The Effect of Aromatherapy with Citrus aurantium Aroma on Pain after Orthopedic Surgery: A Randomized Clinical Trial.

Introduction: Postoperative pain is one of the most common physiological and psychological stress in patients that disrupts body function and can endanger patients' health. This study aims to determine the effect of aromatherapy with Citrus aurantium essential on pain after orthopedic surgery. Methods: This randomized clinical trial was performed on 60 candidates for orthopedic surgery. Patients were selected through convenience sampling and divided into intervention and control groups through randomized block allocation. If the visual analogue scale (VAS) score was above 3, patients in the intervention group received aromatherapy with C. aurantium essential and the patients in the control group received a placebo (almond oil). VAS was used to measure pain. Data analysis was performed using independent t test, paired t test, and analysis of variance with repeated measures using SPSS software version 13. Results: Mean (SD) of pain intensity after intervention in experimental and control groups within 4, 8, and 12 hours after surgery was 7.30 (1.23) vs. 7.90 (0.99), 5.30 (0.98) versus 5.53 (0.68) and 2.53 (0.9) vs. 3.60 (0.77) respectively. The findings indicated that there was a significant difference in mean pain intensity between the experimental and control groups at 4 and 12 hours after surgery. Use of analysis of variance with repeated measures test with taking into account the interaction of time and group also showed a significant difference in mean pain intensity between the two experimental and control groups. Conclusion: Aromatherapy with Citrus aurantium essential can be effective in reducing mild to moderate pain after orthopedic surgery. Further studies are recommended to confirm this finding.

Potential of the genetically transformed root cultures of Plumbago europaea for biomass and plumbagin production.

Plumbago europaea L. is the main source of plumbagin which is a well-known pharmacological active compound. In this investigation, genetically transformed roots of P. europaea were obtained by improving some factors affecting the efficiency of Agrobacterium rhizoigenes-mediated transformation such as explant type, A. rhizoigenes strain, bacterial infection period, co-cultivation period and acetosyringone concentration. The leaf, hypocotyl and stem explants from in vitro grown plantlets were infected with bacterial strains (A4, ATCC15834, MSU440 and A13). The highest transformation rate of 69.3% was achieved after 7-9 days by inoculating A. rhizogenes MSU440 strain onto the 3-week-old stem explants followed by a co-cultivation period of 2 days on a medium containing 100 µM acetosyringone. To investigate the existence of the rolB gene, polymerase chain reaction was carried out using specific primers. Effects of growth media (MS, 1/2 MS, MS-B5 and ½ MS-B5), different sucrose concentrations and illumination on biomass production and plumbagin biosynthesis in P. europaea hairy root cultures were analyzed using stem explants after infection with MSU440 strain. ½ MS-B5 liquid medium containing 30 g L-1 sucrose incubated in the dark resulted in the efficient biomass production of transformed hairy roots (12.5 g fresh weight, 1.8 g dry weight) with 3.2 mg g-1 DW plumbagin accumulation. This procedure provides a framework for large-scale cultivation of hairy roots for plumbagin production. This is the first report describing the establishment of P. europaea hairy root culture with special emphasis on plumbagin production.

Cell Suspension Culture of Plumbago europaea L. Towards Production of Plumbagin.

