6 Amazing Health Benefits of Small Flower Willow Herb

Willow herb (Epilobium parviflorum) is a perennial herbal plant. It has thick rhizomes with short shoots at it base. The stem is tall and cylindrical with hairs. It has narrow-lanceolate leaves which are small and sharply toothed. The flowers of willow herb are small and red-purple in color with four petals, eight stamens and a stigma with four lobes.

The fruits of willow flower herb are elongated capsules which contain seeds that are covered with numerous silky hairs. Willow herbs usually bloom between June and August.

Phytochemical Composition of Epilobium parviflorum

The chemical composition of willow herb can be classified accordingly as follows:

Flavonoids

These include Kaempferol, Kaempferol-3-O-rhamnoside, Kaempferol-3-O-glucoside, Quercetin, Quercetin-3-O-rhamnoside, Quercetin-3-O-glucoside, Quercetin-3-O-galactoside, Myricetin, and Myricetin-3-O-rhamnoside.

Phenolic acids

Ellagic, Gallic, Protocatechuric, Syringic, Vanillic, Curinamic, Caffeic and Ferulic acids.

Tannins

Oenothein A and Oenothein B.

Fatty acids

The fatty acids include Oleic, Linoleic, α-linoleic, Palmitic, Stearic and Arachidonic acids.

 

6 Amazing Health Benefits of Small Flower Willow herbs

Small flower Willow herb contains 6 amazing health benefits that are in high demand.

 

  1. Treatment of Rheumatoid Arthritis (RA)

Willow herb is used in the treatment of RA and other inflammatory diseases. Just like Monkey sugarcane, Willow herb contains various groups of kaempferol compounds which suppresses NF-kB inflammatory response by blocking its signaling pathways. Kaempferol also regulates the production of IFN-ϒ and IL-2, both of which are pro-inflammatory factors.

Aside Kaempferol compounds, small flower willow herb also contains Quercetin compounds. Quercetin suppresses the NLRP3 elevation in RA synovial tissues. It also inhibits the release of cytokines and decreases lipopolysaccharide-induced cyclooxigenase (COX-2). It antagonizes bone resorption by suppressing NF-kB and AP-1 activities.

Chemical structure of Kaempferol

Fig. 1. Chemical structure of Kaempferol

 

 

  1. Treatment of Hepatitis Infection

The Oenothein B component of the Tannins present in Willow herb inhibits hepatitis C virus (HCV) invasion. Hepatitis C is a liver infection, which can be transmitted through blood contact with infected objects or through sexual transmission. When left untreated, HCV can cause serious damage to the liver.

 

Chemical structure of Oenothein B

Fig. 2. Chemical structure of Oenethein B.

  1. Treatment of Tumors

Another benefit of Willow herb is in the treatment of tumors. The Oenothein B in Small flower Willow herb serves as an immunomodulator and antitumor substance. It carries this activity by stimulating macrophages as well as the release of LAF and IL-1β from macrophages.

  1. Treatment of Prostate Cancer

Willow herb is widely known for its efficacy in the treatment of prostate cancer. Its chemical compounds such as Kaempferol, Quercetin and Oenothein B possess among others, anti-proliferation activities. Oenothein B, inhibits 5α-reductase and Aromatase, which are involved in the etiology of benign prostatic hyperplasia.

 

 

Chemical structure of Quercetin

Fig.3. Chemical structure of Quercetin

  1. Antioxidants

Willow herb is made into and taken as an antioxidant tea. It increases glutathione levels and the activity of superoxide dismutase (SOD). This maintains a youthful body by mopping up free radicals that attack and destroy the cells.

 

  1. Treatment of microbial infections

Willow herb is beneficial for treating bacterial and viral infections such as the urinary tract diseases. Tannins contribute to this efficacy of Willow herb against bacterial and viral infection.

 

 

5 Amazing Health Benefits of Monkey Sugarcane

Monkey sugarcane (Costus afer) has five amazing health benefits that would surprise you. The plant, which is always greenish and perennial, is usually found in West African countries ad beers white and yellow flowers. Every part of Monkey sugarcane offers an amazing health benefits. Other common names of Costus afer include Okpete, Tete-egun, or Mbritem.

The plant contains some bioactive compounds that have nephroprotective properties on the kidneys. It also protects against neurodegenerative diseases as well as protection of the pancreatic beta cells.

 

Phytochemical Components of Costus afer

 

Monkey sugarcane leaves are usually green.

Costus afer contains several phytochemicals in their roots, stems, rhizomes and leaves. Some of the phytochemicals include:

  • Alkaloids
  • Tannins
  • Phenols
  • Saponins
  • Triterpenes
  • Glycosides

The rhizome contains steroidal saponins such as

  • Diocin
  • Paryphllin C
  • Aferoside B
  • Aferoside C

The aerial parts contain kaempferol-3-O-R-L-rhamnopyranoside while the roots contain additional Aferoside A, Aferoside B and Aferoside C.

 

Health benefits of Monkey Sugarcane

The health benefits of Monkey sugarcane, especially in the treatment of rheumatoid arthritis, may be attributed to its bioactive compounds such as kaempferol and Aferosides. It is used in treating a wide range of illness which include:

  1. Treatment of Ulcer

The rhizome pulp and leave extracts are used in treating ulcers when taken, mostly by oral administration. Both the leaves and rhizome extracts increase gastroprotective factors, antioxidants such as glutathione, and decreases lipid peroxidation.

