Therapeutic Promises of Bioactive Rosavin: A Comprehensive Review with Mechanistic Insight.

Rosavin is an alkylbenzene diglycoside primarily found in Rhodiola rosea (L.), demonstrating various pharmacological properties in a number of preclinical test systems. This study focuses on evaluating the pharmacological effects of rosavin and the underlying molecular mechanisms based on different preclinical and non-clinical investigations. The findings revealed that rosavin has anti-microbial, antioxidant, and different protective effects, including neuroprotective effects against various neurodegenerative ailments such as mild cognitive disorders, neuropathic pain, depression, and stress, as well as gastroprotective, osteoprotective, pulmoprotective, and hepatoprotective activities. This protective effect of rosavin is due to its capability to diminish inflammation and oxidative stress. The compound also manifested anticancer properties against various cancer via exerting cytotoxicity, apoptotic cell death, arresting the different phases (G0/G1) of the cancerous cell cycle, inhibiting migration, and invading other organs. Rosavin also regulated MAPK/ERK signaling pathways to exert suppressing effect of cancer cell. However, because of its high-water solubility, which lowers its permeability, the phytochemical has low oral bioavailability. The compound's relevant drug likeness was evaluated by the in silico ADME, revealing appropriate drug likeness. We suggest more extensive investigation and clinical studies to determine safety, efficacy, and human dose to establish the compound as a reliable therapeutic agent.

Attenuating Colorectal Cancer Using Nine Cultivars of Australian Lupin Seeds: Apoptosis Induction Triggered by Mitochondrial Reactive Oxygen Species Generation and Caspases-3/7 Activation.

As Australian lupin cultivars are rich sources of polyphenols, dietary fibers, high-quality proteins, and abundant bioactive compounds with significant antioxidant, antidiabetic, and anticancer activities, this research work is aimed at investigating the colon cancer alleviation activity of nine cultivars of lupin seeds on HCT116 and HT29 colon carcinoma cell lines through anti-proliferation assay, measurement of apoptosis, and identification of the mechanism of apoptosis. Nine cultivars were pre-screened for anti-proliferation of HCT116 and HT29 cells along with consideration of the impact of heat processing on cancer cell viability. Mandelup and Jurien showed significant inhibition of HCT116 cells, whereas the highest inhibition of HT29 cell proliferation was attained by Jurien and Mandelup. Processing decreased the anti-proliferation activity drastically. Lupin cultivars Mandelup, Barlock, and Jurien (dose: 300 µg/mL) induced early and late apoptosis of colon cancer cells in Annexin V-FITC assay. The mechanism of apoptosis was explored, which involves boosting of caspases-3/7 activation and intracellular reactive oxygen species (ROS) generation in HCT116 cells (Mandelup and Barlock) and HT29 cells (Jurien and Mandelup). Thus, the findings showed that lupin cultivars arrest cell cycles by inducing apoptosis of colorectal carcinoma cells triggered by elevated ROS generation and caspases-3/7 activation.

A Review on Mechanistic Insight of Plant Derived Anticancer Bioactive Phytocompounds and Their Structure Activity Relationship.

Cancer is a disorder that rigorously affects the human population worldwide. There is a steady demand for new remedies to both treat and prevent this life-threatening sickness due to toxicities, drug resistance and therapeutic failures in current conventional therapies. Researchers around the world are drawing their attention towards compounds of natural origin. For decades, human beings have been using the flora of the world as a source of cancer chemotherapeutic agents. Currently, clinically approved anticancer compounds are vincristine, vinblastine, taxanes, and podophyllotoxin, all of which come from natural sources. With the triumph of these compounds that have been developed into staple drug products for most cancer therapies, new technologies are now appearing to search for novel biomolecules with anticancer activities. Ellipticine, camptothecin, combretastatin, curcumin, homoharringtonine and others are plant derived bioactive phytocompounds with potential anticancer properties. Researchers have improved the field further through the use of advanced analytical chemistry and computational tools of analysis. The investigation of new strategies for administration such as nanotechnology may enable the development of the phytocompounds as drug products. These technologies have enhanced the anticancer potential of plant-derived drugs with the aim of site-directed drug delivery, enhanced bioavailability, and reduced toxicity. This review discusses mechanistic insights into anticancer compounds of natural origins and their structural activity relationships that make them targets for anticancer treatments.

