The effects of medicinal herbs and marine natural products on wound healing of cutaneous leishmaniasis: A systematic review.

This study aimed to investigate the effects of medicinal herbs and marine natural products on wound healing of cutaneous leishmaniasis. To carry out this literature review, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) instructions were used. Articles on the potential of medicinal plants and natural substances of marine origin against wound healing of cutaneous leishmaniasis were explored. The scientific databases considered were PubMed, Science Direct, Google Scholar, Web of Science, Scopus, and SpringerLink. The scientific documents collected were mainly scientific articles, books, book chapters, and doctoral thesis. The research considered 73 manuscripts published in the period from 1990 to 2020. From all the data collected, it appears that the scientific literature is rich in medicinal herbs and marine products to be valorized in the wound healing of cutaneous leishmaniasis. We have identified 15 medicinal plants traditionally used in the management of healing or ulcer of cutaneous leishmaniasis, 32 medicinal plants whose efficacy has been demonstrated in vitro or in vivo against cutaneous leishmaniasis, 5 marine products active against cutaneous leishmaniasis. It is also clear that the option of medicinal herbs/marine products in the management of cutaneous leishmaniasis is less expensive and allows to avoid the side effects of conventional products. It is necessary to encourage the development of dermatological topicals for the management of cutaneous leishmaniasis based on the data collected. In vivo research should be intensified on medicinal herbs traditionally used in wound healing of cutaneous leishmaniasis.

Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile.

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species.Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development.Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action.Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure.Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major.Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.

A Phospholipase-A Activity in Soluble Leishmania Antigens Causes Instability of Liposomes.

AIM: This study aimed to investigate the existence of phospholipase-A (PLA) activity in Soluble L. major Antigens (SLA) because of no reports for it so far. Liposomes were used as sensors to evaluate PLA activity. OBJECTIVES: Liposomal SLA consisting of Egg Phosphatidylcholine (EPC) or Sphingomyelin (SM) were prepared by two different methods in different pH or temperatures and characterized by Dynamic Light Scattering (DLS) and Thin Layer Chromatography (TLC). METHODS: Lipid hydrolysis led to the disruption of EPC liposomal SLA in both methods but the Film Method (FM) produced more stable liposomes than the Detergent Removal Method (DRM). RESULT: The preparation of EPC liposomal SLA at pH 6 via FM protected liposomes from hydrolysis to some extent for a short time. EPC liposomes but not SM liposomes were disrupted in the presence of SLA. CONCLUSION: Therefore, a phospholipid without ester bond such as SM should be utilized in liposome formulations containing PLA as an encapsulating protein.

Development of nano-carriers for Leishmania vaccine delivery.

Introduction: Leishmaniasis is a neglected tropical infection caused by several species of intracellular protozoan parasites of the genus Leishmania. It is strongly believed that the development of vaccines is the most appropriate approach to control leishmaniasis. However, there is no vaccine available yet and the lack of an appropriate adjuvant delivery system is the main reason.Areas covered: Adjuvants are the utmost important part of a vaccine, to induce the immune response in the right direction. Limitations and drawbacks of conventional adjuvants have been necessitated the development of novel particulate delivery systems as adjuvants to obtain desirable protection against infectious diseases such as leishmaniasis. This review focused on particulate adjuvants especially nanoparticles that are in use to develop vaccines against leishmaniasis. The list of adjuvants includes generally lipids-, polymers-, or mineral-based delivery systems that target antigens specifically to the site of action within the host's body and enhance immune responses.Expert opinion: Over the past few years, there has been an increasing interest in developing particulate adjuvants as alternatives to immunostimulatory types. The composition of nano-carriers and particularly the physicochemical properties of nanoparticles have great potential to overcome challenges posed to leishmaniasis vaccine developments.

Comparison of clinical efficacy and safety of thermotherapy versus cryotherapy in treatment of skin warts: A randomized controlled trial.

