Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. CONCLUSION: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease: Relevance to its anti-inflammatory and antioxidant effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. AIM OF THE STUDY: The objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. MATERIALS AND METHODS: The maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. RESULTS: LC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. CONCLUSION: FE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.

Lavender and metformin effectively propagate progesterone levels in patients with polycystic ovary syndrome: A randomized, double-blind clinical trial.

BACKGROUND: The present study aimed to evaluate the impacts of lavender and metformin on polycystic ovary syndrome (PCOS) patients. METHODS: We performed a randomized, double-blind clinical trial including 68 females aged 18 to 45, fulfilling the Rotterdam criteria for PCOS. The patients were randomized to receive lavender (250 mg twice daily) or metformin (500 mg three times a day) for 90 days. The serum progesterone was measured at baseline and after 90 days, one week before their expected menstruation. Moreover, the length of the menstrual cycle was documented. RESULTS: Our results showed that lavender and metformin treatment notably increased the progesterone levels in PCOS patients (increasing from 0.35 (0.66) and 0.8 (0.69) to 2.5 (6.2) and 2.74 (6.27) ng/mL, respectively, P < 0.001). However, we found no significant differences between the increasing effects of both treatments on progesterone levels. In addition, all patients in the lavender or metformin groups had baseline progesterone levels <3 ng/mL, reaching 14 (45.2%) patients >3 ng/mL. Lavender and metformin remarkably attenuated the menstrual cycle length in PCOS patients (decreasing from 56.0 (20.0) and 60 (12.0) to 42.0 (5.0) and 50.0 (14.0) days, respectively, P < 0.001). Furthermore, the decreasing effects of lavender on the menstrual cycle length were greater than the metformin group; however, it was not statistically significant (P = 0.06). CONCLUSION: Lavender effectively increased progesterone levels and regulated the menstrual cycles in PCOS patients, similar to metformin. Therefore, lavender may be a promising candidate for the treatment of PCOS.

Is Consumption of Pomegranate Supplementation Effective on Oxidative Stress Biomarkers Including MDA, ox-LDL, POX 1, GPX, TAC, and TBRAS? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Punica granatum (Family Lythraceae) comprises considerable content of phenolic components and it proves the antioxidant activity of pomegranate. Some clinical trial investigations display that consumption of pomegranate is able to boost the antioxidant status. This systematic review assessed the efficacy of pomegranate extract to reduce oxidative stress. Pomegranate was used in some studies as capsules (between 250 mg and 250 g) and some in liquid form (between 10 and 500 ml), and the follow-up duration varied from 3 weeks to 12 months. Standardized mean difference and its corresponding 95% confidence interval (CI) was used as the effect size of pomegranate supplementation on oxidative stress biomarkers. Based on the results, pomegranate decreased but it was not statistically significant and the same result was obtained for ox-LDL and POX 1. In addition, the results showed that pomegranate consumption can significantly increase GPX and TAC. Result of combination of on TBRAS showed significantly effect of pomegranate use on reduction of TBRAS. Since this study has evaluated mostly Eastern countries' studies it could be concluded that pomegranate supplements are effective in modifying oxidative stress in Eastern countries. The evidence to support this study is low, therefore, needs the future studies to confirm the results.

Evaluation of the Cytotoxicity of Aqueous Extract and Oleo-Essential Oil of Dorema ammoniacum Plant Oleo-Gum Resin in Some Human Cancer Cell Lines.

Results: Aqueous extract and essential oil reduced the viability of A549 cancer cells in a concentration-dependent manner. The lowest inhibitory concentrations (IC50) for both samples of D. ammoniacum oleo-gum resin were 10 and 2.5 µg/ml for 24 hours in A549 cell line, respectively. After treatment with extract and essential oil of D. ammoniacum oleo-gum resin, ROS increased significantly compared to the control group. Although changes in caspase-3 did not show a significant increase in extract, the caspase-3 was found to be increased after exposure to essential oil and caspase-9 was downregulated after exposure to essential oil. Also, exposure to essential oil of D. ammoniacum caused a reduction in MMP level. Conclusion: Based on results, the cytotoxic effect of essential oil of D. ammoniacum can induce apoptosis toward A549 cell line via induction of oxidative stress, MMP depletion, and caspase-3 activation, which is independent to mitochondrial cytochrome c release and caspase-9 function.

A systematic review on potential anticancer activities of Ficus carica L. with focus on cellular and molecular mechanisms.

