Cytotoxicity, apoptosis inducing activity and Western blot analysis of tanshinone derivatives from Stachys parviflora on prostate and breast cancer cells.

Cytotoxic activities of methanolic crude extract of Stachys parviflora (Lamiaceae family) and its sub-fractions were primarily evaluated against human breast adenocarcinoma (MCF-7 and MDA-MB-231) and prostate (PC3) cell lines. The methanolic extract exhibited the highest activity, and was chosen for the isolation procedure. Four diterpenoid quinones, namely miltirone [1], tanshinone IIA [2], 1-hydroxy-tanshinone IIA [3], and cryptotanshinone [4] were isolated. Notably, this is the first report on the isolation and/or characterization of the mentioned diterpenoids from the Stachys genus. In this study, 1-hydroxy-tanshinone IIA [3] displayed the highest cytotoxicity among the isolated compounds. The mechanism of the cytotoxicity of methanolic extract and isolated compounds was further investigated by the utilization of propidium iodide staining (PI) assay. The results showed that the methanolic extract and 1-hydroxy-tanshinone IIA [3] enhanced DNA fragmentation in PC3 and MCF-7 cells. Moreover, the western blotting analysis demonstrated increasing and decreasing protein levels of Bax and Bcl2, respectively, and cleaved poly ADP-ribose polymerase (PARP). Further bioassay-guided phytochemical assessments of S. parviflora can be suggested as a promising approach for discovering potent bioactive secondary metabolites.

Evaluation of the efficacy of Thymus kotschyanus extract as an additive treatment in patients with ulcerative colitis: a randomized double-blind placebo-controlled trial.

BACKGROUND: Ulcerative colitis (UC) is one of the chronic diseases which is increasing in prevalence and patients suffer from illness flare-ups. UC standard regimen treatment has various side effects besides the efficacy, so there is an interest in administering complementary medicine to reduce adverse effects and increase the efficacy, as well. The aim of this study was to evaluate the efficacy and anti-inflammatory effect of Thymus kotschyanus as an additive treatment in a randomized double-blind placebo-controlled trial of UC patients. METHODS: Thirty UC out-patients with mesalazine regimen treatment that fulfilled the inclusion criteria were participated in a 12 week trial and were randomly chosen for the treatment and control group. Fifteen patients were administered a placebo as a control and 15 patients were received Thymus kotschyanus extract by a dose of 0.5 g in a day in the treatment group. Laboratory tests were performed at baseline and week 12. The primary outcome was a reduction in fecal calprotectin as the main intestine inflammatory marker. Likewise, reduction in SCCAI, SIDBQ, and SEO indices were considered as secondary aims. RESULTS: Fecal calprotectin was decreased by 54.74% in the treatment group, as compared with the placebo group at week 12 (p = 0.02). A significant reduction in SCCAI was also shown between the two study groups (p = 0.01). Thymus kotschyanus extract was safe and no severe side effects were reported. CONCLUSION: Administration of Thymus kotschyanus revealed improvement in UC symptoms by the intestinal anti-inflammation effect of the plant and could be suggested as a potential additive treatment in UC patients. The study protocol has been registered under the identification code: IRCT20200406046965N2.

Turmeric and Curcumin: From Traditional to Modern Medicine.

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.

Updated Review on the Role of Curcumin in Gastrointestinal Cancers.

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.

Genus Rosas : A Review of Ethnobotany, Phytochemistry and Traditional Aspects According to Islamic Traditional Medicine (ITM).

Rosa spp. is an important genus in the Rosaceae family which is a source of medicinal natural products, particularly polyphenolic and terpenoid compounds and is used in several traditional medicines such as Islamic Traditional Medicine (ITM) to cure various diseases. Plants in this genus are known to possess anti-inflammatory, antidiabetic, anti-constipation, cardioprotective and neuroprotective activities. Furthermore, phytochemical investigations have reported Rosa species to contain a wide range of chemical compounds including quercetin, kaempferol, catechin, citronellol, limonene, lycopene, carvacrol, thymol, ascorbic acid (vitamin C), rosmarinic acid, etc. The current review is an attempt to cover the available findings on the ethnobotany and photochemistry of this genus as well as its medicinal aspects in ITM.

