Analysis of hyperforin (St. John's wort) action at TRPC6 channel leads to the development of a new class of antidepressant drugs.

St. John's wort is an herb, long used in folk medicine for the treatment of mild depression. Its antidepressant constituent, hyperforin, has properties such as chemical instability and induction of drug-drug interactions that preclude its use for individual pharmacotherapies. Here we identify the transient receptor potential canonical 6 channel (TRPC6) as a druggable target to control anxious and depressive behavior and as a requirement for hyperforin antidepressant action. We demonstrate that TRPC6 deficiency in mice not only results in anxious and depressive behavior, but also reduces excitability of hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. Using electrophysiology and targeted mutagenesis, we show that hyperforin activates the channel via a specific binding motif at TRPC6. We performed an analysis of hyperforin action to develop a new antidepressant drug that uses the same TRPC6 target mechanism for its antidepressant action. We synthesized the hyperforin analog Hyp13, which shows similar binding to TRPC6 and recapitulates TRPC6-dependent anxiolytic and antidepressant effects in mice. Hyp13 does not activate pregnan-X-receptor (PXR) and thereby loses the potential to induce drug-drug interactions. This may provide a new approach to develop better treatments for depression, since depression remains one of the most treatment-resistant mental disorders, warranting the development of effective drugs based on naturally occurring compounds.

Cytotoxic terpenoids from Tripterygium hypoglaucum against human pancreatic cancer cells SW1990 by increasing the expression of Bax protein.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium hypoglaucum (Kunmingshanhaitang in Chinese) is a plant of the genus Tripterygium which have been used as anti-tumor folk medicines in Yi and Bai ethnic groups in Yunnan province, China for hundreds of years. Terpenoids from T. hypoglaucum presented therapeutic effects on multiple tumors. But there were few studies about pancreatic cancer treatment of these terpenoids. Pancreatic cancer is an aggressive malignancy and lacked of specific drugs. Currently, anti-tumor drugs have poor therapeutic effect and prognosis for pancreatic cancer. AIM OF THE STUDY: This study aimed to elucidate the terpenoids from T. hypoglaucum and illuminate their anti-pancreatic cancer bioactivities. MATERIAL AND METHODS: Terpenoids were obtained through sequential chromatographic methods including silica gel, MCI gel, Sephadex LH-20, and preparative HPLC. Their structures were determined by HRESIMS, 1D and 2D NMR spectroscopic analysis. The absolute configurations of some new diterpenoids were assigned through comparison of experimental and calculated circular dichroism spectra. The cytotoxicity of isolates was measured using the MTT method on human pancreatic cancer cells SW1990. The effects on expressions of AKT, Erk1/2, p-AKT, p-Erk1/2, and Bax proteins in human pancreatic cancer cells SW1990 of these compounds were determined by western blotting assays. RESULTS: Eleven new (compounds 1∼11) and fourteen known terpenoids (compounds 12∼25) were isolated from the underground parts of T. hypoglaucum. These compounds were belonged to abietane diterpenoids, isoprimara diterpenoids, ent-kaurane diterpenoids, oleanane triterpenoids, and friedelane triterpenoids. Compounds 5, 7, 8, 9, 16, 18, 22, 24, and 25 possessed significant cytotoxicity against SW1990 cells with IC50 values of 19.28 ± 4.39, 9.91 ± 2.23, 27.32 ± 5.89, 56.43 ± 6.92, 0.16 ± 0.05, 0.58 ± 0.15, 0.81 ± 0.04, 0.48 ± 0.11, and 10.01 ± 1.39 µM respectively. After compounds 16, 22, and 24 been treated with the pancreatic cancer cells in medium and high doses, the protein expressions of AKT, p-AKT, Erk, and p-Erk were not remarkably reduced and the expressions of Bax protein were significantly increased. CONCLUSION: This study indicated that terpenoids from T. hypoglaucum could inhibit human pancreatic cancer cells SW1990. Especially, compounds 16, 22, and 24 possessed significant cytotoxicity against SW1990 cells with low IC50 values and could increase the expressions of Bax protein. These compounds shared a wide variety of structural characteristics which provided us more candidate molecules for the development of anti-pancreatic cancer drugs and further prompted us to investigate their anti-pancreatic mechanisms.

