In Vitro and In Vivo Anti-Parasitic Activity of Artemisinin Combined With Glucantime and Shark Cartilage Extract on Iranian Strain of Leishmania major (MRHO/IR/75/ER)

Background: The adverse effects and increased resistance of drugs necessities the discovery of novel combination therapy. Objectives: This study aimed to examine the effects of Artemisinin plus glucantime or shark cartilage extract on the Iranian strain of Leishmania major (MRHO/IR/75/ER) in vitro and in vivo. Methods: In in vitro experiments, the effects of drugs and their combination in different concentrations (3.12 - 400 µg/mL) on the promastigotes, amastigotes, and un-infected macrophage cells were evaluated. In in vivo experiments, infected BALB/c mice were used as a cutaneous leishmaniasis model to evaluate the effects of the drugs and their combinations with different routes of administrations (namely Artemisinin: oral, ointment, and intraperitoneal; glucantime: intraperitoneal, intramuscular, intralesional, and subcutaneous; shark cartilage extract: oral) on parasite burden, lesion size, and immune system modulation. Results: The results revealed that Artemisinin and glucantime in combination with shark cartilage extract had greater effects on promastigotes than either Artemisinin or glucantime (P < 0.05), and that the combinations also had high cytotoxic effects on promastigotes and uninfected macrophages (P = 0.001). These combinations had more inhibitory effects on amastigotes and infected macrophages than promastigotes. The lesion sizes and parasite burden in the spleen decreased against the combinations of the drugs in different administrations. It was also noticed that the best combination administration route of Artemisinin and glucantime, as strong inducers of INF-γ and Th1 immune response, were ointment and IM, respectively (P < 0.05). Conclusions: The findings indicate that Artemisinin- glucantime or Artemisinin- Shark cartilage combinations are effective inhibitors of L. major. However, further clinical trials are recommended to evaluate the effects of these combinations in human subjects.

Determination of the protective effect of shark cartilage and shark liver oil (SLO) on colon cancer by using experimental DMH

Objectives: It is a known fact that cancer is one of the biggest health problems. There are many different alternative products that are preferred for use among cancer patients. Our study is based on shark cartilage and liver oil as alternative products within alternative treatment (CAM) due to low incidence of cancer in sharks. Method: With this study; it was aimed to search the toxic effects of DMH on colon, SC and SLO ‘s conservative effects against these toxic and carcinogic effects. 40 rats have been classified as follows: 40 DMH group: 4; control group – 6; given DMH but not cured group – 15; given DMH and cured with SC group – 15; given DMH and cured with SLO group. Results and Conclusion: The negative effects of DMH on biochemical, genetic, and pathological were observed in rat column; The treatment of SLO and SC against to colon cancer is thought to be associated with damage and regression of tumor cells. When we look at the numerical results, it can be said that SC is more successful and effective in correcting the effect of DMH. It can be said that our experimental model provides the desired aim and success in this direction.

Fe3O4@Bio-MOF Nanoparticles Combined with Artemisinin, Glucantime®, or Shark Cartilage Extract on Iranian Strain of Leishmania major (MRHO/IR/75/ER): An In-Vitro and In-Vivo Study

Background: In the present study, we examined the effects of Fe3O4@bio-MOF nanoparticle (Nano-FO) plus artemisinin (Art) and glucantime (Glu) or shark cartilage extract (ShCE) on Leishmania major in vitro and in vivo. Methods: This experimental study was conducted at the laboratory of Department of Parasitology, Tarbiat Modares University, Tehran, Iran during 2016-2017. The promastigote and amastigote assays were performed were conducted at the presence of 3.12- 400 µg/mL of the drug combinations. According to in vitro IC50 results, the combinations of 12.5µg/mL Nano-FO with 25 µg/mL Art as well as 200 µg/mL Glu and 0.5 mL of 20 mg/kg of ShCE were used to treat BALB/c mice. During and at the end of the treatment, the lesion sizes were measured. Parasite loads, cytokine levels were evaluated at the end of the treatment. Results: The IC50 of Fe3O4@bio-MOF-Artemisinin (Nano-FO/Art), Fe3O4@bio-MOF-Glucantime (Nano-FO/Glu), and Fe3O4@bio-MOF-Shark cartilage extract (Nano-FO/ShCE) on promasitigotes were 12.58±0.12, 235±0.17, and 18.54±0.15, respectively. These results on amastigotes were 10.32±0.01, 187±0.03, and 338±0.07 µg/mL, respectively. The apoptosis percentage of these combinations were 32.54%, 20.59%, and 15.68% in promastigotes and 15.68%, 12.84%, and 3.51% in infected macrophages, respectively with no toxicity on uninfected macrophages. In vivo results showed that the size of lesions significantly decreased against all drugs combinations, but Nano-FO/Art combination with Selectivity Index of 23.62 value was safe, and more effective on healing of lesions than other drugs combinations (P=0.003). Conclusion: This study suggested that Nano-FO/Art combination can be considered as an anti-leishmania combination therapy in CL induced by L. major.

Study on the relationships between molecular weights of chondroitin sulfate oligosaccharides and Aβ-induced oxidative stress and the related mechanisms

In the present study, we studied anti-Alzheimer′s disease (AD) activities of chondroitin sulfate (CS) oligosaccharides with different molecular weights. CS from shark cartilage was degraded by a recombinant CS endolyase, chondroitinase ABC I (CHSase ABC I), and CS disaccharide (DP2), tetrasaccharide (DP4), hexasaccharide (DP6), octasaccharide (DP8), decasaccharide (DP10) and dodecasaccharide (DP12) were obtained by separation with gel filtration. Anti-AD activities of CS oligosaccharides were assessed using Aβ-injured SH-SY5Y cells and BV2 cells. It was shown that CS oligosaccharides could block Aβ-induced oxidative stress, mitochondrial dysfunction and activation of intrinsic apoptotic pathway for SH-SY5Y cells. Furthermore, these activities increased with the increase of molecular weights. For Aβ-injured BV2 cells, CS oligosaccharides inhibited oxidative stress, the production of proinflammatory cytokines and the activation of toll-like receptor pathway, and CS DP2 had the best activity among them. In conclusion, CS oligosaccharides suppressed Aβ-induced oxidative stress and relevant injury in vitro, and these effects had different relationships with the molecular weights of CS oligosaccharides for different cell lines, which might be caused by different mechanisms.