Objective: Dysregulation of cholesterol metabolism in the brain is responsible for many lipid storage disorders, including Niemann-Pick disease type C (NPC). Here, we have investigated whether cyclodextrin (CD) and apolipoprotein A-I (apoA-I) induce the same signal to inhibit cell cholesterol accumulation by focusing on the main proteins involved in cholesterol homeostasis in response to CD and apoA-I treatment. Materials and Methods: In this experimental study, astrocytes were treated with apoA-I or CD and then lysed in RIPA buffer. We used Western blot to detect protein levels of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) and ATP-binding cassette transporter A1 (ABCA1). Cell cholesterol content and cholesterol release in the medium were also measured. Results: ApoA-I induced a significant increase in ABCA1 and a mild increase in HMGCR protein level, whereas CD caused a significant increase in HMGCR with a significant decrease in ABCA1. Both apoA-I and CD increased cholesterol release in the medium. A mild, but not significant increase, in cell cholesterol content was seen by apoA-I; however, a significant increase in cell cholesterol was detected when the astrocytes were treated with CD. Conclusion: CD, like apoA-I, depletes cellular cholesterol. This depletion occurs in a different way from apoA-I that is through cholesterol efflux. Depletion of cell cholesterol with CDs led to reduced protein levels of ABCA1 along with increased HMGCR and accumulation of cell cholesterol. This suggested that CDs, unlike apoA-I, could impair the balance between cholesterol synthesis and release, and interfere with cellular function that depends on ABCA1.

Background: Sustainable and commercial production of taxol as an anti-cancer drug is a critical point to its clinical application. Nowadays, hazel because of rapid growth and wide range distribution is considered as an alternative source of Taxol.Objective: To increase taxol production the cDNA encoding 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) from Iranian hazel (GeneBank accession number KF306244, showed by CiHMGR) was isolated and over-expressed in pCAMBIA1304 binary vector. The effect of transient over-expression of HMGR in callus and leaf were evaluated on Taxol production.Methods: The calli was established through the culture of immature cotyledon on Murashige and Skoog basal medium supplemented with 2, 4-D and BA. The first strand cDNA of CiHMGR was synthesized by specific primers. Enzymatic assay of recombinant CiHMGR in E. coli were done by western blott and His-tag affinity techniques. Also production of taxol in transformed callus and leaf were evaluated by HPLC analysis.Results: An Open Reading Frame (ORF) with 1698 bp length and a deduced polypeptide with 566 amino acid residues were amplified. The highest and lowest amount of taxol was 0.016 mg/g.DW and 0.004 mg/gDW in transformed calli and untransformed leaves respectively.Conclusion: Generally the over-expression of HMGR increase the total isoprenoids yield, therefore to have high production of target secondary metabolites (taxol) we need both of network of transformed genes and elicited cell culture.

Introduction: Triphala, consisting of three fruits, Phyllanthus emblica L. (Phyllanthaceae), Terminalia bellirica (Gaertn. ) Roxb. (Combretaceae), and T. chebula Retz, is a well-recognized Ayurvedic herbal formulation, used for various therapeutic purposes, including the treatment of dyslipidemia. Inhibitory activity against 3‑, hydroxy‑, 3‑, methylglutaryl‑, coenzyme A (HMG‑, CoA) reductase, a rate-limiting enzyme in the endogenous cholesterol synthesis pathway, is an essential target for the management of hypercholesterolemia. This in silico study aimed to investigate the HMG-CoA reductase inhibitory activity of the phytochemical compounds derived from Triphala formulation by employing molecular docking analysis. Methods: Ten phytochemical constituents of Triphala formulation were selectively used for docking study by using the HMG-CoA reductase template (PDB: 1HWK). Docking analysis was performed using AutoDock 4. 2. The candidates were ranked by the binding energy parameters. Results: From the docking studies, the phytochemical compounds with HMG-CoA reductase inhibition could be classified into 4 groups, including phytosterols, polyphenols, tannins, and flavonoids. Beta-sitosterol exhibited the highest binding affinity to HMG-CoA reductase with a binding energy of-7. 75 kcal/mol. Conclusion: These 10 phytochemical compounds in Triphala potentially exert their cholesterol-lowering effects via inhibition against HMG-CoA reductase. Nonetheless, further in vitro and in vivo experiments should be conducted subsequently to confirm this finding.

Background and Objectives Drought is a major abiotic stress that limits agricultural crop production. Thyme (Thymus vulgaris L. ) is an aromatic and medicinal plant which is very important for the herbal industry. This study was aimed to investigate the variation some of the secondary metabolites and morphological traits as well as changes in expression of genes involved in the biosynthesis of thymol (including HMGR and TPS2) by real-time PCR. One of the main goals of the present study was to find out the relationship between the transcript of these genes and related metabolites in thyme. Materials and Methods This study was conducted in the greenhouse of Iranian Institute of Medicinal Plants of Jahad Daneshgahi (Karaj, Iran) in 2016. The experimental design was a randomized complete block design with 5 replication and 4 water deficit stress treatments, including 100% (T1, control), 70% (T2, mild stress), 40% (T3, moderate stress), and 20% (T4, severe stress) of field capacity (FC). Total RNA was extracted from leaves using TRIzol reagent following the manufacturer’ s instructions. First strand synthesis of cDNA was performed immediately using 1 µ g of total RNA with simultaneous use of oligo-dT (50 µ M) primers and random hexamer and reverse transcriptase enzyme following the manufacturer protocol. In order to examine gene expression by real-time PCR, the method of fluorescence dye SYBR green (Fermentase, USA) was used. The amount of thymol and carvacrol were measured by HPLC. Results Results of morphological traits showed that increasing the water deficit stress caused a decrease in root biomass, shoot fresh weight, plant height, root length, and the number of side branches. Results of gene expression profiling showed that the highest expression of TPS2 and HMGR genes and the highest amount of thymol and carvacrol was obtained in treatment T2 (70% FC). Discussion TPS2 and HMGR gene expression changes were similar to the changes of monoterpenes thymol and carvacrol in all treatments and the highest number of monoterpenes and gene expression were obtained in mild water deficit stress treatment in comparison with control, moderate, and severe stresses. Altogether, according to the results of this study, mild stress had a significant effect on increasing the expression of HMGR and TPS2 and led to a higher production of monoterpenes.

Introduction: Zingiber officinale Roscoe, commonly known as ginger, is used as a cooking spice and therapeutically for its antioxidant and androgenic activities. We investigated the effects of Z. officinale hydro-alcoholic extract on HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase level in the testis of streptozotocin (STZ) -induced diabetic rats.Methods: The current experimental study was performed on four groups of male Wistar rats one of them was kept as a healthy control, while the others were rendered diabetic via a single intraperitoneal injection of STZ (60 mg kg-1). One group was considered as diabetic control; while the others were given orally hydro-alcoholic extract (200 and 400 mg kg-1) for 56 consecutive days. Body weight, blood glucose and insulin concentrations were evaluated using standard methods. The HMG-COA reductase level was determined by western blot analysis.Results: Treatment with the extract resulted in a significant reduction of serum glucose concentration and HMG-COA reductase level in the rat’s testis compared to diabetic controls (P<0.01). A significant increase in body weight was observed in treated diabetic rats. Also, serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P<0.05).Conclusion: Ginger has a potential influence on the regulation of cholesterol homeostasis by modulating of HMG-COA reductase level. The results provide scientific evidence to confirm the traditional use of Z. officinale in the treatment of diabetes mellitus.