PMID: 

Food Funct. 2018 Jul 17 ;9(7):3895-3905. PMID: 29968885

Abstract Title: 

Triterpenoids from Ziziphus jujuba induce apoptotic cell death in human cancer cells through mitochondrial reactive oxygen species production.

Abstract: 

Ziziphus jujuba var. inermis Rehder is an edible fruit-producing species of the Rhamnaceae family. In the present study, we isolated eight triterpenoids (1-8) from the fruits of Z. jujuba var. inermis and evaluated their apoptotic cell-death-inducing activities in human cancer cell lines (A549, PC-3, and MDA-MB-231). The structures of compounds 1-8 were determined by spectroscopic methods. Among these, four isomers of coumaroyl alphitolic acid showed potent cytotoxic activities on these cancer cells: 3-O-cis-p-coumaroyl alphitolic acid (3), 3-O-trans-p-coumaroyl alphitolic acid (4), 2-O-trans-p-coumaroyl alphitolic acid (5), and 2-O-cis-p-coumaroyl alphitolic acid (6). Moreover, compounds 3-6 induced apoptotic cell death in a concentration-dependent manner. We further investigated the apoptosis-inducing effects of compound 4 in PC-3 cells which triggered the cleavage of procaspase-3, procaspase-7, procaspase-8, bid, and PARP. Compound 4 increased both the mitochondrial reactive oxygen species (ROS) production and the phosphorylation of p38 MAPK (mitogen-activated protein kinase), but decreased the mitochondrial membrane potential. Pretreatment with Mito-TEMPO (a specific mitochondrial-targeted antioxidant) or a specific p38 inhibitor (SB203580) attenuated apoptotic cell death triggered by compound 4 which suggests that compound 4 may induce apoptotic cell death in these cancer cells by increasing the mitochondrial ROS production as well as the subsequent p38 MAPK activation. The study findings provide a rational base to use Ziziphus extracts for cancer treatments in traditional oriental medicine.

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PMID: 

Open Access Maced J Med Sci. 2018 May 20 ;6(5):757-766. Epub 2018 May 15. PMID: 29875842

Abstract Title: 

Anti-Inflammatory, Anti-Bacterial and Anti-Diarrhoeal Activity ofFruit Extract.

Abstract: 

BACKGROUND: belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative).AIM: To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities offruit ethanolic extract.METHOD: The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil andinduced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat's treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of(EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat's paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin.RESULTS: EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right pawwere affected compared to the negative control group.CONCLUSION: EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin.

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PMID: 

Curr Med Chem. 2019 Dec 11. Epub 2019 Dec 11. PMID: 31830883

Abstract Title: 

Therapeutic potential of natural psychoactive drugs for central nervous system disorders: A perspective from polypharmacology.

Abstract: 

In drug development, the creation of highly selective ligands has been unsuccessful for the treatment of central nervous system disorders. Multi-target ligands, from the polypharmacology paradigm, are being proposed as treatments for these complex disorders, since they offer enhanced efficacy and a strong safety profile. Natural products are the best examples of multi-target compounds, so they are of high interest within this paradigm. Additionally, recent research on psychoactive drugs of natural origin, such as ayahuasca and cannabis, has demonstrated promising therapeutic potential for the treatment of some psychiatric and neurological disorders. In this text, we describe how research on psychoactive drugs can be effectively combined with the polypharmacology paradigm, providing ayahuasca and cannabis research as examples. The advantages and disadvantages are also discussed.

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PMID: 

Psychopharmacology (Berl). 2020 Jan 11. Epub 2020 Jan 11. PMID: 31927605

Abstract Title: 

Ayahuasca's 'afterglow': improved mindfulness and cognitive flexibility in ayahuasca drinkers.

Abstract: 

RATIONALE: There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca's therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an 'afterglow' effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.OBJECTIVE: To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS: Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.RESULTS: Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.CONCLUSIONS: The present study supports ayahuasca's ability to enhance mindfulness and further reports changes in cognitive flexibility in the 'afterglow' period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.

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PMID: 

Psychopharmacology (Berl). 2020 Jan 14. Epub 2020 Jan 14. PMID: 31938878

Abstract Title: 

Therapeutic potential of ayahuasca in grief: a prospective, observational study.