 

  1. Treatment of Diabetes Mellitus

Diabetic patients would find the leaf and stem extracts of Monkey sugarcane useful in treating diabetes mellitus, as both extracts enhance glucose clearance and reduce hyperglycemia by increasing cellular glucose uptake.

 

  1. Monkey Sugarcane Possesses Antioxidant Properties

The extracts of the various parts of Costus afer, especially the leaf extract is used in treating oxidative stress. It increases the activity of plasma superoxide dismutase (SOD) and increases the levels of glutathione and serum electrolytes such as Na+ and HCO3 . Other enzymes whose activities, Costus afer extract increases include catalase and glutathione-S-transferase.

 

  1. Protection of The Kidneys From Toxic Damage

The plant leaves, when taken, protect the kidneys from toxic and harmful substances. It also protects the β-cells of the pancreas from alloxan-induced damage. This supports its anti-diabetic efficiency as healthy β-cells promotes insulin production and glucose transport across the inter- and intra-cellular compartments.

 

  1. Possesses Anti-inflammatory Activity

Costus afer contains strong anti-inflammatory components such as Kaempferol, Aferoside A and Zn2+. They exert their anti-inflammatory activities by regulation the signaling activity of NF-kB pathways. Also, they inhibit the production of IFN-ϒ and IL-2, both which are proinflammatory factors. This regulatory effect of Costus afer extracts makes them useful in the treatment of rheumatoid arthritis and other inflammatory diseases. Aside the regulatory role they play on NF-kB signaling pathways, they also exert inhibitory effect on the cyclo-oxygenase-2 (COX-2) and interfere with G-protein-mediated signal transduction.

 

Side Effects of Monkey sugarcane

When taken for a long period of time, the side effects from the use of Costus afer may include:

Sufficient reduction of red blood cells, which results in anemia.

Increased weight of the liver and vacuolar changes in the hepatic cells.

When taken by pregnant women, may lead to miscarriage.

 

                                                REFERENCES

G. E. Omokhua, “Medicinal and socio-cultural importance of Costus afer (Ker Grawl) in Nigeria,” African Research Review, vol. 5, no. 5, pp. 282–287, 2011.

G. N. Anyasor, O. Ogunwenmo, O. A. Oyelana, and B. E. Akpofunure, “Phytochemical constituents and antioxidant activities of aqueous and methanol stem extracts of Costus afer Ker Gawl. (Costaceae),” African Journal of Biotechnology, vol. 9, no. 31, pp. 4880–4884, 2010.

A. N. Ezejiofor, Z. N. Igweze, N. A. Udowelle, and O. E. Orisakwe, “Histopathological and biochemical assessments of Costus afer stem on alloxan-induced diabetic rats,” Journal of Basic and Clinical Physiology and Pharmacology, vol. 28, no. 4, pp. 383–391, 2017.

A. N. Ezejiofor, C. N. Orish, and O. E. Orisakwe, “Cytological and biochemical studies during the progression of alloxan-induced diabetes and possible protection of an aqueous leaf extract of Costus afer,” Chinese Journal of Natural Medicines, vol. 12, no. 10, pp. 745–752, 2014.

 

Monkeypox Virus Infection

Monkeypox is a smallpox-like rare infectious disease that is mainly spread by wild animals such as rodents and squirrels. Monkeypox virus belongs to the Orthopoxvirus genus in the Poxviridae family. The disease is mainly spread in West and Central Africa, but was discovered during the pox-like disease outbreak of the virus in Denmark in 1958.

 

How Do You Get Infected by Monkeypox Virus?

Monkeypox virus infection is transmitted to human through the handling of infected animals or by direct contact with an infected animal’s body fluid. It can also be transmitted from one person to another through contact with large infective respiratory droplets or direct contact with infected person.

 

What Is The Incubation Period Of Monkeypox Virus?

The incubation period of Monkeypox may vary from person to person depending on the person’s immune defense system. However, the incubation period for the virus is between 7 to 21 days.

 

What Are The Symptoms Of Monkeypox?

The symptoms of Monkeypox include:

  • High fever
  • Sore throat
  • Headache
  • Malaise
  • Cough
  • Swollen lumph nodes

Rashes appear on the patient’s body within 1 to 3 days after the appearance of fever. The rashes often begins from the face and spread throughout the body.

Before falling off, the lesions progress through the following stages:

  • Macules
  • Papules
  • Vesicles
  • Pustules
  • Scabs

 

How Long Can Monkey Infection Last?

The illness usually lasts for four weeks or less in some cases. The death rate of Monkeypox is as many as 1 in 10 persons who contact the disease.

 

How Can You Prevent Monkeypox Infection?

To prevent yourself from contacting Monkeypox virus, do the following:

  • Avoid contact with animals that are carriers of the virus such as rodents and squirrels.
  • Infected persons should be isolated and quarantined.
  • Avoid contact with materials used by infected persons.
  • Always maintain good hygiene and wash hands after contact with infected patients.
  • Use personal protective equipment when attending to patients.

 

Treatment Of Monkeypox

There is currently no treatment for Monkeypox virus infection. However, smallpox vaccines, antiviral medicines, and vaccinia immune globulin (VIG) can be used in preventing the outbreak of the disease.

