Photodynamic therapy for leishmaniasis: Recent advances and future trends.

Leishmaniasis has infected more than 12 million people worldwide. This neglected tropical disease, causing 20,000-30,000 deaths per year, is a global health problem. The emergence of resistant parasites and serious side effects of conventional therapies has led to the search for less toxic and non-invasive alternative treatments. Photodynamic therapy is a promising therapeutic strategy to produce reactive oxygen species for the treatment of leishmaniasis. In this regard, natural and synthetic photosensitizers such as curcumin, hypericin, 5-aminolevulinic acid, phthalocyanines, phenothiazines, porphyrins, chlorins and nanoparticles have been applied. In this review, the recent advances on using photodynamic therapy for treating Leishmania species have been reviewed.

Evaluation of Bacillus velezensis for Biological Control of Rhizoctonia solani in Bean by Alginate/Gelatin Encapsulation Supplemented with Nanoparticles.

Plant growth promoting rhizobacteria (PGPR) are a group of bacteria that can increase plant growth; but due to unfavorable environmental conditions, PGPR are biologically unstable and their survival rates in soil are limited. Therefore, the suitable application of PGPR as a plant growth stimulation is one of the significant challenges in agriculture. This study presents an intelligent formulation based on Bacillus velezensis VRU1 encapsulation enriched with nanoparticles that was able to control Rhizoctonia solani on the bean. The spherical structure of the capsule was observed based on the Scanning Electron Microscope image. Results indicated that with increasing gelatin concentration, the swelling ratio and moisture content were increased; and since the highest encapsulation efficiency and bacterial release were observed at a gelatin concentration of 1.5%, this concentration was considered in mixture with alginate for encapsulation. The application of this formulation which is based on encapsulation and nanotechnology appears to be a promising technique to deliver PGPR in soil and is more effective for plants.

Antidiabetic Properties of Curcumin: Insights on New Mechanisms.

Plant extracts have been used to treat a wide range of human diseases. Curcumin, a bioactive polyphenol derived from Curcuma longa L., exhibits therapeutic effects against diabetes while only negligible adverse effects have been observed. Antioxidant and anti-inflammatory properties of curcumin are the main and well-recognized pharmacological effects that might explain its antidiabetic effects. Additionally, curcumin may regulate novel signaling molecules and enzymes involved in the pathophysiology of diabetes, including glucagon-like peptide-1, dipeptidyl peptidase-4, glucose transporters, alpha-glycosidase, alpha-amylase, and peroxisome proliferator-activated receptor gamma (PPARγ). Recent findings from in vitro and in vivo studies on novel signaling pathways involved in the potential beneficial effects of curcumin for the treatment of diabetes are discussed in this review.

Paving the Road Toward Exploiting the Therapeutic Effects of Ginsenosides: An Emphasis on Autophagy and Endoplasmic Reticulum Stress.

Programmed cell death processes such as apoptosis and autophagy strongly contribute to the onset and progression of cancer. Along with these lines, modulation of cell death mechanisms to combat cancer cells and elimination of resistance to apoptosis is of great interest. It appears that modulation of autophagy and endoplasmic reticulum (ER) stress with specific agents would be beneficial in the treatment of several disorders. Interestingly, it has been suggested that herbal natural products may be suitable candidates for the modulation of these processes due to few side effects and significant therapeutic potential. Ginsenosides are derivatives of ginseng and exert modulatory effects on the molecular mechanisms associated with autophagy and ER stress. Ginsenosides act as smart phytochemicals that confer their effects by up-regulating ATG proteins and converting LC3-I to -II, which results in maturation of autophagosomes. Not only do ginsenosides promote autophagy but they also possess protective and therapeutic properties due to their capacity to modulate ER stress and up- and down-regulate and/or dephosphorylate UPR transducers such as IRE1, PERK, and ATF6. Thus, it would appear that ginsenosides are promising agents to potentially restore tissue malfunction and possibly eliminate cancer.

