Scopoletin Improves Glucose Homeostasis in the High-Fructose High-Fat Diet-Induced Diabetes Model in Wistar Rats.

Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)-induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 ± 0.12) and HD group (5.271 ± 0.11) in comparison to the EC (6.37 ± 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, ß-cell function significantly improved (53.073 ± 4.67) in the MD group versus 29.323 ± 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 ± 4.67) was compared to the metformin-treated group (24.80 ± 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development.

Ameliorative Effect of Palm Oil in Aluminum Lactate Induced Biochemical and Histological Implications in Rat Brain.

α-Tocotrienol is one of the major constituents of palm oil. It is a well-known antioxidant and cholesterol-lowering neuroprotectant. To prevent the initiation of Alzheimer's like symptoms, much attention has been shifted to the major role played by antioxidants. Previous epidemiological reports correlate the increasing incidence of developing Alzheimer's disease (AD), to the aluminum (Al) content in drinking water. Al, being a ubiquitous element, has a long history of being particularly reactive towards multiple aspects of neurobiology. So, the current study examines the effect of Al-induced behavioral, biochemical, and histopathological changes in rat brain; and the ameliorative effect of palm oil in reducing the resulting neurotoxicity. The experimental design consisted of 4 groups: control group which received rodent chow diet and water ad libitum; Al group received aluminum lactate (50 mg/kg bw); Al + palm oil group was administered with Al (50 mg/kg bw) and palm oil (60 mg/kg bw); and palm oil group received palm oil (60 mg/kg bw). Al was given by oral gavage once daily for 6 weeks and palm oil was administered intraperitoneally. After 6 weeks of supplementation, Al + palm oil group showed significantly lower malondialdehyde (MDA) content, but higher superoxide dismutase (SOD), catalase (CAT), GST, and GPx activity as compared to Al group. Al group has significantly higher level of MDA content, but lower SOD, CAT, GST, and GPx activity as compared to control group. In conclusion, this study suggested that palm oil was effective in preventing the Al-induced brain damage in rats.

Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics.

The decreasing effectiveness of conventional drugs due to multidrug-resistance is a major challenge for the scientific community, necessitating development of novel antimicrobial agents. In the present era of coronavirus 2 (COVID-19) pandemic, patients are being widely exposed to antimicrobial drugs and hence the problem of multidrug-resistance shall be aggravated in the days to come. Consequently, revisiting the phenomena of multidrug resistance leading to formulation of effective antimicrobial agents is the need of the hour. As a result, this review sheds light on the looming crisis of multidrug resistance in wake of the COVID-19 pandemic. It highlights the problem, significance and approaches for tackling microbial resistance with special emphasis on anti-microbial peptides as next-generation therapeutics against multidrug resistance associated diseases. Antimicrobial peptides exhibit exceptional mechanism of action enabling rapid killing of microbes at low concentration, antibiofilm activity, immunomodulatory properties along with a low tendency for resistance development providing them an edge over conventional antibiotics. The review is unique as it discusses the mode of action, pharmacodynamic properties and application of antimicrobial peptides in areas ranging from therapeutics to agriculture.

Neuroprotective effects of carbenoxolone against amyloid-beta 1-42 oligomer-induced neuroinflammation and cognitive decline in rats.

