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Current treatments for rheumatoid arthritis produce untoward effects; thus, considerable effort has been made to recognize effective herbal medicines against the condition. In the present study, the therapeutic effect of Diospyros kaki fruit hydroalcoholic extract (DFHE) on complete Freund's adjuvant (CFA)-induced arthritis in rats was investigated. The extract was characterized using liquid chromatography-electrospray mass spectrometry (LC-ESIMS). Male Wistar rats were grouped as follows (eight rats in each): control, CFA, CFA + indomethacin (5 mg/kg), CFA + DFHE (50 mg/kg), and CFA + DFHE (100 mg/kg). Paw volume, mechanical allodynia, thermal hyperalgesia, and arthritis score were evaluated. Serum levels of malondialdehyde (MDA), thiol groups, tumor necrosis factor-alpha (TNF-α), as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were evaluated. Carotenoids were found to be the major components of DFHE. Administration of DFHE (100 mg/kg) significantly decreased arthritis score, paw volume, and thermal hyperalgesia, and improved mechanical allodynia. MDA and TNF-α levels were decreased while thiol levels and SOD and GPx activities were increased in DFHE-treated groups compared to the CFA group. These results suggest that D. kaki extract caused an improvement in clinical signs of rheumatoid arthritis symptoms possibly through suppression of oxidative stress and inflammation., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: A somatosensory nerve lesion or disease causes neuropathic pain. Presently, prescribed treatments are unsatisfactory or ineffective. The kernel oil of the apricot tree ( Prunus armeniaca L) is known for its anti-inflammatory and antioxidant effects. This study investigated the effect of apricot kernel oil in chronic constriction injury (CCI)- induced neuropathic pain in rats., Materials/methods: Liquid chromatography-electrospray mass spectrometry (LC-ESIMS) analysis was carried out to gain a deeper understanding of the apricot kernel oil's main compounds. Rats were treated daily with apricot kernel oil (2 and 4 ml/kg) or gabapentin (100 mg/kg) for 14 days after CCI induction. Hot plate, acetone drop, and Von Frey hair tests were performed to evaluate thermal and mechanical activity. Spinal cord malondialdehyde (MDA), total thiol, interleukin (IL)-1β, and tumor necrosis factor α (TNF-α) levels were assessed to measure biochemical changes., Results: The most detected compounds in apricot kernel oil were lipids and fatty acids. CCI produced a significant increase in thermal hyperalgesia, mechanical allodynia, and cold allodynia. Moreover, CCI increased the inflammation and oxidative stress markers in spinal cord samples. Oral administration of apricot kernel oil and gabapentin significantly decreased the CCI-induced nociceptive pain threshold. Besides, spinal cord biochemical changes were attenuated., Conclusions: Our findings suggest that apricot kernel oil could attenuate neuropathic pain, possibly through anti-inflammatory and antioxidant properties., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Helichrysum leucocephalum Boiss. (Asteraceae) is an endemic plant to Iran. No reports have studied the cytotoxicity of the plant. The current study aimed to evaluate the cytotoxicity of H. leucocephalum collected from Fars province (Iran) against MCF-7 and HDF cell lines using HPLC-based activity profiling and to annotate the active constituents by LC-ESIQTOF-MS/MS., Methods: H. leucocephalum was collected from three locations in Fars province. The dried flowers and leaves were separately extracted by percolation using methanol. The crude extracts were fractionated by liquid-liquid partitioning with dichloromethane (DCM) and aqueous methanol. The cytotoxicity of the fractions was evaluated against MCF-7 and HDF cells by Alamarblue assay. HPLC-based activity profiling was used to track the active constituents. LC-MS dereplication strategy was used for the annotation of the compounds in the active time window. LC-MS data were preprocessed by MZmine 3.3.0 and submitted to multivariate analysis to compare the differences and similarities in the metabolites of the samples., Results: The DCM fractions showed a dose-dependent cytotoxicity against the cancerous cells (IC50s, 9.8-105.1 μg/ml). In general, the metabolites of the flowers and their cytotoxicity were higher than the leaves. LCESIMS/MS analyses revealed that prenylated and geranylated α,β-unsaturated spiroketal phloroglucinols were among the active constituents., Conclusion: It can be concluded that H. leucocephalum is a rich source of phloroglucinol derivatives with cytotoxic activities. Further phytochemical analysis is needed to characterize the bioactive components., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aim: To investigate antifungal activity of the extract and major metabolite of the endophytic fungus Acrophialophora jodhpurensis (belonging to Chaetomiaceae) against crown and root rot caused by Rhizoctonia solani (teleomorph: Thanatephorus cucumeris), as an important pathogen of tomato., Methods and Results: The endophytic fungus A. jodhpurensis, has high inhibitory effect against R. solani AG4-HG II in vitro and in vivo. The media conditions were optimized for production of the endophyte's metabolites. The highest amounts of secondary metabolites were produced at pH 7, 30°C temperature, and in the presence of 0.5% glucose, 0.033% sodium nitrate, and 1 gl-1 asparagine as the best carbon, nitrogen, and amino acid sources, respectively. The mycelia were extracted by methanol and the obtained extract was submitted to various chromatography techniques. Phytochemical analysis via thin-layer chromatography (TLC) and nuclear magnetic resonance (NMR) spectroscopy showed that ergosterol peroxide was the major component in the extract of this endophyte. Antifungal activities of the methanolic extract and ergosterol peroxide in the culture media were studied against R. solani. Minimum inhibitory concentrations of the extract and ergosterol peroxide against the pathogen were 600 and 150 µg ml-1, respectively. Ergosterol peroxide revealed destructive effects on the pathogen structures in microscopic analyses and induced sclerotia production. Histochemical analyses revealed that it induced apoptosis in the mycelia of R. solani via superoxide production and cell death. Application of ergosterol peroxide in the leaf disc assay reduced the disease severity in tomato leaves., Conclusions: Antifungal metabolites produced by A. jodhpurensis, such as ergosterol peroxide, are capable of controlling destructive Rhizoctonia diseases on tomato., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Senna Mill. (Fabaceae) is an important medicinal plant distributed worldwide. Senna alexandrina ( S. alexandrina ), the officinal species of the genus, is one of the most well-known herbal medicines traditionally used to treat constipation and digestive diseases. Senna italica ( S. italica ), another species of the genus, is native to an area ranging from Africa to the Indian subcontinent, including Iran. In Iran, this plant has been used traditionally as a laxative. However, very little phytochemical information and pharmacological reports investigating its safety of use are available. In the current study, we compared LC-ESIMS metabolite profiles of the methanol extract of S. italica with that of S. alexandrina and measured the content of sennosides A and B as the biomarkers in this genus. By this, we were able to examine the feasibility of using S. italica as a laxative agent like S. alexandrina. In addition, the hepatotoxicity of both species was evaluated against HepG2 cancer cell lines using HPLC-based activity profiling to localize the hepatotoxic components and evaluate their safety of use. Interestingly, the results showed that the phytochemical profiles of the plants were similar but with some differences, particularly in their relative contents. Glycosylated flavonoids, anthraquinones, dianthrones, benzochromenones, and benzophenones constituted the main components in both species. Nevertheless, some differences, particularly in the relative amount of some compounds, were observed. According to the LC-MS results, the amounts of sennoside A in S. alexandrina and S. italica were 1.85 ± 0.095% and 1.00 ± 0.38%, respectively. Moreover, the amounts of sennoside B in S. alexandrina and S. italica were 0.41 ± 0.12 % and 0.32 ± 0.17%, respectively. Furthermore, although both extracts showed significant hepatotoxicity at concentrations of 50 and 100 µg/mL, they were almost non-toxic at lower concentrations. Taken together, according to the results, the metabolite profiles of S. italica and S. alexandrina showed many compounds in common. However, further phytochemical, pharmacological, and clinical studies are necessary to examine the efficacy and safety of S. italica as a laxative agent.