The effect of thermotherapy in the treatment of skin warts in comparison to cryotherapy, as the standard conventional method, has remained uncertain. This study aimed to assess the clinical efficacy and safety of thermotherapy and cryotherapy in removing skin warts. This randomized controlled trial was conducted on 52 patients aged 18 years and over with ≤ 10 skin warts. The participants were randomly assigned into two groups to receive cryotherapy (every 2 to 3 weeks up to six sessions if required) or thermotherapy (one session). The patients in both groups were followed every 2 to 3 weeks for the first three months, and then three months after the last treatment session. The clearance rate was 79.2% in the thermotherapy group and 58.3% in the cryotherapy group with no significant difference (p = 0.212). The rate of scarring in the thermotherapy group was 20% (p = .018). A higher clearance rate was achieved in the thermotherapy group. However, this result was not statistically significant. There were some minimal post-treatment complications. Patients needed only one session of thermotherapy. Due to the risk of scarring, we suggest thermotherapy only as a suitable treatment method for palmoplantar warts.

Iranian Native Plants on Treatment of Cutaneous Leishmaniosis: A Narrative Review.

BACKGROUND: Chemotherapy still relies on the use of pentavalent antimonials, amphotericin B, paromomycin, miltefosin, and allopurinol. In this study, we explained about the native plant that grows in different regions of Iran and used as anti-leishmanial in Iran and even many other countries. METHODS: This narrative review covers all information about local herbal medicine in Iran that used in treatment of cutaneous leishmaniasis in all the worlds, published in local and international journals from 1996 to 2015 using various databases including PubMed, SID, Google Scholar, Scopus, and Science Direct. RESULTS: Overall, 150 articles in databases were identified. Many local plants grown in some places of Iran were used to treat this endemic disease. CONCLUSION: The cutaneous leishmaniasis is also a major health problem in Iran, especially in Mashhad (Northeast of Iran). Therefore, many patients seek for herbal therapy that is cheaper and readily available. This review provides information regarding plant that exists in Iran and exhibiting effects on anti-Leishmania activity. Among the anti-leishmanial mentioned in this review, most have never been tested for cytotoxicity and very few have been tested for in vivo activity.

Alginate microspheres encapsulated with autoclaved Leishmania major (ALM) and CpG-ODN induced partial protection and enhanced immune response against murine model of leishmaniasis.

A suitable adjuvant and delivery system are needed to enhance efficacy of vaccines against leishmaniasis. In this study, alginate microspheres as an antigen delivery system and CpG-ODN as an immunoadjuvant were used to enhance immune response and induce protection against an experimental autoclaved Leishmania major (ALM) vaccine. Alginate microspheres were prepared by an emulsification technique and the characteristics of the preparation such as size, encapsulation efficiency and release profile of encapsulates were studied. Mean diameter of microspheres was determined using SEM (Scanning Electron Microscopy) and particle size analyzer. The encapsulation efficiency was determined using Lowry protein assay method. The integrity of ALM antigens was assessed using SDS-PAGE. Mean diameter of microspheres was 1.8±1.0µm. BALB/c mice were immunized three times in 3-weeks intervals with ALM+CpG-ODN loaded microspheres [(ALM+CpG)(ALG)], ALM encapsulated alginate microspheres [(ALM)(ALG)], (ALM)(ALG)+CpG, ALM+CpG, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection was observed in group of mice immunized with (ALM+CpG)(ALG). The groups of mice received (ALM+CpG)(ALG), (ALM)(ALG)+CpG, (ALM)(ALG) and ALM+CpG were also showed a significantly (P<0.05) smaller footpad swelling compared with the group that received either ALM alone or PBS. The mice immunized with (ALM+CpG)(ALG) or ALM+CpG showed the significantly (P<0.05) highest IgG2a/IgG1 ratio. The IFN-γ level was significantly (P<0.0001) highest in group of mice immunized with either (ALM)(ALG)+CpG or ALM+CpG. It is concluded that alginate microspheres and CpG-ODN adjuvant when are used simultaneously induced protection and enhanced immune response against ALM antigen.