Therapeutic Potential of Pomegranate in Metabolic Disorders.

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.

The Use of Medicinal Plants for the Treatment of Alopecia in the Canon of Avicenna: An Evidence-Based Review.

Although mostly seen in the scalp, alopecia can occur in any hair- bearing site of the body. In spite of various modern treatments, total cost, efficacy, safety and drug dependency have caused a global willing towards natural remedies. The aim of this chapter is to focus on medicinal plants mentioned in Canon of Avicenna, one of the most primary medicinal books, for the treatment of alopecia. Databases like PubMed, Scopus and Google Scholar were searched for plants mentioned in Canon for managing alopecia to find studies on their clinical efficacy or mechanisms, which may have attributed to the treatment of alopecia. 25 plants belonging to 16 families have been mentioned in Canon. Most of them have a history of use in ethno-medicine and some are used in hair growth products nowadays. Investigating literatures has shown that anti- inflammatory and immunomodulatory properties are the proposed mechanisms for the treatment of some types of alopecia. Islamic traditional medicine can give new insights for development of multiple natural treatment, which their use in human have been tested for thousands of years. By confirming their efficacy and safety, traditional herbal remedies are appropriate alternatives for chemicals mainly used for alopecia.

Ethnobotanical Uses, Phytochemistry and Pharmacology of Different Rheum Species (Polygonaceae): A Review.

Today, there is an increased tendency to use herbal remedies. Rhubarb refers to several species of the genus Rheum L. in the Polygonaceae family. This species-rich genus is mainly distributed in Asian countries. Several medicinal effects have been attributed to the Rheum spp. in the traditional and modern medicine such as healing lungs, liver, kidney, womb and bladder diseases, cancer, diabetes, insect bites, relapsing fevers, diarrhea and constipation. Various in vitro, in vivo and clinical studies have investigated the therapeutic effect of extracts, fractions and pure compounds isolated from different species of this genus. Considering the positive findings, several pharmaceutical formulations containing rhubarb extract like capsules, drops, mouthwashes and different topical formulations are now present in the market. However, there are other traditional therapeutic effects of rhubarb that have not been studied yet and it is of great importance to perform confirmatory experiments or clinical investigations. The current review summarizes general information regarding botany, phytochemistry, ethnobotany and pharmacological aspects of Rheum spp. It is hoped that the present review could motivate subsequent research on the other medicinal properties of these plants that have been neglected until today.

Medicinal Species of the Genus Berberis: A Review of Their Traditional and Ethnomedicinal Uses, Phytochemistry and Pharmacology.

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'at-Tibbe (Comprehensive Book of Medicine), Kâmel al-Sinâh at-Tibbiyah (Complete Book of the Medical Art), Al-Qânun fi' at-Tibbe (Canon of Medicine), Dakhireh 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.

Antiviral Plants in View of Avicenna's The Canon of Medicine and Modern Medicine Against Common Cold.

Common cold is known as a serious clinical problem worldwide. Coronaviruses have long been identified as respiratory pathogens causing "common cold" in healthy people. The pandemic of 2019 novel coronavirus as a serious public health problem and concern has resulted in severe illness and death especially in the elderly. COVID-19 is picking up pace around the world and has spread to more than 219 countries. Due to the very easy spread of COVID-19 and its lack of recognized appropriate treatments and vaccines as well as potential therapeutic effects of several traditional herbal remedies, we decided to gather, evaluate, and compare the potential pharmacological effects of medicinal herbs from Avicenna's perspective and modern medicine with antiviral properties which may lead to the discovery of suitable traditional treatments to prevent or reduce the adverse symptoms of common cold.

The Effects of Ivy (Hedera helix) on Respiratory Problems and Cough in Humans: A Review.

Hedera helix (ivy) belongs to the genus Hedera of the Araliaceae family. The leaf of this plant has several active ingredients with medicinal uses. The active constituents of H. helix include monodesmoside α-hederin, hederacoside B, hederacoside C, and hederacoside D.H. helix leave have been used for the treatment of cough and respiratory problems, and now, other uses have emerged. As a medicinal plant, H. helix has been approved by the German Commission E due to its antispasmodic, spasmolytic, antimicrobial, anti-inflammatory, anthelmintic, antioxidative, antitumor, and antileishmanial activities. It comes with several formulations, including tablets, liquids, and topical ointments. In this review, we focus on the respiratory effects of tablet and liquid forms of H. helix.