In the great Persian Empire, pomegranate ( Punica granatum L.) had a wide reputation for use both as an herbal medicine and nutritious food. It was also a symbol of peace and love according to Achaemenid limestones in the great Persia. This paper aims to review the traditional uses of pomegranate in Persian and Islamic traditional medicine and have thorough and current information regarding the pharmacology and phytochemistry of this valuable plant for practical use and further research. Relevant information about P. granatum was collected from scientific publishers and databases including Elsevier, Wiley, PubMed, and Google Scholar between 1950 and 2022. The traditional knowledge was extracted from Persian and Islamic traditional textbooks. Based on traditional textbooks, pomegranate has beneficial effects on diseases related to gastrointestinal, upper and lower respiratory, visual, and reproductive systems. In addition, pomegranate and its preparations have been prescribed for treating metabolic disorders, skin problems, and wounds as well as dental protection. Preclinical and clinical evidence supports many therapeutic potentials of pomegranate in traditional medicine. Its therapeutic effects are mostly attributed to its polyphenols. The knowledge in Persian and Islamic traditional textbooks about pomegranate and its preparations can be used as a guide for further preclinical and mainly clinical studies to discover the therapeutic potential of this valuable plant.

Objectives: A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is poorly understood., Materials and Methods: Herein MF, CP, and their mixtures were subjected to various stress conditions. Also, stability-indicating HPLC was developed and validated according to ICH guidelines with Box-Behnken design. The degradation products (DPs) were predicted in silico and identified using LC-MS. The bioactivity and toxicity of DPs were studied using molecular docking and alamarBlue assay, respectively. Spectroscopic techniques of the first derivative, first-derivative ratio, and the mean-centering of ratio spectra were also used to determine MF and CP in the mixture because of spectra overlapping., Results: The major degradants for MF in alkaline conditions were DP1, DP2, and DP3, while in thermal and UV conditions, only DP1 was generated. CP gave one degradant in all conditions. No new impurity was observed in the MF and CP mixtures. The results of spectrophotometry showed good linearity in the range of 4-50 and 2-20 µg/ml, while linearity for HPLC was in the range of 4-50 and 0.5-2.5 µg/ml for MF and CP, respectively. Recovery was 99.61-100.38% for UV and 100.4% for HPLC methods of MF and 100.6-101.4% for UV and 99.5% for HPLC methods of CP., Conclusion: The developed methods can be used as simple, accurate, precise, and rapid techniques for routine quality control of MF and CP mixtures., Competing Interests: None.

