Herbal medicinal products have been documented as a significant source for discovering new pharmaceutical molecules that have been used to treat serious diseases. Many plant species have been reported to have pharmacological activities attributable to their phytoconstituents such are glycosides, saponins, flavonoids, steroids, tannins, alkaloids, terpenes, etc. Syzygium aromaticum (clove) is a traditional spice that has been used for food preservation and possesses various pharmacological activities. S. aromaticum is rich in many phytochemicals as follows: sesquiterpenes, monoterpenes, hydrocarbon, and phenolic compounds. Eugenyl acetate, eugenol, and β-caryophyllene are the most significant phytochemicals in clove oil. Pharmacologically, S. aromaticum has been examined toward various pathogenic parasites and microorganisms, including pathogenic bacteria, Plasmodium, Babesia, Theileria parasites, Herpes simplex, and hepatitis C viruses. Several reports documented the analgesic, antioxidant, anticancer, antiseptic, anti-depressant, antispasmodic, anti-inflammatory, antiviral, antifungal, and antibacterial activity of eugenol against several pathogenic bacteria including methicillin-resistant Staphylococcus epidermidis and S. aureus. Moreover, eugenol was found to protect against CCl4−induced hepatotoxicity and showed a potential lethal efficacy against the multiplication of various parasites including Giardia lamblia, Fasciola gigantica, Haemonchus contortus, and Schistosoma mansoni. This review examines the phytochemical composition and biological activities of clove extracts along with clove essential oil and the main active compound, eugenol, and implicates new findings from gas chromatography-mass spectroscopy (GC-MS) analysis.
While both human and animal trypanosomiasis continue to present as major human and animal public health constraints globally, detailed analyses of trypanosome wildlife reservoir hosts remain sparse. African animal trypanosomiasis (AAT) affects both livestock and wildlife carrying a significant risk of spillover and cross-transmission of species and strains between populations. Increased human activity together with pressure on land resources is increasing wildlife–livestock–human infections. Increasing proximity between human settlements and grazing lands to wildlife reserves and game parks only serves to exacerbate zoonotic risk. Communities living and maintaining livestock on the fringes of wildlife-rich ecosystems require to have in place methods of vector control for prevention of AAT transmission and for the treatment of their livestock. Major Trypanosoma spp. include Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma cruzi, pathogenic for humans, and Trypanosoma vivax, Trypanosoma congolense, Trypanosoma evansi, Trypanosoma brucei brucei, Trypanosoma dionisii, Trypanosoma thomasbancrofti, Trypanosma elephantis, Trypanosoma vegrandis, Trypanosoma copemani, Trypanosoma irwini, Trypanosoma copemani, Trypanosoma gilletti, Trypanosoma theileri, Trypanosoma godfreyi, Trypansoma simiae, and Trypanosoma (Megatrypanum) pestanai. Wildlife hosts for the trypansomatidae include subfamilies of Bovinae, Suidae, Pantherinae, Equidae, Alcephinae, Cercopithecinae, Crocodilinae, Pteropodidae, Peramelidae, Sigmodontidae, and Meliphagidae. Wildlife species are generally considered tolerant to trypanosome infection following centuries of coexistence of vectors and wildlife hosts. Tolerance is influenced by age, sex, species, and physiological condition and parasite challenge. Cyclic transmission through Glossina species occurs for T. congolense, T. simiae, T. vivax, T. brucei, and T. b. rhodesiense, T. b. gambiense, and within Reduviid bugs for T. cruzi. T. evansi is mechanically transmitted, and T. vixax is also commonly transmitted by biting flies including tsetse. Wildlife animal species serve as long-term reservoirs of infection, but the delicate acquired balance between trypanotolerance and trypanosome challenge can be disrupted by an increase in challenge and/or the introduction of new more virulent species into the ecosystem. There is a need to protect wildlife, animal, and human populations from the infectious consequences of encroachment to preserve and protect these populations. In this review, we explore the ecology and epidemiology of Trypanosoma spp. in wildlife.
Although hookworms are known to stimulate inflammatory responses in the intestinal mucosa of their hosts, there is little quantitative data on this aspect of infection. Here we report the results of experiments conducted in hamsters infected with Ancylostoma ceylanicum. Infection resulted in a marked increase in goblet cells in the intestinal mucosa, which was dependent on the number of adult worms present and was sustained as long as worms persisted (over 63 days) but returned to baseline levels within 7 days of the removal of worms by treatment with ivermectin. Increased mast cell responses were also recorded. Levels were again dependent on the intensity of worm burdens and lasted as long as 63 days after infection. When worms were eliminated, mast cell numbers took over 2 weeks to return to normal. Paneth cell numbers fell soon after infection, the degree of reduction being dependent on the worm burden. After clearance of worms, Paneth cell numbers returned to normal within a week, but then rebounded and numbers rose to higher levels than those in control naïve animals. The time course of the response was similar whether animals experienced a chronic low-intensity infection without loss of worms or a higher intensity infection during the course of which worm burdens were gradually reduced. Clearly, A. ceylanicum was able to induce a marked inflammatory response in its host's intestine which was sustained for over 9 weeks after infection, and which hamsters appeared able to tolerate well. Our data draw attention to the resilience of hookworms which, unlike many other nematodes, are able to survive for many weeks in a highly inflamed intestinal tract.
