Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review.

Selective permeability of biological membranes represents a significant barrier to the delivery of therapeutic substances into both microorganisms and mammalian cells, restricting the access of drugs into intracellular pathogens. Cell-penetrating peptides usually 5-30 amino acids with the characteristic ability to penetrate biological membranes have emerged as promising antimicrobial agents for treating infections as well as an effective delivery modality for biological conjugates such as nucleic acids, drugs, vaccines, nanoparticles, and therapeutic antibodies. However, several factors such as antimicrobial resistance and poor drug delivery of the existing medications justify the urgent need for developing a new class of antimicrobials. Herein, we review cell-penetrating peptides (CPPs) used to treat microbial infections. Although these peptides are biologically active for infections, effective transduction into membranes and cargo transport, serum stability, and half-life must be improved for optimum functions and development of next-generation antimicrobial agents.

Dyslipidaemia-related cardiovascular risk among pregnant women attending Aminu Kano Teaching Hospital Kano: A longitudinal study.

OBJECTIVE: Maternal dyslipidaemia and atherogenic lipid profiles have undesirable effects on maternal and foetal well-being throughout gestation. This study investigates the changes in serum lipid profiles, the prevalence of dyslipidaemia, and the risk of cardiovascular disease among pregnant women attending the antenatal care unit of the Aminu Kano Teaching Hospital (AKTH), Kano. METHODS: A total of 112 pregnant women visiting AKTH in their second trimester were recruited and followed up within their third trimester. The demographic characteristics, daily dietary consumption patterns, and lipid profiles of all women were assessed using standard methods. RESULTS: The results revealed that the mean age and gestational age of the pregnant women were approximately 29 ± 6 years and 20 ± 3 weeks, respectively. Most pregnant women were multiparous (76) and multigravida (93). Regarding daily dietary consumption patterns, 20.5%, 63.4%, 13.4%, and 8.0% of the pregnant women consumed nuts, palm oil, butter, and sardines at least one to three times, respectively. Moreover, the serum lipid profiles revealed that the prevalence of dyslipidaemia, hypercholesterolaemia, hypertriglyceridaemia, increased low-density lipoprotein levels, and decreased high-density lipoprotein levels among pregnant women during the second trimester were 69.6%, 19.6%, 36.6%, 18.8%, and 49.1%, respectively. All these parameters significantly increased to 91.8%, 54.1%, 75.3%, 40.0%, and 62.4%, respectively, in the third trimester. Pregnant women showed a high risk of cardiovascular disease in both the second (81.0%) and third (85.0%) trimesters. CONCLUSION: Progression from mid-pregnancy to delivery is associated with an increased risk of maternal dyslipidaemia and cardiovascular diseases among pregnant women.

Chrysin alleviates alteration of bone-remodeling markers in ovariectomized rats and exhibits estrogen-like activity in silico.

BACKGROUND: Evidences are beginning to accrue that flavonoids, particularly phytoestrogens, could have beneficial effects against several age-related diseases linked to estrogen deficiency including postmenopausal osteoporosis. METHODS: In this study, the effect of chrysin on selected bone-remodeling markers in ovariectomized rats and its estrogen-like activity in silico were investigated. RESULTS: The data indicated that administration of chrysin at 50 mg/kg and 100 mg/kg for 6 weeks to OVX rats significantly (p < 0.05) prevented body weight gain and partially reverse uterine weight loss. In addition, treatment of OVX rats significantly (p < 0.01) increased femur dry weight, femur ash weight, bone ash calcium, and phosphorous levels in a dose-dependent manner. However, there was significant (p < 0.001) decline in serum estradiol level in all OVX rats compared to the sham-operated group. Interestingly, administration of chrysin significantly (p < 0.05) reversed the reduction of estradiol induced by ovariectomy compared to untreated OVX rats. Moreover, administration of chrysin to OVX rats significantly (p < 0.05) suppressed excessive elevation of bone-remodeling markers expression compared to untreated OVX rats. Similarly, molecular docking analysis revealed that chrysin interacts with both α and ß estrogen receptors with exothermic binding energies of -229.83 kcal/Mol and -252.72 kcal/Mol, respectively, and also fits perfectly into the active site of both α and ß estrogen receptors. CONCLUSION: This study demonstrated that chrysin exhibits potential antiosteoporotic effects against bone loss in OVX rats through enhanced bone mineral contents and preventing excessive elevation of bone-remodeling markers and bone-resorbing cytokine.

Cardioprotective Activities of Ethanolic Extract Root of Ageratum conyzoides on Alloxan-Induced Cardiotoxicity in Diabetic Rats.

