Potentially effective natural drugs in treatment for the most common rheumatic disorder: osteoarthritis.

Osteoarthritis (OA) is a chronic condition in which imbalance between anabolic and catabolic mediators occurs leading to the destruction of homeostasis of articular cartilage. The current drugs in the management of OA can just alleviate symptoms. Hence, the research tendency toward exploration of novel sources has been grown up in order to achieve safe and efficacious drugs. Meanwhile, various components exist as novel natural drugs that may possess favorable properties for the management of OA. This review focuses on the most efficacious medicinal plants and their phytochemical agents, which have been consumed for the management of OA. Moreover, evaluation of their efficacy and molecular mechanisms of action are discussed based on numerous modern experimental investigations. More research is needed to develop therapeutic agents with disease-modifying properties to treat OA.

Parsley: a review of ethnopharmacology, phytochemistry and biological activities.

OBJECTIVE: To summarize comprehensive information concerning ethnomedicinal uses, phytochemistry, and pharmacological activities of parsley. METHODS: Databases including PubMed, Scopus, Google Scholar, and Web of Science were searched for studies focusing on the ethnomedicinal use, phytochemical compounds and biological and pharmacological activities of parsley. Data were collected from 1966 to 2013. The search terms were: "Parsley" or "Petroselinum crispum" or "Petroselinum hortence". RESULTS: Parsley has been used as carminative, gastro tonic, diuretic, antiseptic of urinary tract, anti-urolithiasis, anti-dote and anti-inflammatory and for the treatment of amenorrhea, dysmenorrhea, gastrointestinal disorder, hypertension, cardiac disease, urinary disease, otitis, sniffle, diabetes and also various dermal disease in traditional and folklore medicines. Phenolic compounds and flavonoids particularly apigenin, apiin and 6"-Acetylapiin; essential oil mainly myristicin and apiol; and also coumarins are the active compounds identified in Petroselinum crispum. Wide range of pharmacological activity including antioxidant, hepatoprotective, brain protective, anti-diabetic, analgesic, spasmolytic, immunosuppressant, anti-platelet, gastroprotective, cytoprotective, laxative, estrogenic, diuretic, hypotensive, antibacterial and antifungal activities have been exhibited for this plant in modern medicine. CONCLUSION: It is expectant that this study resulted in improvement the tendencies toward Petroselinum crispum as a useful and important medicinal plant with wide range of proven medicinal activity.

Poisoning by Medical Plants.

BACKGROUND: Herbal medications are becoming increasingly popular with the impression that they cause fewer side effects in comparison with synthetic drugs; however, they may considerably contribute to acute or chronic poisoning incidents. Poison centers receive more than 100000 patients exposed to toxic plants. Most of these cases are inconsiderable toxicities involving pediatric ingestions of medicinal plants in low quantity. In most cases of serious poisonings, patients are adults who have either mistakenly consumed a poisonous plant as edible or ingested the plant regarding to its medicinal properties for therapy or toxic properties for illegal aims. METHODS: In this article, we review the main human toxic plants causing mortality or the ones which account for emergency medical visits. Articles addressing "plant poisoning" in online databases were listed in order to establish the already reported human toxic cases. RESULTS: The current review introduces herbal plants toxicity and herb-drug interactions to warn the health professionals about possible consequences of unconscious uses of medicinal plants. The reported cases extracted from our prepared database were classified on the basis of the main toxic effects of plants, and the most prominent constituents of the plants which are responsible for specific toxic effects. CONCLUSION: Considering the long history of consumption of herbal medicines in different societies, people may wrongly think that medicinal plants are fully harmless and nontoxic. Prescription, preparation and consumption regulations of medicinal plants are not clear and strict as well as their marketing regulations that differ from country to country. The extensive and various consumption of medicinal plants without adequate observation is the most important reason for poisoning by medicinal plants.

Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective.

OBJECTIVES: Diabetic neuropathy (DNP) is a widespread and debilitating complication with complex pathophysiology that is caused by neuronal dysfunction in diabetic patients. Conventional therapeutics for DNP are quite challenging due to their serious adverse effects. Hence, there is a need to investigate novel effective and safe options. The novelty of the present study was to provide available therapeutic approaches, emerging molecular mechanisms, signaling pathways and future directions of DNP as well as polyphenols' effect, which accordingly, give new insights for paving the way for novel treatments in DNP. EVIDENCE ACQUISITION: A comprehensive review was done in electronic databases including Medline, PubMed, Web of Science, Scopus, national database (Irandoc and SID), and related articles regarding metabolic pathways on the pathogenesis of DNP as well as the polyphenols' effect. The keywords "diabetic neuropathy" and "diabetes mellitus" in the title/abstract and "polyphenol" in the whole text were used. Data were collected from inception until May 2019. RESULTS: DNP complications is mostly related to a poor glycemic control and metabolic imbalances mainly inflammation and oxidative stress. Several signaling and molecular pathways play key roles in the pathogenesis and progression of DNP. Among natural entities, polyphenols are suggested as multi-target alternatives affecting most of these pathogenesis mechanisms in DNP. CONCLUSION: The findings revealed novel pathogenicity signaling pathways of DNP and affirmed the auspicious role of polyphenols to tackle these destructive pathways in order to prevent, manage, and treat various diseases. Graphical Abstract .