Natural products isolation studies of the paleoendemic plant species Nothofagus gunnii and Nothofagus cunninghamii.

The first natural product isolation studies of Nothofagus gunnii (Hook.f.) Oerst and Nothofagus cunninghamii (Hook.f.) Oerst have been undertaken. A previously unreported stilbene derivative, pinosylvin monoacetate, was isolated from the leaves of N. gunnii, in addition to 14 known compounds; including the flavonoids galangin, pinobanksin, catechin and quercetin; sesquiterpenoids such as, ilicol and (+)-ß-costol acetate; 2,4-dihydroxy-6-methoxychalcone and pinosylvin. Four known flavonoid natural products, catechin, quercetin, ayanin, and avicularin were isolated from the leaves of N. cunninghamii. This study reveals that N. gunnii is a rich source of flavonoid, chalcone and stilbene compounds, while primarily hydroxyflavonoid compounds are found in N. cunninghamii. The isolated phytochemicals are consistent with the evolutionary relationships suggested to exist among Nothofagus species.

New enantiomeric lignans and new meroterpenoids with nitric oxide release inhibitory activity from Piper puberulum.

Six new lignans with various type of linkage between two C6-C3 fragments (1a, 1b, 2a, 2b, 3, 4), two new meroterpenoids (5, 6) and 24 known compounds (7-30) were isolated from an EtOH extract of the stems and leaves of Piper puberulum. The absolute configurations of enantiomers 1a and 1b were determined by single-crystal X-ray diffraction analysis, 2a and 2b were determined by comparing their calculated and experimental ECD spectra. Biogenetically, all the new lignans may come from the polymerization of two molecules of hydroxychavicol (30). In the anti-neuroinflammation activity assay, the IC50 values of fifteen compounds were lower than those of the positive control minocycline, and compound 1a showed good activity, but its enantiomer 1b showed no activity. Compound 1a have notable anti-neuroinflammatory activity, and can significantly decrease mRNA levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in a dose-dependent manner.

An in vitro investigation of the phytochemical contents of Marsdenia macrantha root and its antibacterial activity against selected foodborne pathogens.

INTRODUCTION: Marsdenia macrantha is a crucial source of traditional medicine in Northern Namibia. Its roots are used to treat various health conditions ranging from mouth infections to urinary retention. Despite its medicinal application, there is no known knowledge of its therapeutic properties. Thus, we investigated the phytochemical content and antibacterial activity of M. macrantha. METHODS: M. macrantha root extracts were obtained using three different solvents (distilled water, methanol and acetone) - in the soxhlet and maceration extraction methods. Total phytochemical (terpenoid, alkaloid and/or flavonoid) content was determined by spectrophotometry. Antibacterial activity against common foodborne pathogens (Staphylococcus aureus, Escherichia coli and Salmonella typhi) was determined by both well and disc diffusion method. RESULTS: we detected the presence of all the tested phytochemicals. Methanol gave the highest percentage yield of extraction (mean: 13.95 ± standard deviation: 0.41%) followed by water (10.92 ± 0.11%) and acetone (6.85 ± 0.23%), F-ratio=326.71 and p<0.0003. The total content determined showed that M. macrantha root extract contained more flavonoids than alkaloids (mg of standard per grams of the dry material). Antibacterial analyses showed inhibitory activity against all the selected pathogens, with the highest inhibition zone against S. typhi (19.7 ± 0.3 mm) - for the acetone-prepared root extract. There were variations in minimum inhibitory concentrations of the extracts prepared by the different solvents. CONCLUSION: this is the first study demonstrating the presence of phytochemicals and antibacterial properties of M. macrantha roots. Further studies are needed to isolate and characterize the phytochemicals for antibacterial application.

Potential Biological Activities of Clausena Essential Oils for the Treatment of Diabetes.