Diabetes mellitus has developed into one of the debilitating diseases disturbing the health of many people living with cardiovascular diseases in modern times. The root of Ageratum conyzoides was investigated for its effects on alloxan-induced diabetic Wistar rats' cardiac tissues. Thirty-two (32) Wistar rats weighing between 180 and 190 g were randomly divided into four groups. The animals in groups B-D were induced with a single dose of 150 mg/kg body weight of alloxan (ALX) intraperitoneally. They were confirmed hyperglycemic after 72 hours of induction and then sustained in hyperglycemic condition for 2 weeks. Animals in groups C and D received AC intervention, as stated above, for four weeks. The body weight of the experimental animals and blood collection for glucose estimation were taken weekly for six weeks using appropriate instruments. Biochemical assays for lipid profile, antioxidant enzymatic, and nonenzymatic markers were carried out. Histopathological changes in the cardiac tissues were also studied. Administration of 150 mg/kg of ALX to experimental rats induced diabetes and significantly reduced the body weights, significantly (p < 0.05) increased the glucose level, triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels, and decreased the levels of high-density lipoprotein (HDL) and antioxidant enzymatic markers such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) while the antioxidant nonenzymatic marker such as malondialdehyde (MDA) level was significantly increased. By contrast, rats given the ethanolic extract root of A. conyzoides had significantly (p < 0.05) increased the body weight gain, whereas the glucose levels significantly (p < 0.05) improved in treated diabetic rats. This extract also improved the cardiovascular system of the diabetic rats by significantly decreasing TG and LDL levels, significantly (p < 0.05) increasing the HDL level, significantly reducing the cardiac contents of CAT, SOD, and GPx, and significantly (p < 0.05) decreasing MDA. Ethanolic extract root of A. conyzoides exhibited antihyperglycemic and antihyperlipidemic activities and mitigates damage to the heart from the ALX-induced myocardial toxicity associated with type-1 diabetes.

Nrf2 dependent antiaging effect of milk-derived bioactive peptide in old fibroblasts.

Prolonged passaging of primary fibroblast cells totally shapes the natural biological phenomena and leads to the appearance of features related to senescence. As a result, it is a good natural tool to delineate the molecular mechanism of cellular aging. The present investigation revealed the antiaging effect of milk-derived novel bioactive peptide (VLPVPQK). The peptide played an important role in downregulating apoptosis-related markers in late passages of cultured fibroblast cells. The peptide treatment to aged fibroblasts caused enhancement in cell migration, DNA integrity, and decrease in the lipid peroxidation, reactive oxygen species, nitric oxide production as well as pro-inflammatory cytokines, TNF-α and IL-6. Moreover, the peptide decreased the expression of apoptotic caspases, Bax, and senescence-associated ß-galactosidase (SA-ß-gal) proteins. The peptide pretreatment also enhanced the extracellular collagen protein and antiapoptotic, Bcl-xL. In addition, the peptide treatment reversed the senescence-related activity in fibroblasts by stimulating Nrf2 mediated antioxidative defense system and inhibiting the action of NFkB/p38MAPK signaling, similar to the commercially available inhibitor (SB203580) of p38MAPK. Thus, the peptide exhibits the antiaging effect in dermal fibroblast cells.

Consumption of Probiotic Lactobacillus fermentum MTCC: 5898-Fermented Milk Attenuates Dyslipidemia, Oxidative Stress, and Inflammation in Male Rats Fed on Cholesterol-Enriched Diet.

There is a growing and alarming prevalence that increased serum cholesterol is closely related to increased cardiovascular disease risk. Probiotic consumption could be a safe and natural strategy to combat. Therefore, we sought to examine the cholesterol-lowering potential of co-supplementation of probiotic bacteria Lactobacillus fermentum MTCC: 5898-fermented buffalo milk (2.5% fat) in rats fed cholesterol-enriched diet. Male Wistar rats were divided into three groups on the basis of feed, viz. group 1, fed standard diet (SD); group 2, fed cholesterol-enriched diet (CED); and group 3, fed cholesterol-enriched diet along with L. fermentum MTCC: 5898-fermented milk (CED+LF) for 90 days. At the endpoint, significantly higher levels of serum total cholesterol, low-density lipoprotein cholesterol, triacylglycerols, very low density lipoprotein cholesterol, atherogenic index, coronary artery risk index, hepatic lipids, lipid peroxidation, and mRNA expression of inflammatory cytokines (TNF-α and IL-6) in the liver while significantly lower levels of serum high-density lipoprotein cholesterol and anti-oxidative enzyme activities, catalase, superoxide dismutase, and glutathione peroxidase in the liver and kidney were observed in the CED group compared to the SD group. Compared to the CED group, these adverse physiological alterations were found significantly improved in the CED+LF group. Hence, this study proposes that L. fermentum MTCC: 5898 is a potential probiotic bacteria that can be consumed to tackle hypercholesterolemia. Graphical Abstract ᅟ.

Postmenopausal osteoporosis and breast cancer: The biochemical links and beneficial effects of functional foods.

