Royal jelly and its hormonal effects in breast cancer: a literature review.

BACKGROUND: Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer. METHODS: Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included. RESULTS: According to the collected preclinical data, consumption of royal jelly at daily doses below 200 mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells. CONCLUSION: Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

Antioxidative and Anti-inflammatory Effects of Plant-derived Hypoglycemic Medicines: An In vivo/In vitro Systematic Review.

BACKGROUND: The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. OBJECTIVE: This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. METHODS: The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. RESULTS: Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1ß, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. CONCLUSION: Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

Petroselinum crispum (Mill.) Fuss (Parsley): An Updated Review of the Traditional Uses, Phytochemistry, and Pharmacology.

Petroselinum crispum (Mill.) Fuss (parsley) is a popular medicinal plant widely used in different traditional medicines all over the world. This paper provides an updated review on the traditional use, phytochemistry, and pharmacological activities of parsley. Parsley contains volatile compounds such as terpenes and terpenoids in the essential oil, as well as phenolic compounds in the plant extract. Parsley is traditionally used as a diuretic, liver and stomach tonic, and for urolithiasis and indigestion. Pharmacological investigations also confirm several biological activities of parsley including hepatoprotective, nephroprotective, antiurolithiatic, neuroprotective, cardioprotective, and antineoplastic effects in animal and cell-based studies. Parsley has currently demonstrated several pharmacological activities in preclinical studies; however, there is a big lack in clinical evidence. Considering parsley as a possible valuable medicinal food, future clinical trials are recommended to evaluate the clinical efficacy and safety of the plant in different health conditions.

Toll-like receptors in inflammatory bowel disease: A review of the role of phytochemicals.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation within the gastrointestinal tract with a remarkable impact on patients' quality of life. Toll-like receptors (TLR), as a key contributor of immune system in inflammation, has a critical role in the pathogenesis of IBD and thus, can be a suitable target of therapeutic agents. Medicinal plants have long been considered as a source of bioactive agents for different diseases, including IBD. PURPOSE: This review discusses current state of the art on the role of plant-derived compounds for the management of IBD with a focus on TLRs. METHODS: Electronic database including PubMed, Web of Science, and Scopus were searched up to January 2023 and all studies in which anticolitis effects of a phytochemical was assessed via modulation of TLRs were considered. RESULTS: Different categories of phytochemicals, including flavonoids, lignans, alkaloids, terpenes, saccharides, and saponins have demonstrated modulatory effects on TLR in different animal and cell models of bowel inflammation. Flavonoids were the most studied phytochemicals amongst others. Also, TLR4 was the most important type of TLRs which were modulated by phytochemicals. Other mechanisms such as inhibition of pro-inflammatory cytokines, nuclear factor-κB pathway, nitric oxide synthesis pathway, cyclooxygenase-2, lipid peroxidation, as well as induction of endogenous antioxidant defense mechanisms were also reported for phytochemicals in various IBD models. CONCLUSION: Taken together, a growing body of pre-clinical evidence support the efficacy of herbal compounds for the treatment of IBD via modulation of TLRs. Future clinical studies are recommended to assess the safety and efficacy of these compounds in human.

Citrus flavonoids and adhesion molecules: Potential role in the management of atherosclerosis.

Atherosclerosis as a chronic inflammatory disorder is accompanied with oxidative stress which causes a high morbidity and mortality. Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin, are amongst the most important contributors in atherosclerosis. In such cases, dietary interventions with functional foods containing natural antioxidant and anti-inflammatory constituents are of a great interest. Citrus fruits are rich sources of flavonoids as natural pigments with potent antioxidant and anti-inflammatory activities. This study aims to review current evidence regarding the role of citrus flavonoids in the management of atherosclerosis with a focus on their effect on adhesion molecules. Electronic databases including PubMed, Scopus, and Web of Science were searched with the names of adhesion molecules and flavonoids from inception until January 2023. The included articles highly support the beneficial effects of citrus flavonoids in preclinical models of atherosclerosis. Quercetin, naringin and naringenin, hesperidin and hesperetin, nobiletin, rutin, luteolin, apigenin, and kaempferol are the most common flavonoids in citrus fruits which could modulate adhesion molecules including ICAM-1, VCAM-1, E-selectin, and P-selectin. Additionally, markers of chronic inflammation such as interleukins, tumor necrosis factor-α, nuclear factor-κB, and nitric oxide signaling, as well as oxidative stress markers like superoxide dismutase and glutathione were all normalized upon administration of citrus flavonoids. Conclusively, this review confirms the modulatory role of flavonoids on adhesion molecules in atherosclerosis based on the preclinical evaluations. Thus, citrus fruits can be further studied in atherosclerotic patients regarding their activity in reducing adhesion molecules.

