Phenolic enriched fraction of Clerodendrum glandulosum Lindl. leaf extract ameliorates hyperglycemia and oxidative stress in streptozotocin-nicotinamide induced diabetic rats.

BACKGROUND: Clerodendrum glandulosum Lindl. is an important ethnomedicinal shrub of Northeast India, used by traditional healers to control various ailments like diabetes, hypertension, arthritis, etc. OBJECTIVES: The present study was conducted to explore the anti-hyperglycemic and antioxidative effects of the polyphenol-rich fraction (PRF) of C. glandulosum leaf extract and identification of its major bioactive compounds. Further, an in-silico molecular docking study was also performed to understand the molecular interactions of the identified major compounds with some target proteins associated with diabetic complications. MATERIALS AND METHODS: PRF was purified from the hydromethanolic (80% MeOH) extract of leaves and subjected to assessment of in-vitro antioxidant and anti-diabetic properties. It was also subjected to evaluate the ameliorative effect during streptozotocin-nicotinamide-induced hyperglycemia in Wistar albino rats. An in-silico molecular docking study was also performed to complement the in-vitro/in-vivo studies. RESULTS: Chemical analysis of PRF showed the presence of phenolics like caffeic acid, verbascoside, isoverbascoside, and apigenin, of which verbascoside (598.14 ± 1.24 mg/g) was found to be the principal compound. In-vitro studies showed potent antioxidant (IC50 of DPPH:32.45 ± 2.16 µg/mL; ABTS:39.08 ± 0.53 µg/mL) properties and excellent aldose reductase inhibition potential (IC50 2.18 ± 0.10 µg/mL). Treatment with PRF showed reduced blood glucose levels and increased plasma insulin levels. The results also indicate an improvement of endogenous antioxidants and suppression of inflammatory cytokines (IL-6 and TNF-α) comparable to the standard. Molecular docking studies predicted promising interactions between the identified molecules and the crucial amino acid residues of the enzymes involved in the development of hyperglycemia. CONCLUSION: This study revealed the antihyperglycemic and antioxidant potential of partially purified fraction PRF of C. glandulosum leaves.

Recent Advances in the Development of Antibiotics-Coated Gold Nanoparticles to Combat Antimicrobial Resistance.

Antimicrobial resistance (AMR) has become an alarming threat to the successful treatment of rapidly growing bacterial infections due to the abuse and misuse of antibiotics. Traditional antibiotics bear many limitations, including restricted bioavailability, inadequate penetration and the emergence of antimicrobial-resistant microorganisms. Recent advances in nanotechnology for the introduction of nanoparticles with fascinating physicochemical characteristics have been predicted as an innovative means of defence against antimicrobial-resistant diseases. The use of nanoparticles provides several benefits, including improved tissue targeting, better solubility, improved stability, enhanced epithelial permeability and causes minimal side effects. However, except for gold nanoparticles (AuNPs), the biological safety of the majority of metal nanoparticles remains a serious problem. AuNPs appear to be promising for drug delivery and medicinal applications because of their minimal toxicity, biocompatibility, functional flexibility, chemical stability and versatile biological activities, such as their antiviral, antifungal, anti-inflammatory and antimicrobial properties. Hence, we are focusing on the gold nanoparticles possessing antimicrobial activity in this article. This review will cover recent strategies in the preparation of gold nanoparticles, with special emphasis placed on antibiotics-coated AuNPs with enhanced antimicrobial properties and how they fight against disease-causing bacteria and eradicate biofilms, along with their activities and physicochemical properties.

Nutritional Composition and Pharmacological Activity of Musa balbisiana Colla Seed: An Insight into Phytochemical and Cellular Bioenergetic Profiling.

Musa balbisiana Colla belongs to the family Musaceae which is well-known for its nutritional and pharmacological properties. Here, we have analysed the phytochemical content and evaluated the nutritional, antioxidant, anti-glycation, α-amylase, and α-glucosidase inhibition potential. Moreover, for the first time, we have studied the bioenergetic profiles of the bioactive fractions of M. balbisiana seeds extract against oxidative stress-related mitochondrial and cellular dysfunction using XFe24 extracellular flux analyzer. M. balbisiana seeds have high nutritional values with significant levels of carbohydrates, starch, protein, and minerals (Ca, Na, Mg, Cu, Fe, and Zn). Bioactivity-guided fractionation of the methanolic extract of M. balbisiana seeds revealed that the ethyl acetate fraction (EAF) showed the highest antioxidant, anti-glycation, and phytochemical content as compared to other fractions. Moreover, the EAF showed a lower α-amylase inhibition and a higher α-glucosidase inhibitory activity. Most importantly, our GC-MS analyses of EAF revealed the presence of unique and previously unreported 14 phytochemical compounds. A strong correlation between the biological activities and total phenolic/tannin content was observed. In addition, the bioactive fraction of M. balbisiana seeds (EAF) improved the bioenergetic profiles of free fatty acid-induced oxidative stress with a concomitant increase in ATP production, and respiratory and glycolytic capacity. Altogether, our findings suggest that M. balbisiana seeds can be used as a natural supplement to boost antioxidant levels and combat oxidative stress and non-enzymatic glycation.

