Current Drug Discovery Technologies - Volume 19, Issue 5, 2022

Background: Genus Dracocephalum belongs to the Lamiaceae family, representing 11 species in Iran, containing D. ghahremanii Jamzad, D. lindbergii Rech. F, D. oligadenium Bornm. & Gauba, D. kotschyi Boiss., D.multicaule, D.Aucheri, D.Subcapitatum, D.Thymifolium, D.Moldavica, D. polychaetum Borm, and D. surmandinum Rech.f. The current study aimed to investigate the morphological and phytochemical properties of Dracocephalum species in Iran and their pharmacological effects. Methods: The search was restricted to scientific articles from PubMed, Google Scholar, Science Direct, SpringerLink, and Scopus. The search was limited to scientific journals, books, and book chapters focusing on the medicinal properties of Dracocephalum in Iran for the era from 1993 to 2020. Results: Findings show that Dracocephalum species were utilized to treat various disorders in traditional medicine. Phytochemical studies show that the main constituents isolated from the plant consist of lignans, phytosterol, flavonoids, phenols, alkaloids, Sesquiterpenes, and oxygenated and hydro carbonated monoterpenes. These main components are responsible for antihyperlipidemic, antimicrobial, anticancer, antispasmodic, antioxidant, and cardiovascular effects of the plant. Conclusion: This plant has a good potential for drug discovery and curing different diseases. Therefore, more research will be done on the Iranian species of Dracocephalum based on clinical and animal studies to develop an effective drug formulation.

Introduction: Candidiasis infection is caused by different species of Candida, which are characterized by host immunologic weakness. Black cumin seeds (Nigella sativa) have shown an inhibitory effect against Candida albicans. In this work, the inhibitory effect of standardized extract and different fractions of Nigella sativa seeds has been evaluated on both nystatin-susceptible and resistant strain of C. albicans. Materials and Methods: Canadida albicans (NSCA) with ATCC 76645 and nystatin-resistant Candida albicans (NRCA) were prepared from oral samples of HIV individuals. Total extract and different fractions of N. sativa were prepared using maceration and sonication methods. Thymoquinone (TQ) content of the plant was determined by spectrophotometric method. Total extract (TTE) and the fractions along with TQ were evaluated on NSCA and NRCA by the microdilution method. Results: TQ content of the plant was 0.92 ± 0.37g/100g dried extract. The least MIC and MFC (62.5 and 125 μg/ml, respectively) were due to petroleum ether fraction (PEF) against both NSCA and NRCA, followed by chloroform fraction (CHF) with MIC and MFC of 125 and 250 μg/ml, respectively. TQ exhibited MIC of 0.78 and 3.12 μg/ml against NSCA and NRCA, stronger than nystatin (MIC of 2 and 16 μg/ml, respectively). Thymoquinone was detected in the PEF and CHF. Conclusion: Considering more inhibitory effects of PEF and CHF than TTE, we can conclude that active components of the plant belong to non-polar compounds. PEF showed identical inhibitory effects on NRCA and NSCA, which is a valuable result for finding novel medicaments against NRCA infections.

Background: Individual extracts of Garcinia kola and Kigelia africana have been shown to have therapeutic effects against a variety of variables linked to the development of diabetes mellitus. However, there is still a lack of information about the combined effects of these extracts on Insulin and Paraoxonase 1 (PON-1) in Streptozotocin-Nicotinamide-induced type-2 diabetic Wistar rats. Methods: Forty-two young male rats (180-200g) were randomly divided into six groups (n = 7/group). Diabetes was intraperitoneally induced with 110 mg/kg of nicotinamide constituted in distilled water and fifteen minutes later with 65 mg/kg of streptozocin freshly prepared in 0.1M citrate buffer (pH of 4.5) and treated for six weeks as follows: the control rats received either 0.9% normal saline (NS) or 250 mg/kg extract by gavage. The remaining animals were diabetes induced and subsequently treated with either NS, graded doses of the extract (250 mg/kg and 500 mg/kg), or 5 mg/kg Glibenclamide + 100mg/kg Metformin. Gas chromatography-mass spectrometry (GCMS) of the combined extracts was also analyzed to identify the bioactive compounds present in it. Insulin, PON-1 levels, lipid profiles, and atherogenic index were assessed. Results: Our findings show that Insulin and PON-1 levels in the plasma of diabetic rats treated with the combined extracts were significantly increased when compared to the control rats. Moreover, the GCMS of the extract shows the presence of both monounsaturated (oleic acid) and polyunsaturated (linoleic acid) fatty acids. Conclusion: The current findings suggest that the extract may help improve glucose homeostasis and prevent atherosclerosis through the established mechanism of the identified bioactive compounds.