Breast cancer as a multifactorial disease has been classified among the major causes of morbidity and mortality in women across the world, with a higher prevalence among post-menopausal women. Osteoporosis, a condition characterized by altered bone mineralization is also commonly found among post-menopausal women. Consequently, post-menopausal women are at risk of morbidity and mortality associated with breast cancer and postmenopausal osteoporosis. This may not be unconnected to the fact that, there may be existent biochemical links between the two mayhems, which might rally round between the cellular and molecular connectivity based on the actions and inactions of RANKL, estrogen, free radicals-induced oxidative stress and metabolic implications of age related obesity among others. Cells and tissues including breast and bone are more prone to oxidative stress with age, and oxidative stress could alter the activity of key proteins and pathways required for protection against breast cancer and osteoporosis. As a result, the potentials of antioxidant rich functional foods in preventing, managing and possibly treating breast cancer and postmenopausal osteoporosis cannot be overemphasised. This review mainly uses ISI, SCOPUS and PubMed indexed journals and books containing various experimental reports vacillating from humans, animals and in vitro studies in relation to breast cancer and postmenopausal osteoporosis, biochemical links and possible beneficial effects of functional foods. One distinct feature of the review is that it categorically intends to provide a critical appraisal on the said available experimental data within the variables of breast cancer and osteoporosis among females vis-à-vis the potentials of functional foods.

Antioxidative peptide from milk exhibits antiosteopenic effects through inhibition of oxidative damage and bone-resorbing cytokines in ovariectomized rats.

OBJECTIVES: Oxidative stress has been implicated as a crucial pathogenic factor in the development of postmenopausal osteoporosis. Milk-derived antioxidative peptides are gaining much attention toward the development of prodrugs for alleviating several human diseases, including osteoporosis. The aim of the present study was to determine whether antioxidant peptides are good candidates for alleviating postmenopausal osteoporosis. METHODS: In the present study, an ovariectomized (OVX) osteoporotic rat model was used to investigate the protective effects of buffalo milk casein-derived novel peptide VLPVPQK (PEP) against OVX-induced bone loss and the related mechanisms. RESULTS: Results of the present study indicated that daily administration of antioxidative peptide PEP at 50 and 100 µg/kg for 8 wk prevents body weight gain, uterine weight loss, and atrophy of endometrial lumen. Moreover, PEP increased femur dry weight, ash weight, bone ash calcium, and serum calcium and phosphorus level. Interestingly, PEP increased bone mineral density and improved trabecular microarchitecture in both femur and tibia of OVX rats. Additionally, PEP increased bone strength, reduced serum bone turnover markers, inhibited bone resorbing cytokines and decreased malondialdehyde level in OVX rat. Furthermore, PEP-elevated serum transforming growth factor-ß, increased, reduced glutathione levels, superoxide dismutase, and catalase activity altered by OVX. CONCLUSION: We demonstrated that PEP exhibits antiosteopenic effects via enhancement of antioxidant activity and reduction of bone-resorbing cytokines expression.

Buffalo casein derived peptide can alleviates H2O2 induced cellular damage and necrosis in fibroblast cells.

Oxidative stress is one of a critical pathogenic factor in the progression of aging and chronic diseases such as cancer, myocardial inflammation and diabetes. In the present scenario, peptides with short half life and more biological specificities are gaining much attention as prodrugs. Thus, the present investigation carried out to screen potential antioxidative peptide, VLPVPQK to cope with the cellular oxidative damage. Our results showed that treatment of rat fibroblast cells with 0.2mM H2O2 for 6h significantly declined different oxidative stress biomarkers such as SOD, CAT, GSH, and promoted LDH activity. In addition, ROS and TNF-α levels were also increased upon H2O2 exposure for 6h and thereby, it induced cell death. Amazingly, pretreatment of the peptide (VLPVPQK) significantly elevated cell survivability, by reversing all H2O2 induced alterations in fibroblast cells. Therefore, our results indicated that, the peptide (VLPVPQK) acted as a potential cytoprotective agent, who restored redox balance and cell homeostasis in cultured fibroblast cells, even after H2O2 exposure, suggesting that the peptide can be valuable as an effective remedy in treatment of oxidative stress related diseases and skin inflammation related disorders.

Akt drives buffalo casein-derived novel peptide-mediated osteoblast differentiation.

Milk is a potential nutraceutical with wide range of bioactive compounds that are antioxidative, antimicrobial, antithrombotic, immunomodulatory, opioid and antihypertensive. Various intervention studies with milk reflect its stupendous role in elevating bone mineral density. Milk and milk products have shown a preventive effect in bone loss during pre- and postmenopausal women. Since, milk is proved to have a vital role in bone health promotion, there is a need to identify bioactive compounds within it. Recently we have reported four novel peptides from milk casein for their osteoblast proliferation activity. Their role in differentiation and the signaling cascade evoked by them have not been studied. Thus, the present study has been designed to investigate the differentiation potential and signaling cascade of one of the novel peptides, that is, NAVPITPTL by analyzing osteoblast differentiation markers such as alkaline phosphatase activity, osteocalcin and mineral deposition. All the experimentations suggested a significant role of this peptide in osteoblast differentiation. The inhibitor studies, immunocytochemistry and immunoblotting have proven that the peptide-induced differentiation through pAkt signaling cascade as pAkt was observed in nucleus. Moreover, the peptide was found to be bioaccessible up to 1%.