Effects of cinnamon oil and its main constituents, cinnamic acid and cinnamaldehyde, on 1 - methyl - 4 - phenyl - 1,2,3,6 - tetrahydropyridine - induced neurodegeneration in PC - 12 cells / Efectos del aceite de canela y sus principales componentes, ácido cinámico y cin amaldehído en la neurodegeneración inducida por 1 - metil - 4 - fenil - 1,2,3,6 - tetrahidropiridina en células PC 12

Cinnamon ( Cinnamomum verum J. Presl) is a well - known medicinal plant considered as an effective treatment for neurological disorders based on Persian medicine . The aim of the present study was assessing the effect of cinnamon oil, cinnamic acid, and cinnamaldehyde, on the in vitro model of Parkinson's disease (PD). Cinnamon oil, prepared in sesame oil, was phytochemically analyzed using high performance liquid chromatography (HPLC). Pheochromocytoma - 12 (PC - 12) cells were treated with 1 - methyl - 4 - phenyl - 1,2,3,6 - tetrahydropyridine (MPTP) as an in vitro model of neurodegeneration in PD. Cell viability, activity of caspase enzymes, and formation of reactive oxygen sp ecies (ROS) were evaluated. MPTP significantly decreased cell viability and increased Casp activity, as well as ROS formation. Cinnamon oil and cinnamic acid at 200 µg/m L could significantly reverse MPTP - induced abnormalities in PC - 12 cells including Casp activity and ROS formation. Our study supports the beneficial effect of cinnamon oil in neurodegeneration. Furt her investigations are needed to clarify the mechanisms and main active components.

La canela ( Cinnamomum verum J. Presl) es una planta medicinal m uy conocida, y considerada como un tratamiento efectivo para patologías neurológicas según la medicina persa. El objetivo de este estudio fue evaluar el efecto del aceite de canela, el ácido cinámico, y el cinamaldehído, en un modelo in vitro de la enferme dad de Parkinson (PD). El aceite de canela, preparado en aceite de sésamo, fue analizado fitoquímicamente usando cromatografía líquida de alta eficacia (HPLC). Se trataron células con feocromocitoma - 12 (P - 12) usando 1 - metil - 4 - fenil - 1,2,3,6 - tetrahidropiridi na (MPTP) como un modelo in vitro de neurodegeneración en PD. Se evaluó la viabilidad celular, actividad de enzimas caspasa, y formación de especies reactivas del oxígeno (ROS). El tratamiento con MPTP disminuyó significativamente la viabilidad celular y a umentó la actividad casp, así la formación de ROS. Aceite de canela y ácido cinámico a 200 µg/mL podría revertir significativamente las anormalidades inducidas por MPTP en células PC - 12, incluyendo la actividad casp y la formación de ROS. Nuestro estudio e ntrega sustento sobre los efectos benéficos del aceite de canela en la neurodegeneración. Se requiere más investigación para clarificar los mecanismos y los principales componentes activos.

Antioxidative hypoglycemic herbal medicines with in vivo and in vitro activity against C-reactive protein; a systematic review.