Ultrasound-Assisted Extraction of Verbascoside from Clerodendrum glandulosum Leaves for Analysis of Antioxidant and Antidiabetic Activities.

Verbascoside (VER) is a phenylethanoid glycoside compound found in Clerodendrum species and is an important part of traditional medicine. It is found in the leaves of Clerodendrum glandulosum, which is taken as a soup or vegetable and also utilized in traditional medicine by the people of Northeast India, especially against hypertension and diabetes. In the present study, VER was extracted from C. glandulosum leaves using ultrasound-assisted extraction through the solvent extraction method (ethanol-water, ethanol, and water). The ethanol extract had the highest phenolic and flavonoid contents, viz., 110.55 mg GAE/g and 87.60 mg QE/g, respectively. HPLC and LC-MS were used to identify the active phenolic compound, and VER was found to be the main component present in the extraction with a molecular weight of 624.59 g/mol. NMR (1H, 2D-COSY) analysis showed the presence of hydroxytyrosol, caffeic acid, glucose, and rhamnose in the VER backbone. Further, different antioxidant activities and antidiabetic and antihyperlipidemia enzyme markers' inhibition against VER-enriched ethanol extract were evaluated. The results showed that ultrasound extraction of polyphenols using ethanol from C. glandulosum could be a promising technique for the extraction of bioactive compounds.

Pharmacologically active chemical composite of Musa balbisiana ameliorates oxidative stress, mitochondrial cellular respiration, and thereby metabolic dysfunction.

The ripe fruit pulp of different Musa species is known for its excellent source of nutrient contents. Musa balbisiana (MB) is one such variety of Musa species, mainly found in the southern part of Asia, especially in the North-eastern part of India, remains unexplored despite its continuous use by the local traditional healers. The present study focuses on identifying and quantifying the active chemicals present in the ripe fruit pulp of Musa balbisiana (RFPMB) to understand its combined efficacy and nutritional benefit to control human metabolic complications specially related to diabetes and cardiovascular disorder. Characterization and confirmation through targeted LC-MS and HPLC-PDA based assays followed by quantitative analysis led us to identify the major bioactive compounds in RFPMB as shikimic acid, p-hydroxybenzoic acid, vanillic acid, ferulic acid, sinapic acid, caffeic acid, syringic acid, chlorogenic acid, trans-cinnamic acid, and two essential fatty acids; linolenic acid and linoleic acid. The ripe fruit pulp is further analyzed to understand the nutritional and mineral content and found a substantial presence of calcium and potassium (15.74 ± 0.43 and 395.20 ± 9.5 mg/100 g of raw pulp, respectively) compared to other reported varieties. The active portion of RFPMB reduces the production of ROS, the expression of inflammatory marker genes TNF-α and TGF-ß, and accelerates the mitochondrial oxygen consumption rate (OCR) by enhancing the basal respiration, maximal respiration, and ATP production capacity of the targeted cells. The present study concluded that, a particular phytopharmaceutical composition of RFPMB with 11-biomarker compounds might be an efficacious formulation for developing a value-added nutraceutical product in managing metabolic complications and its related oxidative stress. PRACTICAL APPLICATIONS: This study has provided the prior information regarding the potential nutraceutical and phytochemical advantages of Musa balbisiana (MB) fruit pulp over other reported banana varieties. The HPLC-based quantification will give a clear understanding of the food values in comparison of bioactive compounds present in the active fraction of RFPMB, which can be an effective phytopharmaceutical in combating metabolic disorders and oxidative stress. Overall this study will help to commercialize a value-added product from this variety of banana with proper scientific validation.

Dietary phytochemicals/nutrients as promising protector of breast cancer development: a comprehensive analysis.

Genetic change, particularly epigenetic alteration, is one of the imperative factors for sporadic breast cancer development in the worldwide population of women. The DNA methylation process is essential and natural for human cellular renewal and tissue homeostasis, but its dysregulation contributes to many pathological changes, including breast tumorigenesis. Chemopreventive agents mainly protect the abnormal DNA methylation either by hindering the division of pre-malignant cells or looming the DNA damage, which leads to malignancy. The present review article is about understanding the potential role of dietary phytochemicals in breast cancer prevention. Accordingly, a literature search of the published article until August 2021 has been performed. Further, we have investigated the binding affinity of different phytochemicals isolated from diverse dietary sources against the various oncogenic proteins related to breast cancer initiation to understand the common target(s) in breast cancer prevention mechanisms. Various small phytochemicals, especially dietary phytochemicals including sulforaphane, mahanine, resveratrol, linolenic acid, diallyl sulfide, benzyl/phenethyl isothiocyanate, etc. are being investigated as the chemopreventive agent to manage breast cancer development, and some of them have shown promising outcomes in the cited research. In this present review, we discuss the recent advancement in acceptance of such types of potential dietary phytochemicals as a chemopreventive agent against breast cancer development and their inner lining mechanism. The critical clinical trials and cohort studies have also been considered to understand the progress in contemporary perspectives.