Biological and Therapeutic Effects of Troxerutin: Molecular Signaling Pathways Come into View.

Flavonoids consist a wide range of naturally occurring compounds which are exclusively found in different fruits and vegetables. These medicinal herbs have a number of favourable biological and therapeutic activities such as antioxidant, neuroprotective, renoprotective, anti-inflammatory, anti-diabetic and anti-tumor. Troxerutin, also known as vitamin P4, is a naturally occurring flavonoid which is isolated from tea, coffee and cereal grains as well as vegetables. It has a variety of valuable pharmacological and therapeutic activities including antioxidant, anti-inflammatory, anti-diabetic and anti-tumor. These pharmacological impacts have been demonstrated in in vitro and in vivo studies. Also, clinical trials have revealed the efficacy of troxerutin for management of phlebocholosis and hemorrhoidal diseases. In the present review, we focus on the therapeutic effects and biological activities of troxerutin as well as its molecular signaling pathways.

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.

Progress in Natural Compounds/siRNA Co-delivery Employing Nanovehicles for Cancer Therapy.

Chemotherapy using natural compounds, such as resveratrol, curcumin, paclitaxel, docetaxel, etoposide, doxorubicin, and camptothecin, is of importance in cancer therapy because of the outstanding therapeutic activity and multitargeting capability of these compounds. However, poor solubility and bioavailability of natural compounds have limited their efficacy in cancer therapy. To circumvent this hurdle, nanocarriers have been designed to improve the antitumor activity of the aforementioned compounds. Nevertheless, cancer treatment is still a challenge, demanding novel strategies. It is well-known that a combination of natural products and gene therapy is advantageous over monotherapy. Delivery of multiple therapeutic agents/small interfering RNA (siRNA) as a potent gene-editing tool in cancer therapy can maximize the synergistic effects against tumor cells. In the present review, co-delivery of natural compounds/siRNA using nanovehicles are highlighted to provide a backdrop for future research.

Berberine Administration in Treatment of Colitis: A Review.

Berberine (Brb) is one of the well-known naturally occurring compounds exclusively found in Berberis vulgaris and other members of this family, such as Berberis aristata, Berberis aroatica, and Berberis aquifolium. This plant-derived natural compound has a variety of therapeutic impacts, including anti-oxidant, anti-inflammatory, anti-diabetic, and anti-tumor. Multiple studies have demonstrated that Brb has great anti-inflammatory activity and is capable of reducing the levels of proinflammatory cytokines, while it enhances the concentrations of anti-inflammatory cytokines, making it suitable for the treatment of inflammatory disorders. Colitis is an inflammatory bowel disease with chronic nature. Several factors are involved in the development of colitis and it appears that inflammation and oxidative stress are the most important ones. With respect to the anti-inflammatory and antioxidant effects of Brb, its administration seems to be beneficial in the treatment of colitis. In the present review, the protective effects of Brb in colitis treatment and its impact on molecular pathways are discussed.

Resveratrol targeting tau proteins, amyloid-beta aggregations, and their adverse effects: An updated review.

Resveratrol (Res) is a non-flavonoid compound with pharmacological actions such as antioxidant, antiinflammatory, hepatoprotective, antidiabetes, and antitumor. This plant-derived chemical has a long history usage in treatment of diseases. The excellent therapeutic impacts of Res and its capability in penetration into blood-brain barrier have made it an appropriate candidate in the treatment of neurological disorders (NDs). Tau protein aggregations and amyloid-beta (Aß) deposits are responsible for the induction of NDs. A variety of studies have elucidated the role of these aggregations in NDs and the underlying molecular pathways in their development. In the present review, based on the recently published articles, we describe that how Res administration could inhibit amyloidogenic pathway and stimulate processes such as autophagy to degrade Aß aggregations. Besides, we demonstrate that Res supplementation is beneficial in dephosphorylation of tau proteins and suppressing their aggregations. Then, we discuss molecular pathways and relate them to the treatment of NDs.