Objective: Increased quinolinic acid (QA) accumulation has been found in many neurodegenerative diseases. Artemisia absinthium (A. absinthium) has been reported to have neuroprotective and antioxidant activities. This study was designed to evaluate the effect of A. absinthium in QAinduced neurotoxicity in OLN-93 Cells., Methods: OLN-93 cells were cultured in a DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100 μg/ml streptomycin. The cells were pretreated with concentrations of A. absinthium extract for two h and then exposed to QA for 24 h. After 24 h cell viability, the level of malondialdehyde (MDA), reactive oxygen species (ROS), and apoptotic cells were quantitated in OLN-93 Cells., Results: Pretreatment with A. absinthium extract prevented the loss of cell viability in OLN-93 cells. ROS generation, lipid peroxidation, and apoptosis in QA-injured OLN-93 cells were reduced following A. absinthium extract pretreatment., Conclusion: A. absinthium extract exerts its neuroprotective effect against QA-induced neurotoxicity via oxidative stress and apoptosis modulation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: A narrow margin between the therapeutic and toxic doses of digoxin can result in an increased incidence of toxicity. Since digoxin has an enterohepatic cycle, multiple oral doses of absorbents like montmorillonite may be useful in the treatment of digoxin toxicity., Materials and Methods: In this study, 4 groups of 6 rats received intraperitoneal digoxin (1 mg/kg), and half an hour later, distilled water (DW) or oral adsorbents, including montmorillonite (1 g/kg), activated charcoal (1 g/kg) (AC) alone or in combination in the ratio of 70:30. Half of the mentioned doses were also gavaged at 3 and 5.5 hr after digoxin injection. The serum level of digoxin, biochemical factors, and activity score were assessed during the experiment. Three control groups only received DW, montmorillonite, or AC., Results: All adsorbents were able to significantly decrease the serum level of digoxin compared to the digoxin+DW group ( P< 0.01). Only montmorillonite reversed the digoxin-induced hyperkalemia ( P< 0.05). Multiple dose administration of adsorbents also significantly reduced the digoxin area under the curve and half-life and increased digoxin clearance ( P< 0.05). However, there was no significant difference in the kinetic parameters between groups that received digoxin plus adsorbents., Conclusion: Multiple-dose of montmorillonite reversed digoxin toxicity and reduced serum digoxin levels by increasing the excretion and reducing the half-life. Montmorillonite has also corrected digoxin-induced hyperkalemia. Based on the findings, a multiple-dose regimen of oral montmorillonite could be a suitable candidate for reducing the toxicity issue associated with drugs like digoxin that undergo some degree of enterohepatic circulation., Competing Interests: The authors declare that there are no conflicts of interest.

Forced degradation studies have been used to simplify analytical methodology development and achieve a deeper knowledge about the inherent stability of active pharmaceutical ingredients (API) and drug products. This provides insight into degradation species and pathways. Identification of impurities in pharmaceutical products is closely related to the selection of the most appropriate analytical methods like HPLC-UV, LC-MS/MS, LC-NMR, GC-MS, and capillary electrophoresis. Herein, recent trends in analytical perspectives during 2018-April 14, 2021, are discussed based on forced and impurity degradation profiling of pharmaceuticals. Literature review showed that several methods have been used for experimental design and analysis conditions such as matrix type, column type, mobile phase, elution modes, detection wavelengths, and therapeutic category. Thus, since these factors influence the separation and identification of the impurities and degradation products, we attempted to perform a statistical analysis for the developed methods according to the abovementioned factors.

Scutellaria genus, a member of the Lamiaceae family, distributed worldwide and known as skullcaps, contains a wide range of pharmacologically active constituents including flavonoids and diterpenes. There are different classes of diterpenes in the plant kingdom, of which many have medicinal applications. Scutellaria spp. contain neo-clerodane diterpenes, a large group of naturally occurring specialized metabolites found in both plant species and in organisms from other taxonomic groups, such as fungi, bacteria, and marine sponges. Although many phytochemical studies have been established reporting interesting specialized diterpene structures from Scutellaria spp., there has not been a comprehensive study reviewing these compounds. Hence, the present review reports on natural diterpenoids from the Scutellaria genus and their pharmacological activities. For this purpose, the scientific databases including Scopus, PubMed, and Google Scholar were searched using the keywords "Scutellaria" and "Diterpenes" or "Diterpenoids". The literature review showed that up to now, more than 300 diterpenes have been isolated and reported from the Scutellaria genus, belonging to neo-clerodane scaffolds. Anticancer, antifeedant, phytotoxic, antimicrobial, and nitric oxide production inhibitory activities are the most reported properties for the diterpenoids from the Scutellaria genus. Diterpenes of Scutellaria spp. have therapeutic potentials to be used for the treatment of different diseases. Further phytochemical, pharmacological, and clinical studies are required in this regard., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hypericum perforatum (Hypericaceae), known as Saint John's wort (SJW), has been used in different systems of traditional medicine such as Chinese traditional medicine, Greek traditional medicine, and Islamic traditional medicine. The plant and its active constituents such as hyperforin and hypericin have a wide range of medicinal uses, particularly as anti-depressant, wound-healing, and antibacterial agents. In recent decades, many clinical trials have been performed to investigate the safety and efficacy of this medicinal plant. However, to the best on our knowledge, there is no comprehensive review article in this regard. In the current study, we aim to have a comprehensive review of the clinical trials of SJW to evaluate its efficacy and safety as well as its application in traditional medicine. Clinical studies investigating the safety, interactions, and efficacy of SJW were identified and summarized, including contributions from 2000 until December 2021. According to the results, these clinical studies were divided into three main categories based on the type of disease: psychiatric, endocrine, and skin problems. Important details of the studies, including the type and duration of the study, the type and percentage of the effective compounds or the extract used, the number of patients, and the obtained results were also discussed. In addition, co-administration and drug interaction of SJW with other drugs were summarized. SJW is a valuable medicinal plant, especially for psychiatric disorders. However, precautions should be taken while administrating the plant., Competing Interests: The authors have no conflicts of interest to declare.

