miR-15b-5p targeting amyloid precursor protein is involved in the anti-amyloid eflect of curcumin in swAPP695-HEK293 cells.

Curcumin exerts a neuroprotective effect on Alzheimer's disease; however, it is not known whether microRNAs are involved in this protective effect. This study was conducted using swAPP695-HEK293 cells as an Alzheimer's disease cell model. swAPP695-HEK293 cells were treated with 0, 0.5, 1, 2, 5, and 10 µM curcumin for 24 hours. The changes in miR-15b-5p, miR-19a-3p, miR-195-5p, miR-101-3p, miR-216b-5p, miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction. The mRNA and protein levels of amyloid precursor protein, amyloid-ß40 and amyloid-ß42 were evaluated by quantitative real-time polymerase chain reaction, western blot assays and enzyme-linked immunosorbent assays. swAPP695-HEK293 cells were transfected with miR-15b-5p mimic, or treated with 1 µM curcumin 24 hours before miR-15b-5p inhibitor transfection. The effects of curcumin on amyloid precursor protein, amyloid-ß40 and amyloid-ß42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay. Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3'-untranslated region of amyloid precursor protein. The results show that amyloid precursor protein and amyloid-ß expression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells. Curcumin suppressed the expression of amyloid precursor protein and amyloid-ß and up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells. In addition, we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-ß levels in the curcumin-treated cells. Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3'-untranslated region of amyloid precursor protein. These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-ß in swAPP695-HEK293 cells, which was partially mediated by miR-15b-5p via targeting of the 3'-untranslated region of amyloid precursor protein.

Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective.

Synergy is a process in which some substances cooperate to reach a combined effect that is greater than the sum of their separate effects. It can be considered a natural "straight" strategy which has evolved by nature to obtain more efficacy at low cost. In this regard, synergistic effects may be observed in the interaction between herbal products and conventional drugs or biochemical compounds. It is important to identify and exploit these interactions since any improvement brought by such kind of process can be advantageously used to treat human disorders. Even in a complex disease such as cancer, positive synergistic plant-drug interactions should be investigated to achieve the best outcomes, including providing a greater benefit to patients or avoiding adverse side effects. This review analyzes and summarizes the current knowledge on the synergistic effects of plant-drug interactions with a focus on anticancer strategies.

Structure and histochemistry of medicinal species of Solanum

ABSTRACT Studies on native medicinal plants strengthen initiatives to preserve the environments where those species naturally occur, many of them already strongly menaced even before their potential to humankind is known. Root and stem barks, leaves, and pericarps samples of Solanum agrarium Sendtn., S. lycocarpum A. St.-Hil., S. palinacanthum Dunal, S. paniculatum L., and S. stipulaceum Roem. & Schult., species that occur in the Cerrado (Brazililan savanna) were processed according to common light microscopy techniques for structural analysis, and histochemical tests were performed to locate and identify classes of chemical compounds. The distinctive features identified were low concentration of crystal sand in the root and stem, presence of terpene resin in the root, and absence of hypodermis in the leaf, in S. agrarium; bright spots (group of sclereids) in the root, isobilateral mesophyll, thickened cell walls with hemicelluloses and strong aroma in the fruit, in S. lycocarpum; high concentration of crystal sand in the root and stem, oval-shaped limb, presence of isolated crystals in the exocarp, in S. palinacanthum; strong sclerification and rays with great height in the root and stem, in S. paniculatum; and accumulation of soluble protein in the root and stem, presence of conspicuous membranaceous stipules, absence of spiniform trichomes, in S. stipulaceum. This work identifies distinctive structural features, its ecological importance, and determines the distribution of secondary compounds associated with the medicinal properties reported for these species and contributes to the conservation of the natural environments where they occur.

Effects of Ziziphus jujuba fruit extracts on cytochrome P450 (CYP1A2) activity in rats.