BACKGROUND: Inflammation is a double-edged sword in the pathophysiology of chronic diseases, such as type 2 diabetes mellitus (T2DM). The global rise in the prevalence of T2DM in one hand, and poor disease control with currently-available treatments on the other hand, along with an increased tendency towards the use of natural products make scientists seek herbal medicines for the management of diabetes and its complications by reducing C-reactive protein (CRP) as an inflammatory marker. PURPOSE: To systematically review the literature to identify the efficacy of various medicinal plants with antioxidative and anti-inflammatory properties considering their effect on CRP in animal models of T2DM. STUDY DESIGN: systematic review. METHODS: Electronic databases including PubMed, Scopus, Web of Science and Cochran Library were searched using the search terms "herbal medicine", "diabetes", "c-reactive protein", "antioxidants" till August 2021. The quality of evidence was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE's) tool. The study protocol was registered in PROSPERO with an ID number CRD42020207190. A manual search to detect any articles not found in the databases was also made. The identified studies were then critically reviewed and relevant data were extracted and summarized. RESULTS: Among total of 9904 primarily-retrieved articles, twenty-three experimental studies were finally included. Our data indicated that numerous herbal medicines, compared to placebo or hypoglycemic medications, are effective in treatment of diabetes and its complications through decreasing CRP concentrations and oxidative stresses levels. Medicinal plants including Psidium guajava L., Punica granatum L., Ginkgo biloba L., Punica granatum L., Dianthus superbusn L.. Moreover, Eichhornia crassipes (Mart.) Solms, Curcuma longa L., Azadirachta indica A. Juss., Morus alba L., and Ficus racemosa L. demonstrated potential neuroprotective effects in animal models of diabetes. CONCLUSION: Hypoglycemic medicinal plants discussed in this review seem to be promising regulators of CRP, and oxidative stress. Thus, these plants are suitable candidates for management of diabetes' complications. Nevertheless, further high-quality in vivo studies and clinical trials are required to confirm these effects.

Endoplasmic reticulum as a therapeutic target in type 2 diabetes: Role of phytochemicals.

Type 2 diabetes mellitus (T2DM) is a metabolic disorders characterized by insulin resistance and ß-cell dysfunction with an increasing worldwide incidence. Several studies have revealed that long-term glucotoxicity results in ß-cell failure and death through induction of endoplasmic reticulum (ER) stress. Owing to the chronic progression of T2DM and the low effectiveness of antidiabetic drugs in long-term use, medicinal plants and their secondary metabolites seem to be the promising alternatives. Here we have provided a comprehensive review regarding the role of phytochemicals to alleviate ER stress in T2DM. Ginsenoside compound K, baicalein, quercetin, isopulegol, kaempferol, liquiritigenin, aspalathin, and tyrosol have demonstrated remarkable improvement of T2DM via modulation of ER stress. Arctigenin and total glycosides of peony have been shown to be effective in the treatment of diabetic retinopathy through modulation of ER stress. The effectiveness of grape seed proanthocyanidins and wolfberry is also shown in the relief of diabetic neuropathy and retinopathy. Resveratrol is involved in the prevention of atherosclerosis via ER stress modulation. Taken together, the data described herein revealed the capability of herbal constituents to prevent different complications of T2DM via a decrease in ER stress which open new doors to the treatment of diabetes.

Apigenin and its dermatological applications: A comprehensive review.

Apigenin is one of the abundant flavonoids in fruits and vegetables of human diet with several demonstrated health benefits. The aim of the present study is to provide an overview of the current evidence regarding the effect of apigenin on different dermatological complications. Electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve all papers assessing the dermatological effects of apigenin. Preclinical studies support beneficial effects of apigenin on UV-induced skin damage, vitiligo, dermatitis, wounds, skin aging, and some types of skin cancer. The compound mostly acts via inhibition of inflammation through suppression of pro-inflammatory cytokines and intracellular inflammatory mediators, as well as antioxidant properties such as improvement of endogenous antioxidant defense mechanisms. There are also some studies for the design and development of novel drug delivery systems for apigenin to improve its oral and topical bioavailability. Nevertheless, no clinical study has evaluated apigenin as a natural supplement for skin conditions. Considering the benefits of apigenin in preclinical models of dermatological disorders, as well as the acceptable safety of this compound, apigenin may be a future candidate to be used in dermatological disorders. Future clinical studies are needed to further confirm the safety and efficacy of apigenin in skin care products.