Pharmacological effects of gallic acid in health and diseases: A mechanistic review.

OBJECTIVES: Gallic acid is a natural phenolic compound found in several fruits and medicinal plants. It is reported to have several health-promoting effects. This review aims to summarize the pharmacological and biological activities of gallic acid in vitro and animal models to depict the pharmacological status of this compound for future studies. MATERIALS AND METHODS: All relevant papers in the English language were collected up to June 2018. The keywords of gallic acid, antioxidant, anticancer, antimicrobial, gastrointestinal-, cardiovascular-, metabolic-, neuropsychological-, and miscellaneous- diseases were searched in Google Scholar, PubMed, and Scopus. RESULTS: Several beneficial effects are reported for gallic acid, including antioxidant, anti-inflammatory, and antineoplastic properties. This compound has been reported to have therapeutic activities in gastrointestinal, neuropsychological, metabolic, and cardiovascular disorders. CONCLUSION: Current evidence confirms the pharmacological and therapeutic interventions of gallic acid in multiple health complications; however, available data are limited to just cellular and animal studies. Future investigations are essential to further define the safety and therapeutic efficacy of gallic acid in humans.

Biochemical and Histopathological Evidence on Beneficial Effects of Standardized Extract from Tragopogon graminifolius as a Dietary Supplement in Fatty Liver: Role of Oxidative Stress.

Nonalcoholic fatty liver disease (FLD) is a worldwide common liver disorder. Tragopogon graminifolius is used as a dietary supplement for liver disorders. This study aimed to assess the beneficial effects of a standardized preparation from T. graminifolius extract (TGE) in animal model of FLD induced by high-fat diet (HFD). The standardization of TGE based on phenolic compounds was performed using high-performance liquid chromatography (HPLC) analysis. The HFD induced metabolic and hepatic damages. TGE significantly reduced the elevations of serum triglyceride, cholesterol, low-density lipoprotein (LDL), and hepatic enzymes (p =.001 for 25, 50, and 100 mg/kg of TGE). Histopathological studies also confirmed beneficial effects of TGE in FLD. Activity of total antioxidant power, content of total thiol, myeloperoxidase (MPO) enzyme activity, and lipid peroxidation were significantly improved (p <.001). Dietary supplementation with TGE results in improvement of biochemical as well as histopathological parameters. Clinical trials are warranted to prove its efficacy and tolerability in patients with FLD.

Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review.

The term "metabolic syndrome" (MetS) refers to a combination of diabetes, high blood pressure, and obesity. The origin of MetS includes a combination of multiple factors, such as sedentary lifestyle, unhealthy diet choice, and genetic factors. MetS is highly prevalent and adversely affects the general population by elevating risk of cardiovascular complications, organ failure, and much other pathology associated with late-stage diabetes. Anthocyanins (ANTs) are health-promoting bioactive compounds belonging to the flavonoids subclass of polyphenols. Numerous studies have reported the potential therapeutic benefits on MetS syndrome and diabetes from fruits rich in ANTs. This review summarizes the role of several dietary ANTs on preventing and managing MetS as well as the pharmacological mechanisms and biopharmaceutical features of their action. We also discuss potential nanoformulation and encapsulation approaches that may enhance the bioefficacy of ANTs in MetS. Experiments have demonstrated that ANTs may attenuate the symptoms of MetS via improving insulin resistance, impaired glucose tolerance, dyslipidaemia, cholesterol levels, hypertension, blood glucose, protecting ß cells, and preventing free radical production. In brief, the intake of ANT-rich supplements should be considered due to their plausible ability for prevention and management of MetS. Additionally, randomized double-blind clinical trials are obligatory for evaluating the bioefficacy and pharmacological mechanisms of ANTs and their pharmaceutical formulations in patients with MetS.

A Mechanistic Review on Medicinal Plants Used for Diabetes Mellitus in Traditional Persian Medicine.