BACKGROUND: Plumbagin is as an important bioactive secondary metabolite found in the roots of Plumbago spp. The only one species, Plumbago europaea L., grows wild in Iran. The therapeutic use of plumbagin is limited due to its insufficient supply from the natural sources as the plants grow slowly and take several years to produce quality roots. OBJECTIVES: To develop an efficient protocol for the establishment of callus and cell suspension cultures of P. europaea and to evaluate production of plumbagin in callus and cell suspension cultures of P. europaea for the first time. MATERIAL AND METHODS: Stems and leaves explants were cultured on agar solidified (7% w/v) MS media, supplemented with different combination of 2, 4-D and Kin or 6-Benzylaminopurin (BA) for callus induction. The rapid growing calli were cultured in liquid Murashige and Skoog (MS) media in agitated condition for establishing cell suspension cultures of P. europaea. Moreover, the effects of light and dark conditions on the cell growth, cell viability and plumbagin production in cell suspension cultures of P. europaea were assessed. RESULTS: Friable calli were successfully induced using stem segments of P. europaea in semisolid MS medium supplemented with 1 mg.L-1 2, 4-Dichlorophenoxy acetic acid (2, 4-D) and 0.5 mg.L-1of kinetin (Kin). Optimal cell growth was obtained when the cells were grown in MS liquid media supplemented with 1 mg.L-1 2, 4-D and 0.5 mg.L-1 kinetin with an initial cell density of ~3×105 cells per ml incubated in the dark at 25 ± 1 °C. Growth curve revealed that the maximum cell growth rate (14.83×105 cells per ml) achieved on the day 18 and the highest plumbagin content (0.9 mg.g-1 Dry Cell Weight (DCW)) in the cells was obtained at the late exponential phase under dark condition which determined by High Performance Liquid Chromatography (HPLC) technique. Based on the obtained results, cell viability remained around 82.73% during the 18 days of cell culture in darkness. These suspension cultures showed continuous and stable production of plumbagin. CONCLUSIONS: Our study suggests that cell suspension cultures of P. europaea represent an effective system for biosynthesis and production of plumbagin as a valuable bioactive compound.

Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics.

Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.

Natural activators of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and their pharmacological activities.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme which monitors cellular energy status and regulates metabolism with energy balance. AMPK activation, as a master regulator of metabolism, plays role in key tissues like liver, skeletal muscles, and heart as well as central nervous system (CNS). Activation of the enzyme by indirect activators attracts scientific attentions to treat diabetes, obesity, cancer, and other related metabolic disorders like physiological and pathophysiological states in CNS. A number of hormones and pharmacological agents have been reported to activate AMPK including paroxetine, metformin, thiazolidinediones, adiponectin, leptin, interleukin-6, and etc. AMPK activity is prominent in regulation of glucose, lipid, and proteins metabolism as well as mitochondrial biogenesis and autophagy. Activation of AMPK in the liver decrease blood glucose and in skeletal muscles stimulates glucose uptake independently of insulin through modulation of activity of several downstream substrates. Activation of AMPK inhibits synthesis and induces oxidation of fatty acids, which may reduce ectopic lipid accumulation and improve insulin action. The enzyme activation promotes cardiovascular homeostasis by ensuring optimum redox balance of heart and vascular tissue. In addition, AMPK signaling may link to cancer development via regulation of checkpoints of cell cycle. Numerous of conventional drugs have been derived from natural resources, while the application of this fruitful source of chemical structures have not been explored in depth. A number of these compounds are discussed in this review that exhibit beneficial effects in metabolic disorders through AMPK activation.

Piperine as a Potential Anti-cancer Agent: A Review on Preclinical Studies.

Recently many studies showed anticancer activities of piperine, a pungent alkaloid found in black pepper and some other Piper species. We attempted to summarize acquired data that support anticancer potential of this natural agent. Piperine has been reported to possess effective chemopreventive activity. It has been studied to affect via several mechanisms of action, in brief enhancing antioxidant system, increasing level and activity of detoxifying enzymes and suppressing stem cell self-renewal. Moreover, piperine has been found to inhibit proliferation and survival of various cancerous cell lines via modulating cell cycle progression and exhibiting anti-apoptotic activity, respectively. This compound has been shown to modify activity of various enzymes and transcription factors to inhibit invasion, metastasis and angiogenesis. Interestingly, piperine has exhibited antimutagenic activity and also inhibited activity and expression of multidrug resistance transporters such as P-gp and MRP-1. Besides, about all reviewed studies have reported selective cytotoxic activity of piperine on cancerous cells in compared with normal cells. Altogether, the studies completely underline promising candidacy of piperine for further development. The collected preclinical data we provided in this article can be useful in the design of future researches especially clinical trials with piperine.