Immune response and protection assay of recombinant major surface glycoprotein of Leishmania (rgp63) reconstituted with liposomes in BALB/c mice.

In this study the ability of recombinant gp63 entrapped in liposomes to induce immune response and protection against L. major infection in susceptible BALB/c mice was studied. Liposomes containing rgp63 (Lip-rgp63) were prepared from egg lecithin and cholesterol using detergent solubilization method. Immunization of BALB/c mice with rgp63 alone conferred a partial protection while entrapment of rgp63 in liposomes significantly increased the rate of protection (P<0.05). The parasite burden of spleen in mice challenged with L. major was significantly (p<0.001) lower in group of mice immunized with rgp63 alone or Lip-rgp63, however, the least parasite burden was seen in Lip-rgp63 group. Both rgp63 alone and Lip-rgp63 elicited significant delayed-type hypersensitivity (DTH) response compared to controls (p<0.01), however, the DTH response of PBS-rgp63 was less than the Lip-rgp63. Titration of anti-Leishmania IgG isotypes (IgG2a/IgG1) showed a preferential Th1 type of immune response only in mice immunized with Lip-rgp63. The results indicate that liposomes might be used as a suitable immunoadjuvant for development of Leishmania vaccine.

Enhancement of peritoneal macrophage phagocytic activity against Leishmania major by garlic (Allium sativum) treatment.

It has been shown that garlic (Allium sativum) extract modulates immune responses. Macrophage activation is required to establish control of the intracellular infection and progressive disease of leishmaniasis. In this study, we consider the effect of a garlic extract and a fraction isolated from it on the engulfment and destruction of Leishmania major by resident peritoneal macrophages of Balb/c mice. In regard to this study, the infiltration of macrophages in the peritoneal cavity after garlic treatment and the rate of amastigotes per macrophage were determined. The results show that a single dose of 20 mg/kg garlic extract intraperitoneally (i.p.) alters the number of peritoneal macrophages for at least 2 weeks. Intraperitoneal injection of garlic extract (20 mg/kg) or its protein fraction (0.04 mg/kg) augments parasite engulfment and destruction of intracellular amastigotes by macrophages.

Opium and risk of laryngeal cancer.

OBJECTIVES/HYPOTHESIS: The study was performed to investigate the possible association between opium dependency and laryngeal cancer. STUDY DESIGN: A hospital-based, group-matched, case-control study was presented. METHODS: Ninety-eight patients with laryngeal cancer and 312 age- and gender-matched control subjects were selected at the otorhinolaryngology ward of a referral university-affiliated hospital. Data on cigarette smoking and alcohol and opium dependency were collected before surgery through semi-structured interview. RESULTS: The crude odds ratios of laryngeal cancer were 15.07 (95% confidence interval [CI], 6.92-32.8 [P <.0001]) for cigarette smoking, 21.55 (95% CI, 10.54-44 [P <.0001]) for opium dependency, and 1.84 (95% CI, 1.008-3.38 [P <.048]) for male gender. Because of strong associations, a logistic regression model was prepared; the odds ratio for gender in the final model was 0.87 (95% CI, 0.39-1.92 [P =.11]). According to the results, it seemed that gender was not an independent risk factor for laryngeal cancer. Also, the adjusted odds ratios for smoking (5.21) (95% CI, 2.33-11.67 [P <.002]) and opium dependency (10.74) (95% CI, 5.76-20.02 [P <.002]) were lower than the crude odds ratios, but both ratios were significant. The mean patient ages were 55.1 years (SD = 12.05 y) in opium-dependent patients and 65.6 years (SD = 12.8 y) in opium-nondependent patients (P =.01). CONCLUSION: The results of the study suggest that opium dependency is not only an independent possible risk factor for laryngeal cancer but also significantly increases the likelihood of developing of the disease at a younger age.