Reversal mechanism of multidrug-resistant cancer cells by lectin as chemo-adjuvant and targeted therapy- a systematic review.

BACKGROUND: Cancer is characterized as the leading cause of death, and the susceptibility of cancer cells to develop resistance due to long-term exposure to complementary chemotherapeutic treatment is referred to as multidrug resistance cancer cells (MDRC), which is a significant obstacle in the treatment of malignancies. Since complementary medicine lost its effectiveness, the development of potential alternative and novel therapeutic approaches has been elevated to a top priority in recent years. In this context, a bioactive protein lectin from plant and animal sources exhibits an invaluable source of anticancer agents with vast therapeutic potential. PURPOSE: This manuscript's primary purpose is to enlighten the evidence-based (from 1986 to 2022) possible molecular mechanism of alternative treatment approaches using lectins over the complementary medicines used for cancer treatment. METHODS: The PRISMA rules have been followed properly and qualitative and quantitative data are synthesized systematically. Articles were identified based on Clinical and preclinical reports published on lectin that investigated the in-depth cellular mechanisms, of reverse drug integrative oncology, as a nano-carried targeted delivery. Articles were systematically screened from 1986 to 2022 and selected based on electronic database searches, Medline (PubMed), Google Scholar, Web of Science, Encyclopaedias, Scopus, and ClinicalTrials.gov database. RESULTS: The search turned up 4,212 publications from 38 different nations, of which 170 reference articles were used in our analysis, in 16 combination therapy and their mode of action, and 27 clinical trial studies including dosage and mechanism of action were included. Reports from the 30 lectins belonging to 28 different families have been included. The reversal mechanism of lectin and alternative therapy against MDRC is critically screened and according to a few clinical and preclinical reports, lectin can suppress the overexpressing genes like P-53, EGFR, and P-gp, MRP, and ABC transporter proteins associated with intracellular transportation of drugs. Since, the drug efflux mechanism leads to MDRC, in this phenomenon, lectin plays a key role in reversing the efflux mechanism. Few preclinical reports have mentioned that lectin shows synergism in combination with complementary medicine and as a nano drug carrier helps to deliver to the targeted site. CONCLUSION: We have discussed the alternative therapy using lectin and an in-depth insight into the reversal drug resistance mechanisms to combat MDRC cancer, enhance the efficacy, reduce toxicity and adverse events, and ensure targeted delivery, and their application in the field of cancer diagnosis and prognosis has been discussed. However, further investigation is necessary in drug development and clinical trials which could be helpful to elaborate the reversal mechanism and unlock newer treatment modalities in MDRC cancer.

Jackfruit waste: an invented anticancer therapy using Jacalin lectin from jackfruit seed.

Every food source contains both edible and inedible waste components. Millions of tonnes of trash from the food business are made from fruits, and these wastes are containing higher-value medicinal components, such as alkaloids, flavonoids, phenolic contents, a huge amount of proteins and secondary metabolites. These bioactive phytoconstituents are being used for the treatment of many serious fatal diseases. So, utilizing the recovered bioactive molecules from food wastes as functional ingredients offers a long-term alternative source of therapeutically active components that will lead to the discovery of novel phytoconstituents or novel treatment approaches. The goal of this systematic study is to provide an overview of the jackfruit (Artocarpus heterophyllus Lam, Moraceae) edible byproducts, such as jackfruit seeds that are largely neglected. This seed contains numerous bioactive lead molecules, such as carbohydrate-binding protein jacalin, which exhibits potent anticancer activity against colon cancer, blood cancer and breast cancer as well as can enlighten the new possible treatment approaches in targeted therapy and photodynamic chemotherapy. Moreover, jackfruit waste seed can be taken as a dietary food, which is having property to prevent and treat cancer and other lifestyle diseases. The works that have been carried out to utilize jackfruit waste other than the juicy edible bulbs have been reviewed in this article.

Inhibition of calculi forming oxalate by dietary Basella rubra organs: Litholytic activity

Abstract The inhibition of calculi forming oxalate by dietary Basella rubra plant organs leaf and stem pod has been investigated. The weight reduction assay was studied. Also a concoction of the plant organs was tested. Leaf extract was found with considerable activity whereas the concoction seems to be not much active as the stem pod extract. Soluble oxalate of the plant organs are partially removed prior to extraction of active constituents. The active component/s seem to be a non-protein and non-tannin molecule/s that may act through inhibition of calcium accumulation there by proving the positive activity against the calculi or kidney stone. Regular consumption of leaf and stem pod extracts of our plant would be helpful in calculi prophylaxis.

A combination of resveratrol and 3,3'-diindolylmethane, a potent radioprotector.

PURPOSE: Exposure to ionizing radiation causes damage to the genomic integrity and stability of the cell. Though a large number of molecules have been studied for their radioprotective capability, no single agent is available today that meets all the requirements of a good radiprotector. In this study, we have investigated a combination of Resveratrol (RSV) and 3,3'-Diindolyl methane (DIM) for its efficacy for radioprotection. It is our hypothesis that this combination that possesses less toxicity than synthetic compounds, free radical scavenging potential, and the capacity to interfere with the several of the signaling cascades that trigger damage to cell by ionizing radiation may possess good radioprotective capability. MATERIALS AND METHODS: Mice were pre-treated with a combination of RSV and DIM and the 30-day mortality assay, endogenous antioxidant levels in intestinal mucosa, metaphase chromosomal aberrations, and micronuclei formation were assessed after exposed to ionizing radiation. RESULTS: The dose modifying factor (DRF) obtained for RSV, DIM, and the combination is 1.15, 1.17, and 1.3, respectively. Pre-treatment of mice with the combination results in significant (***p = .001) protection of the endogenous antioxidant levels, chromosomal aberrations, micronuclei formation, after exposure to ionizing radiation. CONCLUSIONS: Our findings suggest that pre-treatment with the combination of RSV and DIM protects effectively from the ionizing radiation-induced damage at the molecular, cellular, and tissue levels by counteracting both the direct and indirect effects.