Curcumin in cancer therapy: A novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects.

Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal candidate in overcoming and eradication of cancer. To date, various chemotherapeutic agents have been applied in cancer therapy and paclitaxel (PTX) is one of them. PTX is a key member of taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia, and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. Besides, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, cardiotoxicity and so on, demanding novel strategies in obviating PTX issues. Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, anti-oxidant, anti-inflammatory, anti-diabetic and so on. In the current review, we demonstrate that curcumin, a naturally occurring nutraceutical compound is able to enhance anti-tumor activity of PTX against different cancers. Besides, curcumin administration reduces adverse effects of PTX due to its excellent pharmacological activities. These topics are discussed with an emphasis on molecular pathways to provide direction for further studies in revealing other signaling networks.

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways.

Cancer therapy is a growing field, and annually, a high number of research is performed to develop novel antitumor drugs. Attempts to find new antitumor drugs continue, since cancer cells are able to acquire resistance to conventional drugs. Natural chemicals can be considered as promising candidates in the field of cancer therapy due to their multiple-targeting capability. The nobiletin (NOB) is a ubiquitous flavone isolated from Citrus fruits. The NOB has a variety of pharmacological activities, such as antidiabetes, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective. Among them, the antitumor activity of NOB has been under attention over recent years. In this review, we comprehensively describe the efficacy of NOB in cancer therapy. NOB induces apoptosis and cell cycle arrest in cancer cells. It can suppress migration and invasion of cancer cells via the inhibition of epithelial-to-mesenchymal transition (EMT) and EMT-related factors such as TGF-ß, ZEB, Slug, and Snail. Besides, NOB inhibits oncogene factors such as STAT3, NF-κB, Akt, PI3K, Wnt, and so on. Noteworthy, onco-suppressor factors such as microRNA-7 and -200b undergo upregulation by NOB in cancer therapy. These onco-suppressor and oncogene pathways and mechanisms are discussed in this review.

Tangeretin: a mechanistic review of its pharmacological and therapeutic effects.

To date, a large number of synthetic drugs have been developed for the treatment and prevention of different disorders, such as neurodegenerative diseases, diabetes mellitus, and cancer. However, these drugs suffer from a variety of drawbacks including side effects and low efficacy. In response to this problem, researchers have focused on the plant-derived natural products due to their valuable biological activities and low side effects. Flavonoids consist of a wide range of naturally occurring compounds exclusively found in fruits and vegetables and demonstrate a number of pharmacological and therapeutic effects. Tangeretin (TGN) is a key member of flavonoids that is extensively found in citrus peels. It has different favorable biological activities such as antioxidant, anti-inflammatory, antitumor, hepatoprotective, and neuroprotective effects. In the present review, we discuss the various pharmacological and therapeutic effects of TGN and then, demonstrate how this naturally occurring compound affects signaling pathways to exert its impacts.

Potential therapeutic effects of curcumin mediated by JAK/STAT signaling pathway: A review.

Curcumin is a naturally occurring nutraceutical compound with a number of therapeutic and biological activities such as antioxidant, anti-inflammatory, anti-diabetic, antitumor, and cardioprotective. This plant-derived chemical has demonstrated great potential in targeting various signaling pathways to exert its protective effects. Signal transducers and activator of transcription (STAT) is one of the molecular pathways involved in a variety of biological processes such as cell proliferation and cell apoptosis. Accumulating data demonstrates that the STAT pathway is an important target in treatment of a number of disorders, particularly cancer. Curcumin is capable of affecting STAT signaling pathway in induction of its therapeutic impacts. Curcumin is able to enhance the level of anti-inflammatory cytokines and improve inflammatory disorders such as colitis by targeting STAT signaling pathway. Furthermore, studies show that inhibition of JAK/STAT pathway by curcumin is involved in reduced migration and invasion of cancer cells. Curcumin normalizes the expression of JAK/STAT signaling pathway to exert anti-diabetic, renoprotective, and neuroprotective impacts. At the present review, we provide a comprehensive discussion about the effect of curcumin on JAK/STAT signaling pathway to direct further studies in this field.

Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms.

Cancer management and/or treatment require a comprehensive understanding of the molecular and signaling pathways involved. Recently, much attention has been directed to these molecular and signaling pathways, and it has been suggested that a number of biomolecules/players involved in such pathways, such as PI3K/Akt, NF-kB, STAT, and Nrf2 contribute to the progression, invasion, proliferation, and metastasis of malignant cells. Synthetic anti-tumor agents and chemotherapeutic drugs have been a mainstay in cancer therapy and are widely used to suppress the progression and, hopefully, halt the proliferation of malignant cells. However, these agents have some undesirable side-effects and, therefore, naturally-occurring compounds with high potency and fewer side-effects are now of great interest. Osthole is a plant-derived chemical compound that can inhibit the proliferation of malignant cells and provide potent anti-cancer effects in various tissues. Therefore, in this review, we presented the main findings concerning the potential anti-tumor effects of osthole and its derivatives and described possible molecular mechanisms by which osthole may suppress malignant cell proliferation in different tissues.

Monoterpenes modulating autophagy: A review study.

From the beginning of the 21st century, much attention has been made towards the medicinal herbs due to their low side effects and valuable biological activities. Among them, terpenes comprise a large group of naturally occurring chemical compounds that are considered as main components of flavours, antifeedants and pheromones. Monoterpenes have demonstrated a favourable profile as compounds that have antioxidant, anti-inflammatory, anti-diabetic, hepatoprotective and anti-tumour activities. On the other hand, autophagy is a 'self-digestion' mechanism which plays a remarkable role in a number of pathological conditions such as cancer, ageing, metabolic disorders and infection. Also, autophagy is considered as a stress adaptor that may lead to apoptotic cell death under severe and sustained stress. Autophagy modulation is a promising strategy in cancer treatment, and a variety of drugs have been designed in line with this strategy. In the present MiniReview, we discuss the effects of monoterpenes on autophagy and its relationship with therapeutic impacts of monoterpenes.

Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress.

Regulated cell death (RCD) guarantees to preserve organismal homeostasis. Apoptosis and autophagy are two major arms of RCD, while endoplasmic reticulum (ER) as a crucial organelle involved in proteostasis, promotes cells toward autophagy and apoptosis. Alteration in ER stress and autophagy machinery is responsible for a great number of diseases. Therefore, targeting those pathways appears to be beneficial in the treatment of relevant diseases. Meantime, among the traditional herb medicine, kaempferol as a flavonoid seems to be promising to modulate ER stress and autophagy and exhibits protective effects on malfunctioning cells. There are some reports indicating the capability of kaempferol in affecting autophagy and ER stress. In brief, kaempferol modulates autophagy in noncancerous cells to protect cells against malfunction, while it induces cell mortality derived from autophagy through the elevation of p-AMP-activated protein kinase, light chain-3-II, autophagy-related geness, and Beclin-1 in cancer cells. Noteworthy, kaempferol enhances cell survival through C/EBP homologous protein (CHOP) suppression and GRP78 increment in noncancerous cells, while it enhances cell mortality through the induction of unfolding protein response and CHOP increment in cancer cells. In this review, we discuss how kaempferol modulates autophagy and ER stress in noncancer and cancer cells to expand our knowledge of new pharmacological compounds for the treatment of associated diseases.

Nano-soldiers Ameliorate Silibinin Delivery: A Review Study.