Diabetes mellitus constitutes one of the most important public health problems. It is defined as a metabolic disorder characterized by a chronic hyperglycemic condition. The inhibition of α-glucosidase and inflammation effects is still considered a strategy for the treatment of diabetes. The aim of this study was to search for new and effective natural functional foods agents for the complementary treatment of diabetes and other related complications. The essential oils from the leaves of three Clausena plants collected in Thailand: C. harmandiana, C. guillauminii and C. excavata were obtained by hydrodistillation. The chemical compositions, antioxidant, anti-α-glucosidase and anti-inflammatory activities of these essential oils were evaluated. The C. excavata and C. harmandiana essential oils contained seselin and terpinen-4-ol, respectively, as the major components and showed strong inhibition of DPPH free radical, α-glucosidase, lipoxygenase and nitric oxide activities with the IC50 values ranging from 0.031±0.005 to 0.702±0.003 mg/mL. From these results, it may be concluded that seselin and terpinen-4-ol are important for high antioxidant, anti-α-glucosidase, and anti-inflammatory activities. Therefore, these Clausena essential oils may be useful in industrial applications for the treatment of diabetes and other related complications.

Terpene-rich fractions of Ficus mucoso (Welw) modulate lipopolysaccharide-induced inflammatory mediators and aberrant permeability of the inner mitochondrial membrane in murine animal model.

Ficus mucoso is traditionally used to treat bronchial infections. This study compared the efficacy of terpene-rich fractions of F. mucoso root bark on lipopolysaccharide(LPS)-induced inflammation, liver mitochondrial permeability transition (mPT), an index of mitochondrial health, and associated pathological alterations. Terpene-Rich Fractions of Dichloromethane (TRDF) and Ethylacetate Fractions of F. mucoso (TREF) were obtained according to standard procedures. To induce systemic inflammation, a single intraperitoneal injection of 1mgLPS/kgbw was given to mice. Spectrophotometric techniques were used to evaluate the effects of the oral administration of TRDF and TREF (3 days) on levels of pro-inflammatory mediators (TNF-α, IL-1ß, IL-6) using ELSA techniques as well as antioxidant indices in normal and LPS-treated mice. The mPT pore opening, mitochondrial ATPase activity and lipid peroxidation were monitored spectrophotometrically. Our results revealed that treatment with LPS caused significant elevation in serum cytokine levels while administration of 50 and 100 mg/kg TRDF and TREF significantly reduced elevated serum levels of cytokines (TNF-α, IL-1ß, IL-6) in LPS-challenged mice. In addition, activitities of superoxide dismutase, catalase and liver marker enzymes (ALT and AST) as well as levels of mitochondrial lipid peroxides were significantly reduced in mice treated with TRDF and TREF relative to LPS-fed mice. Furthermore, LPS caused induction of opening of the liver mPT pore which was significantly inhibited by TRDF at 100 and 200 mg/kg bw by 71% and 88%, respectively, but only at 100 mg/kg TREF. Furthermore, mitochondrial ATPase activity was inhibited largely by TRDF. UPLC-ESI-MS analysis revealed the presence of terpenoid derivatives and a few aromatic metabolites in TRDF. The terpene dominance of TRDF metabolites was further justified on the 1H NMR fingerprint. Overall, TRDF is more effective as a cocktail of anti-inflammatory compounds than TREF against LPS-induced acute systemic inflammation.

Cochlioquinone derivatives produced by coculture of endophytes, Clonostachys rosea and Nectria pseudotrichia.

Three new meroterpenoid derivatives, furanocochlioquinol (1) and furanocochlioquinone (2), as well as nectrianolin D (3), together with two known biogenetically related compounds 4 and 5 were isolated from a mixed culture of two mangrove-derived fungi, Clonostachys rosea B5-2 and Nectria pseudotrichia B69-1. The structures of 1-3 were deduced based on the interpretation of HRMS and NMR data. Compounds 1-5 exhibited cytotoxicity against human promyelocytic leukemia (HL60) cells with IC50 values ranging from 0.47 to 10.16 µM.

Assessment of Chemopreventive Potential of the Plant Extracts against Liver Cancer Using HepG2 Cell Line.

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.

Modulation of the PGE2-Mediated Pathway in the Eclosion Blocking Effect of Flumethrin and Terpenoid Subfraction Isolated from Artemesia nilagirica in Rhipicephalus annulatus.

