Azadirachta indica (A. Juss) commonly known as Neem is an important source of valuable natural products and occupies an important place in traditional healthcare system. Naturally, this plant synthesizes a number of tetranortriterpenoids utilizing isoprenoid as substrate flux. Although various phytochemical and pharmacological studies in A. indica have been carried out, but very limited information is available about the biosynthetic pathway as well as structural and regulatory genes involved in synthesis of bioactive molecules. In this study, we have cloned and characterized two genes, AiHMGR1 and AiHMGR2, encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34) catalyzing the rate limiting step of the isoprenoid biosynthesis. Two isoforms, AiHMGR1 and AiHMGR2, contain an open reading frame of 1707 and 1695 bp encoding polypeptides of 568 and 545 amino acid residues, respectively. The nucleotide and encoded amino acid sequence analyses suggest that both genes encode polypeptides with necessary structural domains present in other plant HMGRs, however, have different genomic organization. The relative expression analysis suggests that two genes express differentially in various tissues. Out of the two genes, expression of AiHMGR2 showed a direct correlation with azadirachtin accumulation in fruit tissue. The common as well as unique cis-regulatory elements present in both genes might be responsible for differential expression of both the genes in various tissues. The color complementation assay in Escherichia coli suggests that though both AiHMGR1 and AiHMGR2 encode functional proteins, AiHMGR2 is more active as compared to AiHMGR1.

Genes encoding members of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) gene family from Azadirachta indica and correlation with azadirachtin biosynthesis

Leishmaniasis are neglected diseases and a public health problem; they are caused by protozoan species belonging to the genus Leishmania and mostly influences the poor populations in many developing countries. The lack of effective medications, and an approved vaccine, high toxicity and life-threatening side effects and many cases of drug resistance reported in different countries have resulted in the necessity to discover new, efficient, inexpensive, and safe antileishmanial compounds with less or no toxicity. This increase in consumer demand of natural herbal-derived plant extracts as alternative medicines continues despite the low scientific information to establish their efficacy and safety profiles. Various studies have been conducted so far concerning the application of herbal medicines for the treatment of leishmaniasis, but research on relatively effective and low toxic substances is still needed. In this review, we have summarized recent developments and reported studies concerning about herbal and naturally derived therapeutics in the treatment of leishmaniasis, conducted by several researchers worldwide. Some of these medical herbs with promising results have undergone prospective clinical researches, but many others have either not yet been explored. Recent articles described these medical herbs and their active and important molecules, including quinones, phenolic derivatives, lignans, tannins, terpenes, and oxylipins. We searched ISI Web of Science, PubMed, SID, Scholar, Scopus, and Science Direct, and articles published up to 2019 were included. The keywords of leishmaniasis and some words associated with herbal medicines and natural products were used in our search. This review can serve as a quick reference database for researchers.

Recent researches in effective antileishmanial herbal compounds: narrative review

Could Araucaria heterophylla resin extract be used as a new treatment for toxoplasmosis

Summary Objective Among the fungi, dermatophytes are the major cause of spectrum of superficial mycoses medically known as dermatophytosis (tinea) in human and animal. Treatment of these infections has still remained difficult. The aim of this survey was to evaluate in vitro anti-dermatophytic activity of ethanolic extract (EtOH) from Satureja khuzestanica leaf (SKLE) against some clinically important dermatophyte species from the genera of Trichophyton , Microsporum and Epidermophyton . Minimal inhibition concentration (MIC) of SKLE was tested against 14 dermatophyte strains of 5 species by using agar dilution method. Phytochemical screening of SKLE was carried out by High Performance Thin Layer Chromatography (HPTLC). The results of in vitro anti-dermatophytic activity of SKLE showed with MIC values between 1.250 and 10 mg/mL. MIC90 and MIC50 values were as 0.625–1.250 and 0.156–0.312 mg/mL, respectively. The MFC values of SKLE were in the range of 1.250–2.50 mg/mL and possessed biological activity against dermatophytes. Morever, phytochemical analysis by HPTLC revealed that the ethyl acetate (EtOAc) extracts of SKL contain triterpenes which are known to have biological activity and it seems that this compound be responsible for the anti-dermatophytic activity of this plant. In conclusion, the results of in vitro antifungal susceptibility testing and phytochemical screening revealed that SKLE had both fungistatic and fungicidal activities against dermatophytes and can potentially be helpful as a supplementary or alternative for treatment of dermatophytosis.

Isolation and antifungal activity evaluation of Satureja khuzestanica Jamzad extract against some clinically important dermatophytes.

Toxoplasmosis is known as a parasitic protozoan disease which is globally distributed. It is caused by Toxoplasma gondii. Sulfadiazine and pyrimethamine are two medicines utilized as parts of a standard therapy for toxoplasmosis. Since the curative medicines currently used in the treatment of toxoplasmosis bring about serious host toxicity, conducting a research on an effective and new substance characterized by relatively low toxicity is required urgently. The naturally derived herbs and plants’ extracts as alternative medicines are getting increasing interest in the world.  Various studies have been conducted so far concerning the application of herbal medicines for the treatment of toxoplasmosis, but a research on relatively effective and low toxic substances is still needed. Due to increasing interest in the use of natural products to treat of infectious diseases, we conducted this study.  In this review, we have summarized the information of those herbal medicines which are reported to have anti- Toxoplasma gondii activity. We referred to the information databases of Medline, PubMed, Scopus and Google Scholar. The keywords include a combination of T.gondii and some words associated with herbal medicines and natural products.

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Anti-toxoplasmosis activity of herbal medicines: Narrative review

Background and Aim: Leishmaniasis is endemic in 98 countries including Iran. Pentavalent antimony compounds resistance as first-line therapy is increasing in some local areas. Also side effects of these drugs are limited at the beginning of treatment, but the toxicity increases with time. The aim of this study was to assess the effect of Satureja khuzestanica essential oil (SKEO) on promastigote and amastigote Leishmania major forms. Materials and Methods: The components of S. khuzestanica oil were identified by gas chromatography/mass spectroscopy (GC/MS) analysis. To evaluate antipromastigote activity the different concentrations of extract  and glucantime were added to the wells that contained L. major . The plates were incubated at 26±1°C for a week. On days 1, 3 and 5, the number of live promastigotes in each well was counted. For assessment of SKEO effect on intracellular amastigotes, mouse peritoneal macrophages were isolated and infected with promastigotes. Different concentrations of the extract and glucantime were added to the cultures. The cultures were incubated at 37°C and CO 2 5%. The number of infected macrophages and amastigotes within each macrophage were counted. Toxicity assessment of SKEO on macrophages was done by MTT method. Results and Conclusions: The mean number of promastigotes, infected macrophages and amastigotes in a macrophage in the control and treated groups had significantly difference. So that their number in the treated groups was less as a dose-dependent response. The present research showed potent antileishmanial activity of, SKEO; additionally this plant had no toxic effect on mammalian cells.

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Mahboubeh Jabari

Papers

The Cytotoxic and Antileishmanial Effects of Satureja khuzestanica Essential Oil