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Extracts of passion fruit peel and seed of Passiflora edulis (Passifloraceae) attenuate oxidative stress in diabetic rats

Kandandapani S, Balaraman AK, Ahamed HN

Chin J Nat Med, 2015 Sep;13(9):680-6.
PMID: 26412428 DOI: 10.1016/S1875-5364(15)30066-2

This study was aimed at evaluating the anti-diabetic potential of passion fruit Passiflora edulis (EPE) extracts in diabetic rats, following Streptozotocin (STZ) induced oxidative stress. Thirty adult Wistar rats were divided into five groups, with six rats in each group. The control rats were injected intraperitoneally with citrate buffer (pH 4.5). The remaining groups of rats were administered single dose of 45 mg·kg(-1) of STZ by intraperitoneal route to induce diabetes. The diabetic animals were treated with 250 and 500 mg·kg(-1) of EPE and glibenclamide 0.6 mg·kg(-1) for fifteen days by oral route. Blood glucose, end organ oxidative stress marker, and anti-oxidants were assayed. Further, histopathological investigation of pancreas was studied at the end of the experimentation. The results revealed that subacute administration of EPE significantly (P < 0.001) controlled the blood glucose level in the diabetic rats. In addition, EPE extract protected the end organs by restoring the anti-oxidants enzyme, significantly increasing super oxide dismutase level (SOD) and decreasing catalase (CAT) and TBARS level in visceral organs. In conclusion, that EPE extracts showed anti-diabetic and anti-oxidant potential against streptozotocin-induced diabetes.
Attenuation of COX-2 enzyme by modulating H2O2-mediated NF-κB signaling pathway by monoamine oxidase inhibitor (MAOI): a further study on the reprofiling of MAOI in acute inflammation

Sur D, Mondal C, Balaraman AK, Haldar PK, Maji HS, Bala A

Inflammopharmacology, 2023 Jun;31(3):1305-1317.
PMID: 36826724 DOI: 10.1007/s10787-023-01165-5

OBJECTIVE: This study aims to investigate the anti-inflammatory mechanism of monoamine oxidase inhibitor (MAOI) in carrageenan (CARR) induced inflammation models to reprofile their use. We also aimed to explore the role of monoamine oxidase (MAO)-mediated H2O2-NF-κB-COX-2 pathway in acute inflammation.
METHODS: In vitro anti-inflammatory activity and hydrogen peroxide (H2O2) scavenging activity were performed according to the established procedure. Inflammation was induced using CARR in BALB/c mice at the foot paw and peritoneal cavity. Hourly measurement of paw swelling was performed. The level of nitric oxide (NO), myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and nuclear factor κB (NF-κB) was determined using enzyme-linked immunosorbent assay (ELISA). Peritoneal fluid was collected to investigate total count, differential count of leukocytes, and capillary permeability.
RESULTS: In vitro anti-inflammatory evaluations revealed the potential role of MAOI to inhibit heat-induced protein denaturation and human red cell membrane destabilization. H2O2 inhibition activity of MAOI also proved their powerful role as an H2O2 scavenger. Treatment with MAOI in CARR-induced mice significantly reduced paw edema, leukocyte extravasation, and total and differential leukocyte count. The result of ELISA showed MAOI effectively reduce the level of COX-2, PGE2 and NF-κB in inflamed tissue.
CONCLUSIONS: In short, this study demonstrates that inhibition of H2O2 by MAOI alleviates CARR-induced paw edema possibly by inhibiting the H2O2-mediated NF-κB-COX-2 pathway. The present investigation identifies MAOI might reprofile for the treatment of acute inflammation also, the MAO enzyme may use as a novel therapeutic target to design and develop new class of anti-inflammatory agents.
Programmed Cell Death Protein 1 (PD-1) in Relation to PANoptosis: Immune Pharmacological Targets for Management of Breast Adenocarcinoma

Maitra S, Bhattacharya D, Paul S, Chowdhury PG, Mandal D, Haldar PK, et al.