A pharmacological perspective of banana: implications relating to therapeutic benefits and molecular docking.

Banana is one of the most nutritious fruits, as it is rich in carbohydrates, proteins, fatty acids, and minerals. Banana has been used in traditional medicines for managing coughs and colds, ulcers, burns, and diarrhea. Banana contains various bioactive compounds, such as alkaloids, phenols, flavonoids, tannins, and saponins, with reported therapeutic benefits, including antioxidant, anti-diabetic, anti-cancer, anti-inflammatory, and anti-microbial activities. The present review focuses on a comprehensive overview of the nutritional and biological properties and phytochemicals of different species of banana and its different parts. Although detailed characterization of the compounds that are present in many parts of the plant has been carried out, chemical profiling of the seed, pseudostem, and leaves of banana is lacking and requires further exploration. Moreover, the functions of the reported compounds were elucidated using computational tools, supporting their potential role in managing life-threatening diseases and physiological complications.

Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability.

Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil's physiochemical and microbial parameters of its cultivation sites.

The Prognostic Impact of Epidermal Growth Factor Receptor (EGFR) in Patients with Acute Myeloid Leukaemia.

Expression of Epidermal Growth Factor Receptor (EGFR), an important proto-oncogene, regulates cell differentiation, proliferation, cell migration and survival in most of the cancer types. EGFR expression has been reported in Acute Myeloid Leukaemia (AML), however, many other reports nullified EGFR expression in AML. These contradictory data prompted us to reevaluate the expression of EGFR in AML and carry out a comparative survival analysis between EGFR expressing and non-expressing AML patients (Children and Acute Promyelocytic Leukaemia patients excluded). Bone marrow and/or peripheral blood samples were collected from 60 adult patients with AML with written informed consent. PCR, Real-Time Taqman gene expression assays were used for the detection of genetic alterations. Statistical analysis was conducted using SPSS software (IBM SPSS 20). In our study, EGFR expression was detected in 21 out of 60, in 35% (95% C.I. 23.45-48.48) AML patients. Overall survival was significantly shorter in patients with EGFR (p = < 0.01), with an average survival of 18.57 months (95% C.I. 12.42-24.73 months) compared with 31.27 months (95% C.I. 28.19-34.33 months) in patients without EGFR. EGFR expression was significantly higher in female patients compared to male (p = 0.037).This study confirms the presence of EGFR in AML and indicates that EGFR expression confers poor prognosis in AML. However, the underlying cause of this adverse prognostic effect has not been identified. Further clinical studies are warranted to determine the exact mechanism through which EGFR activity might contribute to AML progression and identify the potential therapeutic target for the reversal of resistance to conventional chemotherapeutics.

Musa balbisiana Fruit Rich in Polyphenols Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats via Inhibition of Inflammation and Oxidative Stress.

Musa balbisiana Colla (Family: Musaceae), commonly known as banana and native to India and other parts of Asia, is very rich in nutritional value and has strong antioxidant potential. In the present study, we have developed Musa balbisiana (MB) fruit pulp powder and evaluated its cardioprotective effect in cardiac hypertrophy, which is often associated with inflammation and oxidative stress. An ultra-high-pressure liquid chromatography-mass spectrometer (UPLC-MS/MS) has been used for the detection and systematic characterization of the phenolic compounds present in Musa balbisiana fruit pulp. The cardioprotective effect of MB was evaluated in a rat model of isoproterenol- (ISO-) induced cardiac hypertrophy by subcutaneous administration of isoproterenol (5 mg/kg-1/day-1), delivered through an alzet minipump for 14 days. Oral administration of MB fruit pulp powder (200 mg/kg/day) significantly (p < 0.001) decreased heart weight/tail length ratio and cardiac hypertrophy markers like ANP, BNP, ß-MHC, and collagen-1 gene expression. MB also attenuated ISO-induced cardiac inflammation and oxidative stress. The in vivo data were further confirmed in vitro in H9c2 cells where the antihypertrophic and anti-inflammatory effect of the aqueous extract of MB was observed in the presence of ISO and lipopolysaccharide (LPS), respectively. This study strongly suggests that supplementation of dried Musa balbisiana fruit powder can be useful for the prevention of cardiac hypertrophy via the inhibition of inflammation and oxidative stress.