Alpha-bisabolol (α-bisabolol), an unsaturated monocyclic sesquiterpene alcohol, is known as one of the "most-used herbal constituents" in the world. Various therapeutic and biological properties of α-bisabolol in preventing oxidative stress, inflammatory disorders, infections, neurodegenerative diseases, cancers, and metabolic disorders have been reported. In this review, we evaluated new findings regarding the molecular mechanisms of α-bisabolol published from 2010 until 2021 in PubMed, Science Direct, and Scopus. The antioxidant mechanism of α-bisabolol is mainly associated with the reduction of ROS/RNS, MDA, and GSH depletion, MPO activity, and augmentation of SOD and CAT. Additionally, upregulating the expression of bcl-2 and suppression of bax, P53, APAF-1, caspase-3, and caspase-9 activity indicates the anti-apoptotic effects of α- bisabolol. It possesses anti-inflammatory effects via reduction of TNF-α, IL-1β, IL-6, iNOS, and COX-2 and suppresses the activation of ERK1/2, JNK, NF-κB, and p38. The antimicrobial effect is mediated by inhibiting the viability of infected cells and improves cognitive function via downregulation of bax, cleaved caspases-3 and 9 levels, β-secretase, cholinesterase activities, and upregulation of bcl-2 levels. Finally, due to multiple biological activities, α-bisabolol is worthy to be subjected to clinical trials to achieve new insights into its beneficial effects on human health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glaucium Mill. comprising 28 species with 78 synonyms, 3 subspecies, and 3 varieties worldwide belongs to the Papaveraceae family. The plants are well known for their different types of alkaloids. In the present study, we attempted to review the chemistry and pharmacology of the alkaloids from the genus Glaucium. For this purpose, the relevant data were collected from different scientific databases including, "Google Scholar", "ISI Web of Knowledge", "PubMed", "Scopus", and available books and e-books. Our results showed that aporphine alkaloids are dominated in the species; however, other types of alkaloids including protopines, benzophenanthridines, benzylisoquinolines, protoberberines, and morphinanes have also been reported from the genus. The pharmacological studies have shown that the alkaloids from Glaucium species have several biological activities of which anti-cancer and anti-cholinesterase effects have been highly reported. Besides, the data indicated that most of the species have been investigated neither phytochemically nor pharmacologically. Glaucium flavum, known as yellow horn poppy, is the most studied species. According to the reports, the plants from this genus have anti-cancer and anti-cholinesterase potentials and can be used as a source for aporphine alkaloids., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim of this study was to determine the role of Lawsonia inermis (L. inermis) extract in the chronic constriction injury (CCI)-induced neuropathic pain. Following CCI surgery, L. inermis extract (250 mg/kg and 500 mg/kg) and gabapentin (100 mg/kg) were administered intraperitoneally for 14 consecutive days. Heat hyperalgesia and allodynia were assessed by radiant heat, aceton drop, and von frey filament tests, respectively. Rat pain behaviors were evaluated on -1sh, 3rd, 5th, 7th, 10th and 14th days post CCI surgery. At the end of the study, the spinal levels of malondialdehyde (MDA), total thiol, IL1-β, and TNF-α were estimated. Treatment of L. inermis extract reversed the decreased level of thiol and the elevation of MDA level in the spinal cord of CCI rats. Besides, L. inermis extract treatment decreased the elevation of inflammatory markers including IL1-β, and TNF-α in the spinal cord of CCI rats. These results indicated that L. inermis has potential neuroprotective effects against CCI induced neuropathic pain due to its anti-oxidant, and anti-inflammatory effects., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Discovering new drugs for treating different health problems is one of the basic needs of human societies. There are various strategies to find new lead compounds. One of the most important strategies in this regard is using the knowledge in traditional and folk medicines as a valuable guide. Islamic traditional medicine (ITM) is a well reputed school of medicine with a long history. In the textbooks of this medical system, the properties and applications of many medicinal plants have been described. As a part of an ongoing project on plants used in ITM, in this study we investigated botany, traditional uses, phytochemistry, and pharmacology of Berberis spp. The great genus Berberis (Berberidaceae) consists of 594 species worldwide which have been used in different traditional medicines for a wide range of diseases. In ITM reference books such as Al-Hâwi fi'aṭ-Ṭibbe (Comprehensive Book of Medicine), Kâmel al-Sinâh aṭ-Ṭibbiyah (Complete Book of the Medical Art), Al-Qânun fi' aṭ-Ṭibbe (Canon of Medicine), Ḏakhireh Khârazmshâhi (Treasure of Khârazmshâh), and Makhzan al-Adwyah (Drug Treasure), different parts of B. vulgaris and B. integrimma, known as Zereshk, have been mainly prescribed for skin, liver, stomach, kidney, and eye problems. There are several pharmacological studies reporting beneficial effects of various Berberis plants confirming traditional uses. Most of the activities reported for Berberis is attributed to the presence of an important class of alkaloids namely isoquinolines. Nevertheless, clinical studies are necessary to confirm the therapeutic effects of different species of this genus.

