Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms.

Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy, radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/ß-catenin. However, more numerous experimental and clinical studies should be designed to find the efficacy of baicalin and the related mechanisms of action.

Therapeutic Effects of Berberine against Urological Cancers: Biological Potentials Based on Cellular Mechanisms.

Urological cancers, including prostate, kidney, and bladder cancer are problematic human diseases worldwide. Current strategies for the treatment of these cancers are chemotherapy, radiotherapy, surgery, or a combination of mentioned therapies. Due to the high mortality and morbidity rate of urological cancers and possible side effects of available standard treatments, searching for more effective and safe treatments is a critical issue. The beneficial properties of natural compounds, such as berberine, have been widely investigated in human diseases. Moreover, the anticancer potential of this agent has been extensively documented, especially in experimental studies. In this review, we have tried to discuss the effect of berberine against urological cancers, focusing on cellular and molecular mechanisms.

Protective Roles and Therapeutic Effects of Gallic Acid in the Treatment of Cardiovascular Diseases: Current Trends and Future Directions.

Cardiovascular diseases (CVDs) are serious life-threatening illnesses and significant problematic issues for public health having a heavy economic burden on all society worldwide. The high incidence of these diseases as well as high mortality rates make them the leading causes of death and disability. Therefore, finding novel and more effective therapeutic methods is urgently required. Gallic acid, an herbal medicine with numerous biological properties, has been utilized in the treatment of various diseases for thousands of years. It has been demonstrated that gallic acid possesses pharmacological potential in regulating several molecular and cellular processes such as apoptosis and autophagy. Moreover, gallic acid has been investigated in the treatment of CVDs both in vivo and in vitro. Herein, we aimed to review the available evidence on the therapeutic application of gallic acid for CVDs including myocardial ischemia-reperfusion injury and infarction, drug-induced cardiotoxicity, hypertension, cardiac fibrosis, and heart failure, with a focus on underlying mechanisms.

Anticancer activity of thymoquinone against breast cancer cells: Mechanisms of action and delivery approaches.

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators.

Protective effects of curcumin and its analogues via the Nrf2 pathway in metabolic syndrome.

Metabolic Syndrome (MetS) refers to a set of medical conditions including insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension. Due to these dysregulations, if not treated, MetS could increase the risk of CVA, CVD, and diabetes. As described by WHO, CVD is the leading cause of mortality in the world which motivates researchers to investigate the management of its risk factors, especially MetS. It is reported that oxidative stress secondary to the abundant generation of free radicals oxygen species (ROS) and the ensuing altered redox status play an important role as a mediator in MetS. As a result, using new antioxidant agents with higher bioavailability has been proposed as an efficient treatment. Curcumin (a polyphenol of the diarylheptanoids class), which is used as a traditional medicine for various diseases including cardiovascular diseases and diabetes, is characterized by its antioxidant properties which, at least in part, are mediated via the activation of the Nrf2/ARE signaling pathway. Nrf2 is a transcription factor that plays a key role in regulating internal defense systems and increases antioxidant levels to decrease oxidative damage and cell apoptosis. Nrf2 expression and stability are enhanced by curcumin, leading to a higher rate of Nrf2 migration to the cell nucleus to regulate ARE gene expression, thus protecting cells against oxidative stress. In this article, we provide a comprehensive review of the molecular effect of curcumin and its derivatives via Nrf2 regulation in several conditions, such as diabetes, hypertension, dyslipidemia, and obesity.

Chrysin Effect Against Gastric Cancer: Focus on its Molecular Mechanisms.

Gastric cancer is one of the most prevalent cancers in the world. Various therapeutic modalities have been used for its treatment, but all exhibit severe side effects, establishing the need for novel approaches. Chrysin is a phytomedicine compound belonging to the flavonoid group. It is found in honey and many plants. Its antitumor effects have been documented against gastric cancer cell lines in vitro, establishing its effects are mediated via different pathways and the expression of miRNA. In this review, we summarize the available literature on chrysin and its effects on gastric cancer, focusing on the cellular mechanisms it targets.

The effects of Berberis vulgaris L. and Berberis aristata L. in metabolic syndrome patients: a systematic and meta-analysis study.

INTRODUCTION: This meta-analysis study assessed the effects of Berberis vulgaris L. and Berberis aristata L. in patients with metabolic syndrome. METHODS: Data were analysed through "random-effects meta-regression" performance. RESULTS: The findings indicated that LDL was 0.68 and 2.92 lower in the B. vulgaris L. and B. aristata L.-treated groups versus the controls. The HDL was 0.71-fold higher in the B. aristata L.-treated group versus the controls. The total-cholesterol levels were 1.02 and 2.25 folds lower in the B. vulgaris L. and B. aristata L.-treated groups versus the matched control groups. The triglyceride levels were 1.35 and 1.16-fold lower in the B. vulgaris L. and B. aristata L.-treated groups versus the controls. Glucose was 0.96 and 0.54 folds lower in the B. vulgaris L. and B. aristata L.-treated groups versus the control groups, respectively. CONCLUSION: B. vulgaris L. and B. aristata L. have beneficial effects in patients with metabolic syndrome.