Abstract: 

RATIONALE: Recent studies have assessed the therapeutic potential of ayahuasca for the treatment of depression with promising preliminary results.OBJECTIVES: Here, we examine the course of grief over 1 year of follow-up in a bereaved sample that attended a center in Peru to participate in indigenous Shipibo ayahuasca ceremonies. We also explore the roles of experiential avoidance and decentering as mechanisms of change.METHODS: Bereaved participants who attended the ayahuasca center responded to an online survey that included the Texas Revised Inventory of Grief, Symptom Assessment-45, WHO Quality of Life-Bref, Acceptance and Action Questionnaire, and Decentering. Baseline assessment was completed by 50 individuals (T0). Of these, 39 completed the post-assessment at 15 days (T1), 31 at 3 months (T2), 29 at 6 months (T3), and 27 at 12 months (T4) after leaving the retreat. Pearson's analysis was performed to examine the relationship between the severity of grief and mechanisms of change during the period of T0 and T1.RESULTS: A significant decrease in Texas Revised Inventory was observed at all time points (T1: Cohen's d = 0.84; T2: Cohen's d = 1.38; T3: Cohen's d = 1.16; T4: Cohen's d = 1.39). We found a relationship between experiential avoidance (r = 0.55; p 

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PMID: 

Respir Physiol Neurobiol. 2019 02 ;260:28-36. Epub 2018 Dec 3. PMID: 30521862

Abstract Title: 

Antiasthmatic potential of Zizyphus jujuba Mill and Jujuboside B. – Possible role in the treatment of asthma.

Abstract: 

Zizyphus jujuba Mill, a famous oriental traditional medicine, has been reported to exhibit diverse activities in biological systems including the respiratory system. However, a little information is available on its antiasthmatic activity. Jujuboside B (JB) is a natural saponin and one of the active constituent of fruits of Zizyphus jujuba. In the present investigation, JB was isolated from ethanolic extracts of fruits of Zizyphus jujuba (EZJF). EZJF and JB were then evaluated for anti-asthmatic activity using various screening methods. JB was additionally evaluated using ovalbumin (OVA) -induced allergic asthma in mice. Results obtained in the present study showed that EZJF and JB significantly inhibited clonidine-induced catalepsy, milk-induced leucocytosis and eosinophilia, clonidine-induced mast cell degranulation, and passive paw anaphylaxis. The number of inflammatory cells in bronchoalveolar lavage (BAL) fluid was considerably lowered and the severity of pulmonary inflammation was alleviated in the mice pretreated with JB. The high-level expression of T-helper type 2 (TH2) cytokines was markedly reduced in the serum, BAL fluid, and lung homogenates. Thus EZJF and JB showed potent anti-asthmatic activity. Hence EZJF and JB possess a potential role in the treatment of asthma.

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PMID: 

Int J Prev Med. 2019 ;10:103. Epub 2019 Jun 7. PMID: 31360350

Abstract Title: 

Effect of Training with or without Ziziphus Jujuba Extract on Cardiokines in Heart Tissue of Myocardial Infarcted Rats.

Abstract: 

Background: Today, the importance of physical activity as a preventative way for cardiovascular disease has attracted much attention.The aim of this study is to investigate the effect of 6 weeks of interval training with or without extract of Ziziphus jujuba on lipocalcin-2 (LCN2) and adiponectin levels in heart tissue in male Wistar rats with myocardial infarction.Methods: Thirty male Wistar rats (mean weight, 180-220 g and age, 2-3 months) were divided into five groups, including (1) Healthy control; (2) Isoprenaline-treated group (ISO); (3) ISO + jujube extracts (JE); (4) Trained ISO rats; and (5) Trained ISO rats + JE. Exercise was performed (5 days/week, for 6 week including 54-min cycles with speed of 23 m/min and 54-min cycles with speed of 15 m/min). After 48 h of the last training session, the rats were sacrificed, and their heart tissue was excised. The significant level of statistical data was analyzed by one-way ANOVA test.Results: LCN2 levels significantly decreased in trained ISO rats + JE group after 6 weeks of interval training with JE consumption, compared to ISO group. However, the consumption of jujuba extracts with and without interval training did not show any significant changes in adiponectin levels of rat's heart tissue, compared to ISO (

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PMID: 

Med Chem. 2019 Oct 31. Epub 2019 Oct 31. PMID: 31670624

Abstract Title: 

Therapeutic effects of Ziziphus jujuba Mill. fruit in traditional and modern medicine: a review.

