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results There is a high percentage of slow acetylators in the Eastern Uttar Pradesh population. Four percent of people are fast acetylators, 34% are intermediate acetylators, and 62% are slow acetylators. The frequency of slow acetylators in the NAT2 genotype was commonly present and was not significantly different between the ATDIH (73.33%) and tolerant control groups (61.40%). However, the genotypic distribution of variants of slow-acetylator genotypes (NAT2*6/7, NAT2*5/7, and NAT2*5/6) was also not significantly different in ATDIH. Conclusion In the present study, the slow acetylators of the NAT2 genotype did not contribute to the elevated risk of ATDIH development in tuberculosis patients.
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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.
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Boraginaceae/química , Neuropatías Diabéticas/tratamiento farmacológico , Hexanos/química , Corteza de la Planta/química , Extractos Vegetales/farmacología , Animales , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/patología , Masculino , Extractos Vegetales/química , Ratas , Ratas Sprague-DawleyRESUMEN
Since the first approval of gemtuzumab ozogamicin (Mylotarg; Pfizer; CD33 targeted), two additional antibody-drug conjugates (ADC), brentuximab vedotin (Adcetris; Seattle Genetics, Inc.; CD30 targeted) and inotuzumab ozogamicin (Besponsa; Pfizer; CD22 targeted), have been approved for hematologic cancers and 1 ADC, trastuzumab emtansine (Kadcyla; Genentech; HER2 targeted), has been approved to treat breast cancer. Despite a clear clinical benefit being demonstrated for all 4 approved ADCs, the toxicity profiles are comparable with those of standard-of-care chemotherapeutics, with dose-limiting toxicities associated with the mechanism of activity of the cytotoxic warhead. However, the enthusiasm to develop ADCs has not been dampened; approximately 80 ADCs are in clinical development in nearly 600 clinical trials, and 2 to 3 novel ADCs are likely to be approved within the next few years. While the promise of a more targeted chemotherapy with less toxicity has not yet been realized with ADCs, improvements in technology combined with a wealth of clinical data are helping to shape the future development of ADCs. In this review, we discuss the clinical and translational strategies associated with improving the therapeutic index for ADCs.
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Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Animales , Biomarcadores , Estudios Clínicos como Asunto/normas , Desarrollo de Medicamentos , Monitoreo de Drogas , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Investigación Biomédica Traslacional/normas , Investigación Biomédica Traslacional/tendencias , Resultado del TratamientoRESUMEN
Most strategies used to prepare homogeneous site-specific antibody-drug conjugates (ADCs) result in ADCs with a drug-to-antibody ratio (DAR) of two. Here, we report a disulfide re-bridging strategy to prepare homogeneous ADCs with DAR of one using a dual-maleimide pyrrolobenzodiazepine (PBD) dimer (SG3710) and an engineered antibody (Flexmab), which has only one intrachain disulfide bridge at the hinge. We demonstrate that SG3710 efficiently re-bridge a Flexmab targeting human epidermal growth factor receptor 2 (HER2), and the resulting ADC was highly resistant to payload loss in serum and exhibited potent anti-tumor activity in a HER2-positive gastric carcinoma xenograft model. Moreover, this ADC was tolerated in rats at twice the dose compared to a site-specific ADC with DAR of two prepared using a single-maleimide PBD dimer (SG3249). Flexmab technologies, in combination with SG3710, provide a platform for generating site-specific homogenous PBD-based ADCs with DAR of one, which have improved biophysical properties and tolerability compared to conventional site-specific PBD-based ADCs with DAR of two.
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Antineoplásicos , Benzodiazepinas/química , Inmunoconjugados , Pirroles/química , Receptor ErbB-2/antagonistas & inhibidores , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Femenino , Humanos , Inmunoconjugados/química , Inmunoconjugados/farmacología , Células MCF-7 , Ratones Desnudos , Ratas , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Trastuzumab/química , Trastuzumab/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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.