Possible role of DPP4 inhibitors to promote hippocampal neurogenesis in Alzheimer's disease.

As well-known to the scientific community, Alzheimer's disease (AD) is an irreversible neurodegenerative disease that ends up with impairment of memory and cognition. Patient quality of life can be enhanced by targeting neurogenesis as a therapeutic paradigm. Preserving functional activity of SDF-1α and GLP-1 by DPPIV inhibition will enhance the homing of stem cells and modulate cell signalling pathways. The non-invasive approach presented in this article is a major advantage for managing AD, as regular/conventional stem-cell therapy necessarily relies on the application of regenerative stem cells exogenously. Using DPP-4 inhibitors to achieve the SDF-1α/CXCR4 axis stabilisation and augmenting GLP-1 levels, will enhance the homing/recruitment of brain resident and non-resident circulating stem cells/progenitor cells towards the sites of lesion to increase synaptic plasticity, a promising approach and also a novel one as well.

Assessment of inhibitory potential of Pothos scandens L. on ovalbumin-induced airway hyperresponsiveness in balb/c mice.

Pothos scandens L. was used in Indian traditional medicine as an antiasthmatic drug. The ethanolic and aqueous extracts were prepared with aerial parts of P. scandens (PSE & PSA). ESI MS/MS of PSE ethanolic extract was carried out for the determination of chemical constituents. CP1 is isolated from the PSE, structurally confirmed with NMR and LCMS/MS. PSE, PSA and CP1 are evaluated against ovalbumin (OVA) induced airway hyperresponsiveness (AHR) in balb/c mice. The test drugs are administered p.o. prior to challenge with aerosolized 2.5% w/v OVA. Total and differential leucocyte count, nitrite (NO2), nitrate (NO3), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-13 (IL-13) are estimated in bronchoalveolar lavage fluid (BALF). Similarly, myeloperoxidase (MPO), malonaldehyde (MDA) and total lung protein (TLP) are estimated in the lungs. The results reveal a significant increase in total and differential leucocyte count, NO2, NO3, TNF-α, IL-6, and IL-13 in OVA induced AHR. However, these parameters are significantly decreased in PSE and PSA tested doses (PSE 100 & 200mg/kg). While, treatment with CP1 is less effective at 5 & 10mg/kg doses. Similar observations obtain for MPO and MDA in lungs. However, the mean value indicated that the PSE at 200mg/kg showed a significant restoration in all the parameters. Pro-inflammatory mediators are known to be responsible for AHR. Histopathology revealed justifies the effectiveness. The present investigations suggest PSE are interesting molecules for further research for asthma, with an approach through pro-inflammatory inhibitory pathway. P. scandens is a potential herbal medicine for allergy induced asthma.

Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer's disease.

OBJECTIVES: Adults who develop type 2 diabetes (T2D) at later stages are at a higher risk of developing Alzheimer's disease (AD). Pharmacological agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors that increase the levels of glucagon-like peptide-1 (GLP-1) and ameliorate T2D have also become promising candidates as disease-modifying agents in the treatment of AD. The present study investigates the efficacy of vildagliptin, a DPP-4 inhibitor in a streptozotocin (STZ)-induced rat model of AD. METHODS: Three months following the induction of AD by intracerebral injection of STZ, animals were orally administered with vildagliptin (2.5, 5 and 10 mg/kg) for 30 days. Dose-dependent and time-course effects of vildagliptin on memory retention were investigated during the course of treatment. Following treatment, the animals were sacrificed, and brain tissues were used to evaluate the effects of vildagliptin on hippocampal and cortical GLP-1 levels, amyloid beta (Aß) burden, tau phosphorylation and inflammatory markers. KEY FINDINGS: The results reveal a time-dependent improvement in memory retention and a dose-dependent attenuation of Aß, tau phosphorylation and inflammatory markers and increased GLP-1 levels. CONCLUSIONS: These robust therapeutic effects of vildagliptin demonstrate a unique mechanism for Aß and tau clearance and reverse the cognitive deficits and pathology observed in AD.

Saxagliptin: a dipeptidyl peptidase-4 inhibitor ameliorates streptozotocin induced Alzheimer's disease.

Type 2 diabetes (T2D) is one of the major risk factors associated with Alzheimer's disease (AD). Recent studies have found similarities in molecular mechanisms that underlie the respective degenerative developments in the two diseases. Pharmacological agents, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, which increase the level of glucagon-like peptide-1 (GLP-1) and ameliorate T2D, have become valuable candidates as disease modifying agents in the treatment of AD. In addition, endogenous GLP-1 levels decrease amyloid beta (Aß) peptide and tau phosphorylation in AD. The present study examines the efficacy of Saxagliptin, a DPP-4 inhibitor in a streptozotocin (STZ) induced rat model of AD. Three months following induction of AD by intracerebral administration of streptozotocin, animals were orally administered Saxagliptin (0.25, 0.5 and 1 mg/kg) for 60 days. The effect of the DPP-4 inhibitor on hippocampal GLP-1 levels, Aß burden, tau phosphorylation, inflammatory markers and memory retention were evaluated. The results reveal an attenuation of Aß, tau phosphorylation and inflammatory markers and an improvement in hippocampal GLP-1 and memory retention following treatment. This remarkable therapeutic effect of Saxagliptin mediated through DPP-4 inhibition demonstrates a unique mechanism for Aß and tau clearance by increasing GLP-1 levels and reverses the behavioural deficits and pathology observed in AD.