Background: Gamma-oryzanol (γ-oryzanol) is one of the rice bran oil (RBO) compounds, known as a principal food source throughout the world. In recent numerous experimental studies, γ-oryzanol has been revealed to have several useful pharmacological properties, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, ameliorating unpleasant menopausal symptoms, cholesterol-lowering, improving plasma lipid pattern, etc. Methods: In this study, we reviewed the scientific literature published up until 2020, which has evaluated the biological and pharmacological activity of gamma-oryzanol. This review summarizes the published data found in PubMed, Science Direct, and Scopus., Results and Conclusion: The present review attempts to summarize the most related articles about the pharmacological and therapeutic potential from recent studies on γ-oryzanol to gain insights into design further studies to achieve new evidence that confirm the observed effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The rhizome of turmeric (Curcuma longa L.) has been used as an herbal medicine, coloring agent, spice, and food additive for thousands of years in different parts of the world particularly in Asian countries. It has been used for a range of diseases in many traditional medical schools, including Islamic traditional medicine, Chinese traditional medicine, and Ayurveda. It has been used mainly for digestive problems, as a cardio-, hepato-, and neuroprotective agent as well as in many inflammatory conditions such as arthritis and for enhancing immune system. Curcumin, a diarylheptanoid derivative found in turmeric, has anti-inflammatory, antioxidant, and anticancer properties; controls obesity and metabolic problems; and improves memory and mood disorders. Therapeutically, curcumin exhibits promising potential in preclinical and clinical studies and is currently in human trials for a variety of conditions, including metabolic syndrome, nonalcoholic fatty liver disease, rheumatoid arthritis, migraine, premenstrual syndrome, ulcerative colitis, knee osteoarthritis, polycystic ovarian syndrome, atherosclerosis, liver cirrhosis, amyotrophic lateral sclerosis, depression, psoriasis, and Alzheimer's disease. Among all beneficial activities reported for curcumin, the research toward the obesity and metabolic-preventing/suppressing aspects of curcumin is growing. These findings emphasize that most of the traditional applications of turmeric is due to the presence of its key constituent, curcumin. According to the traditional background of turmeric use and clinical values of curcumin, further preclinical studies for unstudied properties and clinical studies with larger sample sizes for confirmed activities are expected., (© 2021. The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Metabolic syndrome and associated disorders have become one of the major challenging health problems over the last decades. Considerable attention has been paid to natural products and herbal medicines for the management of metabolic disorders in recent years. Many studies have investigated the therapeutic effects of different parts (arils, peels, seeds, and flowers) of pomegranate (Punica granatum L.) for the prevention and treatment of this syndrome. This study aims to provide an updated review on the in vitro and in vivo studies as well as clinical trials investigating the effects of pomegranate and its active compounds on different components of metabolic problems such as hyperglycemia, hyperlipidemia, hypertension, as well as obesity over the last two decades. Besides, the key mechanisms by which pomegranate affects these pathogenic conditions are also discussed. The studies show that although pomegranate has promising beneficial effects on diabetes, hypertension, hyperlipidemia, and obesity in various cellular, animal, and clinical models of studies, there are some conflicting results, particularly for hyperglycemic conditions. The main mechanisms include influencing oxidative stress and anti-inflammatory responses. Overall, pomegranate seems to have positive effects on the pathogenic conditions of metabolic syndrome according to the reviewed studies. Although pomegranate is not suggested as the first line of therapy or monotherapy, it could be only used as an adjunctive therapy. Nevertheless, further large and long-term clinical studies are still required., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Malignant conditions of the gastrointestinal tract and accessory organs of digestion, including the oral cavity, esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus, are referred to as gastrointestinal cancers. Curcumin is a natural compound derived from turmeric with a wide range of biological activities. Several in vitro and in vivo studies have investigated the effects of curcumin on gastrointestinal cancers. In the current review, we aimed to provide an updated summary on the recent findings regarding the beneficial effects of curcumin on different gastrointestinal cancers in the recent decade. For this purpose, ScienceDirect," "Google Scholar," "PubMed," "ISI Web of Knowledge," and "Wiley Online Library" databases were searched using "curcumin", "cancer", and "gastrointestinal organs" as keywords. In vitro studies performed on different gastrointestinal cancerous cell lines have shown that curcumin can inhibit cell growth through cycle arrest at the G2/M and G1 phases, as well as stimulated apoptosis and autophagy by interacting with multiple molecular targets. In vivo studies performed in various animal models have confirmed mainly the chemopreventive effects of curcumin. Several nano-formulations have been proposed to improve the bioavailability of curcumin and increase its absorption. Moreover, curcumin has been used in combinations with many anti-tumor drugs to increase their anticarcinogenic properties. Taken together, curcumin falls within the category of plant-derived substances capable of preventing or treating gastrointestinal cancers. Further studies, particularly clinical trials, on the efficacy and safety of curcumin are suggested in this regard.

Introduction: Nowadays, hair loss is becoming a major problem for a large number of people. The main factors affecting hair growth include racial, gender, genetics, and hormonal. Furthermore, environment, physiology, and nutrition are the tools that are affecting hair growth., Materials and Methods: This article analyses the effects of silymarin and Vitamin C on the proliferation of dermal papilla cells (DPCs), COX2, inducible nitric oxide synthase (iNOS), total anti-oxidant capacity (TAC), and reactive oxygen species (ROS). The DPCs of the hair follicle treated by 50 and 100 μM of silymarin and 100 μM of Vitamin C on days 2, 7, and 14., Results: A comparatively effect of silymarin and Vitamin C demonstrated that Vitamin C is more effective in the stimulation of dermal papillae in cell culture. Furthermore, the stimulation effects of silymarin are attributed to its antioxidant activity of the cells., Conclusion: The overall result shows that cell proliferation and TAC significantly increased. However, iNOS, ROS, and COX2 levels were decreased., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 International Journal of Trichology.)