 

 

 

 

Matrix Metalloproteinases (MMPs) In Tumor Metastasis

Matrix metalloproteinases (MMPs) are a family of Zinc-dependent endopeptidase that degrade various proteins of the extracellular matrix (ECM). As members of the metzincin group of proteases, they share the conserved zinc-binding motif in their catalytic active site. Initially, MMPs were thought to function mainly in degrading ECM, but recent studies has shown that they also function significantly as regulators of extracellular tissue signaling networks.

MMPs are defined by the presence of two conserved zinc-binding motifs. One motif is a cysteine-containing pro-domain, whose function is partly to restrain catalytic; whereas the other motif is a histidine-rich catalytic domain, responsible for the endopeptidase activity.

MMPs Are Involved in Various Physiological and Pathological Processes.

MMPs are involved in numerous physiological and pathological processes. In physiological process, MMPs are involved in embryonic development, wound repair, ovulation, bone remodeling, macrophage function and in neutrophil function. They are also involved in pathological processes such as inflammation, tumor metastasis, rheumatoid arthritis, gastric ulcer, among others.

 MMPs and EMT in Tumor Metastasis

Epithelia-mesenchymal transition (EMT) plays its central role in normal embryonic development. But recent studies have shown its roles in pathological processes, such as cancer progression, fibrosis, and chronic inflammation.

MMPs associate with EMT in cancer progression through three mechanisms:

  • Elevated levels of MMPs in the tumor microenvironment induce EMT in epithelia cells.
  • EMT in cancer then produces more MMPs, thereby facilitating cell invasion and metastasis.
  • EMT can generate activated stromal-like cells that drive cancer progression through further MMPs production.

Role of MMPs in Tumor Metastasis

The role of MMPs in tumor metastasis was initially believed to be limited to the degradation of ECM and basement membrane collagen. But now, we know that MMPs paly critical roles at every step of tumor progression. MMPs influence several biological functions, such as modification of signaling pathways, regulation of cytokines involved in immune responses, and tumor growth by stimulating angiogenesis, which leads to the spread of cancer.

MMP-11 Plays Dual Roles in Tumors

Unlike many members of MMPs, MMP-8 and MMP-12 were reported to exert antitumor effects, thereby suppressing tumor growth. MMP-11 on the other hand plays a dual role in cancer progression. In one hand, MMP-11 promotes cancer development by inhibiting apoptosis and enhancing the invasion of cancer cells; on the other hand, however, MMP-11 plays a negative role against cancer development through the suppression of metastasis.

 

REFERENCES

Hook D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev. 2003;120(11):1351–83.

Cheng S, Lovett DH. Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol. 2003;162(6):1937–49.

Lopez-Otin C., Matrisian L.M. Emerging roles of proteases in tumour suppression. Nat. Rev. Cancer. 2007;7:800–808.

Zhang X., Huang S., Guo J., Zhou L., You L., Zhang T., Zhao Y. Insights into the distinct roles of MMP-11 in tumor biology and future therapeutics (Review) Int. J. Oncol. 2016;48:1783–1793.

What is Angiogenesis?

Angiogenesis is the formation of new blood vessels. It is the process by which the body forms new blood vessels from existing ones. This process occurs throughout the life of an individual, starting in the uterus and continuing to old age. Angiogenesis occurs both in healthy tissues as well as in diseased ones, such as in cancer cell growths.

Why Does Angiogenesis Occur in the Body?

Angiogenesis takes place when a particular body part or tissue requires the supply of nutrients and to it. In hypoxia tissues, the need for oxygen supply to the parenchymal cells is detected by the oxygen sensing mechanisms, which then demands the formation of new blood vessels to meet this need.

Types of Angiogenesis

There are two types of angiogenesis, they are:

  1. Sprouting angiogenesis
  2. Intrussusceptive angiogenesis

Both sprouting and intrussusceptive angiogenesis, occur in the uterus and in adults.

Sprouting Angiogenesis (SA)

Sprouting angiogenesis is the process of growing new blood capillary vessels from pre-existing ones. When this occurs, the new blood vessels shall provide oxygen to expanding tissues and organs.

Sprouting angiogenesis plays important roles in many diseases, such as diabetes, rheumatoid arthritis, cardiovascular ischemic complications and cancer. In cancer, SA is involved not only in primary tumor but also in metastasis formation and further outgrowth of metastasis.

Steps in Sprouting Angiogenesis

Sprouting angiogenesis involves several steps, which include:

  1. Initiation of growth factors responsible for angiogenesis by low oxygen tension, low pH and high lactate levels.
  2. Expression of a transcription factor, hypoxia-inducible factor (HIF), by endothelia cells, which regulates expression of vascular endothelia growth factor (VEGF) and stimulates angiogenesis.
  3. Binding of growth factors to their receptors on endothelia cells and activating them. This is followed by detachment of pericytes.
  4. Binding of VEGF to its receptors and inducing a signaling cascades which enables one endothelia cell to form a tip cell while adjacent cells form stalk cells.
  5. Tip cells express VEGFR, delta-like ligand-4 (DLL-4), and matrix metalloproteinases (MMPs). They form filopodia, which are slender protrusions of the plasma membrane containing parallel bundles of actin filaments.
  6. Rhoa, Racl and Cdc42, members of Rho small GTPases, regulate the formation of filopodia.
  7. Activation of VEGFR leads to the extension of filopodia and migration of the tip cells forward.
  8. Activated endothelia cells secrete proteases, which are essential for the degradation of basement membrane. They allow tip cells to escape from the parent vessels and allow formation of sprouts and guidance of sprouts through the extracellular matrix (ECM).