Abstract: 

Ziziphus jujuba Mill. belonging to the Rhamnaceae family, has been consumed since ancient times as a medicine and food. In the different traditional medical schools, Z. jujuba has been used to treat various diseases such as respiratory system diseases (asthma, cough, and laryngitis), gastrointestinal problems (constipation, colitis and liver diseases), as well as, cardiovascular and genitourinary system diseases. From the perspective of Islamic traditional medicine (ITM) Z.jujuba fruit is an emollient, laxative, and maturative, it can purify blood and improve blood circulation, relieve internal heat and reduce inflammation. Some therapeutic uses of Z. jujuba such as antibacterial, antioxidant, sedative, hepato-protective, anti-hyperglycemic, and anti-hyperlipidemic activities have been shown in modern pharmacological studies. In the current study, traditional and ethno-medicinal uses, botany, phytochemistry and pharmacological activities of Z. jujuba were reviewed.

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PMID: 

Cardiovasc Hematol Disord Drug Targets. 2019 11 19. Epub 2019 Nov 19. PMID: 31746299

Abstract Title: 

Ethyl acetate and aqueous fractions of Ziziphus jujuba prevent acute hypertension induced by angiotensin II in rats.

Abstract: 

BACKGROUND: Antihypertensive effect of Ziziphus jujube (ZJ) has been reported previously.OBJECTIVE: The present study investigates the effect of two ethyl acetate (polar and semi-polar compound) and aqueous fractions (polar compound) of ZJ on cardiovascular parameters in acute hypertension induced by angiotensin II(AngII).METHODS: Rats randomly were divided into as following groups (n=7 in each group): Control, AngII (50 ng/kg), Losartan (Los, 30 mg/kg) + AngII, ethyl acetate fraction (EA150 and EA300 mg/kg) + AngII and aqueous fraction (A150 and A300 mg/kg) + AngII. Treated rats received Los and ZJ fractions for four weeks orally and in experiment day (28th) received AngII intravenously. In all groups' systolic blood pressure (SBP), heart rate (HR) and mean arterial pressure (MAP) were recorded throughout the experiment after cannulation of femoral artery via power lab system.RESULTS: In AngII group SBP and MAP significantly increased (P

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PMID: 

J Basic Clin Physiol Pharmacol. 2019 Nov 22. Epub 2019 Nov 22. PMID: 31756163

Abstract Title: 

Cytoprotective effects of the aqueous extract of the Ziziphus jujuba fruit on TBHP-induced damage on human fibroblast cells.

Abstract: 

Background Oxidative stress plays a major role in the development of various human diseases. However, many antioxidant compounds can neutralize the excess of free radicals, protect the cells against their toxic effects and help prevent or treat a disease. This study investigated the cytoprotective effects of the aqueous extract of the Ziziphus jujuba fruit on the tert-butyl hydroperoxide (TBHP)-induced damage on human fibroblast cells. Methods Human fibroblast cells were pretreated with different concentrations (1, 2, 4, 8 mg/mL) of Z. jujuba for 24 h and exposed to 75μM TBHP for another 24 h. Cell viability was determined by the MTT assay. The antioxidant activity was determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods, and the intracellular antioxidant activity was evaluated with the Cellular antioxidant activity assay. Results Our data showed that treatment with TBHP reduced cell viability of human fibroblast cells, while pretreatment with Z. jujuba increased cell viability in a dose-dependent manner. This indicated the cytoprotective effects of Z. jujuba. Pretreatment with Z. jujuba increasedthe antioxidant capacity and scavenged the TBHP-produced peroxyl radicals in the human fibroblast cell medium. Moreover, Z. jujuba increased the intracellular antioxidant activity of human fibroblast cells. Conclusions These results demonstrated that the aqueous extract of the Z. jujuba fruit can prevent TBHP-induced cellular toxicity by enhancing the antioxidant activity in cells and their medium. So, Z. jujuba has a therapeutic potential to attenuate oxidative stress-induced diseases.

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