Phytochemical and toxicological evaluation of Tamarix stricta Boiss.

The genus Tamarix includes several plant species well-known for their medicinal properties since ancient times. Tamarix stricta Boiss is a plant native to Iran which has not been previously investigated regarding its phytochemical and biological properties. This study assessed phytochemical and toxicological aspects of T. stricta. The plant was collected from Kerman province of Iran and after authentication by botanist, it was extracted with 70% ethanol. Total phenolic compounds, total flavonoids, and antioxidant properties were measured using spectrophometric methods. Quercetin content of the extract was measured after complete acid hydrolysis with high-performance liquid chromatography. The phytochemical profile of the extract was provided using liquid chromatography-mass spectrometry method. Acute toxicity study with a single intragastric dose of 5000 mg/kg of the extract and sub-chronic toxicity using 50, 100, and 250 mg/kg of the extract was assessed in Wistar rats. Phytochemical analysis showed that polyphenols constitute the major components of the extract. Also, the extract contained 1.552 ± 0.35 mg/g of quercetin. Biochemical, hematological, and histological evaluations showed no sign of toxicity in animals. Our experiment showed that T. stricta is a rich source of polyphenols and can be a safe medicinal plant. Further pharmacological evaluations are recommended to assess the therapeutic properties of this plant.

Bioactive Foods and Medicinal Plants for Cardiovascular Complications of Type II Diabetes: Current Clinical Evidence and Future Perspectives.

Cardiovascular diseases (CVDs) are the main cause of mortality in type 2 diabetes mellitus (T2DM); however, not all patients are fully satisfied with the current available treatments. Medicinal plants have been globally investigated regarding their effect in CVD, yet the field is far from getting exhausted. The current paper aims to provide an evidence-based review on the clinically evaluated medicinal plants and their main therapeutic targets for the management of CVD in T2DM. Electronic databases including PubMed, Cochrane, Embase, Scopus, and Web of Science were searched from 2000 until November 2019, and related clinical studies were included. Lipid metabolism, glycemic status, systemic inflammation, blood pressure, endothelial function, oxidative stress, and anthropometric parameters are the key points regulated by medicinal plants in T2DM. Anti-inflammatory and antioxidant properties are the two most important mechanisms since inflammation and oxidative stress are the first steps triggering a domino of molecular pathological pathways leading to T2DM and, subsequently, CVD. Polyphenols with potent antioxidant and anti-inflammatory effects, essential oil-derived compounds with vasorelaxant properties, and fibers with demonstrated effects on obesity are the main categories of phytochemicals beneficial for CVD of T2DM. Some medicinal plants such as garlic (Allium sativum) and milk thistle (Silybum marianum) have strong evidences regarding their beneficial effects; however, others have low level of evidence which reveals the need for further clinical studies with larger sample sizes and longer follow-up periods to confirm the safety and efficacy of medicinal plants for the management of CVD in T2DM.

Medicinal Plants as Efficacious Agents for Diabetic Foot Ulcers: A Systematic Review of Clinical Studies.