BACKGROUND: Many substances derived from nutritional or medicinal plants have been studied for their chemopreventive and antineoplastic properties. Among those studied, Ficus carica has shown to have a significant ability to inhibit tumor formation and development of cancer cells through modulating various signaling mechanisms and interaction including a large number of cell signaling molecules. PURPOSE: The goal of this study is to provide a critical and complete evaluation of F. carica's anticancer capacity in various malignancies, as well as related molecular targets. METHODS: Research was conducted electronically on scholarly scientific databases, including Science Direct, PubMed, and Scopus. Published papers were analyzed and investigated using the keywords, Ficus carica, figs, cancer, malignancies and tumor based on established selection criteria. In this systematic review, 27 individual studies were considered. RESULTS: Treatment with F. carica alone or in combination with other medications was linked to anticancer activity with significant evidence. Furthermore, F. carica has been shown to use multitargeted pathways to prevent cancer initiation and development by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, apoptosis, autophagy inflammatory processes, metastasis, invasion, and angiogenesis. CONCLUSION: Our findings suggest that F. carica and its phytochemicals have the potential for cancer prevention and therapy. Nonetheless, additional mechanistic studies with pure compounds derived from F. carica and well-designed clinical trials are needed to advance our knowledge to clinical application.

Naringenin Improves Ovalbumin-Induced Allergic Asthma in Rats through Antioxidant and Anti-Inflammatory Effects.

Asthma is a chronic disease with eosinophilic inflammation and oxidative damages leading to airway obstruction. Naringenin is a phytochemical possessing strong antioxidant and anti-inflammatory activities against chronic destructive conditions. The current study is devoted to evaluating naringenin's effects on the attenuation of inflammation and oxidative stress in lung tissue in a rat model of ovalbumin-induced asthma. Male Wistar rats were allocated to five groups of six: normal control (NC, receiving 1 ml/day of normal saline, orally), asthmatic (AS, receiving ovalbumin (1 mg/mL), and alum (1 mg/mL in saline) on days 0 and 14. Then, on days 21, 22, and 23, they were sensitized with the inhalation of ovalbumin), AS treated with dexamethasone (AS, 1 mg/kg/day, orally) [AS + D1], AS treated with naringenin (20 mg/kg/day, orally) [AS + N20], and AS treated with naringenin (40 mg/kg/day, orally) [AS + N40]. All the groups received associated drugs/agents for 28 days. Finally, bronchoalveolar lavage fluid (BALF) and lung tissue samples were taken off from the animals. The eosinophil count in BALF and malondialdehyde (MDA), glutathione (GSH), interleukin-13 and -4 (IL-13 and IL-4) levels were measured. Besides, the expression of urocortin (UCN) and surfactant protein-D (SP-D) were evaluated in the lung tissue using immunohistochemistry (IHC) and western blotting methods, respectively. Hematoxylin and eosin (H&E) staining were utilized to conduct histopathological analysis. Naringenin treatment significantly reduced MDA, remarkably increased GSH, and meaningfully reduced IL-4 and IL-13 levels in lung tissue. The count of eosinophils in the BALF of AS + N20 and AS + N40 was significantly reduced in comparison with the AS group. The UCN and SP-D protein levels were significantly decreased in the AS + N20 and AS + N40 groups compared to the AS group, using the IHC and western blot methods, respectively. Histopathological analysis data also confirm the results. Naringenin improves the symptoms of allergic asthma through antioxidant and anti-inflammatory effects.

Natural products in the treatment of pulmonary emphysema: Therapeutic effects and mechanisms of action.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a class of lung diseases including chronic bronchitis, asthma, and emphysema. Long-time smoking is considered the main reason for developing emphysema. Emphysema can be defined as damage to the walls of the air sacs (alveoli) of the lung. It has been demonstrated that natural compounds with antioxidant and anti-inflammatory effects can effectively improve or protect the lung against this disease. This paper is dedicated to systematically review the effective natural compounds in the treatment of pulmonary emphysema. PURPOSE: This is the first systematic and comprehensive review on the role of plant-derived secondary metabolites in managing and/or treating pulmonary emphysema STUDY DESIGN AND METHODS: A systematic and comprehensive review was done based on Scopus, PubMed, and Cochrane Library databases were searched using the "emphysema", "plant", "herb", and "phytochemical" keywords. Non-English, review, and repetitive articles were excluded from the study. Search results were included in the Prisma diagram. RESULTS: From a total of 1285 results, finally, 22 articles were included in the present study. The results show that some herbs such as Scutellaria baicalensis Georgi and Monascus adlay and some phytochemicals such as gallic acid and quercetin and blackboard tree indole alkaloids affect more factors in improving the lung emphysema. Also, some natural compounds such as marijuana smoke and humic acid also play an aggravating role in this disease. It also seems that some of the medicinal plants such as PM014 herbal formula, pomegranate juice and açaí berry sometimes have side effects that are inconsistent with their therapeutic effects. CONCLUSION: We concluded that natural compounds can effectively improve pulmonary emphysema due to their antioxidant, anti-inflammatory, and anti-apoptotic properties. However, additional studies are suggested to prove efficacy and side effects.