A Review of Medicinal Plants with Antiviral Activity Available in Bangladesh and Mechanistic Insight Into Their Bioactive Metabolites on SARS-CoV-2, HIV and HBV.

Currently, viral infection is the most serious health issue which causing unexpected higher rate of death globally. Many viruses are not yet curable, such as corona virus-2 (SARS-CoV-2), human immunodeficiency virus (HIV), hepatitis virus, human papilloma virus and so others. Furthermore, the toxicities and ineffective responses to resistant strains of synthetic antiviral drugs have reinforced the search of effective and alternative treatment options, such as plant-derived antiviral drug molecules. Therefore, in the present review, an attempt has been taken to summarize the medicinal plants reported for exhibiting antiviral activities available in Bangladesh along with discussing the mechanistic insights into their bioactive components against three most hazardous viruses, namely SARS-CoV-2, HIV, and HBV. The review covers 46 medicinal plants with antiviral activity from 25 families. Among the reported 79 bioactive compounds having antiviral activities isolated from these plants, about 37 of them have been reported for significant activities against varieties of viruses. Hesperidin, apigenin, luteolin, seselin, 6-gingerol, humulene epoxide, quercetin, kaempferol, curcumin, and epigallocatechin-3-gallate (EGCG) have been reported to inhibit multiple molecular targets of SARS-CoV-2 viral replication in a number of in silico investigations. Besides, numerous in silico, in vitro, and in vivo bioassays have been demonstrated that EGCG, anolignan-A, and B, ajoene, curcumin, and oleanolic acid exhibit anti-HIV activity while piperine, ursolic acid, oleanolic acid, (+)-cycloolivil-4'-O-ß-d-glucopyranoside, quercetin, EGCG, kaempferol, aloin, apigenin, rosmarinic acid, andrographolide, and hesperidin possess anti-HBV activity. Thus, the antiviral medicinal plants and the isolated bioactive compounds may be considered for further advanced investigations with the aim of the development of effective and affordable antiviral drugs.

Biofunctionalities of unprocessed and processed flours of Australian lupin cultivars: Antidiabetic and organ protective potential studies.

As lupin has emerged popularity as dietary protein and nutritional source, our present research was aimed to demonstrate the antidiabetic and organ-protective activities of nine cultivars of Australian sweet lupin seed flours by means of in vitro and in vivo assays accompanied by identification of their bioactive phytocompounds and exploration of underlying mechanisms of their hypoglycemic activity using in silico approach. In vitro α-amylase and α-glucosidase activities inhibition and glucose uptake assays identified Jenabillup seed flours for exhibiting the most potential antidiabetic activity amongst the nine cultivars. In vivo antidiabetic and major organ-protective activities were investigated on streptozotocin-induced hyperglycemia and organ damages in Wister rat model. Along with attenuating hyperglycemia and retreating major organ damages, the biochemical imbalance in cardiac, hepatic and renal markers were well-balanced by Jenabillup seed flours treatment. These activities of lupin seed flours were insignificantly affected by thermal processing. Moreover, in silico investigation of 106 phytochemicals identified by gas chromatography-mass spectroscopy (GC-MS) analysis of the seed flour extracts of nine cultivars revealed that more than 35% of compounds possess moderate to high binding affinity to α-amylase and α-glucosidase enzymes. These bioactive compounds act synergistically to exert potential hypoglycemic activity. Cross-docking and binding energy calculation by molecular mechanics/generalized Born volume integration (MM/GBVI) model suggest actinomycin C2 as a potential inhibitor of both α-amylase and α-glucosidase enzymes. These findings acclaim that Australian sweet lupin seed flours may be considered not only as functional food, but also for further development of effective drugs in pharmaceuticals in the treatment of diabetes mellitus and resultant organ damages.

Role of a Solution-Processed V2O5 Hole Extracting Layer on the Performance of CuO-ZnO-Based Solar Cells.