Background: Obsessive-compulsive disorder (OCD) is a severe and debilitating neuropsychiatric condition. Although selective serotonin reuptake inhibitors, tricyclic antidepressants, and cognitive- behavioral therapy are the first-line medication and treatment for OCD, an estimated 30% of patients are treatment-resistant, and complete functional recovery is rare. Natural products as adjuvant or alternative therapies should be examined to find safer and more effective ways to manage OCD. Objectives: To investigate the potential benefits of a combined herbal drug based on Echium amoenum in treating OCD. Methods: Design and Setting: In the psychiatric clinics of Mashhad University of Medical Sciences, 40 patients who met the criteria for the obsessive-compulsive disorder based on DSM-5 were studied in a parallel, double-blind, randomized clinical trial. Intervention: Subjects were randomly assigned to receive Echium amoenum-Melissa officinalis syrup and fluvoxamine or placebo syrup and fluvoxamine for 8 weeks. Outcome Measures: The efficacy of treatment and recurrence of disease were surveyed and compared according to the Yale-Brown Obsessive Compulsive Scale at weeks 0, 4, and 8. Results: Evaluation at the 4th and 8th week showed no significant differences between the two groups (p-value = 0.11, p-value = 0.445, respectively). At the 8th week of treatment, patients in the intervention group showed a remarkable reduction in scores on the Yale-Brown Obsessive-Compulsive Scale questionnaire (p- value= 0.003), and patients in the control group didn't ((p- value= 0.180). This study showed that the E.amoneum-M.officinalis syrup was not significantly more efficacious than the fluvoxamine tablet, but the intervention group showed a significant improving trend (p-value= 0.001). Conclusion: While monotherapy is usually the gold standard methodology, combination or augmentation therapy may also be of merit. Consequently, studies with larger sample sizes and the inclusion of para-clinical assessments such as serologic tests can further shed light on the mechanism of action of the E. amoneum- M. officinalis syrup and deepen our understanding of its effects.

Background: The reduced levels of acetylcholine and dopamine lead to Alzheimer's disease (AD) and Parkinson's disease PD, respectively, due to the action of cholinesterase and monoamine oxidase B. Methods: Therapeutic options for AD and PD involve respective cholinergic and monoaminergic inhibitors, and considering the adverse outcomes of cholinergic- and monoaminergic- inhibitory therapeutics, phytoconstituents may be promising alternatives. Reports have shown that different extracts of the calyx of Hibiscus sabdariffa exhibit anticholinesterase and monoamine oxidase B inhibitory properties with the potential to delay and prevent the development of AD and PD. However, there is limited knowledge on the multitarget cholinergic and monoaminergic inhibitory activities of individual compounds in this plant. Computational methods were used to identify the specific compounds responsible for the observed cholinergic and monoaminergic inhibitory activities of the H. sabdariffa calyx extracts. Results: Results confirm that three flavonoids: delphinidin-3-sambubioside, kaempferol-3-O-rutinoside and quercetin-3-rutinoside showed strong binding affinity with acetylcholinesterase, butyrylcholinesterase and monoamine oxidase B while the observed stability of the ligands-enzymes complexes over the MD simulation time suggests their cholinergic and monoaminergic inhibitory properties. Conclusion: The three flavonoids may be responsible for the reported anticholinergic and monoaminergic inhibitory potentials of H. sabdariffa extracts and could be enlisted as multi-target inhibitory agents for cholinesterases and monoamine oxidase B.