Intrussusceptive Angiogenesis (IA)

In intrussusceptive angiogenesis, also called splitting angiogenesis, the blood vessel wall extends into the lumen, thereby causing a single vessel to split into two. It is fast and efficient compared to SA. This is because IA only requires reorganization of the existing endothelia cells; it does not rely on endothelia proliferation and migration. Like SA, however, IA also occur throughout the life of an individual, but it plays prominent roles in vascular development in embryos, where growth is fast with limited resources.

Promoters of Angiogenesis

Angiogenesis is regulated by a balance between pro-angiogenic and anti-angiogenic factors. The promoters include, HIF-1, VEGF, FGF, PDGE, TGF-β and angiopoietin and proteases.

Hypoxia-induced Factor-1 (HIF-1)

This is the most potent inducer of the expression of genes such as those encoding for glycolytic enzymes, VEGF and erythropoietin. HIF-1 is upregulated in hypoxia tumor cells; it activates transcription of target genes by binding to Cis-actin enhancers, hypoxia response element (HRE) close to the promoters of those genes.

Vascular Endothelia Growth factor (VEGF)

VEGF functions in angiogenesis by inducing the expression of DLL-4 in tip cells. It promotes the migration of endothelia cells by inducing expression of intergrins. It also stimulates production of MMPs, plasminogen activator and proteolytic enzymes by endothelia cells, which in turn promote the degradation of ECM.

Fibroblast Growth Factor (FGF)

FGF promotes proteases production and upregulates VEGF expression by endothelia cells. It also stimulates endothelia cells proliferation and migration.

Inhibition of Angiogenesis by Thymoquinone

Thymoquinone exerts its inhibitory effects on VEGF, FGF, PIGF, PDGF, which are pro-angiogenic factors, by suppressing the Akt/ERK signaling pathway.

 

REFERENCES

Carmeliet, P., & Jain, R. K. (2000). Angiogenesis in cancer and other diseases. Nature, 407, 249–257.

Martin, A., Komada, M. R., & Sane, D. C. (2003). Abnormal angiogenesis in diabetes mellitus. Medicinal Research Reviews, 23, 117–145.

Koch, A. E. (2003). Angiogenesis as a target in rheumatoid arthritis. Annals of the Rheumatic Diseases, 62 Suppl 2, ii60–67.

Cao, Y., Hong, A., Schulten, H., & Post, M. J. (2005). Update on therapeutic neovascularization. Cardiovascular Research, 65, 639–648.

Carmeliet, P. (2005). Angiogenesis in life, disease and medicine. Nature, 438, 932–936.

Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100, 57–70.

Kerbel, R. S. (2000). Tumor angiogenesis: Past, present and the near future. Carcinogenesis, 21, 505–515.

Yi T, Cho SG, Yi Z, Pang X, Rodriguez M, Wang Y, Sethi G, Aggarwal BB, Liu M. Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol Cancer Ther. 2008 Jul;7(7):1789-96.

Effect of Black Seed Thymoquinone on Rheumatoid Arthritis

Thymoquinone (2-isoprpyl-5-methyl-1,4-benzoquinone) is the most active component of Black cumin (Nigella sativa) seed oil. It is widely used in traditional medicine to treat a wide range of illnesses.

According to various research findings, thymoquinone exert important health-beneficial effects including antioxidant, anti-inflammatory and anti-cancer effects. As an antioxidant agent, thymoquinone normalizes glutathione levels and increases the activity of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase.

 

Black Cumin Tea Contains Thymoquinone

Black cumin seed is made into a tea and served as an antioxidant agent. Since it contains thymoquinone and other biologically active phytochemicals, black cumin seed tea should be recommended for patients who suffer rheumatoid arthritis. It can also be served to cancer patients who are undergoing chemotherapy.

How To Prepare Black Cumin Seed Tea

  • To prepare black cumin seed tea, assemble 2 cups of water, 2 tea spoonful of raw black cumin seeds and honey. Then follow the steps as follows:
  • Add the 2 cups of water and black cumin seeds in a pot and heat till it boils.
  • Remove from heat once it boiled.
  • Cover the pot and allow it to steep for about 10 minutes.
  • Strain the water into a cup using a mesh. You may add the seed to enjoy the whole benefits if you so wish.
  • Add two spoonful of honey and stir
  • Serve and enjoy your tea

 

Benefits of Thymoquinone and Black Cumin Seed Tea in Treatment of Rheumatoid Arthritis

The uncontrolled inflammation associated with rheumatoid arthritis arises as a result of the uncontrolled production and activity of various inflammatory cytokines, TNFα, IL-1, IL-17, IL-6 and the resulting inflammation is responsible for the pain, tenderness, swelling, redness and stiffness of joints.

Black cumin seeds and especially thymoquinone has been shown to be beneficial against rheumatoid arthritis and autoimmune diseases.

 

Thymoquinone Inhibits NF-kB Signaling In Rheumatoid Arthritis

NF-kB regulates the expression of many genes, enzymes, cytokines, cell cycle regulatory molecules as well as angiogenic factors. It induces inflammation by influencing the expression several pro-inflammatory cytokines, chemokines , acute phase proteins and growth factors.