Prostaglandins are a group of important cell-signaling molecules involved in the regulation of ovarian maturation, oocyte development, egg laying and associated behaviors in invertebrates. However, the presence of prostaglandin E2 (PGE2), the key enzymes for PGE2 biosynthesis and its interference by drugs were not investigated previously in the ovary of ticks. The present study was undertaken to assess the modulation of the PGE2-mediated pathway in the eclosion blocking effect of flumethrin and terpenoid subfraction isolated from Artemisia nilagirica in Rhipicephalus annulatus ticks. The acaricidal activities and chemical profiling of the terpenoid subfraction were performed. The localization of the cyclooxygenase1 (COX1) and prostaglandin E synthase (PGES) enzymes and the quantification of PGE2 in the ovaries of the ticks treated with methanol (control), flumethrin and terpenoid subfraction were also undertaken. In addition, the vitellogenin concentration in hemolymph was also assayed. Both flumethrin and the terpenoid subfraction of A. nilagirica elicited a concentration-dependent inhibition of fecundity and blocking of hatching of the eggs. The COX1 could not be detected in the ovaries of treated and control ticks, while there was no significant difference observed in the concentration of vitellogenin (Vg) in them. The presence of PGES in the oocytes of control ticks was confirmed while the immunoreactivities against PGES were absent in the vitellogenic oocytes of ticks treated with flumethrin and terpenoid subfraction. The levels of PGE2 were below the detection limit in the ovaries of the flumethrin-treated ticks, while it was significantly lower in the ovaries of the terpenoid subfraction-treated ticks. Hence, the prostaglandin E synthase and PGE2 were identified as very important mediators for the signaling pathway for ovarian maturation and oviposition in ticks. In addition, the key enzyme for prostaglandin biosynthesis, PGES and the receptors for PGE2 can be exploited as potential drug targets for tick control. The detection of PGES by immunohistochemistry and quantification of PGE2 by LC-MSMS can be employed as valuable tools for screening newer compounds for their eclosion blocking acaricidal effects.

Five terpenoids from the gum resin of Boswellia carterii and their cytotoxicity.

One undescribed tetracyclic triterpene (boswellicarin A), four undescribed pentacyclic triterpenes (boswellicarterins A-C) and one undescribed prenylaromadendrane-type diterpene (boscarterin A) were isolated from the gum resin of Boswellia carterii Birdw. (Burseraceae). Their structures were elucidated from NMR and HRESIMS spectroscopic data and ECD spectra. Boswellicarterins A-C and boscarterin A displayed weak and selective cytotoxicity against three human cancer cells (HepG2, A549 and MCF-7) by MTT assay.

Euphorboside A, a cytotoxic meroterpenoid glycoside with an unusual humulene-phloroglucinol skeleton from Euphorbia kansuensis.

Euphorboside A (1), an unusual meroterpenoid glycoside featuring the incorporation of an acylphloroglucinol moiety into a humulene skeleton to form a 6/6/11 ring system, was isolated from the roots of Euphorbia kansuensis. Its structure was elucidated by extensive spectroscopic analysis, chemical methods, and ECD calculations. Compound 1 was screened for the cytotoxicity against nine cancer cell lines, and 1 showed marked inhibitory activities against human colon cancer RKO and human breast cancer MDA-MB-231 cell lines with IC50 values of 3.70 and 4.15 µM, respectively.

Chemical Constituent, Antimicrobial Activity, and Synergistic Effect of the Stem, Leaf, and Flower Essential Oil of the Artemisia fragrans Willd. from Khoy.

Artemisia fragrans is commonly used as a folk medicine as antispasmodic, anti-pyretic, anti-inflammatory, and abortifacient agents. The villagers use its pungent odor to repel rodents, mites, and pests, as well as its essential oil and smoke after burning to treat lung infections after uprooting the plant. Herein, we extracted the essential oils (EOs) of different parts of the plant and analyzed their chemical compositions and antibacterial activities. The chemical analysis led to the identification of 73, 59, and 57 compounds in the EOs of the stem, leaf, and flower, respectively. All of the EOs exhibited antibacterial activities against both G+ and G- bacteria. The EOs of the leaf and flower were more effective against tested bacteria, except B. anthracis and P. aeruginosa, compared to that of the stem. The binary combination of the EOs (stem and flower) or (stem and leaf) showed a synergistic effect. Statistical analysis indicated EOs of leaf and flower are more potent than that of the stem. These findings suggest the application of leaf and flower of the plant, which not only can prevent its uprooting but also ensure better therapeutic function.

Polyprenylated acylphloroglucinol meroterpenoids with PTP1B inhibition from Hypericum forrestii.