Ethnomedicinal Uses, Phytochemistry and Pharmacology of Different Cichorium Species (Asteraceae): A Review.

Cichorium species have been used widely in traditional medicine universally. It is reported as a treatment for various respiratory and gastrointestinal disorders, as well as diabetes and rheumatism. A range of constituents including phenolic and poly phenolic compounds, fatty and organic acids and essential oils comprise the chemical composition of Cichorium species. Furthermore, modern investigations on these species has shown different pharmacological activities such as antioxidant, antiproliferative, anti-inflammation, antibacterial, anti-hyperglycemic, antidiabetic and hepatoprotective effects which are associated with divers molecular pathways and mechanisms. In this chapter, we have summarized comprehensive information regarding traditional and ethnomedicinal uses, phytochemical analysis and pharmacological aspects of Cichorium species.

Ethnobotany, Phytochemistry, Traditional and Modern Uses of Actaea racemosa L. (Black cohosh): A Review.

Actaea racemosa (AR) also known as Cimicifuga racemosa, is a perennial plant from Ranunculaceae family which was used as traditional remedies in treatment of various condition like rheumatoid muscular pain, headache, inflammation and dysmenorrhea. Actaea racemosa was basically native to Canada and the Eastern United State. This chapter proposed the ethnopharmacological uses of Actaea racemosa, and its phytochemical properties. Specifically, in this article we focused on use of Actaea racemose for menopausal and post-menopausal symptoms management. Electronic databases including PubMed and Scopus were searched for studies on Actaea racemose and its administration in management of menopausal symptoms. Chem Office software was also used in order to find chemical structures. The key words used as search terms were Cimicifuga racemose, Actaea racemose, Ranunculaceae, Black cohosh, Menopausal symptoms. We have included all relevant animal and human studies up to the date of publication. The analysis on Actaea racemose showed various indications for different plant's extracts. Approximately 131 chemical compounds have been isolated and identified from Actaea racemosa. According to recently studies, the most important chemicals known of the Actaea racemosa are phenolic compounds, chromones, triterpenoids, nitrogen-containing constituents. In addition, in vivo and in vitro studies reported wide range of pharmacological activities for Black cohosh like attenuating menopausal symptoms. Mechanism of action for some ethnomedicinal indications were made clear while some of its activities are not confirmed by pharmacological studies yet. Further investigations on its pharmacological properties are necessary to expand its clinical effective use. Also, additional large clinical trials are recommended for clarifying the effect of Black cohosh.

Ethnobotany, Phytochemistry and Pharmacological Features of Centella asiatica: A Comprehensive Review.

Centella asiatica (CA) or Gotu cola is an herbal plant from the Apiaceae family with a long history of usage in different traditional medicines. It has long been used for the treatment of various ailments such as central nervous system (CNS), skin and gastrointestinal disorders especially in the Southeast Asia. This chapter focused on the phytochemical constituent and pharmacological activities of CA based on preclinical and clinical studies. Additionally, botanical description and distribution, traditional uses, interactions, and safety issues are reviewed. Electronic databases of Google Scholar, Scopus, PubMed, and Web of Science were searched to obtain relevant studies on the pharmacological activities of CA. Approximately, 124 chemical compounds including triterpenoids, polyphenolic compounds, and essential oils have been isolated and identified from CA. Ethnomedicinal applications of CA mostly include treatment of gastrointestinal diseases, wounds, nervous system disorders, circulatory diseases, skin problems, respiratory ailments, diabetes and sleep disorders in various ethnobotanical practices. Pharmacological studies revealed a wide range of beneficial effects of CA on CNS, cardiovascular, lung, liver, kidney, gastrointestinal, skin, and endocrine system. Among them, neuroprotective activity, wound healing and treatment of venous insufficiency, as well as antidiabetic activity seem to be more frequently reported. At the moment, considering various health benefits of CA, it is marketed as an oral supplement as well as a topical ingredient in some cosmetic products. Additional preclinical studies and particularly randomized controlled trials are needed to clarify the therapeutic roles of CA.