Quercetin- and rutin-based nano-formulations for cancer treatment: A systematic review of improved efficacy and molecular mechanisms.

BACKGROUND: Natural products, with incredible chemical diversity, have been widely studied for their antitumor potential. Quercetin (QU) and quercetin glycoside (rutin), both polyphenolic flavonoids, stick out amongst the natural products, through various studies. Rutin (RU) and its aglycone (QU) have various biological properties that include antioxidant, anti-inflammatory, and anticarcinogenic activities. However, several side effects have restricted the efficacy of these polyphenolic flavonoids, which makes it necessary to use new strategies involving low and pharmacological doses of QU and RU, either alone or in combination with other anticancer drugs. PURPOSE: The aim of this study is to present a comprehensive and critical evaluation of the anticancer ability of different nano-formulations of RU and QU for improved treatment of various malignancies. METHODS: Studies were recognized via systematic searches of ScienceDirect, PubMed, and Scopus databases. Eligibility checks were conducted based upon predefined selection criteria. Ninety articles were included in this study. RESULTS: There was conclusive evidence for the association between anticancer activity and treatment with RU or QU. Furthermore, studies indicated that nano-formulations of RU and QU have greater anticancer activities in comparison to either agent alone, which leads to increased efficiency for treating cancer. CONCLUSION: The results of this systematic review demonstrate the anticancer activities of nano-formulations of RU and QU and their molecular mechanisms through preclinical studies. This paper also attempts to contribute to further research by addressing the current limitations/challenges and proposing additional studies to realize the full potential of RU- and QU-based formulations for cancer treatment.

The formulation and efficacy of topical Dorema ammoniacum in treating Melasma: a randomized double-blind, placebo-controlled trial.

OBJECTIVES: An acquired melanin-related hyperpigmentation that occurs in sun exposure areas is Melasma which presents as gray-brown ridges and macules with prominent margins on the skin. The aim of this assay was to assess the formulation and efficacy of topical Dorema ammoniacum among Melasma patients. METHODS: This study was a 30 days double-blind, randomized clinical trial in Melasma with a placebo group. The study was carried out on 49 patients with Melasma attending Haji Daii Nursing Center in Kermanshah, Iran. Optimized topical formulation of D. ammoniacum gum extract was prepared by evaluating the characteristics of different topical formulations of this plant. Mean Melasma severity index (MMASI) instrument was applied to assess the product effectiveness and to determine the skin stains. Patients were pursued to receive the treatment throughout the 30 days trial. This scaling was accomplished before the intervention and 30 days after the use of the herbal product. To analyze the quantitative variables, t-test and Mann-Whitney test were evaluated by SPSS 21 software, and p-value <0.05 was considered as the statistically significant. RESULTS: The survey was performed on 40 female subjects (81.6%) and nine male subjects (18.4%) with the mean age of 32.18 ± 8.69. According to the results, the mean MSI in the drug group was significantly lower than before treatment and decreased from 86.98 ± 69.48 to 31.03 ± 32.62 (p-value <0.05). CONCLUSIONS: In compliance with findings this survey revealed a positive effect of the cream formulation of D. ammoniacum extract on Melasma. As it was represented no side effects, this formulation is appropriate for the treatment of Melasma.

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.

Garlic constituents for cancer prevention and therapy: From phytochemistry to novel formulations.