Three new polyprenylated acylphloroglucinol meroterpenoids, hyperiforins A-C (1-3), were isolated from Hypericum forrestii (Chittenden) N. Robson, together with twelve known analogues (4-15). Their structures were established by extensive physical and spectroscopic data analysis. Compounds 1, 2, 5, 7, and 13-15 showed potent inhibitory effects on protein tyrosine phosphatase 1B with IC50 values from 6.63 ± 2.40 to 14.21 ± 3.51 µM.

Therapeutic indications, chemical composition and biological activity of native Brazilian species from Psidium genus (Myrtaceae): A review.

ETHNOPHARMACOLOGICAL IMPORTANCE: Brazilian medicinal species of the Psidium genus are rich in secondary metabolites such as terpenes and phenolic compounds and present biological activities for several human diseases. For the native Psidium species, there are no specific research reports for any member of the genus about ethnobotanical research, hindering the joint analysis of its therapeutic indications together with the scientific evidence already investigated. STUDY OBJECTIVE: Analyze the therapeutic indications, the main chemical constituents, and the biological activities of native species of the Psidium to Brazil. MATERIALS AND METHODS: Systematic research was carried out in the Scopus, ScienceDirect, PubMed, and Web of Science databases over a period of ten years. Articles in English, Portuguese and Spanish were used. The research was divided into three phases, seeking information on ethnobotany, chemical composition and biological activities. The words were combined to structure the descriptors used in the search. RESULTS: A total of 13 native species belonging to the Psidium genus were identified in this analysis, Psidium acutangulum DC., Psidium brownianum Mart. ex DC., Psidium cattleyanum Sabine, Psidium densicomum Mart. ex DC., Psidium grandifolium Mart. ex DC., Psidium guineense Sw., Psidium laruotteanum Cambess., Psidium myrsinites DC, Psidium myrtoides O. Berg, Psidium salutare (Kunth) O. Berg, Psidium schenckianum Kiaersk., Psidium sobralianum Proença & Landrum, Psidium striatulum Mart. ex DC. Of these, six were indicated in folk medicine, digestive system disorders being their main therapeutic indication. Most species presented an investigation of chemical composition and biological activity. They are rich in phenolic compounds, flavonoids, and terpenes and have antimicrobial, antioxidant, antiproliferative, and repellent activities. CONCLUSIONS: Native species of the Psidium genus are important sources of active ingredients in combating adversities that affect the human health, especially regarding the digestive system. They have a rich chemical composition, responsible for the biological activities demonstrated for the species.

Pronounced anti-neuroinflammatory jasmonates and terpenes isolated from lychee seeds.

Lychee is a favorite fruit of the Cantonese and native to Southeast Asia. In this study, the anti-neuroinflammatory bioactive compounds of lychee seeds have been carried out. Five new jasmonates (1, 2, 6-8) and seventeen known compounds were isolated using a series of chemical and chromatographic methods. Their chemical structures were identified through comprehensive spectroscopic analysis. Anti-neuroinflammatory activities were assayed and evaluated for the purified compounds. Most of the compounds exhibited pronounced anti-neuroinflammatory activities on nitric oxide (NO) induced by lipopolysaccharide (LPS) in BV-2 microglia cells. Moreover, compounds 1, 2 and 20 could reduce the expression of LPS-induced pro-inflammatory factors (iNOS and COX-2), inhibit the expression of mRNA levels of iNOS, COX-2, IL-6 and block NF-κB nuclear translocation in dose-dependent manners. This study suggested that lychee phytochemicals could be benefit to some neuroinflammatory-associated diseases, such as Alzheimer's disease.

Phytochemical Profile and Antioxidant Activity of Nigella sativa L Growing in Morocco.