Curcumin Combats against Organophosphate Pesticides Toxicity: A Review of the Current Evidence and Molecular Pathways.

Organophosphate compounds are regarded as a class of pesticides that are used in farming. Their extensive use, especially in developing countries, is a serious public health problem. Numerous studies have shown the effects of these toxins on various parts of the human and other vertebrates' bodies, including the cardiovascular, hepatobiliary, renal, and reproductive systems. Curcumin is a polyphenol compound obtained from the rhizome of the Curcuma longa. Curcumin has been known as a dietary spice, food additive, and traditional medicine since many years ago. In recent decades, the medicinal characteristics, clinical aspects, and biological activity of curcumin have been extensively examined. The most examined positive characteristics of curcumin are its anti- inflammatory and anti-oxidant qualities. This review will deal with the pharmacological properties of curcumin as well as an update of currently available studies in terms of curcumin's uses and function against organophosphate pesticides-induced toxicity on different human organs.

Protective effect of Sophora pachycarpa seed extract on carbon tetrachloride-induced toxicity in rats.

The aim of the present study was to investigate the protective effect of the Sophora pachycarpa (S. pachycarpa) seed extract against carbon tetrachloride-induced toxicity on body organs, blood, and biochemical factors. In this investigation, 40 male Wistar rats weighing 200-250 g were randomly divided into 5 groups: group I was used as control, group II received carbon tetrachloride (CCl4) (IP, 1 mL/kg) on day 21, group III and group IV received S. pachycarpa seed extract at doses of 150 mg/kg and 300 mg/kg, respectively for 21 days by oral gavage and CCl4 on day 21, group V received silymarin (300 mg/kg) for 21 days by oral gavage and CCl4 on day 21. CCl4 showed an increase of serum renal and hepatic markers creatinine, urea, blood urea nitrogen (BUN), and uric acid, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Also, it significantly increased MDA level, and decreased CAT, FRAP, GSH, and SOD in the liver and kidney tissues. These changes and also hematological and histopathological alterations were significantly ameliorated by S. pachycarpa seed extract before CCl4 administration. In conclusion, the data obtained in our investigation confirm the protective effect of S. pachycarpa against acute exposure to CCl4-induced organ toxicity in rats.

Metabolic impact of saffron and crocin: an updated systematic and meta-analysis of randomised clinical trials.

The present systematic and meta-analysis study was designed to show the protective impact of saffron and crocin supplementation on hyperlipidaemia and hyperglycaemia in randomised and clinical trials (RCTs). A pooled analysis using a model for random-effects showed that HDL-C levels were 0.21 fold higher in the saffron and 0.01 fold higher in the crocin group than placebo. LDL-C levels in the saffron group reduced by 0.51 and 0.04 fold in the crocin group versus the placebo. Moreover, TC levels in the saffron group were 0.19 lower and 0.11 fold lower in crocin group than in the placebo group. TG level in saffron group was 0.04 lower and 0.02 fold lower in crocin than the control group. The blood glucose levels did not significantly differ from the control group. This study suggests that saffron and crocin may modulate the serum lipid profile in patient with metabolic disorders.

Assessment of Iodofolic Supplementation on Thyroid Function in Pregnant Women with Iodine Sufficient Status and their Infants in Birjand.

BACKGROUND: Maintaining iodine at sufficient levels is necessary throughout the pregnancy to prevent adverse outcomes in infants. This study aimed to assess iodofolic supplementation's impact on thyroid function in women at the end of the third trimesters of gestation. METHODS: This case-control study was conducted on 130 pregnant women in the Birjand, east of Iran, during the period from August 2017 to February 2019. We assessed iodofolic supplementation effect in the women at the first trimesters of gestation and followed them at the end of the third trimesters and also their infants on days 3-5. Serum samples were obtained from women and infants for measuring levels of thyroid-stimulating hormone (TSH). Urinary iodine concentration (UIC) was also determined at the end of the third trimester. RESULTS: The median serum TSH concentration in the folic acid consumed group (3.26 ± 1.91) did not significantly differ from another group (2.98 ± 1.41), (p = 0.68). There is also no considerable difference in the mean serum TSH concentration between infants born from mothers who consumed folic acid in the first trimester of pregnancy and another group (p = 0.50). The TSH concentration in all infants was below 5 µM/L. The significant difference in the mean of UIC was also not observed between pregnant women in the folic acid consumed group (188.02 ± 105.38) and iodofolic consumed group (225.77 ± 130.26), (p = 0.13). CONCLUSION: Iodine intake in our study was sufficient according to the WHO recommendation and idofolic supplementation was not emphasized.

