Pharmaceutical and Biomedical Research
Volume:5 Issue: 2, June 2019

Natural-based drugs are the important bioactive substances that have been used for prevention and treatment of diseases. Natural products should be prepared in commercial scale from relevant medicinal plants. Hence, large amounts of the plants have been needed for extraction and isolation of compounds of natural origin. Plant cells technology is the best strategy for the production of the plant-derived drugs, which have difficulty in high scale preparation. This study was conducted for types, frequencies and efficacies of production methods for natural-based drugs in plant cell technology as alternative method to whole herb. Pharmaceutical and biomedical databases including PubMed/Medline, Scopus, Web of Science, Embase, ProQuest and Google Scholar were searched in this study. Moreover, keywords words were ''secondary metabolite production'', ''pharmaceutical natural compounds'', ''high scale production'', ''cell suspension'', ''immobilized plant cell'', “hairy root”, ''elicitor'', ''substrate'', ''plant cell'', ''callus'', ''medicinal plants'', ''isolation and purification''. The correlations have been investigated by random effect model in an Excel program. Findings of this meta-analysis study showed all production methods had high efficacies and percentages of high scale production from 90 to 100%, which were comparable with conventional direct extractions. In addition to, median efficacy values for cell suspension, callus, hairy root and immobilized plant cell methods in production of selected drugs (atropine, paclitaxel, vincristine, camptothecin and colchicine) with 1124, 257, 797 and 969 events were 92.49 (CI95%: 89.78-95.86), 91.98 (CI95%: 89.13-95.25), 95.69 (CI95%: 92.84-98.68) and 93.86% (CI95%: 91.12-96.35), respectively. The plant cell technology for production of secondary metabolites has various advantages including high accuracy, repeatability and productivity, that is a best strategy for production of natural-based drugs.

Various natural oils/extracts and their constituents incorporated into biopolymer-based edible films as a promising technology with the knowledge that these compounds have been able to reduce microbial growth and chemical changes of packed foodstuffs. The objective of this study was to evaluate the effect of incorporation of Ziziphora clinopodioides essential oil (ZEO; 0, 0.25 and 0.5%) and sesame oil (SO; 0, 0.5 and 0.75%) into chitosan-flaxseed mucilage (CH-FM) film against Listeria monocytogenes, Salmonella typhimurium, Staphylococcus aureus and Escherichia coli O157:H7 in vitro condition and raw minced trout fillets during refrigerated condition. The in vitro antibacterial and antioxidant properties of CH-FM films were evaluated using agar disk diffusion method and free radical scavenging activity assay, respectively. The most important constituents of ZEO were found to be carvacrol (65.22%), thymol (19.51%), ɣ-terpinene (4.63%) and p-cymene (4.86%). The lowest and highest antimicrobial effect against S. aureus, L. monocytogenes, E. coli O157:H7 and S. typhimurium were found for CH-FM films enriched with SO 0.5% (0.98-1.24 mm) and ZEO 0.5% + SO 0.75% (5.01-6.25 mm), respectively. The antioxidant property of CH-FM based films were found to be ranged 5.45% ± 0.04-37% ± 0.45. In treated trout fillets, the counts of L. monocytogenes, S. aureus, E. coli O157:H7 and S. typhimurium were 1.54-4.18, 0.34-3.35, 0.29-1.45 and 0.19-1.27 log CFU/g significantly lower than control groups after two weeks of refrigerated storage, respectively. The designated films had good antibacterial effect against some food borne pathogenic bacteria including L. monocytogenes, S. aureus, S. typhimurium and E. coli O157:H7 in raw rainbow trout fillets.

Carvedilol (CVD) is an antihypertensive agent with a short half-life, pH-dependent solubility, and narrow absorption window. The purpose of this research was to prepare a floating-drug delivery-system of carvedilol to increase its half-life. The present study investigates the preparation of carvedilol-floating microspheres, evaluates the floating-drug delivery-system (FDDS) (by scanning electron microscope), it’s in vitro stability, and in vivo profile. Floating microspheres were prepared by solvent-evaporation (oil-in-water emulsion) technique using hydroxypropyl methylcellulose (HPMC) and ethyl cellulose (EC) as the rate controlling polymers. The surface morphology of the prepared microspheres w:as char:acterized by scanning electron microscopy. In this study, the particle size analysis, drug entrapment efficiency, surface morphology, buoyancy percentage, and release studies were performed. The microspheres were found to be spherical and porous. The results showed that the mean/mean (SD) values of tapped density, Carr's compressibility index, angle of repose, percentage yield, in vitro buoyancy, %entrapment efficiency of CVD-loaded floating microspheres were 0.42 (0.012), 12.5 (1.895), 23.5 (1.856), 80.2 %, 79.0 %, and 85.81(1.40), respectively. The developed floating-microsphere of CVD released the drug for 24 h and based on in vivo studies, the drug-loaded floating microspheres help in maintaining the mean (SD) systolic blood pressure within the range of 120 (0.32) to 120 (1.02) mmHg and diastolic pressure within 91 (0.71) to 92 (0.79) mmHg. Thus, floating microsphere of CVD offers a suitable and practical approach for prolonged release of the drug over an extended period, and thus improves the oral bioavailability and efficacy of the drug as well as the patient’s compliance.