Garlic (Allium sativum L.) is one of the oldest plants cultivated for its dietary and medicinal values. This incredible plant is endowed with various pharmacological attributes, such as antimicrobial, antiarthritic, antithrombotic, antitumor, hypoglycemic, and hypolipidemic activities. Among the various beneficial pharmacological effects of garlic, the anticancer activity is presumably the most studied. The consumption of garlic provides strong protection against cancer risk. Taking into account the multi-targeted actions and absence of considerable toxicity, a few active metabolites of garlic are probably to play crucial roles in the killing of cancerous cells. Garlic contains several bioactive molecules with anticancer actions and these include diallyl trisulfide, allicin, diallyl disulfide, diallyl sulfide, and allyl mercaptan. The effects of various garlic-derived products, their phytoconstituents and nanoformulations have been evaluated against skin, prostate, ovarian, breast, gastric, colorectal, oral, liver, and pancreatic cancers. Garlic extract, its phytocompounds and their nanoformulations have been shown to inhibit the different stages of cancer, including initiation, promotion, and progression. Besides, these bioactive metabolites alter the peroxidation of lipid, activity of nitric oxide synthetase, nuclear factor-κB, epidermal growth factor receptor, and protein kinase C, cell cycle, and survival signaling. The current comprehensive review portrays the functions of garlic, its bioactive constituents and nanoformulations against several types of cancers and explores the possibility of developing these agents as anticancer pharmaceuticals.

Targeting Mitochondria by Plant Secondary Metabolites: A Promising Strategy in Combating Parkinson's Disease.

Parkinson's disease (PD) is one of the most prevalent and debilitating neurodegenerative conditions, and is currently on the rise. Several dysregulated pathways are behind the pathogenesis of PD; however, the critical targets remain unclear. Accordingly, there is an urgent need to reveal the key dysregulated pathways in PD. Prevailing reports have highlighted the importance of mitochondrial and cross-talked mediators in neurological disorders, genetic changes, and related complications of PD. Multiple pathophysiological mechanisms of PD, as well as the low efficacy and side effects of conventional neuroprotective therapies, drive the need for finding novel alternative agents. Recently, much attention has been paid to using plant secondary metabolites (e.g., flavonoids/phenolic compounds, alkaloids, and terpenoids) in the modulation of PD-associated manifestations by targeting mitochondria. In this line, plant secondary metabolites have shown promising potential for the simultaneous modulation of mitochondrial apoptosis and reactive oxygen species. This review aimed to address mitochondria and multiple dysregulated pathways in PD by plant-derived secondary metabolites.

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.

The effects of co-administration of artichoke leaf extract supplementation with metformin and vitamin E in patients with nonalcoholic fatty liver disease: A randomized clinical trial.

Medicinal plants are widely used as a complementary therapy to treat complex diseases, such as nonalcoholic fatty liver disease (NAFLD). Therefore, this study was done to investigate the effect of co-administration of artichoke leaf extract supplement (ALES) with conventional medicines on patients with NAFLD. The clinical trial was based on patients randomly divided into three groups involving metformin-vitamin E (ME), metformin-ALES (MA), and vitamin E-ALES (EA). The effectiveness of treatment in the treated groups was evaluated using liver ultrasonography and biochemical markers. After 12 weeks of treatment, the results showed that the rate of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was significantly reduced within all the study groups (p < .05). Liver ultrasonographic findings revealed that the rate of fat accumulation in liver of patients was decreased significantly within all the study groups and it was increased in the subjects with grade 0 fatty liver (without fat accumulation) in the MA and EA groups by 23.3 and 17.2%, respectively. In summary, the results of the present study showed that the concomitant use of ALES with metformin and vitamin E can have beneficial effects on amelioration of complications in patients with NAFLD. However, larger-scale clinical trial studies are required in this regard.

Targeting miRNA by Natural Products: A Novel Therapeutic Approach for Nonalcoholic Fatty Liver.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) as multifactorial chronic liver disease and the lack of a specific treatment have begun a new era in its treatment using gene expression changes and microRNAs. This study aimed to investigate the potential therapeutic effects of natural compounds in NAFLD by regulating miRNA expression. MicroRNAs play essential roles in regulating the cell's biological processes, such as apoptosis, migration, lipid metabolism, insulin resistance, and adipocyte differentiation, by controlling the posttranscriptional gene expression level. The impact of current NAFLD pharmacological management, including drug and biological therapies, is uncertain. In this context, various dietary fruits or medicinal herbal sources have received worldwide attention versus NAFLD development. Natural ingredients such as berberine, lychee pulp, grape seed, and rosemary possess protective and therapeutic effects against NAFLD by modifying the gene's expression and noncoding RNAs, especially miRNAs.

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.

Natural products attenuate PI3K/Akt/mTOR signaling pathway: A promising strategy in regulating neurodegeneration.