In this research, a heterostructure of the CuO-ZnO-based solar cells has been fabricated using low-cost, earth-abundant, non-toxic metal oxides by a low-cost, low-temperature spin coating technique. The device based on CuO-ZnO without a hole transport layer (HTL) suffers from poor power conversion efficiency due to carrier recombination on the surface of CuO and bad ohmic contact between the metal electrode and the CuO absorber layer. The main focus of this research is to minimize the mentioned shortcomings by a novel idea of introducing a solution-processed vanadium pentoxide (V2O5) HTL in the heterostructure of the CuO-ZnO-based solar cells. A simple and low-cost spin coating technique has been investigated to deposit V2O5 onto the absorber layer of the solar cell. The influence of the V2O5 HTL on the performance of CuO-ZnO-based solar cells has been investigated. The photovoltaic parameters of the CuO-ZnO-based solar cells were dramatically enhanced after insertion of the V2O5 HTL. V2O5 was found to enhance the open-circuit voltage of the CuO-ZnO-based solar cells up to 231 mV. A detailed study on the effect of defect properties of the CuO absorber layer on the device performance was theoretically accomplished to provide future guidelines for the performance enhancement of the CuO-ZnO-based solar cells. The experimental results indicate that solution-processed V2O5 could be a promising HTL for the low-cost, environment-friendly CuO-ZnO-based solar cells.

Risk factors associated with retinopathy in young people with type 1 diabetes in Bangladesh.

Objectives: Diabetic retinopathy (DR) is the most common microvascular complications seen in children and adolescents with type 1 diabetes. The aim of this study was to evaluate the prevalence of retinopathy and its association with other risk factors in young people with type 1 diabetes. Methods: This study was a cross-sectional study, which was done as part of the ongoing complication assessment in the paediatric diabetes clinic in BIRDEM (Bangladesh Institute of Research and Rehabilitation of Diabetes Endocrine and Metabolic Disorders), a tertiary care hospital. Children, adolescents and young adults with type 1 diabetes who were having diabetes duration >2 years were included in this study. Retinopathy was detected using fundal photography, and grading was done by National Screening Committee of UK by trained ophthalmologists. Results: Diabetic retinopathy was observed in 44 (6.6%) patients. Majority (95.4%) of them had early diabetic retinopathy in the form of mild NPDR (nonproliferative diabetic retinopathy) (R1). Patients with retinopathy had higher HbA1c 9.6[8.4-12.3] vs 9.1 [7.9-10.8] (P = .013), longer duration of diabetes 7.6 [5.5-10.7] vs 6.0 [4.5-8.2] years (P = .001) and were older 21.5 [18.0-23.0] vs 18 [16.0-21.0] years (P = .0001) compared with those without retinopathy. On multivariate regression analysis, higher age and median HbA1c were significantly associated with DR. Conclusions: Higher HbA1c was the only modifiable risk factor for development of DR in our study population. Early detection of DR with improvement of glycaemic control may reduce the risk of progression of severe stages of the disease.

Identification of bioactive metabolites and evaluation of in vitro anti-inflammatory and in vivo antinociceptive and antiarthritic activities of endophyte fungi isolated from Elaeocarpus floribundus blume.

ETHNOPHARMACOLOGICAL RELEVANCE: Functional disability associated with rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease is a challenging concern in healthcare systems. Along with environmental factors and epigenetic disorders, multiple pathways are reported as prominent mechanism for the progression of RA symptoms including; pain, swelling and stiffness of joints. Elaeocarpus floribundus Blume has been used as a folklore medicine for RA from ancient times. This plant harbours a suite of endophytic fungi that produce a range of metabolites of potential interest. Thus, for the establishment of a scientific basis for this folklore use, it is essential to find out the involvement, if any, of the endophytic fungi living in this plant and the metabolites they elaborate, for the management of RA. AIM OF THE STUDY: This study was designed to isolate, identify and evaluate the in vitro anti-inflammatory and in vivo antinociceptive and antiarthritic activities of the compounds produced by the endophytic fungi living in different parts of Elaeocarpus floribundus Blume. MATERIALS AND METHODS: Endophytic fungi from different parts of the plant were isolated and cultured for the production of secondary metabolites. Chromatographically fractionated fungal extracts were assessed for anti-inflammatory and antinociceptive activities. For the evaluation of anti-inflammatory activity, in vitro cyclooxygenase (COX1/COX2) and 5-lipoxygenase (5-LOX) inhibitory assays were performed. For the evaluation of in vivo antinociceptive activity, hot plate acetic acid induced writhing, and formalin induced paw licking methods were adopted, whereas complete Freund's adjuvant (CFA) induced poly-arthritic method was adopted for the evaluation of antiarthritic activity. The most effective fraction was analyzed by liquid chromatography-mass spectroscopy (LC-MS) in search of the bioactive extracellular metabolites. RESULTS: Five endophytic fungi viz. Aspergillus fumigatus, Aspergillus niger, Rhizoctonia oryzae, Rhizopus oryzae, and Syncephalastrum racemosum were isolated. COX1/COX2 and 5-LOX inhibitory assays state that the Aspergillus niger fraction possesses the greatest activity against these enzymes of inflammatory process. In vivo antinociceptive showed significant (***P<0.001) reduction of pain in a dose dependent manner. As well, significant (***P<0.001) reduction of paw volume was observed in CFA induce poly-arthritic test. LC/MS analysis of the Aspergillus niger fraction revealed the presence of bioactive compounds including tensyuic acid, hexylitaconic acid, chlorogenic acid, nigragillin, TMC-256C1, asnipyrone B, asperenone, fumaric acid and fusarubin, all having reported pharmacological activities. CONCLUSION: The present study demonstrates that secondary metabolites produced by endophytic fungi living in various parts of Elaeocarpus floribundus Blume had potential to relief pain and inflammation. The endophytes were found to contain multiple biomolecules effective in rheumatoid arthritis. These findings provide a rationale for the folklore use of the plant in the management of rheumatoid arthritis.

