Nanoformulation of Curcumin and Its Derivatives as Adjunctive Therapy for the Prevention and Treatment of Malignancies

Introduction: Cancer is defined as the abnormal cell growth. It has always been a great health problem all over the world despite growing advances in its prevention and treatment strategies, which can cause life-threatening malignancies with high financial costs for patients as well as the health care system. Mounting evidence suggested that curcumin is potentially able to act as chemo-preventive and chemotherapeutic agent in different types of cancer. Nanotechnology has shown promising effects in the treatment of cancer. Nanoformulation provides improvements in bioavailability, biodistribution, specificity, and pharmacokinetics of drugs delivered to the site of tumor. The aim of current study is to comprehensively review the pharmacological effects and molecular mechanisms of nanoformulated curcumin and its derivatives as adjunctive therapy in preventing and treating malignancies.   Methods and Results: Electronic databases including “Scopus”, “PubMed”, and “ScienceDirect” were searched with the keywords “cancer” in title/abstract, along with “curcumin” and “nanoformulation” in the whole text. Data were collected from the inception date until June 2017. Articles that had assessed nanoformulations of curcumin derivatives in an in vitro or in vivo model of cancer were selected for this study, and conventional formulations without using a nano­nization technique were excluded. Various curumin nanoformulations have been prepared as anticancer agents including PLGA nanoparticles, cyclodextrin/cellulose nanocrystals, folate-modified PLA-PEG micelles, dendrosomal nanoparticles and lipid–polymer hybrid nanoparticles. Curcumin nanoformulations perform their anticancer activity via several cellular mechanisms, including induction of cell cycle arrest at different phases of cancer cell cycle, acti­vation of caspase enzymes, reduction of tumor vasculariza­tion, reducing tumor cell invasion and metastasis, induction of mitochondrial damage, as well as apoptosis in the neoplasm. Conclusions: Nanoformulations of curcumin, result in better bioefficacy for the prevention and treatment of cancer. The most important improvement in nanoformulated curcuminoids, in comparison to their free molecules, is their better antineoplastic function and improved bioavailability that can result in production of natural anticancer agents with passive targeting of cancerous cells. However, a long path lies ahead of commercializing these agents, including assessment of their safety and efficacy in healthy as well as cancerous subjects in clinical settings

Medicinal plants and their natural components as future drugs for the treatment of burn wounds: an integrative review

Abstract Burn wound healing is a complicated process including inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Several biochemicals are involved in burn healing process including antioxidants, cytokines and liver and kidney damage biomarkers. Although several preparations are available for the management of burn wound, there is still a necessity of researching for efficacious medicine. The aim of the present study was to evaluate herbal preparations and their phytochemical constituents for burn wound management. For this purpose, electronic databases including Pubmed, Scirus, Scopus and Cochrane library were searched from 1966 to July 2013 for in vitro, in vivo or clinical studies which examined the effect of any herbal preparation on different types of burn wound. Only 3 human studies were found to include in this review. In contrast, there were 62 in vivo and in vitro studies that show the need for more clinical trials to prove the plant's potential to cure burn wound. Among single herbal preparations, Allium sativum, Aloe vera, Centella asiatica and Hippophae rhamnoides showed the best burn wound healing activity. Flavonoids, alkaloids, saponins and phenolic compounds were active constituents present in different herbs facilitating wound closure. Glycosides including madecassoside and asiaticoside and proteolytic enzymes were among the main active components. Phytochemicals represented positive activity at different stages of burn wound healing process by various mechanisms including antimicrobial, antiinflammatory, antioxidant, collagen synthesis stimulation, cell proliferative and angiogenic effect. Overall, several herbal medicaments have shown marked activity in the management of wounds-especially burn wounds-and therefore can be considered as an alternative source of treatment. Furthermore, various natural compounds with verified burn-induced wound healing potential can be assumed as future natural drugs

The neuroprotective effects of astaxanthin: therapeutic targets and clinical perspective

As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also consideredS

Management of Multiple sclerosis complications with herbal medicines in clinic: a review

