Curcumin in treatment of hematological cancers: Promises and challenges.

Hematological cancers include leukemia, myeloma and lymphoma and up to 178.000 new cases are diagnosed with these tumors each year. Different kinds of treatment including radiotherapy, chemotherapy, immunotherapy and stem cell transplantation have been employed in the therapy of hematological cancers. However, they are still causing death among patients. On the other hand, curcumin as an anti-cancer agent for the suppression of human cancers has been introduced. The treatment of hematological cancers using curcumin has been followed. Curcumin diminishes viability and survival rate of leukemia, myeloma and lymphoma cells. Curcumin stimulates apoptosis and G2/M arrest to impair progression of tumor. Curcumin decreases levels of matrix metalloproteinases in suppressing cancer metastasis. A number of downstream targets including VEGF, Akt and STAT3 undergo suppression by curcumin in suppressing progression of hematological cancers. Curcumin stimulates DNA damage and reduces resistance of cancer cells to irradiation. Furthermore, curcumin causes drug sensitivity of hematological tumors, especially myeloma. For targeted delivery of curcumin and improving its pharmacokinetic and anti-cancer features, nanostructures containing curcumin and other anti-cancer agents have been developed.

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.

The protective impact of curcumin, vitamin D and E along with manganese oxide and Iron (III) oxide nanoparticles in rats with scrotal hyperthermia: Role of apoptotic genes, miRNA and circRNA.

BACKGROUND: Infertility is one of the major factors affecting most people around the world. Short-term exposure to high temperatures can cause hyperthermia, which is one of the causes of male infertility. The aim of this study was to investigate the protective effect of curcumin, vitamins D and E along with Iron (III) oxide nanoparticles (Fe2O3-NPs) and manganese oxide nanoparticles (MnO2-NPs) on semen parameters and its effect on miRNA21 and circRNA0001518 expression. MATERIAL AND METHODS: In this study, the lower part of the rat was exposed to 43 °C for 5 weeks every other day for 5 weeks. Then the animals were killed. Tissue samples were collected for sperm parameters analysis, and tissue samples were taken for evaluation of apoptosis levels in germ cells, and RNA extraction in order to examine the expression of Bax, Bcl-2, miRNA, and CircRNA genes. RESULTS: The results of this study showed that administration of curcumin, vitamin D, and vitamin E with Fe2O3-NPs and MnO2-NPs can improve the parameters of semen, Bax gene expression, Bcl-2 as well as miRNA and CircRNA in rats with testicular hyperthermia. In addition, curcumin by reducing the toxicity of Fe2O3 nanoparticles was able to reduce its negative effects and also reduce apoptosis in germ cells. This decrease in apoptosis was attributed to decreased Bcl-2 gene expression and increased expression of Bax, miRNA-21, and circRNA0001518. CONCLUSION: All the results of this study confirmed that Fe2O3-NPs and Mno2-NPs containing antioxidants or vitamins are useful in improving fertility in rats due to scrotal hyperthermia. Although Fe2O3-NPs and Mno2-NPs containing both antioxidants and vitamins had a greater effect on improving fertility and reducing the toxic effects of nanoparticles.

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.

Wnt/ß-catenin Signaling in Lung Cancer: Association with Proliferation, Metastasis, and Therapy Resistance.

The capacity of cancer cells for abnormal growth and metastasis has made it difficult to find a cure for tumor. Both males and females suffer from lung tumors, and physicians still deem them incurable. The initiation and development of lung tumors can be forced by genomic mutations. Wnt is a critical pathway for regulating growth, differentiation and migration. However, its oncogenic function has been observed in lung cancer. Wnt is able to increase the proliferation of lung tumors. The metastasis potential of lung tumors can be accelerated by Wnt/EMT axis. Overexpression of Wnt/ß-catenin prevents chemotherapy-mediated cell death in lung tumors. This pathway promotes cancer stem cell features in lung tumors which induce radioresistance. Anti-cancer agents, such as curcumin, are able to inhibit Wnt in lung tumor treatment. Wnt interaction with other factors in lung tumors is essential in controlling biological behavior, and non-coding RNA transcripts are the most well-known ones. It can be concluded from the current study that Wnt is an important regulator of lung tumorigenesis, and the translation of these findings into the clinic is vital.