Drug-drug interactions have become a serious problem in the clinic, since plant-based medicines are extensively used. The present study investigated the effects of Ziziphus jujuba fruit (ZJ) extract on the pharmacokinetics of phenacetin, a typical substrate of a cytochrome P450 enzyme CYP 1A2, in rats. The rats were pretreated with the water extract (1.0 g · kg(-1)) or the ethanolic extract (3.6 g · kg(-1)) of ZJ for 10 days, and the pharmacokinetics of phenacetin was investigated after intravenous administration. In an in vitro assay, acetaminophen formation in the hepatic microsomes of ZJ-treated rats was investigated to assess CYP1A2 activity. Our results demonstrated that the treatment with the water and ethanolic extracts of ZJ decreased the plasma concentration of phenacetin and increased the plasma concentration of acetaminophen, resulting in a 43.2% and 15.5% reduction in the AUC0-120 of phenacetin, respectively, and a 53.2% and 64.9% increase in the AUC0-120 of acetaminophen, respectively after intravenous administration. The water or ethanolic extract of ZJ significantly increased the clearance of phenacetin and acetaminophen formation in hepatic microsomes. In conclusion, ZJ extracts displayed effects on the pharmacokinetics of phenacetin and increased the CYP1A2 activity in rats. Therefore, precaution on drug-drug interactions should be taken when ZJ is co-administered with drugs metabolized by CYP1A2, which may result in decreased concentrations of these drugs.

Avaliação fitoquímica e potencial cicatrizante do extrato etanólico dos frutos de Jucá (Libidibia ferrea) em ratos Wistar / Phytochemical evaluation and wound healing potential of the fruit extract ethanolic of Jucá (Libidibia ferrea) in Wistar rats

Libidibia ferrea é uma planta muito utilizada popularmente para fins terapêuticos, inclusive para acelerar processos de cicatrização de feridas cutâneas. O presente trabalho pesquisou a composição química e avaliou o potencial cicatrizante do extrato etanólico dos frutos de L. ferrea (Mart. ex Tul.) em ratos. Foram utilizados 24 ratos Wistar divididos em quatro grupos. De todos os animais, foi retirado um fragmento de pele do dorso e cada grupo recebeu um tratamento diferente: solução de NaCl 0,9%, digliconato de clorexidina 1%, extrato etanólico dos frutos de Libidibia ferrea 12,5% e 50%. O processo de cicatrização foi avaliado macro e microscopicamente. Para a cicatrização de pele em ratos o extrato etanólico dos frutos de L. ferrea a 12,5% é significativamente mais eficiente do que a 50%. Saponinas, ácidos orgânicos, açúcares redutores, fenóis e taninos, sesquiterpenolactonas e outras lactonas, e antraquinonas foram encontrados no extrato.

Libidibia ferrea is a plant popularly used for therapeutic purposes, including processes to accelerate wound healing. The present investigation analyzed the chemical composition and the healing potential of ethanolic extract of the fruits of L. ferrea (Mart. ex Tul.) in rats. This study used 24 Wistar rats divided into four groups. In all animals a piece of skin on the back was removed and each group received a different treatment: NaCl 0.9%, Chlorhexidine digluconate 1%, ethanol extract of the fruits of Libidibia ferrea 12.5% and 50%. The healing process was evaluated macroscopically and microscopically. The ethanolic extract of the fruits of L. ferrea 12.5% was significantly more efficient than the 50% healing in rat skin.

Effects of Ziziphus jujuba fruit extracts on cytochrome P450 (CYP1A2) activity in rats / 中国天然药物

Drug-drug interactions have become a serious problem in the clinic, since plant-based medicines are extensively used. The present study investigated the effects of Ziziphus jujuba fruit (ZJ) extract on the pharmacokinetics of phenacetin, a typical substrate of a cytochrome P450 enzyme CYP 1A2, in rats. The rats were pretreated with the water extract (1.0 g · kg(-1)) or the ethanolic extract (3.6 g · kg(-1)) of ZJ for 10 days, and the pharmacokinetics of phenacetin was investigated after intravenous administration. In an in vitro assay, acetaminophen formation in the hepatic microsomes of ZJ-treated rats was investigated to assess CYP1A2 activity. Our results demonstrated that the treatment with the water and ethanolic extracts of ZJ decreased the plasma concentration of phenacetin and increased the plasma concentration of acetaminophen, resulting in a 43.2% and 15.5% reduction in the AUC0-120 of phenacetin, respectively, and a 53.2% and 64.9% increase in the AUC0-120 of acetaminophen, respectively after intravenous administration. The water or ethanolic extract of ZJ significantly increased the clearance of phenacetin and acetaminophen formation in hepatic microsomes. In conclusion, ZJ extracts displayed effects on the pharmacokinetics of phenacetin and increased the CYP1A2 activity in rats. Therefore, precaution on drug-drug interactions should be taken when ZJ is co-administered with drugs metabolized by CYP1A2, which may result in decreased concentrations of these drugs.