A Review of Glycyrrhiza glabra (Licorice) Effects on Metabolic Syndrome.

Metabolic syndrome is a pathological condition characterized by diabetes with insulin resistance, abdominal obesity, dyslipidemia, and hypertension. A wide body of research is emerging on Glycyrrhiza glabra L. (licorice) as a traditional herb with various therapeutic effects. Animal and human studies have indicated that licorice affects blood glucose, blood lipid profile, and blood pressure. Licorice seems to be effective in hyperglycemia and dyslipidemia; however, it can increase blood pressure. In this study, we intend to explain its role in regard with metabolic syndrome.

Evaluation of the Anti-constipation Effects of Abdominal Application of Olive Oil Ointment in Children 1-4 Years Old: A Pilot Placebo-Controlled, Double-Blind, Randomized Clinical Trial.

OBJECTIVE: With a prevalence of 0.7 to 29.6%, functional constipation (FC) is a common pediatric complaint worldwide. Current therapeutic strategies for FC mainly include prevention and treatment of fecal impaction, by administration of oral laxatives or rectal medications. However, these agents have been reported to have limited efficacy and a number of serious side effects. In traditional Persian medicine, local application of olive oil was used to relieve childhood constipation. In this pilot placebo-controlled, double-blind, randomized clinical trial, the laxative effects of the external use of olive oil ointment in 1- to 4-year-old children with functional constipation were investigated. METHODS AND MATERIALS: Forty patients with FC were randomly assigned in olive oil ointment or placebo groups, receiving either an ointment containing 85% olive oil or a comparable placebo or an ointment containing 85% liquid paraffin adjusted to have color and odor similar to those of intervention ointment, twice a day for 4 days. Rome III criteria for functional gastrointestinal disorders (FGIDs) were used to identify eligible patients from three hospitals. The primary outcome measure was treatment success, defined as ≥1 spontaneous stools per day, without episodes of fecal impaction at endpoint (day 4). The secondary outcome measure was the frequency of fecal incontinence, abdominal discomfort or flatulence, painful defecation, and dermal irritations (adverse effect). RESULTS: Improvements in stool frequency started from day 1 and continued up to day 4 (end of the study) and were significantly greater in patients receiving olive oil ointment in comparison with placebo group (p < 0.05). No adverse effect (including fecal incontinence, painful defecation, gripe and skin reaction, etc.) was reported in intervention and placebo groups during the study. CONCLUSION: Olive oil ointment used in this study can be presented as a safe, well-tolerated, and effective herbal preparation in children with functional constipation.

Artemisia: a promising plant for the treatment of cancer.

Due to the promising features of the ancient herbal plant Artemisia, its biologic activity has been investigated for use in modern medicine. In this regard, Artemisia and its active phytochemicals have been introduced as having antimalarial, antioxidant, cytotoxic, antispasmodic, anthelmintic, neuroprotective, anti-inflammatory, and antimicrobial agents. In the case of cancer treatment, the plant species and its bioactive compounds target multiple pathways. Here we reviewed the scientific literature published up until 2018, which have explained the cytotoxic activity of the Artemisia species and their constituents. This review summarizes the published data found in PubMed, Science Direct and Scopus. Here, studies about the cytotoxicity and antitumor action on cancer cells and tumor bearing animals are discussed. Also, detailed molecular pathways affected by the plant and the phytochemistry of the cytotoxic active components are presented. Among all species and chemical constituents, the active ones have been selected and discussed in detail. The cytotoxic comparison made here may open a window for future works and selection of agents for cancer chemotherapy.

Protective effects of Cinnamomum verum, Cinnamomum cassia and cinnamaldehyde against 6-OHDA-induced apoptosis in PC12 cells.

