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.

Escaping the enemy's bullets: an update on how malaria parasites evade host immune response.

Malaria continues to cause untold hardship to inhabitants of malaria-endemic regions, causing significant morbidity and mortality that severely impact global health and the economy. Considering the complex life cycle of malaria parasites (MPs) and malaria biology, continued research efforts are ongoing to improve our understanding of the pathogenesis of the diseases. Female Anopheles mosquito injects MPs into its hosts during a blood meal, and MPs invade the host skin and the hepatocytes without causing any serious symptoms. Symptomatic infections occur only during the erythrocytic stage. In most cases, the host's innate immunity (for malaria-naïve individuals) and adaptive immunity (for pre-exposed individuals) mount severe attacks and destroy most MPs. It is increasingly understood that MPs have developed several mechanisms to escape from the host's immune destruction. This review presents recent knowledge on how the host's immune system destroys invading MPs as well as MPs survival or host immune evasion mechanisms. On the invasion of host cells, MPs release molecules that bind to cell surface receptors to reprogram the host in a way to lose the capacity to destroy them. MPs also hide from the host immune cells by inducing the clustering of both infected and uninfected erythrocytes (rosettes), as well as inducing endothelial activation. We hope this review will inspire more research to provide a complete understanding of malaria biology and promote interventions to eradicate the notorious disease.

Overhauling the ecotoxicological impact of synthetic pesticides using plants' natural products: a focus on Zanthoxylum metabolites.

The reduction in agricultural production due to the negative impact of insects and weeds, as well as the health and economic burden associated with vector-borne diseases, has promoted the wide use of chemicals that control these "enemies." However, the use of these synthetic chemicals has been recognized to elicit negative impacts on the environment as well as the health and wellbeing of man. In this study, we presented an overview of recent updates on the environmental and health impacts of synthetic pesticides against agro-pest and disease vectors while exhaustive reviewing the potentials of natural plant products from Zanthoxylum species (Rutaceae) as sustainable alternatives. This study is expected to spur further research on exploiting these plants and their chemicals as safe and effective pesticide entities to minimize the impact of their chemical and synthetic counterparts on health and the environment.

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.

The use of calcium carbide in food and fruit ripening: Potential mechanisms of toxicity to humans and future prospects.

The global increase in the demand for ripe fruits has induced unhealthy use of toxic chemicals in fruit ripening. One of such chemicals in common use is calcium carbide (CaC2). Due to its nature, commercial CaC2 is consistently found to contain impurities such as Arsenic and other toxic and carcinogenic chemicals. Few studies have only reported acute associative effects of CaC2, whereas there is only sparse evidence of its chronic and long-term impact. This article reviewed all the information on the nature of commercial CaC2 used for food processing. Meanwhile, all reports on the acute effects of CaC2, such as skin burns, skin irritations and inflammation, were summarized. Despite reported acute cases, an increase in commercial CaC2 for fruit ripening has been reported in recent times, especially in developing countries, as many vendors may consider the toxic effects/risks as negligible. Therefore, this study highlighted the paucity in research studies on the chronic impact of commercial CaC2 while proposing possible mechanisms for CaC2 induction of cancer, cardiovascular dysfunction, diabetic mellitus and others. Furthermore, suggestions on further studies to unravel the chronic impacts of CaC2 on health and recommendations for viable alternatives of fruit ripening with minimal or zero toxicity were proffered. Finally, other suggestions such as improving CaC2 detection technologies and innovative grassroots educational programs will strengthen national and international agencies to enforce restrictions on the illicit use of the toxicant for fruit ripening.

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.

Zanthoxylum Species: A Review of Traditional Uses, Phytochemistry and Pharmacology in Relation to Cancer, Infectious Diseases and Sickle Cell Anemia.