Introduction: Multiple sclerosis (MS) is an inflammatory chronic neurological disease, which affects young and middle aged adults, leading to demyelination, neuronal and axonal damage and finally atrophy of the brain, the spinal cord, and the retina in most patients. MS can cause sensory, motor and visual defects, lack of coordination and cognitive disabilities resulting in quality of life reduction. The aim of the present article was to review the clinical evidence related to medicinal plants in the treatment of symptoms associated with MS patients. Methods and Results: Electronic databases, including the Pubmed, Scopus and Cochrane Library were searched for clinical studies that evaluated the positive effects of medicinal plants in MS. The searched keywords were ‘multiple sclerosis’ in the title/abstract, and ‘plant’, ‘herb’, and ‘phytochemical’ in the whole text. To ensure a better comparison between trials, the Jadad score was used to assess the methodological quality of trials. Findings of the study revealed significant effects of different medicinal plants on MS. This plants are including Andrographis paniculata (King of bitters), Boswellia papyrifera (Bitter frankincense), Cannabis sativa (Hemp), Ginkgo biloba (Ginkgo), Aloysia citrodora (Lemon verbena), Ruta graveolens (Rue) and Panax ginseng (Korean ginseng). C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms. The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Conclusions: Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS

Hesperidin as a neuroprotective agent: a review of animal and clinical evidence

Neuroprotection is the preservation of function and networks of neural tissues from damages caused by various agents, as well as neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Huntington’s diseases, and multiple sclerosis. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases. Our review discusses neuropharmacological mechanisms for preventive and therapeutic effects of hesperidin in neurodegenerative diseases. In addition, the review examines clinical evidence confirming its neuroprotective function. Various cellular and animal models specific to neurodegenerative diseases have been conducted to evaluate the underlying neuropharmacological mechanisms of hesperidin. Neuroprotective potential of this flavonoid is mediated by improvement of neural growth factors and endogenous antioxidant defense functions, diminishing neuro-inflammatory and apoptotic pathways. Despite the various preclinical studies on the role of hesperidin in the neurodegenerative diseases, less is known about its definite effect on humans. A limited number of clinical trials showed that hesperidin-enriched dietary supplements can significantly improve cerebral blood flow, cognition, and memory performance. Further clinical trials are also required for confirming neuroprotective efficacy of this natural flavonoid and evaluating its safety profileS

CHEMICAL COMPOSITION OF ESSENTIAL OIL AND EVALUATION OF ACUTE AND SUB-ACUTE TOXICITY OF DOREMA AMMONIACUM D. DON. OLEO-GUM-RESIN IN RATS

Background: Dorema Ammoniacum is a perennial herb which has been used in Persian Traditional Medicine for different indications, including gastrointestinal disorders and sciatica. Despite numerous medicinal uses, there is a lack of toxicological studies on Dorema Ammoniacum; therefore, the aim of the present study is to investigate its possible toxic effects as well as the determining chemical composition of its essential oil. Materials and Methods: Acute toxicity study was performed by administration of single increasing geometric doses of oleo-gum-resin solution (1250, 2500, and 5000 mg/kg) to Wistar rats. For sub-acute toxicity study, repeated doses of oleo-gum-resin solution (100, 200 and 500 mg/kg) were administered orally to rats for 4 weeks. At the end of the treatment, histopathological studies, hematological assessments, and biochemical parameters were performed. Results: GC-MS was performed to determine the chemical composition of the essential oil. Acute toxicity results demonstrated no mortality, and the Median Lethal Dose (LD50) was greater than 5000 mg/kg. Sub-acute treatment did not show any significant changes in biochemical and hematological parameters at any doses compared to the control group. Histopathological analysis of the organs revealed varying effects. At the level of the liver, vacuolar degeneration and mild inflammation at 200 and 500 mg/kg doses were observed. At the level of kidney, congestion of glomeruli and a widening of the urinary space at 500mg/kg were observed compared to the control group. The principle components of the essential oil were Cuperene (14.31%) and β-Funebrene (12.74%). Conclusion: The results suggest that the acute administration of the oleo-gum-resin of D. Ammoniacum is not accompanied with signs of toxicity; however, its administration over the long term might associate with renal toxicity and hepatotoxicity