Thymoquinone inhibits NF-kB induced inflammatory response in rheumatoid arthritis patients by inhibiting its translocation into the nucleus. Thymoquinone also inhibits NF-kB activities by suppressing TNF-induced-NF-kB activation. This is done by inhibiting TNF-induced IKBα phosphorylation and degradation as well as p65 phosphorylation and nuclear translocation.

 

Thymoquinone Inhibits Prostaglandins and COX-2 in Rheumatoid Arthritis

Prostaglandins (PGs) are arachidonic acid metabolites. They are found at elevated levels in synovial fluid and also in synovial membrane, where they function in the development of vasodilation, fluid extravasation and pain in synovial tissues. Aside these functions, Prostaglandin E2 (PGE2) and COX are upregulated in synovial tissues in rheumatoid arthritis patients, where PGE2 synergizes with IL-23 to stimulate Th17 cell proliferation.

Th17 in turn stimulates the release of pro-inflammatory cytokines and promotes bone resorption. PGE2 also mediates complex interactions that lead to the development of articular cartilage erosions and juxta-articular bone.

Cyclooxygenase enzymes (COX), especially COX-2 are involved in inflammatory responses. COX-2 is induced by pro-inflammatory cytokines, mainly IL-1.

Thymoquinone suppresses the expression of COX-2 protein by inhibiting NF-kB signaling pathway activation and induces the expression of cytoprotective enzymes.

Effect of Thymoquinone on PI3k/Akt Signaling Pathway

Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway is an intracellular regulatory signal transduction pathway that is activated by toxic substances or cellular stimuli that regulate many cellular processes including cell growth, survival and apoptosis.

When abnormally activated, PI3K/Akt signaling pathway is involved in the pathogenesis of many diseases including diabetes mellitus, cancer, and rheumatoid arthritis. In RA, PI3K/Akt signaling pathway play important role through the expression of different types of pro-inflammatory mediators that degrade IKβ and activate NF-kB signaling pathway.

Thymoquinone induces apoptosis by blocking PI3K/Akt signaling pathway in DU-145 cell line. It also deactivate PI3K/Akt and NF-kB signaling pathway and regulate various gene products such as p65 and COX-2.

 

REFERENCES

J.K. Kundu, L. Liu, J.-W. Shin, Y.-J. Surh., Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo Biochem. Biophys. Res. Commun., 438 (4) (2013), pp. 721-727

 

Umar, J. Zargan, K. Umar, S. Ahmad, C.K. Katiyar, H.A. Khan Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats Chem. Biol. Interact., 197 (1) (2012), pp. 40-46

 

Vaillancourt, P. Silva, Q. Shi, H. Fahmi, J.C. Fernandes, M. Benderdour

Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis J. Cell. Biochem., 112 (1) (2011), pp. 107-117

 

Thymoquinone inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by suppressing NF-κB and MAPKs signaling pathway Inflammation, 38 (6) (2015), pp. 2235-2241

 

Khan, A. Sureda, T. Belwal, S. Çetinkaya, İ. Süntar, S. Tejada, H.P. Devkota, H. Ullah, M. Aschner. Polyphenols in the treatment of autoimmune diseases. Autoimmun. Rev., 18 (7) (2019), pp. 647-657

 

Stańczyk J, Kowalski ML. Rola cyklooksygenaz oraz prostaglandyn w patogenezie reumatoidalnego zapalenia stawów [The role of cyclooxygenase and prostaglandins in the pathogenesis of rheumatoid arthritis]. Pol Merkur Lekarski. 2001 Nov;11(65):438-43.

 

Molecular Mechanism of Malaria Parasite Infection

Malaria is a life-threatening disease that is caused by Plasmodium parasites. It is transmitted to individuals through the bite of an infected female anopheles mosquito. Malaria is a tropical disease that is prevalent in Sub-Saharan African populations.

There are five species of plasmodium parasites, which affect humans. They are:

  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium malariae
  • Plasmodium ovale

Among the five species of plasmodium parasite, Plasmodium falciparum causes the most severe and life-threatening malaria, while Plasmodium vivax is the most widely distributed, representing 53% of malaria incidences.

 

Symptoms of Malaria

The signs and symptoms if malaria may include:

  • Fever
  • Headache
  • Chills
  • Vomiting and diarrhea
  • Nausea
  • Tiredness
  • Muscular pain

 

How Is Malaria Parasite Transmitted?

Malaria parasite can only be transmitted when an infective female anopheles mosquito bites and feeds on the blood of and person. At first, the female anopheles mosquito bites and feeds on the blood of an infective person, thereby taking along the blood plasmodium sporozoites. When the mosquito bites another individual, it injects the plasmodium sporozoites into the blood circulation, from it they move to the liver of the newly infected person.

When the sporozoites get to the liver cells they rapidly bind and invade the liver cells and undergo rapid multiplication. This leads to the release of infective merozoites which invade red blood cells and destroy them.

 

Life Cycle of Plasmodium Falciparum

The life cycle of malaria parasites involves two hosts which are the female anopheles mosquito and human hosts. In humans, the parasite grows and multiply in the liver cells and then in the red blood cells, where successive broods of parasites grow and destroy the cells, releasing the merozoites, which continue to the cycle by invading other red blood cells.