Background: Adequate oxygenation is essential for sick newborns. Each disease determines the target of oxygenation. Nevertheless, hyperoxia and hypoxia are related to adverse outcomes. Most studies related to this aspect have been conducted in preterm infants or term babies with pulmonary pathology. Introduction: Congenital heart diseases may also require careful oxygenation control and management of oxygen supply. Methods: Presurgical stabilization of complex heart diseases (CHD) may be difficult, especially after the physiological decrease of pulmonary resistance, which generates pulmonary edema (due to overcirculation) and systemic hypoperfusion. Several strategies have been described to avoid this phenomenon, such as prostaglandin, vasodilators, inotropes, positive airway pressure, and even hypoxic mixture (inspired fraction of oxygen (FiO2) below 21%). Discussion: The latter therapy is mainly used in single ventricular physiology heart diseases, such as the hypoplasic left heart syndrome (HLHS) or systemic ductus-dependent flow CHD (interruption of the aortic arch and coarctation of the aorta). Alveolar oxygen affects pulmonary vascular resistance modifying lung flow. This modification could help the stabilization during the presurgical period of complex CDH. Many centers use hypoxic therapy to avoid hypotension, metabolic acidosis, coronarycerebral ischemia, and liver, renal and intestinal injury. Despite the theoretical benefits, there are doubts about how tissue oxygen supply would change during hypoxic gas ventilation. It is worrisome that FiO2 < 21% causes a decrease in brain oxygenation, adding neurological injury as a complication to the already established disease of CHD and other not modifiable factors. Brain monitoring through near-infrared spectroscopy (NIRS) during hypoxic gas therapy is mandatory. Recent studies have shown that hypoxic gas ventilation therapy in patients with HLHS in the preoperative period decreases the ratio between systemic and pulmonary circulation (Qp/Qs) but does not improve regional oxygenation delivery. The use of hypoxic gas ventilation therapy continues to be controversial. It could be an option in some complex CHD, mainly HLHS.

Background: Obsessive-compulsive disorder (OCD) is a potentially debilitating disease that affects 1-4% of the general population. It is characterized by the presence of obsessions and compulsions which interfere with the individual's life and functioning. Although conventional treatments such as drug therapies and cognitive behavioral therapy exist for OCD, these treatments are not universally successful and can cause side effects, which has created a demand for alternative and complementary therapies. Methods: In this review, we summarize randomized clinical trials on the effectiveness of herbal medicines for the treatment of OCD, and review the possible mechanisms of action for these medicines. A search in PubMed, Scopus, and The Cochrane Library found 1022 studies, of which 7 were included in our review. Results: The studies that we found were conducted over 6 to 12 weeks, and had an average sample size of 37. The plant species studied included Crocus sativus, Echium amoenum, Hypericum perforatum, Silybum marianum, Valeriana officinalis, and Withania somnifera. The trials demonstrated the effectiveness of all plants as treatments for OCD except H. perforatum. The phytochemicals found in these plants produce their effects through a variety of means such as inhibiting the reuptake of monoamines, GABAergic effects, and neuroendocrine modulation. The small number of studies and their small sample sizes, poor methodology, and lack of replication highlight the need for further research into herbal medicines for the treatment of OCD. Conclusion: Overall, herbal medicines can be used as stand-alone therapies for OCD or in conjunction with other methods.

Background: Polyalthia cerasoides is well known for its therapeutic effects and is extensively used by the tribal people of South India and Africa to treat infertility, toothache, inflammation, rheumatism, fever, and to combat stress. Objective: In the present research, the anti-proliferative potential of two bioactive compounds isolated from the stem bark of P. cerasoides (Roxb.) Bedd. of the Annonaceae family was investigated. Methods: The dried stem bark was powdered and subjected to extraction using methanol and further partitioned using petroleum ether. Yellow viscous oil was isolated from the petroleum ether fraction using column and preparative thin-layer chromatography. The chromatographic fractions were characterized using GC-MS. The anti-proliferative effect of the isolated compounds was assessed against HepG2 Cells using MTT- Cytotoxicity test. Furthermore, comparative in-silico docking studies were performed to predict the binding pattern of isolated molecules individually, as well as simultaneously with α, β-tubulin, a critical protein involved in the molecular mechanism of microtubule formation. Results: GC-MS analysis of yellow viscous oil from petroleum fraction confirmed the presence of two labdane diterpenes that were identified as 12E-3,4-Seco-labda-4(18),8(17),12,14-tetraen-3-oic acid, and methyl harvadate C by mass fragmentation analysis. The MTT-cytotoxicity assay showed the dose-dependent cytotoxic effect on HepG2 Cells. The comparative docking studies of the isolated compounds exhibited strong interactions with the α, β-tubulin protein. Conclusion: The prominent anti-proliferative effect exhibited by the isolated compounds, along with effective binding to α, β-tubulin protein, encourages their future utilization as prominent anti-cancer molecules.