BACKGROUND: Nigella sativa L (NS) is a powerful antioxidant and medicinal plant with many therapeutic applications particularly in traditional medicine for respiratory, gastrointestinal, rheumatic, and inflammatory disorders, as well as cancer. OBJECTIVE: The aim of this study is to extract the active ingredients from the Moroccan Nigella sativa L and determine its antioxidant properties. We hypothesize that the separation of the compounds from Nigella sativa L has either a positive or negative effect on antioxidants. To study this, we explored different methods to simultaneously extract and separate compounds from Nigella sativa L and performed antioxidant tests (ß-carotene and DPPH) for all collected fractions. METHODS: Nigella sativa L was hot-extracted by Soxhlet and mother extracts and was separated using silica column chromatography with adequate eluents. Qualitative phytochemical tests to determine the chemical families in Nigella sativa L seeds were performed on the fractions. They were also identified and characterized by GC-MS and HPLC-DAD. Then, antioxidant activity was examined by ß-carotene bleaching and DPPH radical scavenger tests. Results and Conclusion. The mother extract hexane FH generated eight different fractions (SH1-8) and the acetone extract FA generated 11 fractions (SA1-11). The FH fractions had a high percentage of fatty acids, and the FA fractions had some interesting polyphenols derivative compounds. Phytochemical screening revealed secondary metabolites such as polyphenols flavonoids, alkaloids, steroids, terpenes coumarins, tannins, and saponins. We found that only two solvents (hexane, acetone) of different polarities could easily extract and simultaneously separate the components of Nigella sativa L. The antioxidant fractions that we collected had close activity to reference compounds but were more active than the corresponding mother extracts. Moreover, several IC50 values of fractions from acetone extract were better than those from hexane. Therefore, the antioxidant activity of Nigella sativa L is more attributed to flavonoids and polyphenols than fatty acids. In summary, the separation of hexane extract presents a more pronounced positive effect for antioxidant tests than acetone extract.

Evaluation of Antioxidant and Enzyme Inhibition Properties of Croton hirtus L'Hér. Extracts Obtained with Different Solvents.

Croton hirtus L'Hér methanol extract was studied by NMR and two different LC-DAD-MSn using electrospray (ESI) and atmospheric pressure chemical ionization (APCI) sources to obtain a quali-quantitative fingerprint. Forty different phytochemicals were identified, and twenty of them were quantified, whereas the main constituents were dihydro α ionol-O-[arabinosil(1-6) glucoside] (133 mg/g), dihydro ß ionol-O-[arabinosil(1-6) glucoside] (80 mg/g), ß-sitosterol (49 mg/g), and isorhamnetin-3-O-rutinoside (26 mg/g). C. hirtus was extracted with different solvents-namely, water, methanol, dichloromethane, and ethyl acetate-and the extracts were assayed using different in vitro tests. The methanolic extracts presented the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) values. All the tested extracts exhibited inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with a higher activity observed for dichloromethane (AChE: 5.03 and BChE: 16.41 mgGALAE/g), while the methanolic extract showed highest impact against tyrosinase (49.83 mgKAE/g). Taken together, these findings suggest C. hirtus as a novel source of bioactive phytochemicals with potential for commercial development.

Crocus sativus L. Extracts and Its Constituents Crocins and Safranal; Potential Candidates for Schizophrenia Treatment?

Schizophrenia is a chronic mental devastating disease. Current therapy suffers from various limitations including low efficacy and serious side effects. Thus, there is an urgent necessity to develop new antipsychotics with higher efficacy and safety. The dried stigma of the plant Crocus sativus L., (CS) commonly known as saffron, are used in traditional medicine for various purposes. It has been demonstrated that saffron and its bioactive components crocins and safranal exert a beneficial action in different pathologies of the central nervous system such as anxiety, depression, epilepsy and memory problems. Recently, their role as potential antipsychotic agents is under investigation. In the present review, I intended to critically assess advances in research of these molecules for the treatment of schizophrenia, comment on their advantages over currently used neuroleptics as well-remaining challenges. Up to our days, few preclinical studies have been conducted to this end. In spite of it, results are encouraging and strongly corroborate that additional research is mandatory aiming to definitively establish a role for saffron and its bioactive components for the treatment of schizophrenia.

Diacylglycerol acyltransferase inhibitory new meroterpenes from the seeds of Psoralea corylifolia, and their structure-activity relationship study.

Five new meroterpenes, 12α-Psoracorylifol F (1), 7ß,8α-hydroxy-12ß-Psoracorylifol F (2), 8-ketone-Cyclobakuchiol C (3), 7α,8ß-hydroxy-12ß-Cyclobakuchiol C (4) and 8α-hydroxy-Cyclobakuchiol C (5) together with six known compounds (6-11) were isolated from seeds of Psoralea corylifolia, and their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 1-6 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 61.5 ± 1.1 to 89.1 ± 1.2 µM.