The Assessment of Some Metabolic Markers by Combination of Ursolic Acid Supplementation and Resistance Training in Young Older Obese Women.

BACKGROUND: In this study, we explored the impacts of moderate-to-high intensity resistance circuit training (MHRCT) and Ursolic acid (UA) supplementation to improve these pathological changes in young older obese women (women between the ages of 50 and 70). METHODS: The study included twenty-five young older women (age > 50 years and ≤70 years) with stage I-II obesity (BMI ≥ 30 and <40 kg/m2), who received eight weeks placebo with MHRCT, and MHRCT with UA supplementation. UA or placebo orally was ingested as a capsule three times per day for eight weeks. The following parameters were evaluated post- and pre-intervention. Data were analyzed using ANOVA with repeated measures. RESULTS: Interleukin-15 (IL-15), Interleukin-6 (IL-6), Insulin, and HOMA-IR decreased significantly in the placebo and UA groups versus control, but the UA group significantly decreased compared with the placebo (p<0.05). In turn, the Brain-Derived Neurotrophic Factor (BDNF) and Irisin levels showed a significant increase in the placebo and UA groups versus control. However, the BDNF in the UA group significantly increased compared with the placebo (p < 0.05). CONCLUSION: We demonstrated that applying resistance training can reverse the pathological changes that may occur with aging and a sedentary lifestyle. Our results showed that UA could enhance the effects of this type of exercise. Therefore, a combination of the resistance training program and UA supplementation may be considered as a novel and influential intervention to metabolic derangements and may also decrease the burden associated with this condition.

A systematic review of clinical and laboratory findings of lead poisoning: lessons from case reports.

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management.

An updated review on the versatile role of chrysin in neurological diseases: Chemistry, pharmacology, and drug delivery approaches.

Neurological diseases are responsible for a large number of morbidities and mortalities in the world. Flavonoids are phytochemicals that possess various health-promoting impacts. Chrysin, a natural flavonoid isolated from diverse fruits, vegetables, and even mushrooms, has several pharmacological activities comprising antioxidant, anti-inflammatory, antiapoptotic, anticancer, and neuroprotective effects. The current study was designed to review the relationship between chrysin administration and neurological complications by discussing the feasible mechanism and signaling pathways. Herein, we mentioned the sources, pharmacological properties, chemistry, and drug delivery systems associated with chrysin pharmacotherapy. The role of chrysin was discussed in depression, anxiety, neuroinflammation, Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, cerebral ischemia, spinal cord injury, neuropathy, Multiple Sclerosis, and Guillain-Barré Syndrome. The findings indicate that chrysin has protective effects against neurological conditions by modulating oxidative stress, inflammation, and apoptosis in animal models. However, more studies should be done to clear the neuroprotective effects of chrysin.

Nutraceuticals-based therapeutic approach: recent advances to combat pathogenesis of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanying memory deficits. The available pharmaceutical care has some limitations mostly entailing side effects, shelf-life, and patient's compliance. The momentous implications of nutraceuticals in AD have attracted scientists. Several preclinical studies for the investigation of nutraceuticals have been conducted.Areas covered: This review focuses on the potential use of a nutraceuticals-based therapeutic approach to treat and prevent AD. Increasing knowledge of AD pathogenesis has led to the discovery of new therapeutic targets including pathophysiological mechanisms and various cascades. Hence, the present contribution will attend to the most popular and effective nutraceuticals with proposed brief mechanisms entailing antioxidant, anti-inflammatory, autophagy regulation, mitochondrial homeostasis, and more. Therefore, even though the effectiveness of nutraceuticals cannot be dismissed, it is essential to do further high-quality randomized clinical trials.Expert opinion: According to the potential of nutraceuticals to combat AD as multi-target directed drugs, there is critical importance to assess them as feasible lead compounds for drug discovery and development. To the best of the authors' knowledge, modification of blood-brain barrier permeability, bioavailability, and features of randomized clinical trials should be considered in prospective studies.

Therapeutic Potential of Saffron (Crocus sativus L.) in Ischemia Stroke.