Solution-Processed Synthesis of Copper Oxide (Cu x O) Thin Films for Efficient Photocatalytic Solar Water Splitting.

This article reports a solution-processed synthesis of copper oxide (Cu x O) to be used as a potential photocathode for solar hydrogen production in the solar water-splitting system. Cu x O thin films were synthesized through the reduction of copper iodide (CuI) thin films by sodium hydroxide (NaOH), which were deposited by the spin coating method from CuI solution in a polar aprotic solvent (acetonitrile). The phase and crystalline quality of the synthesized Cu x O thin films prepared at various annealing temperatures were investigated using various techniques. The X-ray diffraction and energy dispersive X-ray spectroscopy studies confirm the presence of Cu2O, CuO/Cu2O mixed phase, and pure CuO phase at annealing temperatures of 250, 300, and 350 °C, respectively. It is revealed from the experimental findings that the synthesized Cu x O thin films with an annealing temperature of 350 °C possess the highest crystallinity, smooth surface morphology, and higher carrier density. The highest photocurrent density of -19.12 mA/cm2 at -1 V versus RHE was achieved in the photoelectrochemical solar hydrogen production system with the use of the Cu x O photocathode annealed at a temperature of 350 °C. Therefore, it can be concluded that Cu x O synthesized by the spin coating method through the acetonitrile solvent route can be used as an efficient photocathode in the solar water-splitting system.

Bioactive Variability and In Vitro and In Vivo Antioxidant Activity of Unprocessed and Processed Flour of Nine Cultivars of Australian lupin Species: A Comprehensive Substantiation.

The aim of this present investigation was to analyze bioactive compounds, as well as demonstrate the antioxidant activities of nine cultivars of Australian lupin species accompanied by observing the effect of domestic heat processing on their antioxidant activities adopting in vivo and in vitro approaches. Gas chromatography mass spectroscopy (GC-MS) analysis was performed for profiling bioactive compounds present in lupin cultivars. Multiple assay techniques involving quantification of polyphenolics, flavonoids and flavonol, electron transfer (ET) based assay, hydrogen atom transfer (HAT)-based assay and in vivo assays were performed. The major compounds found were hexadecanoic acid methyl ester, 9,12-octadecadienoic acid methyl ester, methyl stearate, lupanine,13-docosenamide and 11-octadecenoic acid (Z)- methyl ester. Mandelup was found to show excellent antioxidant activity. Moreover, Jurien, Gunyidi and Barlock had strong antioxidant activity. Both positive and negative impacts of heat processing were observed on antioxidant activity. Heating and usage of excess water during processing were the key determinants of loss of antioxidants. Negligible loss of antioxidant activity was observed in most of the assays whereas inhibition of both lipid peroxidation (33.53%) and hemolysis of erythrocytes (37.75%) were increased after processing. In addition, in vitro and in vivo antioxidant assays are found to show statistically significant (* p < 0.05 and ** p < 0.01) results, which are supported by the presence of a number of antioxidant compounds in GC-MS analysis.