Cinnamon (Cinnamomum verum and C. cassia) is a medicinal plant, widely-used as a culinary spice. It possesses various therapeutic effects and can slow down the progression of neurological disorders impressively. In this article, the effects of hydro-alcohol extract and essential oil of C. verum and C. cassia and its main bioactive component cinnamaldehyde, has been examined on 6-OHDA-exposed PC12 cells as an in vitro model of Parkinson's disease. The cytotoxicity and cell apoptosis has been induced by 6-OHDA in PC12 cells. The protective effect was determined by measuring cell viability, the amount of reactive oxygen species (ROS), and apoptosis. Cell viability and apoptosis were assessed using resazurin assay, flow cytometry of propidium iodide (PI) stained cells, and western blot analysis. 6-OHDA resulted in the death and apoptosis of cells while, pretreatment with the extract and essential oil of C. verum and C. cassia at 20 µg/ml and cinnamaldehyde at 5 and 10 µM for 24 h could significantly increase the viability (p < 0.001), and decrease ROS content (p < 0.05). Pretreatment with the extracts increased survivin and decreased cyt-c whereas, pretreatment with the essential oil decreased cyt-c, increased survivin, and reduced P-p44/42/p44/42 levels to a level near that of the related control. The extract and essential oil of C. verum and C. cassia can be effective against 6-OHDA cytotoxicity. It is suggested that, the synergistic effects of cinnamaldehyde and other components of extract and essential oil promote cinnamon's medicinal properties.

Absolute configuration and anti-cancer effect of prenylated flavonoids and flavonostilbenes from Sophora pachycarpa: Possible involvement of Wnt signaling pathway.

A new prenylated flavonostilbene, namely, alopecurone P together with three known compounds sophoraflavanone G, 2-(4-hydroxyphenyl)-2,3-dihydrobenzo[b]furan-3,4,6-triol and alopecurone J were characterized from the roots of Sophora pachycarpa. The absolute configuration of alopecurones J and P were characterized by comparison of experimental electronic circular dichroism (ECD) spectroscopy and simulated data using time-dependent density functional theory (TDDFT) for possible stereoisomers. The cytotoxic properties of isolated compounds have also been evaluated on two breast cancer cell lines (MCF-7 and MDA-MB-231) and normal cell line (NIH/3T3) using AlamarBlue®, flowcytometry and western blot assays. Alopecurone J and P showed cytotoxic effect on MCF-7 cell line through Wnt signaling pathway. It seems that the presence of lavandulyl substitution in C-8 position of flavanone structure increased the cytotoxic effect.

Safranal protects against beta-amyloid peptide-induced cell toxicity in PC12 cells via MAPK and PI3 K pathways.

Alzheimer's disease is a type of cerebrovascular problem with progressive mental disabilities for the patient. This study aimed to investigate the protective effect of safranal on toxicity and oxidative damage induced by beta-amyloid (Aß) and hydrogen peroxide (H2O2) in PC12 cells as an appropriate model of Alzheimer's cell damage. PC12 cells pretreated with saffron extract (2.5-40 µg/ml), essential oil (2.5-40 µg/ml), safranal (2.5-5-40 µM) and donepezil (5, 10 and 20 µM) for 120 min. Then exposed to either Aß (25 µM) for 48 h or H2O2 (150 µM) for 24 h. In the end, the cell survival and intracellular reactive oxygen species (ROS) production analyzed. The anti-apoptotic effects of safranal in PC12 cells were studied using flow cytometry after PI staining. Also, western blot analysis of Cyt c, survivin, p44/42 MAPK (ERK1/2), Phospho-p44/42 MAPK (ERK1/2), PI3 Kinase P85, Phospho-PI3 Kinase P85, phospho SAPK/JNK, SAPK/JNK and caspase 3 performed for detection of apoptosis. Safranal (2.5 and 5 µM) and donepezil (10 and 20 µM) significantly decreased the Aß toxicity. The ROS significantly attenuated when cells pretreated with essential oil, saffron extract, safranal, and donepezil. Cell apoptosis significantly increased after treatment with Aß (25-35) (25 µM) compared to control. However, after pretreatment with safranal (2.5 µM) apoptosis was significantly reduced. Western blot analysis of PC12 cells showed that 25 µM Aß (25-35) could increase proteins involved in apoptosis signaling and pretreatment with safranal (2.5 µM) could decrease the apoptosis. According to the results, safranal showed anti-apoptotic and antioxidant effects and may exert promising potential for the prevention of Alzheimer's disease.