High-mobility group box 1 (HMGB1), a multifunctional nuclear protein, exists mainly within the nucleus of all mammal eukaryotic cells. It is actively secreted by the necrotic cells as a response to the inflammatory signaling pathway. HMGB1 binds to receptor ligands as RAGE, and TLR and becomes a pro-inflammatory cytokine with a robust capacity to trigger inflammatory response. It is a critical mediator of the pathogenesis of systemic inflammation in numerous inflammatory disorders. Release of HMGB1 is associated with different viral infections and strongly participates in the regulation of viral replication cycles. In COVID-19 era, high HMGB1 serum levels were observed in COVID-19 patients and linked with the disease severity, development of cytokine storm (CS), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). SARS-CoV-2-induced cytolytic effect may encourage release of HMGB1 due to nuclear damage. Besides, HMGB1 activates release of pro-inflammatory cytokines from immune cells and up-regulation of angiotensin I-converting enzyme 2 (ACE2). Therefore, targeting of the HMGB1 pathway by anti-HMGB1 agents, such as heparin, resveratrol and metformin, may decrease COVID-19 severity. HMGB1 signaling pathway has noteworthy role in the pathogenesis of SARS-CoV-2 infections and linked with development of ALI and ARDS in COVID-19 patients. Different endogenous and exogenous agents may affect release and activation of HMGB1 pathway. Targeting of HMGB1-mediated TLR2/TLR4, RAGE and MAPK signaling, might be a new promising drug candidate against development of ALI and/or ARDS in severely affected COVID-19 patients.
Hookworms are known to cause marked changes to the intestinal mucosa, especially in relation to erosion of the villi. However, since the development of enteropathy has not been examined thoroughly through quantitative experiments on infected animals, the results of experiments conducted in hamsters infected with Ancylostoma ceylanicum are reported. Changes to intestinal architecture were first apparent between 12 and 14 days after infection, and then increased in intensity for 3-4 weeks, persisting for as long as worms were present (. 63 days). Following infection, the height of villi declined from a mean of 1002 mm in naïve controls to less than 200 mm and as low as 18 mm in one case. The depth of the crypts of Lieberkuhn increased from a baseline value of 166 mm in naïve controls to in excess of 600 mm within 6 weeks of infection. Mitotic figures had a baseline value of 5.5 per villus-crypt unit, and this rose to in excess of 25 in some experiments. Changes were dependent on the intensity of the parasite burden on day 20, but by 30 days after infection changes in all three values were maximal and density-dependent relationships were no longer clearly apparent. Villus height and crypt depth returned to near normal values within a week of the removal of worms, although group means for both remained different from naïve controls for at least 3 weeks after treatment. Cellular division, as reflected in numbers of mitotic figures, stayed elevated for over 5 weeks after removal of worms. The results suggest that enteropathy in hookworm infections stems from a combination of intestinal immune responses and from the grazing activities of the adult worms on the mucosal surface, but is not sufficient per se for expulsion of this parasite.
Coronavirus disease 2019 (COVID-19) a global infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) affects various organs, primarily the respiratory system, and presented with pulmonary manifestations such as acute lung injury (ALI) and acute respiratory distress syndrome. Levamisole (LVM) is an anthelminthic drug; it has immune-modulating effects through induction of type 1 immune response. Based on these findings several recent studies highlighted that LVM might be effective in preventing and treating SARS-CoV-2 infections. The aim of this report is to illustrate the potential role of LVM in SARS-CoV-2 infection and in the management of COVID-19. Different studies proposed that LVM may inhibit proliferation of SARS-CoV-2 through inhibition of papain-like protease. LVM may prevent ALI and acute kidney injury through activation of glucocorticoid receptors. In general, LVM has strong immune stimulant effects by modulating cellular and humoral immune responses. This effect is beneficial in the early phase of COVID-19 and harmful in the late phase. In the early phase, immune stimulation facilitates SARS-CoV-2 clearance and tissue repair, however, in the late phase, immune stimulation in COVID-19 may increase propagation risk of cytokine storm. In conclusion, LVM therapy in COVID-19 has bidirectional effects, beneficial in the early phase and harmful effects in the late phase of COVID-19. Clinical trial and prospective studies are warranted in this regard to confirm the efficacy and timing administration of LVM in the management of COVID-19.
Background: The antiprotozoal and antioxidant activities of Viola tricolor and Laurus nobilis have been reported recently. Thus, the existing study pursued to assess the growth inhibition effect of methanolic extract of V. tricolor (MEVT) and acetonic extract of L. nobilis (AELN) against five Babesia parasites and Theileria equi in vitro and in vivo. Results: MEVT and AELN suppressed Babesia bovis, B. bigemina, B. divergens, B. caballi, and T. equi growth at halfmaximal inhibitory concentration (IC 50) values of 75.
We assessed the mucosal response of previously infected hamsters to low-dose challenge with the hookworm, Ancylostoma ceylanicum. Hamsters were assigned to five treatment groups (Groups 1-5, respectively): naïve, controls; uninterrupted primary infection from day 0; infected, but treated with anthelmintic on day 35 p.i.; challenge control group given only the second infection on day 63; infected initially, cleared of worms and then challenged. Animals were culled on days 73 and 94 (10 and 31 days after challenge), but additional animals were culled from Group 5 on days 80 and 87. The results showed that villus height declined markedly and progressively over time after challenge in Group 5, whilst depth of the Crypts of Lieberkühn and number of mitotic figures in the crypts increased. Mucosal mast cell numbers were only marginally higher than those in naïve controls and not as high as those in mice with uninterrupted infections. Goblet cell counts showed a major increase, as did eosinophils in relation to naïve controls. Paneth cells were also elevated, but did not change over the course of the experiment. The results also drew attention to the tremendous resilience of hookworms, some adult worms surviving throughout, despite highly inflamed intestines.
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