Natural terpenoids as a promising source for modulation of GABAergic system and treatment of neurological diseases.

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter reducing neural excitability in the mammalian central nervous system (CNS) with three subclasses of receptors. Several conventional drugs and compounds modulate the GABAergic system, demonstrating different pharmacological effects. In this review, interactions of natural terpenoids with the GABAergic system are highlighted with relation to disorders like anxiety, insomnia, convulsion, pain, and cognitive deficits. Terpenoids with various structures affect the function of the GABAergic system via dissimilar mechanisms. Most of the discussed compounds interact with GABA receptors, but especially with the GABAA subtype. This may be due to the fact that researchers tend to assess the interaction of compounds using GABAA receptors. However, bilobalide, a sesquiterpene, showed anticonvulsant properties through the activation of glutamic acid decarboxylase (GAD) enzyme, which is a key enzyme in biosynthesis of GABA. Therefore, further studies evaluating and comparing terpenoids of different classes and their interaction with the GABA system, along with their pharmacokinetic properties, could be worthwhile in future studies.

Role of natural phenolic compounds in cancer chemoprevention via regulation of the cell cycle.

Natural phenolic compounds have been considered as one of the interesting secondary metabolites for their chemopreventive and chemotherapeutic effects in cancer for a long time. These are a large and diverse family of phytochemicals classified into several subgroups such as simple phenols, lignans, phenylpropanoids, flavonoids, coumarins, etc. The antioxidant potential of phenolic compounds is almost bolded in the treatment and prevention of cancer. Due to the concerns on the diverse effects of antioxidants in cancer, differentiation and clarification of their anti-neoplastic mechanisms are necessary. An important mechanism for phenolic compounds is related to their direct effect on the cell cycle progression, which has not been discussed in detail so far. This study aims to criticize the evidence on regulatory mechanisms of phenolic compounds in the cell cycle. Recent studies indicate that phenolic compounds from several subgroups significantly inhibit the proliferation of different cancer cells. The structural diversity of these compounds influences various components involved in cell cycle regulation. Forming active metabolites and sensitizing cancerous cells to chemotherapeutic medicines are additional values of these compounds. In the recent years, many studies on neoplastic cell cultures have been carried out to investigate the mechanisms of action of these compounds but dissimilarity of in vitro systems in comparison with human body in terms of metabolism and bioavailability is a major concern. Therefore, further studies are still needed.

Personalized medicine: a confluence of traditional and contemporary medicine.

CONTEXT: Traditional systems of medicine have attained great popularity among patients in recent years. Success of this system in the treatment of disease warrants consideration, particularly in cases for which conventional medicine has been insufficient. OBJECTIVE: This study investigates the similarities in principles and approaches of 3 traditional systems and explores whether conventional medicine is able to exploit the advantages of traditional systems. DESIGN: This study first identifies and explores the advantages of 3 well-known systems-traditional Iranian medicine (TIM), ayurveda, and traditional Chinese medicine (TCM)-that are similar in their basic principles and methods. Second, it clarifies whether and how conventional medicine could exploit the advantages of traditional systems as it modernizes, to become more personalized. Finally, this study investigates the possibility that conventional medicine could benefit from traditional typology to improve its personalization. RESULTS: The acknowledgment of the unity of humans and nature, applying rational methods, and personalized approaches is fundamentally similar in the 3 systems. Additionally, they all promote the holistic view that health is harmony and disease is disharmony of the body. Other similarities include their recognition of the unique nature of every person and their categorization of people into different body types. Although conventional medicine has mostly failed to incorporate the advantages of traditional medicine, its integration with traditional medicine is achievable. For instance, exploiting traditional typologies in genomic and other studies may facilitate personalization of conventional medicine. CONCLUSION: From its review, the research team concludes that prospects are bright for the integration of traditional and conventional medicines and, consequently, for a dramatic improvement in health systems.