A diabetic foot ulcer (DFU) is a chronic, nonhealing wound that occurs in approximately 15% to 25% of patients with diabetes, and amputation is necessary in approximately 5% to 24% of these patients. Medicinal plants have demonstrated promising wound healing activities in animal models of DFUs as well as in clinical studies. These plants, which are described as medicinal in different regions of the world, are not considered to be standard medicinal treatments in Western medicine at this time. Some medicinal products, such as bromelain-an herbal protease currently used for enzymatic debridement of wounds-have been obtained from plants, showing the important role of these natural products as sources of wound healing agents. This paper aims to review clinical studies on the effects of medicinal plants in patients with DFUs based on the improvement of local and systemic parameters related to wound healing. Electronic databases including PubMed, Scopus, and Cochrane Library were searched for studies from inception through May 2019 using the keywords "diabetic foot ulcer" and "plant," "phytochemical," "extract," or "herb." Inclusion criteria were controlled or before-after clinical studies with English-language full-text in which topical or systemic herbal preparations for DFUs were evaluated by considering outcomes such as reduction of wound healing time and wound area, markers of inflammation and oxidative stress, and number of cases requiring amputation. Studies on non-herbal materials and human studies other than clinical trials were excluded. Fourteen studies were included in the present review. Herbal medicines were administered as add-on therapy to standard wound care in the form of topical (cream, gel, oil) or systemic (capsule, decoction, injection) preparations. Parameters such as ulcer width and depth, phagocytic function, tumor necrosis factor α level, epithelialization, vascularization, and wound closure were evaluated in clinical trials, several of which were significantly improved in patients compared with their baseline values or control group. Per the studies included in this review, medicinal plants can be recommended as promising adjuvant therapies to conventional wound care to accelerate wound healing in patients with DFUs.

Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review.

A newly diagnosed coronavirus in 2019 (COVID-19) has affected all human activities since its discovery. Flavonoids commonly found in the human diet have attracted a lot of attention due to their remarkable biological activities. This paper provides a comprehensive review of the benefits of flavonoids in COVID-19 disease. Previously-reported effects of flavonoids on five RNA viruses with similar clinical manifestations and/or pharmacological treatments, including influenza, human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, were considered. Flavonoids act via direct antiviral properties, where they inhibit different stages of the virus infective cycle and indirect effects when they modulate host responses to viral infection and subsequent complications. Flavonoids have shown antiviral activity via inhibition of viral protease, RNA polymerase, and mRNA, virus replication, and infectivity. The compounds were also effective for the regulation of interferons, pro-inflammatory cytokines, and sub-cellular inflammatory pathways such as nuclear factor-κB and Jun N-terminal kinases. Baicalin, quercetin and its derivatives, hesperidin, and catechins are the most studied flavonoids in this regard. In conclusion, dietary flavonoids are promising treatment options against COVID-19 infection; however, future investigations are recommended to assess the antiviral properties of these compounds on this disease.

In vitro and in vivo antidiabetic activity of Tamarix stricta Boiss.: Role of autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Type 2 diabetes mellitus (DM) is a complicated metabolic disorder with no definite treatment. Different species of the genus Tamarix (tamarisk) are used by local people to treat DM. Tamarix stricta Boiss. is an endemic species to Iran with several traditional therapeutic uses in Persian Medicine. This study aimed to assess the antidiabetic activity of T. stricta. MATERIALS AND METHODS: Hydroethanolic extract of the plant was prepared and analyzed by High-performance liquid chromatography (HPLC). The protective effect of the extract was evaluated in streptozotocin (STZ)-induced toxicity and markers of autophagy in pancreatic RIN-5F cells. The effect of intragastric 10 or 20 mg/kg of the extract was compared with negative control (water) or positive control (metformin) treatment during four weeks of administration in high-fat diet + STZ-induced DM in Balb/c mice. RESULTS: Results showed the presence of 8.436 mg of gallic acid in each gram of the extract. A significant cytoprotective effect was observed by T. stricta in STZ-induced toxicity in RIN-5F cells, partially due to the modulation of autophagy. Also, animals treated with the extract showed a significant improvement in glycemic and lipid profiles, liver function, and histopathologic features of pancreas and liver compared with the negative control. CONCLUSION: T. stricta demonstrated beneficial effects in animal model of DM; though, further studies are recommended to confirm the clinical use of this plant in DM.

Hot and Cold Theory: Evidence in Pharmacology.