Cupressus sempervirens, Platycladus orientalis, Juniperus communis, J. excelsa, J. foetidissima, J. polycarpos var. turcomanica, J. sabina, and Taxus baccata are conifers in Iran. These plants have a long reputation in different systems of traditional medicines for a variety of diseases. This review aims to provide comprehensive and up-to-date information about the ethnopharmacological uses, chemical constituents, and pharmacology of these conifers. Furthermore this study comprises a bibliographical survey of major Islamic Traditional Medicine (ITM) books regarding different medical aspects of these species. A literature search was conducted on the applications of these conifers both in traditional and modern medicines by referencing traditional textbooks and scientific databases. Ethnobotanical literature review indicates that various parts of the plants including cones, berries, leaves, bark, wood, and resin have been used for a broad spectrum of applications. In Iran, C. sempervirens, J. sabina, J. communis, and T. baccata have been used traditionally for the treatment of urinary, digestive, nervous, respiratory, and integumentary systems-related problems. The phytochemical constituents of these plants can be divided into two main categories: volatile and non-volatile components, all dominated by terpenes. Considering the pharmacological and clinical evidence, while some of the traditional applications of these plants are supported by modern medicine, implying the value of the traditional and folklore knowledge for finding new lead compounds in drug discovery, some have remained unexamined showing the need for much more studies in this regard., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chaharmahal and Bakhtiari Province is one of the most important endemism states of the flora of Iran with a considerable plant species diversity. In the present study, the cytotoxic activity of 13 plant species grown in Chaharmahal and Bakhtiari have been evaluated on prostate (PC-3), breast (MCF-7), liver (HepG2), ovary (CHO), and melanoma (B16-F10) cancer cell lines. The cytotoxicity and apoptotic activity of methanol extracts was evaluated using resazurin reagent and flow cytometry of PI stained cells, respectively. Methanol extracts of Dionysia sawyeri , Stachys obtusicrena and Cicer oxyodon on CHO cell line ( p <0.05) and D. sawyer and Linum album on B16/F10 cell line ( p <0.05) showed significant cytotoxic effects and increased apoptosis. It is generally suggested that the plant extracts with low IC 50 values are likely to be used as anti-cancer compounds in reducing cancer progression in scientific studies.

In a screening of Iranian plants for antiprotozoal activity a dichlomethane extract from the aerial parts of Helichrysum oocephalum showed in vitro antiprotozoal activity against Plasmodium falciparum and Leishmania donovani, with IC 50 values of 4.01 ± 0.50 and 5.08 ± 0.07 μg/mL, respectively. The activity in the extract was tracked by HPLC-based activity profiling, and subsequent targeted preparative isolation afforded 24 compounds, including pyrones 22-24, phloroglucinol derivatives 12-19, and compounds containing both structural motifs (1-11, 20, and 21). Of these, 15 compounds were new natural products. The in vitro antiprotozoal activity of isolates was determined. Compound 3 showed good potency and selectivity in vitro against L. donovani (IC 50 1.79 ± 0.17 μM; SI 53).

Background: In this study, the essential oil composition and cytotoxic activities of five Artemisia species were determined., Methods: The collected plants were water-distilled separately to obtain oils which were then subjected to gas chromatography (GC) and gas chromatography/mass spectrometry GC/MS analyses to identify their compositions. Cancer cells were exposed to different concentrations of samples and cell viability was measured using AlamarBlue® assay. Apoptotic cells were analyzed by propidium iodide (PI) staining and flow cytometry., Results & Conclusion: To study the amount of pro-apoptotic proteins and the apoptosis mechanism, Western blot method was used. Although all samples were cytotoxic at the highest concentration, the oil of A. kulbadica showed the strongest activity among other plants. Carvacrol (IC50 21.11 μg/ml) had the most cytotoxic effects among other components. Carvacrol, 1,8-cineole and 4-terpineole caused an increase in the amount of Bax protein and cleaved peroxisome proliferator-activated receptors (PPAR) and caspase proteins in DU 145 cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nepeta (Lamiaceae) is an important genus with beneficial medicinal properties. N. sintenisii Bornm. has been used in folk medicine of Iran to cure various diseases. We investigated the anti-melanogenesis effects of n -hexane, MeOH, CH 2 Cl 2 , n -BuOH, EtOAc, and H 2 O extracts isolated from the plant in B16 melanoma cells. Various assays including cytotoxicity, mushroom tyrosinase inhibition, inhibition of cellular tyrosinase, melanin content, the amount of reactive oxygen species and western blotting were done to assess the plant activities on melanogenesis inhibition. All extracts of N. sintenisii could significantly reduce both tyrosinase activity and the cellular melanin content. Reactive oxygen species were also significantly decreased following the treatment of cell with n -BuOH and EtOAc extracts with no cytotoxicity. The plant significantly decreased the amount of microphthalmia-associated transcription factor proteins. Collectively, N. sintenisii inhibited melanin synthesis and tyrosinase activity in B16 melanoma cells with no cytotoxic effects. Hence, it might merit further investigations for elucidation of anti-hyperpigmentation agents.

Objectives: Black cumin ( Nigella sativa ) belonging to Ranunculaceae family has a long history of medicinal use in various folk and traditional systems of medicine, including Iranian traditional medicine (ITM). These valuable medicinal seeds have been used traditionally against a variety of diseases such as dyspepsia, diabetes, headache, influenza and asthma. In addition, several scientific investigations have reported the therapeutic properties of N. sativa and thymoquinone (TQ), one of the most important constituent of black cumin, for treatment of a large number of diseases, including ischemia. As there is no comprehensive review study about the anti-ischemic activity of black cumin and its mechanism of action, in the current study, we aimed to review the anti-ischemic activities of N. sativa and TQ in different organ-related disorders., Materials and Methods: We searched the words N. sativa or black cumin and ischemia in the combination of related organs through available databases including Scopus, Web of Science, and Google Scholar., Results: Several studies were found reporting the anti-ischemic activity of black cumin and its active constituent on different organs including brain, kidneys, heart, and liver. Black cumin exert its beneficial effects as an antioxidant, anti-inflammatory, anti-apoptosis, and anti-necrosis agent through inhibition of growth factors, biochemical and oxidative stress markers and regulating gene expression., Conclusion: Thus, N. sativa could be a potential candidate for treatment of ischemia related disorders in key organs such as brain, liver, digestive system, kidney, and heart. To figure out the exact mechanism of action, further investigations are proposed in this regard.