The health benefits and toxicity of plant products are largely dependent on their secondary metabolite contents. These compounds are biosynthesized by plants as protection mechanisms against environmental factors and infectious agents. This review discusses the traditional uses, phytochemical constituents and health benefits of plant species in genus Zanthoxylum with a focus on cancer, microbial and parasitic infections, and sickle cell disease as reported in articles published from 1970 to 2021 in peer-reviewed journals and indexed in major scientific databases. Generally, Z. species are widely distributed in Asia, America and Africa, where they are used as food and for disease treatment. Several compounds belonging to alkaloids, flavonoids, terpenoids, and lignans, among others have been isolated from Z. species. This review discusses the biological activities reported for the plant species and their phytochemicals, including anticancer, antibacterial, antifungal, antiviral, anti-trypanosomal, antimalarial and anti-sickling properties. The safety profiles and suggestions for conservation of the Z. species were also discussed. Taken together, this review demonstrates that Z. species are rich in a wide range of bioactive phytochemicals with multiple health benefits, but more research is needed towards their practical application in the development of functional foods, nutraceuticals and lead compounds for new drugs.

Zanthoxylum Species: A Comprehensive Review of Traditional Uses, Phytochemistry, Pharmacological and Nutraceutical Applications.

Zanthoxylum species (Syn. Fagara species) of the Rutaceae family are widely used in many countries as food and in trado-medicinal practice due to their wide geographical distribution and medicinal properties. Peer reviewed journal articles and ethnobotanical records that reported the traditional knowledge, phytoconstituents, biological activities and toxicological profiles of Z. species with a focus on metabolic and neuronal health were reviewed. It was observed that many of the plant species are used as food ingredients and in treating inflammation, pain, hypertension and brain diseases. Over 500 compounds have been isolated from Z. species, and the biological activities of both the plant extracts and their phytoconstituents, including their mechanisms of action, are discussed. The phytochemicals responsible for the biological activities of some of the species are yet to be identified. Similarly, biological activities of some isolated compounds remain unknown. Taken together, the Z. species extracts and compounds possess promising biological activities and should be further explored as potential sources of new nutraceuticals and drugs.

Methanol extracts of Fagara zanthoxyloides leaves possess antimalarial effects and normalizes haematological and biochemical status of Plasmodium berghei-passaged mice.

Context: The resistance of Plasmodium species to many available antimalarials calls for a continuous search for newer antimalarial agents. One possible source of new antimalarials is from natural sources such as Fagara zanthoxyloides Lam (Rutaceae), a medicinal plant used traditionally for treating malaria in South-Eastern Nigeria, Uganda and Asia. Objectives: To investigate the application of methanol extracts of F. zanthoxyloides in combating malaria infection and its associated disorders. Materials and methods: Methanol extracts of F. zanthoxyloides leaves (MEFZ) were evaluated for in vivo antimalarial activity. MEFZ at doses of 200, 400, and 600 mg/kg/d were administered orally for 4 consecutive days (days 0-4) to P. berghei-infected mice. The possible ameliorative effects of MEFZ on malaria-associated organ malfunctions were also assessed. Results: At 200, 400 and 600 mg/kg b.w., respectively, MEFZ produced 82.37% and 68.39%, 84.84%, and 90.75%, 95.95% and 92.67% chemosuppression and inhibition of P. berghei, respectively, comparable to 98.67% and 97.29% by combisunate, a standard antimalarial. The IC50 of MEFZ was estimated to be 235.23 mg/kg b.w. Similarly, treatment of parasitized mice with MEFZ significantly restored the malaria-modified haematological and biochemical status of the parasitized-MEFZ-treated mice compared with parasitized-untreated mice. MEFZ was tolerable up to 5000 mg/kg b.w dose; hence, the LD50 is above 5000 mg/kg b.w. Discussion and conclusions: The results of this curative assay demonstrated that MEFZ has antimalarial effects and normalized haematological and biochemical aberrations generated by malaria. The isolation of the antimalarial principles in MEFZ is warranted; they could be lead molecules for the development of new antimalarials.