Traditional and folk medicine from different countries are valuable sources of new ideas to design novel natural products for health and diseases. In this field, the classification of medicinal plants and other natural medicinal materials into hot or cold categories is a common concept within different doctrines of complementary and alternative medicine such as Persian medicine, traditional Chinese medicine, and Indian medicine. Today, a growing body of evidence is being provided to support different pathophysiologic bases of this categorization, as well as the pharmacological targets affected by natural products from each of the two categories. Different body systems such as endocrine and nervous systems are influenced by the hot/cold materials, some of which have been studied in animals or humans. This chapter focuses on the pharmacological evidence supporting the hot/cold nature of medicinal plants.

An Evaluation of Traditional Persian Medicine for the Management of SARS-CoV-2.

A new coronavirus causing severe acute respiratory syndrome (SARS-CoV-2) has emerged and with it, a global investigation of new antiviral treatments and supportive care for organ failure due to this life-threatening viral infection. Traditional Persian Medicine (TPM) is one of the most ancient medical doctrines mostly known with the manuscripts of Avicenna and Rhazes. In this paper, we first introduce a series of medicinal plants that would potentially be beneficial in treating SARS-CoV-2 infection according to TPM textbooks. Then, we review medicinal plants based on the pharmacological studies obtained from electronic databases and discuss their mechanism of action in SARS-CoV-2 infection. There are several medicinal plants in TPM with cardiotonic, kidney tonic, and pulmonary tonic activities, protecting the lung, heart, and kidney, the three main vulnerable organs in SARS-CoV-2 infection. Some medicinal plants can prevent "humor infection", a situation described in TPM which has similar features to SARS-CoV-2 infection. Pharmacological evaluations are in line with the therapeutic activities of several plants mentioned in TPM, mostly through antiviral, cytoprotective, anti-inflammatory, antioxidant, and anti-apoptotic mechanisms. Amongst the primarily-introduced medicinal plants from TPM, rhubarb, licorice, garlic, saffron, galangal, and clove are the most studied plants and represent candidates for clinical studies. The antiviral compounds isolated from these plants provide novel molecular structures to design new semisynthetic antiviral agents. Future clinical studies in healthy volunteers as well as patients suffering from pulmonary infections are necessary to confirm the safety and efficacy of these plants as complementary and integrative interventions in SARS-CoV-2 infection.

Nanophytomedicines for the Prevention of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review.

Metabolic syndrome includes a series of metabolic abnormalities that leads to diabetes mellitus and cardiovascular diseases. Plant extracts, due to their unique advantages like anti-inflammatory, antioxidant, and insulin sensitizing properties, are interesting therapeutic options to manage MetS; however, the poor solubility and low bioavailability of lipophilic bioactive components in the herbal extracts are two critical challenges. Nano-scale delivery systems are suitable to improve delivery of herbal extracts. This review, for the first time, focuses on nanoformulations of herbal extracts in MetS and related complications. Included studies showed that several forms of nano drug delivery systems such as nanoemulsions, solid lipid nanoparticles, nanobiocomposites, and green-synthesized silver, gold, and zinc oxide nanoparticles have been developed using herbal extracts. It was shown that the method of preparation and related parameters such as temperature and type of polymer are important factors affecting physicochemical stability and therapeutic activity of the final product. Many of these formulations could successfully decrease the lipid profile, inflammation, oxidative damage, and insulin resistance in in vitro and in vivo models of MetS-related complications. Further studies are still needed to confirm the safety and efficacy of these novel herbal formulations for clinical application.

Plant-derived natural agents as dietary supplements for the regulation of glycosylated hemoglobin: A review of clinical trials.