 

Stages of Life Cycle of Plasmodium Falciparum

As seen above, malaria parasite passes through several stages in its life cycle. We shall look at the major stages which are the human stages and the mosquito stages of the life cycle of plasmodium falciparum.

 

The human stage (Exo-erythrocytic schizogony)

In the liver, the sporozoites infect the liver cells and mature into Schizonts, which rupture and release the Merozoites. In plasmodium vivax, and plasmodium ovale a dormant stage called hypnozoites can persist in the liver, if untreated, and cause relapses by invading the bloodstream weeks or months later.

 

Human Blood Stage (Erythrocytic Schizogony)

In this stage, the merozoites released infect red blood cells and form a ring-stage, trophozoites. The trophozoites differentiate into sexual erythrocytic stage called gametocytes.

The blood stage parasites are responsible for the clinical manifestations of the disease.

 

Mosquito stage (Sporogonic cycle)

During blood meal, the female anopheles mosquito ingests the male and female gametocytes. The male gametocyte is called microgametocyte while the female gametocyte is called macrogametocyte.

In the mosquito’s stomach, the microgametes penetrate the macrogametes to form the zygotes. The zygotes then become motile and elongated, and are called Ookinetes. The ookinetes invade the mid gut of wall of the mosquito, where they develop into Oocysts. The Oocysts grow, rupture and release sporozoites. These then make their way to the mosquito’s salivary glands.

When the mosquito bites and feeds on another person’s blood, the sporozoites are inoculated, thereby repeating the life cycle of malaria.

 

Molecular Mechanism of Plasmodium Falciparum Erythrocyte Invasion

The entry of parasite into the erythrocytes is the key to establishing blood stage infection and thus, central to both acute and severe malaria. When the merozoites invades the red blood cells, it changes its orientation until its apical end containing specialized secretory organelles called micronemes, rhoptries and base granules is pointed at the erythrocyte.

The binding and invasion of erythrocytes are carried out by two proteins of the apical secretory organelles. These proteins are the reticulocyte-binding protein homologous (RHs) and erythrocyte-binding-like proteins (EBLs).

In EBLs, a dufy-binding-like (DBL) domain mediates specific binding to different host cell receptors, including glycophorins A, B, and C as well as duffy blood antigen. But in RHs, complement receptor 1 (CR1) and basigin are the receptors for PfRH4 and PfRH5 respectively.

Whereas RHs have early role in host sensing, EBLs play a direct role in junction formation. This suggests that RH sensing and subsequent interaction with a suitable host erythrocyte sends a signal to the merozoite that triggers the subsequent steps of invasion.

 

PfRH1 interaction with its receptor on erythrocyte surface initiates invasion of parasite.

The complex invasion process of merozoite erythrocyte invasion begins with the interaction of a relatively small amount of PfRH1 with its receptor on the erythrocyte surface. This interaction leads to a signaling cascade that leads to the release of intracellular Ca2+ stores, followed by triggering of microneme and rhoptry discharge and junction formation.

PfRH1 is located at the Rhoptry duct. Whereas its role in parasite invasion is known, its receptor on erythrocyte is unknown. PfRH1 is sialic acid-dependent and binds to its receptor in a protease sensitive manner.

EBA-175 binding and parasite invasion of red blood cells

EBA-175 is located on the microneme and is responsible for the binding and invasion of merozoites to erythrocytes. Unlike PfRH1, EBA-175 receptor is known; it binds to the glycophorin A (GpA). GpA is the major glycoprotein found on human erythrocytes and is heavily sialylated. It is a 131 amino acid transmembrane dimer. Each monomer spans the membrane once exposing its N terminus extracellularly. The EBA-175/GpA is the dorminant chymotrypsin-resistant invasion pathway.

 

 

REFERENCES

 

Templeton, T. J., and Kaslow, D. C. (1997) Mol. Biochem. Parasitol. 84, 13–24

Collins, W. E., Miller, L. H., Glew, R. H., Contacos, P. G., Howard, W. A., and Wyler, D. J. (1973) J. Parasitol. 59, 855–858

Schmidt, L. H. (1978) Am. J. Trop. Med. Hyg. 27, 671–702

Collins, W. E., Galland, G. G., Sullivan, J. S., and Morris, C. L. (1994) Am. J. Trop. Med. Hyg. 51, 224–232

Pei X, Guo X, Coppel R, Mohandas N, An X. Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) destabilizes erythrocyte membrane skeleton. J Biol Chem. 2007; 282:26754– 26758. [PubMed: 17626011]

Safeukui I, Correas JM, Brousse V, Hirt D, Deplaine G, Mule S, Lesurtel M, Goasguen N, Sauvanet A, Couvelard A, Kerneis S, Khun H, Vigan-Womas I, Ottone C, Molina TJ, Treluyer JM, Mercereau-Puijalon O, Milon G, David PH, Buffet PA. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen. Blood. 2008; 112:2520–2528. [PubMed: 18579796]

Camus, D. Hadley, T.J. A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science. 1985; 230: 553-556

Triglia, T., M. T. Duraisingh, R. T. Good, and A. F. Cowman. 2005. Reticulocyte-binding protein homologue 1 is required for sialic acid-dependent invasion into human erythrocytes by Plasmodium falciparumMol. Microbiol. 55:162-174.

Triglia, T., W. H. Tham, A. Hodder, and A. F. Cowman. 2009. Reticulocyte binding protein homologues are key adhesins during erythrocyte invasion by Plasmodium falciparumCell. Microbiol. 11:1671-1687.