Endocr Metab Immune Disord Drug Targets, 2023;23(13):1571-1585.
PMID: 36788687 DOI: 10.2174/1871530323666230213121803

Programmed cell death protein 1 or Programmed death-1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) research have tremendously been taken into great consideration in the field of cancer immune pharmacology. Cancer immunotherapy has been convoyed by a capable outcome over the past few years. PD-1 and PD-L1 play a pivotal role in attenuating immune involvement, modulating the activity of T-cells, and promoting different types of programmed cell death. Participation of antigen-specific T cells and regulatory T cells and their acute mutations during cancer cell invasion and migration may lead to challenges for three programmed cell death methods, namely, pyroptosis, apoptosis, and necroptosis called "PANoptosis". This review aimed to explore the correlation between the PD-1/PD-L1 pathway in "PANoptosis" using available recently published literature with several schematic representations. Hopefully, the review will facilitate the biomedical scientist targeting cancer immune pharmacological aspect for the management of Breast Adenocarcinoma shortly.
Revolutionizing Neurotherapeutics: Nanocarriers Unveiling the Potential of Phytochemicals in Alzheimer's Disease

Kamath AP, Nayak PG, John J, Mutalik S, Balaraman AK, Krishnadas N

Neuropharmacology, 2024 Jul 29.
PMID: 39084596 DOI: 10.1016/j.neuropharm.2024.110096

Neurological disorders pose a huge worldwide challenge to the healthcare system, necessitating innovative strategies for targeted drug delivery to the central nervous system. Alzheimer's disease (AD) is an untreatable neurodegenerative condition characterized by dementia and alterations in a patient's physiological and mental states. Since ancient times, medicinal plants have been an important source of bioactive phytochemicals with immense therapeutic potential. This review investigates new and safer alternatives for prevention and treatment of disease related to inevitable side effects associated with synthetic compounds. This review examines how nanotechnology can help in enhancing the delivery of neuroprotective phytochemicals in AD. Nevertheless, despite their remarkable neuroprotective properties, these natural products often have poor therapeutic efficacy due to low bioavailability, limited solubility and imperfect blood brain barrier (BBB) penetration. Nanotechnology produces personalized drug delivery systems which are necessary for solving such problems. In overcoming these challenges, nanotechnology might be employed as a way forward whereby customized medication delivery systems would be established as a result. The use of nanocarriers in the design and application of important phytochemicals is highlighted by this review, which indicate potential for revolutionizing neuroprotective drug delivery. We also explore the complications and possibilities of using nanocarriers to supply nutraceuticals and improve patients' standard of living, and preclinical as well as clinical investigations displaying that these techniques are effective in mitigating neurodegenerative diseases. In order to fight brain diseases and improve patient's health, scientists and doctors can employ nanotechnology with its possible therapeutic interventions.
Protein Kinase C (PKC)-mediated TGF-β Regulation in Diabetic Neuropathy: Emphasis on Neuro-inflammation and Allodynia

Changkakoti L, Das JM, Borah R, Rajabalaya R, David SR, Balaraman AK, et al.

Endocr Metab Immune Disord Drug Targets, 2023 Nov 06.
PMID: 37937564 DOI: 10.2174/0118715303262824231024104849

According to the World Health Organization (WHO), diabetes has been increasing steadily over the past few decades. In developing countries, it is the cause of increased morbidity and mortality. Diabetes and its complications are associated with education, occupation, and income across all levels of socioeconomic status. Factors, such as hyperglycemia, social ignorance, lack of proper health knowledge, and late access to medical care, can worsen diabetic complications. Amongst the complications, neuropathic pain and inflammation are considered the most common causes of morbidity for common populations. This review is focused on exploring protein kinase C (PKC)-mediated TGF-β regulation in diabetic complications with particular emphasis on allodynia. The role of PKC-triggered TGF-β in diabetic neuropathy is not well explored. This review will provide a better understanding of the PKC-mediated TGF-β regulation in diabetic neuropathy with several schematic illustrations. Neuroinflammation and associated hyperalgesia and allodynia during microvascular complications in diabetes are scientifically illustrated in this review. It is hoped that this review will facilitate biomedical scientists to better understand the etiology and target drugs effectively to manage diabetes and diabetic neuropathy.
Fulltext Clinical Investigation of Chemotherapeutic Resistance and miRNA Expressions in Head and Neck Cancers: A Thorough PRISMA Compliant Systematic Review and Comprehensive Meta-Analysis