¹H-qNMR for direct quantification of stachydrine in Leonurus japonicus and L. cardiaca.

(1)H-qNMR-spectroscopy was successfully applied to quantify the pharmacologically active alkaloid stachydrine ((2S)-1,1-dimethylpyrrolidinium-2-carboxylic-acid) in aerial parts of Leonurus japonicus (Leonuri herba, yimucao; Chin.Ph.2010, DAB2012) which are used in TCM and Kampo for the treatment of various gynaecological and cardiovascular disorders. Pharmacological publications on this betaine describe cardiovascular, hypotensive, and tissue-protective effects. However, its pharmacopeial analytics poses severe difficulties as it does not contain any chromophore suitable for HPLC-UV-detection. Nine samples from three countries were prepared as decoctions and freeze-dried. (1)H-NMR-spectra were recorded in D2O. The direct-quantitative (1)H-qNMR-procedure was carried out using the N-CH3-singlet at δ 3.03 ppm in comparison to the δ 6.18 ppm singlet of the two vinylic protons of maleic-acid, which was identified as a most favourable internal standard. The quantification limit of stachydrine was 0.44 mg/g drug material. Neither reference-compounds for calibration-curves nor sample-pre-purification was necessary. This protocol revealed stachydrine contents in the range from 0.09 up to 1.01% (w/w) for the tested yimucao samples. Furthermore, between 0.18 and 0.21% of stachydrine was found in the L. japonicus fruit-drug (Leonuri fructus, chongweizi; Chin.Ph.2010) which was examined for this constituent for the first time. In four co-investigated samples of the closely related and similarly used European herb Leonurus cardiaca Ph.Eur., even higher contents up to 1.55% were attested. The presented quantitative (1)H-qNMR-method was shown to be precise with respect to concentration, and yielded highly reproducible data in a series of inter-day repetitions. Methodically, (1)H-qNMR may be a powerful tool for quality assurance of stachydrine containing plants and herbal drugs, especially for industrial routine protocols.

Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test.

AIM: In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B12) and a mixture of vitamins B1+B6+B12 was investigated in the mouse formalin test. METHODS: Individual dose response curves of the Rhodiola rosea ethanol extract, as well as B-vitamins alone or in a mixture were evaluated in mice in which nociception was induced with 2% formalin intraplantarly. The antinociceptive mechanisms of the Rhodiola rosea were investigated by exploring the role of the opioid and serotonin receptors and the nitric oxide pathway. Isobolographic analysis was used to evaluate the pharmacological interactions between the Rhodiola rosea ethanol extract and each B-vitamin individually or the mixture of vitamins B1+B6+B12 by using the ED30 and a fixed 1:1 ratio combination. RESULTS: Administration of the Rhodiola rosea extract alone or in combination with all of the vitamins produced a significant and dose-dependent antinociceptive response. The antinociceptive effect of the Rhodiola rosea extract (ED50=81 mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT1A, GABA/BDZs and opioid receptors and by blocking mediators of the nitric oxide/cGMP/K(+) channels pathway. Isobolograms demonstrate that all of the combinations investigated in this study produced a synergistic interaction experimental ED30 values were significantly smaller than those calculated theoretically. CONCLUSIONS: These results provide evidence that a Rhodiola rosea ethanol extract in combination with B-vitamins produces a significant diminution in the nociceptive response in a synergistic manner, which is controlled by various mechanisms. These findings could aid in the design of clinical studies and suggest that these combinations could be applied for pain therapy.

Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers.

Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

Results of bone fracture treatment by electrophoresis with plant drug / Монголын Анагаах Ухаан

Introduction: The biologically active substances from medicinal plants contributed to humankind’s development. Thus the medicinal plants are used for medicinal purpose throughout the world from ancient time until now. Nowadays more than 300 medicinal plant species are used in the medicine. The type and quantity of phytopreparation, obtained from medicinal plants, is increasing in the recent times. Goal: We have three goals for implementing the study purpose.1. To decrease or reduce pain of bone fracture2. To reduce or relieve edema (less or more)3. To recover joint movement.Materials and Methods: In the rehabilitation department of Second General Hospital we observed 59 patients, who is fractured tibia or forearm bone three months ago, during 21-42 days. The electrophoresis treatment with 5% solution of plant “Rhodiola rosea” is done by 3-6 times in connection with patient’s age, gender, stage of disease and clinical feature.Results: In the result of the electrophoresis treatment with solution of plant “Rhodiola rose” the pain, swallowing, and limitation of movement have been increased by 71-80% after 3 times of the treatment. Besides effect of the electrophoresis have been increased by 97-98,9% after six times of the treatment. Discussion and conclusion: The study proposed that electrophoresis treatment with extract of plant Rhodiola rosea have healing effect on bone fracture. The plant contains 13 essential microelements which absorbs to the body through application of electrophoresis treatment with 5% of the plant solution. In our study, we observed that patient’s complains as pain, swallowing, limitation of movement in first three month of injury reduced in 56%-56,5% after the treatment. Effect of electrophoresis treatment with 5% of Rhodiola rosea increases to 74,2%-76,6% after three times, and effect of 97,9%-98,5% observed after six times of the treatment.

Walls are thin 1 (WAT1), an Arabidopsis homolog of Medicago truncatula NODULIN21, is a tonoplast-localized protein required for secondary wall formation in fibers.

By combining Zinnia elegans in vitro tracheary element genomics with reverse genetics in Arabidopsis, we have identified a new upstream component of secondary wall formation in xylary and interfascicular fibers. Walls are thin 1 (WAT1), an Arabidopsis thaliana homolog of Medicago truncatula NODULIN 21 (MtN21), encodes a plant-specific, predicted integral membrane protein, and is a member of the plant drug/metabolite exporter (P-DME) family (transporter classification number: TC 2.A.7.3). Although WAT1 is ubiquitously expressed throughout the plant, its expression is preferentially associated with vascular tissues, including developing xylem vessels and fibers. WAT1:GFP fusion protein analysis demonstrated that WAT1 is localized to the tonoplast. Analysis of wat1 mutants revealed two cell wall-related phenotypes in stems: a defect in cell elongation, resulting in a dwarfed habit and little to no secondary cell walls in fibers. Secondary walls of vessel elements were unaffected by the mutation. The secondary wall phenotype was supported by comparative transcriptomic and metabolomic analyses of wat1 and wild-type stems, as many transcripts and metabolites involved in secondary wall formation were reduced in abundance. Unexpectedly, these experiments also revealed a modification in tryptophan (Trp) and auxin metabolism that might contribute to the wat1 phenotype. Together, our data demonstrate an essential role for the WAT1 tonoplast protein in the control of secondary cell wall formation in fibers.

Identificação de amostras comerciais de raiz de taiuiá como Wilbrandia ebracteata Cogn / Identification of commercial samples of taiuia-roots as Wilbrandia ebracteata Cogn

A droga vegetal Taiuiá é comercializada pela indústria farmacêutica do Rio Grande do Sul como sendo proveniente de Cayaponia tayuy. (Veil.) Cogn. A análise cromatográfica de duas amostras comerciais fornecidas pela indústria mostrou-se tratar-se de Wilbrandia ebracteat. Cogn.

The vegetable drug Taiuia is used by the pharmaceutical industries of the state Rio Grande do Sul and the original plant is assigned to Coyaponia tayuya (Vell.) Cogn. The chromatographic analysis of two commercial samples supplied by the industry showed to be Wilbrandia ebracteata Cogn.