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.

Targeting Nrf2 in ischemia-reperfusion alleviation: From signaling networks to therapeutic targeting.

The nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of redox balance and it responds to various cell stresses that oxidative stress is the most well-known one. The Nrf2 should undergo nuclear translocation to exert its protective impacts and decrease ROS production. On the other hand, ischemic/reperfusion (I/R) injury is a pathological event resulting from low blood flow to an organ and followed by reperfusion. The I/R induces cell injury and organ dysfunction. The present review focuses on Nrf2 function in alleviation of I/R injury. Stimulating of Nrf2 signaling ameliorates I/R injury in various organs including lung, liver, brain, testis and heart. The Nrf2 enhances activity of antioxidant enzymes to reduce ROS production and prevent oxidative stress-mediated cell death. Besides, Nrf2 reduces inflammation via decreasing levels of pro-inflammatory factors including IL-6, IL-1ß and TNF-α. Nrf2 signaling is beneficial in preventing apoptosis and increasing cell viability. Nrf2 induces autophagy to prevent apoptosis during I/R injury. Furthermore, it can interact with other molecular pathways including PI3K/Akt, NF-κB, miRNAs, lncRNAs and GSK-3ß among others, to ameliorate I/R injury. The therapeutic agents, most of them are phytochemicals such as resveratrol, berberine and curcumin, induce Nrf2 signaling in I/R injury alleviation.

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.

Gallic acid for cancer therapy: Molecular mechanisms and boosting efficacy by nanoscopical delivery.

Cancer is the second leading cause of death worldwide. Majority of recent research efforts in the field aim to address why cancer resistance to therapy develops and how to overcome or prevent it. In line with this, novel anti-cancer compounds are desperately needed for chemoresistant cancer cells. Phytochemicals, in view of their pharmacological activities and capacity to target various molecular pathways, are of great interest in the development of therapeutics against cancer. Plant-derived-natural products have poor bioavailability which restricts their anti-tumor activity. Gallic acid (GA) is a phenolic acid exclusively found in natural sources such as gallnut, sumac, tea leaves, and oak bark. In this review, we report on the most recent research related to anti-tumor activities of GA in various cancers with a focus on its underlying molecular mechanisms and cellular pathwaysthat that lead to apoptosis and migration of cancer cells. GA down-regulates the expression of molecular pathways involved in cancer progression such as PI3K/Akt. The co-administration of GA with chemotherapeutic agents shows improvements in suppressing cancer malignancy. Various nano-vehicles such as organic- and inorganic nano-materials have been developed for targeted delivery of GA at the tumor site. Here, we suggest that nano-vehicles improve GA bioavailability and its ability for tumor suppression.

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.

Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer.

As a phenolic acid compound, caffeic acid (CA) can be isolated from different sources such as tea, wine and coffee. Caffeic acid phenethyl ester (CAPE) is naturally occurring derivative of CA isolated from propolis. This medicinal plant is well-known due to its significant therapeutic impact including its effectiveness as hepatoprotective, neuroprotective and anti-diabetic agent. Among them, anti-tumor activity of CA has attracted much attention, and this potential has been confirmed both in vitro and in vivo. CA can induce apoptosis in cancer cells via enhancing ROS levels and impairing mitochondrial function. Molecular pathways such as PI3K/Akt and AMPK with role in cancer progression, are affected by CA and its derivatives in cancer therapy. CA is advantageous in reducing aggressive behavior of tumors via suppressing metastasis by inhibiting epithelial-to-mesenchymal transition mechanism. Noteworthy, CA and CAPE can promote response of cancer cells to chemotherapy, and sensitize them to chemotherapy-mediated cell death. In order to improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid and p-coumaric acid. Due to its poor bioavailability, nanocarriers have been developed for enhancing its ability in cancer suppression. These issues have been discussed in the present review with a focus on molecular pathways to pave the way for rapid translation of CA for clinical use.

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.