Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.

Recently many studies showed anticancer activities of piperine, a pungent alkaloid found in black pepper and some other Piper species. We attempted to summarize acquired data that support anticancer potential of this natural agent. Piperine has been reported to possess effective chemopreventive activity. It has been studied to affect several mechanisms of action, in brief enhancing antioxidant system, increasing level and activity of detoxifying enzymes and suppressing stem cell self-renewal. Moreover, piperine has been found to inhibit proliferation and survival of various cancerous cell lines via modulating cell cycle progression and exhibiting anti-apoptotic activity, respectively. This compound has been shown to modify activity of various enzymes and transcription factors to inhibit invasion, metastasis and angiogenesis. Interestingly, piperine has exhibited antimutagenic activity and also inhibited activity and expression of multidrug resistance transporters such as P-gp and MRP-1. Besides, about all reviewed studies have reported selective cytotoxic activity of piperine on cancerous cells in compared with normal cells. Altogether, the studies completely underline promising candidacy of piperine for further development. The collected preclinical data we provided in this article can be useful in the design of future researches especially clinical trials with piperine.

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter reducing neural excitability in the mammalian central nervous system (CNS) with three subclasses of receptors. Several conventional drugs and compounds modulate the GABAergic system, demonstrating different pharmacological effects. In this review, interactions of natural terpenoids with the GABAergic system are highlighted with relation to disorders like anxiety, insomnia, convulsion, pain, and cognitive deficits. Terpenoids with various structures affect the function of the GABAergic system via dissimilar mechanisms. Most of the discussed compounds interact with GABA receptors, but especially with the GABAA subtype. This may be due to the fact that researchers tend to assess the interaction of compounds using GABAA receptors. However, bilobalide, a sesquiterpene, showed anticonvulsant properties through the activation of glutamic acid decarboxylase (GAD) enzyme, which is a key enzyme in biosynthesis of GABA. Therefore, further studies evaluating and comparing terpenoids of different classes and their interaction with the GABA system, along with their pharmacokinetic properties, could be worthwhile in future studies.

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BackgroundMelia azedarach L. is an important medicinal plant that is used for variety of ailments in Iranian traditional medicine. Azadirachta indica A. Juss is its allied species and possesses similar properties and effects. The present study was undertaken to investigate anticancer activity of these M. azedarach in comparison with A. indica on cancer cell lines and also to evaluate their safety in humans by testing them on normal cell line. The study also aimed to determine the active components that are responsible for medicinal effects of M. azedarach in traditional usages.MethodsIn this study, the cytotoxic activity of crude extracts from M. azedarach and A. indica leaves, pulps and seeds as well as three main fractions of their leaf extracts were assayed against HT-29, A-549, MCF-7 and HepG-2 and MDBK cell lines. MTT assay was used to evaluate their cytotoxic activities. Methanol leaf fraction of M. azedarach as the safest leaf fraction in terms of cytotoxicity was subjected for phytochemical study.ResultsResults of the present study indicated that seed kernel extract of M. azedarach had the highest cytotoxic activity and selectivity to cancer cell lines (IC50 range of 8.18- 60.10 μg mL-1). In contrast to crude seed extract of A. indica, crude pulp and crude leaf extracts of this plant showed remarkably stronger anti-prolifrative activity (IC50 ranges of 83.45 - 212.16 μg mL-1 and 34.11- 95.51 μg mL-1 respectively) than those of M. azedarach (all IC50 values of both plants > 650 μg mL-1). The phytochemical analysis led to the isolation of four flavonol 3-O-glycosides including rutin, kaempferol-3-O-robinobioside, kaempferol-3-O-rutinoside and isoquercetin along with a purin nucleoside, β-adenosine.ConclusionsThe anti-prolifrative potentials of extracts from different parts of M. azedarach and A. indica were determined. By comparison, methanol leaf fraction of M. azedarach seems to be safer in terms of cytotoxicity. Our study shows that flavonols are abundant in the leaves of M. azedarach and these compounds seem to be responsible for many of medicinal effects exploited in the traditional uses.

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Background Plumbagin is as an important bioactive secondary metabolite found in the roots of Plumbago spp. The only one species, Plumbago europaea L., grows wild in Iran. The therapeutic use of plumbagin is limited due to its insufficient supply from the natural sources as the plants grow slowly and take several years to produce quality roots. Objectives To develop an efficient protocol for the establishment of callus and cell suspension cultures of P. europaea and to evaluate production of plumbagin in callus and cell suspension cultures of P. europaea for the first time. Material and Methods Stems and leaves explants were cultured on agar solidified (7% w/v) MS media, supplemented with different combination of 2, 4-D and Kin or 6-Benzylaminopurin (BA) for callus induction. The rapid growing calli were cultured in liquid Murashige and Skoog (MS) media in agitated condition for establishing cell suspension cultures of P. europaea . Moreover, the effects of light and dark conditions on the cell growth, cell viability and plumbagin production in cell suspension cultures of P. europaea were assessed. Results Friable calli were successfully induced using stem segments of P. europaea in semisolid MS medium supplemented with 1 mg.L -1 2, 4-Dichlorophenoxy acetic acid (2, 4-D) and 0.5 mg.L -1 of kinetin (Kin). Optimal cell growth was obtained when the cells were grown in MS liquid media supplemented with 1 mg.L -1 2, 4-D and 0.5 mg.L -1 kinetin with an initial cell density of ~3×10 5 cells per ml incubated in the dark at 25 ± 1 °C. Growth curve revealed that the maximum cell growth rate (14.83×10 5 cells per ml) achieved on the day 18 and the highest plumbagin content (0.9 mg.g -1 Dry Cell Weight (DCW)) in the cells was obtained at the late exponential phase under dark condition which determined by High Performance Liquid Chromatography (HPLC) technique. Based on the obtained results, cell viability remained around 82.73% during the 18 days of cell culture in darkness. These suspension cultures showed continuous and stable production of plumbagin. Conclusions Our study suggests that cell suspension cultures of P. europaea represent an effective system for biosynthesis and production of plumbagin as a valuable bioactive compound.