Antiangiogenic effects of coumarins against cancer: from chemistry to medicine

Angiogenesis, the process of formation and recruitment of new blood vessels from pre-existing vessels, plays an important role in the development of cancer. Therefore, the use of antiangiogenic agents is one of the most critical strategies for the treatment of cancer. In addition, the complexity of cancer pathogenicity raises the need for multi-targeting agents. Coumarins are multi-targeting natural agents belonging to the class of benzopyrones. Coumarins have several biological and pharmacological effects, including antimicrobial, antioxidant, anti-inflammation, anticoagulant, anxiolytic, analgesic, and anticancer properties. Several reports have shown that the anticancer effect of coumarins and their derivatives are mediated through targeting angiogenesis by modulating the functions of vascular endothelial growth factor as well as vascular endothelial growth factor receptor 2, which are involved in cancer pathogenesis. In the present review, we focus on the antiangiogenic effects of coumarins and related structure-activity relationships with particular emphasis on cancerS

Evaluating the Role of Biochanin A in Acetic acid-Induced Colitis in Rats: Involvement of Nitric Oxide Pathway

Background and objectives: Inflammatory bowel disease (IBD) refers to idiopathic chronic and inflammatory bowel disorders such as ulcerative colitis. Considering the lack of definitive treatment and the side effects of existing drugs, finding efficient compounds is needed. Biochanin A has attracted the attention of researchers due to its wide range of medicinal activities. Until now, no study was conducted to evaluate its effects on colitis. Therefore, the aim of this study was to determine the effect of biochanin A on the nitrogen pathway in rats with acetic acid-induced colitis. Methods: Male rats were divided into five groups: normal group, negative control group, positive control group, and groups receiving biochanin A (10 and 20 mg/kg). Colitis was induced with 4% acetic acid. Next, the samples were evaluated at different macroscopic and microscopic levels, and biochemical test of superoxide dismutase (SOD) and nitric oxide activity was investigated. Results: Macroscopic and microscopic investigations showed that treatment with biochanin A decreased mucosal damage in rats with acetic acid-induced colitis. Biochanin A reduced neutrophil infiltration in the intestinal tissue. It also led to the reduction in nitric oxide and enhancement of SOD in rats. The optimal dose of biochanin A was 20 mg/kg, which had the best effect on reducing inflammation and mucosal lesions in rats. Conclusion: Biochanin A, due to its anti-inflammatory effects by reducing nitric oxide and enhancement of SOD and reducing mucosal damage in rats with acetic acid-induced colitis, can be a useful alternative drug for the prevention or treatment of IBD patients

PROTECTIVE EFFECT OF IRIS GERMANICA L. IN Β-AMYLOID-INDUCED ANIMAL MODEL OF ALZHEIMER’S DISEASE

Background: Alzheimer's disease (AD) is the most common cause of dementia that is an irretrievable chronic neurodegenerative disease. In the current study, we have examined the therapeutic effects of Iris germanica extract on Amyloid β (Aβ) induced memory impairment. Materials and Methods: Wistar rats were divided into five groups of 8 per each. Groups were as followed: control group which were normal rats without induction of AD, Aβ group which received Aβ (50 ng/side), iris 100 group which received Aβ + Iris (100 mg/kg), iris 200 group which received Aβ + Iris (200 mg/kg), and iris 400 group which received Aβ + Iris (400 mg/kg). AD was established by intrahippocampal injection of 50 ng/μl/side Aβ1-42. The day after surgery, animals in treatment groups received different doses of the aqueous extract of Iris by gavage for 30 days. Morris water maze test (MWM) was performed to assess the effects of I. germanica on learning and memory of rats with Aβ induced AD. Results: Data from MWM tests, including escape latency and traveled distance, demonstrated that I. germanica extract could markedly improve spatial memory in comparison to control. Moreover, the plant had a significantly better effect on the performance of AD rats in the probe test. Conclusion: I. germanica extract can successfully reverse spatial learning dysfunction in an experimental model of AD. Further neuro psyco-pharmacological studies are mandatory to reveal the mechanism of action of this natural remedy in the management of AD symptoms

Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates

Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host–pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidatesJ.E. gratefully acknowledges funding from CONICYT (PAI/ACADEMIA N°79160109)S