Diabetes mellitus is the most common endocrine disorder and a major cause of morbidity and mortality. Traditional medicines worldwide suggest a wide range of natural remedies for the prevention and treatment of chronic disorders, including diabetes mellitus. This mechanistic review aims to highlight the significance of medicinal plants traditionally used as dietary supplements in Persian medicine in adjunct with restricted conventional drugs for the prevention and treatment of diabetes mellitus. Mounting evidence suggests that these natural agents perform their protective and therapeutic effect on diabetes mellitus via several cellular mechanisms, including regeneration of pancreatic ß cell, limitation of glycogen degradation and gluconeogenesis, anti-inflammatory, immunoregulatory, antiapoptosis, antioxidative stress, as well as modulation of intracellular signaling transduction pathways. In conclusion, traditional medicinal plants used in Persian medicine can be considered as dietary supplements with therapeutic potential for diabetes mellitus and maybe potential sources of new orally active agent(s).

Promising effect of Rosa damascena extract on high-fat diet-induced nonalcoholic fatty liver.

NAFLD is a chronic liver disease that affects a high proportion of the world's population which causes metabolic and hepatic damages. Rosa damascena Mill is traditionally used as a dietary supplement for liver disorders. This study was carried out to determine the beneficial effect of standardized extract of R. damascena on animal model of nonalcoholic fatty liver disease (NAFLD). NAFLD was induced by high-fat diet (HFD) in Wistar rats. HFD rats showed an increase (p < 0.05) in the plasma lipid levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and reduced the high-density lipoprotein (HDL) levels. R. damascena significantly reduced the elevation of final body weight, liver fat accumulation, TG, TC, LDL-C concentrations and hepatic enzymes (p < 0.05). Histopathological examination of hepatic tissue confirmed the therapeutic effect of R. damascena. Improvement of total antioxidant power activity, total thiol content, MPO enzyme activity, and also lipid peroxidation were also considered in treated animals (p < 0.05). HPLC analysis showed that phenolic compounds including gallic acid, quercetin and syringic acid are the main bioactive compounds of R. damascena hydroalcoholic extract. In conclusion, R. damascena dietary supplementation has a therapeutic effect in NAFLD. Improvement of oxidative stress associated damage in liver tissue is among the main pharmacological mechanisms involved in therapeutic activity of the plant.

Phytochemicals as future drugs for Parkinson's disease: a comprehensive review.

Parkinson's disease (PD) is the second most common chronic neurodegenerative disease that affects motor skills and cognitive performance. The conventional therapeutic approaches for the management of PD are just able to alleviate symptoms. Exploring for achieving novel substances with therapeutic benefits in PD patients is the focus of a wide range of current investigations. The aim of the present study is to comprehensively review phytochemicals with protective or therapeutic activities in PD and focus on their neuropsychopharmacological mechanisms. Various subgroups of polyphenols (flavonoids, phenolic acids, stilbenes, and lignanes) and terpenes are the most abundant groups of phytochemicals with well-established antiparkinsonian effects. Other phytochemical categories, such as alkaloids, cinnamates, carbohydrates, amino acids, and fatty acid amides, also have some representatives with positive effects in PD. Phytochemicals perform their antiparkinsonian effect through several mechanisms of action, including suppressing apoptosis (via the reduction of Bax/Bcl-2, caspase-3, -8, and -9, and α-synuclein accumulation), decreasing dopaminergic neuronal loss and dopamine depletion, reducing the expression of proinflammatory cytokines (such as prostaglandin E2, interleukin-6, interleukin-1ß, and nuclear factor-κB), and modulating nuclear and cellular inflammatory signaling, elevation of neurotrophic factors, and improvement of antioxidant status. Plant-derived natural products can be considered as future pharmaceutical drugs or adjuvant treatment with conventional therapeutic approaches to improve their efficacy and alleviate their psychological adverse effects in the management of PD. Well-designed clinical trials are mandatory to evaluate the protective and healing benefits of phytochemicals as promising future drugs in the management of neurodegenerative diseases.

A mechanistic review on medicinal plants used for rheumatoid arthritis in traditional Persian medicine.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease, which affects synovial tissue in multiple joints. Although conventional treatments of RA commonly alleviate the symptoms, high incidence of adverse reactions leads to research tendency towards complementary and alternative medicine. As various medicinal plants are traditionally used for the management of symptomatologies associated with RA in Persian medicine, we reviewed medicinal literature to confirm their efficacy in the management of RA. KEY FINDINGS: Scientific evidence revealed that traditional medicaments exert beneficial effects on RA through several cellular mechanisms including downregulation of pro-inflammatory cytokines such as TNF-α, IL-6 and NF-κB, suppression of oxidative stress, inhibition of cartilage degradation with destructive metalloproteinases and enhancement of antioxidant performance. Various active constituents from different chemical categories including flavonols, lignans, coumarins, terpenes, glycosylflavons, dihydroflavonols, phytoestrogens, sesquiterpene lactones, anthraquinones, alkaloids and thymoquinones have been isolated from the medicinal plants. SUMMARY: The pharmacological mechanisms of the medicinal plants traditionally used for RA in Persian medicine are discussed in the current review. Further investigations are mandatory to focus on bioefficacy of these phytochemicals for finding novel natural drugs.