BACKGROUND: As common, progressive, and chronic causes of disability and death, neurodegenerative diseases (NDDs) significantly threaten human health, while no effective treatment is available. Given the engagement of multiple dysregulated pathways in neurodegeneration, there is an imperative need to target the axis and provide effective/multi-target agents to tackle neurodegeneration. Recent studies have revealed the role of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) in some diseases and natural products with therapeutic potentials. PURPOSE: This is the first systematic and comprehensive review on the role of plant-derived secondary metabolites in managing and/or treating various neuronal disorders via the PI3K/Akt/mTOR signaling pathway. STUDY DESIGN AND METHODS: A systematic and comprehensive review was done based on the PubMed, Scopus, Web of Science, and Cochrane electronic databases. Two independent investigators followed the PRISMA guidelines and included papers on PI3K/Akt/mTOR and interconnected pathways/mediators targeted by phytochemicals in NDDs. RESULTS: Natural products are multi-target agents with diverse pharmacological and biological activities and rich sources for discovering and developing novel therapeutic agents. Accordingly, recent studies have shown increasing phytochemicals in combating Alzheimer's disease, aging, Parkinson's disease, brain/spinal cord damages, depression, and other neuronal-associated dysfunctions. Amongst the emerging targets in neurodegeneration, PI3K/Akt/mTOR is of great importance. Therefore, attenuation of these mediators would be a great step towards neuroprotection in such NDDs. CONCLUSION: The application of plant-derived secondary metabolites in managing and/or treating various neuronal disorders through the PI3K/Akt/mTOR signaling pathway is a promising strategy towards neuroprotection.

Natural Formulations: Novel Viewpoint for Scleroderma Adjunct Treatment.

BACKGROUND: Scleroderma is a complex disease involving autoimmune, vascular, and connective tissues, with unknown etiology that can progress through any organ systems. OBJECTIVE: Yet, no cure is available; the thorough treatment of scleroderma and current treatments are based on controlling inflammation. Nowadays, medicinal plants/natural-based formulations are emerging as important regulators of many diseases, including autoimmune diseases. Here, we provided an overview of scleroderma, also focused on recent studies on medicinal plants/natural-based formulations that are beneficial in scleroderma treatment/prevention. METHODS: This study is the result of a search in PubMed, Scopus, and Cochrane Library with "scleroderma", "systemic sclerosis", "plant", "herb", and "phytochemical" keywords. Finally, 22 articles were selected from a total of 1513 results entered in this study. RESULTS: Natural products can modulate the inflammatory and/or oxidative mediators, regulate the production or function of the immune cells, and control the collagen synthesis, thereby attenuating the experimental and clinical manifestation of the disease. CONCLUSION: Natural compounds can be considered an adjunct treatment for scleroderma to improve the quality of life of patients suffering from this disease.

Evaluation of the Effectiveness of Cinnamon Oil Soft Capsule in Patients with Functional Dyspepsia: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND: Different effects of cinnamon and its oil in traditional medicine in the treatment of diseases, including gastrointestinal diseases, were reported. The aim of this study is to evaluate the efficacy and safety of cinnamon oil (Cinnamomum zeylanicum) in patients with functional dyspepsia in a double-blind, randomized placebo-controlled trial. METHODS: Soft gelatin capsule was made using the rotary die process, and the final capsule was standardized based on its cinnamaldehyde amount and analyzed by high-performance liquid chromatography (HPLC) method. Sixty-four patients with symptomatic functional dyspepsia were randomized to receive cinnamon oil soft capsule (n = 29) or sesame oil soft capsule as placebo (n = 35) for 6 weeks. The primary efficacy variable was the sum score of the patient's gastrointestinal symptom (five-point scale). Secondary variables were the scores of each dyspeptic symptom including severity of vomiting, sickness, nausea, bloating, abdominal cramps, early satiety, acidic eructation/heartburn, loss of appetite, retrosternal discomfort, and epigastric pain/upper abdominal pain, as well as any reported adverse events. RESULTS: The results showed that, after 6 weeks of treatment, the cinnamon oil and placebo groups significantly decreased the total dyspepsia score compared to the baseline at the endpoint (P < 0.001). However, there was no significant difference between the cinnamon oil and placebo groups in terms of the baseline and endpoint values of the outcome variables (P=0.317 and P=0.174, respectively). Two patients in the cinnamon oil group complained of rashes, and three patients in the placebo group complained of nausea. CONCLUSION: This study showed significant improvements in gastrointestinal symptom score in both treatment and placebo groups. However, there was no significant difference between the cinnamon oil and sesame oil groups in terms of the baseline and endpoint values of the outcome variables. This study was registered as https://clinicaltrials.gov/ct2/show/IRCT20170802035460N2, 29 December 2017, in the Iranian Registry of Clinical Trials with https://www.IRCT.ir.