Role of CETP, PCSK-9, and CYP7-alpha in cholesterol metabolism: Potential targets for natural products in managing hypercholesterolemia.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide, primarily affecting the heart and blood vessels, with atherosclerosis being a major contributing factor to their onset. Epidemiological and clinical studies have linked high levels of low-density lipoprotein (LDL) emanating from distorted cholesterol homeostasis as its major predisposing factor. Cholesterol homeostasis, which involves maintaining the balance in body cholesterol level, is mediated by several proteins or receptors, transcription factors, and even genes, regulating cholesterol influx (through dietary intake or de novo synthesis) and efflux (by their conversion to bile acids). Previous knowledge about CVDs management has evolved around modulating these receptors' activities through synthetic small molecules/antibodies, with limited interest in natural products. The central roles of the cholesteryl ester transfer protein (CETP), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cytochrome P450 family 7 subfamily A member 1 (CYP7A1), among other proteins or receptors, have fostered growing scientific interests in understanding more on their regulatory activities and potential as drug targets. We present up-to-date knowledge on the contributions of CETP, PCSK9, and CYP7A1 toward CVDs, highlighting the clinical successes and failures of small molecules/antibodies to modulate their activities. In recommendation for a new direction to improve cardiovascular health, we have presented recent findings on natural products (including functional food, plant extracts, phytochemicals, bioactive peptides, and therapeutic carbohydrates) that also modulate the activities of CETP, PCSK-9, and CYP7A1, and emphasized the need for more research efforts redirected toward unraveling more on natural products potentials even at clinical trial level for CVD management.

Osteo-modulatory dietary proteins and peptides: A concise review.

The integrity of the bone is dependent on the strict balance between osteoclastogenesis and osteoblastogenesis, and any imbalance results in bone diseases. Dietary proteins (DP) have been shown to promote osteogenesis while inhibiting bone resorption in cultured osteoblasts, and in animal models of bone diseases such as ovariectomy, 1α,25-dihydroxy-vitamin D3 (VD3), and prostaglandin E2 (PGE2)-induced bone resorption. Hydrolysis of some of these DPs with osteo-modulatory properties has been shown to generate hydrolysates with bioactive peptides that exhibit higher osteo-modulatory properties in comparison to intact (parent) proteins. The higher bioactivity of the isolated peptides and protein hydrolysates compared to intact proteins indicates that the osteo-modulatory properties are dependent on the degree of exposure of the functional groups of amino acid residues involved in target interaction. This review provides an overview of the preparation of DP and select peptides with osteo-modulatory properties, and summarizes the potential underlying mechanisms of action through which the bioactive peptides help maintain bone health. PRACTICAL APPLICATIONS: Bone diseases such as osteoporosis (OP), osteoarthritis (OA), bone cancer (BC), and others have negative impacts on the quality of life, especially in older women after menopause. Current drugs used in treating many bone diseases such as bisphosphonates, anabolic steroids, and selective estrogen receptor modulators have been limited by worrisome adverse effects such as organ toxicity, increased risk of cancer, and cardiovascular abnormalities, and gastrointestinal discomfort. There is growing scientific evidence that certain multifunctional dietary proteins and bioactive peptides may positively modulate bone health by modifying risk factors for bone diseases including inflammation, oxidative stress, hyperlipidemia, and hyperglycemia.

A review on the techno-functional, biological, and health-promoting properties of hempseed-derived proteins and peptides.

Protein-energy malnutrition is a global challenge that demands urgent attention, especially with the increasing population growth and unmatched food security plans. One strategy is to expand the list of protein sources, such as neglected and underutilized crops, with high protein content. A good number of plant proteins, in addition to their nutritional benefits, exert therapeutic properties as seen in seeds derived from legumes and emerging sources such as hemp. In this review, the transepithelial transport, functional, and biological properties of hempseed proteins (HSPs) and peptides were discussed. The review also described the potential safety issues of incorporating hempseeds in food products. Due to the multitargeted effects of hempseed-derived proteins and their peptides against many chronic diseases, and their functional properties, current knowledge shows that hempseed has tremendous potential for functional food and nutraceutical applications. PRACTICAL APPLICATIONS: The alarming rate of malnutrition and the attendant health consequences demand that underexploited nutrient-rich crops should be incorporated as part of our common dietary sources. Among these crops, hempseed is gaining attention as an emerging source of proteins and peptides with promising potential in prevention and management of chronic diseases such as diabetes, hypertension, cancer, hypercholesterolemia, obesity, and diseases whose etiology involves oxidative stress and inflammation. Fortunately, a growing body of research evidence is demonstrating that hempseed is a reservoir of proteins and peptides with nutraceutical potentials for curbing life-threatening diseases.

Therapeutic benefits of Salvia species: A focus on cancer and viral infection.

Man is increasingly being faced with many health conditions, including viral infection, some of which increases the risk to cancer. These infectious agents contribute to the large number of persons with cancer and the worrisome number that die from the diseases. A good range of drugs are currently in place for treating patients infected with viruses, however, some of the drugs' effectiveness are limited by the emergence of drug-resistant strains of the viruses, as well as adverse effects of the drugs. Similarly, the inability of many anticancer drugs to selectively kill cancer cells while sparing hosts' normal cells limit their use. This warrants more research for newer drugs, especially from chemicals naturally encrypted in plants with anticancer and antiviral activities. In response to infection with cancer-inducing viruses, plants such as Salvia species synthesize and store secondary metabolites to protect themselves and kill these viruses as well as inhibit their ability to induce carcinogenesis. Hence, this review presented a discussion on the potential application of Salvia species in the prevention and management of cancer and viral infection. The study also discusses the cellular mechanisms of action of these herbal products against cancer cells and viruses, where available and provided suggestions on future research directions. The study is believed to spur more research on how to exploit Salvia phytochemicals as candidates for the development of nutraceuticals and drugs for managing cancers and viral infection.

Molecular mechanisms of hematological and biochemical alterations in malaria: A review.

Malaria is a dangerous disease that contributes to millions of hospital visits and hundreds of thousands of deaths, especially in children residing in sub-Saharan Africa. Although several interventions such as vector control, case detection, and treatment are already in place, there is no substantive reduction in the disease burden. Several studies in the past have reported the emergence of resistant strains of malaria parasites (MPs) and mosquitoes, and poor adherence and inaccessibility to effective antimalarial drugs as the major factors for this persistent menace of malaria infections. Moreover, victory against MP infections for many years has been hampered by an incomplete understanding of the complex nature of malaria pathogenesis. Very recent studies have identified different complex interactions and hematological alterations induced by malaria parasites. However, no studies have hybridized these alterations for a better understanding of Malaria pathogenesis. Hence, this review thoroughly discusses the molecular mechanisms of all reported hematological and biochemical alterations induced by MPs infections. Specifically, the mechanisms in which MP-infection induces anemia, thrombocytopenia, leukopenia, dyslipidemia, hypoglycemia, oxidative stress, and liver and kidney malfunctions were presented. The study also discussed how MPs evade the host's immune response and suggested strategies to limit evasion of the host's immune response to combat malaria and its complications.