Stroke is the second leading cause of death and a main cause of disability worldwide. The majority (approximately 80%) of strokes are ischemic. Saffron (Crocus sativus L.) has been considered for medicinal purposes since ancient times. Pharmacological effects of saffron are attributed to the presence of crocin, crocetin, picrocrocin, and safranal. In the present review, we summarized the reported neuroprotective effects of saffron and its active constituents against cerebral ischemia stroke. Saffron and its components exert its beneficial effects as an antioxidant, anti-inflammatory, and antiapoptotic agent though inhibition of biochemical, inflammatory, and oxidative stress markers. Taken together, this review indicates that saffron and its ingredients could be a potent candidate in the process of new drug production for the treatment of ischemia stroke.

New insights into the role of the Nrf2 signaling pathway in green tea catechin applications.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional signaling pathway that plays a crucial role in numerous clinical complications. Pivotal roles of Nrf2 have been proved in cancer, autoimmune diseases, neurodegeneration, cardiovascular diseases, diabetes mellitus, renal injuries, respiratory conditions, gastrointestinal disturbances, and general disorders related to oxidative stress, inflammation, apoptosis, gelatinolysis, autophagy, and fibrogenesis processes. Green tea catechins as a rich source of phenolic compounds can deal with various clinical problems and manifestations. In this review, we attempted to focus on intervention between green tea catechins and Nrf2. Green tea catechins especially epigallocatechin gallate (EGCG) elucidated the protective role of Nrf2 and its downstream molecules in various disorders through Keap-1, HO-1, NQO-1, GPx, GCLc, GCLm, NF-kB cross-link, kinases, and apoptotic proteins. Subsequently, we compiled an updated expansions of the Nrf2 role as a gate to manage and protect different disorders and feasible indications of green tea catechins through this signaling pathway. The present review highlighted recent evidence-based data in silico, in vitro, and in vivo studies on an outline for future clinical trials.

Curcumin and cardiovascular diseases: Focus on cellular targets and cascades.

Cardiovascular diseases (CVDs) are one of the leading causes of the most considerable mortality globally, and it has been tried to find the molecular mechanisms and design new drugs that triggered the molecular target. Curcumin is the main ingredient of Curcuma longa (turmeric) that has been used in traditional medicine for treating several diseases for years. Numerous investigations have indicated the beneficial effect of Curcumin in modulating multiple signaling pathways involved in oxidative stress, inflammation, apoptosis, and proliferation. The cardiovascular protective effects of Curcumin against CVDs have been indicated in several studies. In the current review study, we provided novel information on Curcumin's protective effects against various CVDs and potential molecular signaling targets of Curcumin. Nonetheless, more studies should be performed to discover the exact molecular target of Curcumin against CVDs.

Biological and therapeutic activities of thymoquinone: Focus on the Nrf2 signaling pathway.

Thymoquinone is a monoterpenoid compound, which is derived from volatile and fixed oil of Nigella sativa (Ranunculaceae). This phytochemical compound has several biological effects, including antioxidant, antibacterial, antineoplastic, nephroprotective, hepatoprotective, gastroprotective, neuroprotective, anti-nociceptive, and anti-inflammatory activities. Thymoquinone shows pharmacological activities, including anti-hepatocellular carcinoma, nephroprotection, neuroprotection, retina protection, gastroprotection, cardioprotection, anti-allergy, reproductive system protection, bladder protection, and respiratory protection. It was found that these beneficial effects are mostly related to modulation of the Nrf2 signaling pathway by blockage of Keap1, stimulating the expression of the Nrf2 gene, and inducing the nuclear translocation of Nrf2. In the present review, the therapeutic effects of thymoquinone are overviewed through the Nrf2 signaling pathway.

Protective Effect of Resveratrol against Glioblastoma: A Review.

BACKGROUND: One of the most common tumors of the central nervous system is Glioblastoma (GBM). OBJECTIVE: There is not still an appropriate cure for this malignant tumor. Plant-derived natural products have demonstrated great potential in cancer therapy, and Resveratrol (Res) is among them. Therefore, the current study focused on the protective effect of resveratrol against glioblastoma and its underlying mechanism. METHODS: PubMed, Medline, Scopus, Web of Science, and Google Scholar were searched by using the following keywords: Resveratrol, Glioblastoma, Brain tumor, Cancer therapy, Medicinal herbs to July 2020. RESULTS: Res is a non-flavonoid polyphenol responsible for the protection of plants against pathogen attacks. Res has multiple pharmacological effects, including antioxidant, anti-inflammatory, anti-diabetic, and anti-tumor. Res is capable of penetration into the blood-brain barrier, making it suitable for brain tumor therapy. Besides, Res targets various molecular signaling pathways in cancer therapy. CONCLUSION: In the present review, it was found that Res administration is beneficial in GBM therapy by inhibition of proliferation, viability, and migration via modulation of molecular pathways.