 

 

 

 

 

 

How zinc supplementation prevents Viral replication in covid-19 patients

Covid-19 is a systemic disease that affects the lungs and multiple organs and tissues. It is transmitted, rapidly from one person to another in close proximity, through contact with virus laden aerosols discharged in coughs and sneezes. Most affected patients die as a result of acute respiratory distress syndrome.

There are several variants of Covid-19, but the Alpha, Delta, and Omicron variants are most widely spread with severe health breakdown.

 

Symptoms Of Covid-19

The symptoms of covid-19 are similar to those of normal cold and flu. They are:

  • High temperature or chills
  • Continuous cough
  • Change in the sense of smell and taste
  • Short breath
  • Feeling of tiredness
  • Headache and body pains

 

Viral Life Cycle And Cell Invasion Of Covid-19

Once the virus gained entrance into the host body, it binds to host receptors and enters the host cells through endocytosis or membrane fusion. The virus is made up of for structural proteins, which are the,

  • Spike (S) protein
  • Membrane (M) protein
  • Envelope (E) protein
  • Nucleocapsid (N) protein

The S protein protrudes from the viral surface and is the most important viral protein for host attachment and penetration. It is composed of two functional subunits (S1 and S2). The S1 is responsible for viral binding to the host cell receptor, angiotensin-converting enzyme 2 (ACE-2) and the S2 subunit plays a role in the fusion of viral and host cellular membranes.

 

Corona Virus Undergoes Two-step Protease Cleavage After Activation

After binding to the ACE-2, the S protein undergoes activation through a two-step protease cleavage. The first cleavage is for priming at the S1/S2 cleavage site. The second cleavage activation occurs at a position adjacent to a fusion peptide within S2 subunit. Thus, the initial cleavage is for stabilization of S2 subunit while the second cleavage is activates the S protein and causes a conformational change that leads to viral and host cell membrane fusion.

Once the virus has gained entrance into the host cell, it undergoes viral replication and formation of a negative strand RNA by the pre-existing single-stranded positive RNA through RNA polymerase activity. The negative stranded RNA newly formed starts to produce new strands of positive RNAs, which then synthesize new proteins in the cytoplasm.

The viral N protein now binds the new genomic RNA and the M protein facilitates its integration to the cellular endoplasmic reticulum (ER). The newly formed nucleocapsids are then enclosed in the ER membrane and transported to the lumen. From the lumen, it is transported through Golgi vesicles to the cell membrane and then, through exocytosis to the extracellular space. The new viral particles are now ready to infect the next epithelia cell.

 

How Does Zinc Protect The Body From Entering Of The Virus?

When an individual is infected with coronavirus, the virus first targets the epithelium and ciliary dyskinesia for damage, thereby impairing mucocilia clearance. But zinc supplementation increases ciliary beat frequencies and thereby improves ciliary clearance of viral particles. The improved ciliary clearance also reduces bacterial infection.

 

How Does Zinc Directly Inhibit Viral Replication?

At first, zinc prevents viral fusion with the host membrane, decreases the viral polymerase functions, impairs the protein translation and processing and blocks viral particle release. It also destabilizes the viral envelope. When supplemented with a small concentration of the zinc ionophores pyrithione or hinokitol, zinc decreases viral RNA synthesis by directly inhibiting the RNA-dependent RNA polymerase of the virus.

 

REFERENCES

Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients. (2017) 9:1286. doi: 10.3390/nu9121286

Gammoh NZ, Rink L. Zinc in infection and inflammation. Nutrients. (2017) 9:624. doi: 10.20944/preprints201705.0176.v1

Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; in press.

Benefits of Zinc in Boosting Male Fertility

According to studies, male infertility is responsible for approximately 30-55% of infertility cases. The commonest cause of male infertility is sperm dysfunction. And this may be due to some risk factors like

  • Varicocele
  • Obstructive lesions
  • Cryptorchidism
  • Cystic fibrosis
  • Trauma
  • Genitourinary infections
  • Environmental factors and
  • Nutritional deficiency of trace elements, especially zinc, selenium, and vitamins.

During ejaculation, the sexual accessory glands secrete serminal plasma which contains some elements that protect spermatozoa. Some of the serminal contents include,

  • Acid phosphatase
  • Alanine transaminase
  • Alkaline phosphatase
  • Aspartate transaminase
  • Lipids and

 

Zinc plays important role in male fertility by enhancing germinal cell proliferation, cell division, immune system and gene expression. And a dietary zinc deficiency is a risk factor low quality of sperm and idiopathic male infertility.

Zinc Enhances Testosterone Production

Low sperm zinc levels have a negative effect on serum testosterone concentration. It also affects the normal function of the hypothalamus-pituitary-gonadal axis. Zinc helps the body maintain proper thyroid function by producing hormones called thyroid-releasing hormones in the brain.

 

How Does Zinc Enhances Testosterone production?

Zinc boosts male fertility via enhancing testosterone production by modulating the balance between testosterone and 5α dihydro testosterone (DHT). This is done by regulating the activity of 5α-reductase, which converts testosterone to DHT. It is important for the leydig cells and play important role in the physiology of spermatozoa.

 

Zinc Enhances Sperm Count and Motility

During initiation of spermatogenesis, zinc participates in the ribonuclease activity as well as involves in spermatozoa maturation, maintains germinal epithelium and seminiferous tubule. It also enhances sperm motility and concentration during ejaculation.