BACKGROUND & AIMS: Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting a growing number of patients all over the world. T2DM complications are positively associated with HbA1c which is a long-term glycemic marker. Medicinal plants and their isolated phytochemicals have been extensively used as dietary supplements for the management of chronic disorders including T2DM. Current paper aims to review clinical trials evaluated the effect of phytochemicals for long-term management of T2DM considering the HbA1c level. METHODS: Electronic databases including PubMed, Scopus and Cochrane were searched using the keywords "phytochemical", "extract", "herb", or "plant" and "HbA1c" or "glycosylated hemoglobin" in the title/abstract from the date of inception until May 2017. English and Persian language papers were included. References of the retrieved papers were also screened for relevant studies. RESULTS: Of 2435 studies, 39 relevant clinical trials were finally included in which phytochemicals including berberine, curcumin, catechin, silymarin, resveratrol, pycnogenol, isoflavones, lignans, isohumulone, saponins, corn bran hemicellulose and pinitol were examined. Berberine and silymarin had the strongest evidence regarding their effectiveness in long-term management of HbA1c; however, lack of enough toxicological studies suggests to stay on the safe side for the administration of these agents in diabetic patients. CONCLUSIONS: Current data regarding the efficacy of other phytochemicals are still controversial due to small follow-up period, methodological problems and small sample size. Future well-designed clinical trials are necessary to confirm the safety and efficacy of phytochemicals for long-term glycemic control of diabetic patients.

The genus Tamarix: Traditional uses, phytochemistry, and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Tamarix L., with the common name of tamarisk, consists of more than 60 species of halophyte plants which are used for medicinal purposes such as infections, wounds, and liver and spleen disorders by local people mostly in Asian and African countries. AIM OF THE REVIEW: In spite of the potential health benefits of Tamarix spp., the plant is not yet well-known in modern medicine; thus, the aim of the present review is to provide a critical appraisal of the current state of the art regarding the ethnomedicinal uses, phytochemistry, and pharmacological properties of Tamarix spp. MATERIALS AND METHODS: Electronic databases (Medline, Cochrane library, Science Direct, and Scopus) were searched with the words "Tamarix" and "Tamarisk" to collect all available data regarding different Tamarix species from the inception until May 2019. RESULTS: Tamarix spp. is traditionally used for gastrointestinal disorders, wounds, diabetes, and dental problems. Phenolic acids, flavonoids, and tannins constitute the main phytochemicals of these plants. Preclinical pharmacological evaluations have demonstrated several biological activities for Tamarix spp. including antidiabetic, hepatoprotective, wound healing, and anti-inflammatory; however, no clinical evidence have yet been provided to support the health benefits of these plants. CONCLUSIONS: Tamarix spp. are plants rich in polyphenolic compounds with valuable medicinal properties; though, there are several methodological problems such as lack of a mechanistic approach and taxonomic ambiguities in the current available data. High-quality preclinical studies, as well as well-designed clinical trials are necessary to confirm the safety and efficacy of these plants in humans.

Advances on Natural Polyphenols as Anticancer Agents for Skin Cancer.

Polyphenols are one of most important phytochemicals distributing in herb plants, vegetables and fruits, which known as important anticancer agents. Given the high incidence and mortality of skin cancer, this study aimed to uncover the chemopreventive effects of polyphenols against skin cancer metastasis. Electronic databases including Scopus, PubMed, and Cochrane library were used to compile the literature from 2000 to August 2019. Only in vivo mechanistic studies with English full-texts were chosen for this review. Polyphenols were included in this study if they were administered in purified form; while total extract and fractions were excluded. Among the 8254 primarily selected papers, only a final number of 34 studies were included. The chemopreventive effects of polyphenols as anthocyanins, ellagitanins, EGCG, oleuropeindihydroxy phenyl, punicalagin, quercetin, resveratrol and theaflavin, were mainly examined in treatment of melanoma as the highly metastatic form of this cutaneous cancer. Those properties are mediated by modulation of angiogenesis, apoptosis, inflammation, metastasis, proliferation, pathways such as EGFR/MAPK, mTOR/PI3K/Akt, JAK/STAT, FAK/RTK2, PGE-2/VEGF, PGE-1/ERK/HIIF-1α, and modulation of related signals including NF-κB, P21WAF/CIP1, Bim, Bax, Bcl2, Bclx, Bim, Puma, Noxa, ILs and MMPs. Chemopreventive effects of polyphenols are mediated by several signaling pathways against skin carcinogenesis and metastasis, implying the importance of polyphenols to open up new horizons in development of anti-skin cancer therapeutic strategies.