Jayaraj R, Polpaya K, Kunale M, Kodiveri Muthukaliannan G, Shetty S, Baxi S, et al.

Genes (Basel), 2022 Dec 10;13(12).
PMID: 36553594 DOI: 10.3390/genes13122325

Background: Chemoresistance is a significant barrier to combating head and neck cancer, and decoding this resistance can widen the therapeutic application of such chemotherapeutic drugs. This systematic review and meta-analysis explores the influence of microRNA (miRNA) expressions on chemoresistance in head and neck cancers (HNC). The objective is to evaluate the theragnostic effects of microRNA expressions on chemoresistance in HNC patients and investigate the utility of miRNAs as biomarkers and avenues for new therapeutic targets. Methods: We performed a comprehensive bibliographic search that included the SCOPUS, PubMed, and Science Direct bibliographic databases. These searches conformed to a predefined set of search strategies. Following the PRISMA guidelines, inclusion and exclusion criteria were framed upon completing the literature search. The data items extracted were tabulated and collated in MS Excel. This spreadsheet was used to determine the effect size estimation for the theragnostic effects of miRNA expressions on chemoresistance in HNC, the hazard ratio (HR), and 95% confidence intervals (95% CI). The comprehensive meta-analysis was performed using the random effects model. Heterogeneity among the data collected was assessed using the Q test, Tau2, I2, and Z measures. Publication bias of the included studies was checked using the Egger's bias indicator test, Orwin and classic fail-safe N test, Begg and Mazumdar rank collection test, and Duval and Tweedie's trim and fill methods. Results: After collating the data from 23 studies, dysregulation of 34 miRNAs was observed in 2189 people. These data were gathered from 23 studies. Out of the 34 miRNAs considered, 22 were up-regulated, while 12 were down-regulated. The TaqMan transcription kits were the most used miRNA profiling platform, and miR-200c was seen to have a mixed dysregulation. We measured the overall pooled effect estimate of HR to be 1.516 for the various analyzed miRNA at a 95% confidence interval of 1.303-1.765, with a significant p-value. The null hypothesis test's Z value was 5.377, and the p-value was correspondingly noted to be less than 0.0001. This outcome indicates that the risk of death is determined to be higher in up-regulated groups than in down-regulated groups. Among the 34 miRNAs that were investigated, seven miRNAs were associated with an improved prognosis, especially with the overexpression of these seven miRNAs (miR15b-5p, miR-548b, miR-519d, miR-1278, miR-145, miR-200c, Hsa- miR139-3p). Discussion: The findings reveal that intricate relationships between miRNAs' expression and chemotherapeutic resistance in HNC are more likely to exist and can be potential therapeutic targets. This review suggests the involvement of specific miRNAs as predictors of chemoresistance and sensitivity in HNC. The examination of the current study results illustrates the significance of miRNA expression as a theragnostic biomarker in medical oncology.
Investigation on Anti-diabetic Efficacy of a Cucurbitaceae Food Plant from the North-East Region of India: Exploring the Molecular Mechanism through Modulation of Oxidative Stress and Glycosylated Hemoglobin (HbA1c)

Jana S, Gayen S, Gupta BD, Singha S, Mondal J, Kar A, et al.

Endocr Metab Immune Disord Drug Targets, 2024;24(2):220-234.
PMID: 37691221 DOI: 10.2174/1871530323666230907115818

BACKGROUND: The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India.
AIMS: We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c).
METHODS: Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model.
RESULTS: We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal.
CONCLUSION: Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.