 

Zinc Antibacterial Activities Enhances Sperm Health

 

One of the risk factors of sperm dysfunction is genitourinary infection. The antibacterial activity of zinc improves sperm health and sperm count by clearing bacterial infections. The oxide of zinc, ZnO has antimicrobial activities against both gram negative and gram positive bacteria as well as against spores. But the mechanism of action of ZnO against antimicrobial activity is yet to be elucidated.

 

REFERENCES

Aditya, A., Chattopadhyay, S., Jha, D., Gautam, H. K., Maiti, S., and Ganguli, M. (2018). Zinc oxide nanoparticles dispersed in ionic liquids show high antimicrobial efficacy to skin-specific bacteria. ACS Appl. Mater. Interfaces 10, 15401–15411. doi: 10.1021/acsami.8b01463

Brown, A. N., Smith, K., Samuels, T. A., Lu, J., Obare, S. O., and Scott, M. E. (2012). Nanoparticles functionalized with ampicillin destroy multiple-antibiotic-resistant isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and methicillin-resistant Staphylococcus aureusAppl. Environ. Microbiol. 78, 2768–2774. doi: 10.1128/AEM.06513-11

Khosronezhad N, Hosseinzadeh Colagar A, Mortazavi SM. The Nsun7 (A11337)-deletion mutation, causes reduction of its protein rate and associated with sperm motility defect in infertile men. J Assist Reprod Genet. 2015;32(5):807–15.

Yuyan L, Junqing W, Wei Y, Weijin Z, Ersheng G. Are serum zinc and copper levels related to semen quality? Fertil Steril. 2008;89(4):1008–11.

Khan MS, Zaman S, Sajjad M, Shoaib M, Gilani G. Assessment of the level of trace element zinc in seminal plasma of males and evaluation of its role in male infertility. Int J Appl Basic Med Res. 2011;1 (2):93–6.

Anti-aging Properties of Alpine Rose

Alpine rose (Rhododendron ferrugineum) also known as Alpen rose, belongs to the genus Rhododendron. It is one of the most beautiful flowers of the Alps, and grows at high mountainous altitude.

The ornamental plant thrives in a harsh environment with acidic and poor nutrient soils. Due to the harsh environmental conditions, Alpine rose developed strategies to protect itself against dehydration, UV radiation and attack of radicals and from pathogens.

 

Phytochemical Content With Anti-aging Properties of Alpine Rose

Among the phytochemicals present in Alpine rose extract, flavonoids are the predominant phenolic compounds. Among these flavonoids present in Alpine rose, hyperoside, naringenin, ferrerol and taxifolin are the most probable constituents that are involved in the senolytic and skin-rejuvenation effects.

 

How does Alpine maintain a youthful skin?

The anti-aging properties of Alpine rose are seen in the ability of its phenolic compounds to eliminate senescent cells from the skin.

Senescent cells greatly contribute to skin aging by inducing inflammatory responses and degradation of extracellular matrix.

When the normal human dermal fibroblasts were treated with Alpine rose extract, the number of senescent cells was reduced. Also, the normal proliferating cells were not affected.

 

Molecular Mechanism of Anti-aging Properties of Alpine rose

The phenolic components of Alpine rose maintain a youthful body by eliminating senescent cells. This is carried out by inducing apoptosis through the inhibition of Bcl-2, which is responsible for apoptosis resistance in senescent cells and in cancer cells, as well.

Other Health Benefits of Alpine Rose

Alpine rose has been used, traditionally in treating rheumatism and blood pressure. It also has antiviral activity against Herpes simplex virus I.

Another health benefit of Alpine rose is its inhibitory activity against Porphyromonas gingivalis adhesion to epithelial buccal KB cells, which suggests its antimicrobial potential in preventing periodontal diseases.

 

                              References

 

Gescher, K.; Kühn, J.; Hafezi, W.; Louis, A.; Derksen, A.; Deters, A.; Lorentzen, E.; Hensel, A. Inhibition of viral adsorption and penetration by an aqueous extract from Rhododendron ferrugineum L. as antiviral principle against herpes simplex virus type-1. Fitoterapia 2011, 82, 408–413

Löhr, G.; Beikler, T.; Hensel, A. Inhibition of in vitro adhesion and virulence of Porphyromonas gingivalis by aqueous extract and polysaccharides from Rhododendron ferrugineum L. A new way for prophylaxis of periodontitis? Fitoterapia 2015, 107, 105–113.

Wandrey, F.; Schmid, D.; Zülli, F. Senolytics: Eliminating «zombie cells» in the skin—A novel anti-aging mechanism to combat senescent cells. Ski. Care HPC Today 2020, 15, 18–20.

Chosson, E.; Chaboud, A.; Chulia, A.J.; Raynaud, J. Dihydroflavonol glycosides from Rhododendron ferrugineum. Phytochemistry 1998, 49, 1431–1433.

Abedini, A.; Colin, M.; Hubert, J.; Charpentier, E.; Angelis, A.; Bounasri, H.; Bertaux, B.; Kotland, A.; Reffuveille, F.; Nuzillard, J.M.; et al. Abundant Extractable Metabolites from Temperate Tree Barks: The Specific Antimicrobial Activity of Prunus Avium Extracts. Antibiotics 2020, 9, 111.