In this study, we investigated the role of mitogen-activated protein kinase (MAPK) signaling pathways in mediation of the protective effects of saffron extract, saffron essential oil, safranal and crocin on bovine aortic endothelial cells against oxidative injury. The viability of cells in response to H 2 O 2 -induced toxicity (0.4, 2 and 10 mM) was measured using resazurin assay in the presence or absence of saffron extract (2-40 μg/ml), saffron oil (2-40 μg/ml), safranal (2-40 μM) and crocin (2-40 μM). Dichlorodihydrofluorescin diacetate was used as an indicator for the amount of reactive oxygen species (ROS) in cells at the same concentrations of samples as the former test. In addition, propidium iodide staining of the fragmented DNA was performed to measure the level of apoptotic cells by the application of 2-10 μM of crocin and safranal. Finally, the proteins involved in apoptosis were detected using western blotting at the concentration of 0, 2, 10 μM for crocin and safranal. The results indicated that all tested moieties improved viability and reduced ROS production in H 2 O 2 -treated cells (p < 0.001 compared to H 2 O 2 ). In addition, a significant decrease in apoptosis (3-35%) was observed in the cells that were treated with crocin and safranal. The observed protective effects of crocin and safranal were associated with the activation of SAPK/JNK and inhibition of ERK ½ that are related to MAPK pathways. The antioxidant and anti-apoptotic activities of saffron and its ingredients in endothelial cells are mediated via MAPK signaling pathways and might be of therapeutic potential for endothelial dysfunctionalities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although Iran has a deep history in herbal medicine and great heritage of ancient medical scholars, few efforts have been made to evaluate ethnopharmacological aspects of medicinal plants in this country. In the present study, the authors have reviewed all important literature about the ethnopharmacological investigations on medicinal plants used in the last decade in Iran. All provinces of Iran were categorized according to a phytogeographical division. Information was collected through bibliographic investigations from scientific journals and books. Afterward, the data were analyzed through the construction of specific ecological regions of the country. Fifty-five references reporting medicinal plants in five ecological zones were retrieved. The Irano-Turanian subregion has produced the greatest number of publications in this field among others (47%). Results illustrate that the most reported botanical families were Lamiaceae and Asteraceae (28.57% and 27.73%, respectively). Among various illnesses reported for these plants, gastrointestinal (30.15%), respiratory problems (14.28%), diabetes (11.11%), and cold/flu (11.11%) were the most cited. The most frequently cited medicinal uses were attributed to decoction and infusion preparations. Iran has a rich history of knowledge about phytotherapy and has also a diverse geographical regions, and a plant flora that is a good candidate for drug discovery. Documentation of indigenous knowledge about herbal medicine used by Iranian tribes is vital for the future development of herbal drugs. Ethnopharmacological studies of Iranian folk medicine with quantitative analytical techniques are warranted to find drug candidates, and also to preserve the precious knowledge of the Iranian folk medicine., (© 2017 Wiley Periodicals, Inc.)

A new series of quinoline analogues was designed and synthesized as Hsp90 inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against three human cancer cell lines including MCF-7 (human breast cancer cells), DU145 (human prostate cancer cell lines), and A549 (adenocarcinomic human alveolar basal epithelial cells). Some of our compounds (13a-13f) showed significant cytotoxic activity on MCF-7 cells. The most potent anti-proliferative compounds were also tested against Her2, a client protein of Hsp90. Compound 13d that demonstrated the highest antiproliferative activity in the series, was found the most potent one for both Her2 protein degradation and Hsp70 protein induction as well. Molecular modeling studies displayed possible mode of interaction between this compound and N-terminal ATP-binding site of Hsp90., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Traditional medicine is a useful guide in medical sciences. In the Islamic Iranian traditional medicine, the medicinal properties of many plants have been mentioned that could be exploited in drug discovery. We aimed to explore the nature and properties of Aloe spp. As described in some major Islamic traditional texts including Ferdows al-Hekmah fi'l-Tibbe (The Paradise of Wisdom in Medicine), Al-Hawi fi'l-Tibb (Comprehensive Book of Medicine), Kamel al-Sanaat al-Tibbyyah (Complete Book of the Medical Art), Al-Qanun fi'l-Tibb (Canon of Medicine), Zakhireh Kharazmshahi (Treasure of Kharazmshah), and Makhzan al-Adwiah (Drug Treasure), and assess the conformity of traditional medicine instructions with the findings of modern pharmacological studies. Gastrointestinal activities, hepato-protective properties, beneficial effects against skin problems such as wounds, injuries, and infective diseases are among the most frequently mentioned properties of Aloe spp. Several activities of Aloe spp. described in traditional medicine have been the subject of recent in vitro and in vivo studies as well as clinical trials. Owing to the positive findings, different preparations of Aloe spp. are now present in pharmaceutical markets such as Aloe cosmetic products. On the other hand, there are many traditional therapeutic effects of Aloe spp. which have not been studied and require confirmatory experimental or clinical investigations. It is hoped that the present study could stimulate further research on the unexplored aspects of the medicinal properties of Aloe spp., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Metabolic syndrome is associated with several disorders, including hypertension, diabetes, hyperlipidemia as well as cardiovascular diseases and stroke. Plant-derived polyphenols, compounds found in numerous plant species, play an important role as potential treatments for components of metabolic syndrome. Studies have provided evidence for protective effects of various polyphenol-rich foods against metabolic syndrome. Fruits, vegetables, cereals, nuts, and berries are rich in polyphenolic compounds. Grapes (Vitis vinifera), especially grape seeds, stand out as rich sources of polyphenol potent antioxidants and have been reported helpful for inhibiting the risk factors involved in the metabolic syndrome such as hyperlipidemia, hyperglycemia, and hypertension. There are also many studies about gastroprotective, hepatoprotective, and anti-obesity effects of grape polyphenolic compounds especially proanthocyanidins in the literature. The present study investigates the protective effects of grape seeds in metabolic syndrome. The results of this study show that grape polyphenols have significant effects on the level of blood glucose, lipid profile, blood pressure, as well as beneficial activities in liver and heart with various mechanisms. In addition, the pharmacokinetics of grape polyphenols is discussed. More detailed mechanistic investigations and phytochemical studies for finding the exact bioactive component(s) and molecular signaling pathways are suggested., (Copyright © 2016 John Wiley & Sons, Ltd.)