Cytotoxic evaluation of Melia azedarach in comparison with, Azadirachta indica and its phytochemical investigation.

BACKGROUND: Melia azedarach L. is an important medicinal plant that is used for variety of ailments in Iranian traditional medicine. Azadirachta indica A. Juss is its allied species and possesses similar properties and effects. The present study was undertaken to investigate anticancer activity of these M. azedarach in comparison with A. indica on cancer cell lines and also to evaluate their safety in humans by testing them on normal cell line. The study also aimed to determine the active components that are responsible for medicinal effects of M. azedarach in traditional usages. METHODS: In this study, the cytotoxic activity of crude extracts from M. azedarach and A. indica leaves, pulps and seeds as well as three main fractions of their leaf extracts were assayed against HT-29, A-549, MCF-7 and HepG-2 and MDBK cell lines. MTT assay was used to evaluate their cytotoxic activities. Methanol leaf fraction of M. azedarach as the safest leaf fraction in terms of cytotoxicity was subjected for phytochemical study. RESULTS: Results of the present study indicated that seed kernel extract of M. azedarach had the highest cytotoxic activity and selectivity to cancer cell lines (IC50 range of 8.18- 60.10 λg mL-1). In contrast to crude seed extract of A. indica, crude pulp and crude leaf extracts of this plant showed remarkably stronger anti-prolifrative activity (IC50 ranges of 83.45 - 212.16 λg mL-1 and 34.11- 95.51 λg mL-1 respectively) than those of M. azedarach (all IC50 values of both plants > 650 λg mL-1). The phytochemical analysis led to the isolation of four flavonol 3-O-glycosides including rutin, kaempferol-3-O-robinobioside, kaempferol-3-O-rutinoside and isoquercetin along with a purin nucleoside, β-adenosine. CONCLUSIONS: The anti-prolifrative potentials of extracts from different parts of M. azedarach and A. indica were determined. By comparison, methanol leaf fraction of M. azedarach seems to be safer in terms of cytotoxicity. Our study shows that flavonols are abundant in the leaves of M. azedarach and these compounds seem to be responsible for many of medicinal effects exploited in the traditional uses.

A comparative study of anti-Candida activity and phenolic contents of the calluses from Lythrum salicaria L. in different treatments.

In the study, anti-Candida activity and phenol contents of Lythrum salicaria L. calli and wild species have been evaluated. The seeds of L. salicaria (Lythraceae), collected from Lahidjan City in the north of Iran, were cultured in Murashige and Skoog medium (MSM) with a supplement, gibberellin, to germinate. Callus inductions were performed from segments of seedling on MSM containing different concentrations of plant growth regulators, 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP). The activity of calluses extracts, wild plant, gallic acid, and 3,3',4'-tri-O-methylellagic acid-4-O-ß-D-glucopyranoside (TMEG) as the main phenolic compounds against Candida albicans was assessed using cup plate diffusion method. The total phenols contents of calli and wild plant extracts were analyzed using Folin-Ciocalteu reagent. The callus formation in MSM supplemented with various concentrations of 2,4-D and BAP were 0-100 %. Anti-Candida activity of callus extract which obtained from MSM supplemented with 2,4-D and BAP (1 mgdm(-3)) was similar to the wild plant extract. Minimum inhibitory concentration values of gallic acid and TMEG were obtained as 0.312 and 2.5 mgcm(-3), respectively. Gallic acid equivalent values in all treatments were from 0 to 288 µg GAE mg(-1). Phenolic contents of plant aerial parts (331±3.7 µg GAE mg(-1)) and the callus, which developed in MSM including 1 mgdm(-3) of both 2,4-D and BAP, showed the same phenolic value and exhibited anti-Candida extract activity.