Flavonoids are a large group of naturally occurring compounds, which are of interest due to their great pharmacological effects and health-promoting impacts. These properties have led to their extensive application in a variety of pathological conditions, particularly cancer. Flavonoids are used in large quantities in a human's daily diet and a high amount of flavonoids are found in the intestine after oral usage. However, flavonoid concentrations in tissue/plasma are low because of their low bioavailability, the leading to the low efficacy of flavonoids in different clinical disorders. For this reason, nanotechnology application for delivering flavonoids to tumor sites has recently received significant attention. Silibinin is a key member of flavonoids and a bioactive component of silymarin, which is widely isolated from Silybum marianum. This plant-derived chemical has a number of valuable biological and therapeutic activities such as antioxidant, anti-inflammatory, neuroprotective, anti-tumor, hepatoprotective, cardioprotective and anti-diabetic. These beneficial effects have been demonstrated in in vivo and in vitro experiments. However, it seems that silibinin has a variety of limitations and poor bioavailability is the most important factor restricting its wide application. Hence, there have been attempts to improve the bioavailability of silibinin and it has been suggested that nano-soldiers are potential candidates for this aim. In the present review, we describe the different drug delivery systems for improving the bioavailability of silibinin.

Curcumin Activates the Nrf2 Pathway and Induces Cellular Protection Against Oxidative Injury.

Curcumin is a naturally occurring polyphenol that is isolated from the rhizome of Curcuma longa (turmeric). This medicinal compound has different biological activities, including antioxidant, antibacterial, antineoplastic, and anti-inflammatory. It also has therapeutic effects on neurodegenerative disorders, renal disorders, and diabetes mellitus. Curcumin is safe and well-tolerated at high concentrations without inducing toxicity. It seems that curcumin is capable of targeting the Nrf2 signaling pathway in protecting the cells against oxidative damage. Besides, this strategy is advantageous in cancer therapy. Accumulating data demonstrates that curcumin applies four distinct ways to stimulate the Nrf2 signaling pathway, including inhibition of Keap1, affecting the upstream mediators of Nrf2, influencing the expression of Nrf2 and target genes, and finally, improving the nuclear translocation of Nrf2. In the present review, the effects of curcumin on the Nrf2 signaling pathway to exert its therapeutic and biological activities has been discussed.

Investigating the formulation of alginate- gelatin encapsulated Pseudomonas fluorescens (VUPF5 and T17-4 strains) for controlling Fusarium solani on potato.

Nanotechnology is one of the most fascinating sciences with a great potential to improve many agricultural products. Use of nanoparticles in plant disease management is a novel area which may prove very effective in future. Use of nanomaterials and biocompatible compounds in nano-encapsulation of antagonist bacteria is an important step in enhancing the efficiency of these agents in adverse environmental conditions. Two strains of Pseudomonas fluorescens (VUPF5 and T17-4) were used for alginate-gelatin nanocomposite beads with different concentrations of gelatin. The moisture content, swelling, and releasing of encapsulated viable bacteria was investigated in vitro and in vivo conditions. The results of FT-IR and X-ray diffraction analysis revealed that when gelatin was added into sodium alginate, electrostatic interaction occurred. The swelling and moisture content of nanocomposite beads grew with gelatin enhancement. The maximum encapsulation efficiency at the gelatin concentration of 1.5% in VUPF5 and T17-4 was 91.23% and 87.23%, respectively. Further, the greenhouse experiment showed that inoculation of potato with bacterial strains and nanocomposite beads of these strains reduced disease incidence. The encapsulation method described in this study can be effectively used to protect the plant probiotic bacteria inoculum from harmful conditions of the soil for its successful establishment in the rhizosphere.

Berberine as a potential autophagy modulator.

Today, pharmacognosy is considered a valuable science in the prevention and treatment of diseases. Among herbals, Berberine is an isoquinoline alkaloid found in the Berberis species. Surprisingly, it shows antimicrobial, antiviral, antidiarrheal, antipyretic, and anti-inflammatory potential. Furthermore, it diminishes drug resistance in cancer therapy and enhances tumor suppression in part through autophagy and cell cycle arrest mechanisms. In the present review, we discuss the effect of berberine on diverse cellular pathways and describe how berberine acts as an autophagy modulator to adjust physiologic and pathologic conditions and diminishes drug resistance in cancer therapy.