Ferula communis L., subsp. communis, namely giant fennel, has extensively been used in traditional medicine for a wide range of ailments. Fresh plant materials, crude extracts and isolated components of F. communis showed a wide spectrum of in vitro and in vivo pharmacological properties including antidiabetic, antimicrobial, antiproliferative, and cytotoxic activities. The present paper, reviews the traditional uses, botany, phytochemistry, pharmacology and toxicology of F. communis in order to reveal its therapeutic potential and future research opportunities. A bibliographic literature search was conducted in different scientific databases and search engines including Scopus, Cochrane Library, Embase, Google Scholar, Pubmed, SciFinder, and Web of science. Phytochemical studies have led to the isolation of different compounds such as sesquiterpenes from F. communis. This plant has two different chemotypes, the poisonous and non-poisonous chemotypes. Each chemotype is endowed with various constituents and different activities. The poisonous chemotype exhibits anticoagulant and cytotoxic activities with sesquiterpene coumarins as major constituents, while the non-poisonous one exhibits estrogenic and cytotoxic effects with daucane sesquiterpene esters as the main compounds. In addition, although various pharmacological properties have been reported for F. communis, anti-microbial activities of the plant have been investigated in most studies. Studies revealed that F. communis exhibits different biological activities, and contains various bioactive compounds. Although, antibacterial and cytotoxic activities are the two main pharmacological effects of this plant, further studies should focus on the mechanisms underlying these actions, as well as on those biological activities that have been reported traditionally.

Objective: Boerhaavia elegans L. (Nyctaginaceae) is a medicinal plant used for the treatment of kidney disorders, urinary tract disorders and blood purification in Baluch tribe. The aim of present study is to evaluate the antioxidant property of B. elegans species for the first time., Materials and Methods: Different parts (leaf, stem and fruit) of the plant were extracted by using various solvents (water, methanol, chloroform and ethyl acetate) and evaluated for their antioxidant activity using DPPH (2, 2-diphenyl-1 picryl hydrazyl) and FRAP (ferric reducing antioxidant power) methods. In addition, total phenolic content was determined by Folin-Ciocalteu reagent., Results: Antioxidant results were expressed as IC50. The antioxidant power in DPPH and FRAP assay were evaluated as shown in decreasing order: Methanolic extract > Aqueous extract > Ethyl acetate extract > Chloroform extract, for all parts of the plant. In both methods of antioxidant assay and Folin-Ciocalteu method, methanolic extract of leaf exhibited the highest activity and the most phenolic content IC50= 6.85 ppm and 16.41 mg GA/g d w respectively. Total phenolic content had a positive relationship with antioxidant capacity in extracts and there was a high correlation (r=1.00, p<0.01) between antioxidant activities as determined by both antioxidant assays for various parts., Conclusion: The results of the experiments showed that B. elegans extract had significant antioxidant effects. This high antioxidant activity may be linked to phenolic contents of the plant but complementary investigations are suggested in order to determine active elements.

Objective: The current study summarizes the updated information concerning the ethnopharmacology, Phytochemistry, and pharmacology of Otostegia persica Boiss. (Lamiaceae), an endemic medicinal plant in south and southeast of Iran., Materials and Methods: Information was collected through bibliographic investigation from scientific journals, books, theses, reports, and electronic search (databases SCOPUS, Google Scholar, Web of Science, and Science Direct). Moreover, documentation from unpublished resources and ethnobotanical surveys has been used. The present review covers the literature available from 2003 to 2013., Results: In traditional systems of medicine, this plant is reputed for treating diabetes, arthritis, gastric discomfort, headache, rheumatism, sedative activities, regulating blood pressure, and hyperlipidemia. Phytochemical screening of active components and mineral element evaluation of this species have been reported. Several types of diterpenoids and flavonols including morin, kaempferol, and quercetin are identified from the plant. Most of the pharmacological activity of this plant resides in its flavonoid fraction which causes antimicrobial and antioxidant activities. Various pharmacological studies on O. persica show antimicrobial, antioxidant, anti-inflammatory, anti-diabetic, anti-aphid, and hepatoprotective activities., Conclusion: Being an endemic plant of Iran, this species is an important medicinal herb which can be used for various purposes. This review might be helpful for scientists and researchers to find new chemical entities responsible for its claimed traditional uses and discover new lead compounds for diseases mentioned.