Diabetes mellitus (DM) and hypertension usually co-exist, and when this happens, the prognosis would be worse than each disease alone. Given this, we evaluated the possible effects of valsartan and amlodipine administration on metformin-treated diabetic rats models induced by streptozotocin.
Male Wistar rats (200–350 g) were fasted overnight. Then, we induced DM by administrating a single dose of 40 mg/kg streptozotocin (IP), which was confirmed after 48 h.  Animals with blood sugar ≥ 200 mg/dl were considered diabetic and divided into four diabetic groups of untreated diabetic animals (Group B), diabetic animals treated with metformin (Group C), diabetic animals treated with metformin plus amlodipine (Group D), and diabetic rats treated with metformin plus valsartan (Group E). There was also a group A, consisting of normal rats with no drug treatment. After six weeks of treatment, we sacrificed the animals under chloroform anesthesia, and their blood samples were collected for hematological and biochemical analyses.
The mortality rate in untreated diabetic rats was 100% before 6 weeks, but anti-diabetic treatment (metformin) significantly (P < 0.05) improved the survival rate and controlled their blood glucose level. The addition of antihypertensive drugs (amlodipine and valsartan) enhanced this curative effect. The various treated groups showed ameliorations in pathologic changes and biochemical indices, as well as, evidence of organ protection, compared with the untreated diabetic group.
The study showed that adding an antihypertensive drug (amlodipine or valsartan) to metformin regimen improved  outcomes in diabetic rats compared to using metformin alone.

This study aimed to determine the analgesic properties and the acute toxicity of Ethanol Extract of the Resin Exudate of Boswellia dalzielii (EERBD) in mice animal model.
We used the writhing or acetic acid abdominal constriction, tail-immersion, and hot plate tests to assess the analgesic effect of EERBD at three doses (100, 200, and 400 mg/kg). To study the acute toxicity of EERBD, 24 female mice were divided into four groups (n=6) and were orally treated with EERBD at the doses of 0, 2000, 4000, and 5000 mg/kg, as per OECD (Organization for Economic Co-operation and Development) guidelines No. 420.
In the acetic acid-induced writhing reflex model, the EERBD ministration decreased the mean total number of writhes at the two doses (100 and 400 mg/kg), which were found highly significant (P < 0.001) compared to control group. In the tail immersion model, the EERBD administration at the dose of 400 mg/kg significantly increased the pain reaction time (P < 0.001 as compared to control) at 30 min, but another tested sample had no significant latency. In the hot-plate model, the drug extract created significant (P < 0.001) increase in the latency period compared to the control group at oral doses of 100 and 400 mg/kg when compared to initial time and control group (4.5 ± 1.29 s) with protective effect from 4.25 ± 1.50 s after 30 min.  Administration of EERBD at the dose of 200 mg/kg showed no significant analgesic activity based on writing, tail immersion, and hot-plate tests. The extract did not show toxicity signs or death at dose of less than 5000 mg/kg per oral.
The results suggest that EERBD contain bioactive substances with analgesics effects; hence, it might be a better alternative to conventional drug therapy for pain management.

Purine nucleoside phosphorylase (PNP) is one of the major enzymes in the purine salvage pathway. It is responsible for the elevation of deoxyguanosine, and thus considered as the potent target in T-cell lymphoma. The present study examined acyclovir, reported as a low-affinity PNP inhibitor, for the rational design of new acyclovir derivatives by incorporating halogens, hydroxyl, and bulky amino groups. The molecular actions of designed derivatives were investigated by employing density functional theory, molecular docking, and binding energy calculations. The results revealed that the newly designed compounds were highly stable and showed more affinity to PNP than the parent compound, acyclovir. The quantum mechanics and molecular docking studies suggested that modification of side chains with bulky polar groups provided better binding affinities than substitutions with halogens. The resultant derivatives have strong polar interactions like His257 and Tyr88. Furthermore, the designed derivatives were within the ideal range of ADMET (absorption, distribution, metabolism, elimination, and toxicity) analysis. Considering that, these findings recommend further validation of designed acyclovir derivatives in wet lab confirmatory analysis with the emphasis on the further improvements in the treatment of T-cell-mediated diseases.

Misuse of stimulants similar to amphetamine is a universal problem. These stimulants cause many complications in their abusers. However, myocardial infarction is rarely reported as a complication of amphetamine abuse. Herein, we report a man aged 42 years presented at the Emergency Department with the chief complaint of acute dyspnea following ice inhalation without history of dyspnea. Within the first hour and a half of admission, the patient was treated by nasal oxygen and bronchodilator aminophylline. However, he did not respond to the initial treatment and lost his consciousness; showed ventricular fibrillation, cardiac arrest, and hemodynamic instability. So, cardiopulmonary resuscitation was immediately initiated for him. The patient was intubated, mechanically ventilated. Also, the synchronized electrical shock was delivered 5 times (200-360 J) along with amiodarone (300 mg intravenously [IV] stat, then 1 mg/min IV infusion for 6 hours and next 0.5 mg/min for 18 hours) to treat the ventricular fibrillation. The arrhythmia was subsequently controlled, and his normal sinus rhythm was resumed. Two hours later, condition of the patient improved, and he was extubated. After two days, when the patient got stable, the echocardiography was performed, which was completely normal.