The aggregation of Aß plays a major role in the progression of Alzheimer's disease (AD) and induces neuroinflammation, neurodegeneration and cognitive decline. Recent studies have shown that the soluble aggregates of Aß are the major culprits in the development of these aberrations inside the brain. In this study, we investigated the neuroprotective potential of carbenoxolone (Cbx), which has been found to possess anti-inflammatory and nootropic properties. Male SD rats (250-300 g) were divided into the four groups (n = 8 per group): (1) sham control rats injected with vehicles, (2) Aß 1-42 group rats injected i.c.v. with Aß 42 oligomers (10 µl/rat), (3) Aß 1-42+Cbx group rats injected i.c.v. with Aß 42 oligomers (10 µl/rat) and i.p. with carbenoxolone disodium (20 mg/kg body weight) for six-weeks and (4) Cbx group rats injected i.p. with carbenoxolone disodium (20 mg/kg body weight) for six-weeks. Progressive learning and memory deficits were seen through a battery of behavioral tests and a significant increase in the expressions of GFAP and Iba-1 was observed which resulted in the release of pro-inflammatory cytokines post Aß oligomer injection. The levels of BDNF, Bcl-2 and pCREB were decreased while Bax, caspase-3, caspase-9 and cytochrome c levels were induced. Also, neurotransmitter levels were altered and neuronal damage was observed through histopathological studies. After Cbx supplementation, the expressions of GFAP, IBA-1, pro-inflammatory cytokines, iNOS, nNOS and nitric oxide levels were normalized. The expression levels of pro-apoptotic markers were decreased and neurotrophin levels were restored. Also, neurotransmitter levels and neuronal profile were improved and progressive improvements in behavioural performance were observed. Our results demonstrated that Cbx might have prevented the Aß induced neurodegeneration and cognitive decline by inhibiting the neuroinflammation and inducing BDNF/CREB signalling. These findings suggest that Cbx can be explored as a potential therapeutic agent against the progression of AD.

Modulatory Effects of Ginkgo biloba Against Amyloid Aggregation Through Induction of Heat Shock Proteins in Aluminium Induced Neurotoxicity.

Protein misfolding and aggregation of amyloid beta (Aß) peptide, as well as formation of neurofibrillary tangles (NFTs) are the signature hallmarks of Alzheimer's disease (AD) pathology. To prevent this, molecular chaperones come into play as they facilitate the refolding of the misfolded proteins and cell protection under stress. Here, we have evaluated the possible effects of Ginkgo biloba (GBE) against aggregation of the Aß through activation of heat shock proteins (HSPs) in the Aluminium (Al) induced AD based model. GBE (100 mg/kg body weight) was administered per oral to the female SD rats in conjunction with intraperitoneal (i.p.) injection of Al lactate (10 mg/kg body weight) for six weeks. Pretreated animals were administered GBE for additional two weeks prior to any exposure of Al. GBE administration resulted in decrease in Aß aggregation, ubiquitin deposition, accompanying a significant decline in APP & Tau protein hyperphosphorylation which can be attributed to activation of Heat shock factor (HSF-1) and upregulation in the protein expression of HSPs. Histopathological investigation studies have also shown the decrease in aggregation of Aß peptide by GBE administration. Additionally, the decrease in ROS levels and Aß aggregation by GBE administration prohibited the decline in the neurotransmitter levels and monoamine oxidase levels in hippocampus and cortex. This further caused improvement in learning and memory of the animals. In conclusion, our results indicate that GBE prevents the symptoms of Al induced AD like pathophysiology by upregulating the HSPs levels and decreasing the aggregation load.

Midwifery 2030: a woman's pathway to health. What does this mean?

The 2014 State of the World's Midwifery report included a new framework for the provision of woman-centred sexual, reproductive, maternal, newborn and adolescent health care, known as the Midwifery2030 Pathway. The Pathway was designed to apply in all settings (high-, middle- and low-income countries, and in any type of health system). In this paper, we describe the process of developing the Midwifery2030 Pathway and explain the meaning of its different components, with a view to assisting countries with its implementation. The Pathway was developed by a process of consultation with an international group of midwifery experts. It considers four stages of a woman's reproductive life: (1) pre-pregnancy, (2) pregnancy, (3) labour and birth, and (4) postnatal, and describes the care that women and adolescents need at each stage. Underpinning these four stages are ten foundations, which describe the systems, services, workforce and information that need to be in place in order to turn the Pathway from a vision into a reality. These foundations include: the policy and working environment in which the midwifery workforce operates, the effective coverage of sexual, reproductive, maternal, newborn and adolescent services (i.e. going beyond availability and ensuring accessibility, acceptability and high quality), financing mechanisms, collaboration between different sectors and different levels of the health system, a focus on primary care nested within a functional referral system when needed, pre- and in-service education for the workforce, effective regulation of midwifery and strengthened leadership from professional associations. Strengthening of all of these foundations will enable countries to turn the Pathway from a vision into reality.